tbuckley/cabot-search huggingface dataset:
Effects of sulphasalazine and disodium azodisalicylate on colonic PGE2 concentrations determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls.
Authors: K Lauritsen, J Hansen, P Bytzer, K Bukhave, J Rask-Madsen
Journal: Gut (1984)

The role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium azodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E2 concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE2 concentrations in patients with active ulcerative colitis (n = 11) ranged from 2035-18,000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n = 10; p less than 0.001). In all healthy volunteers PGE2 concentrations decreased slightly (p less than 0.05) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n = 6) increased PGE2 concentrations to values above normal levels (p less than 0.05) which returned to pretrial values (p less than 0.05) on disodium azodisalicylate (2 g/day; n = 7). In conclusion, increased PGE2 in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE2 concentrations were normalised by disodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.
Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis--- cellularity correlates with the degree of enhancement detected by magnetic resonance imaging
Authors: M Bollow
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVE</h3> Sacroiliitis is a hallmark of the spondyloarthropathies (SpA). The degree of inflammation can be quantified by magnetic resonance imaging (MRI). The aim of this study was to further elucidate the pathogenesis of SpA by quantitative cellular analysis of immunostained sacroiliac biopsy specimens and to compare these findings with the degree of enhancement in the sacroiliac joints (SJ) as detected by dynamic MRI. <h3>METHODS</h3> The degree of acute sacroiliitis detected by MRI after intravenous administration of gadolinium-DTPA was quantitatively assessed by calculating the enhancement observed in the SJ and chronic changes were graded as described in 32 patients with ankylosing spondylitis (n=18), undifferentiated SpA (n=12) and psoriatic arthritis (n=2). Back pain was graded on a visual analogue scale (VAS, 0–10) and disease duration (DD) was assessed. Shortly after MRI, SJ of patients with VAS &gt; 5 were biopsied guided by computed tomography. Immunohistological examination was performed using the APAAP technique; only whole sections &gt; 3 mm were counted. <h3>RESULTS</h3> By MRI, chronic changes ⩽ grade II were detected in nine patients (group I, DD 2.5 (SD 2.9) years) and &gt; II in 13 patients (group II, DD 7.3 (SD 4.8) years), while enhancement &lt; 70% was found in eight (group A, DD 5.6 (SD 3.3) years) and &gt; 70% in 12 patients (group B, DD 4.7 (SD 5.8) years). The relative percentage of cartilage (78–93%), bone (7–18%) and proliferating connective tissue (1–4%) was comparable between the groups (range). There were more inflammatory cells in group I compared with group II (mean (SD) 26.7(20.1) versus 5.3 (5.2), p=0.04) and group A compared with B (21.8 (17.3) versus 6.0 (5.6), p=0.05) cells/10 mm<sup>2</sup>), T cells (10.9 (8.5)) being slightly more frequent than macrophages (9.6 (16.8/10 mm<sup>2</sup>)). Clusters of proliferating fibroblasts were seen in three and new vessel formation in seven cases. <h3>CONCLUSION</h3> This study shows that T cells and macrophages are the most frequent cells in early and active sacroiliitis in SpA. The correlation of cellularity and MRI enhancement provides further evidence for the role of dynamic MRI to detect early sacroiliitis.
Molecular epidemiology of multi drug resistance tuberculosis isolates from pulmonary tuberculosis cases from Lucknow, India
Authors: Kanchan Srivastava, Dinesh Kumar Tripathi, Surya Kant, Kishore K. Srivastava
Journal: European Respiratory Journal (2012)

Background: Drug resistant tuberculosis (DR-TB) is a man made problem and major public health concern issue in India as well in abroad. Molecular epidemiology has become an important tool for TB transmission surveillance and it also allows to discriminate between reinfections and relapses as well as to detect cross- contamination of specimens in the laboratory.  Objective: We conducted a molecular epidemiologic analysis of 82 Multi drug resistance  Mycobacterium tuberculosis  isolates from patients presenting pulmonary tuberculosis in Lucknow, India.  Method: We have isolated and cultured mycobacterium on Lowenstein-Jensen medium from sputum samples, collected from patients attending OPD at CSM Medical University, UP. Those isolates which were characterized to be  M. tuberculosis  complex by morphological, biochemical and molecular techniques were tested for their resistance to the four first –line drugs Isoniazid, Rifampicin, Ethambutol and Streptomycin by 1% proportion method on LJ medium. We also performed DR, VNTR typing, and IS6110 on 82 MDR-TB isolates.  Results: The polymorphic data showed significant level of dissimilarities among all isolates. Out of 82 patients, a number of VNTR9s were detected without showing any standard profile. On comparing the DR and VNTR data, we could only demonstrate that polymorphism do occur among clinical isolates of MDR-TB.  Conclusion: Our results suggest that VNTR and DR typing is practically useful for application to molecular epidemiological of  M. tuberculosis.
Gene Expression Profiling Separates Chromophobe Renal Cell Carcinoma from Oncocytoma and Identifies Vesicular Transport and Cell Junction Proteins as Differentially Expressed Genes
Authors: Stephen Rohan, Jiangling J. Tu, Jean Kao, Piali Mukherjee, Fabien Campagne, Xi K. Zhou, Elizabeth Hyjek, Miguel A. Alonso, Yao-Tseng Chen
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To compare gene expression profiles of chromophobe renal cell carcinoma (RCC) and benign oncocytoma, aiming at identifying differentially expressed genes. Experimental Design: Nine cases each of chromophobe RCC and oncocytoma were analyzed by oligonucleotide microarray. Candidate genes that showed consistent differential expression were validated by reverse transcription-PCR using 25 fresh-frozen and 15 formalin-fixed, paraffin-embedded tumor samples. Immunohistochemical analysis was also done for two selected gene products, claudin 8 and MAL2. Results: Unsupervised hierarchical clustering separated the chromophobe RCC and oncocytoma into two distinct groups. By a combination of data analysis approaches, we identified 11 candidate genes showing consistent differential expression between chromophobe RCC and oncocytoma. Five of these genes, AP1M2, MAL2, PROM2, PRSS8, and FLJ20171, were shown to effectively separate these two tumor groups by quantitative reverse transcription-PCR using fresh tissue samples, with similar trends seen on formalin-fixed tissues. Immunohistochemical analysis revealed selective expression of MAL2 and claudin 8 in distal renal tubules, with MAL2 antibody showing differential expression between chromophobe RCC and oncocytoma. Functional analyses suggest that genes encoding tight junction proteins and vesicular membrane trafficking proteins, normally expressed in distal nephrons, are retained in chromophobe RCC and lost or consistently down-regulated in oncocytoma, indicating that these two tumor types, believed to be both derived from distal tubules, are likely distinctive in their histogenesis. Conclusions: We showed that chromophobe RCC and oncocytoma are distinguishable by mRNA expression profiles and a panel of gene products potentially useful as diagnostic markers were identified.
Hyperactivation of the Insulin-like Growth Factor Receptor I Signaling Pathway Is an Essential Event for Cisplatin Resistance of Ovarian Cancer Cells
Authors: Niels Eckstein, Kati Servan, Barbara Hildebrandt, Anne Pölitz, Georg von Jonquières, Sybille Wolf-Kümmeth, Inge Napierski, Alexandra Hamacher, Matthias U. Kassack, Jan Budczies, Manfred Beier, Manfred Dietel, Brigitte Royer-Pokora, Carsten Denkert, Hans-Dieter Royer
Journal: Cancer Research (2009)

Platinum plays a central role in the therapy of ovarian cancer, and the emergence of platinum resistance is a major obstacle for clinical management of the disease. We treated A2780 ovarian cancer cells by weekly cycles of cisplatin over a period of 6 months and unveiled that enhanced insulin-like growth factor I receptor (IGF-IR) expression and autocrine IGF-I are associated with hyperactivation of the IGF-IR and phosphatidylinositol-3-OH kinase (PI3K) pathways in cisplatin-resistant cells. IGF-IR expression levels increased during treatment cycles and correlated with cisplatin resistance. Purified IGF-I induced cisplatin resistance in diverse ovarian cancer cell lines, and small molecule inhibitors proved that IGF-IR and PI3K are essential for cisplatin resistance. Similar results were obtained with BG-1 ovarian cancer cells. Cytogenetic and array comparative genomic hybridization analyses revealed selection and de novo formation of chromosomal alterations during resistance development. An analysis of gene expression profiles of primary ovarian carcinomas identified the regulatory subunit PIK3R2 of PI3-kinase as a significant negative prognosis factor for ovarian cancer. We conclude that targeting the IGF-IR and the PI3K pathways is a promising new strategy to treat cisplatin-resistant ovarian carcinomas.
Perinatal Blockade of B7-1 and B7-2 Inhibits Clonal Deletion of Highly Pathogenic Autoreactive T Cells
Authors: Jian-Xin Gao, Huiming Zhang, Xue-Feng Bai, Jing Wen, Xincheng Zheng, Jinqing Liu, Pan Zheng, Yang Liu
Journal: The Journal of Experimental Medicine (2002)

A number of in vitro studies have suggested that costimulatory molecules B7-1 and B7-2 and their receptor CD28 can promote clonal deletion, and limited in vivo studies have indicated that CD28 is involved in the clonal deletion of some T cells. However, the significance of B7-mediated clonal deletion in preventing autoimmune diseases has not been studied systematically. Here we report that the perinatal blockade of B7-1 and B7-2 substantially inhibits the clonal deletion of T cells in the thymus and leads to an accumulation of T cells capable of inducing fatal multiorgan inflammation. These results reveal a critical role for costimulatory molecules B7-1 and B7-2 in deleting pathogenic autoreactive T cells in the thymus. The critical role of B7-1 and B7-2 in T cell clonal deletion may explain, at least in part, the paradoxical increase of autoimmune disease in mice deficient for this family of costimulatory molecules, such as cytotoxic T lymphocyte associated molecule 4, CD28, and B7-2. The strong pathogenicity of the self-reactive T cells supports a central hypothesis in immunology, which is that clonal deletion plays an important role in preventing autoimmune diseases.
Expression of R120G–αB-Crystallin Causes Aberrant Desmin and αB-Crystallin Aggregation and Cardiomyopathy in Mice
Authors: Xuejun Wang, Hanna Osinska, Raisa Klevitsky, A. Martin Gerdes, Michelle Nieman, John Lorenz, Timothy Hewett, Jeffrey Robbins
Journal: Circulation Research (2001)

Abstract —Upregulation of αB-crystallin (CryAB), a small heat shock protein, is associated with a variety of diseases, including the desmin-related myopathies. CryAB, which binds to both desmin and cytoplasmic actin, may participate as a chaperone in intermediate filament formation and maintenance, but the physiological consequences of CryAB upregulation are unknown. A mutation in CryAB, R120G, has been linked to a familial desminopathy. However, it is unclear whether the mutation is directly causative. We created multiple transgenic mouse lines that overexpressed either murine wild-type CryAB or the R120G mutation in cardiomyocytes. Overexpression of wild-type CryAB was relatively benign, with no increases in mortality and no induction of desmin-related cardiomyopathy even in a line in which CryAB mRNA expression was increased ≈104-fold and the protein level increased by 11-fold. In contrast, lines expressing the R120G mutation were compromised, with a high-expressing line exhibiting 100% mortality by early adulthood. Modest expression levels resulted in a phenotype that was strikingly similar to that observed for the desmin-related cardiomyopathies. The desmin filaments in the cardiomyocytes were overtly affected, myofibril alignment was significantly impaired, and a hypertrophic response occurred at both the molecular and cellular levels. The data show that the R120G mutation causes a desminopathy, is dominant negative, and results in cardiac hypertrophy.
Mechanistic insight into digoxin inactivation by<i>Eggerthella lenta</i>augments our understanding of its pharmacokinetics
Authors: Henry J Haiser, Kristen L Seim, Emily P Balskus, Peter J Turnbaugh
Journal: Gut Microbes (2014)

The human gut microbiota plays a key role in pharmacology, yet the mechanisms responsible remain unclear, impeding efforts toward personalized medicine. We recently identified a cytochrome-encoding operon in the common gut Actinobacterium Eggerthella lenta that is transcriptionally activated by the cardiac drug digoxin. These genes represent a predictive microbial biomarker for the inactivation of digoxin. Gnotobiotic mouse experiments revealed that increased protein intake can limit microbial drug inactivation. Here, we present a biochemical rationale for how the proteins encoded by this operon might inactivate digoxin through substrate promiscuity. We discuss digoxin signaling in eukaryotic systems, and consider the possibility that endogenous digoxin-like molecules may have selected for microbial digoxin inactivation. Finally, we highlight the diverse contributions of gut microbes to drug metabolism, present a generalized approach to studying microbe-drug interactions, and argue that mechanistic studies will pave the way for the clinical application of this work.
Correlation of salivary and gastric acid secretions in duodenal ulcer patients in tropics
Authors: P. L. Nagwani, S. R. Naik, S. Sachdev, P. N. Srivastava, H. K. Chuttani
Journal: Gut (1979)

Salivary flow rates on mechanical stimulation by forced spitting method and by chemical stimulation with 10% citric acid and gastric acidity using an augmented histamine test were determined in 20 adult patients suffering from duodenal ulcer and in 20 adult control subjects matched with respect to age, sex, and body weight. Salivary flow rates were found to be much higher in response to chemical than to mechanical stimulus in both the groups. Duodenal ulcer patients exhibited an unexplained exaggerated response to chemical stimulation. Salivary pH, amylase, sodium, and potassium levels showed no significant differences between the two groups. The flow rates by either method generally showed a positive correlation with body weight in both the groups. Histamine stimulated gastric acid secretion was higher in duodenal ulcer patients than in controls. Acid secretion did not appear to be related to weight and also showed no consistent correlation with the salivary flow rates. It was concluded that (1) the salivary flow was dependent on body weight in duodenal ulcer patients as well as in controls, and (2) although salivary gland hyperplasia could be postulated in duodenal ulcer patients on the basis of increased salivary flow, the latter was poorly related to maximal acid secretion and therefore, if a combination of parietal cell and salivary gland hyperplasia did exist, it should be considered as incidental.
Concerted evolution of the cow epsilon 2 and epsilon 4 beta-globin genes.
Authors: J C Schimenti, C H Duncan
Journal: Molecular Biology and Evolution (1985)

The nucleotide sequences of the cow epsilon 2 and epsilon 4 globin genes were determined. The sequences were 95% identical. These genes arose via a four-gene block duplication that also gave rise to the bovine fetal (gamma) and adult (beta) genes. Their deduced amino acid sequences are unlike any previously reported fetal or adult globins; rather, comparison to other mammalian globin genes indicates that they are embryonic in nature. The sequence data indicate that these two genes have converted each other during evolution. Pairwise comparison to the corresponding goat genes shows greater similarity between paralogues than between more directly related orthologues. This is in direct contrast to the situation between the cow and goat fetal and adult genes. These observations suggest that the frequency of DNA conversion or the fixation of conversion events may vary in different locations of the cow beta-globin cluster.
Maintenance of remission in autoimmune chronic active hepatitis with azathioprine after corticosteroid withdrawal
Authors: Anthony J. Stellon, John J. Keating, Philip J. Johnson, Ian G. McFarlane, Roger Williams
Journal: Hepatology (1988)

Forty-seven patients with autoimmune chronic active hepatitis in remission on azathioprine and/or prednisolone were entered into a randomized controlled trial to assess the value of azathioprine alone in maintenance of remission. The trial design involved administering azathioprine at a dose of 2 mg per kg to one-half of the patients, in whom prednisolone was then gradually withdrawn, whereas the remaining patients, the “control” group, were maintained on the conventional combination regimen of azathioprine (1 mg per kg) with prednisolone. At 1 year there was no significant difference in respect of standard liver function tests or histological appearances between the two groups. Two patients in the azathioprine group required dosage reduction because of myelosuppression and both subsequently relapsed. Following withdrawal of corticosteroids Cushingoid features were lost with a return of weight and blood pressure to normality. In 75% of the patients, corticosteroid withdrawal was marked by arthralgias and myalgias which lasted for up to 12 months: no other major side effects of corticosteroid withdrawal were noted. Thus in the majority of cases, remissions in autoimmune chronic active hepatitis which are induced by corticosteroids can be maintained with azathioprine alone.
Laboratory capability and surveillance testing for Middle East respiratory syndrome coronavirus infection in the WHO European Region, June 2013
Authors: D Pereyaslov, P Rosin, D Palm, H Zeller, D Gross, C S Brown, M  J Struelens, Collective on behalf of the MERS-CoV Working Group
Journal: Eurosurveillance (2014)

Since September 2012, over 90 cases of respiratory disease caused by a novel coronavirus, now named Middle East respiratory syndrome coronavirus (MERSCoV), have been reported in the Middle East and Europe. To ascertain the capabilities and testing experience of national reference laboratories across the World Health Organization (WHO) European Region to detect this virus, the European Centre for Disease Prevention and Control (ECDC) and the WHO Regional Office for Europe conducted a joint survey in November 2012 and a follow-up survey in June 2013. In 2013, 29 of 52 responding WHO European Region countries and 24 of 31 countries of the European Union/European Economic Area (EU/EEA) had laboratory capabilities to detect and confirm MERS-CoV cases, compared with 22 of 46 and 18 of 30 countries, respectively, in 2012. By June 2013, more than 2,300 patients had been tested in 23 countries in the WHO European Region with nine laboratory-confirmed MERS-CoV cases. These data indicate that the Region has developed significant capability to detect this emerging virus in accordance with WHO and ECDC guidance. However, not all countries had developed capabilities, and the needs to do so should be addressed. This includes enhancing collaborations between countries to ensure diagnostic capabilities for surveillance of MERS-CoV infections across the European Region.
Specific enrichment of the suppressor T cell bearing I-J determinants: parallel functional and serological characterizations.
Authors: K Okumura, T Takemori, T Tokuhisa, T Tada
Journal: The Journal of Experimental Medicine (1977)

A simple procedure to enrich the antigen (keyhole limpet hemocyanin, KLH)-specific suppressor T cell was described. The suppressor T cell from KLH)-immunized mice specifically bound to the KLH-coated Sephadex G-200 column at 37 degrees C, and was eluted from the column by cold (0-4 degrees C) medium. The helper T cell did not bind to the column under the identical condition. The suppressor T cell thus obtained had 100 times as potent suppressor activity as the original spleen cells in in vivo and in vitro secondary antibody responses against a hapten coupled to KLH. This procedure also enriched the cells bearing I-J determinants and Lyt-2,3 alloantigens, allowing us to study the phenotypic expressions on the suppressor T cell by direct serological procedures as well as by the use of the fluorescence activated cell sorter. Parallel functional and serological analyses indicated that the antigen-specific suppressor T cell belongs to a population of I-J+, Lyt-2+,3+ and Fc R- T cells.
Pressure Ulcer Prevention and Management
Authors: Courtney H. Lyder
Journal: JAMA (2003)

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