tbuckley/cabot-search huggingface dataset:
Acetylated sialic acid residues and blood group antigens localise within the epithelium in microvillous atrophy indicating internal accumulation of the glycocalyx
Authors: A D Phillips, A Brown, S Hicks, S Schüller, S H Murch, J A Walker-Smith, D M Swallow
Journal: Gut (2004)

Microvillous atrophy, a disorder of intractable diarrhoea in infancy, is characterised by the intestinal epithelial cell abnormalities of abnormal accumulation of periodic acid-Schiff (PAS) positive secretory granules within the apical cytoplasm and the presence of microvillous inclusions. The identity of the PAS positive material is not known, and the aim of this paper was to further investigate its composition.Formaldehyde fixed sections were stained with alcian blue/PAS to identify the acidic or neutral nature of the material, phenylhydrazine blocking was employed to stain specifically for sialic acid, and saponification determined the presence of sialic acid acetylation. The specificity of sialic acid staining was tested by digestion with mild sulphuric acid. Expression of blood group related antigens was tested immunochemically.Alcian blue/PAS staining identified a closely apposed layer of acidic material on the otherwise neutral (PAS positive) brush border in controls. In microvillous atrophy, a triple layer was seen with an outer acidic layer, an unstained brush border region, and accumulation within the epithelium of a neutral glycosubstance that contained acetylated sialic acid. Blood group antigens were detected on the brush border, in mucus, and within goblet cells in controls. In microvillous atrophy they were additionally expressed within the apical cytoplasm of epithelial cells mirroring the PAS abnormality. Immuno electron microscopy localised expression to secretory granules.A neutral, blood group antigen positive, glycosubstance that contains acetylated sialic acid accumulates in the epithelium in microvillous atrophy. Previous studies have demonstrated that the direct and indirect constitutive pathways are intact in this disorder and it is speculated that the abnormal staining pattern reflects accumulation of glycocalyx related material.
Indicator Dispersal by Convection and Diffusion in Fluid Flow Through a Tube
Authors: DAVID C. RICH, JOHN W. GOODMAN
Journal: Circulation Research (1965)

A tube is filled with water containing indicator and then the indicator is washed out by laminar flow of indicator-free water. Given a measurement of mean volume concentration of indicator in the effluent as a function of time, a theoretical expression is derived for the pattern of indicator delivery in the case where diffusion is superimposed on convective transport. Satisfactory experimental verification of the theoretical expressions was obtained.
Connective tissue deposits in MRL/1 mice.
Authors: A Pataki, C H Rordorf
Journal: Annals of the Rheumatic Diseases (1987)

IgA serum levels and diseaseIdiopathic haemarthrosis with activity in ankylosing spondylitis chondrocalcinosis SIR, I read with considerable interest the report by Franssen and associates of a prospective study of IgA serum levels and disease activity in ankylosing spondylitis (AS).'In their comparative trial of phenylbutazone and diflunisal, serum IgA, erythrocyte sedimentation rate, and disease activity all decreased during regular drug treat- ment, suggesting a disease modifying effect of the non- steroidal anti-inflammatory drugs (NSAIDs) in AS.That NSAIDs affect favourably the natural course of AS is not widely appreciated.2In fact this concept first became clear to me after completion of a five year trial of indomethacin in 28 patients that dates back to 1968.3As judged by several criteria, including articular pain, dura- tion of morning stiffness, onset of fatigue, and joint mobility, the overall response to indomethacin was rated as good in 21 patients, fair in five, and poor in two.After receiving indomethacin for an average period of 33 months, 21 of the 28 patients were in the American Rheumatism Association functional class I.4 Only one patient had been so classified before the drug trial.The average Westergren erythrocyte sedimentation rate values for all 28 patients decreased during the drug trial from 39 to 26 mm/h (p<0-01, Student's t test).Indomethacin was discontinued in three patients-in two because of a poor response to the drug and in one because of an adverse reaction.Clearly, the results of this trial suggest that indomethacin favourably alters the course of AS.In 1981, 18 years after the first patients were entered into this trial, it was possible to locate and reassess 14 of the remaining 25 patients.5Of the 14, four had achieved remission and required no further drug therapy.In- domethacin had been discontinued in four patients-in two because of gastrointestinal side effects and in two because of a more favourable effect from another NSAID.The remaining six patients continue to receive indomethacin at an average daily dosage of 100 mg (range 75-100 mg) and continue to benefit from its long term use.
First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)—a systematic review and individual patient data meta-analysis
Authors: B. Kasenda, A.J.M. Ferreri, E. Marturano, D. Forst, J. Bromberg, H. Ghesquieres, C. Ferlay, J.Y. Blay, K. Hoang-Xuan, E.J. Pulczynski, A. Fosså, Y. Okoshi, S. Chiba, K. Fritsch, A. Omuro, B.P. O'Neill, O. Bairey, S. Schandelmaier, V. Gloy, N. Bhatnagar, S. Haug, S. Rahner, T.T. Batchelor, G. Illerhaus, M. Briel
Journal: Annals of Oncology (2015)

To investigate prognosis and effects of first-line therapy in elderly primary central nervous system lymphoma (PCNSL) patients.A systematic review of studies about first-line therapy in immunocompetent patients ≥60 years with PCNSL until 2014 and a meta-analysis of individual patient data from eligible studies and international collaborators were carried out.We identified 20 eligible studies; from 13 studies, we obtained individual data of 405 patients, which were pooled with data of 378 additional patients (N = 783). Median age and Karnofsky Performance Score (KPS) was 68 years (range: 60-90 years) and 60% (range: 10%-100%), respectively. Treatments varied greatly, 573 (73%) patients received high-dose methotrexate (HD-MTX)-based therapy. A total of 276 patients received whole-brain radiotherapy (median 36 Gy, range 28.5-70 Gy). KPS ≥ 70% was the strongest prognostic factor for mortality [hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.41-0.62]. After a median follow-up of 40 months, HD-MTX-based therapy was associated with improved survival (HR 0.70, 95% CI 0.53-0.93). There was no difference between HD-MTX plus oral chemotherapy and more aggressive HD-MTX-based therapies (HR 1.39, 95% CI 0.90-2.15). Radiotherapy was associated with an improved survival, but correlated with an increased risk for neurological side-effects (odds ratio 5.23, 95% CI 2.33-11.74).Elderly PCNSL patients benefit from HD-MTX-based therapy, especially if combined with oral alkylating agents. More aggressive HD-MTX protocols do not seem to improve outcome. WBRT may improve outcome, but is associated with increased risk for neurological side-effects. Prospective trials for elderly PCNSL patients are warranted.
Risk Factors for Advanced Colonic Neoplasia and Hyperplastic Polyps in Asymptomatic Individuals
Authors: David A. Lieberman
Journal: JAMA (2003)

Knowledge of risk factors for colorectal neoplasia could inform risk reduction strategies for asymptomatic individuals. Few studies have evaluated risk factors for advanced colorectal neoplasia in asymptomatic individuals, compared risk factors between persons with and without polyps, or included most purported risk factors in a multivariate analysis.To determine risk factors associated with advanced colorectal neoplasia in a cohort of asymptomatic persons with complete colonoscopy.Prospective, cross-sectional study of 3121 asymptomatic patients aged 50 to 75 years from 13 Veterans Affairs medical centers conducted between February 1994 and January 1997. All participants had complete colonoscopy to determine the prevalence of advanced neoplasia, defined as an adenoma that was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. Variables examined included history of first-degree relative with colorectal cancer, prior cholecystectomy, serum cholesterol level, physical activity, smoking, alcohol use, and dietary factors.An age-adjusted analysis was performed for each variable to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) associated with having advanced neoplasia compared with having no polyps. We developed a multivariate logistic regression model to identify the most informative risk factors. A secondary analysis examined risk factors for having hyperplastic polyps compared with having no polyps and compared with having advanced neoplasia.Three hundred twenty-nine participants had advanced neoplasia and 1441 had no polyps. In multivariate analyses, we found positive associations for history of a first-degree relative with colorectal cancer (OR, 1.66; 95% CI, 1.16-2.35), current smoking (OR, 1.85; 95% CI, 1.33-2.58), and current moderate to heavy alcohol use (OR, 1.02; 95% CI, 1.01-1.03). Inverse associations were found for cereal fiber intake (OR, 0.95; 95% CI, 0.91-0.99), vitamin D intake (OR, 0.94; 95% CI, 0.90-0.99), and use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR, 0.66; 95% CI, 0.48-0.91). In the univariate analysis, the inverse association was found with cereal fiber intake greater than 4.2 g/d, vitamin D intake greater than 645 IU/d, and daily use of NSAIDs. Marginal factors included physical activity, daily multivitamin use, and intake of calcium and fat derived from red meat. No association was found for body mass index, prior cholecystectomy, or serum cholesterol level. Three hundred ninety-one patients had hyperplastic polyps as the worst lesion found at colonoscopy. Risk variables were similar to those for patients with no polyps, except that past and current smoking were associated with an increased risk of hyperplastic polyps.Our data endorse several important risk factors for advanced colonic neoplasia and provide a rationale for prudent risk reduction strategies. Further study is needed to determine if lifestyle changes can moderate the risk of colorectal cancer.
Medical ethics teaching. Report of a National Medical School Survey
Authors: R. M. Veatch
Journal: JAMA (1976)

Medical ethics teaching was surveyed at American medical schools. Of 107 schools that responded, 97 indicated some kind of medical ethics teaching. This included, however, 19 schools where teaching was only by discussion of ethical issues in courses not primarily identified as ethics courses. Fifty-six institutions (up from 17 in 1972) reported that they conducted special conferences, lectures, or seminars on issues in medical ethics. Specific medical ethics electives were offered in 47 schools; some kind of required course existed at six institutions. The number of faculties with major commitments to medical ethics teaching increased approximately 50% (from 19 to 31). Several schools now have departments or interdepartmental teaching programs with formal structure and permanent staff.
Procarbazine, Lomustine, and Vincristine (PCV) Chemotherapy for Anaplastic Astrocytoma: A Retrospective Review of Radiation Therapy Oncology Group Protocols Comparing Survival With Carmustine or PCV Adjuvant Chemotherapy
Authors: Michael D. Prados, Charles Scott, Walter J. Curran, Diana F. Nelson, Steve Leibel, Simon Kramer
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To determine any differences in outcome for patients with anaplastic astrocytoma (AA) treated with adjuvant carmustine (BCNU) versus procarbazine, lomustine, and vincristine (PCV) chemotherapy. MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) database was reviewed for patients with newly diagnosed AA treated according to protocols that included either BCNU or PCV adjuvant chemotherapy. All patients were treated with radiation therapy. The outcome analysis included overall survival, taking into account patient age, extent of resection, Karnofsky performance status (KPS), and treatment group (BCNU v PCV). Stratified and nonstratified Cox proportional hazards models were used, as well as an analysis using matched cases between the groups. RESULTS: A total of 257 patients were treated with BCNU according to RTOG protocols 70-18, 83-02, and 90-06; 175 patients were treated with PCV according to RTOG protocol 94-04. All pretreatment characteristics except KPS were well balanced by treatment group; 61% of the BCNU group had a KPS of 90 to 100 compared with 73% of the PCV group (P = .0075). No statistically significant difference in survival was observed in any age group or by KPS or extent of surgery. The stratified analysis also showed no trends for improved survival by treatment group (P = .40). The Cox model identified only age, KPS, and extent of surgery as important variables influencing survival, not treatment group. Matching cases between groups using age, KPS, and surgery resulted in 133 matched pairs. No difference in survival was observed (P = .41). In a Cox model in which each matched pair is a strata, there was no difference between groups (P = .20). CONCLUSION: Using this retrospective analysis, there does not seem to be any survival benefit to PCV chemotherapy. Future phase III studies for patients with AA may need to consider whether BCNU or PCV is used in the control arm.
Treatment of shoulder complaints in general practice: long term results of a randomised, single blind study comparing physiotherapy, manipulation, and corticosteroid injection
Authors: J. C Winters, W. Jorritsma, K. H Groenier, J. S Sobel, B. M.-d. Jong, H. J Arendzen
Journal: BMJ (1999)

Descriptive studies have shown that shoulder complaints can be persistent and recurrent, requiring long term evaluation of treatment.1 Unfortunately, in most randomised studies comparing treatments for shoulder complaints the study period varies from a few weeks (trials of non-steroidal anti-inflammatory drugs) to 3-6 months (injection therapy and physiotherapy trials).2–4)

In a trial in 1994-5 of treatment of shoulder complaints in general practice we showed that in a study period of 11 weeks, injection therapy with a corticosteroid was superior to physiotherapy and manipulative therapy in the patients whose complaints originated from the structures of the glenohumeral joint, the subacromial space, or the acromioclavicular joint (synovial group).5 In the patients whose complaints related to functional disorders of the cervical spine, the upper thoracic spine, or the adjoining ribs (shoulder girdle group), manipulation was superior to physiotherapy. To assess the various treatments in …
Interleukin 4 counteracts the interleukin 2-induced proliferation of monoclonal B cells.
Authors: S Karray, T DeFrance, H Merle-Béral, J Banchereau, P Debré, P Galanaud
Journal: The Journal of Experimental Medicine (1988)

B cells from patients suffering from B-type chronic lymphocytic leukemia (B-CLL) are susceptible to the effects of several interleukins. Using the cells from 12 different patients we show that IL-4 does not synergize with anti-mu antibody for the enhancement of DNA synthesis. Moreover IL-4 profoundly (90%) suppresses the response to IL-2 in the 10 patient responders to this interleukin. This suppression occurs whether IL-2 is used alone, in costimulation with anti-mu antibody, or in synergy with IFN-gamma. In no instance did IL-4 induce terminal differentiation. This negative effect of IL-4 can take place in monoclonal B-CLL cells where IL-4 enhances the expression of CD23. IL-4 does not interfere with the upregulation of CD25 by IL-2. Thus, IL-4 may display inhibitory effects on the proliferative response of selected B cell populations. The antagonism between IL-4 and IL-2 has important implications for the potential use of cytokines in the management of B-CLL patients.
The role of autophagy emerging in postinfarction cardiac remodelling
Authors: Hiromitsu Kanamori, Genzou Takemura, Kazuko Goto, Rumi Maruyama, Akiko Tsujimoto, Atsushi Ogino, Toshiaki Takeyama, Tomonori Kawaguchi, Takatomo Watanabe, Takako Fujiwara, Hisayoshi Fujiwara, Mitsuru Seishima, Shinya Minatoguchi
Journal: Cardiovascular Research (2011)

Autophagy is activated in cardiomyocytes in ischaemic heart disease, but its dynamics and functional roles remain unclear after myocardial infarction. We observed the dynamics of cardiomyocyte autophagy and examined its role during postinfarction cardiac remodelling. Myocardial infarction was induced in mice by ligating the left coronary artery. During both the subacute and chronic stages (1 and 3 weeks postinfarction, respectively), autophagy was found to be activated in surviving cardiomyocytes, as demonstrated by the up-regulated expression of microtubule-associated protein-1 light chain 3-II (LC3-II), p62 and cathepsin D, and by electron microscopic findings. Activation of autophagy, specifically the digestion step, was prominent in cardiomyocytes 1 week postinfarction, especially in those bordering the infarct area, while the formation of autophagosomes was prominent 3 weeks postinfarction. Bafilomycin A1 (an autophagy inhibitor) significantly aggravated postinfarction cardiac dysfunction and remodelling. Cardiac hypertrophy was exacerbated in this group and was accompanied by augmented ventricular expression of atrial natriuretic peptide. In these hearts, autophagic findings (i.e. expression of LC3-II and the presence of autophagosomes) were diminished, and activation of AMP-activated protein kinase was enhanced. Treatment with rapamycin (an autophagy enhancer) brought about opposite outcomes, including mitigation of cardiac dysfunction and adverse remodelling. A combined treatment with bafilomycin A1 and rapamycin offset each effect on cardiomyocyte autophagy and cardiac remodelling in the postinfarction heart. These findings suggest that cardiomyocyte autophagy is an innate mechanism that protects against progression of postinfarction cardiac remodelling, implying that augmenting autophagy could be a therapeutic strategy.
Molecular Profiling of ADAM12 in Human Bladder Cancer
Authors: Camilla Fröhlich, Reidar Albrechtsen, Lars Dyrskjøt, Lise Rudkjær, Torben F. Ørntoft, Ulla M. Wewer
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We have previously found ADAM12, a disintegrin and metalloprotease, to be an interesting biomarker for breast cancer. The purpose of this study was to determine the gene and protein expression profiles of ADAM12 in different grades and stages of bladder cancer. Experimental Design: ADAM12 gene expression was evaluated in tumors from 96 patients with bladder cancer using a customized Affymetrix GeneChip. Gene expression in bladder cancer was validated using reverse transcription-PCR, quantitative PCR, and in situ hybridization. Protein expression was evaluated by immunohistochemical staining on tissue arrays of bladder cancers. The presence and relative amount of ADAM12 in the urine of cancer patients were determined by Western blotting and densitometric measurements, respectively. Results: ADAM12 mRNA expression was significantly up-regulated in bladder cancer, as determined by microarray analysis, and the level of ADAM12 mRNA correlated with disease stage. Reverse transcription-PCR, quantitative PCR, and in situ hybridization validated the gene expression results. Using immunohistochemistry, we found ADAM12 protein expression correlated with tumor stage and grade. Finally, ADAM12 could be detected in the urine by Western blotting; ADAM12 was present in higher levels in the urine from patients with bladder cancer compared with urine from healthy individuals. Significantly, following removal of tumor by surgery, in most bladder cancer cases examined, the level of ADAM12 in the urine decreased and, upon recurrence of tumor, increased. Conclusions: ADAM12 is a promising biomarker of bladder cancer.
Effect of initial sarcomere length on sarcomere kinetics and force development in single frog atrial cardiac cells.
Authors: M Tarr, J W Trank, K K Goertz, P Leiffer
Journal: Circulation Research (1981)

We studied sarcomere performance in single isolated intact frog atrial cells using techniques that allow direct measurement of sarcomere length and force. The purpose of this investigation was to determine whether length-dependent alterations in contractile activation occur in the single isolated cardiac cell. This was accomplished by determining the effect of initial sarcomere length on the time course of sarcomere shortening and force development during auxotonic twitch contractions. The results presented in this paper demonstrate that the velocity of sarcomere shortening, the rate of force development, and the magnitude of force development during auxotonic twitch contractions all increase as initial sarcomere length increases over the range of about 2 micrometers to greater than 3 micrometers. These results indicate that the level of contractile activation increases as initial sarcomere length increases. Also, results are presented that indicate that the rate of increase of contractile activation during a twitch contraction also increases as initial sarcomere length increases. These length-dependent effects on contractile activation in conjunction with the slow time course of contractile activation cause the force-velocity-length relationship to be time-dependent: i.e., the velocity of sarcomere shortening at a given sarcomere length and load depends on the time during the contraction when the sarcomere reaches that length. The results suggest that length-dependent alterations in contractile activation may play a major role in the improved contractile performance that accompanies an increase in initial sarcomere length in cardiac muscle.