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pubmed_419_9573
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Coronavirus disease 2019 (COVID-19) affects numerous systems of the body during the illness, and there have been long-lasting effects. BDNF plays an important role in synaptic plasticity and synaptic communication. According to the inclusion and exclusion criteria, 54 patients who had COVID-19 infection participated in this study. Thirty-six age-, sex-, body mass index (BMI)-, education level- and smoking status-matched healthy controls were included in the present study. All participants were individually administered the Stroop test and Visual Aural Digit Span Test Form B (VADS-B). Serum BDNF levels were measured by ELISA. Stroop test word reading spontaneous correction number and reading time, word color saying wrong number, spontaneous correction number and reading time, box color speaking spontaneous correction number and reading time, Stroop interference and speed factor duration were significantly higher in the COVID-19 group than in the control group. All scores of the VADS-B test were found to be significantly lower in the COVID-19 group. The mean serum BDNF levels were found to be 10.9 ± 6.9 ng/ml in the COVID-19 group and 12.8 ± 6.4 ng/ml in the healthy control group. Two-way ANOVA showed that the serum mean BDNF level was significantly lower in the COVID-19 group than in the control group. Gender had a significant effect on BDNF levels (F = 12.21; p = 0.008). The present study is the first to demonstrate the association between the role of serum BDNF and cognitive decline in patients with COVID-19 infection. Additionally, there is a significant role of male gender in terms of lower BDNF level and cognitive decline.
|
10.1007/s00406-022-01514-5
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pubmed_927_15148
|
The high incidence of surgical complications following renal transplantation is well known. Urologic complications, however, present some of the most challenging problems to the transplant surgeon. The authors present here a detailed case report of spontaneous (delayed) bladder rupture (SDBR) which occurred 90 days after kidney transplantation in a recipient with cytomegalovirus infection (CMV). Urinary catheter drainage is recommended in preference to surgical intervention for the successful correction of SDBR. It is postulated further that, despite a negative bladder biopsy, CMV may have infiltrated the bladder and contributed to this "spontaneous" bladder wall rupture.
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pubmed_927_15148
|
pubmed_40_11724
|
PURPOSE
Hospitalizations for ambulatory care-sensitive conditions (ACSCs) are seen as potentially avoidable with optimal primary care. Little is known, however, about how primary care physicians rate these hospitalizations and whether and how they could be avoided. This study explores the complex causality of such hospitalizations from the perspective of primary care physicians.
METHODS
We conducted semistructured interviews with 12 primary care physicians from 10 primary care clinics in Germany regarding 104 hospitalizations of 81 patients with ACSCs at high risk of rehospitalization.
RESULTS
Participating physicians rated 43 (41%) of the 104 hospitalizations to be potentially avoidable. During the interviews the cause of hospitalization fell into 5 principal categories: system related (eg, unavailability of ambulatory services), physician related (eg, suboptimal monitoring), medical (eg, medication side effects), patient related (eg, delayed help-seeking), and social (eg, lack of social support). Subcategories frequently associated with physicians' rating of hospitalizations for ACSCs as potentially avoidable were after-hours absence of the treating physician, failure to use ambulatory services, suboptimal monitoring, patients' fearfulness, cultural background and insufficient language skills of patients, medication errors, medication nonadherence, and overprotective caregivers. Comorbidities and medical emergencies were frequent causes attributed to ACSC-based hospitalizations that were rated as being unavoidable.
CONCLUSIONS
Primary care physicians rated a significant proportion of hospitalizations for ACSCs to be potentially avoidable. Strategies to avoid these hospitalizations may target after-hours care, optimal use of ambulatory services, intensified monitoring of high-risk patients, and initiatives to improve patients' willingness and ability to seek timely help, as well as patients' medication adherence.
|
10.1370/afm.1498
|
pubmed_386_16282
|
Human melanoma contains multipotent stem cells that express the neural crest stem cell marker CD271. CD271-expressing melanoma cells in murine xenografts give rise to metastatic tumor. However, a comprehensive clinical investigation of its role in different stages of melanomagenesis has not been well studied. We studied CD271 expression with immunohistochemistry in 11 cases of banal melanocytic nevus, 9 cases of primary cutaneous melanoma, 10 cases of primary mucosal melanoma, 5 cases of metastatic melanoma in regional lymph nodes, and 11 cases of metastatic melanoma in the brain. In addition, 9 cases of metastatic, high-grade adenocarcinomas from breast and lung to the brain were studied as controls. The staining was scored based on the number of positive cells and analyzed by student t-test. All banal melanocytic nevi showed negative to equivocal staining. Primary cutaneous melanomas showed variable patterns, mucosal melanomas were mostly negative, and metastases to lymph nodes ranged from negative to moderate positivity. In contrast, all 11 cases of metastatic melanoma to the brain showed moderate (4 cases) to strong positivity (7 cases). Metastases from lung and breast origin were used as controls and showed negative to weakly positive staining in all but one case. Statistically, CD271 has significantly increased expression in metastatic melanoma to the brain when compared to the other groups studied (P < 0.05). The findings suggest that CD271 expression is specifically increased in metastatic melanoma to the brain. Further prospective study for the role of CD271 in prediction of melanoma brain metastasis as well as prognosis assessment will be of great clinical significance.
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pubmed_386_16282
|
pubmed_282_15209
|
BACKGROUND
Few studies have evaluated the relationship between changes in diet quality over time and the risk of death.
METHODS
We used Cox proportional-hazards models to calculate adjusted hazard ratios for total and cause-specific mortality among 47,994 women in the Nurses' Health Study and 25,745 men in the Health Professionals Follow-up Study from 1998 through 2010. Changes in diet quality over the preceding 12 years (1986-1998) were assessed with the use of the Alternate Healthy Eating Index-2010 score, the Alternate Mediterranean Diet score, and the Dietary Approaches to Stop Hypertension (DASH) diet score.
RESULTS
The pooled hazard ratios for all-cause mortality among participants who had the greatest improvement in diet quality (13 to 33% improvement), as compared with those who had a relatively stable diet quality (0 to 3% improvement), in the 12-year period were the following: 0.91 (95% confidence interval [CI], 0.85 to 0.97) according to changes in the Alternate Healthy Eating Index score, 0.84 (95 CI%, 0.78 to 0.91) according to changes in the Alternate Mediterranean Diet score, and 0.89 (95% CI, 0.84 to 0.95) according to changes in the DASH score. A 20-percentile increase in diet scores (indicating an improved quality of diet) was significantly associated with a reduction in total mortality of 8 to 17% with the use of the three diet indexes and a 7 to 15% reduction in the risk of death from cardiovascular disease with the use of the Alternate Healthy Eating Index and Alternate Mediterranean Diet. Among participants who maintained a high-quality diet over a 12-year period, the risk of death from any cause was significantly lower - by 14% (95% CI, 8 to 19) when assessed with the Alternate Healthy Eating Index score, 11% (95% CI, 5 to 18) when assessed with the Alternate Mediterranean Diet score, and 9% (95% CI, 2 to 15) when assessed with the DASH score - than the risk among participants with consistently low diet scores over time.
CONCLUSIONS
Improved diet quality over 12 years was consistently associated with a decreased risk of death. (Funded by the National Institutes of Health.).
|
10.1056/NEJMoa1613502
|
pubmed_194_12275
|
The levels of RNA and protein and activity levels of acetylcholinesterase decreased in the brain of developing tadpoles of 13-15-day-old Bufo melanostictus on in vivo administration of progesterone (200 mug/0.1 ml refined peanut oil). These changes suggest decelaration in the activity of the protein-synthetic machinery in progesterone administered animals.
|
10.1007/BF01919848
|
pubmed_1067_4186
|
OBJECTIVE
To amplify the full-length cDNA and characterize the structure and biological function of a novel expression sequence tag ST55 (GenBank Accession No. BM121646).
METHODS
Rapid amplification of cDNA ends was used to clone the full-length of cDNA of ST55 in this study. Then, its tissue distribution was checked by Northern blots, and the associated protein was screened by GAL 4-based yeast two-hybrid. The effect of stable transfection of the cDNA on cell proliferation was evaluated in ECV304 cells.
RESULTS
A full-length 1404 bp cDNA was cloned, and it was accepted as a novel human mRNA by GenBank (No. AY074889), named endothelial-overexpressed lipopolysaccharide-associated factor 1 (EOLA1). Bioinformatic analysis found that the EOLA1 encoded 158 amino acids, 17.89 kDa protein, and mapped to chromosome Xq27.4 with 5 exons. EOLA1 expressed in different human normal tissues and cancer cell lines. Using the EOLA1 cDNA as bait, we performed a yeast two-hybrid screening of a human liver cDNA library and identified metallothionein 2A (MT2A) as associated protein. The interaction between EOLA1 and MT2A was confirmed by co-immunoprecipitation experiments. Stable transfection of EOLA1 was noted to stimulate ECV304 cell proliferation (P < 0.05).
CONCLUSION
The findings suggest that EOLA1 is a novel gene and the interaction of EOLA1 and MT2A may play an important role in cell protection in inflammation reaction.
|
pubmed_1067_4186
|
pubmed_181_2668
|
Mass spectrometry imaging with desorption electrospray ionization mass spectrometry (DESI-MS) is used to characterize cancer from ex vivo slices of tissues. The process is time-consuming. The use of tissue smears for DESI-MS analysis has been proposed as it eliminates the time required to snap-freeze and section the tissue. To assess the utility of tissue smears for rapid cancer characterization, principal component analysis (PCA) was performed to evaluate the concordance between DESI-MS profiles of breast cancer from tissue slices and smears prepared on various surfaces. PCA suggested no statistical discrimination between DESI-MS profiles of tissue sections and tissue smears prepared on glass, polytetrafluoroethylene (PTFE), and porous PTFE. However, the abundances of cancer biomarker ions varied between sections and smears, with DESI-MS analysis of tissue sections yielding higher ion abundances of cancer biomarkers compared with smears. Coefficient of variance (CV) analysis suggests DESI-MS profiles from tissue smears are as reproducible as the ones from tissue sections. The limit of detection with smear samples from single pixel analysis is comparable to tissue sections that average the signal from a tissue area of 0.01 mm2. The smears prepared on the PTFE surface possessed a higher degree of homogeneity compared with the smears prepared on the glass surface. This allowed single MS scans (~1 s) from random positions across the surface of the smear to be used in rapid cancer typing with good reproducibility, providing pathologic information for cancer typing at speeds suitable for clinical utility. Graphical Abstract ᅟ.
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10.1007/s13361-016-1506-x
|
pubmed_248_24591
|
Autologous chondrocyte implantation (ACI) is a surgical technique that is increasingly being used in the treatment of full-thickness defects of articular cartilage in the knee. It involves the arthroscopic harvesting and in vitro culture of chondrocytes that are subsequently implanted into a previously identified chondral defect. The aim is to produce a repair tissue that closely resembles hyaline articular cartilage that gradually becomes incorporated, restoring joint congruity. Over the long term, it is hoped that this will prevent the progression of full-thickness articular cartilage defects to osteoarthritis. This article reviews the indications and operative procedure performed in ACI. Magnetic resonance imaging (MRI) sequences that provide optimal visualization of articular cartilage in the post-operative period are discussed. Normal appearances of ACI on MRI are presented along with common complications that are encountered with this technique.
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10.1007/s00330-005-0051-y
|
pubmed_143_24253
|
The objective of this in vitro study was to determine the effects of different barley and oat varieties on CH4 production, digestibility, and rumen fermentation patterns in dairy cows. Our hypothesis was that oat-based diets would decrease CH4 production compared with barley-based diets, and that CH4 production would differ between varieties within grain species. To evaluate this hypothesis, we conducted an in vitro experiment using a fully automated gas production technique, in which the total gas volume was automatically recorded by the system. The experiment consisted of triplicate 48-h incubations with 16 treatments, including 8 different varieties of each grain. The grain varieties were investigated as a mix with an early-cut grass silage (1:1 ratio of grain to silage on a dry matter basis) and mixed with buffered rumen fluid. We estimated predicted in vivo total gas production and CH4 production by applying a set of models to the gas production data obtained by the in vitro system. We also evaluated in vitro digestibility and fermentation characteristics. The variety of grain species did not affect total gas production, CH4 production, or fermentation patterns in vitro. However, in vitro-determined digestibility and pH were affected by variety of grain species. Grain species affected total gas and CH4 production: compared with barley-based diets, oat-based diets decreased total gas production and CH4 production by 8.2 and 8.9%, respectively, relative to dry matter intake. Grain species did not affect CH4 production relative to in vitro true dry matter digestibility. Oat-based diets decreased digestibility and total volatile fatty acid production, and maintained a higher pH at 48 h of incubation compared with barley-based diets. Grain species did not affect fermentation patterns, except for decreased molar proportions of valerate with oat-based diets. These results suggest that replacing barley with oats in dairy cow diets could decrease enteric CH4 production.
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10.3168/jds.2019-16995
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pubmed_870_9498
|
Studied were the changes taking place in the protein content of the colostrum of cows during the first six hours following calving. The protein fractions were identified by the method of disk polyacrylamide electrophoresis. It was established that the amount of the total protein dropped with the increase in the secretion time. Changes were found to take place in the gamma-globulin fractions, the casein, and the soluble proteins.
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pubmed_870_9498
|
pubmed_1015_8745
|
Experiments were performed which demonstrate that low power, pulsed microwave exposure induces a significant increase in local cerebral blood flow within the brain of the conscious rat. Previous studies purporting to examine changes in brain vascular permeability induced by microwave radiation must be re-evaluated in the light of these observed changes in blood flow.
|
10.1016/0006-8993(81)90668-5
|
pubmed_432_7806
|
Pulsed magnetic fields (PMFS) are routinely used in the medical community to facilitate bone repair in clinical cases of non-union or pseudarthoses [(1984) Orth. Clin. No. Am. 15, 61-87]. Although this therapeutic regimen appears to be reasonably effective, the mechanism of action between specific PMFs and the target tissue remains unknown. Adding urgency to the need to understand the mechanism are a wide number of reports that have appeared which demonstrate that PMFs similar to those in clinical use can alter many basic physiological functions. We report that a 24 h exposure to PMFs alters the cell surface of Physarum polycephalum amoebae. Further, using the technique of aqueous two-phase partitioning, we present evidence for individual magnetic and electric field, cell surface effects.
|
10.1016/0014-5793(86)80494-x
|
pubmed_1080_12645
|
Bile alcohols in rat bile were analyzed by gas-liquid chromatography-mass spectrometry. Six bile alcohols were newly identified as minor constituents in addition to 5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol, major bile alcohol of rat bile. The bile alcohols newly identified were 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol, 5 alpha-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,26-pentol, 5 alpha-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol, and 5 beta-cholestane-3 alpha,6 beta,7 beta,25,26-pentol. The biliary bile alcohols of the rat occurred mainly as the sulfuric acid esters and, in lesser amounts, as glucuronoconjugated and unconjugated forms. The amount of total bile alcohols was about 27.9 nmol in 1 ml of bile.
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pubmed_1080_12645
|
pubmed_291_16881
|
INTRODUCTION
Fluctuations in atmospheric pollution are responsible for an important morbidity and mortality in the patients suffering from chronic obstructive pulmonary disease (COPD).
BACKGROUND
Epidemiological studies show a significant increase in the mortality and hospitalization rates in COPD patients in relation to moderate increases in atmospheric pollution. In vitro and in vivo studies demonstrate a pro-inflammatory role and an oxidative toxicity of atmospheric particles and secondary morphological and functional changes in the respiratory epithelium and the immune system. An excess of particulate matter, ozone, NO(2), SO(2) and CO is directly correlated to the number of episodes of acute respiratory failure in different countries all over the world. The mechanisms implicated are complex and variable, dependent on the different pollutant agents, climatic variations and inter-individual susceptibility.
VIEWPOINT
Further experimental studies are necessary in order to clarify our fundamental understanding and, alongside better control of air quality, to reduce short-term respiratory complications.
CONCLUSION
The consequences of atmospheric pollution fluctuations on the exacerbation rate and therefore on the morbidity and mortality of patients with COPD emphasize the importance of preventive environmental management in the field of public health.
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10.1016/j.rmr.2010.04.009
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pubmed_443_11608
|
The micturition syncope is a special manifestation of the so called "situational syncopes". These reflex syncopes share efferent mechanisms with the neurocardiogenic, or vasovagal syncope. A case of a patient is reported, who presented with micturition syncope. The patient's tendency for vasovagal syncope was documented by a positive tilt table test. The uniform premonitory symptoms preceding the two fainting attacks indicated the relation between the episodes. The authors review the literature of the micturition syncope, and discuss the potential pathomechanisms.
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pubmed_443_11608
|
pubmed_895_339
|
This study assessed functional balance among older adults at all grades of chronic obstructive pulmonary disease (COPD) and explored balance impairment predictors. A cross-sectional study with outpatients with COPD (N = 160; M = 72.2 years, SD = 7.9; mean forced expiratory volume in 1 s = 63.8% predicted, SD = 23.7) was conducted. The Timed Up and Go (TUG) test was used to assess functional balance. Functional balance impairment was defined as a TUG score exceeding the upper limit of the confidence intervals of normative values for healthy older adults. Participants performed the TUG test in 11.0 s (SD = 4.8 s). Functional balance impairment was present in 44.4% of the participants and was significantly more frequent in severe to very severe COPD (62.5%). Body mass index (odds ratio [OR] = 1.12), number of medications (OR = 1.20), restriction in recreational activities (OR = 1.66), and depression score (OR = 1.14) were multivariate predictors of functional balance impairment. Functional balance impairment is present in early COPD, although more evident at advanced grades. These findings highlight the importance of balance assessment in older patients at all COPD grades.
|
10.1123/japa.2012-0319
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pubmed_675_24061
|
Prebiotics can stimulate the growth and activity of probiotics and have a variety of physiological functions. However, the study of walnut oligopeptides as prebiotics to promote probiotics is rarely reported. Therefore, in order to explore the beneficial effect of walnut oligopeptide (WOPs) on Lactobacillus plantarum Z7, WOPs was added to the medium of L. plantarum Z7, and the utilization of WOPs, the effect of WOPs on the biofilm, extracellular polymeric substances, and bacterial death were explored. The results showed that the growth-promoting effect was strengthened with the increasing concentrations of WOPs. The content of bacterial biofilm and EPS increased significantly, and the number of dead bacteria decreased. The beneficial effect of WOPs was probably because that it enhanced the secretion of biofilm which was regulated by bacterial quorum sensing system and promoted the ability of bacteria to resist the adverse environment, thus promoting the growth and reproduction of bacteria.
|
10.1002/fsn3.2029
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pubmed_494_10334
|
The complexity and diversity of biological samples in proteomics require intensive fractionation ahead of mass spectrometry identification. This work developed a chromatographic method called virtual three-dimensional chromatography to fractionate complex protein mixtures. By alternate elution with different pHs and salt concentrations, we implemented pH and salt steps by turns on a single strong cation exchange column to fully exploit its chromatographic ability. Given standard proteins that were not resolved solely by pH or salt gradient elution could be successfully separated using this combined mode. With a reversed phase column tandem connected behind, we further fractionated as well as desalted proteins as the third dimension. This present strategy could readily be adapted with respect to special complexity of biological samples. Crude plasma without depleting high abundance proteins were fractionated by this three-dimensional mode and then analyzed by reversed phase liquid chromatography coupled with LTQ mass spectrometry. In total, 1933 protein groups with wide dynamic ranges were identified from a single experiment. Some characteristics that correlated to the behavior of proteins on strong cation exchange columns are also discussed.
|
10.1021/pr800318j
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pubmed_590_24208
|
BACKGROUND AND AIMS
Anastomotic leaks (AL) continue to be a devastating complication after colorectal surgery. The purpose of this experimental study was to confirm if Pebisut® applied to intestinal suture lines increases tensile strength in the critical days of healing and to evaluate its anti-inflammatory properties.
METHODS
Bursting pressures and histological evaluation of suture lines in dogs were performed, comparing the burst strength with collagen or fatty tissue patches with/without Pebisut® (patent granted in the USPTO 8,252.333, 26.01.2006, in the European Union 2,062,602, 01.12.2010, in Canada 2,661,686, 21.08.2007 and in Mexico P.C.T./MX/a/2009/001737).
RESULTS
Pebisut® significantly increases burst strength in suture lines in long-term procedures with both collagen and fat pad patches. The adhesive penetrates rapidly into the suture lines, sealing them and progressing towards the intestinal lumen, disappearing in 14-20 days. It was well tolerated without any evidence of "foreign body" reaction.
CONCLUSIONS
Application of the biodegradable adhesive Pebisut® is easy, well tolerated by mammalian tissues and consistently increases the burst strength of suture lines. Therefore, it may provide more tensile strength in anastomosis and help protect AL, one of the most serious complications in gastrointestinal surgery. If this experimental finding could be translated to clinical surgery, the protection of colorectal anastomosis could be beneficial to patients. Additionally, this could also have a positive impact on the economic expenditures of healthcare systems and patients.
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pubmed_590_24208
|
pubmed_992_10101
|
Interdural hematomas are primarily observed in infants, and adult interdural hematomas are rare. We describe a 54-year-old woman with a round, well-defined mass. The mass was an interdural hematoma that was misdiagnosed as an epidural hematoma. Unlike an epidural hematoma, interdural hematomas are located between the two layers of the dura mater, and the dural tail sign can be observed.
|
10.2176/nmccrj.cr.2015-0293
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pubmed_641_12161
|
The political crisis in Haiti has had a severe impact on the health of the population. Mortality among Haitians is 13 per 1000, much higher than the Latin American rate of seven per 1000, and the incidence of AIDS, tuberculosis, and malnourishment is increasing among children. Although food and medicine are exempt, United Nations sanctions have had a negative impact on most of the population. In particular the embargo on fuel has limited most people's access to health care. The difficulties of distributing aid and health care without softening the embargo on fuel are immense, and the health of Haitians is not likely to improve until the political crisis is resolved.
|
10.1136/bmj.309.6953.525
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pubmed_709_2042
|
Peripheral blood lymphocytes from both normal subjects and kidney allograft recipients, before and on the 4th to 5th days after transplantation, were examined for antibody-dependent cellular cytotoxicity (ADCC) and lectin-induced cellular cytotoxicity (LICC). The graft recipients were treated with standard immunosuppression, which included azathioprine and prednisolone. 51Cr-labeled L1210 cells were used as targets for these two tests. ADCC and LICC activity were evaluated in the presence of rabbit anti-L1210 anti-serum and phytohemagglutinin (PHA), respectively. Comparison of the results obtained from healthy subjects with those of patients before grafting showed a significantly higher LICC activity in the latter group. The ADCC activity did not differ between the groups of healthy females and those awaiting transplantation but it was significantly decreased in the group of males awaiting transplantation as compared to healthy males. Four to 5 days after transplantation, the activity of ADCC and LICC remained unchanged in spite of the immunosuppressive treatment in 37 and 61% of the patients studied, respectively. In most of the patients, high ADCC and/or LIcC activity was followed by an accelerated acute rejection episode. A correlation between the ADCC and LICC activities, measured 4 to 5 days after transplantation, and the time of the first rejection episode was found. We conclude that double screening with ADCC and LICC tests in the 1st week after transplantation is valuable.
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10.1097/00007890-198109000-00007
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pubmed_601_1597
|
Fourteen male patients with ankylosing spondylitis, admitted for a 2-week period of inpatient treatment, had their spinal mobility assessed on admission and at the end of treatment by clinical measures and a three-dimensional radiographic technique. The patients were given injections of low-dose corticotrophin (ACTH) or placebo under a double-blind protocol. Initially all the patients had restricted movements compared with normal. After treatment all showed some improvement of mobility but no additional benefit accrued from ACTH. Clinical measures of mobility must be interpreted with care as the changes in these measurements were not closely reflected in the lumbar movements measured radiographically. Changes seen in plain radiographs were of little predictive value for improvements in mobility.
|
10.1097/00007632-198506000-00013
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pubmed_246_3570
|
Rapid regression of all symptoms was obtained after moderate chemotherapy in two women aged 69 and 77 years respectively with malignant non-Hodgkin's lymphomas. Cervico-facial locations of these tumors are discussed in relation to definition, etiology, geographic factors, genetic markers, and associated immunologic disorders. Diagnosis requires a series of explorations including, obviously as a last resort, exploratory cervicotomy. Other regions may be involved and must be investigated, but lesions not affecting lymph nodes occur in only approximately 2 p. cent of patients with cervico-facial malignant non-Hodgkin's lymphoma (approximately 10 p. cent of all malignant non-Hodgkin's lymphomas). Other localizations include the hard palate, gums, sinuses, and salivary glands. Burkitt's lymphoma represents, on the contrary, 30 p. cent of malignant non-Hodgkin's lymphoma seen in European children. The different therapeutic modalities available are discussed.
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pubmed_246_3570
|
pubmed_415_22662
|
BACKGROUND
Nitrite is a key ingredient the manufacture of meat products, forming a stable pink color characteristic of cured products, retarding the development of rancidity and off-odors and flavors during storage, and preventing microbial growth. The negative aspects of nitrite and the demands for healthy foods result in the need to reduce nitrite in cured meat products. Paprika or tomato has been employed as natural pigments in meat products. The objective of this work was to determine the effect of incorporating paprika powder or tomato paste on the texture, rancidity and instrumental and sensory color compensation in nitrite-reduced meat batters.
RESULTS
Addition of tomato paste improved moisture content, resulting in harder but less cohesive samples as compared to control and paprika-containing meat batters. Color characteristics of reduced nitrite samples obtained higher a* red coloration (8.9 for paprika and 7.7-8.0 for tomato paste), as compared to control samples (5.65). Instrumental color was low in control samples, with high values for tomato paste and paprika samples. Nonetheless, tomato paste used to compensate color in nitrite-reduced meat batters was ranked closer to the control sample in sensory evaluation.
CONCLUSION
Color characteristics-instrumental and sensory-in these kinds of meat products were enhanced by the addition of 2.5-3.0% of tomato paste, presenting results close to the non-reduced nitrite control. Similarly, antioxidant components of tomato paste or paprika reduced lipid oxidation. Nitrite reduction from 150 to 100 ppm could be achieved employing tomato paste as a natural pigment to improve color and texture.
|
10.1002/jsfa.4748
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pubmed_663_1949
|
BACKGROUND
Toluene diisocyanate (TDI) is the most important cause of occupational asthma, but the genetic mechanism of TDI-induced asthma is still unknown.
OBJECTIVE
The objective of the study was to identify susceptibility alleles associated with the TDI-induced asthma phenotype.
METHODS
We conducted a genome-wide association study in 84 patients with TDI-induced asthma and 263 unexposed healthy normal controls using Affymetrix 500K SNPchip. We also investigated the relationships between genetic polymorphisms and transcript levels in Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with TDI-induced asthma enrolled in this study.
RESULTS
Genetic polymorphisms of CTNNA3 (catenin alpha 3, alpha-T catenin) were significantly associated with the TDI-induced asthma phenotype (5.84 x 10(-6) for rs10762058, 1.41 x 10(-5) for rs7088181, 2.03 x 10(-5) for rs4378283). Carriers with the minor haplotype, HT2 [GG], of two genetic polymorphisms (rs10762058 and rs7088181) showed significantly lower PC(20) methacholine level (P=0.041) and lower mRNA expression of CTNNA3 than non-carriers (P=0.040). A genetic polymorphism in the 3' downstream region of CTNNA3 (rs1786929), as identified by DNA direct sequencing, was significantly associated with the TDI-induced asthma phenotype (P=0.015 in recessive analysis model) and the prevalence of serum-specific IgG to cytokeratin 19 (P=0.031).
CONCLUSION
These findings suggested that multiple genetic polymorphisms of CTNNA3 may be determinants of susceptibility to TDI-induced asthma.
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10.1111/j.1365-2222.2008.03117.x
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pubmed_345_24316
|
PURPOSE
To investigate the expression and localization of CXCLl6 and its receptor CXCR6 in gingival tissues of patients with chronic periodontitis and analyze the roles in the occurrence and development of periodontitis.
METHODS
Gingival tissues with moderately severe periodontitis were collected from 39 patients treated in People's Hospital of Liaoning Province. Forty persons with healthy gingiva were used as control. The age of the enrolled subjects ranged from 35 to 74 years old. Immunohistochemical technique was applied to detect the expression and localization of CXCLl6 and CXCR6 protein gingival tissues of all subjects. The data was analyzed with SPSS 15.0 software package.
RESULTS
Compared with normal group, the expression of CXCLl6 and CXCR6 were significantly up-regulated in patients with periodontitis (P<0.05). There was a positive relationship between the protein expression of CXCLl6 and CXCR6 in gingival tissues of patients with periodontitis (r=0.580, P<0.05).
CONCLUSIONS
CXCLl6 and CXCR6 may be involved in the development of chronic periodontitis. The expression of CXCLl6 and CXCR6 may work coordinately to promote the development of chronic periodontitis.
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pubmed_345_24316
|
pubmed_447_6034
|
The symptoms of non-temporomandibular disorders, including mass lesions of the central nervous system, may mimic or be masked by symptoms of temporomandibular disorders, and thus not be detected. The dentist must remain alert to this possibility and maintain a high level of suspicion. Three cases illustrate how the TMJ Scale was used in patients having internal derangements of the temporomandibular joints to screen for and detect non-temporomandibular disorders, which, on further evaluation or referral, led to the diagnosis of brain tumors that had not been detected previously.
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10.1080/08869634.1991.11678361
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pubmed_1042_23197
|
The intersex (ix) gene acts in concert with doublesex (dsx) at the end of the sex determination hierarchy to control somatic sexual differentiation in Drosophila melanogaster. Here, we report the Drosophila ix homolog in Bemisia tabaci (Btix) with differential splicing events. Four isoforms were found in B. tabaci adults, including two sex-specific transcripts (Btix and Btix ). Knockdown of Btix had no measurable effects on female morphological phenotypes but reduced the expression of the vitellogenin gene and resulted in the production of significantly fewer eggs, a lower eclosion rate, and a shorter body size of female progeny in comparison with control females. These results increase our understanding of the genes underlying sex determination in B. tabaci and reveal a potential target for RNA interference-based pest management.
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10.3389/fphys.2020.00055
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pubmed_596_24961
|
Current vancomycin dosing guidelines in our acute myeloid leukemia population too often achieve suboptimal initial drug concentrations. Our aim was to assess vancomycin pharmacokinetic parameters in acute myeloid leukemia patients and develop an improved dosing equation to attain more accurate initial therapeutic trough levels. Acute myeloid leukemia patients receiving vancomycin for a presumed or documented gram positive infection were eligible. Patients hospitalized in the intensive care unit, those with creatinine clearance <30 mL/min or with limb amputation were excluded. Three samples were collected at the following post-infusion time ranges: 1 h, 3-8 h, and 8-24 h post-infusion, contingent on the dosing interval. Pharmacokinetic data were then fit using a Bayesian-based population pharmacokinetic model. A total of 25 acute myeloid leukemia patients were studied with a mean volume in the central compartment (Vc; L/65 kg), volume of distribution at steady state (Vss; L/65 kg) and distributional clearance (CLd; L/h/65 kg) of 15, 38.9, and 9.32, respectively. CLslope was 0.59 (mg of vancomycin clearance per unit of creatinine clearance in mL/min); this value is 21.4% lower than the established literature value (0.75). The derived equation, based upon these values, was reasonably precise at achieving the desired trough concentration using a priori dosing. The mean (CV%) of the achieved trough was 94% (29%) with a range of 66-188%; 3/25 at <75% and >125%]. We have established that the derived dosing equation can place ≈ 75% of adult acute myeloid leukemia patients at vancomycin trough levels within 75-125% of the target trough level.
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10.1177/1078155211402107
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pubmed_112_5891
|
The origins of several phenomena of number-fact retrieval were investigated by having children in Grades 3 and 4 memorize alphaplication facts (arithmetic-like memory items composed of letters instead of numbers). Alphaplication performance paralleled memory for arithmetic facts in several important respects: Results showed (a) a large performance advantage for tie (e.g., E, E = j) over nontie problems (E, I = p), (b) that most errors involved answers from the correct alpha-table, (c) that response times and error rates were strongly correlated across problems, (d) that the correct answers to poorly learned problems tended to be the most common error responses, and (e) that performance was lower for problems introduced later in the learning sequence. Taken together, these findings support a network-interference approach (Campbell & Graham, 1985) to memory for arithmetic facts.
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10.1037/h0084310
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pubmed_632_11368
|
Background/Aims
Correct renal function evaluation is based on estimated glomerular filtration rates (eGFR) and complementary renal damage biomarkers, such as neutrophil gelatinase associated lipocalin (NGAL). The aim of this study was to evaluate eGFR and NGAL modifications and renal impairment during treatment with a direct acting antiviral (DAA) for chronic hepatitis C virus (HCV) infection.
METHODS
A retrospective cohort study evaluated eGFR modification during treatment with DAA. Subgroup analysis on serum NGAL was conducted in those receiving sofosbuvir/ledipasvir, with complete follow-up until week 12 after the end of treatment (FU-12).
RESULTS
In the 102 enrolled patients, eGFR reduction was observed (from 86.22 mL/min at baseline to 84.43 mL/min at FU-12, P=0.049). Mean NGAL increased in 18 patients (from 121.89 ng/mL at baseline to 204.13 ng/mL at FU-12, P=0.014). At FU-12, 38.8% (7/18) of patients had a plasmatic NGAL value higher than the normal range (36-203 ng/mL) compared with 11.1% (2/18) at baseline (χ 2 =3,704; P=0.054). In contrast, eGFR did not change significantly over the follow-up in this subgroup.
Conclusions
In conclusion, compared to a negligible eGFR decline observed in the entire cohort analyzed, a significant NGAL increase was observed after HCV treatment with DAA in a small subgroup. This could reflect tubular damage during DAA treatment rather than glomerular injury.
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10.3350/cmh.2017.0059
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pubmed_990_5390
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The microfilaments and vinculin-containing attachment complexes of rat dermal fibroblasts (RDF) incubated on microtextured surfaces were investigated with confocal laser scanning microscopy (CLSM) and digital image analysis (DIA). In addition, depositions of bovine and endogenous fibronectin and vitronectin were studied. Smooth and microtextured silicone substrata were produced that possessed parallel surface grooves with a groove and ridge width of 2.0, 5.0, and 10.0 microns. The groove depth was approximately 0.5 micron. CLSM and DIA make it possible to visualize and analyze intracellular and extracellular proteins and the underlying surface simultaneously. It was observed that the microfilaments and vinculin aggregates of the RDFs on the 2.0 microns grooved substrata were oriented along the surface grooves after 1, 3, 5, and 7 days of incubation while these proteins were significantly less oriented on the 5.0 and 10.0 microns grooved surfaces. Vinculin was located mainly on the surface ridges on all textured surfaces. In contrast, bovine and endogenous fibronectin and vitronectin were oriented along the surface grooves on all textured surfaces. These proteins did not seem to be hindered by the surface grooves since many groove-spanning filaments were found on all the microgrooved surfaces. In conclusion, it can be said that microtextured surfaces influence the orientation of intracellular and extracellular proteins. Although results corroborate three earlier published hypotheses, they do not justify a specific choice of any one of these hypotheses.
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10.1002/(sici)1097-4636(199805)40:2<291::aid-jbm14>3.0.co;2-p
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pubmed_258_21167
|
Eating disorders (EDs) are highly comorbid with obsessive-compulsive disorder (OCD), with comorbidity rates as high as 41%. In the current review, we summarize the literature regarding the prevalence of ED-OCD comorbidity. We also identify and review the literature assessing shared features (i.e., shared characteristics or symptoms) and mechanisms (i.e., variables that may explain ED or OCD symptoms) of EDs and OCD. Potential shared features of EDs and OCD include age of onset, course of illness, obsessions, compulsions and ritualistic behaviors, and thought action fusion. Shared mechanisms that may explain ED-OCD comorbidity include genetic and neurobiological mechanisms, anxiety and fear, repetitive negative thinking, perfectionism, intolerance of uncertainty, distress tolerance, and impulsivity. Based on these shared features and mechanisms, a theoretical conceptualization of ED and OCD comorbidity is developed, and outline considerations for assessment, differential diagnosis, treatment, and future research regarding ED-OCD comorbidity are described.
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10.1891/JCPSY-D-2021-0011
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pubmed_1037_2970
|
The versatile properties make hydrogels a potential multipurpose material that finds wide applications. However, the preparation of multipurpose hydrogels is very challenging. Here, we report a method based on free radical reaction and composite mechanisms to prepare mechanical and electrical self-healing multifunctional hydrogels. In this study, the introduction of imidazolium salt ionic liquids and glycerol in the hydrogel system endows the gels with good antibacterial, conductive, and adhesive properties and excellent antifreeze properties. The testing results show that the as-prepared hydrogel has stable mechanical and electrical properties even under the extremely cold condition of -50°C after self-healing. Moreover, the active esters formed in the dynamic radical reaction have better reducibility, thus further investing the as-prepared hydrogel with high antioxidant activity. The application results show that these comprehensive properties make such hydrogel system very useful in wound repair and wearable strain sensors.
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10.1016/j.mtbio.2021.100138
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pubmed_839_14677
|
The current economic crisis illustrates a critical need for new and fundamental understanding of the structure and dynamics of economic networks. Economic systems are increasingly built on interdependencies, implemented through trans-national credit and investment networks, trade relations, or supply chains that have proven difficult to predict and control. We need, therefore, an approach that stresses the systemic complexity of economic networks and that can be used to revise and extend established paradigms in economic theory. This will facilitate the design of policies that reduce conflicts between individual interests and global efficiency, as well as reduce the risk of global failure by making economic networks more robust.
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10.1126/science.1173644
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pubmed_891_27317
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The Baylor University Medical Center Department of Medical Education hosted its seventh annual Medical Education Research Forum on April 21, 2021, to showcase the research efforts of its medical students, residents, and fellows. Thirty-six posters were shared and 18 oral presentations were given. Here we present 17 award-winning abstracts.
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10.1080/08998280.2021.1949926
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pubmed_216_8618
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Half-centimeter-high mats of vertically aligned single-walled carbon nanotubes were grown at 600 degrees C by point-arc microwave plasma chemical vapor deposition. The mats were produced from 0.5 nm of an Fe catalyst layer, thus showing one of the highest catalytic yields of approximately 105 times. The growth process shows a lack of poisoning of the catalyst, in contrast to other reports. The experimental results confirm that the growth rate is ultimately limited by the gas phase diffusion of hydrocarbon radicals.
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10.1021/jp067776s
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pubmed_189_5523
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BACKGROUND
Senescence marker protein 30 (SMP30), which plays a pivotal role as a suppressor protein in cell proliferation, among other regulatory actions, is a marker of aging that shows decreased expression during senescence. Decreased SMP30 has been identified in several human cancers, but its expression and role in human non-small cell lung cancer (NSCLC) remain unclear.
METHODS
Using tumor tissue and matched adjacent normal tissue from 341 patients with resected NSCLC, we assessed SMP30 expression using immunohistochemical methods. The relationship between SMP30 expression and clinicopathologic characteristics was investigated by Kaplan-Meier survival analysis and multivariate analysis. Cell viability assay, colony formation assay, EdU incorporation assay and in vivo tumor xenograft models were also performed to investigate NSCLC cell proliferation using A549 and H1299 cell lines. Recombinant lentivirus-meditated in vivo gene overexpression and Western blot were performed to clarify the underlying molecular mechanism of SMP30 inhibiting NSCLC proliferation.
RESULTS
SMP30 expression was frequently downregulated in NSCLC tissue, as compared with adjacent non-tumor tissue. Kaplan-Meier survival analyses revealed NSCLC patients with low SMP30 expression had a significantly worse overall survival (OS), with median OS of 18 vs. 67 months in high SMP30 expression group. SMP30 overexpression significantly inhibited A549 and H1299 cell proliferation both in vitro and in tumor xenografts and downregulated the expression of c-Myc and CyclinD1 protein. Moreover, Western blot analyses confirmed that SMP30 overexpression significantly inhibited the histone deacetylase 4 (HDAC4) level in NSCLC cells, and HDAC4 overexpression reversed SMP30-mediated NSCLC repression both in vitro and in vivo.
CONCLUSIONS
SMP30 inhibited NSCLC proliferation by reducing HDAC4 expression, and SMP30 and HDAC4 may serve as new prognostic biomarkers and future therapeutic targets for NSCLC.
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10.21037/tlcr-21-982
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pubmed_290_1237
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Biodiversity is in crisis due to habitat destruction and climate change. The conservation of many noncharismatic species is hampered by the lack of data. Yet, natural history research-a major source of information on noncharismatic species-is in decline. We here suggest a remedy for many mammal species, i.e., metagenomic clean-up of fecal samples that are "crowdsourced" during routine field surveys. Based on literature data, we estimate that this approach could yield natural history information for circa 1,000 species within a decade. Metagenomic analysis would simultaneously yield natural history data on diet and gut parasites while enhancing our understanding of host genetics, gut microbiome, and the functional interactions between traditional and new natural history data. We document the power of this approach by carrying out a "metagenomic clean-up" on fecal samples collected during a single night of small mammal trapping in one of Alfred Wallace's favorite collecting sites.
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10.1371/journal.pbio.3000517
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pubmed_1128_14623
|
In order to clarify the relative contribution of the liver to the short term disposition of propofol, hepatic blood flow was measured during induction of anaesthesia with an i.v. bolus dose of propofol 2 mg kg-1. Total clearance of the drug was 2390 (SD 340) ml min-1, hepatic extraction 82% and hepatic clearance 1060 (260) ml min-1. During the 60-min period of observation, hepatic extraction of propofol increased from 79% to 92%. It is concluded that, within 1 h, only 44% of the administered dose is removed by the liver. Consequently, drug accumulation may occur with repeated dosing or infusion of propofol. The increase in extraction results presumably from slow release of propofol from the soy-bean emulsion.
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10.1093/bja/64.5.563
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pubmed_552_5740
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Cardiac oxygen availability and oxygen consumption were used in a theoretical study as indexes of myocardial energy supply and utilization, respectively. A detailed computer simulation of the closed-loop canine cardiovascular system was utilized to study the dependence of these indexes on timing of the intraaortic balloon pump. Oxygen availability exhibited higher sensitivity to balloon timing than oxygen utilization. While maximum augmentation of oxygen availability was 58 percent, oxygen consumption could be reduced by only 13 percent. Animal experiments were initiated to validate the theoretical results. The results of both the animal experiments and the computer simulation suggested that neither balloon timing which maximizes oxygen availability nor timing which minimizes oxygen consumption correlates with timing which minimizes aortic end diastolic pressure. Thus, end diastolic pressure, presently used as a determinant of proper timing in patients undergoing cardiac assistance, was found to be a poor index of ventricular energy consumption. A performance index comprised of clinically available variables, was formulated to reflect myocardial energy balance. In this performance index, mean diastolic pressure was used to represent energy availability and peak systolic pressure was used as an index of oxygen consumption. Their relationship to oxygen balance and their dependence on timing were studied using the computer simulation of the canine cardiovascular system and animal experiments. Theoretical and experimental results suggest that such an index is capable of representing O2 balance and can be used to control phasing of the device.
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10.1109/10.46257
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pubmed_1088_24147
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A polysaccharide fraction was isolated from fresh Aloe barbadensis Miller leaves, which can promote the wound healing of the superficial II scald model mice. The monosaccharide composition and linkage determination were investigated by methylation and GC-MS, acetylation and GC, 13C NMR and DEPT. The results show that its glycosyl components contain D-glucose, D-galactose, D-xylose in a molar ratio of 5:5:1, and the API consists of a backbone of -->2)-alpha-D-Galp-(1-->2)-alpha-D-Glcp-(1-->, having a branch of alpha-D-xylofuranosyl residue that is (1-->3) linkage at O-3 of alpha-D-galactopyranosyl residue. It was found that the API could enhance proliferation of the human fibroblasts in vitro. The mechanisms of promotion proliferation were studied preliminarily.
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10.1016/j.ijbiomac.2009.04.013
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pubmed_819_9760
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We describe our studies on the characterization of the cell phenotypes in the wall of the aortic-arch-derived arteries from "late" chicken embryos. Using immunocytochemistry with antibodies against smooth muscle cytoskeletal and basement membrane proteins, we show that the smooth muscle of the aortic-arch-derived arteries from 13- to 19-d-old embryos contains two cell phenotypes organized in interchanging lamellae. One cell phenotype (lamellar cells), but not the other cell phenotype (interlamellar cells), expresses the cytoskeletal proteins desmin and alpha smooth muscle actin (alpha SMactin). Both cell phenotypes express the cytoskeletal protein vimentin. Furthermore, the lamellar cells but not the interlamellar cells are surrounded by the basement membrane proteins laminin and collagen type IV. Performing quail-chick transplantation experiments and using a quail specific antibody, we show that both lamellar and interlamellar cells in the "aortic arches" of a 15-d-old chimeric embryo are derived from neural crest cells. We conclude that the aortic smooth muscle cells from "late" chicken embryos consist of two distinct cell phenotypes which are derived from a common lineage.
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pubmed_819_9760
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pubmed_842_9095
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The pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing crescentic GN (NCGN) is incompletely understood. Dipeptidyl peptidase I (DPPI) is a cysteine protease required for the activation of neutrophil serine proteases (NSPs) cathepsin G, neutrophil elastase, and proteinase 3, which are enzymes that modulate inflammation. We used a mouse model of anti-myeloperoxidase (MPO) antibody-induced NCGN to determine whether active NSPs contribute to its pathogenesis. MPO-deficient animals immunized with murine MPO, irradiated, and transplanted with wild-type bone marrow developed NCGN. In contrast, transplantation with bone marrow that lacked DPPI or lacked both neutrophil elastase and proteinase 3 protected mice from NCGN induced by anti-MPO antibody. The kidneys of mice reconstituted with DPPI-deficient bone marrow generated significantly less IL-1β than did those of mice reconstituted with wild-type bone marrow; similarly, in vitro, DPPI-deficient monocytes produced significantly less IL-1β in response to anti-MPO antibody than did wild-type monocytes. This reduction in IL-1β was NSP dependent; exogenous addition of PR3 restored IL-β production in DPPI-deficient monocytes. Last, the IL-1 receptor antagonist anakinra protected animals against anti-MPO antibody-induced NCGN (16.7%±6.0% versus 2.4%±1.7% crescents), suggesting that IL-1β is a critical inflammatory mediator in this model. These data suggest that the development of anti-MPO antibody-induced NCGN requires NSP-dependent IL-1β generation and that these processes may provide therapeutic targets for ANCA-mediated diseases in humans.
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10.1681/ASN.2010080892
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pubmed_164_14659
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Recently, metal-assisted chemical etching (MaCE) has been proposed as a promising wet-etching method for the fabrication of micro- and nanostructures on silicon with low cost. However, uniform vertical trench etching with high aspect ratio is still of great challenge for traditional MaCE. Here we report an innovated MaCE method, which combined the use of a nanoporous gold thin film as the catalyst and a hydrofluoric acid (HF)-hydrogen peroxide (H2O2) mixture solution with a low HF-to-H2O2 concentration ratio (ρ) as the etchant. The reported method successfully fabricated vertical trenches on silicon with a width down to 2 μm and an aspect ratio of 16. The geometry of the trenches was highly uniform throughout the 3D space. The vertical etching direction was favored on both (100)- and (111)-oriented silicon substrates. The reported method was also capable of producing multiple trenches on the same substrate with individually-tunable lateral geometry. An etching mechanism including a through-catalyst mass-transport process and an electropolishing-favored charge-transport process was identified by a comparative study. The novel method fundamentally solves the problems of distortion and random movement of isolated catalysts in MaCE. The results mark a breakthrough in high-quality silicon trench-etching technology with a cost of more than 2 orders of magnitude lower than that of the currently available methods.
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10.1021/am4046519
|
pubmed_690_21729
|
Melanin, the natural pigment found in human skin, absorbs and protects against the ultraviolet (UV) components of sunlight. Melanin production (melanogenesis) is increased by exposure to sunlight, causing a darker skin colour which is regarded as aesthetically pleasing by many humans, who therefore expose themselves to large amounts of potentially damaging sunlight. We have found that topically applied all-trans retinoic acid, a metabolic derivative of vitamin A, greatly enhances UV light-induced melanogenesis: the same preparation on its own had no effect on skin pigmentation. An orally administered retinoid, temarotene, did not have this effect. These observations were made using a lightly pigmented mouse strain, HRA: Skh-2, and confirmed in 2 human volunteers. This is the first time that metabolic derivatives of vitamin A have been shown to augment UV light-induced melanogenesis, suggesting a role for vitamin A in this process.
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10.1097/00008390-199205000-00006
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pubmed_1125_10696
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This study presents data for 27 nonpolar narcotic compounds regarding toxicity to Pseudokirchneriella subcapitata as evaluated using a closed-system algal toxicity test with an exposure time of 48 h. Two test endpoints, dissolved oxygen production and algal growth rate, were used to assess the toxicity of nonpolar narcotic chemicals on algae. Hydrophobicity (1-octanol-water partition coefficient [K(OW)]) provided satisfactory descriptions for the toxicity of nonpolar narcotic compounds, and quantitative structure-activity relationships based on log K(OW) were established. The relative sensitivity of various aquatic organisms to nonpolar chemicals was as follows: P. subcapitata > Vibriofischeri > or = Nitrosomonas sp. > fathead minnow > Daphnia magna > polytox > activated sludge. In addition, linear relationships were found between the toxicity observed in P. subcapitata and other aquatic organisms, except in the case of Nitrosomonas sp. Therefore, for nonpolar toxicants, the closed-system technique applied in the present study can be an ideal surrogate for other tests, such as fathead minnow and D. magna, that are either time-consuming or labor-intensive. However, because the current toxicity database is based primarily on the conventional batch tests, it cannot provide adequate assessment regarding the effects of various organic toxicants. Therefore, more extensive research is needed to revise the database for the toxicity of organic compounds on phytoplankton using the closed-system technique.
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10.1897/06-127r.1
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pubmed_766_1346
|
Postoperative wound infections were evaluated in 1271 patients who had 1389 surgical procedures. There were 49 postoperative wound infections identified, of which 26 (53%) were discovered after discharge. Wound infections varied from 2.5% for clean wounds up to 13.3% for dirty wounds. Among the specialties, the infection rate ranged from no infection for otolaryngologists and urologists to 8.6% for general surgeons. With routine hospital surveillance, the overall infection rate was 1.8% or 2.2%, including readmissions for infection, but less than the actual rate of 3.8%. Persons who had three procedures had no infection rate of 27.3%; for two procedures, 8.1%; and for one procedure, 3.2%. Most postoperative wound infections detected after discharge were based on clinical grounds and not positive cultures. Rehospitalization was required for seven patients because of infection. This study demonstrates that postoperative wound infection surveillance must be continued after discharge.
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pubmed_766_1346
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pubmed_865_2752
|
The genomic structure of Pelargonium line pattern virus (PLPV), a tentative member of a proposed new genus within the family Tombusviridae, has been recently determined. However, little is known about the genetic variability and population structure of this pathogen. Here, we have investigated the heterogeneity of PLPV isolates from different origins by sequence analysis of a 1817nt fragment encompassing the movement (p7 and p9.7) and coat protein genes as well as flanking segments including the complete 3' untranslated region. We have evaluated the selective pressures operating on both viral proteins and RNA genome in order to assess the relative functional and/or structural relevance of different amino acid or nucleotide sites. The results of the study have revealed that distinct protein domains are under different selective constraints and that maintenance of certain primary and/or secondary structures in RNA regulatory sequences might be an important factor limiting viral heterogeneity. We have also performed covariation analyses to uncover potential dependencies among amino acid sites of the same protein or of different proteins. The detection of linked amino acid substitutions has permitted to draw a putative network of intra- and interprotein interactions that are likely required to accomplish the different steps of the infection cycle. Finally, we have obtained phylogenetic trees that support geographical segregation of PLPV sequences.
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10.1016/j.virusres.2010.10.022
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pubmed_224_14209
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The growth and development of XO and XX mice were compared from 7 1/4 to 18 1/2 days of gestation. The 7 1/4-day XO egg cylinders were retarded in development (and consequently small) when compared with XX egg cylinders, and this lag in development remained until 10 1/2 days. By 12 1/4 days there was a considerable degree of 'catch-up', but this was not fully maintained. A subgroup of very severely retarded XO fetuses were preferentially located near the cervix. The placentas of XO fetuses were of normal size until 18 1/2 days when they were significantly larger than those of XX controls.
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10.1530/jrf.0.0680387
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pubmed_393_7939
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Fifty out of sixty-five isolates of coagulase-negative staphylococci displayed a positive CAMP-reaction due to synergism of an extracellular toxin with S. aureus beta-toxin on sheep erythrocytes. Of the CAMP-positive isolates, 40 were identified as S. epidermidis, 8 as S. hemolyticus, and 2 each as S. hominis and S. saprophyticus. CAMP-positivity did not appear to be an indication of pathogenicity, and the incidence of CAMP-positive strains derived from wound infections did not differ from that found in clinically insignificant isolates. In five cases of mixed wound infection with S. aureus and a CAMP-positive S. epidermidis, no synergism between the toxins of the respective, paired isolates could be demonstrated since the S. aureus strains in these cases did not produce beta-toxin. The results show that most coagulase-negative staphylococci produce one or more toxins, possibly delta-toxin, detectable by the CAMP-reaction. The biological significance of toxin production remains to be elucidated.
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10.1007/BF02124812
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pubmed_1049_5306
|
Ubiquitin-mediated proteolysis has a central role in controlling the intracellular levels of several important regulatory molecules such as cyclins, CKIs, p53, and IkappaBalpha. Many diverse proinflammatory signals lead to the specific phosphorylation and subsequent ubiquitin-mediated destruction of the NF-kappaB inhibitor protein IkappaBalpha. Substrate specificity in ubiquitination reactions is, in large part, mediated by the specific association of the E3-ubiquitin ligases with their substrates. One class of E3 ligases is defined by the recently described SCF complexes, the archetype of which was first described in budding yeast and contains Skp1, Cdc53, and the F-box protein Cdc4. These complexes recognize their substrates through modular F-box proteins in a phosphorylation-dependent manner. Here we describe a biochemical dissection of a novel mammalian SCF complex, SCFbeta-TRCP, that specifically recognizes a 19-amino-acid destruction motif in IkappaBalpha (residues 21-41) in a phosphorylation-dependent manner. This SCF complex also recognizes a conserved destruction motif in beta-catenin, a protein with levels also regulated by phosphorylation-dependent ubiquitination. Endogenous IkappaBalpha-ubiquitin ligase activity cofractionates with SCFbeta-TRCP. Furthermore, recombinant SCFbeta-TRCP assembled in mammalian cells contains phospho-IkappaBalpha-specific ubiquitin ligase activity. Our results suggest that an SCFbeta-TRCP complex functions in multiple transcriptional programs by activating the NF-kappaB pathway and inhibiting the beta-catenin pathway.
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10.1101/gad.13.3.270
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pubmed_91_12692
|
To determine the hepatic and intestinal toxicity of sodium cyanate, this compound was administered to rats by orogastric tube (PO) or intraperitoneal injection (IP). At low dosage (50 mg. per kilogram per day PO for 8 weeks), the animals showed no clinical effects other than mild lethargy. They had normal intestinal absorption studies, but demonstrated decreased liver G6PD activity and a slight increase in hepatic glycogen. At higher dose levels (200 mg. per kilogram per day PO for 10 days, 400 mg. per kilogram per day PO for 3 days, and 100 mg. per kilogram per day IP for 10 days), the animals became very lethargic and developed hind-limb paralysis; many animals died during the period of dosing. The severity and rate of onset of symptoms increased proportionally with the dose level. Liver sections from rats receiving these higher doses showed striking increases in glycogen deposition. Activities of hepatic enzymes involved in glycogen synthesis and degradation were measured in rats receiving 200 mg. per kilogram per day PO or 100 mg. per kilogram per day IP. Significant decreases were noted in the activities of glucose-6-phosphatase and G6PD in PO-dosed rats. The activities of phosphorylase, UDPG-pyrophosphorylase, glycogen synthetase, phosphoglucomutase, and debrancher did not differ from control rats. In IP-dosed rats, significant decreases were observed in the activities of glucose-6-phosphatase, G6PD, phosphorylase, and UDPG-pyrophosphorylase, but not in the other glycogen-related enzymes. Our data suggest that sodium cyanate affects several enzymes of hepatic glycogen metabolism but that the enzymes vary in their susceptibility (glucose-6-phosphatase and G6PD greater than phosphorylase and UDPG pyrophosphorylase.
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pubmed_91_12692
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pubmed_808_24062
|
Bacteria use two-component signaling systems to adapt and respond to their competitors and changing environments. For instance, competitor bacteria may produce antibiotics and other bioactive metabolites and sequester nutrients. To survive, some species of bacteria escape competition through antibiotic production, biofilm formation, or motility. Specialized metabolite production and biofilm formation are relatively well understood for bacterial species in isolation. How bacteria control these functions when competitors are present is not well studied. To address fundamental questions relating to the competitive mechanisms of different species, we have developed a model system using two species of soil bacteria, Bacillus subtilis and Streptomyces sp. strain Mg1. Using this model, we previously found that linearmycins produced by Streptomyces sp. strain Mg1 cause lysis of B. subtilis cells and degradation of colony matrix. We identified strains of B. subtilis with mutations in the two-component signaling system yfiJK operon that confer dual phenotypes of specific linearmycin resistance and biofilm morphology. We determined that expression of the ATP-binding cassette (ABC) transporter yfiLMN operon, particularly yfiM and yfiN, is necessary for biofilm morphology. Using transposon mutagenesis, we identified genes that are required for YfiLMN-mediated biofilm morphology, including several chaperones. Using transcriptional fusions, we found that YfiJ signaling is activated by linearmycins and other polyene metabolites. Finally, using a truncated YfiJ, we show that YfiJ requires its transmembrane domain to activate downstream signaling. Taken together, these results suggest coordinated dual antibiotic resistance and biofilm morphology by a single multifunctional ABC transporter promotes competitive fitness of B. subtilisIMPORTANCE DNA sequencing approaches have revealed hitherto unexplored diversity of bacterial species in a wide variety of environments that includes the gastrointestinal tract of animals and the rhizosphere of plants. Interactions between different species in bacterial communities have impacts on our health and industry. However, many approaches currently used to study whole bacterial communities do not resolve mechanistic details of interspecies interactions, including how bacteria sense and respond to their competitors. Using a competition model, we have uncovered dual functions for a previously uncharacterized two-component signaling system involved in specific antibiotic resistance and biofilm morphology. Insights gleaned from signaling within interspecies interaction models build a more complete understanding of gene functions important for bacterial communities and will enhance community-level analytical approaches.
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10.1128/JB.00186-17
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pubmed_1064_3151
|
In this study, we generated transgenic tobacco plants that express the beta-glucuronidase (GUS) gene under the control of the 305-bp 5'-upstream region of a gene coding for sporamin A of sweet potato. Expression of GUS in excised tobacco leaves was induced by sucrose, mimicking the sugar-inducible expression of the endogenous sporamin genes in sweet potato. Deletion of the sequences extending from position -305 (relative to the transcription start site) to -283 and from -146 to -87 resulted in an approximately 40-fold enhancement in GUS reporter expression. Furthermore, the sequence from -282 to -165 conferred sucrose-inducibility on the -89 core promoter of the Cauliflower Mosaic Virus 35S RNA gene. Analysis of internal deletions, linker scanning and the introduction of base substitutions in the sequence between positions -282 and -165 indicated that sucrose-responsiveness conferred by this region was dependent on the presence of two cis-acting elements, termed CMSREs (carbohydrate metabolite signal responsive elements) 1 and 2, which are separated by a spacer. A sequence similar or identical to the core of CMSRE-1 (TGGACGG) is also present in the promoters of several other sugar-inducible genes, and sequences encopassing the TGGACGG-related motifs from two of these could functionally replace the CMSRE-1 in the truncated sporamin A promoter. These results suggest that the TGGACGG element plays an important role in the sucrose-inducible expression of a group of plant genes.
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10.1007/s00438-004-1100-y
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pubmed_881_7950
|
Two novel elicitor peptides that are produced by the race 1 of the cowpea rust fungus Uromyces vignae and that specifically induce a hypersensitive response (a putative form of programmed cell death) in a resistant cultivar of cowpea (Vigna unguiculata L. Walp) have been purified to homogeneity. Purification steps included gel filtration, anion-exchange chromatography, continuous elution electrophoresis, and reversed-phase C18 high performance liquid chromatography. The relative molecular masses of the peptide elicitors as deduced from Tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis were 5600 Da (major) and 5800 Da (minor), respectively. Peptide 1 (major) and the minor copurifying peptide (peptide 2) resolved at the final C18 high performance liquid chromatography step. The NH2 terminus of peptide 1 was deblocked with anhydrous trifluoroacetic acid prior to sequencing. However, the NH2 terminus of peptide 2 was free. The acidic and hydrophobic peptides show some homology between themselves but do not show any significant similarity with known proteins. The two specific elicitors may be products of two avirulence genes corresponding to the two genes for resistance in the resistant cultivar.
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10.1074/jbc.272.7.3924
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pubmed_318_5231
|
A study was made on cats of the dependence of latency, peak latency, amplitudes and slopes of I and II phases of primary evoked potentials in the chiasm, the colliculi, the lateral geniculate body and visual cortex on the intensity of the photic stimulus in the range of intensities of II orders above the threshold. Practically in the whole examined range, the logarithmic connection is retained, testifying to the extremely wide possibility of the visual system to discriminate a signal in securing a reflex act.
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pubmed_318_5231
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pubmed_365_12256
|
Understanding the concept of community is crucial to improving the health status of our citizens. This author used her knowledge of community, understanding of nursing principles, and strong commitment to volunteerism to create the first outreach clinic in Atlanta. Her career story unfolds as she tells of moving from a single community to a role of advocate for a national community population.
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pubmed_365_12256
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pubmed_863_503
|
The preliminary building program suggested in this paper makes use of outlines, graphs, charts, and lists, rather than long-winded paragraphs, to describe the needs, objectives, and philosophy of the library. It is hoped that a short, concise, but detailed, report using these methods will save time and make the report more attractive to read, thereby encouraging the many people who will need to assist in the building planning to use the report.
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pubmed_863_503
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pubmed_707_9970
|
The aim of this study is to share our experience of a baby boy patient who presented with rare endogenous endophthalmitis that ended up with exudative retinal detachment; emphasizing the clinical presentation, follow-ups progression, and the management plan. A case report of a one-month-old preterm baby boy presented with eye discharge in his left eye (OS) associated with eyelid swelling and chemosis for four days. His clinical examination revealed a congested left eye with proptosis, absent red reflex, and normal intraocular pressure (IOP) while a portable slit-lamp examination showed an edematous left eye with cloudy cornea but no infiltrates and no view to the posterior segment. Blood, cerebrospinal fluid (CSF), and ocular discharge were cultured, and all came negative and the patient started on empirical antibiotics. B-scan shows dense infiltrates in the vitreous cavity with subretinal fluid. Diagnostic intravitreal paracentesis was done which showed the growth of Pseudomonas aeruginosa and a diagnosis of endogenous endophthalmitis is made then a directed management plan was initiated. Unfortunately, a few days later a repeated B-scan was ordered to the left eye and it shows exudative retinal detachment, and a referral to retinal surgery service was consulted. After further follow-ups, B-scan showed resolving retinal detachment with a short shrunken eye, marked ocular wall thickening, and a relatively short axial length which is consistent with prephthisical changes hence, an oculoplasty referral was done for ocular prosthesis later on. Endogenous endophthalmitis is a rarely encountered intraocular infection yet it carries devastating consequences that may threaten vision. Therefore, a high index of suspicion is essential for early detection of the disease to prevent serious complications and achieve good visual outcomes.
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10.7759/cureus.22256
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pubmed_118_23909
|
BACKGROUND
We explored the value of admission levels of N-terminal pro-brain natriuretic peptide (NTProBNP) that best predicts poor myocardial tissue perfusion following primary percutaneous coronary intervention (PPCI) in patients admitted with acute ST-segment-elevation myocardial infarction (STEMI).
METHODS
We enrolled 90 consecutive patients admitted with acute STEMI who underwent PPCI and achieved post-procedural TIMI flow grade 3 in the infarct-related artery. We measured levels of NTProBNP from admission blood samples. Thereafter, we assessed post-procedural myocardial blush grade (MBG) at the end of PPCI, and further measured ST segment resolution (STR) 90 minutes following PPCI. The primary endpoint was STR < 50%; furthermore, the co-primary angiographic endpoint was postprocedural MBG 0/1.
RESULTS
The mean age of study subjects was 53.6 ± 10.9 years (74.4% males). We found that NTProBNP was higher in patients with STR < 50% versus those with STR ≥ 50% (p < 0.001), and in patients with post-procedural MBG 0/1 versus those with MBG 2/3 (p < 0.001). A value of NTProBNP ≥ 420 ng/L was the optimal cutoff value that best predicted < 50% STR; it predicted < 50% STR with sensitivity, specificity, positive and negative predictive value of 98.4%, 92.3%, 96.9%, and 96%, respectively. Likewise, a value of NTProBNP ≥ 570 ng/L was the optimal cutoff value that best predicted postprocedural MBG 0/1; it predicted MBG 0/1 with sensitivity, specificity, positive and negative predictive value of 92.2%, 66.7%, 78.3%, and 86.7%, respectively.
CONCLUSIONS
In patients with STEMI who underwent PPCI and ended up with successful recanalization of the epicardial infarct-related artery, elevated admission levels of NTProBNP predicted incomplete post-procedural STR with good sensitivity and specificity, and predicted poor post-procedural myocardial blush with good sensitivity and moderate specificity.
|
10.6515/acs20151112b
|
pubmed_836_4685
|
Tet Repressor (TetR) recognizes the inducer tetracycline (tc) with high affinity. The tc analog 4-de(dimethylamino)-6-deoxy-6-demethyl-tetracycline (cmt3) is not an inducer for TetR. Induction specificity for cmt3 was generated by employing a directed evolution approach to screen appropriate TetR mutants in four successive steps. The specificity of the best TetR mutant is more than 20,000-fold increased for cmt3 over tc as judged by the ratio of their respective binding constants. Two rounds of directed evolution via DNA shuffling revealed His64 as a key residue for inducer specificity. The best TetR mutant with cmt3 specificity contains the H64K exchange, leading to a 300-fold decreased tc and a 20-fold increased cmt3 affinity. Another round of directed evolution made use of randomized oligonucleotides to mutate selected residues close to the tc-binding pocket of TetR and yielded TetR S135L with a 250-fold increased cmt3 affinity. The double mutant TetR H64K S135L was constructed and again subjected to directed evolution using randomized oligonucleotides to alter residues in the "secondary shell" of the tc-binding pocket. The resulting best mutants TetR H64K E114Q S135L, TetR A61V H64K Q109E Q116E S135L and TetR H64K T112K S135L are fully inducible by cmt3 and not by tc. Thus, their inducer specificity has been redesigned. The molecular mechanism of changed inducer recognition is discussed, based on binding constants with several tc analogs and in light of the TetR crystal structure.
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10.1016/s0022-2836(03)00427-3
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pubmed_110_10762
|
Despite the recent advent of total parenteral nutrition (TPN), the long-term survival of the patients with short gut syndrome is not satisfactory with complications of catheter-related sepsis and cholestasis. The causes of short gut syndrome in pediatric surgery are multiple intestinal atresias, necrotizing enterocolitis (NEC), and midgut volvulus. For the multiple atresias, multiple anastomosis without resection has been successfully undertaken to avoid developing short gut syndrome for the last 17 years. For the massive involvement of the intestines due to NEC or volvulus, high jejunostomy and peritoneal drainage with TPN support have been tried for the last two patients and successfully weaned from the TPN within two months after closure of jejunostomy. However, in case 2 malabsorption has been persistent presumably due to a severe degree of mucosal damage occurring in the remaining intestines. Whether this eventually gets back to the normal or not is unknown. For the patients with short gut syndrome, small bowel reversal procedure was successfully done and now doing well 10 years after surgery. This paper reports details of these 3 cases.
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pubmed_110_10762
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pubmed_49_20588
|
The idiopathic, accelerated phase of bone loss associated with postmenopausal and surgically induced menopausal women is rapidly becoming a large public health problem due to the great expense involved in caring for those with vertebral, hip and distal radial fractures. The method of therapy with the least incidence of ill effects is physical exercise. This is a valid, appropriate alternative, but is, however, the most overlooked and unappreciated form of treatment. Studies have shown that bone mineral content can be increased, not just maintained as with the other forms of therapy. The question may then be asked: what about exercise therapy for women already clinically diagnosed? Would exercise increase their risk of fracture, and if not, what forms of exercise would be the most effective? Although osteoporosis prevention and treatment is a multifactorial process, it appears that extension exercises are one form of physical activity necessary to prevent further fracture once it has occurred. A review of the literature will address this conservative noninvasive approach to preventive and ongoing treatment of involutional osteoporosis.
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pubmed_49_20588
|
pubmed_501_2014
|
During 1975-1977 twenty-nine males surviving acute myocardial infarction at an age between 40-44 years were registered in Gothenburg, Sweden. Twenty-five of these were studied and compared with two control groups. One group, the reference group (RG, n = 76), was randomly selected from the male population from which the acute myocardial infarction (AMI) group was derived. A second group, the matched control group (MC, n = 47), consisted of men with no history of coronary heart disease, matched with patients for age, serum cholesterol and body weight index. Serum triglyceride levels were higher and alphalipoprotein cholesterol lower in the AMI group than in RG. Prior to infarction, patients had a higher degree of physical activity at work and a higher tobacco consumption than RG. When AMI cases were compared with MC subjects lower alphalipoprotein cholesterol levels were found in AMI, and they also had a higher tobacco consumption prior to infarction. There was a negative correlation between alphalipoprotein cholesterol levels and tobacco consumption in the RG. The differences in alphalipoprotein cholesterol levels between AMI cases and controls could not attributed to smoking habits, but smoking may at least to some extent exert its effect as a risk factor through influence on alphalipoprotein cholesterol levels.
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10.3109/00365518009095573
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pubmed_690_14117
|
We used a computer program based on the U.S. Preventive Services Task Force guidelines to identify recommendations for 230 adult patients who presented to an ambulatory family practice residency clinic. We entered risk factors into the computer program from sex-specific questionnaires that patients completed. On average, patients had 15.4 risk factors and 24.5 recommendations for preventive services (13.0 recommendations for screening, 10.5 for counseling, and 1.1 for immunizations). We noted a significant increase in the number of risk factors and recommendations with increasing age, except for counseling recommendations. The average patient incurs a large number of recommendations, which depend on many different risk factors, making the task of complete clinician compliance with the U.S. Preventive Services Task Force guidelines difficult. Many of these recommendations include counseling, which may take more time and require skills that clinicians may think they lack. Complete adherence may require several visits for the physician to address all recommendations. Measures to increase patient responsibility for health maintenance and innovations using comprehensive, interactive, and educational computer programs may help solve these problems.
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pubmed_690_14117
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pubmed_157_265
|
Human cytochrome P450 2C8 is a highly polymorphic gene and shows variation according to ethnicity. The CYP2C8*2 is a slow drug metabolism allele and shows 10-24% frequency in Black populations. The objective of this study was to assess the prevalence of CYP2C8*2 allele in Botswana among the San (or Bushmen) and the Bantu ethnic groups. For that purpose we recruited 544 children of the two ethnicities in three districts of Botswana from primary schools, collected blood samples, extracted DNA and genotyped them through PCR-based restriction fragment length polymorphism analysis. The results demonstrated that in the San the prevalence of the CYP2C8*2 allele is significantly higher than among the Bantu-related ethnic groups (17.5% and 8.5% for San and Bantu, respectively; P=0.00002). These findings support the evidence of a different genetic background of the San with respect to Bantu-related populations, and highlight a possible higher risk of longer drug clearance or poor level of activation of pro-drugs among the San group.
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pubmed_157_265
|
pubmed_1014_22347
|
Circulating tumor cells (CTCs) originate from the primary tumor mass and enter into the peripheral bloodstream. CTCs hold the key to understanding the biology of metastasis and also play a vital role in cancer diagnosis, prognosis, disease monitoring, and personalized therapy. However, CTCs are rare in blood and hard to isolate. Additionally, the viability of CTCs can easily be compromised under high shear stress while releasing them from a surface. The heterogeneity of CTCs in biomarker expression makes their isolation quite challenging; the isolation efficiency and specificity of current approaches need to be improved. Nanostructured substrates have emerged as a promising biosensing platform since they provide better isolation sensitivity at the cost of specificity for CTC isolation. This review discusses major challenges faced by CTC isolation techniques and focuses on nanostructured substrates as a platform for CTC isolation.
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10.1016/j.nantod.2013.07.001
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pubmed_729_7893
|
A simple and economic method of radial immunodiffusion is developed for diagnostic measurements of beta 2-microglobulin in human serum. Human serum and plasma concentrations of beta 2-microglobulin can be measured sufficiently accurately; the results are reproducible. The reproducibility and addictiveness of the method were evaluated. The error of the method is no more than 15% (3-36 mg/liter), which is permissible for methods of this type.
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pubmed_729_7893
|
pubmed_824_15041
|
DNA ligases catalyze the repair of phosphate backbone breaks in DNA, acting with highest activity on breaks in one strand of duplex DNA. Some DNA ligases have also been observed to ligate two DNA fragments with short complementary overhangs or blunt-ended termini. In this study, several wild-type DNA ligases (phage T3, T4, and T7 DNA ligases, Paramecium bursaria chlorella virus 1 (PBCV1) DNA ligase, human DNA ligase 3, and Escherichia coli DNA ligase) were tested for their ability to ligate DNA fragments with several difficult to ligate end structures (blunt-ended termini, 3'- and 5'- single base overhangs, and 5'-two base overhangs). This analysis revealed that T4 DNA ligase, the most common enzyme utilized for in vitro ligation, had its greatest activity on blunt- and 2-base overhangs, and poorest on 5'-single base overhangs. Other ligases had different substrate specificity: T3 DNA ligase ligated only blunt ends well; PBCV1 DNA ligase joined 3'-single base overhangs and 2-base overhangs effectively with little blunt or 5'- single base overhang activity; and human ligase 3 had highest activity on blunt ends and 5'-single base overhangs. There is no correlation of activity among ligases on blunt DNA ends with their activity on single base overhangs. In addition, DNA binding domains (Sso7d, hLig3 zinc finger, and T4 DNA ligase N-terminal domain) were fused to PBCV1 DNA ligase to explore whether modified binding to DNA would lead to greater activity on these difficult to ligate substrates. These engineered ligases showed both an increased binding affinity for DNA and increased activity, but did not alter the relative substrate preferences of PBCV1 DNA ligase, indicating active site structure plays a role in determining substrate preference.
|
10.1371/journal.pone.0190062
|
pubmed_241_7275
|
The adsorption and photocatalytic efficiency of several TiO(2) suspended catalysts were compared to see how well they could degrade the organic pollutant anthraquinone dye Reactive Blue 2 (RB2). The adsorption of RB2 on catalysts follows the Langmuir model and adsorption capacity's influence on degradation performance has been established. Correlations between degradation kinetics and the amount of dye adsorbed (q(ads)) were then determined. The expected correlation between specific surface and q(max) was verified. The addition of sulphate ions in the case of catalysts Degussa P25 and TiO(2)-Ishihara ST01 was found to inhibit adsorption of RB2 on the TiO(2) surfaces. The hindrance of adsorption in acidic conditions improved the efficiency of the photocatalytic degradation of ST01. No adsorption was observed in alkaline pH and the photodegradation kinetic was generally higher in this condition except for that seen in photocatalysts with a low recombination rate.
|
10.2166/wst.2010.199
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pubmed_948_18916
|
A novel alpha 1-adrenergic receptor subtype has been cloned from a bovine brain cDNA library. The deduced amino acid sequence is that of a 466-residue polypeptide. The structure is similar to that of the other adrenergic receptors as well as the larger family of G protein-coupled receptors that have a presumed seven-membrane-spanning domain topography. The greatest sequence identity of this receptor protein is with the previously cloned hamster alpha 1B-adrenergic receptor being approximately 72% within the presumed membrane-spanning domains. Localization on different human chromosomes provides evidence that the bovine cDNA is distinct from the hamster alpha 1B-adrenergic receptor. The bovine cDNA clone expressed in COS7 cells revealed 10-fold higher affinity for the alpha 1-adrenergic antagonists WB4101 and phentolamine and the agonist oxymetazoline as compared with the alpha 1B receptor, results similar to pharmacologic binding properties described for the alpha 1A receptor. Despite these similarities in pharmacological profiles, the bovine alpha 1-adrenergic receptor is sensitive to inhibition by the alkylating agent chloroethylclonidine unlike the alpha 1A-adrenergic receptor subtype. In addition, a lack of expression in tissues where the alpha 1A subtype exists suggests that this receptor may actually represent a novel alpha 1-adrenergic receptor subtype not previously appreciated by pharmacological criteria.
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pubmed_948_18916
|
pubmed_399_13842
|
Ascorbic acid, the reduced form of vitamin C, may protect against gastric cancer. Accordingly, this study assessed the variability of ascorbic acid and vitamin C in the gastric juice of 77 patients with dyspepsia. There was a vitamin C concentration gradient from gastric juice down to plasma in subjects with normal gastric mucosa, but not in those with chronic gastritis. Patients with chronic gastritis had significantly lower gastric concentrations of vitamin C and ascorbic acid, and ascorbic acid concentrations were especially low in subjects with hypochlorhydria. The presence of the concentration gradient suggests that a mechanism for the secretion of vitamin C into the stomach exists. This is compromised by chronic gastritis. The very low ascorbic acid concentrations in hypochlorhydria may be a consequence of oxidation by bacterial nitrite. Those patients who by the Correa model are at greatest risk for gastric cancer have the lowest gastric levels of ascorbic acid.
|
10.1016/0016-5085(89)90071-1
|
pubmed_468_600
|
BACKGROUND
Zinc is an essential element required for the cell metabolism, including gene transcription, signal transduction, immunity, and apoptosis. The pathophysiological role of zinc in asthma, however, is not entirely clear. Mast cells have been implicated in atopic asthma, and zinc deprivation has been reported to reduce mast cell activation. Here, we investigate the effects of a zinc chelator, N,N,N',N'-tetrakis (2-pyridyl-methyl) ethylenediamine (TPEN), on asthmatic responses in mouse models of ovalbumin (OVA)-induced airway hyperresponsiveness and allergic airway inflammation.
METHODS
Mice were sensitized with OVA with or without the adjuvant aluminum hydroxide (alum) and subjected to OVA exposure with or without treatment of TPEN. Cell profiles and cytokine levels in bronchoalveolar lavage (BAL) fluids, airway responsiveness to inhaled acetylcholine, and goblet cell hyperplasia after allergen exposure were assessed.
RESULTS
In mice sensitized to OVA without alum, TPEN significantly suppressed airway hyperresponsiveness and eosinophilia in BAL fluids. TPEN also attenuated the upregulation of TNFα, IL-13 and IL-4 in BAL fluids and goblet cell hyperplasia after OVA exposure. By contrast, in mice sensitized to OVA with alum, TPEN suppressed eosinophilia in BAL fluids but not airway hyperresponsiveness and goblet cell hyperplasia.
CONCLUSIONS
In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.
|
10.2332/allergolint.09-OA-0167
|
pubmed_365_14718
|
Repair of apurinic/apyrimidinic (AP) sites is initiated by AP endonucleases, such as the human Ape1 protein (also called Hap1, Apex, and Ref1). This and related enzymes show strong dependence on divalent cations, particularly magnesium. Here we explore the role of this metal in different stages of the Ape1 reaction: substrate binding, cleavage, and product release. We examined DNA binding using an electrophoretic approach and DNA cleavage in single-turnover and steady-state reactions. Magnesium at low to moderate concentrations accelerated both substrate and product release by wild-type Ape1 protein. For a mutant Ape1 protein with an aspartate to alanine substitution at residue 308, substrate in preformed protein-DNA complexes was more efficiently cleaved before release in contrast to wild-type Ape1, whereas product release was accelerated dramatically. The magnesium dependence of steady-state AP endonuclease reactions was sigmoidal for both wild-type and the aspartate 308 to alanine protein but was not sigmoidal for an aspartate 283 to alanine derivative of Ape1. These results show that magnesium affects both DNA interactions with and phosphodiester cleavage by Ape1 and can change the rate-limiting step of the reaction. Structural studies will need to be interpreted in the context of these diverse effects of the metal.
|
10.1074/jbc.273.46.30360
|
pubmed_348_20665
|
INTRODUCTION
Mast cells are normal connective tissue residents. Their densities vary from an organ to other, but are constantly well represented in respiratory tract. Mast cell hyperplasia was found in many malignant tumors, but the significance of this phenomenon is still unknown. In the literature, there are few data about mast cell reaction in malignant laryngeal neoplasm.
MATERIAL AND METHODS
We studied archive blocks from 127 laryngeal carcinomas. For histological diagnosis two sections were prepared for Hematoxylin-Eosin staining and Alcian blue-Safranin histochemistry at pH 0.2 for identifying mast cells. Examination has been performed with Nikon Eclipse 600 microscope. Microscopic images were analyzed with Lucia G program. Microvessel density was calculated using the hot spot method.
RESULTS
Most of the cases were squamous cell carcinoma G1 - 24.4%, G2 - 56.69%, G3 - 18.11%, and 0.78% adenoid cystic carcinoma. Invasive squamous cell carcinoma mast cell microdensity was 2.19 and 4.66 in microinvasive squamous cell carcinoma. Mast cell microdensity in malignant laryngeal papillomatosis was 9.33 and 46.66 in adenoid cystic carcinoma. In carcinoma-associated mast cell hyperplasia, the large majority of mast cells were Alcian blue positive.
CONCLUSIONS
In early stages, the mast cells are numerous (microinvasive squamous cell carcinoma mast cell microdensity 4.66) and rare or even absent in late stages (invasive squamous cell carcinoma mast cell microdensity 2.19). Mast cell microdensity in malignant laryngeal papillomatosis was 9.33 and 46.66 in cystic carcinoma. Alcianophil mast cells are present in tumor area, and safraninophil mast cells are residents of connective and muscular tissue, at a distance from the tumor.
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pubmed_348_20665
|
pubmed_877_14101
|
The value of the right bundle branch block (RBBB) in the treatment of acute myocardial infarction remains unclear. Studies on the RBBB may significantly influence the treatment of acute myocardial infarction. A total of 845 patients with acute myocardial infarction who underwent primary coronary angiography at Henan Provincial People's Hospital were analyzed. Higher peak enzyme levels, a higher ratio of Killip ≥II and closer proximal occlusion of infarct-related artery (IRA) were observed in patients with RBBB compared with those without. The ratio of TIMI flow 0/1 of IRA and ratio of received primary percutaneous coronary intervention (PCI) to IRA in the RBBB group were significantly higher compared with those in the left (L) BBB or no BBB groups. The in-hospital major adverse cardiac events (MACE) incidence in the RBBB group was higher compared with that in the no BBB group, but there was no significant difference between the RBBB and LBBB groups. Logistic regression revealed that proximal occlusion and TIMI flow 0/1 of IRA were predictive factors of RBBB. Cox regression analysis identified RBBB [risk ratio (RR), 4.682; P<0.001] and LBBB (RR, 3.687; P<0.001) as independent predictors of in-hospital MACE. The cumulative one-year survival rate in the RBBB group was significantly lower than those in the no BBB group (P<0.05) and the LBBB group (P<0.05). Similar to the guidelines regarding new onset of LBBB, new onset RBBB should be considered as a standard indicator for reperfusion therapy; as RBBB is associated with more severe symptoms, and higher incidents of complete occlusion of IRA and primary PCI treatment compared with LBBB.
|
10.3892/etm.2017.5661
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pubmed_279_5124
|
The use of stapling instruments to perform gastric surgery in small animal patients provides alternative techniques that are often more reliable and are usually performed more quickly than conventional techniques with manual sutures. In addition to reducing anesthetic and operating times, the risk of contamination of the abdominal cavity may be decreased significantly.
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10.1016/s0195-5616(94)50153-0
|
pubmed_994_18596
|
Liposarcomas are one the most common of over 50 histologic subtypes of soft tissue sarcomas that are mostly resistant to chemotherapy. Histologically, liposarcomas themselves are heterogeneous and fall into four distinct subtypes: well-differentiated/atypical lipomatous tumor, dedifferentiated liposarcoma, myxoid (round cell) liposarcoma, and pleomorphic liposarcoma. Surgical resection with negative margins remains the mainstay for definitive treatment for operable disease. For unresectable disease, retrospective studies have identified myxoid (round cell) and pleomorphic sarcomas to be relatively responsive to chemotherapy. Recent studies have identified distinct genetic aberrations that not only aid in the diagnosis of particular liposarcoma subtypes, but represent actionable targets as they are considered central to disease pathogenesis. Cyclin-dependent kinase 4 (CDK4) and murine double minute 2 (MDM2) are overexpressed in well-differentiated and dedifferentiated liposarcomas and offer tantalizing opportunities that are being pursued in clinical trials. Myxoid (round cell) liposarcomas appear to be sensitive to trabectedin, which is currently under U.S. Food and Drug Administration (FDA) review. Liposarcomas do not represent a uniform disease and understanding the underlying molecular mechanism will help not only in accurate diagnosis but in selecting the appropriate treatment.
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10.14694/EdBook_AM.2015.35.213
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pubmed_1105_19301
|
Lumbar sacralization and lumbarization are congenital spine malformation. 16 cases with lumbar sacralization or lumbarization were reviewed. Through studying the etiopathogenisis and clinical manifestation we analyze the relationship between injury and disease. 6 cases of 16 have lumbar sacralization. 10 cases are attributed to lumbarization. Most of this cases have backleg pain more or less. As a forensic doctor we suggest that pay more attention to this problem in our identify practice and locate the sequence of vertebral body more exactly.
|
pubmed_1105_19301
|
pubmed_51_1835
|
Toxoplasma gondii is an opportunistic parasite, which very unusually may cause acute encephalitis in patients undergoing chemotherapy or hematopoietic stem cell transplant. The prognosis is usually dismal also because of late diagnosis, depending on the limited availability of specific diagnostic tools. An early diagnosis allows effective intervention with specific antibiotics, which may provide a chance for cure. We report 2 cases of cerebral toxoplasmosis in which the use of polymerase chain reaction on cerebrospinal fluid allowed a prompt diagnosis and specific therapy, which was followed by clinical response and negativization at follow-up studies of T. gondii genome on cerebrospinal fluid by polymerase chain reaction and by brain imaging.
|
10.1097/MPH.0b013e318257a15c
|
pubmed_271_5873
|
BACKGROUND
Apoptosis is a form of programmed cell death essential for the maintenance of homeostasis and the removal of potentially damaged cells in multicellular organisms. By binding its cognate membrane receptor, TNF receptor type 1 (TNF-R1), the proinflammatory cytokine Tumor Necrosis Factor (TNF) activates pro-apoptotic signaling via caspase activation, but at the same time also stimulates nuclear factor κB (NF-κB)-mediated survival pathways. Differential dose-response relationships of these two major TNF signaling pathways have been described experimentally and using mathematical modeling. However, the quantitative analysis of the complex interplay between pro- and anti-apoptotic signaling pathways is an open question as it is challenging for several reasons: the overall signaling network is complex, various time scales are present, and cells respond quantitatively and qualitatively in a heterogeneous manner.
RESULTS
This study analyzes the complex interplay of the crosstalk of TNF-R1 induced pro- and anti-apoptotic signaling pathways based on an experimentally validated mathematical model. The mathematical model describes the temporal responses on both the single cell level as well as the level of a heterogeneous cell population, as observed in the respective quantitative experiments using TNF-R1 stimuli of different strengths and durations. Global sensitivity of the heterogeneous population was quantified by measuring the average gradient of time of death versus each population parameter. This global sensitivity analysis uncovers the concentrations of Caspase-8 and Caspase-3, and their respective inhibitors BAR and XIAP, as key elements for deciding the cell's fate. A simulated knockout of the NF-κB-mediated anti-apoptotic signaling reveals the importance of this pathway for delaying the time of death, reducing the death rate in the case of pulse stimulation and significantly increasing cell-to-cell variability.
CONCLUSIONS
Cell ensemble modeling of a heterogeneous cell population including a global sensitivity analysis presented here allowed us to illuminate the role of the different elements and parameters on apoptotic signaling. The receptors serve to transmit the external stimulus; procaspases and their inhibitors control the switching from life to death, while NF-κB enhances the heterogeneity of the cell population. The global sensitivity analysis of the cell population model further revealed an unexpected impact of heterogeneity, i.e. the reduction of parametric sensitivity.
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10.1186/1752-0509-5-204
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pubmed_575_11934
|
BACKGROUND
Anemia is an etiologically heterogeneous condition affecting over half of preschool-aged children in South Asia. An urgent need exists to elucidate context-specific causes of anemia to effectively address this issue.
OBJECTIVES
This study investigated national trends and stability in the prevalence of child anemia and associated risk factors from 2013 to 2016 in Nepal.
METHODS
Same-season national surveys were administered in 2013, 2014, and 2016 in 63 sites across 21 districts, selected using multistage random sampling, representing the mountains, hills, and Tarai (plains). Among consenting households with children aged 6-59 mo, a random sample of capillary blood was selected each year for anemia assessment using an Hb 201+ hemoglobinometer, with n = 835, 807, and 881 children assessed, respectively. Prevalence of child anemia, defined as hemoglobin <11.0 g/dL with adjustment for altitude, was estimated each year and disaggregated by region and child age. Prevalence ratios were estimated using log-binomial regression models with robust SE or robust Poisson regression when models failed to converge. Interaction terms between each risk factor and year were created to test for consistencies in associations over time.
RESULTS
The national prevalence of child anemia decreased from 63.3% (95% CI: 59.0%, 67.5%) in 2013 to 51.9% (95% CI: 46.5%, 57.2%) in 2014 and increased to 59.3% (95% CI: 54.7%, 63.8%) in 2016. Across years, prevalence was highest in the Tarai (58.4-70.2%), followed by the mountains (53.0-61.1%) and hills (37.5-51.4%). Nationally and across time, child age and maternal anemia were significantly associated with child anemia. Child diarrhea and stunting, maternal thinness, and poor water and sanitation conditions also showed consistent trends toward higher anemia prevalence.
CONCLUSIONS
Anemia affects more than half of Nepalese children aged 6-59 mo. Although prevalence varies year to year, the stability of observed risk factors suggests the need to focus on reducing gastrointestinal infection, promoting adequate household sanitation, and improving maternal and child health.
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10.1093/cdn/nzab079
|
pubmed_1093_2129
|
ETHNOPHARMACOLOGICAL RELEVANCE
Investigation of medicinal plant extracts traditionally used against uncomplicated urinary tract infections (UTI) and identification of antiadhesive effects under in vitro conditions against binding of uropathogenic Escherichia coli (UPEC) on bladder cell surface.
MATERIALS AND METHODS
Literature search on traditionally used medicinal plants for UTI was performed by online data bases and standard herbal monographs. For further identification shortlisting was done by intensive evaluation of results by plausibility and phytochemical aspects. Plant material with documented antibacterial effects was not considered for further investigations. Direct cytotoxicity of EtOH-water (1:1; v/v) extracts of the shortlisted plants was investigated against UPEC strain 2980 and bladder cell line T24. Inhibition of UPEC adhesion to T24 cells was monitored either after pretreatment of bacteria or eukaryotic cells by flow cytometry.
RESULTS
Literature search on traditionally used medicinal plants for UTI resulted in 275 plant species, from which 20 were shortlisted by a validated selection process for experimental testing. While direct cytotoxicity of the extracts (1-2000 μg/mL) against UPEC and T24 cells was excluded significant antiadhesive effects were monitored for five plant extracts. Two of them, prepared from the rhizome of Agropyron repens L. and the stigmata of Zea mays L. decreased bacterial adhesion (IC(25) 630 μg/mL, IC(50) 1040 μg/mL, resp.) by interacting with bacterial outer membrane proteins, which was shown by pretreatment of UPEC. Preparations of three plant extracts from the leaves of Betula spp. (according to European pharmacopoeia 7.0), Orthosiphon stamineus BENTH. and Urtica spp. showed antiadhesive effects by interacting with T24 cells (IC(50) 415, 1330 μg/mL, resp. IC(25) 580 μg/mL). Combination of two extracts, one interacting with the bacterial surface (Zea mays L., Agropyron repens L.) and one with the eukaryotic target (Orthosiphon stamineus BENTH.) revealed synergistic effects, as shown by strongly decreased IC(50) values (131 μg/mL, 511 μg/mL, resp.).
CONCLUSIONS
Different plant extracts, traditionally used for UTI, exhibit antiadhesive effects against UPEC under in vitro conditions. Molecular targets can be different, either on the bacterial or on the host cell surface. Combination of these medicinal plants with different targets, as observed often in phytotherapy, results in synergistic effects.
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pubmed_1093_2129
|
pubmed_343_10861
|
In the "post-antibiotic era", healthcare-associated infection has become a global problem that threatens public health and causes huge economic losses. The development of antibacterial coatings based on non-antibiotic strategies is particularly important as drug-resistant bacteria continue to evolve. Photodynamic coatings are a high potential method to treat bacteria, however, the aggregation of photosensitizers on the coating affects the photodynamic capacity seriously. Herein, a photodynamic coating is developed based on the host-guest interaction between β-cyclodextrin and the photosensitizer methylene blue (MB). The host-guest interaction avoids aggregation of MB and results in a high singlet oxygen quantum yield. Consequently, efficient photoantibacterial activity towards methicillin-resistant Staphylococcus aureus is achieved by the photodynamic coating with very low MB density (0.53 ± 0.06 μg cm-2).
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10.1039/c9tb01069f
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pubmed_143_2864
|
BACKGROUND
In recent decades, the prevalence of obesity in children has increased dramatically. This worldwide epidemic has important consequences, including psychiatric, psychological and psychosocial disorders in childhood and increased risk of developing non-communicable diseases (NCDs) later in life. Treatment of obesity is difficult and children with excess weight are likely to become adults with obesity. These trends have led member states of the World Health Organization (WHO) to endorse a target of no increase in obesity in childhood by 2025.
MAIN BODY
Estimates of overweight in children aged under 5 years are available jointly from the United Nations Children's Fund (UNICEF), WHO and the World Bank. The Institute for Health Metrics and Evaluation (IHME) has published country-level estimates of obesity in children aged 2-4 years. For children aged 5-19 years, obesity estimates are available from the NCD Risk Factor Collaboration. The global prevalence of overweight in children aged 5 years or under has increased modestly, but with heterogeneous trends in low and middle-income regions, while the prevalence of obesity in children aged 2-4 years has increased moderately. In 1975, obesity in children aged 5-19 years was relatively rare, but was much more common in 2016.
CONCLUSIONS
It is recognised that the key drivers of this epidemic form an obesogenic environment, which includes changing food systems and reduced physical activity. Although cost-effective interventions such as WHO 'best buys' have been identified, political will and implementation have so far been limited. There is therefore a need to implement effective programmes and policies in multiple sectors to address overnutrition, undernutrition, mobility and physical activity. To be successful, the obesity epidemic must be a political priority, with these issues addressed both locally and globally. Work by governments, civil society, private corporations and other key stakeholders must be coordinated.
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10.1186/s12916-019-1449-8
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pubmed_551_10827
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There is a growing amount of data supporting the concept that cancers originating from the proximal and distal colon are distinct clinicopathological entities. The incidence of MSI and BRAF mutation is strongly associated with right sided tumor location, whereas there are conflicting results for KRAS mutation rates. However, to date, no data exist whether and to what extent defined colonic subsites influence MSI status, KRAS and BRAF mutation rates. We selected primary colon cancer from 171 patients operated on at our institution between 2007 and 2010. BRAF, KRAS mutation rates and microsatellite instability were determined and correlated with clinicopathological features and tumor location. MSI-h cancers were significantly associated with poor histological grade but a lower rate of distant metastases. KRAS-mutated tumors were linked to lower T-stage and better differentiation. Colon carcinomas with BRAF mutation were significantly associated with distant metastatic spread and poor histological grade. Furthermore, we found that MSI-h status, KRAS and BRAF mutation rates varied remarkably among the colonic subsites irrespective of right- and left-sided origin, respectively. The results of the current study provide further evidence that a simple classification into right- and left-sided colon carcinoma does not represent the complexity of this tumor entity.
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pubmed_551_10827
|
pubmed_688_4945
|
Fatty-acid-binding proteins were purified from delipidated cytosols of rat heart and liver by gel filtration and anion-exchange chromatography at pH 8.0 and by repeated gel filtration, respectively. Homogeneity of both proteins was demonstrated by a single band on polyacrylamide gels; each had a molecular weight of about 14 000. Liver fatty-acid-binding protein is more basic (pI, 8.1) than that of heart (pI, 7.0) and contains more basic amino acids. Examination of fatty acid binding by the binding proteins from heart and liver revealed the presence of a single class of fatty-acid-binding sites in both cases with an apparent dissociation constant for palmitate of about 1 microM. Liver fatty- acid-binding protein shows similar binding characteristics for palmitate, oleate and arachidonate. Palmitate bound to heart fatty- acid-binding protein was a good substrate for oxidation by rat heart mitochondria. The results show that the fatty-acid-binding proteins from rat heart and liver are closely related, but that they are distinct proteins.
|
10.1016/0005-2760(85)90085-2
|
pubmed_322_22485
|
BACKGROUND
Two phase 1/phase 2 studies assessed 2 formulations of investigational bivalent Clostridioides (Clostridium) difficile vaccine (QS-21 adjuvanted toxoid and toxoid-alone) in healthy adults 50-85 years of age.
METHODS
The QS-21 adjuvanted toxoid vaccine study randomized subjects 3:1 to 100 μg QS-21-containing C difficile vaccine or placebo administered in a shortened-month (Months 0, 1, 3) or day (Days 1, 8, 30) regimen. The toxoid-alone vaccine study randomized subjects 3:3:1 to receive 100 or 200 μg unadjuvanted C difficile vaccine formulation or placebo in Stages 1 and 2 (sentinel cohorts of different age groups), and 3:1 to receive the selected dose of unadjuvanted C difficile vaccine formulation or placebo in Stage 3 (Days 1, 8, 30). Safety was the primary outcome for both studies. Immunogenicity was determined by measuring serum toxin A- and B-specific neutralizing antibodies.
RESULTS
In the day regimen, 10 reports across both studies of grade 3 injection site redness postdose 2 triggered predefined stopping rules. Local reactions in both studies were more common among vaccine versus placebo recipients. Injection site pain predominated and was generally mild in severity. Systemic events were infrequent and generally mild-to-moderate in severity. Adverse events were reported by 50.0%-75.0% and 16.7%-50.0% of subjects in the QS-21 and toxoid-alone studies, respectively. Immune responses peaked around Day 37 (shortened-month regimen) or between Day 15 and Month 2 (day regimen) and remained above baseline throughout follow-up.
CONCLUSIONS
Both formulations demonstrated robust immunogenicity. Both studies stopped early due to grade 3 injection site redness postdose 2 of the day regimen; neither formulation progressed to later stage development. Instead, an aluminum hydroxide-containing formulation of the vaccine candidate administered at 0, 1, and 6 months, which was safe and immunogenic in phase 1 and 2 studies, advanced to phase 3 studies.
|
10.1016/j.vaccine.2021.05.028
|
pubmed_444_25771
|
Management of posterior tibial plateau fractures has gained much interest over the past few years. Fracture morphology, trauma mechanism, and soft-tissue injury have been identified as the key factors determining the treatment strategy and outcome. We provide a rationale for the operative management of posterior tibial plateau fractures by discussing the interplay between fracture morphology, trauma mechanism, and soft-tissue injury. The trauma mechanism has proven to be an important tool, not only to understand fracture morphology, but also to assess concomitant soft-tissue (i.e. ligamentous) injury. Subsequently, soft-tissue injury might play a role in future classification and diagnostic work-up of tibial plateau fractures, particularly in fractures with posterior involvement. Plate osteosynthesis using a posterior approach is safe and should be considered routinely in coronal fractures of the posterior tibial plateau, as illustrated.
|
10.1016/j.injury.2020.09.011
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pubmed_1046_16908
|
The apical membrane Cl-/oxalate exchanger SLC26A6 has been demonstrated to play a role in proximal tubule NaCl transport based on studies in microperfused tubules. The present study is directed at characterizing the role of SLC26A6 in NaCl homeostasis in vivo under physiological conditions. Free-flow micropuncture studies revealed that volume and Cl- absorption were similar in surface proximal tubules of wild-type and Slc26a6-/- mice. Moreover, the increments in urine flow rate and sodium excretion following thiazide and furosemide infusion were identical in wild-type and Slc26a6-/- mice, indicating no difference in NaCl delivery out of the proximal tubule. The absence of an effect of deletion of SLC26A6 on NaCl homeostasis was further supported by the absence of lower blood pressure in Slc26a6-/- compared with wild-type mice on normal or low-salt diets. Moreover, raising plasma and urine oxalate by feeding mice a diet enriched in soluble oxalate did not affect mean blood pressure. In contrast to the lack of effect of SLC26A6 deletion on NaCl homeostasis, fractional excretion of oxalate was reduced from 1.6 in wild-type mice to 0.7 in Slc26a6-/- mice. We conclude that, although SLC26A6 is dispensable for renal NaCl homeostasis, it is required for net renal secretion of oxalate.
|
10.1152/ajprenal.00309.2018
|
pubmed_1053_4941
|
The efficacy of cefoxitin, a perioperative parenteral antibiotic, combined with mechanical bowel preparation and oral antibiotics to prevent wound infections and other septic complications in patients undergoing elective colorectal operations, was examined in a prospective randomized study. All 197 patients who completed the study received mechanical bowel preparation and oral neomycin/erythromycin base. In addition a perioperative parenteral antibiotic was given in three divided doses to 101 patients. The other 96 patients received no parenteral antibiotics. The overall incidence of intra-abdominal septic complications was 7.3% (7 of 96) in the control group (no cefoxitin) and 5% (5 of 101) in the treatment group (cefoxitin). This difference was not statistically significant. The incidence of abdominal wound infection was 14.6% in the control group and 5% in the treatment group, a statistically significant difference (p = 0.02). The addition of perioperative parenteral cefoxitin greatly reduced the incidence of wound infections in patients undergoing elective colorectal operations who had been prepared with mechanical bowel cleansing and oral antimicrobial agents.
|
10.1097/00000658-199008000-00016
|
pubmed_60_7835
|
OBJECTIVE
Tumor necrosis factor-α (TNF-α) antagonists bring about significant improvement in chronic inflammatory diseases such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). There is some evidence that they can also have negative myocardial effects, but to date this issue has not been clarified. We evaluated changes in electrocardiographic measures [QT interval, corrected, dispersion, and dispersion corrected (QT, QTc, QTd, QTdc, respectively)] in patients with RA or SpA treated with anti-TNF agents (infliximab and etanercept), those treated with other biological agents (rituximab), and with methotrexate.
METHODS
We studied 38 consecutive patients with RA (21 patients) or SpA (19 patients) being treated with TNF-α antagonists, 8 patients with RA being treated with rituximab, and 13 patients (8 with RA and 5 with SpA) taking methotrexate. Electrocardiographs (ECG) were performed on all participants at baseline and 12 months after initiation of treatment, and the QT, QTc, and QTd were calculated with standard procedures.
RESULTS
After 12 months of treatment, significant increases over baseline values were observed in the mean QT (p < 0.009), QTd (p < 0.0001), and QTdc (p < 0.0001) of the anti-TNF group, but no significant changes were observed in those taking rituximab. QT changes in the anti-TNF group were unrelated to the disease (RA vs SpA) or drug (infliximab vs etanercept), and none were associated with clinical manifestations of cardiac disease.
CONCLUSION
In patients with RA and SpA, TNF-α antagonists seem to increase the QT and QTd measures. Although these changes were completely asymptomatic, ECG may be indicated in patients being considered for anti-TNF therapy to identify those at risk for cardiac complications.
|
10.3899/jrheum.110158
|
pubmed_821_17821
|
Heat shock transcription factor 2 (HSF2) is a transcription factor that regulates heat shock protein gene expression, but the mechanisms regulating the function of this factor are unclear. Here we report that HSF2 is a substrate for modification by the ubiquitin-related protein SUMO-1 and that HSF2 colocalizes in cells with SUMO-1 in nuclear granules. Staining with anti-promyelocytic leukemia antibodies indicates that these HSF2-containing nuclear granules are PML bodies. Our results identify lysine 82 as the major site of SUMO-1 modification in HSF2, which is located in a "wing" within the DNA-binding domain of this protein. Interestingly, SUMO-1 modification of HSF2 results in conversion of this factor to the active DNA binding form. This is the first demonstration that SUMO-1 modification can directly alter the DNA binding ability of a transcription factor and reveals a new mechanism by which SUMO-1 modification can regulate protein function.
|
10.1074/jbc.M008066200
|
pubmed_1031_1381
|
PRIMARY OBJECTIVE
To investigate the effectiveness of donepezil hydrochloride (Aricept) in treating persistent memory deficits in people with traumatic brain injury.
RESEARCH DESIGN
Single subject ABAC design was used so that each participant could serve as their own control.
METHODS AND PROCEDURES
Seven TBI survivors with persistent memory dysfunction, at least 1.5 years post-injury, underwent two 6-month trials of Aricept. The following tests were used to assess memory and cognition: Brief Visual Memory Test-Revised (BVMT-R), Hopkins Verbal Learning Test, Digit Span and Letter Number Sequence sub-test of the Wechsler Adult Intelligence Scale-III, Controlled Oral Word Association Test and Memory Functioning Questionnaire.
EXPERIMENTAL INTERVENTION
During the first treatment phase, participants received 5 mg/day of Aricept for 1 month, increasing to 10 mg/day of Aricept for an additional 5 months. During the second treatment phase, participants received 5 mg/day of Aricept for the entire 6 months.
MAIN OUTCOMES AND RESULTS
A repeated measures analysis of variance indicated significant improvement on immediate and delayed memory portions of the BVMT-R when taking 10 mg/day of Aricept.
CONCLUSIONS
Findings contribute to the growing body of research into the use of Aricept in treating memory deficits in TBI survivors and support the need for further research.
|
10.1080/0269905031000088586
|
pubmed_923_12008
|
The Canberra Interview for the Elderly (CIE) has been developed as a field instrument for identifying cases of dementia and depression, according to the diagnostic criteria in both draft ICD-10 and DSM-III-R. It has been designed to be administered by lay interviewers and responses are assembled algorithmically to derive diagnoses. The validity of the CIE was assessed using a sample of 75 elderly patients attending a hospital clinic. The CIE diagnoses were compared with clinical judgements made at the time of recruitment into the study and later by 3 clinicians using the information collected by the lay interviewers. Agreement between the CIE and the clinicians' diagnoses was as great as agreement between the clinicians themselves, meeting or exceeding agreement observed for comparable instruments designed for lay administration.
|
10.1111/j.1600-0447.1993.tb03346.x
|
pubmed_132_1469
|
The major virulence factors of Clostridium difficile infection (CDI) are two large exotoxins A (TcdA) and B (TcdB). However, our understanding of the specific roles of these toxins in CDI is still evolving. It is now accepted that both toxins are enterotoxic and proinflammatory in the human intestine. Both purified TcdA and TcdB are capable of inducing the pathophysiology of CDI, although most studies have focused on TcdA. C. difficile toxins exert a wide array of biological activities by acting directly on intestinal epithelial cells. Alternatively, the toxins may target immune cells and neurons once the intestinal epithelial barrier is disrupted. The toxins may also act indirectly by stimulating cells to produce chemokines, proinflammatory cytokines, neuropeptides and other neuroimmune signals. This review considers the mechanisms of TcdA- and TcdB-induced enterotoxicity, and recent developments in this field.
|
10.3390/toxins2071848
|
pubmed_789_2331
|
BACKGROUND
Fragmented QRS complexes (fQRS) correlate with myocardial scar, and may predict arrhythmias in patients with repaired tetralogy of Fallot (TOF). We investigated the relationship between fQRS in operated TOF patients with right ventricular (RV) dysfunction and RV outflow tract (RVOT) aneurysm.
METHODS
We studied 56 operated TOF patients with moderate/severe pulmonary regurgitation, referred for cardiac magnetic resonance imaging (MRI) over a 4.5 year period. The presence of fQRS (additional notches in the R/S wave in ≥ 2 contiguous leads on the ECG) was correlated with MRI findings.
RESULTS
fQRS was observed in 44 (78.6%) patients. Patients with fQRS had significantly larger RV end diastolic volume index (RVEDVi; 162 ml vs 141 ml, p=0.028) and RV end systolic volume index (RVESVi; 88 ml vs 70 ml, p=0.031). Increasing number of leads with fragmentation was independently associated with increasingly lower RV ejection fraction (adjusted co-efficient -0.97, 95%CI -1.83 to -0.12, p=0.026), greater pulmonary regurgitation fraction (1.65, 0.28 to 3.01, p=0.019), larger RVEDVi (6.78, 2.00 to 11.56, p=0.006) and RVESVi (5.41, 1.66 to 9.15, p=0.005). Anterior fragmentation correlated most significantly with RV dysfunction (p<0.05). fQRS had no significant association with LV dysfunction. Presence of any fQRS (OR 17.5, 95%CI 2.1-147.8, p=0.009) and inferior fQRS (OR 9.0, 95%CI 2.7-30.1, p<0.001) were found to be significant predictors for RVOT aneurysm.
CONCLUSIONS
The presence of fQRS on the ECG is significantly associated with RV dysfunction and RVOT aneurysms in repaired TOF patients. Increasing burden of fragmentation, especially in the anterior leads, is associated with increasing RV dysfunction.
|
pubmed_789_2331
|
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