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pubmed_1127_17158 | To examine the prevalence of obsessive-compulsive symptoms, we evaluated 69 outpatients with panic disorder. We found a 30% prevalence of obsessive-compulsive symptoms. The patients with obsessive-compulsive symptoms had an earlier onset of illness and were more likely to have current and past major depression than the other ones. | 10.1016/0924-9338(96)88393-3 |
pubmed_617_16611 | Malignant vulvar tumors must be treated by radical removal of the tumor as well as a sufficient amount of surrounding healthy tissue. The resulting defects can be resolved by skin transplants, local transfers, skin flaps, muscle flaps or free tissue transfers. We describe the case history of a patient who underwent radical vulvectomy for a malignant tumor with immediate reconstruction by local flaps from the area of inner thighs and mons pubis. The advantages and disadvantages of this method are compared to other reconstructive surgery methods. | pubmed_617_16611 |
pubmed_321_15373 | An episodic memory goes through three different stages: acquisition, consolidation and recall. A new study suggests that distinct microcircuits in the hippocampus underlie the process of memory acquisition and recall. | 10.1016/j.cub.2017.09.042 |
pubmed_139_14216 | At present general practitioners lack a tool for defining the level of disability of individual patients and groups of patients with arthritis. An assessment technique (health assessment questionnaire) developed in the United States is described, and its use in general practice evaluated. Sixty two patients agreed to be visited at home to compare their observed abilities when performing the tasks of the health assessment questionnaire. The health assessment questionnaire (HAQ) is easily understood and takes patients only 10-15 minutes to complete. The numerical scores (range 0-3) for disability obtained on the postal questionnaire are close to the observed scores when patients are visited at home. | 10.1136/ard.46.8.598 |
pubmed_129_22393 | To correlate the hepatitis B virus P gene with the enzymatic activities predicted to participate in hepadnavirus reverse transcription, a series of P gene mutants containing missense mutations, in-phase insertions, and in-phase deletions was constructed by site-directed mutagenesis. These mutants were tested in the context of otherwise intact hepatitis B virus genomes for the ability to produce core particles containing the virus-associated polymerase activity. The results obtained suggest that the P protein consists of three functional domains and a nonessential spacer arranged in the following order: terminal protein, spacer, reverse transcriptase/DNA polymerase, and RNase H. The first two domains are separated by a spacer region which could be deleted to a large extent without significant loss of endogenous polymerase activity. In cotransfection experiments, all P gene mutants could be complemented in trans by constructs expressing the wild-type gene product but not by a second P gene mutant. This indicates that the multifunctional P gene is expressed as a single translational unit and independent of the core gene and furthermore that the gene product is freely diffusible and not processed before core assembly. | 10.1128/JVI.64.2.613-620.1990 |
pubmed_963_6275 | 3'-Deoxy-beta-L-erythro- (3), 3'-deoxy-beta-L-threo- (6), 2'-fluoro- (7) and 2'-azido-2',3'-dideoxy-beta-L-erythro- (10) pentofuranonucleoside derivatives of thymine have been synthesized and their antiviral properties examined. All these derivatives were stereospecifically prepared by glycosylation of thymine with a suitable peracylated 3-deoxy-L-erythro-pentofuranose sugar (1), followed by appropriate chemical modifications. The prepared compounds were tested for their activity against HIV, but they did not show an antiviral effect. | 10.1080/15257770008045443 |
pubmed_516_20112 | The whitefly-transmitted Tomato Yellow Leaf Curl Virus (TYLCV) is the major pathogen of tomato crop in Cuba and one of the most outstanding viral diseases of plants worldwide. In this work, we have developed transgenic tomato plants, transformed with an intron-hairpin genetic construction to induce post- transcriptional gene silencing against the early TYLCV replication associated protein gene (C1). The intron-hairpin RNA produced involves 726 nts of the 3' end of the TYLCV C1 gene as the arms of the hairpin, and the castor bean catalase intron. Transgenic tomato plants belonging to line 126, which harbor a single transgene copy, showed immunity to TYLCV, even in extreme conditions of infection (4-leaf-stage plants and 300 to many hundreds viruliferous whiteflies per plant during 60 days). Dot blot hybridization of these plants showed no TYLCV DNA presence 60 days after inoculation. Small interfering RNA molecules were detected in both inoculated and non-inoculated plants from line 126. These transgenic tomato plants of the otherwise very TYLCV-susceptible Campbell-28 tomato cultivar, are the first report of resistance to a plant DNA virus obtained by the use of the intron-hairpin RNA approach. | 10.1007/s11248-005-5238-0 |
pubmed_429_8205 | The pattern of follicular atresia was studied in nine ovaries from children between the ages 3 months and 8 years. Atretic follicles were found among follicles at all stages of development. The percentage of follicles with signs of atresia became larger as the size of the follicles increased. Only 2% of small follicles (Type 3b) showed signs of atresia, while all follicles greater than 1 mm in diameter (Type 8) were atretic. In follicles of Type 5 and larger, four stages of atresia, which represent consecutive stages of a single atretic process, were defined. The beginning of atresia was characterized by the presence of pyknotic granulosa cells. As atresia progressed, the granulosa layer disappeared, the oocyte became necrotic, the follicle collapsed and the theca cells became hypertrophied. The oocyte can degenerate in several ways: it can be penetrated by cells, the nucleus can become pyknotic or it may complete meiotic prophase. It is suggested that the last event is only possible after the oocyte has reached its full size and has completed RNA synthesis. | 10.1530/jrf.0.0460055 |
pubmed_262_9686 | OBJECTIVE
To analyze the attitude of nursing personnel about organ donation and transplantation in hospitals in Spain and Latin America, and factors that affect this attitude.
METHODS
Data were selected from 12 hospitals and 32 primary care centers participating in an international study (Proyecto Donante, Murcia) in 4 countries including Spain (n = 650), Mexico (n = 428), Cuba (n = 89), and Costa Rica (n = 27). The sample was random and stratified by type of service among nursing personnel (n = 1194). Attitude was evaluated using a psychosocial questionnaire.
RESULTS
Of nursing personnel surveyed, 77% (n = 922) were in favor of organ donation. No differences were found according to whether they were directly involved in transplantation-related services (P < .05). Attitude in favor of organ donation varied between countries: 92% in Cuba, 85% in Costa Rica, 80% in Mexico, and 73% in Spain (P < .001) This attitude was also related to donation of a family member's organs (P < .001), having discussed organ donation and transplantation within the family (P < .001), the concept of brain death (P < .001), fear of body mutilation (P < .001), and manipulation of the body after death (P = .001).
CONCLUSION
Attitude toward deceased organ donation among nurses varies between countries. There is a discrepancy between those in favor vs actual donation rates in countries and work centers. These fears may become worse when donation is seen as common in daily clinical practice. | 10.1016/j.transproceed.2009.11.010 |
pubmed_496_5579 | BACKGROUND
Epidemiological investigations were carried out in the Lazio Region to assess the status of canine filariosis and to evaluate the actual risk for veterinary and medical public health.
METHODS
Since August 2001 to June 2003, a total of 972 canine blood samples, collected in public kennels and from private owners animals of the 5 Provinces of the Region, were tested. The presence of filarial parasites was evaluated by microscopy and bio-molecular techniques; the species identification was performed by means of the same diagnostic tools.
RESULTS
A total of 17/972 (1.75%; 95%CI 1.06%-2.85%) blood samples were parasitized by D. repens,13 out them drawn by dogs resident in the Province of Roma, and 4 in the other provinces. Multivariate analysis was performed in order to evaluate the association between filariosis and risk factors. The origin from coastal territories seems to be a significant risk factor to acquire the infection.
CONCLUSION
This is the first report of canine filariosis in the Lazio Region, where D. repens was before reported only in foxes. The risk of human zoonotic infection is stressed, and the absence of other filarial species is discussed. | 10.1186/1471-2334-5-75 |
pubmed_378_8202 | A method for pharmacokinetic studies using cassette dosing associated with serial bleeding in mice is described. PK profiles of four soluble epoxide hydrolase inhibitors were determined following oral, subcutaneous or intraperitoneal administration individually or in cassette dosing. Parent analyses were performed on only 5 microL of whole blood from serial bleeds (up to 10 per animal), by LC/MS/MS. An accuracy (88-100%) and precision (<10% RSD) were observed, leading to reliable datum points for PK calculation. PK profiles, T(max), C(max) and half-life values after cassette dosing were similar to the individual PK results. This method dramatically increases speed of data collection while dramatically reducing cost and animal usage. The results presented here clearly indicate that this proposed method could be applicable to high-throughput PK studies. | 10.1016/j.aca.2005.11.049 |
pubmed_300_10359 | INTRODUCTION
To report our initial experience of laparostomy and immediate intra-abdominal vacuum therapy in patients with severe peritonitis due to intra-abdominal catastrophes.
PATIENTS AND METHODS
Twenty-seven patients underwent emergency laparotomy and laparostomy formation with the application of immediate intra-abdominal TRAC-VAC therapy (male:female ratio, 1:1.2; median age, 73 years; range, 34-84 years). Predicted mortality was assessed using the P-POSSUM score and compared with clinically observed outcomes.
RESULTS
Ten patients (37%) with a mean predicted P-POSSUM mortality of 72%, died of sepsis and multi-organ failure. Seventeen patients (mean P-POSSUM 48% expected mortality) survived to discharge. One patient with pancreatitis died from small bowel obstruction 1-year post discharge, two patients developed a small bowel fistula. One patient had an allergic reaction to the VAC dressing. Our patients, treated with laparostomy and TRAC VAC therapy, had a significantly improved observed survival when compared to P-POSSUM expected survival (P = 0.004).
CONCLUSIONS
Laparostomy with immediate intraperitoneal VAC therapy is a robust and effective system to manage patients with intra-abdominal catastrophes. There were significantly improved outcomes compared to the mortality predicted by P-POSSUM scores. Damage control surgery with laparostomy formation and intra-abdominal VAC therapy should be considered in patients with severe peritonitis. | 10.1308/003588409X12486167520993 |
pubmed_223_19304 | This study investigated how parents' value-based enculturation and acculturation processes (i.e., Mexican American and mainstream American values trajectories across their youths' development from late childhood to middle adolescence) related to their youths' behavioral, affective, and cognitive components of bicultural competence in late adolescence. Our sample included 749 U.S. Mexican-origin youths (30% Mexico-born; 49% female), and their parents, followed for 7 years (Mage = 10.44 to 17.38 years). Linear latent growth analyses revealed that both parental enculturation and acculturation processes have important implications for U.S. Mexican-origin adolescents' bicultural competence. This work highlights parental promoting and inhibiting influences on the development of bicultural competence, a normative developmental competency among ethnic-racial minority and immigrant adolescents. (PsycInfo Database Record (c) 2020 APA, all rights reserved). | 10.1037/dev0001022 |
pubmed_472_8710 | BACKGROUND
Homeobox genes encode a diverse set of transcription factors implicated in a vast range of biological processes including, but not limited to, embryonic cell fate specification and patterning. Although numerous studies report expression of particular sets of homeobox genes, a systematic analysis of the tissue specificity of homeobox genes is lacking.
RESULTS
Here we analyse publicly-available transcriptome data from human and mouse developmental stages, and adult human tissues, to identify groups of homeobox genes with similar expression patterns. We calculate expression profiles for 242 human and 278 mouse homeobox loci across a combination of 59 human and 12 mouse adult tissues, early and late developmental stages. This revealed 20 human homeobox genes with widespread expression, primarily from the TALE, CERS and ZF classes. Most homeobox genes, however, have greater tissue-specificity, allowing us to compile homeobox gene expression lists for neural tissues, immune tissues, reproductive and developmental samples, and for numerous organ systems. In mouse development, we propose four distinct phases of homeobox gene expression: oocyte to zygote; 2-cell; 4-cell to blastocyst; early to mid post-implantation. The final phase change is marked by expression of ANTP class genes. We also use these data to compare expression specificity between evolutionarily-based gene classes, revealing that ANTP, PRD, LIM and POU homeobox gene classes have highest tissue specificity while HNF, TALE, CUT and CERS are most widely expressed.
CONCLUSIONS
The homeobox genes comprise a large superclass and their expression patterns are correspondingly diverse, although in a broad sense related to an evolutionarily-based classification. The ubiquitous expression of some genes suggests roles in general cellular processes; in contrast, most human homeobox genes have greater tissue specificity and we compile useful homeobox datasets for particular tissues, organs and developmental stages. The identification of a set of eutherian-specific homeobox genes peaking from human 8-cell to morula stages suggests co-option of new genes to new developmental roles in evolution. | 10.1186/s12861-016-0140-y |
pubmed_6_10075 | Historically, chemicals exceeding maximum allowable exposure levels have been disastrous to underdeveloped countries. The global food industry is primarily affected by toxic chemical substances because of natural and anthropogenic factors. Food safety is therefore threatened due to contamination by chemicals throughout the various stages of food production. Persistent Organic Pollutants (POPs) in the form of pesticides and other chemical substances such as Polychlorinated Biphenyls (PCBs) have a widely documented negative impact due to their long-lasting effect on the environment. This present review focuses on the chemical contamination pathways along the various stages of food production until the food reaches the consumer. The contamination of food can stem from various sources such as the agricultural sector and pollution from industrialized regions through the air, water, and soil. Therefore, it is imperative to control the application of chemicals during food packaging, the application of pesticides, and antibiotics in the food industry to prevent undesired residues on foodstuffs. Ultimately, the protection of consumers from food-related chemical toxicity depends on stringent efforts from regulatory authorities both in developed and underdeveloped nations. | 10.3390/ijerph18115795 |
pubmed_621_1751 | BACKGROUND
Bardet-Biedl syndrome (BBS) is a genetic disorder with obesity as one of the major phenotypic criterion, which is proposed to be of neuroendocrine origin. Therefore, disturbances in appetite-regulating hormones have been considered as causative factors. Acyl ghrelin is an orexigenic hormone, whereas its desacylated form, obestatin, and leptin have the opposite functions. Ghrelin is negatively regulated in relation to nutritional status. The aim of this study was to evaluate the impact of hormone alterations on obesity development in BBS patients.
METHODS
Total and acylated ghrelin, obestatin, leptin and adiponectin were measured in eight children with BBS. The results were analyzed in relation to auxological parameters [body mass index (BMI), height].
RESULTS
The mean BMI was significantly increased in BBS patients compared to the controls. Plasma levels of acylated ghrelin, total ghrelin and obestatin were slightly elevated in BBS patients compared to controls, as was the acyl/total ghrelin ratio. Leptin levels were significantly elevated in BBS patients.
CONCLUSION
BBS patients lack the negative regulatory mechanisms of appetite-regulating hormones with respect to nutritional status and exhibit resistance to anorexigenic leptin. This results in a shift towards the orexigenic effects of this self-regulating system. These alterations may in part be responsible for the disturbed appetite regulation in BBS patients. | 10.1007/s00467-012-2220-y |
pubmed_776_20984 | To reliably detect early pregnancy factor (EPF) in cattle, monoclonal antibody specific for bovine CD2 molecule, which is the sheep red blood cell (SRBC) receptor on bovine T cell surface, was applied to the rosette inhibition test. The rosette inhibition titers (RITs) were significantly higher in pooled sera from early pregnant cattle than in those of non-pregnant cattle using two anti-bovine CD2 monoclonal antibodies, B26A4 (P < 0.001) and BAQ95A (P < 0.01). The dissociation value of RITs between pregnancy and non-pregnancy with B26A4 was greater than that with BAQ95A. The B26A4 monoclonal antibody was therefore applied to the rosette inhibition test in subsequent experiments. The RITs in serum of individual pregnant and non-pregnant cows 8 days after estrus were significantly different (P < 0.001) by three or more dilutions. When the rosette inhibition test was carried out in sera from individual pregnant and non-pregnant cows at estrus and at 24, 72 and 168 hr after ovulation, the RITs of pregnancy sera increased significantly at 24 hr after ovulation as compared with non-pregnancy sera (P < 0.001). These results indicate anti-bovine CD2 monoclonal antibody can be utilized with the rosette inhibition test to detect EPF in cattle, and that this assay detects bovine EPF for pregnancy serum at least 24 hr after ovulation. | 10.1292/jvms.57.721 |
pubmed_484_21018 | [Reaction: see text] A one-pot Reformatsky/cyclopropanation sequence induced by diethylzinc allows the transformation of omega-unsaturated ketones and aldehydes to omega-cyclopropyl alcohols. | 10.1021/ol048142b |
pubmed_872_9536 | Glucose tolerance and the behaviour of cortisol during an oral glucose tolerance test (OGTT) was investigated in 126 patients with adrenal "incidentalomas" (age: > 45 years) and in 129 age-matched controls. Impaired glucose tolerance (IGT) was found to be more common (p < 0.02) among patients with adrenal incidentalomas. Subdividing these patients by their body weight it was found that 29% (controls: 25%) of those with normal body weight (BMI 20 - 25 kg/m2) had IGT/DM. In overweight (BMI 25 - 30 kg/m2) and obese patients (BMI 30 - 40 kg/m2) the share of IGT/DM was 32% (controls: 19%) and 66% (controls 42%), respectively. The prevalence of a "paradoxical" rise in serum cortisol concentrations during the OGTT was slightly higher (p < 0.05) among patients with adrenal incidentaloma than among controls. Patients as well as controls with this abnormal behaviour of cortisol were characterized by lower basal serum cortisol concentrations (p < 0.01) but no association was seen with either the presence of IGT or with post-dexamethasone concentrations of serum cortisol. Thus both in patients with and without adrenal incidentalomas abnormal glucose tolerance is an age- and weight-dependent phenomenon unrelated to the post-prandial behaviour of serum cortisol concentrations. | 10.1055/s-2003-44288 |
pubmed_54_5517 | Advances in understanding the immunological and molecular basis of autoimmune diseases have made gene therapy a promising approach to treat the affected patients. Gene therapy for autoimmune diseases aims to regulate the levels of proinflammatory cytokines or molecules and the infiltration of lymphocytes to the effected sites through successful delivery and expression of therapeutic genes in appropriate cells. The ultimate goal of gene therapy is to restore and maintain the immune tolerance to the relevant autoantigens and improve clinical outcomes for patients. Here, we summarize the recent progress in identifying genes responsible for autoimmune diseases and present examples where gene therapy has been applied as treatments or prevention in autoimmune diseases both in animal models and the clinical trials. Discussion on the advantages and pitfalls of gene therapy strategies employed is provided. The intent of this review is to inspire further studies toward the development of new strategies for successful treatment of autoimmune diseases. | 10.1007/s12016-014-8451-x |
pubmed_408_10284 | The delayed footpad reaction against syngeneic testicular cells was studied in cyclophosphamide (CY)-pretreated mice whose mononuclear phagocyte system (MPS) was blocked with colloidal carbon or stimulated with Corynebacterium parvum (C. parvum). The delayed footpad reaction was augmented by MPS-blockade, whereas it was depressed by MPS-stimulation. It was observed that syngeneic testicular cells were phagocytized and degraded more effectively by C. parvum-stimulated macrophages in vitro and that the testicular antigen phagocytized by C. parvum-stimulated macrophages proved to become less immunogenic in cell transfer experiments. | pubmed_408_10284 |
pubmed_121_24276 | Low intensity ultrasound (LIUS) has been adopted for a variety of therapeutic purposes because of its bioeffects such as thermal, mechanical, and cavitation effects. The mechanism of impact and cellular responses of LIUS in cellular regulations have been revealed, which helps to understand the role of LIUS in tumor treatment, stem cell therapy, and nervous system regulation. The review summarizes the bioeffects of LIUS at the cellular level and its related mechanisms, detailing the corresponding theoretical basis and latest research in the study of LIUS in the regulation of cells. In the future, the design of specific LIUS-mediated treatment strategies may benefit from promising investigations which is hoped to provide encouraging therapeutic data. | 10.1016/j.pbiomolbio.2022.06.004 |
pubmed_424_11871 | In 38 patients with type 1 diabetes (DM 1) and 24 non-diabetics we investigated LDL susceptibility to in vitro oxidation. Fast and post-prandial glycaemia (PPG), glycated hemoglobin (HbA1c) and lipid profile were determined, together with an spectrophotometric analysis of LDL oxidation before and 1, 3, 6 and 24 hours after addition of the oxidant substance - copper sulphate (CuSO4). The LDL oxidation coefficient in the two groups presented similar basal values; however 3 hours after CuSO4, LDL was more oxidized in patients with DM1. There was a negative correlation with PPG (r= -0.2511; p<0.05) and HbA1c (r= -0.2541; p<0.05). We conclude that in our sample of DM patients LDL was oxidized earlier than in the non-diabetics and that the glycemic control is important in this event. | 10.1590/s0004-27302004000400012 |
pubmed_220_21463 | AIM
To study the effect of Ginkgo biloba extract (EGb 761) containing 22-27% flavonoids (ginkgo-flavone glycosides) and 5-7% terpenoids (ginkgolides and bilobalides) on cell proliferation and cytotoxicity in human hepatocellular carcinoma (HCC) cells.
METHODS
Human HCC cell lines (HepG2 and Hep3B) were incubated with various concentrations (0-1 000 mg/L) of EGb 761 solution. After 24 h incubation, cell proliferation and cytotoxicity were determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and lactate dehydrogenase (LDH) release, respectively. After 48 h incubation, the expression of proliferating cell nuclear antigen (PCNA) and p53 protein was measured by Western blotting.
RESULTS
The results showed that EGb 761 (50-1 000 mg/L) significantly suppressed cell proliferation and increased LDH release (P<0.05) in HepG2 and Hep3B cells compared with the control group. The cell proliferation of HepG2 and Hep3B cells treated with EGb 761 (1 000 mg/L) was 45% and 39% of the control group (P<0.05), respectively. LDH release of HepG2 cells without and with EGb 761 (1 000 mg/L) treatment was 6.7% and 37.7%, respectively, and that of Hep3B cells without and with EGb 761 (1 000 mg/L) treatment was 7.2% and 40.3%, respectively. The expression of PCNA and p53 protein in HepG2 cells treated with EGb 761 (1 000 mg/L) was 85% and 174% of the control group, respectively.
CONCLUSION
Ginkgo biloba extract significantly can suppress proliferation and increase cytotoxicity in HepG2 and Hep3B cells. Additionally, Ginkgo biloba extract can decrease PCNA and increase p53 expression in HepG2 cells. | 10.3748/wjg.v10.i1.37 |
pubmed_439_8627 | The SARS-CoV-2 virus, commonly known as COVID-19, first occurred in December 2019 in Wuhan, Hubei Province, China. Since then, it has become a tremendous threat to human health. With a pandemic threat, it is in the significant interest of the scientific world to establish its method of infection. In this manuscript, we combine knowledge of the infection mechanism with theoretical methods to answer the question of the virus's selectivity. We proposed a two-stage infection mechanism. In the first step, the virus interacts with the ACE2 receptor, with the "proper strength". When the interaction is too strong, the virus will remain in an "improper position"; if the interaction is too weak, the virus will "run away" from the cell. We also indicated three residues (positions 30, 31, and 353) located on the ACE2 protein-binding interface, which seems to be crucial for successful infection. Our results indicate that these residues are necessary for the initiation of the infection process. | 10.3390/molecules27072080 |
pubmed_219_14392 | Whether bilingual children outperform monolingual children on visuospatial and verbal working memory tests was investigated. In addition, relations among bilingual proficiency, language use at home, and working memory were explored. The bilingual Turkish-Dutch children (n=68) in this study were raised in families with lower socioeconomic status (SES) and had smaller Dutch vocabularies than Dutch monolingual controls (n=52). Having these characteristics, they are part of an under-researched bilingual population. It was found that the bilingual Turkish-Dutch children showed cognitive gains in visuospatial and verbal working memory tests when SES and vocabulary were controlled, in particular on tests that require processing and not merely storage. These findings converge with recent studies that have revealed bilingual cognitive advantages beyond inhibition, and they support the hypothesis that experience with dual language management influences the central executive control system that regulates processing across a wide range of task demands. Furthermore, the results show that bilingual cognitive advantages are found in socioeconomically disadvantaged bilingual populations and suggest that benefits to executive control are moderated by bilingual proficiency. | pubmed_219_14392 |
pubmed_954_4401 | BACKGROUND
Genes involved in the angiopoietin and pericyte pathways may become escape mechanisms under antivascular endothelial growth factor (anti-VEGF) therapy. The authors investigated whether variations within genes in these pathways are associated with clinical outcome in patients with colorectal liver metastases who undergo liver resection and receive perioperative, bevacizumab-based chemotherapy.
METHODS
Single nucleotide polymorphisms (SNPs) in 9 genes (angiopoietin-1 [ANGPT1]; ANGPT2; TEK tyrosine kinase, endothelial [TEK]; platelet-derived growth factor β [PDGFB]; β-type platelet-derived growth factor receptor [PDGFRB]; insulin-like growth factor 1 [IGF1]; transforming growth factor β1 [TGFB1]; RalA binding protein 1 [RALBP1]; and regulator of G-protein signaling 5 [RGS5]) were analyzed in samples of genomic DNA from 149 patients and were evaluated for associations with clinical outcome.
RESULTS
RALBP1 reference SNP 329007 (rs329007) A>G resulted in a significant difference in recurrence-free survival (A/A genotype, 14.0 months; A/G or G/G genotype, 9.2 months; hazard ratio [HR], 1.60; P = .024). PDGFB rs1800818 A>G was associated with 3-year overall survival rates (A/A genotype, 78%; A/G genotype, 69%; [HR 1.37]; G/G genotype, 53%; [HR 2.12]; P = .048). In multivariate analysis, RALBP1 rs329007 A>G remained significant (HR, 1.99; P = .002). PDGFB rs1800818 A>G and RALBP1 rs329007 A>G were correlated with radiologic response (A/A or A/G genotype, 86%; G/G genotype, 71% [P = .042]; A/A genotype, 78%; A/G or G/G genotype, 94% [P = .018], respectively). RALBP1 rs329007 A>G demonstrated significantly different rates of histologic response (A/A genotype: major histologic response, 35%; partial histologic response, 34%; no histologic response, 30%; A/G or G/G genotype: 46%, 13%, and 41%, respectively; P = .029). Recursive partitioning analysis revealed that ANGPT2 rs2442599 T>C and RALBP1 rs329007 A>G were the main SNPs that predicted histologic response and recurrence-free survival, whereas PDGFB rs1800818 A>G was the leading SNP that predicted overall survival. ANGPT2 rs2916702 C>T and rs2442631 G>A were significantly associated with the probability of achieving a cure.
CONCLUSIONS
The current data suggest that variations in genes involved in the angiopoietin and pericyte pathways may be predictive and/or prognostic biomarkers in patients with resected colorectal liver metastases who receive bevacizumab-based chemotherapy. | 10.1002/cncr.29259 |
pubmed_5_4921 | We have performed molecular genetic analyses on 160 Brazilian patients diagnosed with cystic fibrosis (CF). Screening of mutations in 320 CF chromosomes was performed through single strand conformation polymorphism (SSCP) and heteroduplex analyses assay followed by DNA sequencing of the 27 exons and exon/intron boundaries of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The frequency of CFTR variants of T-tract length of intron 8 (IVS8 Tn) was also investigated. This analysis enabled the detection of 232/320 CF mutations (72.2%) and complete genotyping of 61% of the patients. The deltaF508 mutation was found in 48.4% of the alleles. Another fifteen mutations (previously reported) were detected: G542X, R1162X, N1303K, R334W, W1282X, G58E, L206W, R553X, 621+1G-->T, V232D, 1717-1G-->A, 2347 delG, R851L, 2789+5G-->A, and W1089X. Five novel mutations were identified, V201M (exon 6a), Y275X (exon 6b), 2686 insT (exon 14a), 3171 delC (exon 17a), and 3617 delGA (exon 19). These results contribute to the molecular characterization of CF in the Brazilian population. In addition, the identification of the novel mutation Y275X allowed prenatal diagnosis in a high-risk fetus. | 10.1089/109065700316516 |
pubmed_470_21445 | The underlying genetic events associated with follicular thyroid tumorigenesis are still ill defined. In this study, we performed a screening for chromosome imbalances by comparative genomic hybridization (CGH) in a group of 12 follicular adenomas (FAs) and 20 follicular carcinomas (FTCs) previously characterized by conventional cytogenetics and flow cytometry analysis. In general, a great similarity was observed between the CGH profiles of the FAs and FTCs. In both benign and malignant tumors, a combination of gains affecting 5, 7, 12, 17, 19, and 20 was observed. Chromosome 7 was the most frequently affected chromosome, with three regions of consensus gains: 7p11-12, 7q11.3-q21, and 7q31. Recurrent gains of chromosomes 5 and 12 involved 5p11, 5p15, 5q13-q22, 5q21-q23, 12p11, and 12q11-q12. DNA sequence losses were also observed in both tumor groups. Chromosomal arms deleted in at least five of the neoplasms were (in order of frequency): in adenomas, 15q, 2p/2q, 3q, 6p/6q, 11q, and 22q; and in FTCs, 3p, 2p, 8q, 1p, 2q, 3q, 6q, 8p, 9p, 11q, 13q, 6p, and 18q. The statistical evaluation of the CGH data demonstrated that 15q loss was significantly associated with FA. Two regions of minimal common loss were defined by CGH at 15: 15q11-q21 and 15q26-qter. The identification of these regions provides a basis for further molecular studies. | 10.1002/gcc.10146 |
pubmed_391_8646 | Five men were exposed to toluene diisocyanate (TDI) atmospheres for 7.5 h. The TDI atmospheres were generated by a gas-phase permeation method, and the exposures were performed in an 8-m3 stainless-steel test chamber. The mean air concentration of TDI was ca. 40 micrograms/m3, which corresponds to the threshold limit value (TLV) of Sweden. The inhaled doses of 2,4- and 2,6-TDI were ca. 120 micrograms. TDI in the test chamber air was determined by an HPLC method using the 9-(N-methylaminomethyl)-anthracene reagent and by a continuous-monitoring filter-tape instrument. After hydrolysis of plasma and urine, the related amines, 2,4- and 2,6-toluenediamine 2,4-, and 2,6-TDA), were determined as pentafluoropropionic anhydride (PFPA) derivatives by capillary gas-chromatography using selected ion monitoring (SIM) in the electron-impact mode. The urinary elimination of the TDAs showed a possible biphasic pattern, with rapid first phases for 2,4-TDA (mean t1/2 for the concentration in urine, 1.9 h) and for 2,6-TDA (mean t1/2 for the concentration in urine, 1.6 h). The cumulative amount of 2,4-TDA excreted in urine within 28 h ranged from 8% to 14% of the estimated dose of 2,4-TDI, and the cumulative amount of 2,6-TDA in urine ranged from 14% to 18% of the 2,6-TDI dose. The average urinary level of 2,4-TDA was 5 micrograms/l in the 6 to 8-h sample (range 2.8-9.6 micrograms/l), and the corresponding value for 2,6-TDA was 8.6 micrograms/l (range, 5.6-16.6 micrograms/l). Biological monitoring of exposure to 2,4- and 2,6-TDI by analysis of 2,4- and 2,6-TDA in urine is feasible. | 10.1007/BF00379069 |
pubmed_161_8217 | Non-invasive measurements of right and left ventricular ejection fraction (RVEF, LVEF) by multiple-gated equilibrium radionuclide ventriculography were performed in 18 control subjects, 16 patients with angina pectoris, and 45 patients with hypoxic chronic bronchitis and emphysema. The mean RVEF in the control subjects was 0.62 +/- 0.09 (SD), which was not significantly different from the mean RVEF in the patients with angina (0.60 +/- 0.09), but was significantly higher (p less than 0.01) than the mean value in patients with chronic bronchitis and emphysema (0.45 +/- 0.11). LVEF was not significantly different in the groups studied. There was a significant correlation between LVEF and RVEF only in patients with chronic bronchitis and emphysema (p less than 0.001). Those patients with chronic bronchitis and emphysema who had clinical evidence of cor pulmonale at the time of the study had significantly lower values of RVEF and LVEF (p less than 0.001) than patients with no previous cor pulmonale or those who had had cor pulmonale in the past. There was a significant correlation between RVEF and arterial oxygen (p less than 0.01) and carbon dioxide tensions (p less than 0.05). Reduced RVEF in patients with chronic bronchitis and emphysema may be an early indicator of the development of cor pulmonale and may be useful as a non-invasive method of assessing the effects of therapeutic interventions. | 10.1136/thx.38.7.494 |
pubmed_683_21516 | OBJECTIVE
to make an inventory of the opinions and attitudes of the Dutch female population (aged 45-65) and their partners on the climacteric period.
DESIGN
Data were collected as part of a weekly computer assisted questionnaire filled in by a representative panel composed of 234 women aged 45-65 and their partners.
SETTING
A random sample of the population of The Netherlands.
RESULTS
12% of the women were current users of hormone replacement therapy (HRT), 21% had been hysterectomized, 32% were smokers. Although the prevalence of climacteric symptoms was as expected, only 1 out of 3 peri- and post-menopausal women were really troubled by the symptoms and had consulted a physician. The attitude towards HRT was neutral. Most women preferred a natural approach as a solution to the problems. Information on the climacteric was mostly obtained via the media, but in general the self-assessed level of knowledge was regarded by the panel as very low, even in current HRT users. Women on HRT were more positive toward treatment, and less confident about the spontaneous disappearance of the problems. Nearly all women, including current HRT users, regarded the absence of menstruation as a relief. Partners of climacteric women had the same opinion as their wives on all items.
CONCLUSION
There is a lack of information on the climacteric and on the use of HRT. The Dutch female population tends to a natural approach of the climacteric without medication, but the general attitude can be regarded as neutral. | 10.1016/0028-2243(94)90050-7 |
pubmed_625_5463 | Community and stakeholder engagement (CSE) is increasingly acknowledged as foundational to global health research. This commentary builds on the multisite framework for CSE described in an eco-health study conducted in Southern Africa. We acknowledge the context-specific nature of some of the challenges for CSE and draw attention to significant issues and concerns that arose from our studies of CSE in the context of multisite HIV prevention trials in South Africa, India, and Canada: (a) Pretrial-historically based mistrust, identification of appropriate gatekeepers, and considering the breadth of community; (b) Trial implementation-impact of early trial cessations, appropriate community roles and responsibilities, and multifaceted stigma; and (c) Posttrial-supporting and sustaining CSE mechanisms independent of particular trials. Many of these challenges are exacerbated by widespread disparities in wealth and power between trial sponsors and participating communities, further supporting the central importance of sound CSE practices and infrastructures to advance ethical biomedical and public health research. | 10.1177/1556264618783560 |
pubmed_877_4419 | Research shows that the association between adverse climate conditions and human migration is heterogeneous. One reason for this heterogeneity is the differential vulnerability of populations to climate change. This includes highly vulnerable, "trapped" populations that are too poor to migrate given deep and persistent poverty, the financial costs of migrating, and the erosion of already fragile economic livelihoods under climate change. Another reason for this heterogeneity is the differential vulnerability of places. However, despite the growing list of studies showing that the climate-migration relationship clearly varies across places, there is surprisingly little research on the characteristics of places themselves that trap, or immobilize, populations. Accordingly, we provide the first account of the "holding power" of places in the association between adverse climate conditions and migration flows among 55 districts in Zambia in 2000 and 2010. Methodologically, we combine high resolution climate information with aggregated census micro data to estimate gravity models of inter-district migration flows. Results reveal that the association between adverse climate conditions and migration is positive only for wealthy migrant-sending districts. In contrast, poor districts are characterized by climate-related immobility. Yet, our findings show that access to migrant networks enables climate related mobility in the poorest districts, suggesting a viable pathway to overcome mobility constraints. Planners and policy makers need to recognize the holding power of places that can trap populations and develop programs to support in situ adaptation and to facilitate migration to avoid humanitarian emergencies. | 10.1007/s10113-017-1224-3 |
pubmed_314_19543 | Cysteine and C-terminal cysteine peptides are selectively S-acylated at 0-20 degrees C by N-(Pg-alpha-aminoacyl)benzotriazoles to give N-Pg-S-acyl-isodi-, -isotri-, and -isotetra-peptides isolated in good yields. N-Fmoc-S-acyl-isopeptides are Fmoc deprotected to afford free S-acyl-isopeptides isolated in high yields. S-Acyl-isodi-, S-acyl-isotetra-, and S-acyl-isopentapeptides undergo chemical ligation; migration of the cysteine S-acyl groups to the N-terminal amino acids via 5-, 11-, and 14-membered transition states giving the corresponding native di-, tetra-, and penta-peptides. By contrast, the Sacyl-isotripeptide prefers intermolecular acylation from one molecule to another over an 8-membered intramolecular transition state. The developed methodology allows convenient isolation of stable, unprotected S-acyl cysteine peptides including the first isolation of S-acyl-isopeptides, which should facilitate the investigation of ligation by physical organic chemistry techniques. | 10.1039/c003234d |
pubmed_588_3995 | Glucocorticoids exert a variety of immunomodulatory activities. Since changes in glucocorticoid homeostasis impact on susceptibility to autoimmune diseases, and synthetic glucocorticoids are widely used in the treatment of multiple sclerosis, a detailed understanding of their mechanism of action is desirable. Experimental autoimmune encephalomyelitis is a common animal model that mirrors many hallmarks of multiple sclerosis, a chronic inflammatory disease of the CNS with presumed autoimmune origin. Experimental autoimmune encephalomyelitis has been instrumental for many years in studying multiple sclerosis, revealing the blood-brain barrier, the microglia and T-cell apoptosis as major targets of glucocorticoids in this disease. Despite the great advances in the field, the answers to many questions concerning the mechanism of glucocorticoids; for example, the contribution of nongenomic effects or the cell-type specificity of their action, remain elusive. This review will critically discuss what we have learned so far from the analysis of animal models of the molecular mode of therapeutic and endogenous glucocorticoid action in multiple sclerosis. With this knowledge in mind, we should be able to further improve the management of multiple sclerosis using this class of drugs. | 10.1586/14737175.6.11.1657 |
pubmed_631_6097 | This article describes the role of vocational assessment in personal injury compensation cases in the United Kingdom. An outline is given of some of the difficulties the writer has confronted in getting vocational assessment accepted as a legitimate resource in such cases, and the rationale for using American vocational assessment tools is presented. Finally, reference is made to two key legal rulings. The first ruling threatened the use of vocational assessment, and the second went some way toward redressing the balance. | 10.3233/WOR-1995-5105 |
pubmed_93_7624 | Escherichia coli is one of the major microorganisms for recombinant protein production because it has been best characterized in terms of molecular genetics and physiology, and because of the availability of various expression vectors and strains. The synthesis of proteins is one of the most energy consuming processes in the cell, with the result that cellular energy supply may become critical. Indeed, the so called metabolic burden of recombinant protein synthesis was reported to cause alterations in the operation of the host's central carbon metabolism. To quantify these alterations in E. coli metabolism in dependence of the rate of recombinant protein production, (13)C-tracer-based metabolic flux analysis in differently induced cultures was used. To avoid dilution of the (13)C-tracer signal by the culture history, the recombinant protein produced was used as a flux probe, i.e., as a read out of intracellular flux distributions. In detail, an increase in the generation rate rising from 36 mmol(ATP)g(CDW)(-1)h(-1) for the reference strain to 45 mmol(ATP)g(CDW)(-1)h(-1) for the highest yielding strain was observed during batch cultivation. Notably, the flux through the TCA cycle was rather constant at 2.5±0.1 mmol g(CDW)(-1)h(-1), hence was independent of the induced strength for gene expression. E. coli compensated for the additional energy demand of recombinant protein synthesis by reducing the biomass formation to almost 60%, resulting in excess NADPH. Speculative, this excess NADPH was converted to NADH via the soluble transhydrogenase and subsequently used for ATP generation in the electron transport chain. In this study, the metabolic burden was quantified by the biomass yield on ATP, which constantly decreased from 11.7g(CDW)mmol(ATP)(-1) for the reference strain to 4.9g(CDW)mmol(ATP)(-1) for the highest yielding strain. The insights into the operation of the metabolism of E. coli during recombinant protein production might guide the optimization of microbial hosts and fermentation conditions. | 10.1016/j.jbiotec.2011.06.016 |
pubmed_947_6714 | Sufficient postoperative dietary intake is crucial for ensuring a better surgical outcome. This study aimed to investigate the postoperative dietary intake achievement and predictors of postoperative dietary intake among gynecologic cancer patients. A total of 118 participants were included in this secondary analysis. Postoperative dietary data was pooled and re-classified into early postoperative dietary intake achievement (EDIA) (daily energy intake (DEI) ≥ 75% from the estimated energy requirement (EER)) and delay dietary intake achievement (DDIA) (DEI < 75% EER) There was a significant difference in postoperative changes in weight (p = 0.002), muscle mass (p = 0.018), and handgrip strength (p = 0.010) between the groups. Postoperative daily energy and protein intake in the EDIA was significantly greater than DDIA from operation day to discharged (p = 0.000 and p = 0.036). Four significant independent postoperative dietary intake predictors were found: preoperative whey protein-infused carbohydrate loading (p = 0.000), postoperative nausea vomiting (p = 0.001), age (p = 0.010), and time to tolerate clear fluid (p = 0.016). The multilinear regression model significantly predicted postoperative dietary intake, F (4, 116) = 68.013, p = 0.000, adj. R2 = 0.698. With the four predictors' recognition, the integration of a more specific and comprehensive dietitian-led supportive care with individualized nutrition intervention ought to be considered to promote functional recovery. | 10.3390/nu14010222 |
pubmed_993_11509 | Following an earlier report, plasma cortisol-binding capacity (CBC) was estimated in a new series of 11 men with unipolar depression and 11 men with bipolar illness admitted to hospital. The two groups were comparable except that the bipolar group tended to have more frequent episodes of illness and to have more family histories of affective disorder. There was no significant difference between the CBC values in each group. | 10.1017/s0033291700056634 |
pubmed_580_4070 | OBJECTIVE
To investigate the predictive/protective role of negative affect/positive affect in late pregnancy on the outcome of postpartum depression.
METHODS
A total of 491 pregnant women participated in the study. The participants were asked to fill out a series of questionnaires, which included the Profile of Mood States, the Beck Depression Inventory-II, psychosocial variables and socio-demographic characteristics and were asked to participate in a psychiatric interview. After delivery, 272 mothers participated again in the study and filled out a similar series of questionnaires.
RESULTS
Negative affect was associated with more intense depressive symptomatology, more self-perceived stress, lower self-reported social support, lower quality of life and perception of having a more difficult infant. By contrast, positive affect was negatively associated with these variables. Negative affect in late pregnancy increased the likelihood of experiencing postpartum depression (DSM-IV/OR = 2.1, 95%CI = 1.3-3.4, p = .003; ICD-10/OR = 2.1, 95%CI = 1.5-3.0, p < .001), while positive affect increased the odds of not having this condition (DSM-IV/OR = 2.0, 95%CI = 1.5-2.7, p = .042).
CONCLUSION
In pregnancy, negative affect was a predictor of postpartum depression, whereas positive affect showed a protective role. Future studies are required to explore whether psychotherapeutic strategies focusing on decreasing negative affect and enhancing positive affect in the last trimester of pregnancy can reduce the risk of postpartum depression. | pubmed_580_4070 |
pubmed_666_9499 | One of salt-induced calcium-dependent protein kinases (CDPKs) gene was isolated from Arachis hypogeae L. by RACE method. The cDNA full length was 2241bp deposited in GenBank (number KF437909), designated as AhCDPK. The coding region sequence of AhCDPK was 1629bp and encoded a protein of 542 amino acids. The molecular weight and the theoretical isoelectric point of AhCDPK was 60.96kDa and 5.61 respectively. Amino acid sequence analysis indicated that AhCDPK has highest similarity and homology with Glycine max L. In addition, the AhCDPK amino acids were predicted to encode a hydrophilic protein which localised in the endoplasmic reticulum. AhCDPK seemed to transcript in all peanut organs, and had the highest expression in seeds. The expression of AhCDPK could be strongly induced by both Ca2+ and NaCl. When exposed to salt stress, overexpressing AhCDPK in tobacco could alleviate PSII photoinhibition by improving physiological states, such as reducing the accumulation of reactive oxygen species (ROS), improving the activity of antioxidant defence system enzymes and improving the accumulation of osmotic regulation substance. These results showed that AhCDPK has the same functions as that of G. max, and it could play an important role for peanut to resist salt stress. | 10.1071/FP14190 |
pubmed_1018_11611 | The relationship between response inhibition and time estimation abilities was investigated in a group of hyperactive and non-hyperactive children. Children performed a discrete trials intertemporal response task under two conditions. Under both conditions children had to respond within a 2 s window, which was delayed for a set period (either 5 or 15 s). In condition one (signalled condition), these response requirements were signalled by changes in the expression of a face drawn on a computer screen. In condition two (unsignalled condition), always presented on the trial following the signalled condition, these changes in expression were obscured by a hand drawn over the mouth of the face so that effective performance depended on the childs ability to estimate the point at which the facial expression changed on the preceding trial. Both groups of children had little difficulty inhibiting responses when the response requirements were signalled. All children made far more errors under the unsignalled condition. Hyperactive children displayed a systematic tendency to respond before the response window occurred. Taken together, these data give no support to the idea that hyperactivity is essentially a problem of disinhibition and raise interesting questions about the role of time mis-estimation in the disorder. | 10.1016/s0166-4328(97)00168-x |
pubmed_106_5757 | OBJECTIVE
To investigate the chest X-ray manifestations of SARS cases.
METHODS
A retrospective study was conducted among 52 clinically confirmed SARS patients from February 9 to May 10, 2003. Chest X-ray scanning was performed at a interval of 1 - 3 days according to the requirements. The manifestations and special features of SARS in X-ray were analyzed.
RESULTS
Small or large patchy shadows with intensive density in both lungs were observed in 31 cases, ground-glass like opacification in 16, small patchy shadows in one lung lobe or one lung segment in 18, nodular shadows in one lung segment in 1, and increased lung marking in lung interstitial tissues in 2. Rapidly changing consolidations revealed in chest X-ray images were found to be associated with SARS infections, and they were not affected by treatment with antibiotics.
CONCLUSION
Chest X-ray provides a sensitive and specific method for the diagnosis and treatment of SARS, and those present with symptoms and signs should undergo chest X-ray scanning every 1 - 3 days. | pubmed_106_5757 |
pubmed_67_14828 | Terrigenous discharge represents a mass movement from land to oceanic environment. While previous studies characterized terrigenous freshwater via oceanographic (physical and biochemical) data, the persistent fresh water in the far-field ocean via satellite-gravimetric observation has been rarely explored. This paper aims to characterize the spatiotemporal extension of Mekong freshwater and the interchangeable role of runoff and climatic factors in the southwestern South China Sea. Employing wavelet coherence analysis between the in situ runoff and oceanic freshwater variations inferred from satellite gravimetry, the coherence and transport duration were obtained at annual, intra- and inter-annual time scales during 2003-2015. Despite weak relationship at 6-month and 24-month scales in regions away from the estuary, the two time series remained significantly correlated at the 12-month scale with a highly positive coherence over 0.97. Spatial pattern of the annual transport duration further indicated that freshwater firstly flowed alongshore before turning eastward offshore, qualitatively consistent with the northeastward western boundary current and an anticyclonic eddy during the summertime generated from the ocean circulation model. Using partial wavelet coherence, the time-variable relationship at all these three scales was found closely related to the Indian Monsoon and Western North Pacific Monsoon. A series of alternating ENSO events during 2007-2011 were responsible for the inter-annual variations, contributing <5 % to the seasonal freshwater extension. Compared with the averaged transport duration of the isotope method (i.e., 21.5 days) and the geostrophic current computation (i.e., 38.8 days) in the summer of 2007, our method yielded a comparable transport duration of 23.9 days with smaller uncertainties. The wind-driven Ekman transport, however, was primarily responsible for the anticyclonic movement of freshwater transport in the southwestern South China Sea during late summer. | 10.1016/j.scitotenv.2022.159583 |
pubmed_236_15410 | During the course of bovine brucellosis, Brucella abortus adheres to and infects cells of the mononuclear phagocyte system. Potential mechanisms of binding, as measured by numbers of phagocytosed bacteria, were studied in two populations of cattle genetically resistant (R) or susceptible (S) to infection with B. abortus. Live B. abortus gained entry into cultured bovine macrophages without organism-specific opsonization. Bacterial entry into macrophages from R was inhibited by the peptide RGDS, outer membrane-peptidoglycan complex from B. abortus strain RB51, anti-LFA-1 monoclonal antibody, anti-C3 antiserum, fibronectin, purified O-antigen from B. abortus lipopolysaccharide, mannan and heat-aggregated IgG. Bacterial entry into macrophages from S was inhibited by outer membrane-peptidoglycan complex, anti-LFA-1 monoclonal antibody, O-antigen and heat-aggregated IgG. The peptide RGES did not inhibit entry into macrophages from R or S. These data support the existence of organism-related receptors on monocyte-derived macrophages for B. abortus which mediate binding in the absence of serum. Secondly, there are demonstrable differences in mechanisms of binding of B. abortus to cells from cattle genetically resistant or susceptible to infection by this organism. These findings further substantiate the importance of phagocytosis and clearance functions of the mononuclear phagocyte system in resistance to bovine brucellosis. Perpetuation of infection in susceptible cattle may occur by establishing an intracellular reservoir of viable organisms. Further studies are necessary to investigate receptor affinities, and the potential for an alternate receptor for this organism in S cattle. | 10.1016/0165-2427(94)90103-1 |
pubmed_207_1216 | The mutagenicity results and data of nine progestins (cyproterone acetate, dehydrospirorenone, gestodene, gestonorone caproate, levonorgestrel, norethisterone, norethisterone acetate, norethisterone enanthate, norethynodrel), one hypothetical metabolite (6,7-epoxy-cyproterone acetate), four estrogens (estradiol, ethinylestradiol, cyclodiol, cyclotriol), and four other sex steroids (atamestane, lilopristone, onapristone, propylmesterolone) are reported. All 17 sex steroids were investigated using the Ames salmonella/microsome direct plate incorporation protocol, and seven were additionally tested using the preincubation modification. Seven sex steroids were also studied in the HG-PRT test with V79 cells for the induction of gene mutations in mammalian cells. The metabolite was examined in the Ames salmonella/microsome assay using the standard protocol and the preincubation modification. In all assays the test compounds were investigated up to concentration levels where cytotoxicity and/or visible precipitation occurred or at least the solubility limit of the test compound was reached. For all assays, evaluation of the data indicates that neither any of the sex steroids nor the hypothetical metabolite was able to induce gene mutations whether in the absence or the presence of an extrinsic metabolizing system (S9 mix). | 10.1002/em.2850210311 |
pubmed_987_18695 | Fiber Bragg grating (FBG) sensors have been widely applied in various applications, especially for structural health monitoring. Low cost, wide range, and low error are necessary for an excellent performance FBG sensor signal demodulation system. Yet the improvement of performance is commonly accompanied by costly and complex systems. A high-performance, low-cost wavelength interrogation method for FBG sensors was introduced in this paper. The information from the FBG sensor signal was extracted by the array waveguide grating (AWG) and fed into the proposed cascaded neural network. The proposed network was constructed by cascading a convolutional neural network and a residual backpropagation neural network. We demonstrate that our network yields a vastly significant performance improvement in AWG-based wavelength interrogation over that given by other machine learning models and validate it in experiments. The proposed network cost-effectively widens the wavelength interrogation range of the demodulation system and optimizes the wavelength interrogation error substantially, also making the system scalable. | 10.1364/OE.449004 |
pubmed_615_18372 | INTRODUCTION
The objectives of this study were to (1) determine the pharmacokinetics of amikacin among children with severe burn and (2) identify influential covariates.
METHODS
Population-based pharmacokinetic modelling was performed in NONMEM 7.2 for hospitalized children who received amikacin at 10-20mg/kg divided two, three, or four times per day as part of early empiric treatment of presumed burn-related sepsis.
RESULTS
The analysis included data from 70 patients (6 months to 17 years) with 282 amikacin serum concentrations. Amikacin's mean Cmax was 33.2±9.4μg/mL and the mean Cmin was 3.8±4.6μg/mL. The final covariate model estimated clearance as 5.98L/h/70kg (4.97-6.99, 95% CI), the volume of distribution in the central compartment as 16.7L/70kg (14.0-19.4, 95% CI), the volume of distribution in the peripheral compartment as 40.1L/70kg (15.0-80.4, 95% CI), and the inter-compartmental clearance as 3.38L/h/70kg (2.44-4.32, 95% CI). In multivariate analyses, current weight (P<0.001) was a significant covariate, while age, sex, height, serum creatinine, C-reactive protein, platelet count, the extent and type of burn, and concomitant vancomycin administration did not influence amikacin pharmacokinetics.
DISCUSSION
Children with burn featured elevated amikacin clearance when compared to healthy adult volunteers. However, peak amikacin concentrations are comparable to those attained in other critically-ill children, suggesting that elevated amikacin clearance may not result in sub-therapeutic antibacterial effects. In this study, we found that amikacin displays two-compartment pharmacokinetics, with weight exerting a strong effect upon amikacin clearance. Further pharmacodynamic studies are needed to establish the optimal dosing regimen for amikacin in paediatric burn patients. | pubmed_615_18372 |
pubmed_216_21044 | Recent advances have shown that atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. Almost 50% of cases are associated with mutations in the three complement regulatory genes, factor H (HF1), membrane co-factor protein (MCP) and factor I (IF). The corresponding gene products act in concert and affect the same enzyme, alternative pathway convertase C3bBb, which initiates the alternative pathway and amplification of the complement system. Factor H (FH) deficiency-associated aHUS usually occurs in infants to middle-aged adults and only rarely in neonates. Moreover, the vast majority of patients are heterozygous for the HF1 gene mutations. We report on a case of neonatal-onset aHUS associated with complete FH deficiency due to novel compound heterozygous mutations in the HF1 gene. A 22-day-old baby girl developed acute renal failure and a remarkably low serum complement C3 level, which was rapidly followed by the development of micro-angiopathic hemolytic anemia. Western blot analysis revealed nearly zero plasma FH levels, and an HF1 gene study showed compound heterozygous mutations, C1077W/Q1139X. Renal pathology findings were compatible with glomerular involvement in HUS. The baby recovered completely after the repetitive infusion of fresh frozen plasma. During follow-up (until she was 20 months old) after the initial plasma therapy, the disease recurred three times; twice after the tapering off of plasma therapy, and once during a weekly plasma infusion. All recurrence episodes were preceded by an upper respiratory tract infection, and were successfully managed by restarting or increasing the frequency of plasma therapy. | 10.1007/s00467-007-0438-x |
pubmed_95_1481 | This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear Matrix Protein 22) as a urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. Urinary NMP22 values were determined for 183 patients with microscopic hematuria by use of a UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All patients were entered in this study before cystoscopy was performed, and were evaluated for NMP22 values and voided urine cytology simultaneously from the same urine samples. Of the 183 patients with microscopic hematuria, 14 cases of urothelial cancer were detected. For the other cases, 65 were of benign diseases and 104 were designated NED (No Evidence of Disease). The median NMP22 values for urothelial cancer, benign diseases, and NED were 26.5 U/ml (95% CI: 18.5-228.2; 4.9 U/ml (95% CI: 3.6-8.3), and 5.9 U/ml (95% CI: 4.8-6.5), respectively. The urinary NMP22 value for urothelial cancer was significantly higher than for benign diseases and NED. When the cut-off value of urinary NMP22 was set at 12 U/ml, the positive rate of NMP22 for urothelial cancer was 85.7%, significantly higher than the 50% positive rate by voided urine cytology. This study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria. | pubmed_95_1481 |
pubmed_117_23940 | Vincristine is a vinca alkaloid anti-mitotic drug with a broad spectrum of effects on solid and hematologic cancers. The major dose-limiting factor of this anti-cancer regimen is painful peripheral neuropathy. However, no gold-standard analgesic option has been used clinically. In this study, we investigated the effects and mechanism of bee venom acupuncture (BVA) to alleviate peripheral neuropathic pain induced by repeated intraperitoneal infusions of vincristine (1 mg/kg/day, days 1-5 and 8-12) in rats. Subcutaneous injection with bee venom (BV, 1.0 mg/kg) at the ST36 acupoint ameliorated cold and mechanical hypersensitivity (i.e., aberrant withdrawal responses in acetone drop and von Frey hair tests, respectively). In vivo extracellular recording demonstrated that BVA inhibited cutaneous cold (acetone) and mechanical (brush, press, and pinch) stimuli-elicited abnormal hyperexcitation of the spinal wide dynamic range (WDR) neurons in vincristine-treated rats. In addition, the microinjection of lidocaine into the ipsilateral locus coeruleus or the antagonism of the spinal α2-adrenergic receptors clearly reversed the effects of BVA on cold and mechanical hypersensitivity, indicating a vital role of the descending noradrenergic modulation in analgesia. These findings suggest that BVA could be a potential therapeutic option for vincristine-induced peripheral neuropathy. | 10.3390/toxins12120775 |
pubmed_596_22013 | Glucans are known to promote wound repair. Noncellulosic β-glucans are recognized as potent immunological activators. β-Glucans are generally safe and are known to attenuate the rate of postoperative infection. Glyc101 is a particulate β-glucan isolated from Saccharomyces cerevisiae. In this study, the hypothesis that Glyc101 regulates wound macrophage function was tested. Glyc101 induced tumor necrosis factor (TNF) α transcription in macrophages isolated from murine wound site. Multiplex assay identified interleukin (IL)-10 and TNFα as two cytokines that are induced by Glyc101 in human blood monocyte-derived macrophages. Glyc101-induced TNFα production was observed to be mediated via the TLR-2 and dectin-1 receptors, receptor tyrosine kinases and NFκB activation. In murine wound macrophages, Glyc101 potentiated phorbol 12-myristate 13-acetate-induced respiratory burst. In vivo, implantation of Glyc101-enriched polyvinyl alcohol-sponges at the wound-site induced TNFα expression in macrophages. Consistently, Glyc101 induced TNFα expression in wound-site macrophages isolated from two patients with chronic wounds. These observations establish the translational significance of the net findings of this study. Activation of wound macrophages by Glyc101 represents one of the potential mechanisms by which this β-glucan may benefit chronic wounds where inefficient inflammatory response is one of the underlying causes of impaired healing. | 10.1111/j.1524-475X.2011.00688.x |
pubmed_415_20663 | Two arene ruthenium complexes [Ru(η(6)-C(6)H(6))(p-MOPIP)Cl](+)1 and [Ru(η(6)-C(6)H(6))(p-CFPIP)Cl](+)2, where p-MOPIP = 2-(4-methoxyphenyl)-imidazo[4,5f][1,10] phenanthroline and p-CFPIP = 2-(4-trifluoromethylphenyl)-imidazo[4,5f][1,10] phenanthroline, were prepared and the interactions of these compounds with DNA oligomers 5'-G3(T2AG3)3-3'(HTG21) have been studied by UV-vis and circular dichroism (CD) spectroscopy, gel mobility shift assay, fluorescence resonance energy transfer (FRET) melting assay, polymerase chain reaction (PCR) stop assay and telomeric repeat amplification protocol (TRAP) assay. The results show that both complexes can induce the stabilization of quadruplex DNA but complex 1 is a better G-quadruplex binder than complex 2. The two ruthenium complexes tested led to an inhibition of the enzyme telomerase and complex 1 was the significantly better inhibitor. A novel visual method has been developed for making a distinction between G-quadruplex DNA and double DNA by our Ru complexes binding hemin to form the hemin-G-quadruplex DNAzyme. Furthermore, in vitro cytotoxicity studies showed complex 1 exhibited quite potent antitumor activities and the greatest inhibitory selectivity against cancer cell lines. | 10.1039/c1dt11676b |
pubmed_1030_1915 | The current pandemic has disproportionally affected the workforce. To improve our understanding of the role that occupations play in the transmission of COVID-19, we analyse real-world network data that were collected in Bucharest between August 1st and October 31st 2020. The data record sex, age, and occupation of 6895 patients and the 13,272 people they have interacted with, thus providing a social network from an urban setting through which COVID-19 has spread. Quite remarkably, we find that medical occupations have no significant effect on the spread of the virus. Instead, we find common transmission chains to start with infected individuals who hold jobs in the private sector and are connected with non-active alters, such as spouses, siblings, or elderly relatives. We use relational hyperevent models to assess the most likely homophily and network effects in the community transmission. We detect homophily with respect to age and anti-homophily with respect to sex and employability. We note that, although additional data would be welcomed to perform more in-depth network analyses, our findings may help public authorities better target under-performing vaccination campaigns. | 10.1038/s41598-022-18392-5 |
pubmed_1058_2837 | Specific bronchial challenge (SBC) testing is a key technique for diagnosing the origin of occupational asthma (OA). SBC is indicated in specific circumstances, including whenever several agents present in the work environment may be the cause of OA, when new or unusual occupational agents need to be identified, when evidence for legal action is required, or when research is conducted. SBC procedures are not standardized, because of the great diversity of occupational agents and the variety of physical and chemical properties involved. Thus, SBC testing with agents found in fumes, gases or vapors can be administered in special cabins or in closed circuits with continuous monitoring of sub-irritant concentrations. Agents found in dust, most but not all of which have high molecular weights, may be appropriate for routine SBC testing in an allergy laboratory. This paper will treat only these cases. SBC must be formed in specialized centers by experienced personnel, as it is a sophisticated and potentially dangerous technique. We describe a series of 20 patients diagnosed of OA in our unit over the past two years in whom SBC provided an etiologic diagnosis. All were exposed to dust or aerosols at work. The cause was a substance of high molecular weight in 17 cases, and low molecular weight in 3. The procedure used is described and models of bronchial response are discussed. | 10.1016/s0300-2896(15)30546-9 |
pubmed_31_14363 | OBJECTIVE
To investigate the effect of microRNA-137 (miR-137) on the migration and invasion of melanoma cells and its mechanism.
METHODS
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-137 in melanoma tissues and cells. miR-137 mimics, phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) small interfering RNA and corresponding controls were transfected into A375 and WM451 cells by lipofection. The expression of PIK3R3 was examined by qRT-PCR and Western blot analysis. The Trans-well assay was conducted to measure cell migration and invasion. Dual luciferase reporter assay was used to detect the interaction between miR-137 and PIK3R3.
RESULTS
Compared with normal pigmented nevus tissue, miR-137 expression was significantly reduced in melanoma tissues. Compared with keratinous HaCaT cells, the level of miR-137 was significantly decreased in melanoma SK-MEL-1, A375, and WM451 cells. Knockdown of miR-137 significantly reduced the migrated and invasive abilities of melanoma A375 and WM451 cells. Moreover, inhibition of PIK3R3 obviously suppressed the migration and invasion abilities of melanoma A375 and WM451 cells. Luciferase activity assay showed that PIK3R3 was a direct target of miR-137. In addition, overexpression of miR-137-inhibited PIK3R3 expression, while knockdown of miR-137-enhanced PIK3R3 abundance. Restoration of PIK3R3 reversed the regulatory effect of miR-137 on cell migration and invasive in melanoma A375 and WM451 cells.
CONCLUSION
miR-137 inhibited melanoma cell migration and invasion by targeting PIK3R3 gene. | 10.1002/jcb.28124 |
pubmed_532_20649 | The current research evaluates how perceptions of one's partner's drinking problem relate to attempts to regulate partner behavior and relationship functioning, and whether this varies by perceptions of one's own drinking. New measures are offered for Thinking about your Partner's Drinking (TPD) and Partner Management Strategies (PMS). Participants included 702 undergraduates who had been in a romantic relationship for at least three months. Participants completed an online survey assessing perceptions of problematic drinking for one's self and partner, ways in which attempts were made to regulate or restrain their partner's drinking, relationship outcomes (i.e., satisfaction, commitment, trust, and need fulfillment), and alcohol use and consequences for self and partner. Factor analyses supported a single factor for Thinking about your Partner's Drinking (TPD) and two factors for the Partner Management Strategies (PMS) scale (i.e., punishment and reward). Results using structural equation modeling indicated that perceiving one's partner to have a drinking problem was associated with lower relationship functioning. Further, this association was mediated by strategies using punishment aimed at changing one's partner's drinking, but was not mediated by strategies using rewards. Finally, moderation results suggested that this relationship was not as detrimental for participants who perceived they also had an alcohol problem. In sum, perceiving one's partner to have a drinking problem was associated with relationship problems through punishing regulation strategies, and was weaker among individuals who also perceived themselves to have a drinking problem. | pubmed_532_20649 |
pubmed_312_19009 | The unusual occurrence of an adenoid cystic carcinoma arising in a pleomorphic adenoma is described, with emphasis on the cytomorphology of the neoplasm in a fine needle aspiration specimen. The ultrastructural findings are detailed, including the acellular hyaline spheres so characteristic of this tumor. | pubmed_312_19009 |
pubmed_526_20408 | Atypical non HLA antibodies are increasingly recognised as causes of immunological injury in allotransplantation. In this report we describe a non HLA sensitized male renal allograft recipient who developed acute vascular rejection on a "for cause" biopsy (Banff v2, g2, ptc 3) at day 4 post first renal allograft in the presence of elevated angiotensin II type 1 receptor antibodies (AT1R-Ab level 14.1). The acute rejection was treated with pulse corticosteroid therapy, anti-thymocyte globulin (ATG × 6), plasma exchange (1.5 plasma volume replacement x6) and oral candesartan. Serum creatinine improved and follow up biopsy confirmed resolution of rejection following treatment. AT1R-Ab should be considered when rejection is diagnosed in the absence of HLA antibodies. | 10.1111/nep.12421 |
pubmed_123_20453 | OBJECTIVE
Low plasma testosterone levels are associated with hyperinsulinemia and glucose intolerance in men. However, it is unclear whether these abnormalities are related to the concomitant alteration in regional adipose tissue (AT) accumulation associated with reduced androgen levels.
RESEARCH DESIGN AND METHODS
We measured plasma steroid levels in a sample of 79 men, ranging from lean to obese (aged 29-42 years), for whom an oral glucose tolerance test (OGTT), anthropometric and computed tomography (CT) measurements of body fatness, and AT distribution were performed. Sex hormone binding globulin (SHBG) and the following steroids were measured after extraction from plasma and chromatography: dehydroepiandrosterone, androstenedione, androst-5-ene-3 beta,17 beta-diol, testosterone, estrone, and estradiol (E2).
RESULTS
Several significant negative correlations were found between adrenal C19 steroid precursors, testosterone, SHBG, and fasting insulin levels, as well as between plasma glucose and insulin concentrations measured during the OGTT (-0.25 < or = r < or = -0.35, 0.05 > or = P > or = 0.001). The best steroid correlate of plasma glucose and insulin homeostasis indexes was the E2: testosterone ratio (0.34 < or = r < or = 0.42, 0.005 > or = P > or = 0.001). However, after correction of steroid levels for either fat mass, body mass index (BMI), or visceral AT area, as measured by CT, no significant residual associations were noted between testosterone, adrenal C19 steroid, SHBG, and estrogen levels and indexes of plasma glucose-insulin homeostasis, although the positive association between the E2: testosterone ratio and glucose area remained significant after adjustment for total body fat mass and BMI. Furthermore, 15 pairs of obese subjects, matched for visceral AT area, showing either low or high levels of the steroids studied, did not differ in fasting insulin and postglucose plasma insulin levels or in glucose tolerance.
CONCLUSIONS
These results suggest that the previously reported relationships between androgen levels and indexes of plasma glucose-insulin homeostasis are mediated, to a large extent, by concomitant alterations in levels of total body fat and visceral AT in men. | 10.2337/diacare.18.3.292 |
pubmed_707_19809 | BACKGROUND
Machismo and acceptance of violence (AV) against women are part of the social construction of hegemonic masculinity and are related to the risk of dating violence. This study aims to analyze the effectiveness of the Lights4Violence program in reducing machismo and AV in secondary school students from different European cities.
METHODS
Quasi-experimental longitudinal study using a convenience sample of 1,146 high school students from different European cities (12-17 years old) including 575 intervention group students (59.1% girls) and 571 control group students (62.7% girls). We performed linear regression models to identify the effect of the intervention, modelling the difference in means in machismo and AV (dependent variables) between wave-2 and wave-1.
RESULTS
An interaction was identified between the group variable and the empathy variable. In wave-2, girls with high empathy at baseline in the intervention group obtained lower mean AV scores (β: -0.131; p = 0.004). However, the boys in the intervention group (reference: control group) with low empathy at baseline registered a significant increase in the mean values of machismo (β: 0.247; p < 0.001).
CONCLUSION
The importance of empathy is shown in the effectiveness of interventions to reduce machismo and AV in adolescents. While the Lights4Violence program focuses on promoting healthy relationships, there were some controversial results. It is possible that some children, especially those with less empathy, may have felt "challenged" during the intervention and/or assessment. This suggests the need for the development of interventions that also consider psychological processes and integrate the promotion of positive expressions of masculinity. | 10.1186/s12889-022-12770-4 |
pubmed_434_5260 | Vitiligo is a cutaneous pigmentary disorder characterized by the loss of epidermal melanocytes. Strong evidence supports the theory that autoimmune mechanisms, namely B cell auto-antibody production and auto-reactive T cell cytotoxicity, are involved in this affliction. It is well known that autoimmunity results from a breakdown of self-tolerance. However, the mechanism which leads to the break-down of self-tolerance and subsequently causes the development of autoimmunity in vitiligo remains obscure. B lymphocyte activating factor of the tumour necrosis factor family is a recently identified ligand that is required for peripheral B-cell survival and homeostasis, the excessive production of which may lead to autoimmunity. Based on a collection of indirect evidences, we postulate that in individuals predisposed through inheritance, over-expression of the B lymphocyte activating factor may cause a breakdown of self-tolerance and subsequently cause autoimmune vitiligo via several possible mechanisms: B lymphocyte activating factor activates self-reactive B cells to produce auto-antibodies against melanocytes; these B cells may function as cellular adjuvants for the activation of the CD4+ T cells, enhancing their helper effect on the activation of the CD8+ T cells; CD4+ T cells assist CD8+ T cells to respond to melanocytes antigen, leading to the autoreactive reaction; B lymphocyte activating factor activated B cells capture antigen and present it directly to the CD8+ T cells; and, B lymphocyte activating factor delivers a complete costimulation signal to the T cells (both CD4+ and CD8+ subset), playing an additional role in the autoimmune response in vitiligo. Future challenges remain to test these propositions. Advancement in the treatment of vitiligo is still unsatisfactory, and thus novel modalities of therapy need to be developed. Recently, B lymphocyte activating factor has been evaluated as an attractive target for immune therapy. Once the hypothesis of B lymphocyte activating factor mediating the breakdown of self-tolerance in vitiligo is corroborated, it can become a novel target for treatment of vitiligo. | 10.1016/j.mehy.2010.10.034 |
pubmed_787_25492 | OBJECTIVE
: To determine the effects of therapeutic hypothermia on coagulation parameters during hemorrhagic shock (HS) and fluid resuscitation and on survival, in a rat HS model.
METHODS
: Under light anesthesia and spontaneous breathing, 24 rats underwent HS (phase I) for 90 minutes, during which 2.5 mL/100 g blood was withdrawn over 15 minutes; fluid resuscitation (phase II) for 60 minutes, during which no blood was reinfused but 5.0 mL/100 g lactated Ringer's solution was infused over 30 minutes; and an observation (phase III) without anesthesia until 72 hour. After the volume-controlled hemorrhage, rats were randomized into a hypothermia group (n = 12, 33 degrees C) or a normothermia group (n = 12, 38 degrees C). The rectal temperature in each group was maintained during phases I and II. Whole blood coagulopathy was assessed by Sonoclot analysis (SA) at baseline and the end of phases I and II. Fibrinolysis parameters of thrombin-antithrombin III complex and plasma-alpha-2-plasmin inhibitor complex were also monitored.
RESULTS
: At 72 hour, 10 of 12 hypothermia group rats, and 5 of 12 normothermia group rats remained alive (p < 0.05). Fluid resuscitation significantly decreased hematocrit (20% +/- 5%) compared with baseline (33% +/- 5%; p < 0.05) in all rats. SA showed no significant differences between groups at the end of phase I. However, at the end of phase of II, SA revealed a decreased "clot rate" in hypothermia compared with normothermia (22 clot signal/min +/- 11 clot signal/min vs. 34 clot signal/min +/- 14 clot signal/min; p < 0.05) and a prolonged "time to peak" in hypothermia (15 minutes +/- 5 minutes versus 6 minutes +/- 2 minutes; p < 0.05). No differences in thrombin-antithrombin III complex and plasma-alpha-2-plasmin inhibitor complex values were seen between groups throughout the experiment.
CONCLUSIONS
: Therapeutic mild hypothermia of 33 degrees C did not cause coagulopathy during HS, but did impair SA coagulation parameters during fluid resuscitation, probably because of dilution. Hypothermia also prolonged survival after HS. Impairments to coagulation parameters did not worsen outcomes in the rat HS model. | 10.1097/TA.0b013e3181a0fbb3 |
pubmed_1096_7500 | Imatinib mesylate (Gleevec) inhibits Abl1, c-Kit, and related protein tyrosine kinases (PTKs) and serves as a therapeutic for chronic myelogenous leukemia and gastrointestinal stromal tumors. Imatinib also has efficacy against various pathogens, including pathogenic mycobacteria, where it decreases bacterial load in mice, albeit at doses below those used for treating cancer. We report that imatinib at such low doses unexpectedly induces differentiation of hematopoietic stem cells and progenitors in the bone marrow, augments myelopoiesis but not lymphopoiesis, and increases numbers of myeloid cells in blood and spleen. Whereas progenitor differentiation relies on partial inhibition of c-Kit by imatinib, lineage commitment depends upon inhibition of other PTKs. Thus, imatinib mimics "emergency hematopoiesis," a physiological innate immune response to infection. Increasing neutrophil numbers by adoptive transfer sufficed to reduce mycobacterial load, and imatinib reduced bacterial load of Franciscella spp., which do not utilize imatinib-sensitive PTKs for pathogenesis. Thus, potentiation of the immune response by imatinib at low doses may facilitate clearance of diverse microbial pathogens. | 10.1371/journal.ppat.1004770 |
pubmed_692_5553 | BACKGROUND
Dioscoreanone (DN) isolated from Dioscorea membranacea Pierre has been reported to exert potent cytotoxic effects against particular types of cancer. The present study was carried out to investigate the cytotoxicity of DN against a panel of different human lung cancer cell lines. The study further examined the underlying mechanisms of its anticancer activity in the human lung adenocarcinoma cell line A549.
METHODS
Antiproliferative effects of DN were determined by SRB and CFSE assays. The effect of DN on cell cycle distribution was assessed by flow cytometric analysis. Apoptotic effects of DN were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses, as well as by changes in caspase-3 activity and relative levels of Bax and Bcl-2 mRNA.
RESULTS
DN exerted antiproliferative and cytotoxic effects on all three subtypes of non-small cell lung cancer (NSCLC) cells, but not on small cell lung cancer (SCLC) cells and normal lung fibroblasts. DN slowed down the cell division and arrested the cell cycle at the G2/M phase in treated A549 cells, leading to a dose- and time- dependent increase of the sub-G1 population (apoptotic cells). Consistently, early apoptotic cells (AnnexinV +/PI-) were detected in those cells that were treated for 24 h and increased progressively over time. Moreover, the highest activity of caspase-3 in DN-treated A549 cells was detected within the first 24 h, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity and also DN-induced apoptosis in a dose-dependent manner. Additionally, DN increased the Bax/Bcl-2 ratio in treated A549 cells with time, indicating its induction of apoptosis via the mitochondrial pathway.
CONCLUSIONS
This study reveals for the first time that the anticancer activity of DN was induced through regulation of the Bcl-2 family protein-mediated mitochondrial pathway and the subsequent caspase-3 activation in A549 cancer cells, thus supporting its potential role as a natural apoptosis-inducing agent for NSCLC. | 10.1186/1472-6882-14-413 |
pubmed_271_16539 | On the basis of density functional theory calculations, we show that edge-decorated graphene nanoribbons (GNRs) by scandium can bind multiple hydrogen molecules in a quasi-molecular fashion. The average adsorption energy of H(2) on Sc ranges from 0.17 to 0.23 eV, ideally suited to hydrogen storage. For the narrowest GNR with either armchair or zigzag edges, the predicted weight percentage of H(2) is >9 wt%, exceeding the gravimetric target value set by the Department of Energy (DOE). The bonding energy between Sc and the GNR is significantly greater than the cohesive energy of bulk Sc so that clustering of Sc will not occur once Sc is bonded with carbon atoms at the edge of GNRs. Moreover, the adsorption energy of H(2) can be modestly tuned (either enhanced or reduced) by applying an external electric field. | 10.1039/c2nr11257d |
pubmed_300_8051 | A system of nanoparticles of mixed lipid monolayer shell and biodegradable polymer core was developed for targeted delivery of anticancer drugs with Docetaxel as a model drug, which provide targeting versatility with a quantitative control of the targeting effect by adjusting the lipid component ratio of the mixed lipid monolayer, and combine the advantages and avoid disadvantages of polymeric nanoparticles and liposomes in drug delivery. X-ray photoelectron spectroscopy (XPS) confirmed the coating of the mixed lipid monolayer on the polymeric core. Fluorescent microscopy proved the targeting efficacy of the folic acid conjugated on the mixed lipid monolayer for the cancer cells of over expression of folate receptors. The folic acid conjugated nanoparticles of mixed lipid monolayer shell and biodegradable polymer core were proved to possess sustainable, controlled and targeted delivery of anticancer drugs with Docetaxel as a model drug, which may provide a drug delivery system of precise control of the targeting effect. | 10.1016/j.biomaterials.2009.09.036 |
pubmed_377_6781 | UNLABELLED
Few studies have comprehensively assessed the evolution asthma disease in recent years.
OBJECTIVES
To determine changes in morbidity, lung function and quality of life and to establish the impact in terms of cost in a cohort of patients with asthma.
METHODS
Prospective, descriptive and realistic study that included 220 asthma patients evaluated 10 years after their inclusion (1994-2004). For all the patients, data for symptoms, lung function, quality of life and financial cost were collected.
RESULTS
There was a decrease in the frequency of health service visits, including: emergency room visits for asthma exacerbations, 0.3 (0.9) versus 0.6 (1) visits per patient per year (P=.003); a reduction in the severity of the disease, with a greater proportion of patients with mild asthma, 121 (54.8%) versus 94 (42.7%) (P=.001); a decrease (improvement in quality of life) in the total SGRQ, 30.1 (16.5) versus 37 (19.6) (P<.001); and reduced total costs, 1,464€ (3,415.8) compared to 2,267€ (4.174) per patient/year (P<.001), mainly due to indirect costs, 617.50€ (2855.9) compared to 1,320.10€ (3,685.3) per patient/year (P=.001). When assessing the changes observed according to asthma severity, no differences were observed between groups.
CONCLUSIONS
The evolution of the morbidity and quality of life of asthma patients between 1994 and 2004 are clearly favorable. This improvement provided a significant reduction in the total costs of disease treatment. | 10.1016/j.arbres.2011.05.014 |
pubmed_86_22085 | Our understanding of the mechanisms involved in B cell activation, proliferation and differentiation to immunoglobulin secreting cells has been facilitated by the use of T-independent and T-dependent antigens. The majority of these studies have used the murine system and only recently, the rat. Because membranes isolated from Mycoplasma neurolyticum are potent B cell mitogens in the rat and some T-independent antigens also activate DNA synthesis in B cells, the in vitro and in vivo antibody responses induced by M. neurolyticum membranes in T-deficient rat systems were examined. The three groups of rats used, i.e., nude; anti-thymocyte serum-treated, neonatally-thymectomized (ATS-Tx); and normal Fischer 344 produced a non-polyclonal antibody response against the membranes. Spleen cell cultures that were T cell deficient and B cell enriched produced plaque-forming cells against the Mycoplasma membranes. Antibody production was depleted upon removal of Sephadex G-10 adherent cells. The antibody response is comprised of both antigen-specific and polyclonal responses. Lipoglycan, found in the aqueous phenol extract of the membranes, is the mitogenic fraction of the membranes, and this study suggests that it may also be the T-independent antigenic component of the M. neurolyticum membranes. | 10.3109/08820138609042017 |
pubmed_373_11318 | Coronary angioplasty during acute coronary syndrome, and particularly in MI, continues to involve a greater risk of acute and subacute occlusion. Stenting for acute or threatened vessel closure has a high initial success rate and reduces the need for emergency bypass surgery. Nevertheless, under these conditions intracoronary thrombus actually appears to be a relative contraindication to stent implantation. We report the successful implantation of two Palmaz Schatz stents to treat a coronary occlusion refractory to multiple ballooning during primary PTCA in myocardial infarction with angiographic evidence of intimal dissection containing thrombus. The good clinical improvement and the results of short- and long-term clinical angiographic follow-up confirm both the feasibility and effectiveness of using this technical approach to manage complications in acute and unstable syndromes. | pubmed_373_11318 |
pubmed_271_4822 | Dermatological research has been very active this year. Most of the numerous fields investigated involve the mechanisms of cutaneous regeneration and barrier function. A novel target of early ultraviolet-induced skin photodamage, the Syk kinase, has been recently identified. Synergistic relationship between telomere damage and cutaneous progerin production during cell senescence may also participate in the natural skin aging process. Interestingly, ultraviolet radiation induces an inhibitory effect on subcutaneous lipogenesis. Androgenetic alopecia or common baldness is not characterized by loss of hair follicle stem cells but by a defect in the conversion of hair follicle stem cells into active progenitor cells. It has been shown that the cornified envelope functions not only as a physicomechanical barrier, but also as both a biochemical line of antoxidant defense and an immunological line of defense. Like human papillomaviruses, Merckel cell polyomavirus belongs to the skin microbiome and different studies have demonstrated the protective role of epidermal resident microflora through the activation of innate immunity. Production of antimicrobial peptides and the activation of inflammasome and plasmacytoid dendritic cells are involved in the modulation of the cutaneous barrier function. Results from different studies suggest that IL-22 and IL-36 may be common mediators of both innate and adaptive immune responses. All these pathways interact not only to maintain cutaneous homeostasis and integrity (wound healing) but also to regulate autoinflammatory and autoimmune dermatoses (psoriasis, lupus, rosacea, atopic dermatitis, etc...). In addition, molecular mechanisms that regulate T helper type 2 differentiation and the retention at the site of inflammation of Th2 cells have been identified. New promising therapeutic targets for different chronic dermatosis are thus suggested. Mechanobiology and mechanotransduction are also emerging fields that investigate mechanical interactions between living cells and their environment and the conversion of mechanical cues into biochemical signals. Electronic second skin is now a current concept through bio-integrated epidermal electronics platforms used for different monitoring and stimulations of body functions. | 10.1016/S0151-9638(11)70096-5 |
pubmed_862_16050 | The parameters of segmental left ventricular (LV) diastolic function were studied by tissue myocardial Doppler echoCG in 54 patients with severe iron-deficit anemia (IDA) before treatment and after one month of treatment with sorbifer combined with triovit. The control group consisted of 16sex- and age-matched practically healthy persons. The following parameters were studied: early diastolic wave velocity (Ve), late diastolic wave velocity (Va), and Ve/Va ratio in 15 LV segments. Alterations in diastolic function were found in the majority of LV segments; they included a decrease in Ve, an increase in Va, and a decrease in Ve/Va in patients with severe IDA. Administration of sorbifer combined with triovit in this category of patients facilitated improvements in the parameters of LV segmental diastolic function. | pubmed_862_16050 |
pubmed_10_1908 | With the emergence of vancomycin-resistant enterococci (VRE) in our public hospitals, territory-wide implementation of directly observed hand hygiene before meals and medications for all conscious hospitalized patients reverted the rising VRE incidence of 16.5% per month (P < .001) to a reduction of -9.8% per month (P < .001). The outbreak rate reverted from an increasing trend of 10.5% per month (P < .001) to a decreasing trend of -13.3% per month (P < .001) between January 2011 and October 2015. | 10.1016/j.ajic.2016.03.050 |
pubmed_915_25297 | The oral cavity is exposed to the external environment and from a very young age is colonized by infectious agents. Under certain circumstances including poor oral hygiene, dry mouth, trauma, and the use of antibiotics, oral infections can occur. They can result in damage to the oral cavity including teeth and their support structures. Oral infections can also lead to the extension of infection into surrounding tissues and to systemic infections. Chronic oral infection is a recognized risk factor for heart disease. Older adults are at high risk for oral infections and associated complications. Tooth loss, for which infection is the most significant cause, leads to cosmetic changes and a decreased ability to masticate certain foods that can lead to malnutrition. Chronic oral infections and the manipulation of teeth and supporting structures can lead to the hematogenous spread of infection including the infection of artificial joints and endocardial implants. Good oral hygiene, the use of fluoride, regular dental care, and the appropriate use of antibiotics can all reduce oral infections and their associated complications. J Am Geriatr Soc 68:411-416, 2020. | 10.1111/jgs.16154 |
pubmed_545_3796 | The spotted-wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), native to Eastern Asia, is an invasive alien species in Europe and the Americas, where it is a severe pest of horticultural crops, including soft fruits and wine grapes. The conventional approach to controlling infestations of SWD involves the use of insecticides, but the frequency of application for population management is undesirable. Consequently, alternative strategies are urgently needed. Effective and improved trapping is important as an early risk detection tool. This study aimed to improve Droskidrink® (DD), a commercially available attractant for SWD. We focused on the chemical and behavioral effects of adding the bacterium Oenococcus oeni (Garvie) to DD and used a new trap design to enhance the effects of attractive lures. We demonstrate that microbial volatile compounds produced by O. oeni are responsible for the increase in the attractiveness of the bait and could be later utilized for the development of a better trapping system. Our results showed that the attractiveness of DD was increased up to two-fold by the addition of commercially available O. oeni when combined with an innovative trap design. The new trap-bait combination increased the number of male and especially female catches at low population densities. | 10.3390/insects12010066 |
pubmed_511_5326 | Glioblastoma (GBM) is regarded as the most common malignant brain tumor but treatment options are limited. Thus, there is an unmet clinical need for compounds and corresponding targets that could inhibit GBM growth. We screened a library of 80 dopaminergic ligands with the aim of identifying compounds capable of inhibiting GBM cell line proliferation and survival. Out of 45 active compounds, 8 were further validated. We found that the dopamine receptor D2 antagonist trifluoperazine 2HCl inhibits growth and proliferation of GBM cells in a dose dependent manner. Trifluoperazine's inhibition of GBM cells is cell line dependent and correlates with variations in dopamine receptor expression profile. We conclude that components of the dopamine receptor signaling pathways are potential targets for pharmacological interventions of GBM growth. | 10.1016/j.bbrc.2018.03.001 |
pubmed_1141_12792 | The expression of laminin isoforms and laminin-binding integrin receptors known to occur in muscle was investigated during myogenic regeneration after crush injury. Comparisons were made between dystrophic 129ReJ dy/dy mice, which have reduced laminin alpha2 expression, and their normal littermates. The overall histological pattern of regeneration after crush injury was similar in dy/dy and control muscle, but proceeded faster in dy/dy mice. In vitro studies revealed a greater yield of mononuclear cells extracted from dy/dy muscle and a reduced proportion of desmin-positive cells upon in vitro cultivation, reflecting the presence of inflammatory cells and "preactivated" myoblasts due to ongoing regenerative processes within the endogenous dystrophic lesions. Laminin alpha1 was not detectable in skeletal muscle. Laminin alpha2 was present in basement membranes of mature myofibers and newly formed myotubes in control and dy/dy muscles, albeit weaker in dy/dy. Laminin alpha2-negative myogenic cells were detected in dy/dy and control muscle, suggesting the involvement of other laminin alpha chains in early myogenic differentiation, such as laminin alpha4 and alpha5 which were both transiently expressed in basement membranes of newly formed myotubes of dy/dy and control mice. Integrin beta1 was expressed on endothelial cells, muscle fibers, and peripheral nerves in uninjured muscle and broadened after crush injury to the interstitium where it occurred on myogenic and nonmyogenic cells. Integrin alpha3 was not expressed in uninjured or regenerating muscle, while integrin alpha6 was expressed mainly on endothelial cells and peripheral nerves in uninjured muscle. Upon crush injury integrin alpha6 increased in the interstitium mainly on nonmyogenic cells, including infiltrating leukocytes, endothelial cells, and fibroblasts. In dy/dy muscle, integrin alpha6 occurred on some newly formed myotubes. Integrin alpha7 was expressed on muscle fibers at the myotendinous junction and showed weak and irregular expression on muscle fibers. After crush injury, integrin alpha7 expression extended to the newly formed myotubes and some myoblasts. However, many myoblasts and newly formed myotubes were integrin alpha7 negative. No marked difference was observed in integrin alpha7 expression between dy/dy and control muscle, either uninjured or after crush injury. Only laminin alpha4 and integrin alpha6 expression patterns were notably different between dy/dy and control muscle. Expression of both molecules was more extensive in dy/dy muscle, especially in the interstitium of regenerating areas and on newly formed myotubes. In view of the faster myogenic regeneration observed in dy/dy mice, the data suggest that laminin alpha4 and integrin alpha6 support myogenic regeneration. However, whether these accelerated myogenic effects are a direct consequence of the reduced laminin alpha2 expression in dy/dy mice, or an accentuation of the ongoing regenerative events in focal lesions in the muscle, requires further investigation. | 10.1006/excr.2000.4842 |
pubmed_918_16299 | Lung cancer screening of high-risk individuals with computed tomography is a promising intervention to reduce lung cancer mortality. Patient Decision Aids (PtDAs) may assist eligible individuals assess the risks and benefits associated with screening. Screening preference is high among lower-risk, screening-ineligible individuals and strategies are needed to reduce screening demand among this group. We developed and evaluated a resource comprising a recruitment pamphlet combined with either a PtDA for screening-eligible individuals or an education pamphlet for screening-ineligible individuals. Quasi-experimental pre-post pamphlet exposure design. Ever-smokers aged 55-80 years attending hospital outpatient clinics were invited. Among screening-eligible participants, the assessed outcome was change in score on the Decisional Conflict Scale (DCS). Among screening-ineligible participants, the assessed outcomes were change in screening preference. In the study 51% (55/107) of invited individuals participated, with mean ± standard deviation age 66.9 ± 6.4 years, 53% (29/55) male, and 65% (36/55) eligible for screening. Median (interquartile range) DCS among screening-eligible participants reduced from 28.9 (22.7-45.3) pre-PtDA to 25 (1.6-29.7) post-PtDA (p < .001), but there was no significant change in the proportion that reached the accepted threshold for decisional certainty (DCS < 25, 10/36 [28%] pre-exposure vs. 14/36 [39%] post-exposure, p = .1). Screening preference among screening-ineligible individuals reduced after viewing the screening-ineligible brochure (pre-exposure median of "Prefer" to post-exposure median of "Unsure," p = .001). Our consumer information pamphlets about lung cancer screening may reduce decisional conflict and improve alignment of screening preference with eligibility. | 10.1093/tbm/ibz029 |
pubmed_1109_20519 | To investigate the role hepatitis B e antigen (HBeAg) plays in the evolution of hepatitis B virus (HBV), we sequenced the basic core promoter (BCP) and precore (preC) regions of 348 clones total from ten HBV Chinese patients. Eleven mutations were more frequent in HBeAg-negative patients than in HBeAg-positive patients. Further, the sequencing of dozens of variants was found to be necessary to obtain mutation profiles. Phylogenetic and median-joining network analyses suggested that variants from each patient had a single common ancestor (monophyly). Higher haplotype and nucleotide diversities were identified in HBeAg-negative patients. Analysis of dN/dS suggested that viruses experiencing a stronger immune response had lower haplotype diversity. Because HBeAg seroconversion was associated with viral diversity it served as an indicator of HBV evolution. Significantly, this study indicated a larger sampling of variants from each patient was required to understand effectively the properties of HBV. | pubmed_1109_20519 |
pubmed_61_22119 | The fruity odours of wine are largely derived from the synthesis of esters and higher alcohols during yeast fermentation. The ATF1- and ATF2-encoded alcohol acetyltransferases of S. cerevisiae are responsible for the synthesis of ethyl acetate and isoamyl acetate esters, while the EHT1-encoded ethanol hexanoyl transferase is responsible for synthesizing ethyl caproate. However, esters such as these might be degraded by the IAH1-encoded esterase. The objectives of this study were: (a) to overexpress the genes encoding ester-synthesizing and ester-degrading enzymes in wine yeast; (b) to prepare Colombard table wines and base wines for distillation using these modified strains; and (c) to analyse and compare the ester concentrations and aroma profiles of these wines and distillates. The overexpression of ATF1 significantly increased the concentrations of ethyl acetate, isoamyl acetate, 2-phenylethyl acetate and ethyl caproate, while the overexpression of ATF2 affected the concentrations of ethyl acetate and isoamyl acetate to a lesser degree. The overexpression of IAH1 resulted in a significant decrease in ethyl acetate, isoamyl acetate, hexyl acetate and 2-phenylethyl acetate. The overexpression of EHT1 resulted in a marked increase in ethyl caproate, ethyl caprylate and ethyl caprate. The flavour profile of the wines and distillates prepared using the modified strains were also significantly altered as indicated by formal sensory analysis. This study offers prospects for the development of wine yeast starter strains with optimized ester-producing capability that could assist winemakers in their effort to consistently produce wine and distillates such as brandy to definable flavour specifications and styles. | 10.1002/yea.1382 |
pubmed_804_5975 | Iron(IV)-oxo porphyrins [FeIV(Por)O] (Por = poprhyrin), commonly called compound II models, were produced in three electron-deficient ligands by visible light irradiation of highly photo-labile porphyrin-iron(III) bromates or chlorates. The kinetics of oxygen transfer atom (OAT) reactions with aryl sulfides by these photo-generated [FeIV(Por)O] (3) were studied in CH3CN solutions. The iron(IV)-oxo porphyrins under study include 5,10,15,20-tetra(2,6-dichlorophenyl)porphyrin-iron(IV)-oxo (3a), 5,10,15,20-tetra(2,6-difluorophenyl)porphyrin-iron(IV)-oxo (3b), and 5,10,15,20-tetra(pentafluorophenyl)porphyrin-iron(IV)-oxo (3c). As expected, complexes 3 were competent oxidants and reacted rapidly with thioanisoles to give the corresponding sulfoxides with minor over-oxidation sulfones. Apparent second-order rate constants determined under pseudo-first-order conditions for sulfide oxidation reactions are (9.8 ± 0.1) × 102-(3.7 ± 0.3) × 101 M-1 s-1, which are 3 to 4 orders of magnitude greater in comparison to those of alkene epoxidations and activated CH bond oxidations by the same oxo species. Conventional Hammett analyses gave non-linear correlations, indicating no significant charge developed at the sulfur during the oxidation process. For a given substrate, the reactivity order for the iron(IV)-oxo species was 3c < 3b < 3a, which is inverted from expectations on the basis of the electron-withdrawing capacity of the porphyrin macrocycles. The absolute rate constants from kinetic studies provided insights into the transient oxidants in catalytic reactions under turnover conditions where actual reactive intermediates are not observable. Our kinetic and catalytic competition results strongly suggest that 3 may undergo a disproportionation reaction to form a higher oxidized iron(IV)-oxo porphyrin radical cations as the true oxidant. | 10.1016/j.jinorgbio.2018.03.004 |
pubmed_987_8871 | RBCs membrane loses its integrity during hemoglobinopathies such as β-thalassemia and sickle cell disease. The severity of β-thalassemia has been historically linked to the presence of XMN polymorphism which is believed to ameliorate the severity. Here, we investigate the effect of XMN polymorphism on RBC membrane lipidome isolated from patients, using LC-MS/MS based approach. A total of 50 patients were recruited and 28 lipid species were identified in all groups after statistical analyses using volcano plot and ANOVA-SCA, and lipids with higher VIP values extracted from OPLS-DA loading plot. Alteration in lipid levels specifically the membrane lipids such as PC and fatty acids were observed. Samples with XMN polymorphism exhibited up-regulation of lipids involved in membrane stability such as cholenoic acid while PC (O-41:1) was down-regulated when compared to non-XMN samples. Additionally, HU administration to samples also had profound effect on the lipids of patients in both groups. A trend of improvement in the membrane lipids was observed in patients with XMN polymorphism. HU administration has proven to further improve the membrane integrity by upregulating certain membrane lipids in such patients. The study presents a comprehensive analysis of RBC membrane lipidome with respect to the genetic variation and HU administration. | 10.1016/j.chemphyslip.2022.105195 |
pubmed_574_16590 | The sequences of the genes for the nine subunits of ATP synthase in the thermophilic cyanobacterium Synechococcus 6716 have been determined. The genes were identified by comparison of the encoded proteins with sequences of ATP synthase subunits in other species, and confirmed for subunits alpha, beta, delta and epsilon, by determining their N-terminal sequences. They are arranged at three separate loci. Six of them are in one cluster in the order a: c: b': b: delta: alpha, and those for the beta and epsilon subunits form a second and separate cluster. The gene for the gamma-subunit is at a third site. As in other bacteria, the gene for subunit a is immediately preceded by a gene coding for a small hydrophobic protein of unknown function, known as uncI in Escherichia coli. The gene orders in Synechococcus 6716 are related to the orders of ATP synthase genes in the plastid genomes of higher plants, and particularly of a red alga and a diatom. The sequences of the subunits are similar to those of chloroplast ATP synthase, the alpha, beta and c subunits being particularly well conserved. Differences in the primary structures of the Synechococcus 6716 and chloroplast gamma subunits probably underlie different mechanisms of activation of ATP synthase. The nucleotide sequences that are presented also contain 12 other open reading frames. One of them encodes a protein sequence related to the E. coli DNA repair enzyme, photolyase, and another codes for a protein that contains internal repeats related to sequences in the myosin heavy chain. | 10.1042/bj2940239 |
pubmed_807_15098 | Do low fertility and population aging lead to economic decline if couples have fewer children, but invest more in each child? By addressing this question, this article extends previous work in which the authors show that population aging leads to an increased demand for wealth that can, under some conditions, lead to increased capital per worker and higher per capita consumption. This article is based on an overlapping generations (OLG) model which highlights the quantity-quality tradeoff and the links between human capital investment and economic growth. It incorporates new national level estimates of human capital investment produced by the National Transfer Accounts project. Simulation analysis is employed to show that, even in the absence of the capital dilution effect, low fertility leads to higher per capita consumption through human capital accumulation, given plausible model parameters. | 10.1007/s10680-009-9186-x |
pubmed_344_3312 | BACKGROUND
Myocardial infarction (MI) can be due to inherited thrombophilia caused by resistance to activated protein C resulting from factor V Leiden (FVL) mutation.
OBJECTIVES
The objectives of this study were to estimate the frequency of FVL mutation among MI cases in various populations and calculate the overall risk related to it.
SUBJECTS AND METHODS
Subjects comprised 7790 cases with MI and 19,276 healthy controls collected from 41 relevant studies in the search databases. The resulting frequency of FVL mutation among cases and the odds ratio were compared and integrated in a meta-analysis format.
RESULTS
Although there was marked variation of the frequency of FVL mutation among different populations including MI and healthy controls, most studies reported a positive risk related to it. Compilation of analyzed studies resulted in an overall frequency of FVL mutation of 6.791% among MI cases, which was significantly higher than that among controls (1.304%, p = 0.0) with an overall odds ratio of 1.608 (95% confidence interval, 1.98-4.44).
CONCLUSION
There is a definite risk related to the carriage of FVL mutation among MI cases. This should have a potential impact on the genetic counseling of family members of affected cases for proper prophylaxis. | 10.1089/gtmb.2010.0017 |
pubmed_892_19637 | For four generations rats were fed a low selenium diet (2-7 micrograms Se kg-1) or the same diet with 250 or 300 micrograms Se kg-1 added as selenite. In male rats of the first generation that had been fed the diets from the age of 20 days onwards, selenium depletion led to slightly delayed testis growth during pubertal development that was compensated for in the later stages of maturation. In adult rats fed the low selenium diet for nearly a year no changes in testicular mass and morphology were observed. The serum concentration of testosterone of 6-month-old, selenium-depleted animals was, however, slightly lower than that of adequately supplied controls, and the stimulation of testosterone secretion by administration of GnRH or LH resulted in a significantly less marked rise in the serum concentration of testosterone. From the second generation onwards the testis mass, expressed as a percentage of the body mass, decreased and in the fourth generation was less than 50% of that of the controls. The male gonads of fourth generation animals showed a severe bilateral atrophy, in which the seminiferous tubules were considerably reduced in diameter and almost entirely lined by Sertoli cells and a few stem cells. Differentiated spermatozoa could not be detected. The alterations were reversible and spermatogenesis was restored by feeding the selenium-adequate diet. The findings indicate that testicular morphology and functions are affected by severe selenium deficiency and that the element is necessary for testosterone biosynthesis and the formation and normal development of spermatozoa. | 10.1530/jrf.0.1060291 |
pubmed_825_17817 | The effect of war on the suicide rate and on the relative likelihood of suicide as a proportion of total personal aggression was examined in the United States for the time period from 1933 to 1986. Once unemployment was controlled for, no effect of war was detected. | 10.1080/07488009108408990 |
pubmed_780_16528 | Because of the ubiquity of phthalates and their potential role in increasing risk for cancer and reproductive dysfunction, the need for human exposure assessment studies is urgent. In response to this need, we developed a high-throughput, robust, sensitive, accurate, and precise assay for simultaneous measurement of trace levels of eight phthalate metabolites in human urine by HPLC-MS/MS. Human urine samples were processed using enzymatic deconjugation of the glucuronides followed by solid-phase extraction. The eluate was concentrated, and the phthalate metabolites were chromatographically resolved by reversed-phase HPLC, detected by APCI-tandem mass spectrometry, and quantified by isotope dilution. This selective analytical method permits rapid detection (7.7 min total run time) of eight urinary metabolites of the most commonly used phthalates with detection limits in the low nanagram per milliliter range. Assay precision was improved by incorporating 13C4-labeled internal standards for each of the eight analytes, as well as a conjugated internal standard to monitor deconjugation efficiency. This selective, sensitive, and rapid method will help elucidate potential associations (if any) between human exposure to phthalates and adverse health effects. | 10.1021/ac000422r |
pubmed_676_1353 | The Medicare Plus project of the Oregon Region Kaiser-Permanente Medical Care Program was designed as a model for prospective payment to increase Health Maintenance Organization (HMO) participation in the Medicare program. The project demonstrated that it is possible to design a prospective payment system that costs the Medicare program less than services purchased in the community from fee-for-service providers; would provide appropriate payment to the HMO; and in addition, creates a "savings" to return to beneficiaries in the form of comprehensive benefits to motivate them to enroll in the HMO. Medicare Plus was highly successful in recruiting 5,500 new and 1,800 conversion members into the demonstration, through use of a media campaign, a recruitment brochure, and a telephone information center. Members recruited were a representative age and geographic cross section of the senior citizen population in the Portland, Oregon metropolitan area. Utilization of inpatient services by Medicare Plus members in the first full year (1981) was 1679 days per thousand members and decreased to 1607 in the second full year (1982). New members made an average of eight visits per year to ambulatory care facilities. | pubmed_676_1353 |
pubmed_659_4346 | Multi-view clustering (MVC) is a mainstream task that aims to divide objects into meaningful groups from different perspectives. The quality of data representation is the key issue in MVC. A comprehensive meaningful data representation should be with the discriminant characteristics in a single view and the correlation of multiple views. Considering this, a novel framework called Dynamic Guided Metric Representation Learning for Multi-View Clustering (DGMRL-MVC) is proposed in this paper, which can cluster multi-view data in a learned latent discriminated embedding space. Specifically, in the framework, the data representation can be enhanced by multi-steps. Firstly, the class separability is enforced with Fisher Discriminant Analysis (FDA) within each single view, while the consistence among different views is enhanced based on Hilbert-Schmidt independence criteria (HSIC). Then, the 1st enhanced representation is obtained. In the second step, a dynamic routing mechanism is introduced, in which the location or direction information is added to fulfil the expression. After that, a generalized canonical correlation analysis (GCCA) model is used to get the final ultimate common discriminated representation. The learned fusion representation can substantially improve multi-view clustering performance. Experiments validated the effectiveness of the proposed method for clustering tasks. | 10.7717/peerj-cs.922 |
pubmed_126_8365 | To characterize fuel utilization of patients with congestive heart failure (CHF), we measured serum free fatty acid (FFA), counterregulatory hormone concentrations, whole body substrate oxidation rates (indirect calorimetry), and the turnover and oxidation rates of FFA ([1-(14)C]-palmitate infusion) in 7 patients with CHF and in 7 cardiac patients without CHF after an overnight fast. Plasma glucose and serum insulin concentrations were comparable, whereas serum FFA, blood ketone body, and fasting blood lactate (p <0.05 for all) concentrations were significantly increased in patients with CHF compared to those without CHF. Fasting plasma norepinephrine (p <0.05), serum cortisol (p <0.01), and growth hormone (p <0.01) concentrations were also higher in patients with CHF than in those without CHF. Rates of energy expenditure at rest (62 +/- 2 vs 56 +/- 1 J x kg(-1) x min(-1), p <0.05), FFA turnover (6.5 +/- 0.5 vs 5.0 +/- 0.4 micromol x kg(-1) x min(-1), p <0.05), and oxidation (2.0 +/- 0.2 vs 1.5 +/- 0.1 micromol x kg(-1) x min(-1)], p <0.05) were significantly higher in patients with CHF than in control subjects. In univariate analysis, the left ventricular ejection fraction was inversely correlated and the plasma norepinephrine concentration positively correlated with both energy expenditure at rest, FFA turnover, and the FFA oxidation rate. In multivariate analysis, the plasma norepinephrine concentration was the most significant predictor of increased FFA oxidation rate. We conclude that release of FFAs to the circulation and their subsequent oxidation are increased in patients with severe CHF after an overnight fast. These changes might reflect stress hormone-induced lipolysis and accompanying stimulation of serum FFA oxidation via mass action. | 10.1016/s0002-9149(97)00804-7 |
pubmed_166_16487 | BACKGROUND
New combinations of divergent genomes can give rise to novel genetic functions in resulting hybrid progeny. Such functions may yield opportunities for ecological divergence, contributing ultimately to reproductive isolation and evolutionary longevity of nascent hybrid lineages. In plants, the degree to which transgressive genotypes contribute to floral novelty remains a question of key interest. Here, we generated an F1 hybrid plant between the red-flowered Ruellia elegans and yellow flowered R. speciosa. RNA-seq technology was used to explore differential gene expression between the hybrid and its two parents, with emphasis on genetic elements involved in the production of floral anthocyanin pigments.
RESULTS
The hybrid was purple flowered and produced novel floral delphinidin pigments not manufactured by either parent. We found that nearly a fifth of all 86,475 unigenes expressed were unique to the hybrid. The majority of hybrid unigenes (80.97%) showed a pattern of complete dominance to one parent or the other although this ratio was uneven, suggesting asymmetrical influence of parental genomes on the progeny transcriptome. However, 8.87% of all transcripts within the hybrid were expressed at significantly higher or lower mean levels than observed for either parent. A total of 28 unigenes coding putatively for eight core enzymes in the anthocyanin pathway were recovered, along with three candidate MYBs involved in anthocyanin regulation.
CONCLUSION
Our results suggest that models of gene evolution that explain phenotypic novelty and hybrid establishment in plants may need to include transgressive effects. Additionally, our results lend insight into the potential for floral novelty that derives from unions of divergent genomes. These findings serve as a starting point to further investigate molecular mechanisms involved in flower color transitions in Ruellia. | 10.1186/s12870-016-0962-6 |
pubmed_1039_8385 | Radioimmunoassay of the hypothalamic-hypophyseal-ovarian interrelationships was performed in 87 patients with cervical cancer and 37 practically healthy women. The patients were examined before concomitant radiation therapy, after administration of the half dose to the focus, immediately after irradiation and 3-12 mos. and 2-5 yrs. after it. The basal level of the follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol as well as their response to the administration of the releasing factor of the hypothalamus (luliberin) were studied. Some disorders that manifested themselves in the decreased level of estradiol, were established in the patients with cervical cancer even before irradiation. Concomitant radiation therapy resulted in pronounced changes in the activities of the hypothalamic-hypophyseal-ovarian system that manifested themselves in the lowered rate of LH increment in response to the administration of luliberin and the absence of estradiol response to the load. These changes persisted long after the termination of concomitant radiation therapy. | pubmed_1039_8385 |
pubmed_954_13377 | In the first half of the twentieth century, more than a million young Italians were found affected by a new disease: the Pende's hyperthymic syndrome. Nicola Pende was the renowned clinician who wrote the first great Italian treatise of endocrinology and who later founded the "sciences" of biotypology and orthogenesis. The paper tells the parable of the syndrome, the story of big lazy children and their fate in radiation therapy for the greater glory of Roman Italic race. | pubmed_954_13377 |
pubmed_273_17612 | AIMS
To assess the incidence, timing, and relation of drug-eluting stent (DES) thrombosis to discontinuation of clopidogrel therapy.
METHODS AND RESULTS
This prospective observational cohort study included 6816 consecutive patients that underwent successful DES implantation. Primary endpoint was definite stent thrombosis (ST). During 4 years of follow-up, definite ST was observed in 73 patients, corresponding to a cumulative incidence of 1.2%. Cumulative incidence of ST at 30 days was 0.5 and 0.8% at 1 year, respectively. Discontinuation of clopidogrel therapy was significantly associated with ST only in the first 6 months after the procedure (P < 0.001). During that period, the median time interval from clopidogrel discontinuation to ST was 9 days [interquartile range (IQR) 5.5-22.5] while thereafter it was 104.3 days (IQR 7.4-294.8).
CONCLUSION
The 4 year incidence of ST after DES implantation is low. A relevant number of ST occur early after discontinuation of clopidogrel therapy. The dependence of ST on discontinuation of clopidogrel therapy seems to be mostly confined to the first 6 months after DES implantation. However, specifically designed randomized studies are required to establish the optimal length of clopidogrel therapy after DES implantation. | 10.1093/eurheartj/ehp275 |
pubmed_1073_14754 | CONTEXT
The effect of aldosterone on vascular smooth muscle cell function is still unclear. One method to measure vascular smooth muscle cell function is endothelial-independent vascular dilation, for which the key factor is sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA).
OBJECTIVE
Our objective was to investigate the effect of aldosterone on vascular smooth muscle cell function and SERCA regulation.
DESIGN
We prospectively analyzed 35 patients with primary aldosteronism (PA; 32 patients with aldosterone-producing adenoma and three patients with idiopathic hyperaldosteronism) and 30 patients with essential hypertension (EH) who were enrolled as the control group. Flow and nitrate-mediated dilation were performed in both groups and 1 year after adrenalectomy in the patients with aldosterone-producing adenoma. In addition, we investigated the effect of aldosterone on SERCA regulation in human aortic smooth muscle cells.
SETTING
This study took place in an academic clinical research center.
PARTICIPANTS
Participants included 35 patients with PA and 30 patients with EH.
INTERVENTIONS
Adrenalectomy was undertaken in patients with aldosterone-producing adenoma.
RESULTS
The PA patients had significantly lower flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) values than the patients with EH (FMD: 13 ± 6 vs 16 ± 4; NMD: 16 ± 6 vs 19 ± 5; both P < .05). FMD/NMD were significantly correlated with log 24 hour-urine aldosterone (FMD: r = -0.287, P = .048; NMD: r = -0.402, P = .005) but not blood pressure. The impaired FMD and NMD values were significantly restored 1 year after adrenalectomy (FMD: 11 ± 4 to 19 ± 7; NMD: 15 ± 6 to 21 ± 6; both P < .01). Under confocal microscopy, aldosterone was shown to suppress the expression of SERCA2a of human aortic smooth muscle cells. Aldosterone significantly suppressed the expression of SERCA2a from 10(-8) M in mRNA and protein levels. This suppression was through down-regulation of mineralocorticoid receptor dependent mitochondrial transcription factors A and B2.
CONCLUSIONS
Aldosterone impairs vascular smooth muscle cell function and suppresses SERCA 2a expression. | 10.1210/jc.2015-2752 |
pubmed_1123_11695 | Resistance of three materials, produced on the basis of concrete compounds to the action of microscopic fungi, isolated from damaged living buildings, has been first investigated. It has been shown that samples of froth-block and thermoeffective block had low fungal resistance, in contrast to samples of cellular polystyrene concrete, which were resistant to fungal action, that can be associated with peculiarities of their component composition. | pubmed_1123_11695 |
pubmed_419_25111 | BACKGROUND
Allergic disorders are common all over the world. The pathogenesis of allergy is unclear. Therapies for allergic disorders require improvement. Endoplasmic reticulum (ER) stress is one of the factors influencing immune response. The purpose of this study is to improve the effectiveness of immunotherapy for experimental respiratory allergy by targeting the ER stress signal pathway.
METHODS
Committed CD4+ T cells were isolated from blood samples collected from patients with allergic rhinitis (AR) and TCR ovalbumin transgenic mice. The effects of TCR engagement and 3-methyl-4-nitrophenol (MNP) on inducing ER stress in committed CD4+ T cells were evaluated.
RESULTS
ER stress was detected in antigen-specific CD4+ T cells (sCD4+ T cells) of AR patients. The environmental pollutant MNP increased the expression of the X-binding protein-1 (XBP1) in the committed CD4+ T cells during the TCR engagement. XBP1 mediated the effects of MNP on inhibiting regulatory T cell (Treg) generation. The effects of MNP on induction of protein 20 (Rnf20) in CD4+ T cells were mediated by XBP1. Inhibition of Rnf20 rescued the Treg development from MNP-primed sCD4+ T cells. The ablation of Rnf20 improved the immunotherapy of AR through the restoration of the Treg generation.
CONCLUSIONS
ER stress can be detected in CD4+ T cells in TCR engagement. Exposure to MNP exacerbates ER stress in committed CD4+ T cells. Regulation of the ER stress-related Rnf20 expression can restore the generation of Treg from CD4+ T cells of subjects with allergic diseases. | 10.1007/s00018-022-04613-7 |
pubmed_637_19855 | BACKGROUND
Post-operative respiratory failure is common in liver transplant patients, with a direct effect on graft and recipient outcomes. We present a case of successful treatment for a patient who had acute respiratory distress syndrome combined with septic shock after living-donor liver transplantation with veno-arterial-venous hybrid mode of extracorporeal membrane oxygenation (ECMO) support.
METHODS
A 49-year-old male patient underwent successful emergency living-donor liver transplantation for acute-on-chronic liver failure associated with alcoholic liver cirrhosis. The patient was diagnosed with concurrent active pulmonary tuberculosis and tuberculosis peritonitis just before emergency liver transplantation. Intermittent post-operative small-bowel obstruction caused by adhesions from tuberculosis peritonitis was nonresponsive to conservative management.
RESULTS
On post-operative day 114, we performed emergency adhesio-lysis because of bowel ischemia signs. However, the patient had progressive deterioration of arterial oxygenation despite conventional ventilatory support and nitric oxide gas inhalation, and septic shock resulted from aspiration pneumonia. Therefore, we decided to administer ECMO. After initiation of ECMO support, hemodynamic status, pneumonic consolidation, and oxygenation status gradually improved, and the patient was weaned from ECMO on the 11th day. Finally, the patient was discharged on post-transplant day 204.
CONCLUSIONS
ECMO can be a beneficial rescue option for the management of refractory cardiopulmonary failure in liver transplant recipients. In addition, the hybrid mode of ECMO is a helpful salvage option when conventional modes of ECMO are inadequate. | 10.1016/j.transproceed.2017.03.030 |
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