tbuckley/cabot-search huggingface dataset:
Evaluation of global DNA hypomethylation in human colon cancer tissues by immunohistochemistry and image analysis
Authors: F J Hernandez-Blazquez
Journal: Gut (2000)

<h3>BACKGROUND</h3> Global hypomethylation of DNA is frequently observed in human tumours. This alteration is detected in early adenomas in colorectal tumorigenesis. Information is currently acquired after extraction of DNA from tissues, digestion with nucleases, and analysis by reverse phase chromatography, or treatment with restriction enzymes followed by gel electrophoresis analysis and Southern hybridisation with radiolabelled probes. <h3>AIMS</h3> The purpose of our work was to evaluate the global methylation status of DNA in malignant lesions without loosing the histopathological features of the samples. <h3>PATIENTS</h3> The investigation was performed on paired normal-tumour tissues from 13 patients undergoing surgical resection of colorectal adenocarcinomas. <h3>METHODS</h3> Antibodies raised against 5-methylcytidine can be used to label methyl rich regions in interphase nuclei. This technique was adapted to the study of paraffin embedded tissues and an immunohistochemical method was developed to assess the global methylation status of individual nuclei while preserving cell morphology and tissue architecture. Computer assisted quantification of the staining intensity was performed on malignant and normal zones of human colon tissues to test the correlation between the immunolabelling signal and the respective histological patterns observed. <h3>RESULTS</h3> Qualitative and quantitative differences were observed and measured between the normal and malignant part of each sample. Morphologically altered nuclei displayed densely labelled spots within faintly labelled areas whereas normal nuclei were darker and uniformly stained. Image analysis allowed calculation of the average integrated optical density of the nuclei in both types of tissues, demonstrating a constant and significantly lower intensity for the former type of cells.
Phenotype and Genotype Characterization of Adenine Phosphoribosyltransferase Deficiency
Authors: Guillaume Bollée, Cécile Dollinger, Lucile Boutaud, Delphine Guillemot, Albert Bensman, Jérôme Harambat, Patrice Deteix, Michel Daudon, Bertrand Knebelmann, Irène Ceballos-Picot
Journal: Journal of the American Society of Nephrology (2010)

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder causing 2,8-dihydroxyadenine stones and renal failure secondary to intratubular crystalline precipitation. Little is known regarding the clinical presentation of APRT deficiency, especially in the white population. We retrospectively reviewed all 53 cases of APRT deficiency (from 43 families) identified at a single institution between 1978 and 2009. The median age at diagnosis was 36.3 years (range 0.5 to 78.0 years). In many patients, a several-year delay separated the onset of symptoms and diagnosis. Of the 40 patients from 33 families with full clinical data available, 14 (35%) had decreased renal function at diagnosis. Diagnosis occurred in six (15%) patients after reaching ESRD, with five diagnoses made at the time of disease recurrence in a renal allograft. Eight (20%) patients reached ESRD during a median follow-up of 74 months. Thirty-one families underwent APRT sequencing, which identified 54 (87%) mutant alleles on the 62 chromosomes analyzed. We identified 18 distinct mutations. A single T insertion in a splice donor site in intron 4 (IVS4 + 2insT), which produces a truncated protein, accounted for 40.3% of the mutations. We detected the IVS4 + 2insT mutation in two (0.98%) of 204 chromosomes of healthy newborns. This report, which is the largest published series of APRT deficiency to date, highlights the underdiagnosis and potential severity of this disease. Early diagnosis is crucial for initiation of effective treatment with allopurinol and for prevention of renal complications.
STUDIES OF TISSUE MAINTENANCE
Authors: Peyton Rous, H. P. Gilding
Journal: The Journal of Experimental Medicine (1929)

The spread through the living animal of various highly diffusible dyes has been utilized as an indicator of the ability of the circulation to serve the tissues under various conditions. The method is direct and searching. Blood service to the viscera, as demonstrated by it, is normally far more profuse than to the skin and muscles, for evident physiological reasons. After hemorrhages which greatly reduce the blood bulk service to the viscera is in general still well maintained even though the animal be in extremis. However great the compensatory contraction of the splanchnic vessels may be,-and physiologists have long supposed it to be very great,-it certainly does not suffice to hinder blood service anywhere in the digestive tract. On the other hand the service to certain unessential abdominal organs (spleen, omentum, urinary bladder) is cut off in large part or wholly; and in comparison with the essential viscera, the skin and most of the skeletal muscles of the bled animal are largely deprived of circulation. This neglect takes a curious form, some regions being still fairly served by the blood while others next them are no longer ministered to. In the skin the areas served, or not served, are highly irregular but are to some extent determined in situation by local pressure factors. Within the muscles the neglect is orderly in arrangement and is largely referable to compensatory vaso-constriction. Certain of the muscles, those used in respiration and in swallowing, furnish significant exceptions to the general rule, being excellently served despite the serious general state. The red bone marrow of the depleted organism continues to be well served by the blood even though situated in limbs that are, for the rest, almost devoid of a circulation. The pregnant uterus also is excellently maintained despite the serious general state. The changes are such as would tend to conserve the forces of the depleted organism and to contribute to its recovery.
Expression of perforin and serine esterases by human gamma/delta T cells.
Authors: H Koizumi, C C Liu, L M Zheng, S V Joag, N K Bayne, J Holoshitz, J D Young
Journal: The Journal of Experimental Medicine (1991)

gamma/delta T cells have recently been described in association with a number of disorders, including autoimmune diseases. gamma/delta T cells are thought to play a cytotoxic role, but their mechanism of action is not known. Several granule mediators of cytotoxicity, including a pore-forming protein (perforin), and a family of serine esterases, have been isolated from cytotoxic T lymphocytes (CTL), lymphokine-activated killer (LAK) cells, and natural killer (NK) cells. We demonstrate here that gamma/delta T cells also express these mediators. Northern blots show that gamma/delta T cells express perforin, serine esterase 1 (SE 1), and SE 2. Three polyclonal antisera - raised against murine perforin, a peptide composed of amino acids 1-34 of human perforin, and human peforin expressed in bacteria - all reacted with a 70-kD protein in gamma/delta T cells on Western blots. Immunostaining with antiperforin antisera shows that primary gamma/delta T cells also contain perforin. Electron microscopy reveals that the granules of gamma/delta T cells resemble those of CTL, LAK, and NK cells. Gamma/delta T cells also resemble LAK cells in possessing inclusion bodies in their nuclei. These results imply that gamma/delta T cells resemble other cytolytic lymphocytes in their mechanism of action.
Factor XIIIa in nodular malignant melanoma and Spitz naevi
Authors: J.DENTON KAREN, D.W.K. COTTON, A. WRIGHT, PATRICIA HIRD
Journal: British Journal of Dermatology (1990)

Journal Article Factor XIIIa in nodular malignant melanoma and Spitz naevi Get access J.DENTON KAREN, J.DENTON KAREN Department of Pathology Royal Hallamshire Hospital, Sheffield S10 2RX, U.K. Search for other works by this author on: Oxford Academic Google Scholar D.W.K. COTTON, D.W.K. COTTON Department of Pathology Royal Hallamshire Hospital, Sheffield S10 2RX, U.K. Dr D.W.K.Cotton. Search for other works by this author on: Oxford Academic Google Scholar A. WRIGHT, A. WRIGHT Department of Dermatology, University of Sheffield Medical School, Royal Hallamshire Hospital, Sheffield S10 2RX, U.K. Search for other works by this author on: Oxford Academic Google Scholar PATRICIA HIRD PATRICIA HIRD Department of Pathology Royal Hallamshire Hospital, Sheffield S10 2RX, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 6, 1 December 1990, Pages 783–786, https://doi.org/10.1111/j.1365-2133.1990.tb04197.x Published: 01 December 1990
Transforming Growth Factor β<sub>1</sub> Expression and Activation Is Increased in the Alcoholic Rat Lung
Authors: Rabih I. Bechara, Lou Ann S. Brown, Jesse Roman, Pratibha C. Joshi, David M. Guidot
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Alcohol abuse increases the incidence of acute respiratory distress syndrome more than threefold in patients with septic shock. We have shown that chronic ethanol ingestion in a rat model impairs alveolar epithelial barrier function and enhances lung injury during sepsis. We speculated that transforming growth factor β1 (TGFβ1), a pluripotent cytokine implicated in models of epithelial barrier disruption and lung injury, could mediate alveolar epithelial injury in the alcoholic lung. We report that chronic ethanol ingestion (6 weeks) in rats increased both TGFβ1 mRNA and protein tissue expression (p < 0.05), but alone did not induce the release of TGFβ1 into the alveolar space. However, during endotoxemia, ethanol-fed rats released fivefold more TGFβ1 protein (by ELISA, p < 0.05) into the alveolar space than control-fed rats. Furthermore, lung lavage fluid from endotoxemic, ethanol-fed rats had more biologically active TGFβ1 protein than control-fed rats (p < 0.05), as reflected by anti-TGFβ1 antibody-inhibitable induction of permeability in rat alveolar epithelial monolayers in vitro. We conclude that chronic ethanol ingestion increases lung expression of TGFβ1, which, during endotoxemia, is released and activated in the alveolar space in which it can disrupt the normally tight epithelial barrier. We speculate that this mechanism could contribute to the increased risk of acute respiratory distress syndrome in alcoholic patients.
Early Sonographic Evaluation for Fetal Growth Delay and Congenital Malformations in Pregnancies Complicated by Insulin-Requiring Diabetes
Authors: Zane A Brown, James L Mills, Boyd E Metzger, Robert H Knopp, Joe Leigh Simpson, Lois Jovanovic-Peterson, Kenneth Scheer, Margot I Van Allen, Jerome H Aarons, George F Reed
Journal: Diabetes Care (1992)

Objective It has been reported that early fetal growth retardation may be a useful marker for congenital malformations in diabetic pregnancies. To test this hypothesis, diabetic and nondiabetic women were sonographically evaluated during the first trimester. Research Desihn and Methods Fetal crown-rump lengths were measured sonographically at least once during the first 15 wk of pregnancy in 329 nondiabetic and 312 diabetic women. Of these, 289 nondiabetic and 269 diabetic women had sonograms before 10 wk of gestation and 283 nondiabetic and 269 diabetic women had sonograms between 10 and 15 wk of gestation. Early fetal growth delay was defined as a sonographic gestational age of ≥6 days less than menstrual gestational age. Results The mean crown-rump lengths at 8 wk were 17.9 ± 4.6 mm in the diabetic and 18.7 ± 4.9 mm in the nondiabetic groups (P = 0.13). At 12 wk, the mean fetal crown-rump length was 58.5 ± 8.8 mm for diabetic subjects and 60.6 ± 8.7 mm for nondiabetic subjects (P = 0.04). Between 5 and 9 wk, 28 of 289 (9.7%) fetuses of nondiabetic subjects, 34 of 259 (13.1%) normal fetuses of diabetic subjects, and 2 of 10 (20%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.31, normal vs. malformed diabetic). Between 10 and 15 wk of gestation, 28 of 283 (9.9%) fetuses of nondiabetic subjects, 32 of 256 (12.5%) normal fetuses of diabetic subjects, and 4 of 13 (30.8%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.06, normal vs. malformed diabetic). Early fetal growth delay did not predict a reduced birth weight at term. Conclusions Among insulin-dependent diabetic subjects who were moderately well controlled at conception, statistically significant but mild early fetal growth delay was present but did not appear to be useful clinically in predicting congenital malformations. Recommendations that growth delay demonstrated on early ultrasound be used as a predictor of congenital malformation require careful reexamination.
Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms
Authors: C. Chilvers
Journal: BMJ (2001)

To compare the efficacy of antidepressant drugs and generic counselling for treating mild to moderate depression in general practice. To determine whether the outcomes were similar for patients with randomly allocated treatment and those expressing a treatment preference.Randomised controlled trial, with patient preference arms. Follow up at 8 weeks and 12 months and abstraction of GP case notes.31 general practices in Trent region.Patients aged 18-70 who met research diagnostic criteria for major depression; 103 patients were randomised and 220 patients were recruited to the preference arms.Difference in mean Beck depression inventory score; time to remission; global outcome assessed by a psychiatrist using all data sources; and research diagnostic criteria.At 12 months there was no difference between the mean Beck scores in the randomised arms. Combining the randomised and patient preference groups, the difference in Beck scores was 0.4 (95% confidence interval -2.7 to 3.5). Patients choosing counselling did better than those randomised to it (mean difference in Beck score 4.6, 0.0 to 9.2). There was no difference in the psychiatrist's overall assessment of outcome between any of the groups. 221/265 (83%) of participants with a known outcome had a remission. Median time to remission was shorter in the group randomised to antidepressants than the other three groups (2 months v 3 months). 33/221 (15%) patients had a relapse.Generic counselling seems to be as effective as antidepressant treatment for mild to moderate depressive illness, although patients receiving antidepressants may recover more quickly. General practitioners should allow patients to have their preferred treatment.
Impact of high-risk cytogenetics and prior therapy on outcomes in patients with advanced relapsed or refractory multiple myeloma treated with lenalidomide plus dexaméthasone
Authors: H Avet-Loiseau, J Soulier, J-P Fermand, I Yakoub-Agha, M Attal, C Hulin, L Garderet, K Belhadj, V Dorvaux, S Minvielle, P Moreau
Journal: Leukemia (2010)
Population-Based Study of Competing Mortality in Head and Neck Cancer
Authors: Brent S. Rose, Jong-Hyeon Jeong, Sameer K. Nath, Sharon M. Lu, Loren K. Mell
Journal: Journal of Clinical Oncology (2011)

Patients with head and neck cancer (HNC) are at high risk of death resulting from noncancer causes and second malignancies (ie, competing mortality). Variation in competing mortality risk complicates individual treatment choices and design and interpretation of clinical studies.Using the Surveillance, Epidemiology, and End Results registry, we identified 34,568 patients with nonmetastatic squamous cell carcinoma of the head and neck diagnosed between 1994 and 2003. We developed a multivariable competing-risk regression model to stratify patients according to competing mortality risk and evaluate the impact of this risk on power loss in clinical studies.The 5-year cumulative incidences of all-cause mortality, HNC-specific mortality, and competing mortality were 51.3% (95% CI, 50.8% to 51.9%), 23.8% (95% CI, 23.3% to 24.2%), and 27.6% (95% CI, 26.8% to 28.3%), respectively. Factors associated with increased competing mortality were increasing age, male sex, black race, unmarried status, localized disease, higher socioeconomic status, nonsurgical treatment, and hypopharyngeal, nasopharyngeal, and oral cavity subsites. The 5-year cumulative incidences of competing mortality for patients in low-, medium-, and high-risk score tertiles were 20.0% (95% CI, 18.8% to 21.3%), 27.7% (95% CI, 26.3% to 29.1%), and 33.7% (95% CI, 32.2% to 35.2%), respectively. Compared with patients with low competing mortality risk, relative sample sizes required to show benefit of a treatment regarding all-cause mortality were 12% and 42% higher in the medium- and high-risk groups, respectively.Multiple factors affect risk of competing mortality among patients with HNC. Risk stratification would be useful to identify patients most likely to benefit from treatment intensification.
Learning and control with chaos: From biology to robotics
Authors: Mathias Quoy, Jean-Paul Banquet, Emmanuel Daucé
Journal: Behavioral and Brain Sciences (2001)

After critical appraisal of mathematical and biological characteristics of the model, we discuss how a classical hippocampal neural network expresses functions similar to those of the chaotic model, and then present an alternative stimulus-driven chaotic random recurrent neural network (RRNN) that learns patterns as well as sequences, and controls the navigation of a mobile robot.
Increased haematopoietic progenitor cells are associated with poor outcome in patients with metastatic renal cancer treated with sunitinib
Authors: T. Powles, S. Chowdhury, J. Shamash, A. Bazeos, S. Gillessen, N. Saunders, L. Lim, N. Sarwar, A. Sadev, P. Wilson, P. Nathan, K. Boleti, J. Peters, S. Agrawal
Journal: Annals of Oncology (2010)
Postmortem examinations: general practitioners' knowledge, behaviour, and attitudes
Authors: A Berlin, R Wagstaff, R Bhopal, J Spencer
Journal: BMJ (1994)

Postmortem examinations help to educate doctors and may reassure the relatives of the person who has died.1 They provide information that may alter the future clinical management and outcome of a condition2; help ensure and indicate the quality of death cerification, on which mortality statistics are based; and may provide some indication of the quality of a patient's care. About a fifth of deaths are followed by a postmortem examination; three quarters of these are requested by coroners for legal, not medical, reasons.3 General practitioners issue over a quarter of death certificates (S Denley and A Berlin, unpublished data, 1992), but rarely request postmortem examinations; exact figures are difficult to obtain. We assessed the knowledge, attitudes, and behaviour of general practitioners with respect to postmortem examinations and reports.

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Vaccine Immunity to Pathogenic Fungi Overcomes the Requirement for CD4 Help in Exogenous Antigen Presentation to CD8+ T Cells
Authors: Marcel Wüthrich, Hanna I. Filutowicz, Tom Warner, George S. Deepe, Bruce S. Klein
Journal: The Journal of Experimental Medicine (2003)

Systemic fungal infections with primary and opportunistic pathogens have become increasingly common and represent a growing health menace in patients with AIDS and other immune deficiencies. T lymphocyte immunity, in particular the CD4+ Th 1 cells, is considered the main defense against these pathogens, and their absence is associated with increased susceptibility. It would seem illogical then to propose vaccinating these vulnerable patients against fungal infections. We report here that CD4+ T cells are dispensable for vaccine-induced resistance against experimental fungal pulmonary infections with two agents, Blastomyces dermatitidis an extracellular pathogen, and Histoplasma capsulatum a facultative intracellular pathogen. In the absence of T helper cells, exogenous fungal antigens activated memory CD8+ cells in a major histocompatibility complex class I–restricted manner and CD8+ T cell–derived cytokines tumor necrosis factor α, interferon γ, and granulocyte/macrophage colony-stimulating factor–mediated durable vaccine immunity. CD8+ T cells could also rely on alternate mechanisms for robust vaccine immunity, in the absence of some of these factors. Our results demonstrate an unexpected plasticity of immunity in compromised hosts at both the cellular and molecular level and point to the feasibility of developing vaccines against invasive fungal infections in patients with severe immune deficiencies, including those with few or no CD4+ T cells.
Training carers of stroke patients: randomised controlled trial
Authors: Lalit Kalra, Andrew Evans, Inigo Perez, Anne Melbourn, Anita Patel, Martin Knapp, Nora Donaldson
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Background</b>Informal care givers support disabled stroke patients at home but receive little training for the caregiving role. <b>Objective</b>To evaluate the effectiveness of training care givers in reducing burden of stroke in patients and their care givers. <b>Design</b>A single, blind, randomised controlled trial. <b>Setting</b>Stroke rehabilitation unit. <b>Subjects</b>300 stroke patients and their care givers. <b>Interventions</b>Training care givers in basic nursing and facilitation of personal care techniques. <b>Main outcome measures</b>Cost to health and social services, caregiving burden, patients9 and care givers9 functional status (Barthel index, Frenchay activities index), psychological state (hospital anxiety and depression score), quality of life (EuroQol visual analogue scale) and patients9 institutionalisation or mortality at one year. <b>Results</b>Patients were comparable for age (median 76 years; interquartile range 70-82 years), sex (53% men), and severity of stroke (median Barthel index 8; interquartile range 4-12). The costs of care over one year for patients whose care givers had received training were significantly lower (£10 133 <i>v</i>£13 794 ($18 087 <i>v</i>$24 619; € 15 204 <i>v</i>€20 697); P = 0.001). Trained care givers experienced less caregiving burden (care giver burden score 32 <i>v</i>41; P = 0.0001), anxiety (anxiety score 3 <i>v</i>4; P = 0.0001) or depression (depression score 2 <i>v</i>3; P = 0.0001) and had a higher quality of life (EuroQol score 80 <i>v</i>70; P = 0.001). Patients9 mortality, institutionalisation, and disability were not influenced by caregiver training. However, patients reported less anxiety (3 <i>v</i>4.5; P &lt; 0.0001) and depression (3 <i>v</i>4; P &lt; 0.0001) and better quality of life (65 <i>v</i>60; P = 0.009) in the caregiver training group. <b>Conclusion</b>Training care givers during patients9 rehabilitation reduced costs and caregiver burden while improving psychosocial outcomes in care givers and patients at one year.