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pubmed_1124_20128 | The intramolecular ruthenium(II)-catalyzed radical addition of the trichloroacetyl pendant group to the 2-oxazolone skeleton is greatly enhanced in the presence of catalytic Lewis acids including rare earth metal triflates, thus providing a convenient route to a highly potential chiral synthon for vic-amino alcohols. | 10.1248/cpb.50.435 |
pubmed_453_18899 | To investigate the influence of human immunodeficiency virus (HIV) coinfection on preexisting long-term chronic C hepatitis (HCV) 68 liver biopsies from 22 HIV/HCV-coinfected, 13 HIV- and 33 HCV-monoinfected patients and 71 livers obtained at autopsy from 26 HIV/HCV-coinfected and 45 HIV-monoinfected patients were studied by histo- and immunohistochemistry. All HIV patients had reached the advanced stage of immunodeficiency (stage III CDC), except for 3 haemophilias (stage II CDC). HCV infection was associated with a higher degree of portal, periportal and lobular inflammation-regardless of whether there was concurrent HIV infection. HIV/HCV coinfection was associated with a significantly higher rate of granulocytic cholangiolitis than HCV and HIV monoinfection (P < 0.05), a histological feature uncommon in C hepatitis. In HIV/HCV coinfection cholestasis was a predominant histological feature. HCV monoinfection and HCV/HIV coinfection were associated with the highest fibrosis index. In HIV/HCV coinfection centrilobular fibrosis was significantly more marked than in HCV monoinfection (P < 0.05), suggesting an HIV-associated fibrogenic effect. Patients with chronic C hepatitis showed a significantly increased rate of posthepatitic cirrhosis compared with the patients without HCV infection (P < 0.05). At autopsy, 10 of the 20 HIV/HCV-coinfected haemophiliacs had developed cirrhosis because of chronic C hepatitis, whereas cirrhosis was found in only 2 of 6 HIV/HCV-coinfected non-haemophiliacs (1 case of chronic B and C hepatitis, and 1 case of chronic alcohol abuse). No cirrhosis was observed in the 45 autopsy patients with HIV monoinfection. The findings suggest that HIV coinfection aggravates the course of preceding long-term chronic C hepatitis by a more marked (centrilobular) fibrosis. HIV/HCV-coinfected patients are threatened by a higher rate of posthepatitic cirrhosis-particularly in multitransfused haemophiliacs-and cholestatic hepatopathy. | 10.1007/BF01092749 |
pubmed_522_10208 | This study examines the effect of capitated contracting on hospital efficiency to better understand strategies related to the recent financial crisis in the California health care market. Our findings indicate that less efficient hospitals are more likely to participate in capitated contracting. As a result, hospitals with capitated contracts are, on average, less efficient than hospitals without capitated contracts. Hospital efficiency generally increases with respect to the degree of capitation involvement. The efficiency improvement, however, becomes insignificant when capitation exposures are already high. Thus, hospital executives should not be overly optimistic about efficiency gains obtained in capitated contracting and should control the degree of capitation involvement. | 10.1097/00004010-200410000-00010 |
pubmed_308_10746 | Satisfied patients are more likely to be compliant, have better outcomes, and are more likely to return to the same provider or institution for future care. The Satisfaction with a Continuum of Care survey (SCC) was designed to improve patient care using measures of patient satisfaction and facilitate a cultural shift from a "silos-of-care" to a "continuum-of-care" mentality by fostering inter-departmental communication as patients moved between environments of care at a Midwestern rehabilitation hospital. This study provides a Rasch measurement framework for investigating issues related to survey reliability and validity. The results indicate that although certain aspects of the survey seem to function in a psychometrically sound manner, the questions are too easy to endorse and provide little information to help improve patient care. Suggestions for future revisions to this survey instrument are provided. | pubmed_308_10746 |
pubmed_722_2894 | BACKGROUND AND PURPOSE
Anatomic changing frequently occurred during fractionated radiotherapy. The aims of this study were to model the potential benefit of adaptive IMRT replanning during fractionated radiotherapy and its potential advantage over clinical outcome in patients with nasopharyngeal carcinoma.
MATERIALS AND METHODS
Thirty-three patients with repeat CT imaging and replanning were retrospectively analyzed. 66 case-matched control patients without replanning were identified by matching for AJCC stage, gender, and age. Hybrid IMRT plans were generated to evaluate the dosimetric changing. Mann-Whitney-Wilcoxon tests were used to evaluate the effect of replanning on volumetric and dosimetric outcomes within individuals. Kaplan-Meier estimators were used to estimate the survival function of patients with or without replanning.
RESULTS
The mean volume of the ipsilateral and contralateral parotid glands decreased during the treatment. The hybrid IMRT plans showed decreased doses to target volumes and increased doses to normal structures in replanning. The clinical outcome comparison indicated that the IMRT replanning improved the 3 years local progression-free survival for patients who had AJCC staged more than T(3) (T(3,4)N(x)) and ease the late effects for patients who had large lymph nodes (AJCC stage T(x)N(2,3)).
CONCLUSION
Repeat CT imaging and IMRT replanning were recommendatory for specific nasopharyngeal carcinoma patients. | 10.1016/j.radonc.2010.10.009 |
pubmed_915_6699 | Stainless steel is a ubiquitous structural material and one that finds extensive use in core-internal components in nuclear power plants. Stainless steel features superior corrosion resistance (e.g., as compared to ordinary steel) due to the formation of passivating iron and/or chromium oxides on its surfaces. However, the breakdown of such passivating oxide films, e.g., due to localized deformation and slip line formation following exposure to radiation, or aggressive ions renders stainless steel susceptible to corrosion-related degradation. Herein, the effects of alkali cations (i.e., K+, Li+) and the interactions between the passivated steel surface and the solution are examined using 304L stainless steel. Scanning electrochemical microscopy and atomic force microscopy are used to examine the inert-to-reactive transition of the steel surface both in the native state and in the presence of applied potentials. Careful analysis of interaction forces, in solution, within ≤10 nm of the steel surface, reveals that the interaction between the hydrated alkali cations and the substrate affects the structure of the electrical double layer (EDL). As a result, a higher surface reactivity is indicated in the presence of Li+ relative to K+ due to the effects of the former species in disrupting the EDL. These findings provide new insights into the role of the water chemistry not only on affecting metallic corrosion but also in other applications, such as batteries and electrochemical devices. | 10.1021/acsomega.8b02227 |
pubmed_597_21143 | BACKGROUND
Choroid plexus tumors (CPTs) are intraventricular lesions originating from ventricular neuroepithelium and represent up to 4% of brain neoplasms affecting pediatric population. They are more frequently benign papillomas, but malignant carcinomas can sometimes occur.
METHOD
The authors present a description of surgical approach for CPTs, particularly focusing on the complications related to the cerebrospinal fluid (CSF) circulation, which may affect outcome.
CONCLUSION
Microsurgical resection represents the first line treatment for CPTs. The goal is the complete removal of the tumor and the restoration of a physiological CSF circulation. | 10.1007/s00701-013-1912-9 |
pubmed_932_2842 | lin-28 is a conserved regulator of cell fate succession in animals. In Caenorhabditis elegans, it is a component of the heterochronic gene pathway that governs larval developmental timing, while its vertebrate homologs promote pluripotency and control differentiation in diverse tissues. The RNA binding protein encoded by lin-28 can directly inhibit let-7 microRNA processing by a novel mechanism that is conserved from worms to humans. We found that C. elegans LIN-28 protein can interact with four distinct let-7 family pre-microRNAs, but in vivo inhibits the premature accumulation of only let-7. Surprisingly, however, lin-28 does not require let-7 or its relatives for its characteristic promotion of second larval stage cell fates. In other words, we find that the premature accumulation of mature let-7 does not account for lin-28's precocious phenotype. To explain let-7's role in lin-28 activity, we provide evidence that lin-28 acts in two steps: first, the let-7-independent positive regulation of hbl-1 through its 3'UTR to control L2 stage-specific cell fates; and second, a let-7-dependent step that controls subsequent fates via repression of lin-41. Our evidence also indicates that let-7 functions one stage earlier in C. elegans development than previously thought. Importantly, lin-28's two-step mechanism resembles that of the heterochronic gene lin-14, and the overlap of their activities suggests a clockwork mechanism for developmental timing. Furthermore, this model explains the previous observation that mammalian Lin28 has two genetically separable activities. Thus, lin-28's two-step mechanism may be an essential feature of its evolutionarily conserved role in cell fate succession. | 10.1371/journal.pgen.1002588 |
pubmed_1132_23159 | Pediatric sacroiliac joint injuries are uncommon lesions, especially when combined with anterior sacroiliac dislocation. Here, we present a rare case of anterior dislocation of the sacroiliac joint associated with ipsilateral acetabulum, subtrochanteric, and pubic rami fractures combined with a contralateral sacral fracture. This appears to be the first such case reported in the literature. At the 6-month follow-up, a favorable clinical outcome was achieved, with radiological healing of the lesion. | 10.1097/BPB.0b013e3283606af9 |
pubmed_147_25353 | BACKGROUND
Adverse event incidence analyses are a critical component for describing the safety profile of any new intervention. The results typically are presented in lengthy summary tables. For therapeutic areas where patients have frequent adverse events, analysis and interpretation are made more difficult by the sheer number and variety of events that occur. Understanding the risk in these instances becomes even more crucial.
PURPOSE
We describe a space-saving graphical summary that overcomes the limitations of traditional presentations of adverse events and improves interpretability of the safety profile.
METHODS
We present incidence analyses of adverse events graphically using volcano plots to highlight treatment differences. Data from a clinical trial of patients experiencing an aneurysmal subarachnoid hemorrhage are used for illustration. Adjustments for multiplicity are illustrated.
RESULTS
Color is used to indicate the treatment with higher incidence; bubble size represents the total number of events that occur in the treatment arms combined. Adjustments for multiple comparisons are displayed in a manner to indicate clearly those events for which the difference between treatment arms is statistically significant. Furthermore, adverse events can be displayed by time intervals, with multiple volcano plots or animation to appreciate changes in adverse event risk over time. Such presentations can emphasize early differences across treatments that may resolve later or highlight events for which treatment differences may become more substantial with longer follow-up.
LIMITATIONS
Treatment arms are compared in a pairwise fashion.
CONCLUSIONS
Volcano plots are space-saving tools that emphasize important differences between the adverse event profiles of two treatment arms. They can incorporate multiplicity adjustments in a manner that is straightforward to interpret and, by using time intervals, can illustrate how adverse event risk changes over the course of a clinical trial. | 10.1177/1740774513485311 |
pubmed_650_6411 | Rhesus monkeys were trained to lever press for infusions of cocaine during daily, 1-h experimental sessions. Following stabilization of the cocaine-maintained baselines, various antihistamines were substituted for cocaine to determine whether they would be self-administered. The results indicated that all monkeys tested self-administered tripelennamine and chlorpheniramine. One monkey out of the four self-administered pyrilamine, but only at a single (300 microgram/kg) high dose. Phenyltoloxamine, cimetidine and hydroxyzine were not self-administered. These results further illuminate differences amongst H1 antagonists in their potential for self-administration and, when examined in context with other reports, suggest that stimulant-like properties may help mediate their reinforcing effects when present. | 10.1016/0376-8716(92)90016-6 |
pubmed_895_19710 | The temporal and serial organization (or timing) of responses in motor skill was investigated in a repetitive motor task, resisted hand cranking. Both positional timing and serial timing were analyzed using strain-gauge techniques and were related to the performance of the preferred and non-preferred hands. The results demonstrated the superiority of the preferred hand on the serial timing criteria and supported the hypothesis that skilled performance is characterized by more effective temporal structuring of the components of the response. | 10.1080/00222895.1970.10734881 |
pubmed_439_13852 | COVID-19 has affected us all. The following collection of short essays highlights various aspects of the pandemic and how it has impacted hand surgery and lessons learned, from the perspective of the Federation of European Societies for Surgery of the Hand (FESSH) Executive Committee members. A range of topics were individually chosen by each of the five committee members and presented. | 10.1177/17531934221093925 |
pubmed_591_4278 | Platelet concentrates (PCs), represented by platelet-rich plasma (PRP), have been widely applied in the fields of regenerative and aesthetic therapies. PCs' mechanisms of action, however, are too complicated, and it is not easy to present the whole picture; besides, clinical outcomes are hardly reproducible in many cases. Therefore, several medically advanced countries seemingly intend to regulate PC therapies weakly or strictly because of the increasing popularity. Japan established laws and regulations for PC therapy in the "Act on the Safety of Regenerative Medicine" along with the "Pharmaceuticals, Medical Devices and Other Therapeutic Products Act" in 2014, which, to our knowledge, represent the strictest regulatory framework for production and therapeutic use of PCs in the world. According to these laws and regulations, PCs produced for topical use should be prepared as cell-based medicinal products, essentially as should stem cells, in accordance with their registered ("licensed" under actual conditions) standard operating procedures. Nonetheless, criteria for their quality are not standardized. In this review, we discuss the quality of PC preparations by focusing on the basic concept and regulatory framework of regenerative medicine in Japan. Within the new framework, PC therapy is regulated by a specific notification and registration system, as is stem cell therapy. In comparison with the latter, however, risk factors that hamper successful PC therapy are much fewer. Via appropriate evaluation of patients' conditions and whole-blood samples by simple and sensitive but not yet fully standardized assays, it is theoretically possible that PC quality will be controlled nearly completely. In addition to or instead of standardization of preparation protocols, standardization of preoperative examination of individual PC preparations is an urgent task for improving and guaranteeing the safety and efficacy of PC therapy. | 10.1155/2018/6389157 |
pubmed_371_13061 | The stereochemical course of the vitamin K dependent carboxylation has been elucidated using a (4S)-4-fluoroglutamyl-containing pentapeptide as a substrate. The absolute configuration of the [13C]-4-carboxy-4-fluoroglutamate obtained when the carboxylation was carried out with 13C-labeled sodium bicarbonate, was determined after reduction of the [13C]-4-carboxy-4-fluoroglutamyl residue into 4-fluoro-5,5'-dihydroxyleucine, hydrolysis, lactonization, and peracetylation. The absolute configuration at C-4 was determined to be S by locating the 13C label in the lactone ring of the trans isomeric lactone and in the hydroxymethyl group of the cis isomer following HPLC separation of both isomers and analysis by GC/MS/MS techniques. It follows that the vitamin K dependent carboxylation occurs with inversion of configuration. | 10.1021/bi00107a020 |
pubmed_663_174 | A clinical neurological syndrome termed peripheral neuropathy (PN) that resembles Marek's disease (MD) occurred at low frequency in a commercial layer strain for several years. Study of chickens from six field cases showed that the PN syndrome could be distinguished pathologically from MD on the basis of several factors, including onset as early as 6 weeks, presence of B-type but not A-type lesions in peripheral nerves, and absence of visceral lymphomas. Serotype 1 MD virus could not be isolated from blood from any chicken or demonstrated in tissues by histochemistry or polymerase chain reaction assays. Moreover, the syndrome was not prevented by MD vaccination, either in the field or in laboratory trials. PN was induced in 3 to 54%of commercial line chickens inoculated at 1 or 6 days of age with whole blood or buffy coat cells from clinically affected donor chickens. Sonicated cells also induced PN, but plasma was ineffective. Chickens did not develop PN if reared in isolators without cellular transfer or when vaccinated solely against MD. However, PN was observed in 9% of 57 B*2/*19 commercial chickens reared in isolators following vaccination against MD, infectious bursal disease, Newcastle disease and infectious bronchitis, suggesting that common vaccines may predispose chickens to PN. The data confirmed a strong influence of the major histocompatibility complex (B-complex) on both naturally occurring and experimentally induced PN with the B*19 haplotype conferring susceptibility compared with other alleles. It is postulated that PN may represent an autoimmune reaction to nerve tissue that may result from response to a combination of common vaccines. These studies confirmed that PN is distinct from MD, provided criteria for its differential diagnosis, identified strategies for its control, and established a model for its experimental induction. | 10.1080/03079450120078680 |
pubmed_701_6670 | Enough information has been gained from clinical trials to allow the conclusion that human gene transfer is feasible, can evoke biologic responses that are relevant to human disease, and can provide important insights into human biology. Adverse events have been uncommon and have been related to the gene delivery strategies, not to the genetic material being transferred. Human gene transfer still faces significant hurdles before it becomes an established therapeutic strategy. However, its accomplishments to date are impressive, and the logic of the potential usefulness of this clinical paradigm continues to be compelling. | 10.1126/science.270.5235.404 |
pubmed_923_13820 | PURPOSE
To test the hypothesis that variable hyperoxia potentiates preretinal neovascularization in newborn rats, and to establish a more reliable animal model of ROP in which therapies designed to inhibit abnormal angiogenesis can be tested.
METHODS
Immediately after birth, litters of Sprague Dawley albino rats and mothers were placed in an incubator containing 40% oxygen. After 12 hours, the oxygen was increased to 80% with a transition time of less than 1 min. For the ensuing 7, 10, or 14 days, the oxygen was altered between 40% and 80% every 12 hr in a stepwise fashion. Other litters were kept in constant 80% oxygen or in room air for the same three time periods. After exposure, rats were either killed or placed in room air for an additional 2, 4, or 7 days before being killed.
RESULTS
When rats were killed immediately after oxygen exposure, the resulting vessel loss in rats exposed to 40%/80% oxygen was identical to that of animals exposed to 80% (vessels constituted 12.2 +/- 2.2% of total retinal area in cyclic oxygen vs 12.0 +/- 1.2% in constant oxygen). However, preretinal neovascularization subsequently occurred in 66% (63/96) of all rats exposed to cyclic oxygen followed by a room air period but in no rats (0/50) exposed to constant oxygen followed by room air. Preretinal vascular proliferation consisted of glomerular tufts of endothelial cells, or mature, lumenized vessels containing red blood cells.
CONCLUSIONS
Consistency of oxygen therapy is more important than overall oxygen level in inducing retinopathy. Consideration should be given to tighter control of intended oxygen therapy in premature infants, regardless of the target saturation level. | pubmed_923_13820 |
pubmed_743_13383 | Current guidelines recommend reducing the daily intake of dietary fats for the prevention of ischemic cardiovascular diseases (CVDs). Avoiding saturated fats while increasing the intake of mono- or polyunsaturated fatty acids has been for long time the cornerstone of dietary approaches in cardiovascular prevention, mainly due to the metabolic effects of these molecules. However, recently, this approach has been critically revised. The experimental evidence, in fact, supports the concept that the pro- or anti-inflammatory potential of different dietary fats contributes to atherogenic or anti-atherogenic cellular and molecular processes beyond (or in addition to) their metabolic effects. All these aspects are hardly translatable into clinics when trying to find connections between the pro-/anti-inflammatory potential of dietary lipids and their effects on CVD outcomes. Interventional trials, although providing stronger potential for causal inference, are typically small sample-sized, and they have short follow-up, noncompliance, and high attrition rates. Besides, observational studies are confounded by a number of variables and the quantification of dietary intakes is far from optimal. A better understanding of the anatomic and physiological barriers for the absorption and the players involved in the metabolism of dietary lipids (e.g., gut microbiota) might be an alternative strategy in the attempt to provide a first step towards a personalized dietary approach in CVD prevention. | 10.3390/nu13113768 |
pubmed_206_928 | A series of Mannich bases of 4-substituted 5-[4-(4-X-phenylsulfonyl)phenyl]-2,4-dihydro-3H-1,2,4-triazole-3-thiones, X=H, Cl, Br, 3 and 5 were synthesized and characterized on the basis of IR, NMR and elemental analyses. The potential antibacterial effects of the synthesized compounds were investigated using the Acinetobacter baumanii ATCC 19606; Citrobacter freundii ATCC 8090; Pseudomonas aeruginosa ATCC 9027; Enterococcus faecalis ATCC 19433; Staphylococcus aureus ATCC 12600; Staphylococcus epidermidis ATCC 14990; Bacillus subtilis ATCC 6633 strains. Some of them exhibited promising activities against A. baumanii and B. subtilis. | 10.1016/j.ejmech.2008.07.003 |
pubmed_597_25412 | BACKGROUND
To assess the treatment pattern and expenditure incurred by cancer patients undergoing treatment at government tertiary hospitals in India.
MATERIALS AND METHODS
A cross-sectional study of 508 cancer patients randomly selected from tertiary cancer hospitals funded by central/state governments located in major cities of five states in India, namely Kerala, Maharashtra, Rajasthan, West Bengal and Mizoram, during March - May 2011 was conducted. Information related to direct costs, indirect costs and opportunity costs incurred on investigations and treatment, major source of payment and difficulties faced by patients during the course of treatment was collected.
RESULTS
About 45% of the patients used private health facilities as the first point of contact for cancer related diseases as against 32% in public hospitals. About 47% sought private health facilities for cancer investigations, 21% at district/sub-district hospitals, and about 4% contacted primary health care facilities. A majority of the patients (76%) faced financial problems while undergoing treatment.
CONCLUSIONS
The results highlight the importance of involving the primary health care system in the cancer prevention activities. | 10.7314/apjcp.2013.14.9.5049 |
pubmed_844_15286 | Pregnancy is accompanied by physiological hyperventilation that may be perceived as shortness of breath; causes are a reduced residual capacity and a reduced expiratory reserve volume due to the swelling uterus, and a larger tidal volume due to increase of the progesterone concentration and of the chemosensitivity to CO2 and O2. Fatigue, lowered exercise tolerance and orthopnoea also may occur, as do basal crepitations at auscultation. In pregnant asthma patients the symptoms may either improve greatly or become aggravated. During an asthma attack the foetus is exposed to hypoxaemia, which may be worsened by a decreased uteroplacental blood circulation in case of maternal alkalosis. Poorly controlled asthma has a stronger adverse effect on the unborn child than the judicious use of anti-asthma drugs. Safe drugs against asthma during pregnancy, around parturition and during breast feeding, are cromoglycic acid and ipratropium; relatively safe drugs are short-acting beta-sympathicomimetics, inhalation corticosteroids and systemic corticosteroids, as well as theophylline from the second trimester; use of long-acting beta-sympathicomimetics is advised against. | pubmed_844_15286 |
pubmed_579_19474 | OBJECTIVE
To characterize groups of subjects according to their trajectory of knee pain and function over 1 to 5 years post total knee arthroplasty (TKA).
METHODS
Patients from one centre who underwent primary TKA (N = 689) between 2006 and 2008. The Knee Society Score (KSS) was collected pre-operatively and annually post-operatively. Latent Class Growth Analysis (LCGA) was used to classify groups of subjects according to their trajectory of knee pain and function over 1-5 years post-surgery.
RESULTS
LCGA identified a class of patients with persistent moderate knee pain (22.0%). Predictors (OR, 95% CI) of moderate pain trajectory class membership were pre-surgery SF12 mental component summary (MCS) per 10 points (0.65, 0.54-0.79) and physical component summary (PCS) per 10 points (0.50, 0.33-0.76), Charlson Comorbidity Index (CCI) one (1.70, 1.07-2.69) and ≥two (2.82, 1.59-4.81) and the absence of computer-navigation (2.26, 1.09-4.68). LCGA also identified a class of patients with poor function (23.0%). Predictors of low function trajectory class membership were, female sex (3.31, 1.95-5.63), advancing age per 10 years (2.27, 1.69-3.02), pre-surgery PCS per 10 points (0.50, 0.33-0.74), obesity (1.69, 1.05-2.72), morbid obesity (3.12, 1.55-6.27) and CCI ≥two (2.50, 1.41-4.42).
CONCLUSIONS
Modifiable predictors of poor response to TKA included baseline co-morbidity, physical and mental well-being and obesity. This provides useful information for clinicians in terms of informing patients of the expected course of longer term outcomes of TKA and for developing prediction algorithms that identify patients in whom there is a high likelihood of poor surgical response. | 10.1016/j.joca.2015.07.005 |
pubmed_770_10407 | A population survey in 1982 confirmed that Nauruan adults suffer from an extremely high prevalence (24%) of non-insulin-dependent diabetes mellitus. A follow-up study of the survey subjects was conducted in 1986. The aim was to assess the burden of diabetes to Nauruans in terms of premature mortality. Age-adjusted mortality rates for diabetic subjects were significantly increased when compared with normal subjects (relative risks for 4-yr mortality were 4.53 in men, P less than .01, and 3.96 in women, P less than .05). Although there was an excess number of deaths among diabetic subjects compared with normal subjects and subjects with impaired glucose tolerance, there was no significant association between cause of death and diabetes. | 10.2337/diacare.11.4.305 |
pubmed_1115_2653 | Chemokines are small chemoattractant cytokines that control a wide variety of biological and pathological processes, ranging from immunosurveillance to inflammation, and from viral infection to cancer. Genetic and pharmacological studies have shown that chemokines are responsible for the excessive recruitment of leucocytes to inflammatory sites and damaged tissue. In the present paper, we discuss the rationale behind interfering with the chemokine system and introduce various points for therapeutic intervention using either protein-based or small-molecule inhibitors. Unlike other cytokines, chemokines signal via seven-transmembrane GPCRs (G-protein-coupled receptors), which are favoured targets by the pharmaceutical industry, and, as such, they are the first cytokines for which small-molecule-receptor antagonists have been developed. In addition to the high-affinity receptor interaction, chemokines have an in vivo requirement to bind to GAGs (glycosaminoglycans) in order to mediate directional cell migration. Prevention of the GAG interaction has been shown to be a viable therapeutic strategy. Targeting chemokine intracellular signalling pathways offers an alternative small-molecule approach. One of the key signalling targets downstream of a variety of chemokine receptors identified to date is PI3Kgamma (phosphoinositide 3-kinase gamma), a member of the class I PI3K family. Thus the chemokine system offers many potential entry points for innovative anti-inflammatory therapies for autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and allergic contact dermatitis. | 10.1042/bst0320366 |
pubmed_910_17428 | INTRODUCTION
The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry (MS). Studies using advanced MS have resulted in new insights into cell biology and the etiology of diseases as well as its use in clinical applications.
AREAS COVERED
This review discusses recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It also discusses the issues around translating the research findings to the clinic and provides an outline of where the field is moving. Expert commentary: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics. | 10.1080/14789450.2016.1182431 |
pubmed_603_1121 | AIMS
Resveratrol (Res) which is a polyphenolic phytoalexin, has various biological properties. In the present study, we investigated whether Res extracted from Polygonum cuspidatum can reduce oxidative damage and cognitive impairment in senescence-accelerated mouse (SAM).
MAIN METHODS
Senescence-accelerated mice were administered with Res (25, 50, 100mg·kg(-1)·d(-1)) for 8weeks. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in mice brain were determined. The gene expression of SOD in mice brain was investigated by real time reverse transcriptase-polymerase chain reaction (RT-PCR).
KEY FINDINGS
The results showed that resveratrol significantly improved learning and memory ability in Morris water maze test and neuromuscular coordination and sensorimotor capacity in tightrope test. Meanwhile, Res increased the activities of antioxidant enzymes with a reduction in lipid peroxidation. And real time RT-PCR analysis also indicated that the change of SOD mRNA was the same as the modification of SOD activity in mice brain. Furthermore, Res could prevent cerebral mitochondrial DNA deletions which might be one of the causes resulting in learning and memory impairment.
SIGNIFICANCE
These results suggest that the pharmacological action of Res may offer a novel therapeutic strategy for the treatment of age-related conditions. | pubmed_603_1121 |
pubmed_954_1563 | Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is often associated with a poor prognosis. The aim of our study was to identify biomarkers predictive of TNBC progression. Primary TNBC breast tissue samples including four with metastasis and six without metastasis were subjected to Affymetrix GeneChip® analysis (human genome U133). Ubiquitin-specific protease 2 (USP2) was identified as an upregulated gene in the metastatic group, and its expression was analyzed by immunohistochemistry in 121 primary breast cancers, 13 paired normal tissues, and 13 paired metastatic lesions. Survival analysis was performed using the log-rank test and Cox regression hazard model. Matrigel migration and invasion assays in USP2-silenced and USP2-overexpressed breast cancer cell lines were used to investigate the mechanisms of USP2 in vitro. Positive immunostaining for USP2 was detected in breast tumors and was correlated with estrogen receptor (ER) and progesterone receptor (PR) statuses and TNBC subtype. USP2 was overexpressed in distant metastatic lesions compared with primary breast cancers. Survival analyses demonstrated that positive USP2 is a poor prognostic factor for disease-free survival. Silencing of USP2 expression decreased migration and invasion in LM2-4175 and SCP46 cells in association with the downregulation of matrix metalloproteinase-2 (MMP2) expression, whereas overexpression of USP2 in MDA-MB-468 and MDA-MB-231 cells enhanced migration and invasion and upregulated the expression of MMP2. The present study showed that USP2 expression is associated with TNBC cell line's invasiveness and poor survival of breast cancer patients and may serve as a prognostic biomarker and therapeutic target for TNBC. | 10.1007/s13277-015-3207-7 |
pubmed_43_25396 | RATIONALE
Ketamine is a novel, rapid-acting antidepressant for treatment refractory depression (TRD); however, clinical durability is poor and treatment response trajectories vary. Little is known about which patient characteristics predict faster or more durable ketamine responses. Ketamine's antidepressant mechanism may involve modulation of glutamatergic signaling and long-term potentiation (LTP); these neuroplasticity pathways are also attenuated with older age.
OBJECTIVE
A retrospective analysis examining the impact of patient age on the speed and durability of ketamine's antidepressant effects in 49 veterans receiving serial intravenous ketamine infusions for TRD.
METHOD
The relationship between age and percent change in Beck Depression Inventory (BDI-II) scores was compared across six serial ketamine infusions (twice-weekly for 3 weeks) using a linear-mixed model.
RESULTS
A significant Age-X-Infusion number interaction (F = 3.01, p = .0274) indicated that the relationship between age and treatment response depended on infusion number. Follow-up tests showed that younger age significantly predicted greater clinical improvement at infusion #4 (t = 3.02, p = .004); this relationship was attenuated at infusion #5 (t = 1.95, p = .057) and was absent at infusion #6. Age was not a significant predictor of treatment durability, defined as percent change in BDI-II 3 weeks following infusion #6.
CONCLUSIONS
These data preliminarily suggest that younger age is associated with a faster response over six serial ketamine infusions; by infusion #6 and subsequent weeks of clinical follow-up, age no longer predicts ketamine's antidepressant activity. Age may mediate the speed but not the durability or total efficacy of ketamine treatment, suggesting that dissociable mechanisms may underlie differing aspects of ketamine's antidepressant activity. | 10.1007/s00213-021-05939-z |
pubmed_248_2682 | AMPA receptor (AMPAR) trafficking at CNS synapses is regulated by several receptor-binding proteins. One model of AMPAR endocytosis entails the cotargeting of the GluR2-interacting protein PICK1 and activated PKC to synapses. We demonstrate that NMDA receptor (NMDAR) activation mediates bidirectional changes in surface AMPARs through two additional forms of PICK1 redistribution. In neurons, NMDAR activation, which induces AMPAR endocytosis, increases endosomal PICK1 clustering. In contrast, stronger NMDAR activation rapidly reduces PICK1 clustering accompanied by decreases in PICK1/GluR2 association and increases in surface AMPAR levels. PICK1-siRNA similarly increases surface AMPARs and occludes the NMDAR-mediated effect, demonstrating the role of PICK1 in this process. Bidirectional NMDAR-mediated changes in PICK1 localization are determined by the magnitude of receptor-activated dendritic calcium signals. Our results show that PICK1 localization in dendrites is subject to multiple forms of regulation that contribute to surface AMPAR expression, likely by modulating the numbers of AMPARs maintained in intracellular compartments. | 10.1016/j.mcn.2005.11.011 |
pubmed_568_5777 | BACKGROUND
Children represent a significant percentage of casualties in modern conflict. Yet, the epidemiology of conflict-related injury among children is poorly understood. A comprehensive analysis of injuries sustained by children in 21st-century armed conflict is necessary to inform planning of local, military, and humanitarian health responses.
METHODS
We conducted a systematic search of databases including PubMed, Embase, Web of Science, World Health Organization Catalog, and Google Scholar to identify records that described conflict-related injuries sustained by children since 2001.
RESULTS
The search returned 5,264 records. 9 eligible reports without potentially duplicative data were included in analysis, representing 5,100 pediatric patients injured in 5 conflicts. Blast injury was the most frequent mechanism (57%), compared to 24.8% in adults. Mortality was only slightly higher among children (11.0% compared to 9.8% among adults; p <0.05). Non-uniform reporting prevented pooled analysis and limited the conclusions that could be drawn.
CONCLUSIONS
Children sustain a higher proportion of blast injury than adults in conflict. Existing data do support the conclusion that child casualties have higher mortality than adults overall; however, this difference is slighter than has been previously reported. Specific subpopulations of children appear to have worse outcomes. Overall, non-uniform reporting renders currently available data insufficient to understand the needs of children injured in modern conflict. | 10.1016/j.injury.2021.04.055 |
pubmed_999_8386 | Fibrates, including fenofibrate, are a class of hypolipidemic drugs that activate peroxisome proliferator-activated receptor α (PPARα), which in-turn regulates the expression of lipid and lipoprotein metabolism genes. We investigated whether fenofibrate can reduce visceral obesity and nonalcoholic fatty liver disease via adipose tissue PPARα activation in female ovariectomized (OVX) C57BL/6J mice fed a high-fat diet (HFD), a mouse model of obese postmenopausal women. Fenofibrate reduced body weight gain (-38%, p < 0.05), visceral adipose tissue mass (-46%, p < 0.05), and visceral adipocyte size (-20%, p < 0.05) in HFD-fed obese OVX mice. In addition, plasma levels of alanine aminotransferase and aspartate aminotransferase, as well as free fatty acids, triglycerides, and total cholesterol, were decreased. Fenofibrate also inhibited hepatic lipid accumulation (-69%, p < 0.05) and infiltration of macrophages (-72%, p < 0.05), while concomitantly upregulating the expression of fatty acid β-oxidation genes targeted by PPARα and decreasing macrophage infiltration and mRNA expression of inflammatory factors in visceral adipose tissue. These results suggest that fenofibrate inhibits visceral obesity, as well as hepatic steatosis and inflammation, in part through visceral adipose tissue PPARα activation in obese female OVX mice. | 10.3390/ijms22073675 |
pubmed_496_4647 | New species may arise via hybridization and without a change in ploidy. This process, termed homoploid hybrid speciation, is theoretically difficult because it requires the development of reproductive barriers in sympatry or parapatry. Theory suggests that isolation may arise through rapid karyotypic evolution and/or ecological divergence of hybrid neospecies. Here, we investigate the role of karyotypic change in homoploid hybrid speciation by generating detailed genetic linkage maps for three hybrid sunflower species, Helianthus anomalus, H. deserticola, and H. paradoxus, and comparing these maps to those previously generated for the parental species, H. annuus and H. petiolaris. We also conduct a quantitative trait locus (QTL) analysis of pollen fertility in a BC2 population between the parental species and assess levels of pollen and seed fertility in all cross-combinations of the hybrid and parental species. The three hybrid species are massively divergent from their parental species in karyotype; gene order differences were observed for between 9 and 11 linkage groups (of 17 total), depending on the comparison. About one-third of the karyoypic differences arose through the sorting of chromosomal rearrangements that differentiate the parental species, but the remainder appear to have arisen de novo (six breakages/six fusions in H. anomalus, four breakages/three fusions in H. deserticola, and five breakages/five fusions in H. paradoxus). QTL analyses indicate that the karyotypic differences contribute to reproductive isolation. Nine of 11 pollen viability QTL occur on rearranged chromosomes and all but one map close to a rearrangement breakpoint. Finally, pollen and seed fertility estimates for F1's between the hybrid and parental species fall below 11%, which is sufficient for evolutionary independence of the hybrid neospecies. | 10.1534/genetics.105.042242 |
pubmed_587_20164 | The specific biochemical steps required for glucose-regulated insulin exocytosis from beta-cells are not well defined. Elevation of glucose leads to increases in cytosolic [Ca2+]i and biphasic release of insulin from both a readily releasable and a storage pool of beta-granules. The effect of elevated [Ca2+]i on phosphorylation of isolated beta-granule membrane proteins was evaluated, and the phosphorylation of four proteins was found to be altered by [Ca2+]i. One (a 18/20-kDa doublet) was a Ca2+-dependent increase in phosphorylation, and, surprisingly, three others (138, 42, and 36 kDa) were Ca2+-dependent dephosphorylations. The 138-kDa beta-granule phosphoprotein was found to be kinesin heavy chain (KHC). At low levels of [Ca2+]i KHC was phosphorylated by casein kinase 2, but KHC was rapidly dephosphorylated by protein phosphatase 2B beta (PP2Bbeta) as [Ca2+]i increased. Inhibitors of PP2B specifically reduced the second, microtubule-dependent, phase of insulin secretion, suggesting that dephosphorylation of KHC was required for transport of beta-granules from the storage pool to replenish the readily releasable pool of beta-granules. This is distinct from synaptic vesicle exocytosis, because neurotransmitter release from synaptosomes did not require a Ca2+-dependent KHC dephosphorylation. These results suggest a novel mechanism for regulating KHC function and beta-granule transport in beta-cells that is mediated by casein kinase 2 and PP2B. They also implicate a novel regulatory role for PP2B/calcineurin in the control of insulin secretion downstream of a rise in [Ca2+]i. | 10.1074/jbc.M203345200 |
pubmed_500_8999 | Three cases presenting with systemic lupus erythematosus (SLE) and minimal change nephrotic syndrome (MCNS) are reported in this paper. All cases were female; they abruptly developed nephrotic syndrome at the age of 30, 11 and 23 years, respectively. In Case 1, the diagnosis of SLE was based on fever, butterfly rash, Raynaud's phenomenon, leukopenia, lymphopenia, hypocomplementemia, a high titer of anti-DNA antibodies, positive DNA and LE test, and the presence of anti-nuclear antibodies (speckled pattern). In Case 2, the diagnosis was based on butterfly rash, central nervous system involvement, lymphopenia, hypocomplementemia, a positive LE cell phenomenon, a high titer of anti-DNA antibodies and a positive DNA test. In Case 3, the diagnosis was based on photosensitivity, alopecia, lymphopenia, hypocomplementemia, a high titer of anti-DNA antibodies, a positive DNA test and a positive LE cell phenomenon. In these three cases, initial symptoms were puffy face and pretibial edema which occurred suddenly. These symptoms disappeared completely after either corticosteroid therapy or a combination therapy using corticosteroids and immunosuppressive drugs. These patients took a favorable course and no aggravation was noted in the findings of urinalysis and renal functions. In two of these cases, the diagnostic criteria for SLE were satisfied, but the remaining patient fulfilled only three criteria except for renal disorder. In each of these cases, minor glomerular abnormalities were disclosed by renal histology. It seems likely that SLE was complicated by MCNS in these cases. From these cases, it is suggested that there is a possibility of immunological abnormalities associated with SLE and MCNS. | pubmed_500_8999 |
pubmed_664_12985 | Envenomation of domestic animals by snakes occurs frequently in certain geographic areas. However, reports describing clinical signs, clinicopathologic abnormalities, therapeutic approaches, and outcomes are sparse. This review summarizes various snake families, venom types associated with harmful snakes, and the significant hematologic, hemostatic, and biochemical abnormalities associated with envenomation. Hematologic abnormalities include RBC membrane abnormalities, hemolysis, hemoconcentration, leukogram changes, and platelet abnormalities, specifically thrombocytopenia. Coagulopathies associated with snake envenomation are well described in human medicine, and many studies have demonstrated properties of venoms that lead to both procoagulation and anticoagulation. As expected, similar abnormalities have been described in domestic animals. Biochemical abnormalities are associated with the effects of venom on tissues such as liver, skeletal and cardiac muscle, vascular endothelium, and kidney as well as effects on protein components and cholesterol. This comprehensive review of clinicopathologic abnormalities associated with envenomation and their relationships to characterized venom constituents should be useful both in the diagnosis and management of envenomation and should serve as a foundation for future research in this field. | 10.1111/j.1939-165X.2011.00335.x |
pubmed_560_8368 | OBJECTIVE
To test the applicability of multi-criteria decision analysis preference elicitation techniques in cognitively impaired individuals.
METHOD
A convenience sample of 16 cognitively impaired subjects and 12 healthy controls was asked to participate in a small pilot study. The subjects determined the relative importance of four decision criteria using five different weight elicitation techniques, namely simple multi-attribute rating technique, simple multi-attribute rating technique using swing weights, Kepner-Tregoe weighting, the analytical hierarchical process, and conjoint analysis.
RESULTS
Conjoint analysis was judged to be the easiest method for weight elicitation in the control group (Z = 10.00; p = 0.04), while no significant differences in difficulty rating between methods was found in cognitively impaired subjects. Conjoint analysis elicitates weights and rankings significantly different from other methods. Subjectively, cognitively impaired subjects were positive about the use of the weight elicitation techniques. However, it seems the use of swing weights can result in the employment of shortcut strategies.
CONCLUSION
The results of this pilot study suggest that individuals with mild cognitive impairment are willing and able to use multi-criteria elicitation methods to determine criteria weights in a decision context, although no preference for a method was found. The same methodologic and practical issues can be identified in cognitively impaired individuals as in healthy controls and the choice of method is mostly determined by the decision context. | 10.2165/01312067-200801020-00008 |
pubmed_912_21046 | This study was aimed to evaluate the applicability of a reciprocating movement technique with conventional nickel-titanium files for root canal preparation. Forty-four simulated canals in resin blocks were used in this study and divided as following four groups according to the instruments used and preparation methods. Group CP (n = 12) and CR (n = 12) were instrumented with continuous rotation using four files of ProFile and RaCe, respectively. Group RP (n = 10) and RR (n = 10) were instrumented with a reciprocation movement by using a single ProFile and RaCe file, respectively. The resin blocks were scanned before and after instrumentation, and the images were superimposed. To compare the efficiency of canal shaping, the preparation time, and centering ratio were calculated. Morphologic changes of tested files were examined by scanning electron microscopy (SEM). Data were analyzed by ANOVA and Duncan's post hoc test at p < 0.05. The preparation time was markedly shorter in Groups RP and RR than in Groups CP and CR. No significant difference in the centering ratio was noted between groups. Although the files used for Groups CP and CR showed no distortion under the SEM evaluation, the files used for Groups RP and RR had considerable torsional distortion. This study suggests that the reciprocating instrumentation technique using conventional nickel-titanium rotary file systems might have a comparable efficacy for the root canal shaping with reduced shaping time. Although the reciprocating technique seems to be an effective alternative to the conventional rotation technique, the risk of torsional distortion and fracture should be considered before clinical application. | 10.1002/sca.21074 |
pubmed_711_8258 | A wide variety of agents other than heat have been reported to induce or suppress heat shock protein (hsp) synthesis in eukaryotic cells. Such agents, termed 'modulators', include inhibitors of respiration, low molecular weight nutrients, oxygen, hormones, sulfhydryl reagents, ionophores and amino acid analogues. The evidence for modulation is critically reviewed and common mechanisms of action that may relate modulation to induction by heat are discussed. | 10.1016/0014-4827(86)90528-8 |
pubmed_524_5227 | This study evaluated if maternal intimate partner violence (IPV) had indirect effects on sensitive parenting in infancy through prenatal depressive symptoms and postpartum parenting stress and if maternal adverse childhood experiences (ACEs) moderated these indirect effects. We hypothesized that: (a) IPV would be associated with greater prenatal depressive symptoms, which would predict greater postpartum parenting stress, and ultimately less sensitive parenting and (b) the link between IPV and depressive symptoms would be strongest for mothers with high ACEs. Participants included 295 mothers and their infants who were assessed prenatally and at 12 months postpartum. Path analyses indicated that mothers with higher IPV endorsed greater prenatal depressive symptoms, which was in turn associated with postpartum parenting stress, and ultimately less sensitive parenting behavior. Moderation analyses revealed that these indirect effects varied as a function of maternal ACEs, with the link between IPV and depressive symptoms only present for mothers who reported high ACEs. Because less sensitive caregiving is often an early indicator of child maltreatment risk, understanding precursors to sensitivity is critical to increase precision in parenting interventions designed to reduce risk for maltreatment. Results may inform evidence-based preventive interventions for mothers and infants at high-risk for child abuse and neglect. | 10.1177/10775595211000431 |
pubmed_471_12628 | INTRODUCTION
Tumour heterogeneity is important in the management of breast cancer. Hormone receptors are established biomarkers for treatment and prognosis of patients with breast cancer. There are three immunohistochemical biomarkers: estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2). We explore whether heterogeneity in hormone receptor status in synchronous bilateral breast alters therapeutic management.
CASE PRESENTATION
This case details a 54 year old woman who was referred to our clinic by her general practitioner for investigation of bilateral breast pain that she had for 6 months. On clinical examination pathological nodes were palpated in bilateral axilla. There was left sided nipple inversion with a palpable mass in the upper outer quadrant of approximately 3 cm diameter. On examination of the right breast there was skin tethering of the nipple and 3 masses were palpated, the largest being in the upper inner quadrant at 5 cm diameter. Ultrasound and mammography of bilateral breasts demonstrated advanced bilateral breast cancer with axillary node metastases. Core biopsies demonstrated invasive carcinoma. The right breast lesion was ER negative whilst the left breast lesion was ER positive.
DISCUSSION
In patients with synchronous bilateral breast cancer ER discordance in patients have been associated with higher mortality than ER concordant positive patients and lower mortality than ER concordant negative patients within the first 5 years of surveillance [1].
CONCLUSION
Heterogeneity in hormone receptor status alters the therapeutic management of patients with synchronous bilateral breast cancer. Both hormone therapy and chemotherapy should be considered in these patients. It is of utmost importance to evaluate the tumor receptor status in cases of synchronous bilateral breast tumour and to assess for change in relation to tumour progression or treatment. Further study in the status change of receptors could open up new treatment modalities. | 10.1016/j.ijscr.2018.10.016 |
pubmed_158_1591 | The DNA minor groove binders netropsin, distamycin and four structurally related bisquaternary ammonium heterocycles (BQA), SN 6999, SN 6570, SN 6132 and SN 6131, were investigated for sequence-specific interactions with the 154 base pair fragment of cDNA of the human Tau 40 protein (h Tau 40 protein), involved in pathology of Alzheimer's disease. The base sequences 5' AATCTT 3', 5' AATATT 3' and 5' TTTCAATCTTTTTATTT 3' were identified as ligand specific binding sites and demonstrate the obvious dA.dT binding preference. Footprinting titration experiments were performed to estimate sequence-specific binding constants (KA). The KA-values were in the order of 10(6)M-1 and dependent on DNA base sequence as well as ligands used. The highest values estimated were for netropsin (KA = 5.0 x 10(6)M-1) and the quinoline derivative SN 6999 (KA = 6.2 x 10(6)M-1) binding to the sequence 5' ATAAT 3'. Microscopic binding constants are determined by the base sequence rather than by the length of dA.dT stretches. In the extended dA.dT run, 5' TTTCAATCTTTTTATTT 3', netropsin and distamycin binding tolerates the presence of two dG.dC base pairs, as indicated by nearly unaffected footprints. In contrast, the failure of BQAs to form footprints demonstrates their significantly decreased binding selectivity. | 10.1080/15216549700201141 |
pubmed_552_8894 | We report here a summary of the data obtained from two HIV-1 antibody counseling and testing sites in Minneapolis-St. Paul for the first 48 months of operation (24,911 persons tested). The HIV-1 antibody seroprevalence rate for all persons tested was 5 percent. The highest seroprevalence rates were in male homosexual/bisexual intravenous drug users (23 percent) and homosexual/bisexual men (13 percent). There was a significant decrease in the HIV-1 antibody seroprevalence rate among clients during the 48-month period from 14 percent in the first six months to 3 percent in the last six months. This decrease coincided with an increase in the number of low-risk female clients and low-risk heterosexual male clients, and a decrease in the number of homosexual/bisexual males participating in the programs. These findings suggest the need for development and implementation of other strategies to identify and reach persons at highest risk for HIV-1 infection. | 10.2105/ajph.80.4.419 |
pubmed_1000_5695 | In order to understand the mechanism of oocyte maturation in seasonal-breeding wild frogs, we have cloned and sequenced a cDNA encoding Cdc2 kinase, a component of the maturation-promoting factor (MPF) in Rana dybowskii. About 1.2-kb cDNA was isolated by reverse transcription coupled to polymerase chain reaction (RT-PCR) and cDNA library screening. The cloned Rana Cdc2 cDNA encodes a complete open-reading frame with 302 amino acid residues, which deduce a 34-kDa protein. Homology of more than 80% was found between the deduced amino acid sequence of Rana Cdc2 and that of five phylogenetically distant organisms, and 94% identity was found between Rana and Xenopus. More importantly, the Thr14, Tyr15, and Thr161 residues, the phosphorylation sites for the activation of the enzyme, are highly conserved. In vitro-translated Rana Cdc2 cross-reacted with Xenopus p34(cdc2) antibody as shown by Western blot. Northern blot analysis showed that a 1.7-kb transcript was highly expressed in the gonads compared to other tissues, indicating the important role of Cdc2 kinase in gonads as a component of MPF. The cloned Rana Cdc2 cDNA also exhibited histone H1 kinase activity when expressed in CV-1 cells. In the present study, therefore, we have characterized the Rana Cdc2 kinase in amphibian, which will be helpful in understanding the process of oocyte maturation related to the reproduction cycle of wild frogs. | 10.1006/gcen.1999.7420 |
pubmed_598_2645 | BACKGROUND
Age-related macular degeneration (AMD) is a complex disease, and recent studies have shown role of complement system genes in its development. Complement factor I regulates the complement pathways, and relationship between CFI polymorphisms and AMD is controversial. We evaluated the possible association of complement factor I rs141853578 (G119R) variation with advanced AMD in Iranian patients.
MATERIALS AND METHODS
We included 371 case-control samples consisting of 220 advanced AMD patients and 151 genetically unrelated healthy controls. Extracted DNA samples amplified to obtain fragment including the polymorphic complement factor I rs141853578 (G119R) region.
RESULTS
The distribution of the genotypes was significantly different in the AMD patients compared to that of controls (p = 0.035). The TT genotype frequencies for CFI were significantly higher in AMD group (7.7 vs. 2%, OR 4.67, CI 1.33-16.45, p = 0.016). This significant difference was maintained after adjustment for the effects of age and gender (OR 5.09, CI 1.42-18.20, p = 0.012). The minor allele frequency (T allele) was also significantly higher in AMD patients compared to that of controls (29.3 vs. 21.5% OR 1.51, CI 1.07-2.13, p = 0.018).
CONCLUSION
Current study showed that CFI rs141853578 (G119R) is a risk factor for developing advanced type AMD. This study also suggests that the frequency of G119R polymorphism in our population is not as rare as reported from other populations. | 10.1007/s10792-018-0835-0 |
pubmed_755_15925 | A pre-embedding immunohistochemical method to detect Met-enkephalin was combined with postembedding immunohistochemistry with GABA and glycine antisera, in order to determine whether or not Met-enkephalin coexisted with either of these inhibitory transmitters in neuronal cell bodies within the superficial dorsal horn of the rat. The distribution of immunostaining with the three antisera was similar to that which has been described previously. Of 74 enkephalin-immunoreactive neurones in laminae II and III, 51 were immunoreactive with the GABA antiserum and 23 were not. All of the neurones which were not GABA-immunoreactive were located in lamina II. None of the enkephalin-immunoreactive cells showed glycine-like immunoreactivity. These results suggest that enkephalin is present both in GABAergic neurones and in neurones which do not contain GABA within the rat superficial dorsal horn. It is likely that the population of neurones immunoreactive with both enkephalin and GABA antisera includes lamina II islet cells and that the population which were enkephalin-immunoreactive but not GABA-immunoreactive includes stalked cells. In addition, this latter group may correspond to those cells which possess both enkephalin- and substance P-like immunoreactivity and which have been described previously in this area. | 10.1016/0006-8993(92)90888-g |
pubmed_845_24850 | α-Terpineol, terpinen-4-ol, and δ-terpineol, isomers of terpineol, are among the compounds that give Cinnamomum longepaniculatum leaf oil its distinguished pleasant smell. The objective of this study was to evaluate the antimicrobial activity of these three isomeric terpineols. The determination of antibacterial activity was based on the minimum inhibition concentration (MIC) and minimum bactericide concentration (MBC). Changes in time-kill curve, alkaline phosphatase (AKP), UV-absorbing material, membrane potential, and scanning electron microscopy (SEM) were measured to elucidate the possible antimicrobial mechanism. α-Terpineol, terpinen-4-ol, and δ-terpineol demonstrated good inhibitory effects against several gram-negative bacteria, particularly Shigella flexneri. MIC and MBC of α-terpineol and terpinen-4-ol were similar (0.766 mg/mL and 1.531 mg/mL, respectively) for S. flexneri, while the MIC and MBC values of δ-terpineol were 0.780 mg/mL and 3.125 mg/mL, respectively. Time-kill curves showed that the antibacterial activities of the tested compounds were in a concentration-dependent manner. Release of nucleic acids and proteins along with a decrease in membrane potential proved that α-terpineol, terpinen-4-ol, and δ-terpineol could increase the membrane permeability of Shigella flexneri. Additionally, the release of AKP suggested that the cell wall was destroyed. SEM analysis further confirmed that S. flexneri cell membranes were damaged by α-terpineol, terpinen-4-ol, and δ-terpineol. Our research suggests that these three isomeric terpineols have the potential of being used as natural antibacterial agents by destroying the cell membrane and wall, resulting in cell death. However, the specific antibacterial activity differences need further investigation. | 10.1007/s12223-020-00818-0 |
pubmed_1028_1527 | ECG-gated cardiac blood pool scintigraphy permits a non-invasive determination of the end-diastolic and end-systolic ventricular volumes and of the ejection fraction as well as a qualitative description of regional ventricular wall motion at rest and during excercise. In 6 healthy persons a significant increase of the ejection fraction from 66 +/- 7% at rest to 78 +/- 3% during exercise (p less than 0.01) was observed. In contrast, the ejection fraction decreased in 15 out of 18 patients with coronary artery disease, with a significant (p less than 0.01) difference between patients with and without angina pectoris. Thus, the ejection fraction fell in 12 patients without angina during excercise from 60 +/- 11% to 52 +/- 11% (p less than 0.05) whereas in 6 patients with angina a decrease from 61 +/- 7% to 30 +/- 8% (p less than 0.01) was observed. This non-invasive technique makes it possible to demonstrate in a simple and safe manner changes of cardiac function during excercise in patients with coronary artery disease. | pubmed_1028_1527 |
pubmed_607_12581 | Successful mitral valve replacement and tricuspid annuloplasty were performed on a 66-year-old woman who had a calcified left atrium, giant right atrium, calcified mural thrombus and normal pulmonary pressures. Successful repair in such cases depends on an adequate preoperative investigation and a surgical approach tailored to the individual. | pubmed_607_12581 |
pubmed_430_4727 | Mean CSF zinc concentration was lower in a group of ex-heroin addicts than in groups of normal controls and neuroleptic-treated schizophrenic patients, but values were generally within the normal range of CSF zinc concentrations. There were no significant differences in mean CSF zinc concentrations between groups of drug-free schizophrenic patients, schizophrenic patients on neuroleptics, and normal controls. CSF zinc concentration may be influenced by differences in racial composition and related dietary and other habits of the groups studied. | pubmed_430_4727 |
pubmed_664_7128 | AIMS
Perivascular adipose tissue (PVAT) is known to secrete vascular relaxation factors, and angiotensin 1-7 [Ang-(1-7)] acting on the endothelium is one of the endothelium-dependent relaxation factors. Mas protein is the receptor for Ang-(1-7). Using aorta from Mas-knockout (K/O) and wild type (FVB) mice, we wished to establish the essential role of Mas receptors in mediating the endothelium-dependent relaxation response induced by relaxation factors from PVAT.
MAIN METHODS
Thoracic aortic rings from K/O and FVB mice were prepared with or without PVAT (PVAT+ and PVAT-) and/or intact endothelium (E+) or with the endothelium removed (E-) for functional studies. The contraction and relaxation responses of these vessels to agonist in the presence of different receptor antagonists were studied.
KEY FINDINGS
PVAT attenuated the contraction induced by phenylephrine (PHE) in the presence of endothelium only in vessels from FVB mice. Mas receptor antagonists D-Ala-Ang-(1-7) (A779) or D-Pro(7)-Ang-(1-7) enhanced the contraction induced by PHE only in vessels from FVB mice. Ang-(1-7) caused a relaxation response only in E+vessels from FVB mice. Transfer of donor solution from PVAT+ vessels to PVAT- recipient vessels caused a relaxation response among FVB vessels and not among vessels from K/O mice.
SIGNIFICANCE
Mas receptors are essential in mediating the endothelium-dependent relaxation response induced by PVAT, therefore highlighting the important role of Ang-(1-7) in the control of vascular functions through PVAT. | 10.1016/j.lfs.2011.07.016 |
pubmed_705_12555 | The study objectives were to examine the morphological progression and dose response of carbon disulfide (CS2) distal axonopathy in the muscular branch of the posterior tibial nerve (MBPTN) and spinal cord. Male and female F344 rats were exposed to 0, 50, 500 or 800 ppm CS2 by inhalation, 6 hours/day, 5 days per week, for 2, 4, 8 or 13 weeks. At 8 weeks, in the MBPTN, single fascicles contained individual swollen axons. By 13 weeks, multiple fascicles had giant swollen axons with thin myelin sheaths and occasional degenerated and regenerated axons. At 8 weeks, in the spinal cord, white matter changes in cervical segments 1 and 2 consisted of prominent multifocal axonal swelling in the fasciculus gracilis nerve tracts. In lumbar segments 1 and 2, multifocal axonal swelling was first present at 8 weeks in the lateral and ventro-medial funiculus. By 13 weeks, axonal swelling was diffuse in the fasciculus gracilis nerve tracts of the cervical spinal cord and the lateral and ventral funiculus nerve tracts in the lumbar spinal cord. Compared to the spinal cord, where axonal swelling was present in rats exposed to 800 and 500 ppm, in the muscular branch of the posterior tibial nerve, axonal swelling was only present at 800 ppm at both 8 and 13 weeks. Electron microscopic examination demonstrated marked accumulations of neurofilaments in swollen axons in the spinal cord and MBPTN. Axonal swelling was not present in the spinal cord at 50 ppm, or in the MBPT at 50 and 500 ppm. Axonal swelling was not present at earlier time points of 2 and 4 weeks in either the spinal cord or MBPTN. | pubmed_705_12555 |
pubmed_170_16932 | BACKGROUND
The General Health Questionnaire (GHQ) - 12 was designed as a short questionnaire to assess psychiatric morbidity. Despite the fact that studies have suggested a number of competing multidimensional factor structures, it continues to be largely used as a unidimensional instrument. This may have an impact on the identification of psychiatric morbidity in target populations. The aim of this study was to explore the dimensionality of the GHQ-12 and to evaluate a number of alternative models for the instrument.
METHODS
The data were drawn from a large heterogeneous sample of cancer patients. The Partial Credit Model (Rasch) was applied to the 12-item GHQ. Item misfit (infit mean square >or= 1.3) was identified, misfitting items removed and unidimensionality and differential item functioning (age, gender, and treatment aims) were assessed. The factor structures of the various alternative models proposed in the literature were explored and optimum model fit evaluated using Confirmatory Factor Analysis.
RESULTS
The Rasch analysis of the 12-item GHQ identified six misfitting items. Removal of these items produced a six-item instrument which was not unidimensional. The Rasch analysis of an 8-item GHQ demonstrated two unidimensional structures corresponding to Anxiety/Depression and Social Dysfunction. No significant differential item functioning was observed by age, gender and treatment aims for the six- and eight-item GHQ. Two models competed for best fit from the confirmatory factor analysis, namely the GHQ-8 and Hankin's (2008) unidimensional model, however, the GHQ-8 produced the best overall fit statistics.
CONCLUSIONS
The results are consistent with the evidence that the GHQ-12 is a multi-dimensional instrument. Use of the summated scores for the GHQ-12 could potentially lead to an incorrect assessment of patients' psychiatric morbidity. Further evaluation of the GHQ-12 with different target populations is warranted. | 10.1186/1477-7525-8-45 |
pubmed_294_3223 | Signs and symptoms of thyroid disease are varied and often vague. ICU patients may have cardiac disorders directly related to altered levels of thyroid hormone rather than inherent cardiac disease. Cardiac manifestations of thyroid disease result from a decrease or an increase in circulating hormone and are usually reversible with treatment. Accurate, ongoing assessment, especially after treatment has begun, is important to help guide safe and effective therapy. Patient education is another priority of nursing care and can be a major factor in helping the patient to achieve and maintain a euthyroid state. | pubmed_294_3223 |
pubmed_1039_9823 | Dimeric hybrid protein molecule consisting of disulfide-linked beta (heavy) subunit of haptoglobin (Hp) and L (light) subunit of immunoglobulin G, was synthesized. Molecular mass of the hybrid was 62.0 kd, sedimentation constant B20 = 2.43. Hemoglobin binding activity of the beta X L hybrid as compared with that of native Hp accounted for 25%. In immunological cross-reactivity the hybrid was found to be deficient in some antigenic determinants present in Hp and in Hp beta chain. Hybridization carried out in three-component mixtures (Hp beta subunits, Hp alpha (light) subunits, IgG-L) showed, that besides reconstituted tetramers of Hp (2 alpha X 2 beta) always the hybrid beta X L was formed, even at an excess of Hp alpha, an excess of IgG-L prevented the formation of tetrameric molecules. Conformational similarity of Hp alpha and IgG-L as disulfide linked with Hp beta is reflected in the interaction of respective conjugates with hemoglobin. | pubmed_1039_9823 |
pubmed_1070_2332 | A case of cervical epidural abscess in a 63-year-old woman with a complex gastrointestinal surgical history is reported. The presenting symptom was neck pain, and blood analysis demonstrated raised erythrocyte sedimentation rate and C-reactive protein. MR imaging of the cervical spine revealed cervical discitis, osteomyelitis, and epidural collection. An ESBL-producing strain of Klebsiella pneumoniae, isolated from a previous episode of bacteraemia, was the causative organism. Surgical treatment was not possible and initial carbapenem therapy was aborted due to development of neutropaenia, and treatment continued with an extended course of temocillin. After 12 weeks of antibiotics the patient was pain-free with radiological improvement and resolution of blood markers of infection. | 10.1016/j.jinf.2008.08.001 |
pubmed_633_5859 | Remarkable progress in optical microscopy has been made in the measurement of nanometre distances. If diffraction blurs the image of a point object into an Airy disk with a root-mean-squared (r.m.s.) size of s = 0.44lambda/2NA (approximately 90 nm for light with a wavelength of lambda = 600 nm and an objective lens with a numerical aperture of NA = 1.49), limiting the resolution of the far-field microscope in use to d = 2.4s approximately = 200 nm, additional knowledge about the specimen can be used to great advantage. For example, if the source is known to be two spatially resolved fluorescent molecules, the distance between them is given by the separation of the centres of the two fluorescence images. In high-resolution microwave and optical spectroscopy, there are numerous examples where the line centre is determined with a precision of less than 10(-6) of the linewidth. In contrast, in biological applications the brightest single fluorescent emitters can be detected with a signal-to-noise ratio of approximately 100, limiting the centroid localization precision to s(loc) > or = 1% (> or = 1 nm) of the r.m.s. size, s, of the microscope point spread function (PSF). Moreover, the error in co-localizing two or more single emitters is notably worse, remaining greater than 5-10% (5-10 nm) of the PSF size. Here we report a distance resolution of s(reg) = 0.50 nm (1sigma) and an absolute accuracy of s(distance) = 0.77 nm (1sigma) in a measurement of the separation between differently coloured fluorescent molecules using conventional far-field fluorescence imaging in physiological buffer conditions. The statistical uncertainty in the mean for an ensemble of identical single-molecule samples is limited only by the total number of collected photons, to s(loc) approximately 0.3 nm, which is approximately 3 x 10(-3) times the size of the optical PSF. Our method may also be used to improve the resolution of many subwavelength, far-field imaging methods such as those based on co-localization of molecules that are stochastically switched on in space. The improved resolution will allow the structure of large, multisubunit biological complexes in biologically relevant environments to be deciphered at the single-molecule level. | 10.1038/nature09163 |
pubmed_407_2027 | To determine whether there are differences in stickiness to hydrophobic surfaces among peptides and proteins under immunoassay conditions, peptides and proteins were radio-labeled with (125)I and competitive adsorption with human serum albumin (HSA) in polystyrene or polypropylene tubes was used to determine the IC (50), the concentration of HSA required to reduce the adsorption of the labeled polypeptides to 50% of maximal. Stickiness was defined as log(10)(10(9) IC (50)). Stickiness varied significantly between the labeled polypeptides (p < 0.00001) and ranged (±sem) from 0.99 ± 0.07 for angiotensin II to 5.30 ± 0.07 for tyr(0)-urocortin II. The stickiness of HSA and γ globulin was 1.62 ± 0.09 and 1.92 ± 0.05, respectively. No significant difference in stickiness between polystyrene and polypropylene was found. We conclude that some peptides are sufficiently sticky to risk adsorptive loss during sampling and analysis, and there may exist peptides so sticky that they remain uncharacterized. | 10.1080/15321819.2011.647188 |
pubmed_191_21471 | The synaptic connections from pressure-sensitive receptors (P cells) to identified neurons of unknown function (known as anterior pagoda or AP cells) were used to study the way in which leeches process information about the position of a mechanical stimulus on its skin. We elicited spikes in P cells by injecting current intracellularly while recording from AP neurons. The postsynaptic responses consisted of an increase in impulse frequency. We show here that the AP neuron can encode positional information in terms of the frequency of its action potentials. Thus, the AP neuron can serve as an indicator of integrative mechanisms used in the processing of sensory information that is important for the behavior of the animal. | 10.1016/s0361-9230(01)00609-8 |
pubmed_834_13769 | A strong research effort has been devoted in recent years to the mammalian lignans enterolactone and enterodiol because of their claimed protective effects against breast and colon cancer. Some plant lignans appear to be precursors of these molecules. This paper reports a novel identification procedure for one of these precursors, the secoisolariciresinol diglucoside, in the extracts of defatted flax-seed meal. The procedure is based on high-performance liquid chromatography coupled with either ionspray or continuous-flow fast-atom bombardment mass spectrometry. The application of these techniques allowed the identification in flax seed of two isomeric forms of this precursor for the first time. The isomers are reasonable the two diastereoisomers, due to the two equivalent stereogenic centers present in the molecule. | 10.1002/rcm.1290081204 |
pubmed_1098_26027 | Many racialized health inequities in the USA have been known for decades. However, academic medicine, individual clinicians, and larger healthcare systems have not yet supported action towards sufficient and meaningful solutions, as evidenced by the persistence of racialized health inequities over time. Recently, academic medicine is increasing efforts to unequivocally identify systemic racism as a public health crisis because it drives health inequity to racially minoritized groups. A health equity emphasis in clinical education, practice, and research differs from a disparities approach because it seeks to dismantle the systems of racism that create inequitable health outcomes in the first place. Therefore, medical education, practice, and research are slowly transitioning from a lens of health disparities to one of health equity. In order to support this transition, authors and journals must restructure the depiction of health inequities caused by racism. Based upon the principles of the social medicine pioneer, Dr. Rudolph Virchow, the knowledge conveyed by scientific and medical academic writing must clearly name the drivers of social disease - which is generalized to the American landscape of racialized health inequity for the purposes of this manuscript - in order to inform action capable of stopping socially mediated health inequity. Yet, the language and construction of health disparities literature perpetuates colorblind and aversive racism by stylistically omitting the driver of inequity quite frequently, which renders such knowledge unable to support action. In this article, three academicians across the spectrum of social justice education identify and classify common writing styles of health disparities research in order to demonstrate how a writing style of racial health equity better supports true progress towards equity. | 10.1007/s40615-022-01424-1 |
pubmed_1058_16198 | CO2 reactivity was tested in patients with transcranial Doppler sonography (TCD) and endtidal CO2 measurements after an average time interval of ten months after subarachnoid haemorrhage (SAH). After deliberately changing breathing there was a significant change in endtidal CO2 and in flow velocities in all three examination groups. Comparing 27 patients with SAH and 5 patients treated for incidental aneurysms and 20 patients without cerebrovascular disease there were no significant differences in CO2 reactivity. Furthermore, there were no right to left differences. In 12 patients with vasospasm, two of them treated by percutaneous transluminal angioplasty for delayed ischaemic deficits, CO2 reactivity was normal at the time of investigation. Furthermore, normal CO2 reactivity was found in patients after SAH and surgery for ruptured aneurysms regardless of the severity of the SAH. | 10.1007/BF01411557 |
pubmed_740_3656 | Trialkylphosphine organocatalysts have enabled regioselective anti-hydroboration of internal alkynes with pinacolborane reagents to provide ( E)-disubstituted alkenylboronate compounds. The alkenylboronate can be used for derivatizations, such as protodeborylation, Suzuki-Miyaura coupling, conjugate reduction, and Diels-Alder reactions. | 10.1021/acs.orglett.8b00390 |
pubmed_58_5421 | OBJECTIVE
To determine how best to measure the provision of comprehensive preventive care assessment of adults with intellectual and developmental disabilities (IDD).
DESIGN
Cross-sectional study.
SETTING
Ontario.
PARTICIPANTS
Adults with IDD between 40 and 64 years of age in 2013 and 2014.
MAIN OUTCOME MEASURES
Health examination was defined using the Ontario Health Insurance Plan billing data fee code A003 (with diagnostic code 917 or 319) or fee code K131, and the Primary Care Quality Composite Score (PCQS), a measure combining 7 different screening maneuvers (lipid, glucose, breast cancer, cervical cancer, colorectal cancer, eye, and hemoglobin A1c screening), was identified using administrative health data.
RESULTS
A total of 28 825 adults with IDD were identified in 2013 and 2014. Overall, 12.1% of adults with IDD received a health examination; 51.2% received a high (≥ 0.6) PCQS. Male patients were more likely to have received all of their eligible screening maneuvers if they had had a health examination compared with female patients (odds ratio of 5.73 vs 3.99, respectively).
CONCLUSION
Less than 60% of adults with IDD appear to be receiving comprehensive preventive care. Future studies assessing the quality of preventive care received by adults with IDD should combine health examination billing codes and the PCQS. | pubmed_58_5421 |
pubmed_126_21765 | A novel, highly hydrophobic, glycine- and proline-rich peptide was characterized in the ovary of the desert locust, Schistocerca gregaria. The peptide was detected as one of the major peaks in a chromatographic separation of an acidic methanolic extract of 50 mature ovaries. Electrospray mass spectrometry yielded a molecular mass of 6305 Da. The partial amino acid sequence as determined by Edman degradation based automated microsequencing is as follows: Ala-Tyr-Pro-Ala-His-Gln-Gly-Tyr- Pro-Ala-His-Val-Gly-Tyr-Ala-Arg-Val-Gly-Tyr-Gly- Gly-Tyr-Pro-Ser-Tyr-Gly-Tyr-Pro-Ala. Four amino acids (Gly, Pro, Ala, and Tyr) account for more than 80% of the composition of this sequence. Gly-Tyr-Pro is the most important repetitive motif. Ala-Tyr-Pro, Gly-Tyr-Gly and Gly-Tyr-Ala occur as variations of this motif. The novel glycine- and proline-rich insect peptide displays structural characteristics similar to those of a new class of glycine- and proline-rich proteins (GPRP) that have recently been identified in Arabidopsis thaliana (thale cress) and Daucus carota (carrot). The GPRP of A. thaliana contains the same repetitive motifs (except for Ala-Tyr-Pro), the Gly-Tyr-Pro motif also being the most abundant. | 10.1006/bbrc.1998.8104 |
pubmed_560_22209 | The aim of this study is to investigate the distribution of methamphetamine (MA) and its metabolite amphetamine (AP) in rat models of acute and subacute MA-ethanol combination abuse. Rats were fed with 20% ethanol for 4 weeks (chronic active-drinking group), and MA was injected intraperitoneally into chronically drinking and normal rats over 5 and 14 days, respectively. Then the rats from the acute and subacute combination abuse groups were euthanized, and ethanol, MA, and AP concentrations in samples were quantified. Except for the similar ethanol concentrations among acute and subacute groups, the MA and AP levels between groups were quite different. The concentrations of MA and AP in rats' liver, lung, kidney, and brain were much higher than other tissues, regardless of combination with ethanol. Also, MA and AP levels in subacute rats groups were higher than those in acute groups, and the levels of MA and the formation of AP in rats subjected to the combination abuse with ethanol were higher than in MA-only intoxicated rats. We conclude that ethanol has no bearing on the MA and AP distribution in body fluids and tissues, yet it can increase MA levels and markedly accelerate the formation of AP in combination-abuse rats. Comparing the acute and subacute combination-abuse rats' samples, it can be deduced that various accumulated amounts of MA and AP were unaffected by ethanol, even after multi-dose injection, regardless of acute or subacute use. | 10.1093/jat/bkr007 |
pubmed_849_13370 | PURPOSE
Colorectal cancer (CRC) has potential to spread within the peritoneal cavity, and this transcoelomic dissemination is termed "peritoneal metastases" (PM). Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a radical strategy to treat selected CRC patients with PM. Studies suggest that identification of CRC patients at high risk of PM may lead to earlier treatment strategies and improve survival in this subset of patients. The aim of this article was to summarise the current evidence regarding CRC patients at high risk of PM.
METHODS
A retrospective review of articles on CRC patients with high risk of PM published up to December 2014 in PubMed, Medline, Embase, and Ovid search engines was conducted. The following combination of search terms were used: "intraperitoneal chemotherapy", "HIPEC", "colorectal cancer", "peritoneal carcinomatosis", "peritoneal metastases", "high risk", "peritoneal recurrence".
RESULTS
Although opinions differ, CRC patients identified as "high risk" of PM included: limited, synchronous PM completely resected with the primary tumor, ovarian metastases (synchronous or metachronous) and spontaneous or iatrogenic perforation of the bowel by the primary tumor. Aggressive early treatment strategies currently used are: CRS and HIPEC for high-risk primary tumors and second-look CRS and HIPEC often following systematic chemotherapy for the primary resection. Positive results have been shown with both approaches in a number of studies. With CRS/HIPEC for the primary tumor, the overall survival in the two groups (25 patients treated with CRS/HIPEC vs 50 treated with conventional surgery) was significantly improved (p<0.03), as was disease-free survival (p<0.04). For second look surgery, in 29 patients treated with CRS and HIPEC, this resulted in 14% morbidity and 0% mortality and a 2-year disease-free survival rate in excess of 50%.
CONCLUSIONS
We are progressively moving to an era of individualised treatment strategies. The management of CRC patients with high risk of PM is ever evolving, with early detection and early treatment strategies showing promising results. The optimal timing of early surgery remains unclear and requires further evaluation. Should current and future randomized trials demonstrate long-term survival benefit, we may potentially see a change in treatment paradigm from current conventional surgery to a more aggressive, early radical approach as the standard of care. | pubmed_849_13370 |
pubmed_525_12796 | BACKGROUND AND OBJECTIVES
When familial non-medullary thyroid cancer (FNMTC) develops with no obvious associated pathogenetic factor, an inherited predisposition may underlie the process. The present study was conducted because detailed pathological findings are lacking in most series of FNMTC.
PATIENTS AND METHODS
Thirteen families comprising 27 cases of FNMTC were included (1.8% of differentiated thyroid carcinoma). The family relationship (20 F, 7 M; age 46 +/- 16 years; mean +/- SD) was 'siblings' in eight families, 'parent and child' in four and 'aunt and niece' in one. Careful pathological review of the thyroid tumours (papillary/follicular: 25/2, size: 16 +/- 11 mm) was performed.
RESULTS
Initial staging according to extension was as follows: grade I (n = 16), II (n = 2), III (n = 6), IV (n = 3). Fourteen tumours were papillary microcarcinomas (size: 8 +/- 2 mm). No tumour phenotype that may be considered specific for FNMTC was found when considering either age, pathological findings or tumour aggressiveness. Although rare events were found in both relatives of some families suggesting a putative 'familial' phenotype of FNMTC, this may be fortuitous.
CONCLUSION
Micro familial non-medullary thyroid cancers are more common than previously reported and further studies are required to be able to distinguish this subgroup from sporadic papillary microcarcinomas. The careful pathological review of the familial non-medullary thyroid cancer in this study does not seem to point to a distinct subgroup of familial differentiated thyroid carcinoma although the data are intriguing. Genetic studies are now required to investigate this issue. | 10.1046/j.1365-2265.1999.00687.x |
pubmed_911_18027 | In order to investigate the cellular immunoresponses mediated by chimeric anti-CD20 monoclonal antibody (anti-CD20 McAb) through dendritic cells (DCs), mononuclear cells were isolated from human peripheral blood (PBMNC) and DCs from PBMNCs in vitro were generated with normal methods. Human CD20 positive lymphoma cell line-Raji cells were treated with different methods including treatment with anti-CD20 McAb (group R), treatment with heat-induced apoptosis (group A) and treatment with anti-CD20 McAb+heat-induced apoptosis (group R+A), then Raji cells treated with above-mentioned methods as tumor antigen were loaded on DCs. The phagocytosis of DCs to tumor antigen was observed by transmission electron microscope (TEM), the auto-mixed lymphocyte reaction was performed with antigen-primed DCs, the release of INF-gammafrom effector cells was detected by ELISPOT, the killing of effector cells on Raji cells was assayed by MTT. The results showed that under TEM, no pronounced phagocytosis of DCs was seen in group R, while the phagocytosis of apoptotic bodies could be easily seen in group A and the more cell fraqments were observed in group R+A. The FCM indicated that the expressions of CD80, CD86 and HLA-DR on DCs in 3 experimental groups were higher than those in group control (p<0.05), while expression positive rate in group R+A was higher than those in group R and A (p<0.05). The detection of lymphocyte surface antigen revealed that proportions of CD8+ cells in all experimental groups were higher than those in group control (p<0.05), count of CD56+ cells in group R and R+A increased, as compared with group A and control, difference was significant (p<0.05). ELISPOT assay indicated that amount of cells releasing IFN-gamma in all experimental groups was higher than that in group control, and also number of spots in group R+A significantly higher than that in other groups at effector-targetor ratio=1:10 (p<0.05). The results of killing assay demonstrated that killing rate on Raji cells in all experimental groups increased as compared with group control (p<0.05), while killing rate in group R+A was higher than that in group R and A. It is concluded that anti-CD20 McAb can mediate DC to induce cellular immunoresponse against lymphoma, that is, to stimulate and amplify specific CTLs and NK cells. Anti-CD20 McAb combined with DCs primed by heat-stressed tumor cells as antigen can further enhance cellular immunoresponse against lymphoma. | pubmed_911_18027 |
pubmed_642_1290 | Luminescent phosphorene quantum dots (PQDs) have emerged as fascinating nanomaterials for potential applications in optoelectronics, catalysis, and sensing. Herein, we investigate the structural distortion of black phosphorus (BP) under an applied electric field to yield blue luminescent PQDs [average diameter 8 ± 1.5 nm ( N = 60)]. The electrosynthesized PQDs exhibit photoluminescence emission independent of excitation wavelength with 84% quantum efficiency. Structural distortion that occurred during the transformation of BP to PQDs is confirmed by results obtained during transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Further, using first-principles-based density functional theory, calculations on oxygenated and nonoxygenated PQDs augment the experimental observations that an optimum oxygen content maintains the structural integrity of PQDs, above which the structural robustness of PQDs is drastically diminished. | 10.1021/acs.jpclett.8b03600 |
pubmed_1081_15475 | Having conversations with new people is an important and rewarding part of social life. Yet conversations can also be intimidating and anxiety provoking, and this makes people wonder and worry about what their conversation partners really think of them. Are people accurate in their estimates? We found that following interactions, people systematically underestimated how much their conversation partners liked them and enjoyed their company, an illusion we call the liking gap. We observed the liking gap as strangers got acquainted in the laboratory, as first-year college students got to know their dorm mates, and as formerly unacquainted members of the general public got to know each other during a personal development workshop. The liking gap persisted in conversations of varying lengths and even lasted for several months, as college dorm mates developed new relationships. Our studies suggest that after people have conversations, they are liked more than they know. | 10.1177/0956797618783714 |
pubmed_652_15431 | BACKGROUND
A long-term in vitro preparation of diseased brain tissue would facilitate work on human pathologies. Organotypic tissue cultures retain an appropriate neuronal form, spatial arrangement, connectivity and electrical activity over several weeks. However, they are typically prepared with tissue from immature animals. In work using tissue from adult animals or humans, survival times longer than a few days have not been reported and it is not clear that pathological neuronal activities are retained.
NEW METHOD
We modified tissue preparation procedures and used a defined culture medium to make organotypic cultures of temporal lobe tissue obtained after operations on adult patients with pharmaco-resistant mesial temporal lobe epilepsies.
RESULTS
Organototypic culture preparation and maintenance techniques were judged on criteria of morphology and the generation of epileptiform activities. Short-duration (30-100 ms) interictal-like population activities were initiated spontaneously in either the subiculum, dentate gyrus or the CA2/CA3 region, but not the cortex, for up to 3-4 weeks in culture. Ictal-like discharges, of duration greater than 10s, were induced by convulsants. Epileptiform activities were modulated by both glutamatergic and GABAergic receptor antagonists.
COMPARISON WITH EXISTING METHODS
Our methods now permit the maintenance in organotypic culture of epileptic adult human tissue, generating appropriate epileptiform activity over 3-4 weeks.
CONCLUSIONS
We have shown that characteristic morphology and pathological activities are maintained in organotypic cultures of adult human tissue. These cultures should permit studies on the effects of prolonged drug treatments and long-term procedures such as viral transduction. | pubmed_652_15431 |
pubmed_482_19553 | BACKGROUND
Abdominal aortic aneurysm (AAA) and acute coronary syndrome (ACS) share common risk factors.
OBJECTIVES
To assess the abdominal aortic diameter (AAD) among patients with ACS using transthoracic echocardiography (TTE).
METHODS
Patients with ACS admitted to our intensive cardiac care unit from December 2013 to June 2014 were screened prospectively for AAA via AAD measurement in the subcostal TTE view. AAA was defined as an aneurysm with a transverse diameter of ≥30 mm.
RESULTS
Sixty seven patients were included. The male-to-female sex ratio was 7 : 1. The vast majority of patients were admitted due to STEMI (73%), and the rest were equally divided as NSTEMI and unstable angina. The mean patient age was 58.4 ± 10.4 years. AAD measurements were feasible in 57 patients (85%); among them, AAA was diagnosed in six patients (10.5%). The average additional time required to measure the abdominal aorta was 4 ± 1 min. All patients with AAA were men and had a higher prevalence of smoking (83.3% vs. 60.6%, p < 0.003) and a lower incidence of diabetes mellitus than those without aneurysm. The prevalence of AAA tended to be related to age (12.5% in those older than 60 years and 18.7% in those older than 65 years).
CONCLUSIONS
The overall prevalence of AAA is significantly high among patients with ACS and increases with age. AAA screening as a part of routine cardiac TTE can be easily, rapidly, and feasibly performed and yield accurate findings. AAD measurement in the subcostal view should be implemented as a part of routine TTE in patients with ACS. | 10.1155/2020/9510546 |
pubmed_183_22320 | Reported here is a rare case of babesiosis with pulmonary complications followed by a review of the literature. Babesiosis presents clinically as a malaria-like illness with fever, chills, headache, fatigue with lymphopenia, atypical lymphocytes, mildly or transiently elevated serum transaminases, thrombocytopenia, and increased lactate dehydrogenase (LDH) levels. The diagnosis of babesiosis is based on identification of Babesia spp. on a peripheral blood smear. Babesiosis is usually mild in normal hosts, but it may be severe or even fatal in asplenic patients. Pulmonary manifestations are rare in babesiosis, but non-cardiogenic pulmonary edema (NCPE) is the most frequent manifestation. NCPE in babesiosis does not appear to be related to the degree of parasitemia or splenic function and its onset may be early or late. NCPE usually resolves rapidly with supportive treatment; it is rarely fatal. Clinicians should suspect NCPE in patients with babesiosis who acutely develop shortness of breath and have chest radiograph findings compatible with acute pulmonary edema without cardiomegaly or pleural effusions. | 10.1007/s10096-007-0325-1 |
pubmed_197_19418 | BACKGROUND
Children living in Roma settlements in Central and Eastern Europe face extreme levels of social exclusion and poverty, but their health status has not been well studied. The objective of this study was to elucidate risk factors for malnutrition in children in Roma settlements in Serbia.
METHODS
Anthropometric and sociodemographic measures were obtained for 1192 Roma children under five living in Roma settlements from the 2005 Serbia Multiple Indicator Cluster Survey. Multiple logistic regression was used to relate family and child characteristics to the odds of stunting, wasting, and underweight.
RESULTS
The prevalence of stunting, wasting, and underweight was 20.1%, 4.3%, and 8.0%, respectively. Nearly all of the children studied fell into the lowest quintile of wealth for the overall population of Serbia. Children in the lowest quintile of wealth were four times more likely to be stunted compared to those in the highest quintile, followed by those in the second lowest quintile (AOR = 2.1) and lastly by those in the middle quintile (AOR = 1.6). Children who were ever left in the care of an older child were almost twice as likely to stunted as those were not. Children living in urban settlements showed a clear disadvantage with close to three times the likelihood of being wasted compared to those living in rural areas. There was a suggestion that maternal, but not paternal, education was associated with stunting, and maternal literacy was significantly associated with wasting. Whether children were ever breastfed, immunized or had diarrhoeal episodes in the past two weeks did not show strong correlations to children malnutrition status in this Roma population.
CONCLUSIONS
There exists a gradient relationship between household wealth and stunting even within impoverished settlements, indicating that among poor and marginalized populations socioeconomic inequities in child health should be addressed. Other areas on which to focus future research and public health intervention include maternal literacy, child endangerment practices, and urban settlements. | 10.1186/1471-2458-10-509 |
pubmed_881_15391 | In differentiated tissues, such as muscle and brain, increased adenosine monophosphate (AMP) levels stimulate glycolytic flux rates. In the breast cancer cell line MCF-7, which characteristically has a constantly high glycolytic flux rate, AMP induces a strong inhibition of glycolysis. The human breast cancer cell line MDA-MB-453, on the other hand, is characterized by a more differentiated metabolic phenotype. MDA-MB-453 cells have a lower glycolytic flux rate and higher pyruvate consumption than MCF-7 cells. In addition, they have an active glycerol 3-phosphate shuttle. AMP inhibits cell proliferation as well as NAD and NADH synthesis in both MCF-7 and MDA-MB-453 cells. However, in MDA-MB-453 cells glycolysis is slightly activated by AMP. This disparate response of glycolytic flux rate to AMP treatment is presumably caused by the fact that the reduced NAD and NADH levels in AMP-treated MDA-MB-453 cells reduce lactate dehydrogenase but not cytosolic glycerol-3-phosphate dehydrogenase reaction. Due to the different enzymatic complement in MCF-7 cells, proliferation is inhibited under glucose starvation, whereas MDA-MB-453 cells grow under these conditions. The inhibition of cell proliferation correlates with a reduction in glycolytic carbon flow to synthetic processes and a decrease in phosphotyrosine content of several proteins in both cell lines. | 10.1074/jbc.272.8.4941 |
pubmed_41_19936 | Experiments on fifteen simulated keyboards with different key sizes and inter-key spacings are reported. It was found that the movement time on these keyboards was well described by the model of Drury (Drury and Hoffmann 1992). Minimum movement times occurred when the inter-key spacing was approximately equal to the finger pad size. There was found to be an effect of the number of keys moved, which was not predicted by the model. This effect remained in a further experiment in which the target keys were marked. | 10.1080/00140139508925161 |
pubmed_1115_1578 | Following recent studies which showed that the most stable structures for (ZnS)(n) clusters (n= 10-47) are the so-called "bubble clusters", in which all the atoms are three-coordinated, we have used simulated annealing techniques to find the most stable structure for a larger cluster, (ZnS)(60). We find an onion-like structure, with one small cluster enclosed inside a bigger one. The inner cluster has the structure of a sodalite cage. Bonding between the inner and the outer clusters creates a network of four-coordinated atoms. | 10.1039/b314104g |
pubmed_1133_23380 | In many countries, general practitioners (GPs) are assigned the task of controlling the validity of their own patients' insurance claims. At the same time, they operate in a market where patients are customers free to choose their GP. Are these roles compatible? Can we trust that the gatekeeping decisions are untainted by private economic interests? Based on administrative registers from Norway with records on sick pay certification and GP-patient relationships, we present evidence to the contrary: GPs are more lenient gatekeepers the more competitive is the physician market, and a reputation for lenient gatekeeping increases the demand for their services. | 10.1016/j.jhealeco.2017.07.008 |
pubmed_398_1396 | Rhodobacter sphaeroides showed chemotaxis to the terminal electron acceptors oxygen and dimethyl sulfoxide, and the responses to these effectors were shown to be influenced by the relative activities of the different electron transport pathways. R. sphaeroides cells tethered by their flagella showed a step-down response to a decrease in the oxygen or dimethyl sulfoxide concentration when using them as terminal acceptors. Bacteria using photosynthetic electron transport, however, showed a step-down response to oxygen addition. Addition of the proton ionophore carbonyl cyanide 4-trifluoromethoxyphenylhydrazone did not cause a transient behavioral response, although it decreased the electrochemical proton gradient (delta p) and increased the rate of electron transport. However, removal of the ionophore, which caused an increase in delta p and a decrease in the electron transport rate, resulted in a step-down response. Together, these data suggest that behavioral responses of R. sphaeroides to electron transport effectors are caused by changes in the rate of electron transport rather than changes in delta p. | 10.1128/jb.177.20.5853-5859.1995 |
pubmed_618_24913 | RATIONALE
Idiopathic pulmonary fibrosis (IPF) is an untreatable and often fatal lung disease that is increasing in prevalence and is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control gene expression and are likely to regulate the IPF transcriptome.
OBJECTIVES
To identify methylation marks that modify gene expression in IPF lung.
METHODS
We assessed DNA methylation (comprehensive high-throughput arrays for relative methylation arrays [CHARM]) and gene expression (Agilent gene expression arrays) in 94 patients with IPF and 67 control subjects, and performed integrative genomic analyses to define methylation-gene expression relationships in IPF lung. We validated methylation changes by a targeted analysis (Epityper), and performed functional validation of one of the genes identified by our analysis.
MEASUREMENTS AND MAIN RESULTS
We identified 2,130 differentially methylated regions (DMRs; <5% false discovery rate), of which 738 are associated with significant changes in gene expression and enriched for expected inverse relationship between methylation and expression (P < 2.2 × 10(-16)). We validated 13/15 DMRs by targeted analysis of methylation. Methylation-expression quantitative trait loci (methyl-eQTL) identified methylation marks that control cis and trans gene expression, with an enrichment for cis relationships (P < 2.2 × 10(-16)). We found five trans methyl-eQTLs where a methylation change at a single DMR is associated with transcriptional changes in a substantial number of genes; four of these DMRs are near transcription factors (castor zinc finger 1 [CASZ1], FOXC1, MXD4, and ZDHHC4). We studied the in vitro effects of change in CASZ1 expression and validated its role in regulation of target genes in the methyl-eQTL.
CONCLUSIONS
These results suggest that DNA methylation may be involved in the pathogenesis of IPF. | 10.1164/rccm.201408-1452OC |
pubmed_181_15231 | BACKGROUND
Cigarettes and other tobacco-related smoking products have traditionally been a major ignition source for residential fire deaths. In the United States, all 50 states and the District of Columbia have passed laws requiring that cigarettes self-extinguish if they are not being smoked (so-called fire-safe cigarette laws). The purpose of this study was to quantify the association between state-level implementation of fire-safe cigarette legislation and the rate of residential fire death.
METHODS
Poisson regression was used to analyze state-years data. Main intervention: Implementation dates for fire-safe cigarette legislation in each state.
OUTCOME
Residential fire mortality rate.
RESULTS
Implementation of fire-safe cigarette legislation was associated with a 19% reduction in overall residential fire mortality rates, adjusted for demographic differences between states (rate ratio = 0.81, 95% confidence interval: 0.79, 0.84). This is approximately similar to the estimated proportion of residential fire deaths in which smoking materials are an ignition source (23%). Legislation implementation was associated with a protective effect for every age, sex, race, and ethnicity strata that we examined. State-specific residential fire mortality death rates decreased (defined as a drop of at least 5%) in 32 states after fire-safe cigarette legislation was implemented. In 12 states there was either less than a 5% decrease or an increase, and seven states had insufficient deaths to evaluate state-level changes.
CONCLUSIONS
Implementation of fire-safe cigarette is associated with reductions in residential fire mortality rates. | 10.1186/2197-1714-1-10 |
pubmed_835_25821 | The recent advances in optic neuromorphic devices have led to a subsequent rise in use for construction of energy-efficient artificial-vision systems. The widespread use can be attributed to their ability to capture, store, and process visual information from the environment. The primary limitations of existing optic neuromorphic devices include nonlinear weight updates, cross-talk issues, and silicon process incompatibility. In this study, a highly linear, light-tunable, cross-talk-free, and silicon-compatible one-phototransistor-one-memristor (1PT1R) optic memristor is experimentally demonstrated for the implementation of an optic artificial neural network (OANN). For optic image recognition in the experiment, an OANN is constructed using a 16 × 3 1PT1R memristor array, and it is trained on an online platform. The model yields an accuracy of 99.3% after only ten training epochs. The 1PT1R memristor, which shows good performance, demonstrates its ability as an excellent hardware solution for highly efficient optic neuromorphic and edge computing. | 10.1002/adma.202204844 |
pubmed_794_3791 | Developing effective therapies and medicines to conquer nonalcoholic steatohepatitis (NASH) is of great significance for public health and is faced with a major challenge. The activation of the thyroid hormone receptor agonist THRβ could be regulated by target drugs that has brought huge potential to the treatment of NASH. In this work, pyridazinone compound YWS01125 was synthesized for the first time. In this study, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for YWS01125 determination was established, and the pharmacokinetics of YWS01125 was evaluated. The half-life values (t1/2)of three different doses of YWS01125 was 189.12 ± 95.27, 152.64 ± 37.98, and 181.95 ± 64.25 min, respectively, and the tissue distribution studies demonstrated that YWS01125 was quickly distributed to various tissues. With successful application in the pharmacokinetics study of YWS01125, the UPLC-MS/MS method has shown characteristics of high sensitivity, rapidity, and good selectivity. | 10.3389/fchem.2022.888587 |
pubmed_581_4987 | Zika virus (ZIKV) causes significant public health concerns because of its association with congenital malformations, neurological disorders in adults, and, more recently, death. Considering the necessity to mitigate ZIKV-associated diseases, antiviral interventions are an urgent necessity. Sofosbuvir, a drug in clinical use against hepatitis C virus (HCV), is among the FDA-approved substances endowed with anti-ZIKV activity. In this work, we further investigated the in vivo activity of sofosbuvir against ZIKV. Neonatal Swiss mice were infected with ZIKV (2 × 107 PFU) and treated with sofosbuvir at 20 mg/kg/day, a concentration compatible with pre-clinical development of this drug. We found that sofosbuvir reduced acute levels of ZIKV from 60 to 90% in different anatomical compartments, such as the blood plasma, spleen, kidney, and brain. Early treatment with sofosbuvir doubled the percentage and time of survival of ZIKV-infected animals. Sofosbuvir also prevented the acute neuromotor impairment triggered by ZIKV. In the long-term behavioural analysis of ZIKV-associated sequelae, sofosbuvir prevented loss of hippocampal- and amygdala-dependent memory. Our results indicate that sofosbuvir inhibits ZIKV replication in vivo, which is consistent with the prospective necessity of antiviral drugs to treat ZIKV-infected individuals. | 10.1038/s41598-017-09797-8 |
pubmed_63_8596 | Under hydrothermal conditions in HF-containing media, the combination of early (Nb(5+), Mo(6+)) and late (Cu(2+)) transition metals with four different organic amine ligands yields eight novel hybrid compounds with chain and layer structures. The eight new compounds were synthesised from a systematic series of reactions and can be subdivided into four pairs, the topologies of which are essentially unique to each ligand, containing in each case a Cu-based cationic species, but alternately either [MoO(2)F(4)](2-) or [NbOF(5)](2-), in an isomorphous manner, as the anionic moiety. The overall structures of theses materials reflect the influences of the organo amine ligands. [Cu(C(2)H(4)N(4))(2)][MoO(2)F(4)].H(2)O () and [Cu(C(2)H(4)N(4))(2)][NbOF(5)].H(2)O () exhibit an infinite copper fluoride amine chain, while the anionic moieties act as 'decoration' to the chain. [Cu(C(3)H(4)N(2))(4)][MoO(2)F(4)] () and [Cu(C(3)H(4)N(2))(4)][NbOF(5)] () form infinite 1D chains with alternating cationic and anionic units. [Cu(2)F(2)(C(10)H(9)N(3))(2)][MoO(2)F(4)] () and [Cu(2)F(2)(C(10)H(9)N(3))(2)] [NbOF(5)] () contain a dimeric copper fluoride complex, bridged through anions to form a 1D infinite chain. [Cu(C(10)H(8)N(2))(2)(H(2)O)(2)][MoO(2)F(4)] () and [Cu(C(10)H(8)N(2))(2)(H(2)O)(2)][NbOF(5)] () contain a 2D interpenetrated network formed from the copper-4,4'-bipy complex, with open channels which accommodate the oxyfluoride anions via hydrogen bond interactions. | 10.1039/b900356h |
pubmed_345_20727 | BACKGROUND
The deficit subtype of schizophrenia is hypothesized to constitute a pathophysiologically distinct subgroup of schizophrenia patients suffering from enduring, idiopathic negative symptoms and various neuropsychological deficits. Matrix metalloproteinases (MMPs) are extracellularly acting endopeptidases the substrates of which are matrix and adhesion molecules. Recently, MMP9 has been shown to be involved in various forms of synaptic plasticity, learning and memory consolidation. The primary aim of the present study was to evaluate associations between the functional MMP-9 -1562C/T gene polymorphism and the deficit and non-deficit subtypes of schizophrenia.
METHODS
The study was conducted between 2009 and 2012. Deficit schizophrenia was diagnosed using the SDS. The sample consisted of 468 patients, Caucasians, of Polish descent with ICD 10 diagnosis of schizophrenia: 189 [51% males] were included in a non-deficit subgroup, 279 patients [53% males] were included in a deficit subgroup. The control group consisted of 532 subjects, Caucasians, of Polish descent [51% males]. MMP-9 -1562C/T gene polymorphism was genotyped using the fluorescence resonance energy transfer (FRET) method and the Light Cycler System 2.0.
RESULTS
The frequencies of genotypes and alleles did not differ between the schizophrenia patients and control group. The deficit and non-deficit patients did not differ in terms of the genotype and allele frequencies. No differences were found in genotype and allele frequencies between the deficit patients and the controls and between the non-deficit patients and the controls.
CONCLUSION
We found no evidence for the association between the functional MMP-9 -1562C/T gene polymorphism and deficit/non-deficit subtypes of schizophrenia. | pubmed_345_20727 |
pubmed_488_3072 | The mydriasis provocative test with 1% cyclopentolate (CPT) was performed on 218 patients with suspected or untreated open-angle glaucoma, on 431 eyes in all. Significant IOP elevations (larger than or equal to 8 mmHg) were demonstrated in 21 eyes of 18 patients. The present paper analyses the responder group and presents some other investigation results and clinical findings to throw additional light on the mechanism of IOP elevation in responders. The responders did not differ from the other patients of the material in age or sex. Patients with capsular glaucoma constituted the biggest group among the responders. 48% of the significant IOP elevations during CPT were encountered in eyes with pseudoexfoliation (PE) and open-angle glaucoma. A positive response during CPT was statistically significantly more common in PE eyes than in eyes without PE. Capsular glaucoma was diagnosed immediately or later in all PE eyes which displayed a larger than or equal to 5 mmHg IOP elevation during the CPT. In addition to the importance of pigment in PE eyes, PE material may play a certain role in the elevation of IOP . The mechanism of this role is not known. No correlation was established between the results of the water drinking test and the CPT. The mechanism that causes the elevation of IOP must be quite different in these two tests. Nor was a statistically significant difference observed in the incidence of cataract, the maximal variation of IOP in the 48-h tension curve, the occurrence of cupping of the optic disc or visual field defects between the responder and non-responder eyes in the glaucomatous group. | 10.1111/j.1755-3768.1976.tb01278.x |
pubmed_1096_22828 | Recent advances in proteomics have become an indispensable tool for a fast, precise and sensitive analysis of proteins in complex biological samples at both, qualitative and quantitative level. In this study, a label-free quantitative proteomic methodology has been optimised for the relative quantitation of proteins extracted from raw pork meat. So, after the separation of proteins by one-dimensional gel electrophoresis and trypsin digestion, their identification and quantitation have been done using nanoliquid chromatography coupled to a quadrupole/time-of-flight (Q/ToF) mass spectrometer. Relative quantitation has been based on the measurement of mass spectral peak intensities, which have been described that are correlated with protein abundances. The results obtained regarding linearity, robustness, repeatability and accuracy show that this procedure could be used as a fast, simple, and reliable method to quantify changes in protein abundance in meat samples. | pubmed_1096_22828 |
pubmed_969_21367 | The epitope recognized by monoclonal antibody directed against the HIV-1 recombinant gp160 protein was precisely delineated by using a number of peptides comprising amino acid positions 302-330 of the protein. Two different enzymes, glucose oxidase and horseradish peroxidase, were then coupled to distinct antibody molecules and the efficacy of the immunoenzymes in killing yeast cells which express the recognized peptide was evaluated by flow cytometry analysis. The antibody-glucose oxidase conjugate alone was cytotoxic only at large doses (over 35 micrograms/ml) while in the presence of the antibody-horseradish peroxidase conjugate, killing was observed at nine times lower concentrations (4 micrograms/ml). The procedure described here may provide a new immunotherapy tool for microbial infection. | 10.1016/0165-2478(90)90208-8 |
pubmed_450_9149 | OBJECTIVE
The aim of this study was to reduce the rate of cesarean section (CS) in severe pregnancy-induced hypertension (PIH) by introducing a set of indicative criteria for CS.
METHODS
Labor induction was attempted in Japanese patients (n = 41) with severe PIH after 34 weeks of gestation. Vital signs and symptoms that may increase the risk of serious complications were defined. Following the appearance of one or more signs or symptoms, labor induction was suspended and CS was performed. The impact of using specific indicative criteria was evaluated by comparing the CS rate among patients who delivered before and after the criteria were introduced.
RESULTS
Labor induction was attempted in 36 of 41 patients. Among the 36 patients in whom vaginal delivery was started, 12 patients required CS, and the remaining 24 patients succeeded in vaginal delivery. The introduction of specific indicative criteria for CS was associated with a significant reduction in the CS rate, from 95% (43/45) to 41% (17/41).
CONCLUSIONS
Unnecessary CS may be avoided by defining the limits of safe labor induction. | 10.3109/10641955.2015.1115061 |
pubmed_624_1608 | Neonatal rat cardiac myocytes were isolated and cultured to evaluate the effects of growth factors and inhibitors on proliferation, survival, and functions in a serum-free medium. Insulin and transferrin in MCDB 107 nutrient medium elicited DNA and protein synthesis in cells on a fibronectin-coated culture surface in serum-free medium. Insulin was most effective on both DNA and protein synthesis in serum-free culture conditions. The serum-free, hormone-supplemented medium eliminated the contamination of noncardiac myocytes and supported the long-term survival (over 18 d) of cardiac myocytes. Dexamethasone was required to induce optimal contractility with or without insulin and transferrin. Serum contained both negative and positive effectors of DNA and protein synthesis of the cardiac myocytes. Concentrations of serum (above 5%) inhibited DNA and protein synthesis. Low density lipoprotein (LDL) accounted in part for the inhibitory activity. The serum-free culture system provides a useful model to elucidate the role of hormones, growth factors, and drugs in heart cell regeneration and function. | 10.1007/BF02623629 |
pubmed_419_15630 | Chromosome damage combined with defective recombinase activity renders cells inviable, owing to deficient double-strand break repair. Despite this, recA polA cells grow well under either DNA damage response (SOS) conditions or catalase medium supplementation. Catalase treatments reduce intracellular reactive oxygen species (ROS) levels, suggesting that recA polA cells are susceptible to not only chronic chromosome damage but also ROS. In this study, we used a reducing agent, vitamin C, to confirm whether cell growth could be improved. Vitamin C reduced ROS levels and rescued colony formation in recAts polA cells under restrictive temperatures in the presence of hslO, the gene encoding a redox molecular chaperone. Subsequently, we investigated the role of hslO in the cell growth failure of recAts polA cells. The effects of vitamin C were observed in hslO cells; simultaneously, cells converged along several ploidies likely through a completion of replication, with the addition of vitamin C at restrictive temperatures. These results suggest that HslO could manage oxidative stress to an acceptable level, allowing for cell division as well as rescuing cell growth. Overall, ROS may regulate several processes, from damage response to cell division. Our results provide a basis for understanding the unsolved regulatory interplay of cellular processes. | 10.3390/ijms232112786 |
pubmed_464_4991 | Young children vary widely in the extent to which they attend to numerical information in their everyday environments without explicit prompting. This tendency to spontaneously focus on numerosity has been linked to children's math skills in past work. However, various measures have been used to quantify children's spontaneous focusing on numerosity (SFON) in previous studies, some of which rely on children's behavioral responses and others of which rely on verbal responses. Furthermore, these measures are not consistently related to one another or to children's math skills. In this study, we compared children's SFON as demonstrated through their behaviors and verbal responses during a set of imitation tasks in a sample of 107 3- and 4-year-olds. We found that children behaviorally demonstrate SFON (e.g., stamping the same number of spikes on a dinosaur as an experimenter) more frequently than they discuss number during the same tasks, but the two indices of SFON were significantly associated when accounting for variability in children's overall speech. Furthermore, we found that children's SFON through their actions was significantly predicted by prior math skills, whereas SFON through speech was not. These findings indicate that SFON may be a multifaceted construct, although more work is needed to extend these findings to other common SFON tasks. | 10.1016/j.jecp.2021.105301 |
pubmed_136_33 | Various levels of protection against x-irradiation damage in bacteriophage T1 may be obtained by the addition of inorganic salts to the aqueous virus suspensions during irradiation. The highest survival values are obtained with the nitrite salts, and their protective power is attributed primarily to their function as reducing agents. The nitrate ion shows greater protection than the corresponding sulfate or chloride ions. This may be due in part to the lower energy level of the nitrate ion, by reason of resonance. Since greater expenditure of incident energy is required to raise the ion from the ground state, the energy thus dissipated may be ineffective in the inactivation of virus particles. The ammonium salts exhibit protection of a different order of magnitude from that of the metallic salts. It is postulated that NH(4) (+) protects in a threefold way: (a) dehydration, (b) reduction, in which the ammonia is oxidized to nitrite and the nitrite to nitrate, and (c) stabilization of the virus protein. Metallic salts likewise protect, but a point of maximum protection is reached in lower concentrations than in the case of the ammonium salts. After this maximum protection is reached, there is a rapid decline in survival with increased concentration. This prevents protection of the order of magnitude that can be obtained with the ammonium salts. It is postulated that a specific cationic interaction with the phage may be responsible for the decreased protection. Bacteriophage is protected during x-irradiation by an alkaline pH, in the case of NH(4)OH. This protection could not be produced with NaOH, presumably because of the greater hydrolysis of the protein components of the virus particle in solutions of NaOH, whereas NH(4)OH stabilizes the protein. | 10.1085/jgp.37.5.663 |
pubmed_218_1533 | Alleged reversal of the phototropism of the sporangiophores of Phycomyces by high intensities of light does not occur if infra-red radiation is properly excluded. Phototropic "indifference" alone occurs at high intensities due to equal photic action on both sides of the sporangiophore. If heat radiation is not screened out, a gradual, negative thermotropic bending takes place. | 10.1085/jgp.15.5.487 |
pubmed_1117_5530 | Regional vascular resistance changes were determined following chemical excitation and inhibition of the rostral vasopressor (RVLM) and caudal vasodepressor (CVLM) areas in the ventrolateral medulla. Mesenteric, renal and hindquarter vascular resistances were assessed in paralyzed and artificially ventilated urethane-anesthetized rats instrumented with pulsed-Doppler flow probes. Microinjection of the excitatory amino acid L-glutamate in the RVLM elicited a significant dose-related transient increase in blood pressure, heart rate and resistance of mesenteric, renal and hindquarter vascular beds. A similar dose-related hemodynamic profile was obtained following microinjection of muscimol, a GABAmimetic, in the CVLM. In contrast, significant dose-related decrease in blood pressure, heart rate and resistance in mesenteric and hindquarter vascular beds was observed following glutamate-induced excitation of the CVLM and muscimol-induced inhibition of the RVLM. Changes in renal vascular resistance were inconsistent in this second hemodynamic profile. Intravenous administration of the alpha 1 adrenergic antagonist, prazosin, abolished all of the hemodynamic effects elicited by excitation of the RVLM except the tachycardia. Intravenous atropine methylnitrate blocked the bradycardia associated with excitation of the CVLM but did not alter the vascular resistance changes. These results indicate that the changes in heart rate did not contribute significantly to the resistance profiles described. The changes in vascular resistance elicited by excitation and inhibition of the RVLM were correlated with increase and decrease in the greater splanchnic nerve activity, respectively. In conclusion, neuron pools in the RVLM and CVLM exert differential effects upon resistance in different vascular beds via changes in sympathetic outflow.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1016/0165-1838(87)90101-9 |
pubmed_251_8217 | BACKGROUND
The AIDS database at Fairfield Hospital, Melbourne, maintains information on eye pathology as identified by the three visiting ophthalmologists. Patients underwent an eye consultation: if they had ocular symptoms; if signs were seen on direct ophthalmoscopy by physicians; or when their CD4+ve cell count fell below 50/microL. The first AIDS-associated eye signs were identified in mid-1984. In the subsequent decade, 3257 patients in Victoria tested positive for HIV, and 845 of the 1123 who developed AIDS were treated at Fairfield Hospital.
METHODS
We undertook a retrospective review of the Fairfield Hospital database to identify the AIDS-associated ocular problems seen.
RESULTS
Some 723 patients had an eye consultation. In the earliest stage of HIV infection, minor non-specific ophthalmic involvement may occur. As the disease progresses, microvasculopathy (cottonwool spots and haemorrhages) appears. External disease also occurs such as molluscum contagiosum and Kaposi's sarcoma of the conjunctiva. With more suppression of the immune system, opportunistic infections become common, and have a considerable visual morbidity. Cerebral toxoplasmosis (117 patients) is only rarely associated with ocular involvement (three patients), but cytomegalovirus (CMV) commonly causes retinitis [204 patients (24%)]. It has been the AIDS-defining illness in 26 patients. A majority had the disease confined to one eye. Mean CD4 cell count at onset is 15 +/- 5 microL and it has been associated with a viraemia in all but two patients. Late complications of CMV retinitis include relapse in 41 (20%), spread to the other eye in 24 (12%), and retinal detachment in 30 (15%). Visual impairment follows from retinal destruction, optic nerve involvement, and retinal detachment.
CONCLUSION
The ophthalmic workload from late ocular complications of AIDS is increasing. Newer and more effective methods of treatment are being developed. Ophthalmologists are becoming more aware of the need for universal precautions to avoid risks from this and other blood-borne infections. | 10.1111/j.1442-9071.1996.tb01553.x |
pubmed_728_2225 | The effects of experimental anaemia on the levels of reduced glutathione (GSH) and the activity of glycolytic enzymes in the erythrocytes of normal and GSH-deficient Merino sheep were investigated. There was a rise in red cell GSH levels in both groups of sheep; the magnitude of this response was, however, quite different. When expressed as a percentage of the initial value, the rise in GSH level was 18% in normal and 263% in GSH-deficient animals. There was also an increase in the activities of various enzymes following phlebotomy but this increase was similar in the two groups of sheep. | 10.1071/bi9750233 |
pubmed_391_14422 | The direct detection of viraemia could improve greatly the efficacy of presently available assays. Due to its sensitivity, the polymerase chain reaction represents the method of choice for direct detection of viral nucleic acid. However, the clinical application of this method is hampered by the requirement of hybridization with radioactively labelled probes. In this study we demonstrate that HCV cDNA, amplified by the polymerase chain reaction from both liver tissues and sera, can be detected specifically by a new non-radioisotopic method, DNA enzyme immunoassay, that is based on an antibody that selectively recognizes double, but not single-stranded DNA. The assay reveals the hybridization events, independently from the DNA sequences, and therefore can be used with any combination of primers and probes. Most importantly, the method has a conventional ELISA format and is compatible with standard facilities of clinical laboratories. The availability of this new approach for revealing amplified sequences may facilitate greatly the use of PCR as the method of choice for early diagnosis of HCV infection. | 10.1016/0166-0934(91)90103-7 |
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