Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum type III procollagen aminopeptide for assessing liver damage in methotrexate‐treated psoriatic patients

Summary This study was designed to establish whether measurement of a serological marker of fibrosis might reduce the need for liver biopsy in psoriatic patients receiving methotrexate (MTX). Levels of type III procollagen aminopeptide (PIIINP‐O and PIITNP‐B) and laminin PI (LamP1‐B) were measured in 147 serum samples taken at the time of liver biopsy in 87 patients receiving long‐term MTX treatment for severe psoriasis. Biopsies were classified as: (1) normal. (2) steatosis. (3) inflammation, (4) fibrosis, or (5) cirrhosis. Groups 3–5 were considered to show clinically relevant abnormality. Compared with controls. PIIINP‐O was significantly raised in the group of MTX‐treated psoriatics (P<0.001). Within this group, levels were significantly higher in patients with inflammation, fibrosis or cirrhosis compared with those with normal histology or steatosis alone (P<0.0001). In contrast. PIIINP‐B and LamP1‐B did not distinguish between controls and MTX‐treated patients or between histological groups. Forty‐two patients had two or more biopsies with simultaneous PIIINP‐O measurement. PIIINP‐O levels at the time of the first biopsy were normal in six of the seven patients whose histology was initially normal and subsequently became abnormal. A single measurement of PIIINP‐O thus did not predict which patients might develop abnormal histology following further MTX. In a group of 17 patients, PIIINP‐O was measured 3‐monthly for up to 6 years during MTX treatment. PPIINP‐O was elevated at some time during follow‐up in all three patients who developed abnormal histology but was consistently normal in eight of the 11 patients whose histology remained or became normal.
Stealth ryanodine‐sensitive Ca2+ release contributes to activity of capacitative Ca2+ entry and nitric oxide synthase in bovine endothelial cells

1 The involvement of ryanodine‐sensitive Ca2+ release (RsCR) in bradykinin (Bk)‐induced Ca2+ release, capacitative Ca2+ entry (CCE) and nitric oxide synthase (NOS) activation was assessed in freshly isolated bovine coronary artery endothelial cells. 2 Using deconvolution microscopy fura‐2 was found throughout the whole cytosol, while the cell membrane impermeable dye FFP‐18 was exclusively in the cell membrane. Thus, perinuclear ([Ca2+]pn) and subplasmalemmal Ca2+ concentration ([Ca2+]sp) were monitored using fura‐2 and FFP‐18. 3 Inhibition of Na+−Ca2+ exchange by lowering extracellular Na+ concentration augmented the Bk‐induced [Ca2+]pn signal in Ca2+‐free solution. This effect was abolished when RsCR was prevented with 25 μmmu;mol l−1 ryanodine, while inhibition of RsCR had no effect on Bk‐induced increase in [Ca2+]pn without inhibition of Na+−Ca2+ exchange. 4 Initiating RsCR by 200 nmol l−1 ryanodine increased [Ca2+]sp, while [Ca2+]pn remained constant. However, when Na+−Ca2+ exchange was prevented, ryanodine was also able to elevate [Ca2+]pn. 5 Blockage of RsCR diminished Ca2+ extrusion in response to stimulation with Bk in normal Na+‐containing solution. 6 Inhibition of RsCR blunted Bk‐activated CCE, while inhibition of Na+−Ca2+ exchange during stimulation enhanced CCE. 7 Although direct activation of RsCR failed to activate NOS, inhibition of RsCR diminished the effect of ATP and Bk on NOS, while the effect of thapsigargin remained unchanged. 8 These data suggest that during stimulation subplasmalemmal RsCR occurs, which contributes to the activities of CCE and NOS. Thus, the function of the subplasmalemmal Ca2+ control unit must be extended as a regulator for CCE and NOS.
Evidence of an Intracellular Angiotensin-Generating System and Non-AT1, Non-AT2 Binding Site in a Human Pancreatic Cell Line

Objectives: To assess the presence of a local angiotensin-generating systems (LAGS) and its participation in tumor growth in the human pancreatic cancer derived cell line Capan-1. Methods: Capan-1 cells were cultured in Dulbecco modified Eagle medium, and angiotensin I was assayed by radioimmunoassay and angiotensin II and vascular endothelial growth factor were assayed by enzyme-linked immunosorbent assay in the supernatant. Immunohistochemistry and reverse transcription-polymerase chain reaction were performed for the expression of AT1 and AT2 receptors. Angiotensin II binding assays and blockade were studied. Results: High levels of both angiotensins I and II were found in Capan-1 cells, although neither angiotensin I nor angiotensin II was detected in the cell culture supernatant. Reverse transcription-polymerase chain reaction and immunocytochemistry revealed that Capan-1 cells do not express AT1 and AT2 receptors; however, specific binding to the cell membrane was identified for angiotensin II. Neither exogenous angiotensin II nor Dup753 (specific AT1 receptor blocker) affected Capan-1 cells' proliferation or vascular endothelial growth factor secretion. Conclusions: Detection of both angiotensin I and angiotensin II along with specific binding of angiotensin II in Capan-1 cells provides evidence of the existence of a LAGS that operates in an intracrine manner. Intracellular angiotensin II may play a role in the aggressiveness of pancreatic cancer and is a possible target for therapeutic agents.
Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion*

Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk−/− mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1−/− mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1+/+ and Romk1−/− mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1+/+, but such regulation by high K intake was diminished with significant hyperkalemia in Romk1−/− mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K+ secretion in the collecting tubule.
Modulation of Alpha Activity in the Parieto-occipital Area by Distractors during a Visuospatial Working Memory Task: A Magnetoencephalographic Study

Oscillatory brain activity is known to play an essential role in information processing in working memory. Recent studies have indicated that alpha activity (8–13 Hz) in the parieto-occipital area is strongly modulated in working memory tasks. However, the function of alpha activity in working memory is open to several interpretations, such that alpha activity may be a direct neural correlate of information processing in working memory or may reflect disengagement from information processing in other brain areas. To examine the functional contribution of alpha activity to visuospatial working memory, we introduced visuospatial distractors during a delay period and examined neural activity from the whole brain using magnetoencephalography. The strength of event-related alpha activity was estimated using the temporal spectral evolution (TSE) method. The results were as follows: (1) an increase of alpha activity during the delay period as indicated by elevated TSE curves was observed in parieto-occipital sensors in both the working memory task and a control task that did not require working memory; and (2) an increase of alpha activity during the delay period was not observed when distractors were presented, although TSE curves were constructed only from correct trials. These results indicate that the increase of alpha activity is not directly related to information processing in working memory but rather reflects the disengagement of attention from the visuospatial input.
Immigration to the USA and risk for mood and anxiety disorders: variation by origin and age at immigration

Background Risk for mood and anxiety disorders associated with US-nativity may vary across immigrant groups. Method Using data from the National Epidemiological Study of Alcohol and Related Conditions (NESARC), we examined the association of lifetime risk for mood and anxiety disorders with US-nativity and age at immigration across seven subgroups of the US population defined by country or region of ancestral origin: Mexico, Puerto-Rico, Cuba, Central and South America, Western Europe, Eastern Europe, and Africa and the Caribbean. Discrete time survival models were used to compare lifetime risk between the US-born, immigrants who arrived in the USA prior to the age of 13 years and immigrants who arrived in the USA at the age of 13 years or older. Results The association of risk for mood and anxiety disorders with US-nativity varies significantly across ancestral origin groups (p<0.001). Among people from Mexico, Eastern Europe, and Africa or the Caribbean, risk for disorders is lower relative to the US-born among immigrants who arrived at the age of 13 years or higher (odds ratios in the range 0.34–0.49) but not among immigrants who arrived prior to the age of 13 years. There is no association between US-nativity and risk for disorder among people from Western Europe and Puerto Rico. Conclusions Low risk among immigrants relative to the US-born is limited to groups among whom risk for mood and anxiety disorder is low in immigrants who spent their pre-adolescent years outside of the USA.
Initial investigation of organisational factors associated with the implementation of active support

Abstract Background Active support (AS) has been shown to increase the amount of time that residents in shared residential settings are involved in purposeful activities. The organisational processes required to implement AS have been less well researched. Method Staff in community houses answered questions about the occurrence of organisational activities and processes thought to assist AS implementation (e.g., training and teamwork), their understanding of engagement, and their experience of changes in staff practice consistent with AS (including implementation problems). Non-house-based managers were also interviewed about their role in AS implementation. Results Reported occurrence of organisational activities and processes (e.g., training and teamwork) and understanding of engagement were associated with more reports of changes in staff practice and fewer staff reports of implementation problems. Staff reports on the role of non-house-based managers were not associated with reports of changes in staff practice or with reports of fewer AS implementation problems. Non-house-based managers' reports overestimated their role in AS implementation when compared with reports from house-based staff groups. Conclusion While there are limitations in the research design (including the reliance on staff reports), the findings support the importance of wider organisational factors (beyond training programs for direct support staff) as integral to the implementation of AS. There is a need for further research on AS implementation.
Clinical profile of AIDS.

OBJECTIVES To study clinical presentation, spectrum of systemic involvement and opportunistic infections in AIDS patients. METHODS Thirty patient HIV positive by ELISA test, admitted in the department of Medicine SMS Hospital, Jaipur during September, 1996 and December, 1997, were studied. Other causes of immunosuppression were ruled out. These patients having opportunistic infections and/or systemic involvement were diagnosed to have AIDS and per CDC Atlanta criteria. The patients and their spouses were interviewed, examined and investigated according to the pre-designed proforma. RESULTS Twenty five male and five female patients (n=30), having mean age of 32.76+/-8.14 years (range 23-55 years) were studied. Ninety percent were in 20-40 years age group. Forty percent were related to transport services, while 43% had migrated to other areas. Sexual mode of transmission was seen in 21 subjects (70%) (20 males and one female), of which 18 were heterosexual and three bisexual. Four patients (13%) had history of blood transfusion. The commonest presentation was fever in ninety six per cent. Significant weight loss (1.5%+/-9.76%) was present in patients having associated Candida infection (n=15). Tubercular disease was seen in 66% and 30% had atypical presentations. A presumptive diagnosis of PCP was made in 10% while 30% had cryptococcal infection. The most common system involved was GIT (70%). All the patients were tested HBsAg negative. AIDS dementia complex was diagnosed in 13% all aged above 35 years. CONCLUSION Occupation and migration were important risk factors for HIV transmission and heterosexual contact is the commonest mode of spread. Amongst infection, tuberculosis and candidiasis were common.
Evaluation of suicidal thoughts and behaviors in children and adolescents taking paroxetine.

OBJECTIVE The aim of this study was to summarize results of a blinded review of potential suicidal events and analyses comparing incidence rates between paroxetine- and placebo-treated pediatric patients. METHOD One thousand one hundred ninety-one (1191) children and adolescents received paroxetine (n = 642) or placebo (n = 549) during placebo-controlled portions of all acute double-blind trials of paroxetine (n = 5). An expert panel blindly reviewed and categorized all identified cases detected by electronic and manual search of adverse events (AEs), serious AEs, and selected cases as suicidal or non-suicidal behavior. Incidence rates were calculated for suicide-related events and for rating scale items assessing suicidality. RESULTS Suicide-related events occurred more often in paroxetine (22 of 642, 3.4%) than placebo groups (5 of 549, 0.9%); odds ratio (OR) 3.86 (95% CI 1.45, 10.26; p = 0.003). All suicide-related events occurred in adolescents of at least 12 years, except for 1 of 156 paroxetine-treated children. All suicide attempts occurred in major depressive disorder (MDD); few suicide-related events occurred in patients with a primary anxiety disorder. Suicide item analyses did not reveal significant differences between paroxetine and placebo. CONCLUSIONS Adolescents treated with paroxetine showed an increased risk of suicide-related events. Suicidality rating scales did not show this risk difference. The presence of uncontrolled suicide risk factors, the relatively low incidence of these events, and their predominance in adolescents with MDD make it difficult to identify a single cause for suicidality in these pediatric patients.
Validity of the Psycho-Oncology Screening Tool (POST)

Identifying cancer patients who are experiencing psychosocial challenges during the early phase of oncology treatment can prevent escalating patient distress. Standardized screening methods allow the medical team to identify those at high risk for poor adjustment. The purpose of this study was to provide preliminary psychometric evidence for a brief, self-administered screening instrument, the Psycho-Oncology Screening Tool (POST), designed to evaluate emotional and physical distress, depressive symptoms, and social concerns. Participants included 944 radiation oncology patients who completed the POST prior to their treatment appointment and a subgroup of 516 patients who completed the POST and one of six concurrent validity measures. Psychometric analysis included construct validity evidence provided through confirmatory factor analysis (CFA), internal reliability estimates, and concurrent validity estimates assessed with bivariate correlations between POST subscales scores and conceptually similar established measures. A three-factor CFA model was found to produce acceptable model fit, supporting the three domain structure of the POST. Furthermore, the three subscales—emotional and physical distress, depressive symptoms and social concerns—were found to produce acceptable internal reliability estimates (α = .73–.88). Concurrent validity evidence was observed with significant, moderate to large correlations between the POST subscales and all relevant measures (i.e., Profile of Mood States, Hospital Anxiety and Depression Scale, Functional Assessment of Cancer Therapy Fatigue, Beck Depression Inventory, Pain Disability Index, and the Interpersonal Support Evaluation List) with correlations ranged from 0.42 to 0.83, p < 0.01. Patients and clinic staff reported no problems administering or completing the POST. Results of this study support the psychometric soundness as well as the feasibility and acceptability of the POST as a brief screening tool for oncology patients receiving outpatient services.
Novel Topology of BfpE, a Cytoplasmic Membrane Protein Required for Type IV Fimbrial Biogenesis in EnteropathogenicEscherichia coli

ABSTRACT Enteropathogenic Escherichia coli (EPEC) produces the bundle-forming pilus (BFP), a type IV fimbria that has been implicated in virulence, autoaggregation, and localized adherence to epithelial cells. The bfpE gene is one of a cluster of bfpgenes previously shown to encode functions that direct BFP biosynthesis. Here, we show that an EPEC strain carrying a nonpolar mutation in bfpE fails to autoaggregate, adhere to HEp-2 cells, or form BFP, thereby demonstrating that BfpE is required for BFP biogenesis. BfpE is a cytoplasmic membrane protein of the GspF family. To determine the membrane topology of BfpE, we fused bfpEderivatives containing 3′ truncations and/or internal deletions to alkaline phosphatase and/or β-galactosidase reporter genes, whose products are active only when localized to the periplasm or cytoplasm, respectively. In addition, we constructed BfpE sandwich fusions using a dual alkaline phosphatase/β-galactosidase reporter cassette and analyzed BfpE deletion derivatives by sucrose density flotation gradient fractionation. The data from these analyses support a topology in which BfpE contains four hydrophobic transmembrane (TM) segments, a large cytoplasmic segment at its N terminus, and a large periplasmic segment near its C terminus. This topology is dramatically different from that of OutF, another member of the GspF family, which has three TM segments and is predominantly cytoplasmic. These findings provide a structural basis for predicting protein-protein interactions required for assembly of the BFP biogenesis machinery.
THE PENNSYLVANIAN‐PERMIAN VEGETATIONAL TRANSITION: A TERRESTRIAL ANALOGUE TO THE ONSHORE‐OFFSHORE HYPOTHESIS

An analysis of 68 floras from the Pennsylvanian and Early Permian of Euramerica reveals distinct patterns of environmental distribution. Wetland assemblages are the most commonly encountered floras from the Early and Middle Pennsylvanian. Floras from drier habitats characterize the Permian. Both wetland and dry‐site floras occur in the Late Pennsylvanian, but floristic overlap is minimal, which implies strong environmental controls on the distributions of the component species. Drier habitats appear to be the sites of first appearance of orders that become prominent during the Late Permian and Mesozoic. Higher taxa originated in physically heterogeneous, drier habitats, which were geographically marginal throughout most of the Pennsylvanian. They then moved into the lowlands during periods of climatic drying in the Permian, replacing older wetland vegetation. This pattern is analogous to the marine onshore‐offshore pattern of origination and migration. The derivation of Mesozoic wetland clades from the Permian dry‐lowland vegetation completes the parallel. The similarities of the marine and terrestrial patterns suggest that the combination of evolutionary opportunity, created by physical heterogeneity of the environment, and migrational opportunity, created by changing extrinsic conditions, may be underlying factors that transcend the specifics of organism and environment.
The Dr. Jekyll and Mr. Hyde complexity of the macrophage response in disease

Macrophages comprise a highly diverse cell population expressing a continuum of biologic activities dictated by exposure to a plethora of inflammatory cues. Moreover, in contrast to most other hematopoietic populations, macrophages can arise from multiple sites—namely, the bone marrow or yolk sac, adding to the complexity of macrophage biology during health and disease. Nonetheless, it is this very type of diversity that is indispensable for macrophages to respond effectively to pathologic insults. Most of the interest in macrophage biology has been devoted to bone marrow‐derived populations, but it is now becoming clearer that tissue‐resident populations, which arise from distinct hematopoietic compartments, serve critical roles in host defense, including protection against neoplastic disease. Depending on the inflammatory milieu, macrophages can behave as a “two‐edged sword,” playing either host‐protective (i.e., antitumor) or host‐destructive (i.e., protumor) roles. Accordingly, we review herein the mechanisms that instruct macrophage functional diversity within their microenvironments, with special emphasis on transcriptional regulation, which is less understood. Given their polarizing positions in disease processes, we will also provide an overview of strategies that target macrophages or their effector mechanisms for therapeutic purposes.