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pubmed_854_11062
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The objective of this study was to determine and compare the quality of life (QOL) of patients with fibromyalgia syndrome (FS) and rheumatoid arthritis (RA) and to assess patients' psychological and functional status in each group. This prospective study included 62 female FS patients and 60 female RA patients diagnosed by the American College of Rheumatology criteria. The Turkish translations of the Arthritis Impact Measurement Scale II (AIMS II) and Beck Depression Index (BDI) were given to all of the patients and they were asked to complete the two questionnaires. The scores of AIMS II, pain, and QOL were evaluated in the FS and RA groups. There were no statistically significant differences between the FS and RA groups (p>0.05) in terms of QOL. The affect subgroup scores of the AIMS II and BDI were highly correlated in the FS and RA groups (p<0.002, r=0.85 and p<0.05, r=0.80, respectively). The results show that the QOL is negatively but similarly affected in FS and RA groups.
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10.1007/s10067-004-1068-3
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pubmed_915_16890
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Only minimal attention has been given to analyzing interactional moments when patients and providers talk about "pain" in general consultations and primary care, and no attention has focused on how pain gets managed during oncology interviews. Conversation analysis (CA) is used to examine a sampling of instances drawn from a collection of 146 pain instances across 65 video recorded and transcribed clinical encounters in a comprehensive cancer clinic. Specific attention is drawn to how pain descriptions are not static but malleable as cancer patients upgrade, downgrade, and produce combined orientations when making their experiences available to oncologists. In response, it is shown that doctors acknowledge patients' descriptions, but do not elaborate nor affiliate with, important pain disclosures. Three interactional environments are closely examined: 1) Reporting and responding to past pain/hurt incidents; 2) Doctor's missing assessments in response to good news announcements about patients' minimal pain; and 3) Patient-initiated pain responses to doctors' questions. These empirical findings confirm identified patterns of interactional asymmetries comprising pain events in UK consultations and USA primary care. Close examination of these social actions provides basic knowledge about how pain communication reframes historical understandings of individuals' pain experiences. Implications for future research are identified, and a protocol is described for how clinical practice and medical education can be improved by refining understandings of pain communication to promote increased sensitivities and more personalized responses to pain expressions.
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10.1080/10410236.2019.1654178
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pubmed_586_3103
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The possibility was investigated that L-glutamic acid is the excitatory transmitter released from the optic nerve terminals of the pigeon optic tectum. (1) Superficial layers of the tectum contained high levels of endogenous glutamate and accumulated L-[3H]glutamate by a high affinity uptake process. (2) Subcellular and autoradiographic studies indicated that 10-30% of the exogenously accumulated L-[3H]glutamate was localized within synaptosomes, and that 11-15% of the synaptosomes had been labelled. (3) The glutamate-accumulating synaptosomes sedimented to the same isopycnic density as pinched-off optic nerve terminals. (4) GABA-and noradrenaline-accumulating synaptosomes were also associated with this subcellular population. (5) Retinal ablation did not change endogenous glutamate concentrations or the high affinity uptake of glutamate. The results are discussed in relation to a possible role for L-glutamate as the 'optic nerve transmitter' and in the context of previous evidence implicating glutamate as an excitatory transmitter.
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10.1016/0006-8993(76)90211-0
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pubmed_666_24929
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Globally, non-steroidal anti-inflammatory drugs (NSAIDs) are highly used to treat pain. With the rise of the COVID-19 pandemic, the safety of NSAIDs use has been called into question. These concerns are worthy of review. At present, there is no compelling data showing that NSAIDs worsen the severity of COVID-19 symptoms or increase one's likelihood of contracting the illness. For patients in pain and without symptoms that could potentially be attributed to COVID-19 (cough, fevers/chills, lethargy, myalgias, anosmia and so on), NSAIDs should continue to remain a viable option to provide analgesia to patients in need.
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10.1136/rapm-2020-101584
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pubmed_504_4174
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OBJECTIVE
To study the effect of MDR1 and CYP3A5 gene polymorphisms on the outcomes of imatinib treatment in patients with chronic myeloid leukemia (CML).
METHODS
A total of 100 patients with CML treated with imatinib were enrolled in this study, including 50 patients with cytogenetic relapse (study group) and 50 without cytogenetic relapse (control group) during the follow-up for 45 months. For all the patients, single nucleotide polymorphisms (SNPs) of C1236T, C3435T, and G2677T/A loci in the MDR1 gene and A6986G locus in CYP3A5 gene were genotyped and the trough levels of imatinib was measured using LC-MS/MS. The relationship between SNPs of the loci and the risk of cytogenetic relapse were analyzed.
RESULTS
The risk of cytogenetic recurrence was significantly higher in patients with CC genotypes of MDR1-C1236T and MDR1-C3435T than in those with CT + TT genotypes (P < 0.05). The median survival time of the patients with TT genotypes of MDR1-C3435T and MDR1-C1236T was significantly higher than that of patients with CC genotypes and CT genotypes (P < 0.05). The incidences of hematologic toxicity and neutropenia were significantly higher in patients with cytogenetic relapse than in those without cytogenetic relapse (P < 0.05). MDR1-C3435T genotype and imatinib concentration were independent predictors of cytogenetic relapse of CML.
CONCLUSIONS
The risk of cytogenetic relapse of CML was significantly affected by SNPs of C1236T and C3435T loci of MDR1 gene and blood imatinib concentration. MDR1-C3435T genotype can be used as a potential biomarker for predicting cytogenetic relapse in CML patients.
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10.3969/j.issn.1673-4254.2018.01.06
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pubmed_103_17380
|
The enigmatical dichotomy between the two CERT/GPBP protein isoforms, their vast panel of biological implications and the scarcity of known antagonist series call for new ligand chemotypes identification. We report the design of iminosugar-based ceramide mimics for the development of new START domain ligands potentially targeting either protein isoforms. Strategic choice of (i) an iminoxylitol core structure and (ii) the positioning of two dodecyl residues led to an extent of protein binding comparable to that of the natural cargo lipid ceramide or the archetypical inhibitor HPA-12. Molecular docking study evidenced a possible mode of protein binding fully coherent with the one observed in crystalline co-structures of known ligands. The present study thus paves the way for cellular CERT inhibition studies en route to the development of pharmacological tools aiming at deciphering the respective function and therapeutic potential of the two CERT/GPBP protein isoforms.
|
10.1016/j.bmc.2017.02.026
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pubmed_990_19418
|
The v-Ski avian retroviral oncogene is postulated to act as a transcription factor. Since protein-protein interactions have been shown to play an important role in the transcription process, we attempted to identify Ski protein partners with the yeast two-hybrid system. Using v-Ski sequence as bait, the human gene skip (Ski Interacting Protein) was identified as encoding a protein which interacts with both the cellular and viral forms of Ski in the two-hybrid system. Skip is highly homologous to the Drosophila melanogaster protein Bx42 which is found associated with chromatin in transcriptionally active puffs of salivary glands. The Ski-Skip interaction is potentially important in Ski's transforming activity since Skip was demonstrated to interact with a highly conserved region of Ski required for transforming activity. Like Ski, Skip is expressed in multiple tissue types and is localized to the cell nucleus.
|
10.1038/sj.onc.1201687
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pubmed_485_1030
|
No study has yet been done to investigate the changes in endothelial cell size, perimeter, and density that may result from the warming of corneas in MK (McCarey-Kaufman) medium for specular microscopy. In the present investigation eye bank eyes were stored in MK medium at 4 degrees C and rewarmed daily for six days at 37 degrees C before specular photography of the endothelium was performed. These photographs were compared with wet mount preparations stained with trypan blue and alizarin red made from the same corneas and those stored without rewarming for six days. In addition all corneas were qualitatively analysed with the scanning electron microscope (SEM). The data from serial specular photography were insufficient to allow significant conclusions to be drawn about day to day changes in cell morphology. However, analysis of wet mount preparations revealed that cell density and perimeter varied significantly between those corneas rewarmed daily and those held in cold storage for six days. SEM studies showed an intact cell monolayer with cell loss along the folds of corneal endothelium. We therefore concluded that repeated rewarming at 37 degrees C of corneas stored in MK medium at 4 degrees has a deleterious effect on cell morphology and that folds induced by swelling of corneal tissue result in endothelial cell damage with some loss.
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10.1136/bjo.72.7.545
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pubmed_1010_654
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Colorectal cancer (CRC) is one of the most common types of human cancers. However, the mechanisms underlying CRC progression remained elusive. This study identified differently expressed messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and small nucleolar RNAs (snoRNAs) between pre-therapeutic biopsies and post-therapeutic resections of locally advanced CRC by analyzing a public dataset, GSE94104. We identified 427 dysregulated mRNAs, 4 dysregulated lncRNAs, and 19 dysregulated snoRNAs between pre- and post-therapeutic locally advanced CRC samples. By constructing a protein-protein interaction network and co-expressing networks, we identified 10 key mRNAs, 4 key lncRNAs, and 7 key snoRNAs. Bioinformatics analysis showed therapy-related mRNAs were associated with nucleosome assembly, chromatin silencing at recombinant DNA, negative regulation of gene expression, and DNA replication. Therapy-related lncRNAs were associated with cell adhesion, extracellular matrix organization, angiogenesis, and sister chromatid cohesion. In addition, therapy-related snoRNAs were associated with DNA replication, nucleosome assembly, and telomere organization. We thought this study provided useful information for identifying novel biomarkers for CRC.
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10.3389/fgene.2019.00803
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pubmed_290_3511
|
BACKGROUND
Although substantial empirical research supports the clinical value of routine outcome measures/clinical feedback systems (ROM/CFS), translation into routine practice poses several challenges. The present case study investigated how stakeholders, clinicians, patients and clinical managers related to the implementation of the Norse Feedback (NF) in ordinary practice.
METHODS
We did an in-depth qualitative case study of the implementation of NF in a public mental-health institution. The settings were two outpatient clinics and two in-patient clinics organized under the same health trust. Data were drawn from three sources: archival sources (n = 16), field notes (n = 23), and 43 in-depth interviews with clinicians (n = 19), clinical managers (n = 5) and patients (n = 12). Ten of the participants were interviewed twice. The data were coded inductively and analyzed using a stringent qualitative methodology.
RESULTS
We present our findings under three inter-related domains. First, we describe what followed the clinical feedback implementation. Second, we present the context experienced as being complex and high on work-pressure. Third, we describe the situated rules about the priority between competing tasks.
CONCLUSIONS
The preliminary results complement and contextualize understandings of known barriers to implementing ROM/CFS in clinical settings. We apply a socio-material perspective to discuss clinicians' responses to complexity, implementation, and why some incentivized tasks prevailed over others regardless of therapists' perceived benefits.
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10.1186/s13033-019-0324-5
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pubmed_539_10157
|
Random mutagenesis coupled with screening of the active enzyme at a low temperature was applied to isolate cold-adapted mutants of a thermophilic enzyme. Four mutant enzymes with enhanced specific activities (up to 4.1-fold at 40 degrees C) at a moderate temperature were isolated from randomly mutated Thermus thermophilus 3-isopropylmalate dehydrogenase. Kinetic analysis revealed two types of cold-adapted mutants, i.e. k(cat)-improved and K(m)-improved types. The k(cat)-improved mutants showed less temperature-dependent catalytic properties, resulting in improvement of k(cat) (up to 7.5-fold at 40 degrees C) at lower temperatures with increased K(m) values mainly for NAD. The K(m)-improved enzyme showed higher affinities toward the substrate and the coenzyme without significant change in k(cat) at the temperatures investigated (30-70 degrees C). In k(cat)-improved mutants, replacement of a residue was found near the binding pocket for the adenine portion of NAD. Two of the mutants retained thermal stability indistinguishable from the wild-type enzyme. Extreme thermal stability of the thermophilic enzyme is not necessarily decreased to improve the catalytic function at lower temperatures. The present strategy provides a powerful tool for obtaining active mutant enzymes at lower temperatures. The results also indicate that it is possible to obtain cold-adapted mutant enzymes with high thermal stability.
|
10.1093/protein/14.2.85
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pubmed_156_14054
|
OBJECTIVE
To find out the changes in the infective pathogens and their drug resistance in burned patients.
METHODS
The patients were divided into two groups. The first group was from July 1991 to June 1996, and the second group was from July 1996 to June 2001. The bacteria of burned body surface and blood were cultured, and the bacteria and their drug sensitivity were analyzed.
RESULTS
Gram-negative bacteria were the major bacteria in burn infection, among which Pseudomonas aeruginosa ranked the top. Staphylococcus aureous ranked the first among the Gram-positive bacteria, and the isolation rate of methicillin resistant Staphylococcus aureus increased; The isolation rate of Enterobacter cloacae (10.4%), Escherichia coli (8.3%), Klebsiella pneumoniae (7.3%), and fungus (4.2%) all rose. The antibiotic resistant strains of Pseudomonas aeruginosa and Staphylococcus aureous increased.
CONCLUSION
The changes in pathogens of burn infection and bacterial drug resistance are related to the wide use of broad spectrum antibiotics such as cefazidime and imepenem, suggesting that dynamic observation of changes in pathogenic strains and sensitivity of bacteria to antibiotics are useful for clinical prevention and cure of burn infection.
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pubmed_156_14054
|
pubmed_1047_19920
|
Hyperacute rejection, mediated by natural antibody, is the major barrier to xenotransplantation. The studies reported herein were aimed at evaluating antibody-mediated cytotoxicity and the role of the Gal alpha(1,3)Gal epitope, which we had previously demonstrated was the major epitope of pig cells detected by naturally occurring human antibodies. Also, we had shown that this epitope could be induced in non-expressing cells by the transfection of a cDNA clone encoding alpha(1,3)galactosyl transferase, the enzyme that produces this epitope. The importance of the Gal alpha(1,3)Gal epitope was supported by (1) sugar inhibition studies; (2) complete absorption of cytotoxic antibodies by melibiose-sepharose columns; and (3) the ability of normal human serum to lyse COS cells after transfection with a cDNA clone encoding alpha(1,3)galactosyl transferase. These findings strongly suggest that the majority of cytotoxic human antibodies that would recognize a xenogeneic graft are directed to the Gal alpha(1,3)Gal epitope.
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10.1097/00007890-199410270-00003
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pubmed_582_7962
|
We used two molecular cytogenetic techniques, multicolor fluorescence in situ hybridization (M-FISH) and comparative genomic hybridization (CGH), to analyze three established lung adenocarcinoma cell lines (A549, H1650, and SPC-A-1) and primary lung adenocarcinoma samples, to identify common chromosomal aberrations. M-FISH revealed numerous complex chromosomal rearrangements. Chromosomes 5, 6, 11, 12, and 17 were most frequently involved in interchromosomal translocations. CGH revealed regions on 1q, 2p, 3q, 5p, 5q, 7p, 8q, 11q, 12q, 14q, 16p, 17p, 19q, 20q, 21q, and 22q to be commonly overrepresented and regions on 2q, 3p, 4p, 5q, 7q, 8p, 9p, 13q, 14q, and 17p to be underrepresented. The most common gains were found in 16p13 (in 50% of samples), and 16p13 amplification was associated with relatively poor differentiation and late stage. M-FISH and CGH can be a powerful tool in identification of genomic alterations in lung cancer, as well as in diagnosis. The overrepresented regions may harbor potential candidate genes involved in lung adenocarcinoma pathogenesis.
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10.1016/j.cancergencyto.2007.11.012
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pubmed_248_13767
|
A gasoline-degrading consortium, originating from a Mexican soil, was used to study its hexane-degradation kinetics in liquid culture and in a biofilter with mineral support. The biodiversity of the consortium depending on the culture conditions and electron and energy source (gasoline, hexane in liquid or hexane in the biofilter) was analyzed using a 16S rRNA-based approach. Significant differences between the populations were observed, indicating a probable adaptation to the substrate. Two strains, named SP2B and SP72-3, isolated from the consortium, belonged to Actinomycetes and demonstrated a high metabolic potential in hexane degradation. Even though the SP2B strain was related to Rhodococcus ruber DSM 43338(T) by phylogenetic studies, it displayed enlarged metabolic properties in hexane and other short-alkane degradation compared with the collection strain.
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10.1111/j.1574-6941.2005.00017.x
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pubmed_113_6749
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Sulphate-reducing bacteria (SRB) cause fouling, souring, corrosion and produce H2S during oil and gas production. Produced water obtained from Periquito (PQO) and Galo de Campina (GC) onshore oilfields in Brazil was investigated for SRB. Produced water with Postgate B, Postgate C and Baars media was incubated anaerobically for 20 days. DNA was extracted, 16S rDNA PCR amplified and fragments were sequenced using Illumina TruSeq. 4.2 million sequence reads were analysed and deposited at NCBI SAR accession number SRP149784. No significant differences in microbial community composition could be attributed to the different media but significant differences in the SRB were observed between the two oil fields. The dominant bacterial orders detected from both oilfields were Desulfovibrionales, Pseudomonadales and Enterobacteriales. The genus Pseudomonas was found predominantly in the GC oilfield and Pleomorphominas and Shewanella were features of the PQO oilfield. 11% and 7.6% of the sequences at GC and PQO were not classified at the genus level but could be partially identified at the order level. Relative abundances changed for Desulfovibrio from 29.8% at PQO to 16.1% at GC. Clostridium varied from 2.8% at PQO and 2.4% at GC. These data provide the first description of SRB from onshore produced water in Brazil and reinforce the importance of Desulfovibrionales, Pseudomonadales, and Enterobacteriales in produced water globally. Identifying potentially harmful microbes is an important first step in developing microbial solutions that prevent their proliferation.
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10.1038/s41598-021-99196-x
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pubmed_101_6677
|
BACKGROUND
From late February 2020, English care homes rapidly adapted their practices in response to the COVID-19 pandemic. In addition to accommodating new guidelines and policies, staff had to adjust to rapid reconfiguration of services external to the home that they would normally depend upon for support. This study examined the complex interdependencies of support as staff responded to COVID-19. The aim was to inform more effective responses to the ongoing pandemic, and to improve understanding of how to work with care home staff and organisations after the pandemic has passed.
METHODS
Ten managers of registered care homes in the East Midlands of England were interviewed by videoconference or phone about their experiences of the crisis from a structured organisational perspective. Analysis used an adapted organisational framework analysis approach with a focus on social ties and interdependencies between organisations and individuals.
RESULTS
Three key groups of interdependencies were identified: care processes and practice; resources; and governance. Care home staff had to deliver care in innovative ways, making high stakes decisions in circumstances defined by: fluid ties to organisations outside the care home; multiple, sometimes conflicting, sources of expertise and information; and a sense of deprioritisation by authorities. Organisational responses to the pandemic by central government resulted in resource constraints and additional work, and sometimes impaired the ability of staff and managers to make decisions. Local communities, including businesses, third-sector organisations and individuals, were key in helping care homes overcome challenges. Care homes, rather than competing, were found to work together to provide mutual support. Resilience in the system was a consequence of dedicated and resourceful staff using existing local networks, or forging new ones, to overcome barriers to care.
CONCLUSIONS
This study identified how interdependency between care home organisations, the surrounding community, and key statutory and non-statutory organisations beyond their locality, shaped decision making and care delivery during the pandemic. Recognising these interdependencies, and the expertise shown by care home managers and staff as they navigate them, is key to providing effective healthcare in care homes as the pandemic progresses, and as the sector recovers afterwards.
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10.1186/s12877-021-02053-9
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pubmed_269_2481
|
Colorectal cancer (CRC) is a common gastrointestinal malignancy, and recurrence and metastasis contribute considerably to its high mortality. It is well known that the epithelial-mesenchymal transition (EMT) accelerates the rate of cancer cell dissemination and migration, thus promoting cancer metastasis. Targeted therapy is a common modality for cancer treatment, and it can play a role in inhibiting cancer progression. In this study, bioinformatics was used to search for genes associated with the prognosis of CRC. First, differential analysis was performed on colon and rectal cancer samples to obtain 2,840 and 3,177 differentially expressed genes (DEGs), respectively. A Venn diagram was then used to identify 262 overlapping genes from the two groups of DEGs and EMT-related genes. The overlapping genes were subjected to batch survival analysis and batch expression analysis successively, and nine genes were obtained whose high expression in CRC led to a poor prognosis. The least absolute shrinkage and selection operator (LASSO) prognostic model was then constructed to obtain the risk score formula. A nomogram was constructed to seek prognostic independent factors to obtain CDKN2A. Finally, CCK-8 assay, flow cytometry and western blotting assays were performed to analyze the cellular biological function of CDKN2A. The results showed that knockdown of CDKN2A expression inhibited HT-29 cell proliferation, promoted apoptosis and cell cycle progression, and affected the EMT process in CRC.
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10.3389/fonc.2022.834235
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pubmed_187_22055
|
The Ohmeda 885A field anesthesia machine is equipped with a non-agent-specific, universal vaporizer that can be used with most volatile anesthetic agents. On a recent humanitarian medical mission to Honduras, the 885A was used to administer general anesthesia to 26 patients utilizing sevoflurane, a new inhalational anesthetic with a variety of clinical benefits, including less airway irritability, making it ideal for inhalation inductions. Flow rates for delivery of anesthetic agent were calculated by using the enflurane portion of the Verni-Trol flow calculator wheel, because sevoflurane and enflurane have similar vapor pressures. Calculated anesthetic concentrations were compared with measured concentrations using linear regression analysis and found to have a Pearson product moment of 0.995. We find that the use of sevoflurane in the 885A is an excellent alternative to other inhalational anesthetic agents and may have applications for use during both military conflicts and peacetime missions in remote areas.
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pubmed_187_22055
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pubmed_146_17626
|
When Escherichia coli cells were grown with limited levels of oxygen, the glucose-induced transcription of ptsG was decreased whereas deletion of the arcA gene partially restored it, which was consistent with the previous report that the ArcA protein represses ptsG transcription. However, under this circumstance, we found that the level of EIICB(Glc) protein encoded by the ptsG gene was rather increased. This paradoxical phenomenon can be explained by the delayed turnover of ptsG mRNA in cells anaerobically grown in the presence of glucose. Finally, our data showed that anaerobic expression of the ptsHIcrr operon is also enhanced by increasing the longevity of the reduced mRNA levels.
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10.1016/j.bbrc.2008.03.145
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pubmed_118_16240
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Inorganic and organic forms of arsenic (As), as well as omega-3 fatty acids were measured in 578 fish/seafood samples that belong to 15 species of commonly consumed seafood in Kuwait. Arsenic speciation data, with the toxicological profile of inorganic arsenic (iAs) and fish consumption rates were applied in a probabilistic risk assessment to estimate the risk from exposure to iAs. The nutritional benefits of omega-3-fatty acid levels in various species of fish were taken into consideration. Results showed that the mean daily intake of iAs through fish consumption among the Kuwaiti population was 0.058 µg/kg/day, and the 95th percentile was 0.15 µg/kg/day. Although the mean intake level did not exceed the incremental lifetime cancer risk (ILCR) at 1 × 10-4, the 95th percentile of iAs intake showed an ILCR of 2.7 × 10-4. Kuwaiti children (aged 6-12 years) were found to have a higher mean intake of iAs at 0.10 µg/kg/day with 68% of children in this category, exceeding the risk specific dose associated with an ILCR of 1 × 10-4. The fish species, hammor (grouper; Epinephelus coioides), is the top contributor to iAs intake, and tuna is the major source of omega 3-fatty acids for the Kuwaiti population.
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10.1007/s00244-016-0329-x
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pubmed_155_9840
|
Most DBA mastocytoma and Sarcoma 180 cells trapped in the lungs of mice after i.v. injection died within 7 h. Rates of cell death were similar for both tumour cell lines. Rates of tumour cell death were unrelated to whether the cells were allogeneic or syngeneic, induced platelet aggregation or not, had different patterns of subsequent tumour growth, or were injected in varying numbers. Cell death was by coagulative necrosis, not apoptosis. Sarcoma 180 tumour cells were quickly localized in the lung and enclosed in platelet aggregates which remained, with degranulation, until the time of tumour cell death. However, platelet aggregation did not appear to play a role in tumour cell killing. The prevention of platelet aggregation by pretreatment of mice with an anticoagulant had little effect on the rate of death of tumour cells in the lung. Mastocytoma tumour cells did not cause platelet aggregation, yet died in the lung at similar rates to Sarcoma 180 cells. The killing of tumour cells in the lung did not appear to be cell-mediated. No mononuclear cells were seen in the vicinity of tumour cells and the type of cell death was not that associated with cell-mediated killing. The tumour cells did not die within 6 h of being injected into the peritoneal cavity. It is suggested that a nonspecific non-immunological process results in the death of intravenously injected tumour cells in the lung. This process was not affected by differing oxygen levels in the inhaled gas.
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pubmed_155_9840
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pubmed_201_503
|
Epichromatin is identified by immunostaining fixed and permeabilized cells with particular bivalent anti-nucleosome antibodies (mAbs PL2-6 and 1H6). During interphase, epichromatin resides adjacent to the inner nuclear membrane; during mitosis, at the outer surface of mitotic chromosomes. By STED (stimulated emission depletion) microscopy, PL2-6 stained interphase epichromatin is ∼76 nm thick and quite uniform; mitotic epichromatin is more variable in thickness, exhibiting a "wrinkled" surface with an average thickness of ∼78 nm. Co-immunostaining with anti-Ki-67 demonstrates Ki-67 deposition between the PL2-6 "ridges" of mitotic epichromatin. Monovalent papain-derived Fab fragments of PL2-6 yield a strikingly different punctate "chromomeric" immunostaining pattern throughout interphase nuclei and along mitotic chromosome arms. Evidence from electrophoretic mobility shift assay (EMSA) and from analytical ultracentrifugation characterize the Fab/mononucleosome complex, supporting the concept that there are two binding sites per nucleosome. The peptide sequence of the Hv3 region (heavy chain variable region 3) of the PL2-6 antibody binding site strongly resembles other nucleosome acidic patch binding proteins (especially, LANA and CENPC), supporting that the nucleosome acidic patch is included within the epichromatin epitope. It is speculated that the interphase epichromatin epitope is "exposed" with favorable geometric arrangements for binding bivalent PL2-6 at the surface chromatin; whereas, the epitope is "hidden" within internal chromatin. Furthermore, it is suggested that the "exposed" nucleosome surface of mitotic epichromatin may play a role in post-mitotic nuclear envelope reformation.
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10.1080/19491034.2017.1380141
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pubmed_716_4283
|
Mycobacterial infectious diseases, including tuberculosis (TB), severely threaten global public health. Nonreplicating Mycobacterium tuberculosis (Mtb) is extremely difficult to eradicate using current TB drugs that primarily act on replicating cells. Novel TB drugs acting on unconventional targets are needed to combat TB efficiently. Although membrane-disrupting antimicrobial peptides and their synthetic mimics exhibit the potential to kill persisters, the lack of microbe selectivity, especially toward mycobacteria, has been a concern. Here, we report that the recently developed poly(guanylurea)-piperazine (PGU-P) shows fast and selective mycobactericidal effects. Using a nonpathogenic model organism, Mycobacterium smegmatis (Msm), we have found that the mycobactericidal effects of PGU-P are correlated to the disruption of the mycobacterial membrane potential and bioenergetics. Accordingly, PGU-P also potentiates bedaquiline, an oxidative phosphorylation-targeting TB drug disturbing mycobacterial bioenergetics. Importantly, PGU-P also exhibits a promising activity against pathogenic Mtb with a minimum inhibitory concentration of 37 μg/mL. Our results support that PGU-P is a novel class of antimycobacterial biomaterial, and the unique structural feature can contribute to developing novel antimycobacterial drugs.
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10.1021/acs.biomac.2c00902
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pubmed_134_3892
|
The receptor tyrosine kinase HER2 and its rat homologue neu were independently identified as close relatives of erbB, the gene encoding the epidermal growth factor receptor (EGFR). Genomic analysis of primary tumors revealed HER2 gene amplification and overexpression in breast and ovarian adenocarcinomas and demonstrated strong correlation with poor prognosis. Since its validation as the first human oncogene, HER2 has been intensively investigated as a target for therapeutic intervention. Nevertheless, it is still poorly understood how HER2 overexpression and enhanced cellular signaling contributes to the development of human cancer. Here we summarize the signaling characteristics of HER2 in regard to its function in tumorigenesis and address recent advances towards the pharmacological intervention in HER2 signaling and anti-cancer therapy.
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10.3233/bd-1999-11102
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pubmed_909_2955
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Membranoproliferative glomerulonephritis (MPGN) has been classified based on its pathogenesis into immune complex-mediated and complement-mediated MPGN. The immune complex-mediated type is secondary to chronic infections, autoimmune diseases or monoclonal gammopathy. There is a paucity of data on MPGN associated with autoimmune diseases. We reviewed the Mayo Clinic database over a 10-year period and identified 12 patients with MPGN associated with autoimmune diseases, after exclusion of systemic lupus erythematosus. The autoimmune diseases included rheumatoid arthritis, primary Sjögren's syndrome, undifferentiated connective tissue disease, primary sclerosing cholangitis and Graves' disease. Nine of the 12 patients were female, and the mean age was 57.9 years. C4 levels were decreased in nine of 12 patients tested. The serum creatinine at time of renal biopsy was 2.2 ± 1.0 mg/dl and the urinary protein was 2,850 ± 3,543 mg/24 h. Three patients required dialysis at the time of renal biopsy. Renal biopsy showed an MPGN in all cases, with features of cryoglobulins in six cases; immunoglobulin (Ig)M was the dominant Ig, and both subendothelial and mesangial electron dense deposits were noted. Median follow-up was 10.9 months. Serum creatinine and proteinuria improved to 1.6 ± 0.8 mg/dl and 428 ± 677 mg/24 h, respectively, except in 3 patients with end-stage renal disease. In summary, this study describes the clinical features, renal biopsy findings, laboratory evaluation, treatment and prognosis of MPGN associated with autoimmune diseases.
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10.1007/s40620-014-0049-0
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pubmed_317_15895
|
A new PC(carbene)P pincer ligand with 2,3-benzo[b]thiophene linkers connecting the flanking dialkyl phosphine donors to the central carbene can be attached to Ir(I). The chloro derivative reacts with N2O with loss of N2 to form an iridaepoxide species by addition of an oxygen atom to the Ir═C linkage. This compound reacts with H2 to afford the oxidative addition product, in which the hydride ligands are trans to the Ir-O bond. Heating this dihydride results in slow release of H2O; kinetic and spectroscopic studies show that conversion of the dihydride to its isomer, in which the hydrides are cis to the Ir-O bond, is required for H2O elimination to take place. Together, these reactions constitute the stoichiometric conversion of N2O and H2 to N2 and H2O; further mechanistic studies suggest ways to make the system catalytic.
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10.1021/ja512602m
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pubmed_884_318
|
On the basis of favorable results recently reported in literature with cimetidine in the prevention and therapy of upper gastrointestinal haemorrhages, the Authors have treated a patient with severe haemorrhage from acute gastric ulcer arised after jejunum-ileal massive resection for mesenteric infarction. Result was very good, with stop of haemorrhage and quickly healing of the lesion. This clinical report is of interest particularly in view of high mortality of postoperative haemorrhagic acute gastropaties with therapeutic means, medical or surgical, just now available. At last the particular physiopathological aspects of the case suggested some considerations about mechanisms of action of the Cimetidine.
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pubmed_884_318
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pubmed_590_20788
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The selection of the right strains is of fundamental important to the success of the algae-based oil industry. From the six newly isolated microalgae strains tested for growth, fatty acid methyl ester (FAME) profiles and biodiesel properties, Scenedesmus SDEC-8, with favorable C16:0 fatty acids (73.43%), showed the best combined results. Then, morphological and molecular identification were examined. From the three wastewaters samples, Scenedesmus SDEC-8 showed good ability to yield oil and remove nutrients, which were comparable with other reports. In b artificial wastewater (TN 40 mg L(-1), TP 8 mg L(-1)), Scenedesmus SDEC-8 achieved the highest value of lipid productivity (53.84 mg L(-1) d(-1)), MUFA content (35.35%) and total FAME content (59.57±0.02 mg g(-1) DW), besides higher removal efficiencies of TN (99.18%) and TP (98.86%) helped effluent directly discharge and smaller dilution factor of N, P (3.3 and 9) which was good for lessening water utilization.
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pubmed_590_20788
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pubmed_4_18649
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Existing clinical intravascular imaging modalities are not capable of accurate detection of critical plaque pathophysiology in the coronary arteries. This study reports the first intravascular catheter combining intravascular ultrasound (IVUS) with multispectral fluorescence lifetime imaging (FLIm) that enables label-free simultaneous assessment of morphological and biochemical features of coronary vessels in vivo. A 3.7 Fr catheter with a fiber-optic channel was constructed based on a 40 MHz clinical IVUS catheter. The ability to safely acquire co-registered FLIm-IVUS data in vivo using Dextran40 solution flushing was demonstrated in swine coronary arteries. FLIm parameters from the arterial wall were consistent with the emission of fluorophores present in healthy arterial wall (collagen, elastin). Additionally, structural and biochemical features from atherosclerotic lesions were acquired in ex vivo human coronary samples and corroborated with histological findings. Current results show that FLIm parameters linked to the amount of structural proteins (e.g. collagen, elastin) and lipids (e.g. foam cells, extracellular lipids) in the first 200 μm of the intima provide important biochemical information that can supplement IVUS data for a comprehensive assessment of plaques pathophysiology. The unique FLIm-IVUS system evaluated here has the potential to provide a comprehensive insight into atherosclerotic lesion formation, diagnostics and response to therapy.
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10.1038/s41598-017-08056-0
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pubmed_310_10817
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Studies of the primary care treatment of depressed elderly patients are constrained by limited time and space and by subject burden. Research assessments must balance these constraints with the need for obtaining clinically meaningful information. Due to the wide-ranging impact of depression, assessments should also focus on suicidality, hopelessness, substance abuse, anxiety, cognitive functioning, medical comorbidity, functional disability, social support, personality, service use and satisfaction with services. This paper describes considerations concerning the assessment selection process for primary care studies, using the PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) study as an example. Strategies are discussed for ensuring that data are complete, valid and reliable.
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10.1002/gps.469
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pubmed_1131_16552
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Purpose To determine if hepatic gadolinium deposition occurs in pediatric patients with iron overload but normal renal and hepatic function who undergo gadolinium-based contrast agent (GBCA)-enhanced magnetic resonance (MR) imaging. Materials and Methods Design and execution of this study was approved by the Ethical Committee of Institute for Research in Maternal and Child Health Burlo Garofolo of Trieste (reference no. 1105/2015). Because of the retrospective nature of the study, the requirement to obtain informed consent was waived. Twenty-one recipients of allogeneic hematopoietic stem cell transplants who underwent GBCA-enhanced MR imaging for suspected infection or relapse followed by liver biopsy comprised the study group. The number of GBCA-enhanced MR examinations and cumulative gadolinium dose for each patient was analyzed by comparing liver histologic analysis and iron and gadolinium liver concentration (GLC). Eight patients had siderosis and underwent chelation therapy. The study group was compared with four control patients who were never exposed to GBCA. Statistical analysis was performed with Spearman rank coefficient for correlation. Results All 21 patients had positive correlations between GLC and total GBCA dose (r = 0.4486; P < .05) and between GLC and liver iron concentration (r = 0.56; P < .05). Patients who underwent deferoxamine therapy had a significant reduction of GLC (from 0.64 μg/g ± 0.29 to 0.20 μg/g ± 0.17 [standard deviation]; P < .05). Conclusion In the presence of siderosis, a transmetallation mechanism may be set off between ferric ion and gadoterate meglumine. Deferoxamine appears capable of binding to gadolinium ion. Further studies of the safety of GBCAs in severe siderosis are needed. Chelation should be considered in patients with iron overload and a history of GBCA exposure. © RSNA, 2016.
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10.1148/radiol.2016152846
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pubmed_270_17128
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Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathological characteristics. The most accredited hypothesis is that both CD and UC result from a deregulated mucosal immune response to normal constituents of the gut microflora. Evidence, however, indicates that the main pathological processes in these two diseases are distinct. In CD, the tissue-damaging inflammatory reaction is driven by activated type 1 helper T-cell (Th1), whereas a humoral response predominates in UC. Consistently, a marked accumulation of macrophages making interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC mucosa. Preliminary studies also indicate that administration of a monoclonal antibody blocking the IL-12/p40 subunit can be useful to induce and maintain clinical remission in CD patients. Notably, the recently described IL-23 shares the p40 subunit with IL-12, raising the possibility that the clinical benefit of the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23 activity. This review summarizes the current information on the expression and functional role of IL-12 and IL-12-associated signaling pathways both in patients with CD and experimental models of colitis, thus emphasizing major differences between IL-12 and IL-23 activity on the development of intestinal inflammation.
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10.3748/wjg.v12.i35.5606
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pubmed_492_1657
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OBJECTIVE
• To evaluate the consequences on male sexual function of intraprostatic injection of botulinum toxin type A (BoNT/A) as a treatment for benign prostatic hyperplasia (BPH). Although BoNT/A is effective in decreasing symptoms of BPH, neuronal impairment caused by the neurotoxin might affect emission/ejaculation. These aspects have not been evaluated before.
PATIENTS AND METHODS
• In all, 16 sexually active men aged >60 years with BPH/benign prostatic enlargement (BPE), International Prostate Symptom Score (IPSS) ≥8 and a maximum urinary flow rate (Q(max)) <15 mL/s refractory to standard medical therapy volunteered for the study. • Patients were injected transrectally, under ultrasonographic control, with 200 U of BoNT/A in the prostate. Evaluation was carried out at baseline and 1, 3 and 6 months post-treatment. Erectile function was evaluated using the International Index of Erectile Function - Short Form (IIEF-5) questionnaire. • Orgasmic/ejaculatory function and libido were evaluated using questions 9, 10, 11 and 12 of the IIEF - Long Form. Total testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were also investigated.
RESULTS
• The mean age was 73 ± 6 years. The IIEF-5 score was 16.5 ± 6 at baseline, 15.7 ± 6 at 1 month, 16.6 ± 6 at 3 months and 15.7 ± 5 at 6 months (differences nonsignificant). • The score for ejaculatory/orgasmic function (questions 9 and 10) remained fairly constant from baseline to the sixth month, 8.3 ± 1.9 and 8 ± 2.1 respectively. • The sexual desire score (questions 11 and 12 of the IIEF) also remained little changed from baseline (5.9 ± 1.6) to month 6 (6.1 ± 2). Total serum testosterone, LH, FSH and prolactin did not change during the study.
CONCLUSIONS
• Intraprostatic injection of BoNT/A in patients with BPE does not impair erectile, orgasmic or ejaculatory functions and does not change libido. • The male hormonal profile is not altered by BoNT/A injection. This facilitates the acceptance of BoNT/A as a treatment for BPH/BPE lower urinary tract symptoms (LUTS) refractory to standard medical management.
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10.1111/j.1464-410X.2010.09841.x
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pubmed_962_15980
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The peptidoglycan (PG) bacterial cell wall glycoconjugate has been well known as a strong immunopotentiator. Partial structures of PG were chemically synthesized for elucidation of precise biological activities. Effective construction of distinct repeating glycans of PG was accomplished by the coupling of a key disaccharide glucosaminyl-beta(1-4)-muramic acid unit. Stereoselective glycosylation of disaccharide units was achieved by neighboring group participation of the N-Troc (Troc = 2,2,2-trichloroethoxycarbonyl) group and appropriate reactivity of N-Troc-glucosaminyl trichloroacetimidate. By using an efficient synthetic strategy, mono-, di-, tetra- and octasaccharide fragments of PG were synthesized in high yields. The biological activity of synthetic fragments of PG was evaluated by induction of tumor necrosis factor-alpha (TNF-alpha) from human monocytes, and toll-like receptor 2 (TLR2) and Nod2 dependencies by using transfected HEK293 cells, respectively. Here we reveal that TLR2 was not stimulated by the series of synthetic PG partial structures, whereas Nod2 recognizes the partial structures containing the MDP moiety.
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10.1039/b511866b
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pubmed_379_20856
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The number of orthodromically evoked population spikes was used to classify brain slice tissue from the dentate gyrus of temporal lobe epileptic patients as "more excitable" (multiple population spikes) or "less excitable" (a single population spike). During orthodromic stimulation, "more excitable" tissue exhibited less paired-pulse depression in comparison to "less excitable" tissue. During antidromic stimulation, both multiple population spikes and paired-pulse depression were observed in "more excitable" tissue. "Less excitable" tissue exhibited a single antidromic spike and often no antidromically evoked paired-pulse depression. The strength of antidromic paired-pulse depression was correlated positively with the number of antidromic spikes and was correlated negatively with orthodromic paired-pulse depression. Although orthodromic and antidromic paired-pulse depression were correlated to the number of orthodromically evoked population spikes, this correlation was not as strong as that between orthodromic paired-pulse depression, antidromic paired-pulse depression, and number of antidromically evoked population spikes. The antidromic paired-pulse depression observed in tissue exhibiting antidromically evoked multiple population spikes was enhanced rather than blocked by bicuculline. In addition, the blockade of the antidromic paired-pulse depression by CNQX indicated that this inhibition is mediated by an AMPA-type glutamatergic synapse. We suggest that alterations in circuitry occur in the dentate gyrus of some temporal lobe epileptic patients and were manifested by both a loss of inhibitory input as well as an increase of inhibition, which was dependent on the pathway of stimulation. The results of pairing antidromic and orthodromic stimuli were consistent with these conclusions.
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10.1002/hipo.450040508
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pubmed_301_10035
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The specific role of the Delta opioid receptor (DOR), in opioid-induced respiratory depression in the ventral respiratory group (VRG) is largely unknown. Here, we sought to determine (1) the relationship between DOR-immunoreactive (ir) boutons, bulbospinal and functionally identified respiratory neurons in the VRG and (2) the effects of microinjection of the selective DOR agonist, D-Pen 2,5-enkephalin (DPDPE), into different subdivisions of the VRG, on phrenic nerve discharge and mean arterial pressure. Following injections of retrograde tracer into the spinal cord or intracellular labelling of respiratory neurons, in Sprague-Dawley rats, brainstem sections were processed for retrograde or intracellular labelling and DOR-ir. Bulbospinal neurons were apposed by DOR-ir boutons regardless of whether they projected to single (cervical or thoracic ventral horn) or multiple (cervical and thoracic ventral horn) targets in the spinal cord. In the VRG, a total of 24 +/- 5% (67 +/- 13/223 +/- 49) of neurons projecting to the cervical ventral horn, and 37 +/- 3% (96 +/- 22/255 +/- 37) of neurons projecting to the thoracic ventral horn, received close appositions from DOR-ir boutons. Furthermore, DOR-ir boutons closely apposed six of seven intracellularly labelled neurons, whilst the remaining neuron itself possessed boutons that were DOR-ir. DPDPE was microinjected (10 mM, 60 nl, unilateral) into regions of respiratory field activity in the VRG of anaesthetised, vagotomised rats, and the effects on phrenic nerve discharge and mean arterial pressure were recorded. DPDPE depressed phrenic nerve amplitude, with little effect on phrenic nerve frequency in the Bötzinger complex, pre-Bötzinger complex and rVRG, the greatest effects occurring in the Bötzinger complex. The results indicate that the DOR is located on afferent inputs to respiratory neurons in the VRG. Activation of the DOR in the VRG is likely to inhibit the release of neurotransmitters from afferent inputs that modulate the pattern of activity of VRG neurons.
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10.1016/s0306-4522(03)00591-8
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pubmed_20_11970
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Compound L, as the procedural sensor for the detection of Cu2+ and Hg2+, was designed and synthesized based on the coumarin-modified rhodamine derivative. The structure of compound L was characterized by NMR, high resolution mass spectrometry and infrared method. Its sensing behavior toward various metal ions was investigated with absorbance methods. The study found that L had good selectivity and sensitivity for Cu2+. When addition of various metal ions (Zn2+, Hg2+, Cu2+, Fe3+, Cd2+, CO2+, Ni2+, Mg2+, Ca2+, Al3+, La3+, K+, Na+, Mn2+, Pb2+ and Ag+), only Cu2+ could induce a visible change of solution from colourless to pink and a new absorption band centered at 534 nm appear, which indicated that compound L could be used for the naked eye detection of Cu2+. From UV titration, the detection limit was about 1.9 X 10(-8) mol x L(-1). Test strips based on L were fabricated, and this test strips could act as a convenient and efficient Cu2+ test kit. The binding ratio of the complex of L-Cu2+ was 1:1 according to the Job's plot and high resolution mass spectrometer (HRMS) experiments. Moreover, Upon addition of 1 equiv. EDTA to the mixture of L and Cu2+ in DMSO solution, colour changed from pink to almost colourless, indicating that the EDTA replaced the receptor L to coordinate with Cu2+. Therefore, L could be classified as a reversible sensor for Cu2+. In addition, when adding Hg2+ to L-Cu2+ complexes, a visible change of solution from pink to colourless was observed, while other metal ions didn't cause this change. Thus, L-Cu2+ complex also could be used for the naked eye recognition of Hg2+, and the detection limit was calculated about 2.9 x 10(-1) mol x L(-1) according to the UV titration. Consequently, this procedural sensor L could be use for the orderly naked eye recognition of Cu2+ and Hg2+.
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pubmed_20_11970
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pubmed_54_14105
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Disorders of the glucose-6-phosphatase (G6Pase)/glucose-6-phosphate transporter (G6PT) complexes consist of three subtypes: glycogen storage disease type Ia (GSD-Ia), deficient in the liver/kidney/intestine-restricted G6Pase-α (or G6PC); GSD-Ib, deficient in a ubiquitously expressed G6PT (or SLC37A4); and G6Pase-β deficiency or severe congenital neutropenia syndrome type 4 (SCN4), deficient in the ubiquitously expressed G6Pase-β (or G6PC3). G6Pase-α and G6Pase-β are glucose-6-phosphate (G6P) hydrolases with active sites lying inside the endoplasmic reticulum (ER) lumen and as such are dependent upon the G6PT to translocate G6P from the cytoplasm into the lumen. The tissue expression profiles of the G6Pase enzymes dictate the disease's phenotype. A functional G6Pase-α/G6PT complex maintains interprandial glucose homeostasis, while a functional G6Pase-β/G6PT complex maintains neutrophil/macrophage energy homeostasis and functionality. G6Pase-β deficiency is not a glycogen storage disease but biochemically it is a GSD-I related syndrome (GSD-Irs). GSD-Ia and GSD-Ib patients manifest a common metabolic phenotype of impaired blood glucose homeostasis not shared by GSD-Irs. GSD-Ib and GSD-Irs patients manifest a common myeloid phenotype of neutropenia and neutrophil/macrophage dysfunction not shared by GSD-Ia. While a disruption of the activity of the G6Pase-α/G6PT complex readily explains why GSD-Ia and GSD-Ib patients exhibit impaired glucose homeostasis, the basis for neutropenia and myeloid dysfunction in GSD-Ib and GSD-Irs are only now starting to be understood. Animal models of all three disorders are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches, including gene therapy.
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10.1007/s10545-014-9772-x
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pubmed_1123_24078
|
INTRODUCTION
The objective of this work is to present results obtained in a three-year study focussed on micturition, defecation and sexual disorders in women of active age.
METHODS
The monitored set consisted of 33 female patients treated in 2004-2009 for unstable pelvic fracture (B-type or C-type according to AO classification). Out of them 25 patients suffered B-type fracture and 8 patients suffered C-type fracture. Their age ranged between 17 and 55 years (the average age was 32 years). Anamnestic data were obtained based on UIQ, UDI and PISQ12 questionnaires. The non-parametric Mann-Whitney U-test was used for answers to individual questions representing nominal/ordinal variables. After finding a statistically significant difference in answers between both groups of patients, it was investigated by means of Pearson Chi2-test which answers are behind this statistically significant difference. If the number of answers to any question was less than 5, the exact Fisher test was used. In the event the rate equalled 0, Haldane correction was applied. All tests were considered statistically significant if the significance level was below 5%.
RESULTS
The occurrence of urologic problems was higher in the B-type fracture patients (84% vs. 50%), however, afflictions were more severe in the C-type fracture patients. Intestinal problems were more frequent in the C-type fracture patients (75% vs. 52%) and they were also more severe. Also sexual problems were more frequent in the C-type fracture patients (75% vs. 40%), although according to individual answers it was not possible to state that their sexual life was unequivocally worse.
CONCLUSION
The analysis of comparison of micturition, sexual and defecation problems in patients one year after the unstable pelvic fracture showed in some respects higher problems in the patients who had suffered the C-type fracture. However, more important are the following observations, generally related to unstable pelvic fracture patients: 1. The occurrence of micturition, sexual and defecation problems was unexpectedly high; 2. Without active examination by a traumatologist during the after-treatment "minor" problems may escape his/her attention and may negatively affect life of each individual patient in the longer run; 3. A targeted method of detection of problems by means of questionnaires could lead to their disclosure; 4. A urologist, urogynaecologist, sexologist and proctologist have an indisputable place in the treatment of women who suffered a severe pelvic trauma.
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pubmed_1123_24078
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pubmed_172_13060
|
The effects of the thromboxane antagonist BM 13.177 (5 mg kg-1 + 0.15 mg kg-1 min-1) was investigated on the ventricular arrhythmias that result from coronary artery occlusion and reperfusion in anaesthetised open-chest greyhounds. BM 13.177 markedly reduced the severity and incidence of arrhythmias resulting from ischaemia; the number of ventricular ectopic beats was reduced from 1,084 +/- 159 (in controls) to 544 +/- 179 (in dogs given BM 13.177) and the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF) were reduced from 86 to 22% and from 30 to 10% respectively. Following reperfusion the incidence of VF was 86% in controls and 44% in dogs given BM 13.177. Thus the total incidence of VF during the combined ischaemia-reperfusion insult was significantly reduced by treatment with BM 13.177 from 90% (in control dogs) to 50%. These results lend further support to the hypothesis that thromboxane is involved in the genesis of arrhythmias and that blockade of thromboxane receptors may be a suitable approach to antiarrhythmic therapy under conditions of ischaemia and reperfusion.
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10.1016/0014-2999(87)90021-5
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pubmed_805_1047
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In hot and dry weather, terrestrial snails withdraw into their shells and remain inactive for long periods of time. This phenomenon, known as aestivation, is the basis for our investigation of the effects of behavioral inactivity on neuronal structure. Several recent studies have shown that the level of afferent electrical activity is an important modifier of structure, even in adult animals. During aestivation, sensory stimulation (and therefore presumably afferent activity) is greatly reduced. We have tested the hypothesis that long-term behavioral inactivity causes a regression of dendrites. Two identified neurons of Achatina fulica were selected for study, the giant cerebral neuron (GCN) and RPall. The cells were viewed on 10-micron-thick sections after intracellular injection of hexamminecobalt chloride. They were reconstructed by using a video camera attached to a light microscope and a digitizing board resident in a microcomputer. Snails in the aestivated group were completely inactive for 8 weeks beginning at age 23 weeks. A quantitative analysis showed that there were no significant differences in either cell, in either the total mass of material or its distribution, comparing cells from the Aestivated snails and cells from the Younger snails (age 23 weeks) and the Older snails (age 33 weeks). These results suggest limits to the modifiability of neuronal structure.
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10.1002/cne.903030113
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pubmed_379_5306
|
The results of typing of 121 strains in the Mycobacterium tuberculosis complex by PFGE are presented. Every isolate from patients in Scotland over a 3-month period for M. tuberculosis and for 1 year for M. bovis were included along with several laboratory strains including those of BCG. The PFGE results suggest that the population structure of all the strains in this complex is distinctly simple with limited genetic diversity and also suggest that M. bovis is not a distinct species.
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10.1017/s0950268800052006
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pubmed_368_12722
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STUDY DESIGN
A retrospective study of clinical cases.
PURPOSE
To evaluate the efficacy of continuous irrigation and drainage for early postoperative deep wound infection after posterior instrumented spinal fusion.
SUMMARY OF BACKGROUND DATA
Aggressive debridement and irrigation has been recommended to treat postoperative wound infections after instrumented spinal fusion. However, this method of management, indicating repeating visits to the operating room until the wound is clean enough for closure, often results in prolonged hospitalization, increased cost, and sometimes compromise of the desired outcome. We hypothesize that repeat visits to the operating room for debridements can be avoided by aggressive debridements and primary closure with continuous irrigation and drainage for postoperative wound infections.
METHODS
From 2004 to 2009, 23 patients with early postoperative deep wound infections after spinal fusion with instrumentation were surgically treated with thorough debridement and primary closure with continuous irrigation and drainage. All patients were followed up for 30.6 months (range, 24-54 mo).
RESULTS
The mean duration of irrigation was 12.0 days (range, 7-16 d). In 21 patients (91.3%), the wound healed after continuous irrigation. The removal of the instrumentation or cages was not required in any case. Spinal fusion was achieved in all cases, except 1, where the patient developed a pseudoarthrosis at the L4-L5 level after L4-S1 fusion. The mean ODI for these 23 patients improved significantly from 53.4±18.7 preoperatively to 18.3±11.2 at the final follow-up visit (P<0.001). The mean JOA scores increased significantly from 15.5±4.1 preoperatively to 24.3±3.8 at the final follow-up (P<0.001).
CONCLUSIONS
Continuous irrigation and drainage is an effective and safe method for the treatment of early postoperative deep wound infection after posterior instrumented spinal fusion.
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10.1097/BSD.0000000000000122
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pubmed_938_2455
|
It is well known that the duodenum of mice or rats infected with Fibricola seoulensis shows atrophy of villi (shortening, blunting, widening, fusion) and hyperplasia of crypts. This study was performed to observe healing process of these pathological changes after deworming with anthelmintic treatment. Albino rats infected each with 1,000 metacercariae of F. seoulensis were treated with single dose of 10 mg/kg praziquantel on day 15 post-infection. On day 1, 3, 5, 7, 15, 21 and 28 after the treatment, they were sacrificed and their duodenums were histopathologically studied. Control (uninfected) rats showed their normal finger-like projections of duodenal villi and well arranged crypts. In comparison, untreated (infected) controls revealed severe mucosal changes characteristic of villous atrophy and crypt hyperplasia in their duodenum. The damaged duodenal mucosa was found to restore its normal morphology after praziquantel treatment; until day 3 post-treatment the mucosa was severely atrophied; on day 5 long and slender villi sometimes appeared among the fused and stout ones; after day 15 the villi were in their normalizing process. From this experiment, it was shown that the mucosal changes in the duodenum of rats caused by F. seoulensis infection were completely reversible in 21-28 days after anthelmintic treatment.
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10.3347/kjp.1989.27.1.35
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pubmed_928_20811
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The clinical and radiologic results of a consecutive series of 59 patients (69 hips) who had primary total hip arthroplasty using cementless prostheses was studied. Harris-Galante acetabular and femoral prostheses, which have a porous fiber-metal mesh coating intended to encourage bone ingrowth fixation, were used in all cases. Two femoral components were revised during the follow-up period, one for aseptic loosening and the other for late septic loosening. In the remaining 67 hips, the average Harris hip score rose from a preoperative 52 to 94 at the last follow-up examination (average follow-up period, 44 months). Eighty-eight percent of these hips had an excellent result (Harris hip score of 90 or more). Radiologic analysis demonstrated that all the acetabular components were stable. Eighty-three percent of the femoral components appeared to have stable bone ingrowth fixation, five components (7%) had stable fibrous ingrowth, and seven (10%) were unstable. Parallel radiodense lines were seen around the smooth portion of the stem in 93% of hips, but this finding appeared to have no clinical importance. Significant stress shielding of the proximal femur was seen in 16% of hips. Endosteal lysis of the distal femur occurred in 22% of hips, including large lesions in two patients who will require future revision surgery because of femoral diaphysis weakening. Femoral lysis was not associated with hip or thigh pain and was most common in young, male patients who had high activity levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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10.1016/s0883-5403(07)80028-3
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pubmed_608_8239
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Alzheimer's disease (AD) is characterized by alterations of amyloid precursor protein (APP) metabolism, accumulation of amyloid peptides (A), hyperphosphorylation of Tau proteins and also by sphingolipids disturbances. These changes lead to oxidative stress, mitochondria dysfunction, synaptic loss and neuro-inflammation. It is known that A may promote ceramides formation and reversely, ceramides could stimulate A peptides release. However, the effect of ceramide and sphingosine-1-phosphate (S1P) on APP metabolism has not been fully elucidated. In this study we investigated the role of ceramide and S1P on APP metabolism. Moreover, the effect of ceramide and SEW 2871 (agonist for S1P receptor-1) on Sirt1 (NAD+-dependent nuclear enzyme responsible for stress response) gene expression under A toxicity was analyzed. Experiments were carried out using pheochromocytoma cells (PC-12) transfected with: an empty vector (used as a control), human wild-type APP gene (APPwt) and Swedish mutated (K670M/N671L) APP gene (APPsw). Our results indicated that C2-ceramide significantly decreased the viability of the APPwt, APPsw as well as empty vector-transfected PC12 cells. It was observed that C2-ceramide had no significant effect on the mRNA level of - and -secretase in APPwt and APPsw cells. However, it significantly decreased transcription of -secretase in control cells. Results also showed a significant increase in Psen1 (crucial subunit of -secretase) gene expression in APPsw cells after incubation with C2-ceramide. We observed that SEW 2871 significantly upregulated the mRNA level of -secretase in control-empty vector-transfected cells subjected to C2-ceramide toxicity. The same tendency, though insignificant, was observed in APPwt and APPsw cells. Moreover, SEW 2871 enhanced the mRNA level of -secretase and Psen1 in APPsw cells after C2-ceramide treatment. Additionally, SEW 2871 significantly upregulated a gene expression of Sirt1 in APPwt and also APPsw cells subjected to C2-ceramide toxicity. Furthermore, it was observed that SEW 2871 significantly enhanced the viability of all investigated cells' lines probably through its positive influence on Sirt1.
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10.5114/fn.2018.78700
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pubmed_692_12246
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In ion beam radiotherapy, PET-based treatment verification provides a consistency check of the delivered treatment with respect to a simulation based on the treatment planning. In this work the region-based MLEM reconstruction algorithm is proposed as a new evaluation strategy in PET-based treatment verification. The comparative evaluation is based on reconstructed PET images in selected regions, which are automatically identified on the expected PET images according to homogeneity in activity values. The strategy was tested on numerical and physical phantoms, simulating mismatches between the planned and measured β+ activity distributions. The region-based MLEM reconstruction was demonstrated to be robust against noise and the sensitivity of the strategy results were comparable to three voxel units, corresponding to 6 mm in numerical phantoms. The robustness of the region-based MLEM evaluation outperformed the voxel-based strategies. The potential of the proposed strategy was also retrospectively assessed on patient data and further clinical validation is envisioned.
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10.1088/0031-9155/59/22/6979
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pubmed_1003_409
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DNA microarrays are a powerful experimental tool for the detection of specific genomic sequences and are invaluable to a broad array of applications: clinical diagnosis, personalized medicine, drug research and development, gene therapy, food control technologies, and environmental sciences. Alloimmunization to human platelet antigens (HPAs) is commonly responsible for neonatal alloimmune thrombocytopenia, post-transfusional purpura and platelet transfusion refractoriness. Using DNA microarrays, we developed a diagnosis to type the biallelic HPA-1 platelet group. The region for the human genomic DNA sequence that contains the polymorphism responsible for HPA-1 alleles was amplified by polymerase chain reaction (PCR). The expected DNA fragments were hybridized on DNA microarrays, and the data were analyzed using specially developed software. Our initial results show that the two HPA-1 antigens polymorphisms containing a single base difference were detected using DNA microarrays.
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10.1007/s10544-005-1593-0
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pubmed_648_13295
|
We have established a novel, simple, and highly reproducible method to generate skeletal muscle cells from mouse skin. Small pieces of skin from the back of mice were cultured in extracellular material-coated dishes in typical culture medium for about 3 weeks. Myotubes formed after about a week, grew into twitching myotubes, and became twitching myotube clumps after 3 weeks. Skeletal muscle cells are formed spontaneously with no induction. Myotubes were immunologically positive for myosin heavy chains, MyoD, and myogenin. Ultrastructural analysis revealed the presence of the sarcomere structure. Furthermore, PAX7+/MyoD- muscle stem cells proliferated around these myotubes, and MyoD+/myogenin+/MHC-- cells were also observed. Moreover, we investigated the formation of skeletal muscle cells from the sialidosis mouse skin, and showed that it is decreased compared to that of the wild type. Our method to generate skeletal muscle cells from skin is thought to be useful for the investigation of muscle cell development and muscle-related disorders.
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10.1016/j.bbrc.2019.12.067
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pubmed_522_22601
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Obese subjects exhibit a delay in insulin action and delivery of insulin to muscle interstitial fluid during glucose/insulin infusion. The aim of the present study was to follow the distribution of insulin to skeletal muscle after an oral glucose load in obese subjects. We conducted an oral glucose tolerance test (OGTT) in 10 lean and 10 obese subjects (BMI 23 +/- 0.6 vs. 33 +/- 1.2 kg/m(2); P < 0.001). Insulin measurements in muscle interstitial fluid were combined with forearm arteriovenous catheterization and blood flow measurements. In the obese group, interstitial insulin was significantly (35-55%) lower than plasma insulin (P < 0.05) during the 1st h after the OGTT, whereas in lean subjects, no significant difference was found between interstitial and plasma insulin levels during the same time period. The permeability surface area product for glucose, representing capillary recruitment, increased in the lean group (P < 0.05) but not in the obese group (NS). Obese subjects had a significantly higher plasma insulin level at 90-120 min after oral glucose (398 +/- 57 vs. 224 +/- 37 pmol/l in control subjects; P < 0.05). The significant gradient between plasma insulin and muscle interstitial insulin during the first hour after OGTT suggests a slow delivery of insulin in obese subjects. The hindered transcapillary transport of insulin may be attributable to a defect in insulin-mediated capillary recruitment.
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10.2337/diabetes.54.1.152
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pubmed_374_11637
|
BACKGROUND
Inflammation is one of a main reason for colon cancer progression and poor prognosis. The high-mobility group box-1 (HMGB1) and glutathione peroxidase 4 (GPX4) are responsible for inflammation, but the relationship between HMGB1 and GPX4 remains unknown about inflammation in colon cancer.
METHODS
RT-qPCR was carried out to investigate the expression of IL1β, IL6 and TNFα in colon cancer cells stimulated with LPS or siHMGB1. To observe the relationship between HMGB1, GPX4 and inflammation or ROS, Western blot assays were adopted. Pull-down, CoIP and immunohistochemistry assays were performed to further investigate the molecular mechanisms of HMGB1 and GPX4 in colon cancer.
RESULTS
We report that HMGB1 mediates lipopolysaccharide (LPS)-induced inflammation in colon cancer cells. Mechanistically, acetylated HMGB1 interacts with GPX4, negatively regulating GPX4 activity. Furthermore, by utilizing siHMGB1 and its inhibitor, our discoveries demonstrate that HMGB1 knockdown can inhibit inflammation and reactive oxygen species (ROS) accumulation via NF-kB.
CONCLUSION
Collectively, our findings first demonstrate that acetylated HMGB1 can interact with GPX4, leading to inflammation, and providing therapeutic strategies targeting HMGB1 and GPX4 for colon cancer.
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10.1186/s12935-020-01289-6
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pubmed_140_22799
|
Mesenchymal stem cells (MSCs) has been used as one of the new cell sources in osteochondral tissue engineering. It has been well known that control of their differentiation into chondrocytes plays a key role in developing engineered cartilages. Therefore, this study aims to develop a fundamental protocol to control the differentiation and proliferation of MSCs to construct an engineered cartilage. We compared the effects of three different culture conditions on cell proliferation, extracellular matrix formation and the mechanical response of engineered cartilage constructed using a collagen-based hybrid scaffold and human MSCs. The experimental results clearly showed that the combined culture condition of the chondrogenic differentiation culture and the chondrocyte growth culture exhibited statistically significant cell proliferation, ECM formation and stiffness responses as compared to the other two combinations. It is thus concluded that the combination of the differentiation culture with the subsequent growth culture is recommended as the culture condition for chondrogenic tissue engineering using hMSCs.
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10.1007/s10856-019-6321-z
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pubmed_833_3396
|
A new organizational species is emerging--the integrated health care delivery system. Aligned with both the anticipated provisions of federal and state health care reform initiatives and emerging purchaser demands, integrated delivery systems could dominate many health care markets by the end of this decade. Integration is both the defining feature and key imperative of such systems. Because of the unique position of boards, governance is potentially the ultimate integrator. Yet little attention had been focused on integrated delivery system governance. Accordingly, this article will address the governance of integrated delivery systems through three questions: (1) What are the distinguishing characteristics of integrated health care delivery systems? (2) What are the distinctive issues and challenges associated with governing integrated delivery systems? and (3) What different forms of governance can be employed by these systems and what factors influence the effectiveness of these forms?
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pubmed_833_3396
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pubmed_166_7110
|
BACKGROUND
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic progressive or relapsing and remitting disease that usually causes weakness and sensory loss. The symptoms are due to autoimmune inflammation of peripheral nerves. CIPD affects about 2 to 3 per 100,000 of the population. More than half of affected people cannot walk unaided when symptoms are at their worst. CIDP usually responds to treatments that reduce inflammation, but there is disagreement about which treatment is most effective.
OBJECTIVES
To summarise the evidence from Cochrane systematic reviews (CSRs) and non-Cochrane systematic reviews of any treatment for CIDP and to compare the effects of treatments.
METHODS
We considered all systematic reviews of randomised controlled trials (RCTs) of any treatment for any form of CIDP. We reported their primary outcomes, giving priority to change in disability after 12 months.Two overview authors independently identified published systematic reviews for inclusion and collected data. We reported the quality of evidence using GRADE criteria. Two other review authors independently checked review selection, data extraction and quality assessments.On 31 October 2016, we searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects (in theCochrane Library), MEDLINE, Embase, and CINAHL Plus for systematic reviews of CIDP. We supplemented the RCTs in the existing CSRs by searching on the same date for RCTs of any treatment of CIDP (including treatment of fatigue or pain in CIDP), in the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus.
MAIN RESULTS
Five CSRs met our inclusion criteria. We identified 23 randomised trials, of which 15 had been included in these CSRs. We were unable to compare treatments as originally planned, because outcomes and outcome intervals differed. CorticosteroidsIt is uncertain whether daily oral prednisone improved impairment compared to no treatment because the quality of the evidence was very low (1 trial, 28 participants). According to moderate-quality evidence (1 trial, 41 participants), six months' treatment with high-dose monthly oral dexamethasone did not improve disability more than daily oral prednisolone. Observational studies tell us that prolonged use of corticosteroids sometimes causes serious side-effects. Plasma exchangeAccording to moderate-quality evidence (2 trials, 59 participants), twice-weekly plasma exchange produced more short-term improvement in disability than sham exchange. In the largest observational study, 3.9% of plasma exchange procedures had complications. Intravenous immunoglobulinAccording to high-quality evidence (5 trials, 269 participants), intravenous immunoglobulin (IVIg) produced more short-term improvement than placebo. Adverse events were more common with IVIg than placebo (high-quality evidence), but serious adverse events were not (moderate-quality evidence, 3 trials, 315 participants). One trial with 19 participants provided moderate-quality evidence of little or no difference in short-term improvement of impairment with plasma exchange in comparison to IVIg. There was little or no difference in short-term improvement of disability with IVIg in comparison to oral prednisolone (moderate-quality evidence; 1 trial, 29 participants) or intravenous methylprednisolone (high-quality evidence; 1 trial, 45 participants). One unpublished randomised open trial with 35 participants found little or no difference in disability after three months of IVIg compared to oral prednisone; this trial has not yet been included in a CSR. We know from observational studies that serious adverse events related to IVIg do occur. Other immunomodulatory treatmentsIt is uncertain whether the addition of azathioprine (2 mg/kg) to prednisone improved impairment in comparison to prednisone alone, as the quality of the evidence is very low (1 trial, 27 participants). Observational studies show that adverse effects truncate treatment in 10% of people.According to low-quality evidence (1 trial, 60 participants), compared to placebo, methotrexate 15 mg/kg did not allow more participants to reduce corticosteroid or IVIg doses by 20%. Serious adverse events were no more common with methotrexate than with placebo, but observational studies show that methotrexate can cause teratogenicity, abnormal liver function, and pulmonary fibrosis.According to moderate-quality evidence (2 trials, 77 participants), interferon beta-1a (IFN beta-1a) in comparison to placebo, did not allow more people to withdraw from IVIg. According to moderate-quality evidence, serious adverse events were no more common with IFN beta-1a than with placebo.We know of no other completed trials of immunosuppressant or immunomodulatory agents for CIDP. Other treatmentsWe identified no trials of treatments for fatigue or pain in CIDP. Adverse effectsNot all trials routinely collected adverse event data; when they did, the quality of evidence was variable. Adverse effects in the short, medium, and long term occur with all interventions. We are not able to make reliable comparisons of adverse events between the interventions included in CSRs.
AUTHORS' CONCLUSIONS
We cannot be certain based on available evidence whether daily oral prednisone improves impairment compared to no treatment. However, corticosteroids are commonly used, based on widespread availability, low cost, very low-quality evidence from observational studies, and clinical experience. The weakness of the evidence does not necessarily mean that corticosteroids are ineffective. High-dose monthly oral dexamethasone for six months is probably no more or less effective than daily oral prednisolone. Plasma exchange produces short-term improvement in impairment as determined by neurological examination, and probably produces short-term improvement in disability. IVIg produces more short-term improvement in disability than placebo and more adverse events, although serious side effects are probably no more common than with placebo. There is no clear difference in short-term improvement in impairment with IVIg when compared with intravenous methylprednisolone and probably no improvement when compared with either oral prednisolone or plasma exchange. According to observational studies, adverse events related to difficult venous access, use of citrate, and haemodynamic changes occur in 3% to17% of plasma exchange procedures.It is uncertain whether azathioprine is of benefit as the quality of evidence is very low. Methotrexate may not be of benefit and IFN beta-1a is probably not of benefit.We need further research to identify predictors of response to different treatments and to compare their long-term benefits, safety and cost-effectiveness. There is a need for more randomised trials of immunosuppressive and immunomodulatory agents, routes of administration, and treatments for symptoms of CIDP.
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10.1002/14651858.CD010369.pub2
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pubmed_938_18355
|
The present study was undertaken to compare the disturbance in bactericidal power of neutrophils in 25 children having protein caloric malnutrition age and sex matched healthy control subjects. There was a highly significant reduction in the percentage of bacteria killed during incubation in children having PCM as compared to healthy control. A direct relationship existed between total serum proteins and bactericidal activity of neutrophils in children having PCM. The impaired bactericidal power of neutrophils can be attributed to impaired synthesis of lysosomal enzymes, glycolytic activity of neutrophils in children having PCM. The exact mechanisms still remain to be elucidated. Decreased bactericidal activity of neutrophils may be one of the mechanisms responsible for infection.
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10.1007/BF02722303
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pubmed_147_14786
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Parvovirus B19 infection is highly prevalent in children and the most common manifestation is a facial rash. In adults, acute polyarthritis and skin rash are often the presenting features. We report three patients with the disease. A 40-year-old female presenting with fever, myalgias and painful swelling of elbows, knees, wrists and feet, with functional limitation, after having a respiratory infection. Additionally, an erythematous skin rash appeared in both extremities. IgM antibodies against Parvovirus B19 were positive. The skin biopsy disclosed a leukocytoclastic vasculitis. The patient was treated with anti-inflammatory drugs and antihistaminics. A 40-year-old female, presenting with skin rash and pain in wrists and hands. IgM antibodies against parvovirus were positive. The patient was treated successfully with acetaminophen. A 38-year-old male with psoriasis, presenting with generalized and progressive polyarthralgia. A Parvovirus viral load determination found 239000 copies of the virus and IgM antibodies were positive. He was successfully treated with non-steroidal anti-inflammatory drugs.
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pubmed_147_14786
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pubmed_603_16998
|
BACKGROUND
Intravaginal practices including vaginal washing have been associated with HIV-1 acquisition. This association may be mediated by mucosal disruption, changes in vaginal flora or genital tract inflammatory responses. Reducing vaginal washing could lower women's risk of HIV-1 acquisition.
METHODS
23 HIV-1 seronegative women who reported current vaginal washing were recruited from a prospective cohort study of high-risk women in Mombasa, Kenya. A theoretical framework including information-motivation-behavioural skills and harm reduction was implemented to encourage participants to reduce or eliminate vaginal washing. At baseline and after 1 month, we evaluated vaginal epithelial lesions by colposcopy, vaginal microbiota by Nugent's criteria and vaginal cytokine milieu using ELISA on cervicovaginal lavage specimens.
RESULTS
The most commonly reported vaginal washing substance was soap with water (N=14, 60.9%). The median frequency of vaginal washing was 7 (IQR 7-14) times per week. After 1 month, all participants reported cessation of vaginal washing (p=0.01). The probability of detecting cervicovaginal epithelial lesions was lower (OR 0.48; 95% CI 0.20 to 1.16; p=0.10) and the likelihood of detecting Lactobacillus by culture was higher (OR 3.71, 95% CI 0.73 to 18.76, p=0.11) compared with baseline, although these results were not statistically significant. There was no change in the prevalence of bacterial vaginosis. Most cytokine levels were reduced, but these changes were not statistically significant.
CONCLUSIONS
A theory-based intervention appeared to have a positive effect in reducing vaginal washing over 1 month. Larger studies with longer follow-up are important to further characterise the effects of vaginal washing cessation on biological markers.
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10.1136/sextrans-2012-050564
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pubmed_540_25990
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Previous event-related potential (ERP) studies reported larger N170, P3, and late positive potential (LPP) amplitudes to sexual than nonsexual stimuli. These ERPs may not be specifically sensitive to processing sexual cues, however, because the sexual stimuli included information beyond sexual cues (e.g., faces, bodies, social interaction) to a greater extent than comparison stimuli. We investigated ERPs to stimuli that focused on sexual and nonsexual body regions, in different states of readiness for activity, to elucidate neural responses involved in processing sexual cues. Forty cisgender, primarily white, undergraduate women who were attracted to men (Mage = 18.6, SD = 0.9) viewed images that varied by male body part (penis, arm) and activity state (rest, poised for activity). Participants viewed 40 images per category (flaccid penises, erect penises, outstretched arms, bent arms). Electroencephalography (EEG) was recorded using a 128-channel net, time-locked to the onset of each image. Using a whole-head cluster-mass approach, we found that the P3 was sensitive to sexual readiness-P3 amplitudes were larger to erect than flaccid penises, but not to bent than outstretched arms. The N170 and LPP components did not show evidence of similarly specific responses to sexual readiness, revealing potential dissociation of different neural processes commonly elicited in response to more complex sexual stimuli. An additional novel finding was that an anterior N270-400 was sensitive to sexual readiness. Findings clarify the brain's rapid responses to sexual stimuli, setting the stage for future research aimed at better understanding the neurocognitive processes that contribute to the coordination of sexual arousal.
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10.1111/psyp.14162
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pubmed_313_16311
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Nowadays, the integrated systems on a plane substrate containing energy harvesting, energy storing, and working units are strongly desired with the fast development of wearable and portable devices. Here, a simple, low cost, and scalable strategy involving ink printing and electrochemical deposition is proposed to fabricate a flexible integrated system on a plane substrate containing an all-solid-state asymmetric microsupercapacitor (MSC), a photoconduct-type photodetector of perovskite nanowires (NWs), and a wireless charging coil. In the asymmetric MSCs, MnO2-PPy and V2O5-PANI composites are used as positive and negative electrodes, respectively. Typical values of energy density in the range of 15-20 mWh cm-3 at power densities of 0.3-2.5 W cm-3 with an operation potential window of 1.6 V are achieved. In the system, the wireless charging coil receives energy from a wireless power transmitter, which then can be stored in the MSC to drive the photoconductive detector of perovskite NWs in sequence. The designed integrated system exhibits a stable photocurrent response comparable with the detector driven by an external power source. This research provides an important routine to fabricate integrated systems.
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10.1021/acsnano.6b06326
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pubmed_663_22773
|
Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations. Methodology is therefore critical. Quantitative studies based on sound methodology strongly indicate that nanomolar levels of cytokine autoantibodies are likely to be involved in a number of "new" syndromes such as acquired immune deficiencies, lung diseases, and certain age-related manifestations. There are many ways in which the autoantibodies could be naturally induced, and they have been experimentally induced with ease. Therefore, a new therapeutic concept of inducing cytokine autoantibodies via anti-cytokine vaccination is currently rapidly emerging.
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10.1016/j.cytogfr.2009.01.003
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pubmed_112_11574
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Extracellular matrices (ECM) present around unfertilized and fertilized mammalian oocytes were studied ultrastructurally in samples prepared in the presence of ruthenium red to facilitate stabilization of extracellular materials. Unfertilized mouse, hamster, and human oocytes have an ECM comprising granules and filaments in their perivitelline spaces (PVS). This matrix is more abundant in the human than in hamsters and mice. The granule/filament matrix appears identical to the matrix seen between cumulus and corona radiata cells following ruthenium red processing and previously shown to comprise protein and hyaluronic acid. By including ruthenium red during fixation, it is possible to demonstrate the existence of cortical granule exudate in the PVS of fertilized oocytes from hamsters, mice, and humans. Much of the cortical granule exudate is trapped in the PVS and forms a new coat around the fertilized oocyte. This material is particulate when stained with ruthenium red and appears to be uniformly dispersed around the entire oocyte surface. We refer to this new coat as the cortical granule envelope. This envelope is observed in the PVS of all developmental stages up to and including blastocysts in all three species. Following hatching of mouse and hamster blastocysts, the cortical granule envelope is no longer present. Possible functions of this envelope are discussed.
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10.1002/mrd.1080310208
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pubmed_370_5799
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The extracranial and digital blood flow was examined in 60 patients with migraine and 15 healthy probands. The reaction of the extracranial vessels was evaluated in the patients with migraine in the interparoxysmal period, as compared with the control healthy individuals exposed to stress stimuli (local cooling, doing mental arithmetics, Valsalva's test), or given electrothermal bath or nitroglycerin. The existence of spontaneous fluctuations of the extracranial blood flow in the migraine patients is demonstrated. It has been found that in patients with the classical form of migraine the pain paroxysms are combined with an increase of the extracranial and a diminution of the digital blood flow.
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pubmed_370_5799
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pubmed_975_13682
|
The progestogen megestrol acetate (160 mg/day PO continuously starting 2 days before chemotherapy) plus chemotherapy with dacarbazine (220 mg/m2/day IV for 3 days), cisplatin (25-30 mg/m2/day IV for 3 days) every 3 weeks, and carmustine (150 mg/m2 IV single dose every 6 weeks) were administered to 22 patients, 18 of whom were evaluable. Toxicity was tolerable, and more than 80% of ideal dosing was achieved during the first two cycles of treatment. A net weight gain of 0.95 kg was observed during this program of treatment. A 56% objective response rate, including visceral responding sites, with a median duration of response of 37.5+ weeks was achieved. A median survival of 15 months for all evaluable study patients was seen, which is somewhat longer than that achieved by most prior studies, including those employing the same chemotherapy regimen plus tamoxifen. Megestrol acetate may contribute to a high objective response rate and prolonged median survival in viscerally dominant metastatic melanoma when used with a chemotherapy regimen of dacarbazine, carmustine, and cisplatin.
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10.1007/BF00299153
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pubmed_77_17212
|
Steinert [Biochem. J. (1975) 149, 39-48] reported that the alpha-keratin polypeptides (the subunits of the intracellular keratin filaments) of bovine hoof and snout epidermis are the same. We now demonstrate that this is not so: in addition to the seven polypeptides previously identified in hoof epidermis, snout epidermis also contains at least three other polypeptides of higher molecular weight. These unique polypeptides were isolated, purified and characterized. They are chemically and structurally very similar to the other polypeptides of bovine epidermis and readily polymerize in vitro with them to form native-type epidermal keratin filaments.
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10.1042/bj1870913
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pubmed_46_4303
|
We have established a method for preparing cDNA sublibraries enriched in sequences from specific chromosome regions, called selection of hybrids by affinity capture (SHAC). This procedure can be described in two stages. In the first stage, a particular chromosome region, in this study mouse chromosome 11, was microdissected, followed by PCR amplification with a universal degenerate primer. This material is referred to as the "target" DNA. In the second stage, a mouse liver cDNA library with unique linker-adapter ends, referred to as the "source" cDNA, was hybridized to the biotin-labeled target DNA prepared during the first stage. The resulting DNA duplexes were captured by streptavidin-coated magnetic beads. The cDNAs were released from their biotin-labeled target homologs by alkaline denaturation and recovered by PCR amplification. These cDNAs were referred to as the SHACcDNAs. Specificity of the SHACcDNA to chromosome 11 was verified by FISH analysis. To examine representation of the SHACcDNA, we confirmed the presence of seven genes or single-copy DNA segments known to be localized on mouse chromosome 11, using a dot blot assay. In addition, a second round of SHAC was performed to achieve even higher specificity for the resulting chromosome 11 SHACcDNA. The SHAC technology should facilitate construction of cytogenetically defined cDNA libraries and should assist in the fields of gene discovery and genome mapping.
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10.1006/geno.1995.0038
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pubmed_78_20380
|
Hybridization and polyploidy can induce rapid genomic changes, including the gain or loss of DNA, but the magnitude and timing of such changes are not well understood. The homoploid hybrid system in Helianthus (three hybrid-derived species and their two parents) provides an opportunity to examine the link between hybridization and genome size changes in a replicated fashion. Flow cytometry was used to estimate the nuclear DNA content in multiple populations of three homoploid hybrid Helianthus species (Helianthus anomalus, Helianthus deserticola, and Helianthus paradoxus), the parental species (Helianthus annuus and Helianthus petiolaris), synthetic hybrids, and natural hybrid-zone populations. Results confirm that hybrid-derived species have 50% more nuclear DNA than the parental species. Despite multiple origins, hybrid species were largely consistent in their DNA content across populations, although H. deserticola showed significant interpopulation differences. First- and sixth-generation synthetic hybrids and hybrid-zone plants did not show an increase from parental DNA content. First-generation hybrids differed in DNA content according to the maternal parent. In summary, hybridization by itself does not lead to increased nuclear DNA content in Helianthus, and the evolutionary forces responsible for the repeated increases in DNA content seen in the hybrid-derived species remain mysterious.
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10.1111/j.1469-8137.2005.01433.x
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pubmed_541_12985
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2',6'-Dimethyl substitution of the Tyr(1) residue of opioid agonist peptides and deletion of the positively charged N-terminal amino group or its replacement with a methyl group has recently been shown to represent a general structural modification to convert opioid peptide agonists into antagonists. This conversion requires the syntheses of opioid peptide analogues containing either 3-(2,6-dimethyl-4-hydroxyphenyl)propanoic acid (Dhp) or (2S)-2-methyl-3-(2,6-dimethyl-4-hydroxyphenyl)propanoic acid [(2S)-Mdp] in place of Tyr(1). Using this approach, delta-, kappa- and mu-selective opioid peptide agonist peptides were successfully converted into corresponding delta-, kappa- and mu-selective antagonists, whereby receptor selectivity was often maintained or even improved. Thus, two (2S)-Mdp(1)-analogues of the delta-selective cyclic enkephalin analogue H-Tyr-c[D-Pen-Gly-Phe(pF)-Pen]-Phe-OH turned out to be potent and selective delta antagonists. Most successful was the development of kappa antagonists derived from dynorphin A (Dyn A), including the highly potent and selective kappa-antagonist [(2S)-Mdp(1)]Dyn A(1-11)-NH(2) (dynantin) and the enzymatically stable octapeptide analogue [(2S)-Mdp(1),MeArg(7),D-Leu(8)]Dyn A(1-8)-NH(2). The (2S)-Mdp(1)-analogues of dynorphin B and alpha-neoendorphin also were kappa antagonists and may be useful as pharmacological tools in studies of kappa receptor subtypes. Finally, the Dhp(1)-analogues of the mu-selective cyclic enkephalin analogue H-Tyr-c[N(epsilon ),N(beta)-carbonyl-D-Lys(2),Dap(5)]enkephalinamide and of endomorphin-2 were moderately potent mu opioid antagonists.
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10.1016/s0024-3205(03)00389-8
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pubmed_32_5016
|
There was a general decline in animal rabies in Europe in 1991 following the peak levels which occurred in 1989. This was ascribed, in France at least, to the normal decline in cases usually experienced following peak occurrence and also to oral immunization of foxes against rabies. European countries in which rabies occurs may be infected by fox, insectivorous bat or dog rabies. This paper makes a general summary of the rabies situation in Europe in 1991 and presents data obtained in 1991 from 15 European countries using oral vaccination against fox rabies.
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pubmed_32_5016
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pubmed_987_21428
|
AIMS/INTRODUCTION
Obstructive sleep apnea (OSA) is related to prediabetes and diabetes. Whether patients with OSA have a higher risk of prediabetes/diabetes remains unclear. We aimed to carry out a meta-analysis of published studies to evaluate the relationships between OSA and prediabetes and diabetes, and the impact of the severity of OSA on diabetes.
MATERIALS AND METHODS
The PubMed, EMBASE and Cochrane databases were searched from January 2011 to July 2021. The associations between OSA and impaired fasting glucose, impaired glucose tolerance, impaired glucose regulation and diabetes mellitus were analyzed. We estimated the pooled odds ratios using fixed or random effects models. We included 25 studies comprising a total of 154,948 patients with OSA and risk factors for prediabetes/diabetes (20 and 16, respectively) in the analysis.
RESULTS
OSA was associated with a higher risk of impaired fasting glucose, impaired glucose tolerance, impaired glucose regulation and diabetes mellitus in the cohort studies and cross-sectional studies. The pooled odds ratios were 2.34 (95% confidence interval [CI] 1.16-4.72), 1.58 (95% CI 1.15-2.15), 1.65 (95% CI 1.12-2.42), 2.15 (95% CI 1.68-2.75) and 3.62 (95% CI 2.75-4.75), respectively. Subgroup analyses were based on the proportions of men and women. The results showed that OSA was a risk factor, and there was no significant difference between the two groups. The risk of diabetes increased with the severity of OSA.
CONCLUSIONS
The risk of developing prediabetes and diabetes was higher in patients with OSA.
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10.1111/jdi.13793
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pubmed_469_23268
|
The objective of this study is to determine the inter-rater reliability of the Pizzi Health and Wellness Assessment (PHWA) by comparing the consistency in scores between clients and their caregivers in the following areas of participation: social, physical, family, occupational, mental/emotional, and spiritual. A retrospective inter-rater correlational design was used to analyze the agreement of scores from a convenience sample consisting of two groups: clients with disabilities (n = 19) and their healthy caregivers (n = 19). Inter-rater reliability was calculated using correlations for the PHWA as a whole, and for the current level of participation and wishing to improve participation subsections. Inter-rater reliability as calculated by an Intraclass Correlation Coefficient, and either the Pearson or Spearman rho correlation and found to be reliable between clients and caregivers (r = .636, p < .001; rho = .642, p < .001). More specifically, current level of participation demonstrated acceptable reliability (rICC = .513, p < .001; r = .521, p < .001) as did wishing to improve participation (rICC = .689, p < .001; r = .725, p < .001). This supports the PHWA as a clinically relevant health and wellness occupational therapy assessment.
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10.1080/07380577.2022.2088916
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pubmed_234_20441
|
Microsatellite instability (MSI) has been reported to occur in a wide variety of sporadic tumours, such as colorectal and gastric cancers. MSI positivity has been associated with a particular clinico-pathologic profile, including the presence of abundant lymphoid infiltration, poor differentiation and a relatively good outcome for the patients. Since medullary breast carcinomas (MBCs) share these clinico-pathologic features with the MSI-positive tumours described above, we evaluated MSI in this particular histologic type of breast cancer. DNA of 24 MBC cases was extracted from formalin-fixed, paraffin-embedded tissue. The presence of MSI was analysed using BAT-26. We also searched mutations in 2 target genes: TGF-beta RII and BAX. Five cases of the series were also analysed for 1 (CA) dinucleotide tandem repeat sequence (D1S158), 8 tetranucleotide repeat sequences (D3S1358, D5S818, D7S820, D8S1179, D13S317, D21S11, FGA and VWA) and 1 pentanucleotide repeat (dAAAAT), localized in intron 1 of p53 gene. We found 2 carcinomas (8.3%) with BAT-26 instability. None of the cases had mutations in the "target genes", TGF-beta RII and BAX, including the 2 cases with BAT-26 instability. No MSI was observed using the panel of tetra- and pentanucleotide markers. Loss of heterozygosity was found in some loci. No significant difference in mean MIB-1 index according to RER status was observed. The low frequency of MSI in MBC is similar to that of other histologic types of breast cancer. Although MBCs share some clinico-pathologic features with colorectal and gastric carcinomas, which exhibit a high frequency of MSI, the underlying genetic events leading to this breast tumour are different from those leading to tumours of the digestive tract.
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10.1002/(sici)1097-0215(19990827)82:5<644::aid-ijc5>3.0.co;2-s
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pubmed_1069_10270
|
The cis-regulatory function of a far-upstream sequence (-1,711 to -186) of the promoter of the wheat gene for histone H3 (TH012) was analyzed in cultured rice and tobacco cells in a transient expression system with the gene for beta-D-glucuronidase as a reporter gene. The far-upstream sequence was necessary for full activity of the H3 promoter in rice cells but did not enhance the activity of the proximal promoter in tobacco cells. Dissection analysis of the far-upstream sequence revealed the existence of several positive and negative cis-acting sequences in this region, some of which functioned differently in rice and tobacco cells. In gain-of-function experiments with rice cells, the sequence from -848 to -704, containing the CCAAT and octamer (CaCGGATC) motifs, functioned in an orientation-independent manner, whereas the sequence from -703 to -486 functioned in an orientation-dependent manner. By contrast, both sequences exhibited an orientation-dependent cis-function in tobacco cells. These findings suggest that some cis-regulatory sequences in the far-upstream region of the H3 promoter function differently in rice and tobacco cells.
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pubmed_1069_10270
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pubmed_836_2441
|
A contralateral extra-axial hematoma sometimes occurs during an operation on an acute subdural hematoma and may become fatal. Using a combined procedure of burr hole evacuation and craniotomy, we treated 2 cases of multiple traumatic acute subdural hematomas. Our policy for such cases is first to perform a burr hole evacuation for the acute subdural hematoma in the emergency room, while simultaneously preparing the operation room for a possible further operation. Next, we perform computed tomography (CT) of the brain. If the evacuation does not provide enough decompression, we either carry out a craniotomy at the same site, or, we observe the patient without resorting to craniotomy. However, if the patient's condition deteriorates, burr hole evacuation is repeated and/or craniotomy is carried out as soon as possible on the lesion at the already prepared operation room. Both of our patients received craniotomy for another subdural hematoma after the burr hole evacuation. Though his intracranial pressure was well managed during the acute stage, one of the patients died 21 days after the trauma due to an extensive brain infarction caused by vasospasm. The other regained consciousness and was able to walk 5 months after the trauma in spite of cerebral infarction from vasospasm. The possible mechanism of vasospasm in severe head injury is also discussed.
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pubmed_836_2441
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pubmed_216_12234
|
OBJECTIVES
To review the value of PSA kinetics in the diagnosis and prognosis of prostate cancer.
METHODS
Review of the literature through a Medline search.
CONCLUSIONS
A pre-tretament PSAV value >2ng/ ml/yr is a risk factor for increased mortality from prostate cancer after surgery or radiation therapy. A PSADT<3ms is indicative of reduced survival after treatment. For patients with PSA recurrence after surgery a PSADT> 10 is more likely associated with local recurrence.
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10.4321/s0004-06142006001000015
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pubmed_744_9590
|
Preparative separation of flavonoid glycosides in leaves extract of Ampelopsis grossedentata was conducted using high-speed counter-current chromatograph (HSCCC) with a solvent system composed of n-hexane-ethyl acetate-methanol-water (1:6:1.5:7.5, v/v). In a single operation, 28 mg of 5,7-dihydroxy-3',4'-trihydroxyflavone-3-O-6''-rhamnose and 18 mg of 5,7-dihydroxy-3',4'-dihydroxyflavone-3-O-6''-rhamnose was obtained from 150 mg of the extract. The chemical structure of the two compounds was elucidated by electrospray ionization (EIS) MS and NMR.
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10.1016/j.chroma.2004.03.062
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pubmed_285_8763
|
BACKGROUND
The box jellyfish, Chironex fleckeri, is the largest and most dangerous cubozoan jellyfish to humans. It produces potent and rapid-acting venom and its sting causes severe localized and systemic effects that are potentially life-threatening. In this study, a combined transcriptomic and proteomic approach was used to identify C. fleckeri proteins that elicit toxic effects in envenoming.
RESULTS
More than 40,000,000 Illumina reads were used to de novo assemble ∼ 34,000 contiguous cDNA sequences and ∼ 20,000 proteins were predicted based on homology searches, protein motifs, gene ontology and biological pathway mapping. More than 170 potential toxin proteins were identified from the transcriptome on the basis of homology to known toxins in publicly available sequence databases. MS/MS analysis of C. fleckeri venom identified over 250 proteins, including a subset of the toxins predicted from analysis of the transcriptome. Potential toxins identified using MS/MS included metalloproteinases, an alpha-macroglobulin domain containing protein, two CRISP proteins and a turripeptide-like protease inhibitor. Nine novel examples of a taxonomically restricted family of potent cnidarian pore-forming toxins were also identified. Members of this toxin family are potently haemolytic and cause pain, inflammation, dermonecrosis, cardiovascular collapse and death in experimental animals, suggesting that these toxins are responsible for many of the symptoms of C. fleckeri envenomation.
CONCLUSIONS
This study provides the first overview of a box jellyfish transcriptome which, coupled with venom proteomics data, enhances our current understanding of box jellyfish venom composition and the molecular structure and function of cnidarian toxins. The generated data represent a useful resource to guide future comparative studies, novel protein/peptide discovery and the development of more effective treatments for jellyfish stings in humans. (Length: 300).
|
10.1186/s12864-015-1568-3
|
pubmed_768_12399
|
Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible.
|
10.1586/14760584.2014.885841
|
pubmed_675_17195
|
Non-hemorrhagic brain infarction (BI) is a recognized complication in adults treated with extracorporeal membrane oxygenation (ECMO) and associated with increased mortality. However, predictors of BI in these patients are poorly understood. The aim of this study was to identify predictors of BI in ECMO-treated adult patients. We conducted an observational cohort study of all adult patients treated with venovenous or venoarterial (VA) ECMO at our center between 2010 and 2018. The primary endpoint was a computed tomography (CT) verified BI. Logistic regression models were employed to identify BI predictors. In total, 275 patients were included, of whom 41 (15%) developed a BI. Pre-ECMO Simplified Acute Physiology Score III, pre-ECMO cardiac arrest, VA ECMO and conversion between ECMO modes were identified as predictors of BI. In the multivariable analysis, VA ECMO demonstrated independent risk association. VA ECMO also remained the independent BI predictor in a sub-group analysis excluding patients who did not undergo a head CT scan during ECMO treatment. The incidence of BI in adult ECMO patients may be higher than previously believed and is independently associated with VA ECMO mode. Larger prospective trials are warranted to validate these findings and ascertain their clinical significance.
|
10.1038/s41598-021-83157-5
|
pubmed_167_4286
|
A 19-year-old woman was referred to our hospital because of a persistent fever and cough that lasted for over a week. Influenza B virus infection was diagnosed using the rapid test kit. Initially, the patient was diagnosed with influenza B infection associated with lobar pneumonia and treated with an anti-influenza virus drug and sulbactam/ampicillin. The patient's fever persisted, and her respiratory condition worsened. On day 5, a computed tomography (CT) scan revealed an extension of the consolidation areas in the left lung and new opacities in the right lung. The antibiotic treatment was changed to meropenem and levofloxacin, and the patient's physical condition gradually improved. A sputum sample revealed the presence of Mycoplasma pneumoniae-specific DNA. Both influenza B virus and M. pneumoniae infections were confirmed serologically. This was a case of coinfection with influenza B virus and M. pneumoniae in a healthy young woman. The M. pneumoniae pneumonia diagnosis was delayed because the predominant feature observed in the CT scan was dense consolidation. M. pneumoniae should be considered as one of the causative pathogens in influenza coinfection cases with CT scan images presenting dense consolidation.
|
10.1155/2018/3529358
|
pubmed_308_6909
|
Fluoride is an important groundwater contaminant, and more than 200 million people are exposed to high fluoride levels in drinking water, the major source of fluoride exposure. Exposure above 2 ppm of fluoride is associated with renal impairment in humans. In rats, moderate levels of fluoride induce kidney injury at early stages in which the glomerular filtration rate (GFR) is not altered. In the present study, we investigated if sub-nephrotoxic stimulus induced by fluoride might impact the response to a subsequent nephrotoxic treatment with gentamicin. Male Wistar rats (~21 days) were exposed to 0, 15 or 50 ppm of fluoride through drinking water during 40 days. Afer that, rats were co-exposed to gentamicin (40 mg kg(-1) day(-1), 7 days). Gentamicin induced a marked decrease in the GFR and an increase in urinary levels as well as the protein and mRNA expression of biomarkers of early kidney injury, such as Kim-1. Interestingly, gentamicin nephrotoxicity was less pronounced in groups previously exposed to fluoride than in the group only treated with gentamicin. Fluoride induced Hsp72, a cytoprotective molecule, which might have improved the response against gentamicin. Moreover, fluoride decreased the expression of megalin, a molecule necessary for internalization of gentamicin into the proximal tubule, potentially reducing gentamicin accumulation. The present results suggest that fluoride reduced gentamicin-induced nephrotoxicity by inducing a compensatory response carried out by Hsp72 and by decreasing gentamicin accumulation. These findings should not be interpreted to suggest that fluoride is a protective agent as megalin deficiency could lead to serious adverse effects on the kidney physiology.
|
10.1002/jat.3186
|
pubmed_1098_834
|
Organisms of all phyla express mechanosensitive ion channels with a wide range of physiological functions. In recent years, several classes of mechanically gated ion channels have been identified. Some of these ion channels are intrinsically mechanosensitive. Others depend on accessory proteins to regulate their response to mechanical force. The mechanotransduction machinery of cochlear hair cells provides a particularly striking example of a complex force-sensing machine. This molecular ensemble is embedded into a specialized cellular compartment that is crucial for its function. Notably, mechanotransduction channels of cochlear hair cells are not only critical for auditory perception. They also shape their cellular environment and regulate the development of auditory circuitry. Here, we summarize recent discoveries that have shed light on the composition of the mechanotransduction machinery of cochlear hair cells and how this machinery contributes to the development and function of the auditory system.
|
10.1016/j.neuron.2022.09.018
|
pubmed_1140_6893
|
Peptides derived from tryptic hydrolysate of jumbo squid (Dosidicus gigas) skin gelatin were assessed for their antioxidant properties in different in vitro assay systems. The hydrolysate itself exhibited a strong lipid peroxidation inhibition and it was much higher than that of natural antioxidant, alpha-tocopherol. In addition, it could scavenge highly active free radicals in oxidative systems, in the order of hydroxyl and carbon-centered radicals. Two representative peptides with comparatively higher antioxidant potency were purified and characterized as Phe-Asp-Ser-Gly-Pro-Ala-Gly-Val-Leu (880.18 Da) and Asn-Gly-Pro-Leu-Gln-Ala-Gly-Gln-Pro-Gly-Glu-Arg (1241.59 Da). Furthermore, viability of radical-mediated oxidation-induced human lung fibroblasts was enhanced following the treatment of two peptides. However it did not exhibit substantial ion chelation, and we presumed that the observed radical scavenging potency of these peptides play a vital role for their strong antioxidant activity. Based on our results we suggest that hydrophobic amino acids present in peptide sequences contributed greatly for observed antioxidant activities.
|
10.1016/j.lfs.2005.03.016
|
pubmed_650_7985
|
A total of 47 patients with sleep disorder (36 male and 11 female) with a mean age of 47.5 +/- 15 years were evaluated for daytime symptoms with a Multiple Sleep Latency Test (MSLT) and a Maintenance of Wakefulness Test (MWT) given on the same day--once at the time of their diagnostic evaluation and again after one to six months of treatment. The MSLT and MWT data are consistent with the notion that sleep tendency, as measured by the MSLT and ability to remain awake, as measured by the MWT, represent different physiologic processes. Data show a marked treatment-related improvement in ability to stay awake as measured by the MWT and no treatment-related improvement in sleepiness as measured by the MSLT. We conclude that there is a heterogeneous subpopulation of patients with sleep disorders whose symptoms of daytime sleepiness will show no treatment-related improvement in daytime symptoms if they are evaluated only by the MSLT. We suggest that, since ability to stay awake (and not ability to fall asleep) is a requisite for all job-related duties, an objective, physiologically based test such as the MWT should be used to assess the impact of sleep disorders in cases where there is a clinical concern about fitness to drive or work.
|
10.1378/chest.102.3.699
|
pubmed_768_4322
|
BACKGROUND
Detecting protein complexes in protein-protein interaction (PPI) networks plays an important role in improving our understanding of the dynamic of cellular organisation. However, protein interaction data generated by high-throughput experiments such as yeast-two-hybrid (Y2H) and tandem affinity-purification/mass-spectrometry (TAP-MS) are characterised by the presence of a significant number of false positives and false negatives. In recent years there has been a growing trend to incorporate diverse domain knowledge to support large-scale analysis of PPI networks.
METHODS
This paper presents a new algorithm, by incorporating Gene Ontology (GO) based semantic similarities, to detect protein complexes from PPI networks generated by TAP-MS. By taking co-complex relations in TAP-MS data into account, TAP-MS PPI networks are modelled as bipartite graph, where bait proteins consist of one set of nodes and prey proteins are on the other. Similarities between pairs of bait proteins are computed by considering both the topological features and GO-driven semantic similarities. Bait proteins are then grouped in to sets of clusters based on their pair-wise similarities to produce a set of 'seed' clusters. An expansion process is applied to each 'seed' cluster to recruit prey proteins which are significantly associated with the same set of bait proteins. Thus, completely identified protein complexes are then obtained.
RESULTS
The proposed algorithm has been applied to real TAP-MS PPI networks. Fifteen quality measures have been employed to evaluate the quality of generated protein complexes. Experimental results show that the proposed algorithm has greatly improved the accuracy of identifying complexes and outperformed several state-of-the-art clustering algorithms. Moreover, by incorporating semantic similarity, the proposed algorithm is more robust to noises in the networks.
|
10.1186/1477-5956-11-S1-S2
|
pubmed_1077_4316
|
INTRODUCTION
This study evaluated several psychometric properties of a newly developed questionnaire designed to assess individuals' self-efficacy (from 0% to 100%) to employ self-initiated cognitive-behavioral strategies intended to reduce the frequency and duration of their pornography use.
METHODS
Using a web-based data collection procedure, we recruited 1298 male users of pornography to complete questionnaires assessing hypersexuality, pornography use history, and general self-efficacy.
RESULTS
Based on a principal component analysis and examination of inter-item correlations, we deleted 13 items from the initial pool of 21 strategies. The resulting 8-item questionnaire had excellent internal consistency reliability, and a moderate mean inter-item correlation considered indicative of unidimensionality. In support of criterion validity, self-efficacy to employ use-reduction strategies was significantly associated with the frequency with which participants used pornography, with scores on a measure of hypersexuality, and with the number of times one had attempted to cut back using pornography. In support of discriminant validity, we found that pornography use-reduction self-efficacy scores were not strongly correlated with general self-efficacy.
CONCLUSIONS
Both researchers and clinicians could use this questionnaire to assess pornography users' confidence to employ self-initiated strategies intended to reduce the duration and frequency with which they use pornography.
|
pubmed_1077_4316
|
pubmed_176_19939
|
The rate of endochondral bone growth determines final height in humans and is tightly controlled. Glycogen synthase kinase-3 (GSK-3) is a negative regulator of several signaling pathways that govern bone growth, such as insulin/IGF and Wnt/β-catenin. The two GSK-3 proteins, GSK-3α and GSK-3β, display both overlapping and distinct roles in different tissues. Here we show that pharmacological inhibition of GSK-3 signaling in a mouse tibia organ culture system results in enhanced bone growth, accompanied by increased proliferation of growth plate chondrocytes and faster turnover of hypertrophic cartilage to bone. GSK-3 inhibition rescues some, but not all, effects of phosphatidylinositide 3-kinase inhibition in this system, in agreement with the antagonistic role of these two kinases in response to signals such as IGF. However, cartilage-specific deletion of the Gsk3b gene in mice has minimal effects on skeletal growth or development. Molecular analyses demonstrated that compensatory up-regulation of GSK-3α protein levels in cartilage is the likely cause for this lack of effect. To our knowledge, this is the first tissue in which such a compensatory mechanism is described. Thus, our study provides important new insights into both skeletal development and the biology of GSK-3 proteins.
|
10.1210/en.2010-1412
|
pubmed_522_23599
|
Lipopolysaccharide (LPS), the major proinflammatory component of gram-negative bacteria, is well known to induce sepsis and microglial activation in the CNS. On the contrary, the effect of products from gram-positive bacteria especially in areas devoid of blood-brain barrier remains to be explored. In the present study, a panel of antibodies, namely, OX-6, OX-42 and ED-1 was used to study the response of microglia/macrophages in the pineal gland of rats given an intravenous LPS or lipoteichoic acid (LTA). These antibodies recognize MHC class II antigens, complement type 3 receptors and unknown lysosomal proteins in macrophages, respectively. In rats given LPS (50 microg/kg) injection and killed 48 h later, the cell density and immunoexpression of OX-6, OX-42 and ED-1 in pineal microglia/macrophages were markedly increased. In rats receiving a high dose (20 mg/kg) of LTA, OX-42 and OX-6, immunoreactivities in pineal microglia/macrophages were also enhanced, but that of ED-1 was not. In addition, both bacterial toxins induced an increase in astrocytic profiles labelled by glial fibrillary acid protein. An interesting feature following LPS or LTA treatment was the lowering effect on serum melatonin, enhanced serotonin immunolabelling and cellular vacuolation as studied by electron microscopy in pinealocytes. The LPS- or LTA-induced vacuoles appeared to originate from the granular endoplasmic reticulum as well as the Golgi saccules. The present results suggest that LPS and LTA could induce immune responses of microglia/macrophages and astroglial activation in the pineal gland. Furthermore, the metabolic and secretory activity of pinealocytes was modified by products from both gram-positive and -negative bacteria.
|
10.1111/j.1600-079X.2004.00170.x
|
pubmed_525_20184
|
PURPOSE
Quantitative hepatobiliary scintigraphy, a noninvasive method frequently used to diagnose several biliary tract disorders, shows abnormalities in bile secretion and outflow. It is well known that there are wide variations in the normal pattern of bile emptying, but the effect of cholecystectomy on the bile flow has not yet been investigated. The goal of the current study was to examine the dynamics and normal variations of bile flow by quantitative hepatobiliary scintigraphy before and after cholecystectomy in a group of patients with uncomplicated gallstone disease.
METHODS
Twenty patients were evaluated before and after cholecystectomy through cholecystokinin octapeptide-augmented quantitative hepatobiliary scintigraphy, and quantitative parameters of bile emptying (Tmax: time to peak activity, T1/2: half-emptying time before and after cholecystokinin octapeptide and duodenum appearance time) were determined and then compared.
RESULTS
Before operation, the bile outflow displayed wide variations, with a moderately delayed common bile duct emptying time in some patients. After cholecystectomy, the T1/2 of the common bile duct decreased significantly when compared with the preoperative status, with only minor patient-to-patient variation, indicating uniformly faster bile emptying (common bile duct T1/2 before and after operation: 30.5 +/- 14.8 and 18.8 +/- 2.6 min, respectively). Cholecystokinin octapeptide administration caused rapid bile outflow from the common bile duct, with a significant decrease in the T1/2 parameters before and after cholecystectomy.
CONCLUSIONS
In patients with their gallbladders in situ, the bile emptying rate showed wide variations and may be moderately slow without distal common bile duct obstruction. After cholecystectomy, the rate of bile emptying accelerated and showed only minor variations, thereby increasing the sensitivity of quantitative hepatobiliary scintigraphy for showing partial biliary obstruction.
|
10.1097/00003072-199909000-00002
|
pubmed_132_16004
|
OBJECTIVE
To verify the efficacy of the double-action mechanism of venlafaxine for depression and climacteric symptoms.
METHODS
A group of 20 postmenopausal women (age range 40-60 years) with diagnosis of major depressive disorder, generalized anxiety disorder and climacteric symptoms was enrolled. All participants received venlafaxine (75 mg/day) for 2 months. Clinical checkup and evaluation test were repeated every 2 weeks for 2 months of treatment.
RESULTS
Before treatment, the mean scores for the clinical evaluation scales (Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale) were 13.9 and 18.7, respectively (mild-moderate severity). The general level of psychopathology was not particularly high (Symptomatology Checklist-90, mean total 103), the most common psychopathological dimensions were depression and somatization. The sample suffered from mild climacteric syndrome (Kupperman Index Score, mean = 19.1). Clinical improvement was visible after 2 weeks of treatment and continued until the last checkup, 2 months after the start of treatment (final Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores: 5.1 and 6.3, respectively). Kupperman Index Scores at the end of the treatment period demonstrated complete resolution of the climacteric syndrome (mean score = 6.57).
CONCLUSION
Venlafaxine is efficacy in treating both psychiatric disorders and climacteric symptomatology.
|
10.3109/09513590.2011.588755
|
pubmed_999_10704
|
Equine herpesvirus-1 (EHV-1) is an important pathogen in horses. It affects horses worldwide and causes substantial economic losses. In this study, for the first time, we characterized EHV-1 isolates from South Korea at the molecular level. We then aimed to determine the genetic divergences of these isolates by comparing them to sequences in databases. In total, 338 horse samples were collected, and 12 EHV-1 were isolated. We performed ORF30, ORF33, ORF68, and ORF34 genetic analysis and carried out multi-locus sequence typing (MLST) of 12 isolated EHV-1. All isolated viruses were confirmed as non-neuropathogenic type, showing N752 of ORF30 and highly conserved ORF33 (99.7-100%). Isolates were unclassified using ORF68 analysis because of a 118 bp deletion in nucleotide sequence 701-818. Seven EHV-1 isolates (16Q4, 19R166-1, 19R166-6, 19/10/15-2, 19/10/15-4, 19/10/18-2, 19/10/22-1) belonged to group 1, clade 10, based on ORF34 and MLST analysis. The remaining 5 EHV-1 isolates (15Q25-1, 15D59, 16Q5, 16Q40, 18D99) belonged to group 7, clade 6, based on ORF34 and MLST analysis.
|
10.3390/pathogens10040425
|
pubmed_778_18941
|
This article reports on the implementation of a problem-based learning (PBL) tutorial in our advanced program for second year students within an existing curriculum. The program was opened on the last 5 days of the summer vacation and students could volunteer to be part of the group. Students separated themselves into small groups by random sampling. The PBL tutorials were done during the first 3 days for medical problems according to our original scenarios (based on medical cases), and during the last 2 days, students made presentations of their learning outcomes, using information technology (IT) by themselves. Throughout this program, students were expected to engage in self-learning, except for a 1(1/2)-h group session with a tutor. Assessment was done by attendance at a group session and by portfolio analysis. Following the portfolio analysis, students identified the number of learning issues (group A, 26 +/- 7 issues; group B, 20 +/- 3 issues; group C, 21 +/- 7 issues). Research, by questionnaire, revealed that 84% of the students were strongly interested in each scenario and 95% of the students felt familiar with each scenario. The levels of satisfaction with the tutor were different in the three groups. All of the students were comfortable in the discussion room and IT center. These results suggested that PBL tutorials are supported by the scenario, the tutor, and the location of the group session, as well as by self-learning. Moreover, one of the most important factors for a PBL tutorial that the student is ready for the free discussions and has enough time for individual self-learning.
|
10.1007/s10266-005-0054-9
|
pubmed_121_18914
|
Conventional analyses of a composite of multiple time-to-event outcomes use the time to the first event. However, the first event may not be the most important outcome. To address this limitation, generalized pairwise comparisons and win statistics (win ratio, win odds, and net benefit) have become popular and have been applied to clinical trial practice. However, win ratio, win odds, and net benefit have typically been used separately. In this article, we examine the use of these three win statistics jointly for time-to-event outcomes. First, we explain the relation of point estimates and variances among the three win statistics, and the relation between the net benefit and the Mann-Whitney U statistic. Then we explain that the three win statistics are based on the same win proportions, and they test the same null hypothesis of equal win probabilities in two groups. We show theoretically that the Z-values of the corresponding statistical tests are approximately equal; therefore, the three win statistics provide very similar p-values and statistical powers. Finally, using simulation studies and data from a clinical trial, we demonstrate that, when there is no (or little) censoring, the three win statistics can complement one another to show the strength of the treatment effect. However, when the amount of censoring is not small, and without adjustment for censoring, the win odds and the net benefit may have an advantage for interpreting the treatment effect; with adjustment (e.g., IPCW adjustment) for censoring, the three win statistics can complement one another to show the strength of the treatment effect. For calculations we use the R package WINS, available on the CRAN (Comprehensive R Archive Network).
|
10.1002/pst.2251
|
pubmed_964_16578
|
Increasing evidence supports the hypothesis that "dose" is critical to the clinical outcomes of cytotoxic chemotherapy for patients with breast cancer. Clinical trials continue to investigate whether higher doses of chemotherapy lead to proportionate improvements in the outcomes of patients. Delivery of dose-intensive chemotherapy has been facilitated by technological advancements in supportive care. Improved antiemetics have led to increased patient tolerance of the most acute symptoms of aggressive chemotherapeutic dosing. Chemotherapy-induced myelosuppression may be minimized in a lineage-specific manner by appropriate use of hematopoietic cytokines such as filgrastim (granulocyte colony-stimulating factor), sargramostim (granulocyte-macrophage colony-stimulating factor), and/or epoetin alfa (erythropoietin). However, cumulative myelotoxicity occurs with dose-intensive chemotherapy over multiple cycles despite adjunctive cytokine support. Additionally, no cytokine has yet been demonstrated to support platelet production to any clinically significant degree although several regulators of platelet production (such as thrombopoietin, IL-6, and IL-11) are in clinical trials. Many cytokines can induce the mobilization of hematopoietic progenitor and stem cells from the bone marrow into the circulating blood pool, where these cells may be harvested. Clinical use of these cytokine-mobilized peripheral blood progenitor cells (also known as PBPCs or, commonly, as blood stem cells) has documented the effectiveness of these cells to reconstitute multilineage blood production following very high-dose chemotherapy. The ease with which PBPCs can be collected and their reproducible clinical effectiveness to support patients through intensive treatment protocols have led to a virtual elimination of bone marrow as the source of cellular support for myeloablative chemotherapy in many transplant centers. Novel investigative approaches are also possible with PBPCs. In this review, the historical background of PBPCs is summarized, and the potential benefits (including economic advantages) of PBPCs to support dose-intensive chemotherapy for treating breast cancer are discussed. While dose intensification of breast cancer chemotherapy to the degree requiring PBPC support remains controversial and, in most centers, investigational, there is no doubt that PBPCs are an effective adjunct to the hematopoietic support of patients undergoing transplant-level cytotoxic treatments. Further study will undoubtedly lead to increased use of PBPCs in novel treatments for patients with breast cancer and other solid tumors.
|
pubmed_964_16578
|
pubmed_258_7553
|
BACKGROUND
Hip fractures in the elderly population are common and the number of patients is rising. For young and geriatric patients with undisplaced fractures osteosynthesis is the primary type of treatment. The dynamic hip screw (DHS) is around for many years and proved its value especially in displaced fractures. Since 2018 the femoral neck system (FNS) is available as an alternative showing promising biomechanical results. The aim of this study is to evaluate clinical results of the FNS and compare it to the DHS.
MATERIALS AND METHODS
Patients older than 18 years with Garden I-IV fractures that were treated with osteosynthesis in a level 1 trauma center were included in the study. Between January 2015 and March 2021, all patients treated with FNS (1-hole plate, DePuy-Synthes, Zuchwil, Switzerland) or DHS (2-hole plate, DePuy-Synthes, Zuchwil, Switzerland) for proximal femur fractures were included in the study. Closed reduction was achieved using a traction table. All operations were carried out by experienced orthopedic trauma surgeons. Primary outcome measures were rate of implant failure (cut out) and surgical complications (hematoma, infection). Secondary outcome measures were Hb-difference, length of hospital stay and mortality.
RESULTS
Overall, 221 patients were included in the study. 113 were treated with FNS, 108 with DHS. Mean age was 69 ± 14 years. There were 17.2% Garden I, 47.5% Garden II, 26.7% Garden III and 8.6% Garden IV fractures. No difference between the groups for age, body mass index (BMI), Charlson comorbidity index (CCI), time to surgery, Pauwels and Garden classification, rate of optimal blade position or tip apex distance was found. FNS showed lower pre- to postoperative Hb-difference (1.4 ± 1.1 g/l vs. 2.1 ± 1.4 g/l; p < 0.05), shorter operating time (36.3 ± 11.6 min vs. 54.7 ± 17.4 min; p < 0.05) and hospital stay (8.8 ± 4.3 d vs. 11.2 ± 6.8 d; p < 0.05). Surgical complications (FNS 13.3% vs. DHS 18.4%, p > 0.05), rate of cut out (FNS 12.4% vs. DHS 10.2%, p > 0.05) and mortality (FNS 3.5%; DHS 0.9%; p > 0.05) showed no difference between the groups. Logistic regression showed that poor blade position was the only significant predictor for cut out and increased the risk by factor 7. Implant related infection (n = 3) and hematoma/seroma (n = 6) that needed revision was only seen in DHS group.
CONCLUSION
FNS proved to be as reliable as DHS in all patients with hip fractures. Not the type of implant but blade positioning is still key to prevent implant failure. Still due to minimal invasive approach implant related infections and postoperative hematomas might have been prevented using the FNS.
|
10.1007/s00402-022-04551-w
|
pubmed_633_5641
|
Patients implanted with mechanical heart valves (MHV) or with ventricular assist devices that use MHV require mandatory lifelong anticoagulation for secondary stroke prevention. We recently developed a novel Device Thrombogenicity Emulator (DTE) methodology that interfaces numerical and experimental approaches to optimize the thrombogenic performance of the device and reduce the bleeding risk associated with anticoagulation therapy. Device Thrombogenicity Emulator uses stress-loading waveforms in pertinent platelet flow trajectories that are extracted from highly resolved numerical simulations and emulates these flow conditions in a programmable hemodynamic shearing device (HSD) by which platelet activity is measured. We have previously compared two MHV, ATS and the St. Jude Medical, and demonstrated that owing to its nonrecessed hinge design, the ATS valve offers improved thrombogenic performance. In this study, we further optimize the ATS valve thrombogenic performance, by modifying various design features of the valve, intended to achieve reduced thrombogenicity: 1) optimizing the leaflet-housing gap clearance; 2) increasing the effective maximum opening angle of the valve; and 3) introducing a streamlined channel between the leaflet stops of the valve that increases the effective flow area. We have demonstrated that the DTE optimization methodology can be used as test bed for developing devices with significantly improved thombogenic performance.
|
10.1097/MAT.0b013e3181e65bf9
|
pubmed_369_7054
|
PURPOSE
A clinical survey was made on the life style and dietary behaviors of people with non-periodontal disease and people with periodontal disease for prevention and treatment of periodontal diseases.
METHODS
72-hour diet analysis and frequency analysis of dietary intake were performed in 60 patients with moderate-to-severe periodontal disease and 60 patients with healthy periodontal tissues randomly selected in the Ninth People's Hospital for dental treatment. The data was analyzed by Student's t test and Chi-square test with SPSS13.0 software package.
RESULTS
There was significant difference (P<0.05) in vitamin C, flavonoids and β-carotene dietary intake between control group and periodontal disease group; In periodontal disease group, dietary intake of selenium and zinc intake was different from the normal control, but the difference was not statistically significant (P>0.05).
CONCLUSIONS
There is a close relationship between oral health and antioxidant nutrients. Lower dietary vitamin C content, flavonoid content and β-carotene intake lead to destruction of periodontal tissue and higher incidence of periodontal disease.
|
pubmed_369_7054
|
pubmed_1103_23091
|
In this study, we analyzed all known protein sequences for repeating amino acid segments. Although duplicated sequence segments occur in 14 % of all proteins, eukaryotic proteins are three times more likely to have internal repeats than prokaryotic proteins. After clustering the repetitive sequence segments into families, we find repeats from eukaryotic proteins have little similarity with prokaryotic repeats, suggesting most repeats arose after the prokaryotic and eukaryotic lineages diverged. Consequently, protein classes with the highest incidence of repetitive sequences perform functions unique to eukaryotes. The frequency distribution of the repeating units shows only weak length dependence, implicating recombination rather than duplex melting or DNA hairpin formation as the limiting mechanism underlying repeat formation. The mechanism favors additional repeats once an initial duplication has been incorporated. Finally, we show that repetitive sequences are favored that contain small and relatively water-soluble residues. We propose that error-prone repeat expansion allows repetitive proteins to evolve more quickly than non-repeat-containing proteins.
|
10.1006/jmbi.1999.3136
|
pubmed_160_23949
|
Human embryonic stem (hES) cells possess the ability to self-renew indefinitely and provide a potential source of differentiated progeny representing all three embryonic germ layers. Although hES cell lines share the expression of typical pluripotency markers, limited data is available regarding their differentiation capabilities. We have earlier reported the in-house derivation of two hES cell lines, KIND-1 and KIND-2 on human feeders. Here, we describe a comparative study carried out on both these cell lines to better understand the differentiation potential of KIND-1 and KIND-2 by gene expression analysis of representative gene transcripts reflecting pluripotency and the three germ layers viz. ectoderm, mesoderm, and endoderm. Gene expression analysis and immunolocalization studies were undertaken on (a) 7- and 14-d old embryoid bodies (EBs) (b) spontaneously differentiated cells from EBs, (c) cells derived from EBs under the influence of various growth factor treatments and (d) KIND-1 and KIND-2 cells co-cultured on mouse embryonic visceral endoderm-like feeder (END-2). Despite both the cell lines being XX, derived, passaged, and cultured similarly, KIND-1 exhibits preferential differentiation towards endodermal lineage whereas KIND-2 spontaneously forms beating cardiomyocytes. Perhaps the occurrence of discrete epigenetic profile in both the cell lines predisposes them to encompass different developmental potential in vitro. Our data provide evidence for existence of distinct differentiation propensity among hES cell lines and emphasizes the need to derive more hES cell lines for future regenerative medicine.
|
10.1007/s11626-011-9420-9
|
pubmed_1053_18210
|
A case of near-drowning in an 11 year old child with severe epilepsy (myoclone-astatic) is described. The child was left alone in a indoor swimming-pool and was found lifeless on the bottom 1-2 minutes later presumably after an epileptic seizure. Resuscitation was instituted immediately and the child survived without sequelae. Leaving children with seizure phenomena without observation in the neighbourhood of swimming pools, is warned against.
|
pubmed_1053_18210
|
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