tbuckley/cabot-search huggingface dataset:
Pancreas after Kidney Transplants in Posturemic Patients with Type I Diabetes Mellitus
Authors: ANGELIKA C. GRUESSNER, DAVID E. R. SUTHERLAND, DAVID L. DUNN, JOHN S. NAJARIAN, ABHI HUMAR, RAJA KANDASWAMY, RAINER W. G. GRUESSNER
Journal: Journal of the American Society of Nephrology (2001)

Pancreas after previous kidney (PAK) transplants are an attractive option for type 1 diabetic patients because of the short waiting time and use of living kidney donors. Factors associated with the increased success rate of PAK transplants in four immunosuppressive eras were analyzed. Between July 1, 1978, and April 30, 2000, 406 PAK transplants were performed in posturemic patients. Four immunosuppressive eras were analyzed: (1) the precyclosporine era, era 1 (n = 65; 16%); (2) the cyclosporine era, era 2 (n = 109; 27%); (3) the tacrolimus era with monoclonal or polyclonal antibody induction therapy, era 3 (n = 104; 26%); and (4) the tacrolimus era with monoclonal and polyclonal antibody induction therapy, era 4 (n = 128; 31%). Patient and graft survival, rejection, and technical failure rates were calculated. Patient survival rates have remained high over time, from 91% (era 1) to 96% (era 4) at 1 yr posttransplant. Pancreas graft survival rates with primary cadaver transplants have significantly increased, from 17% (era 1) to 81% (era 4) at 1 yr. The rate of graft loss from rejection has significantly decreased, from 78% (era 1) to 9% (era 4) at 1 yr. Results were best when donors and recipients were matched for at least one antigen per HLA locus. Kidney graft survival was higher in PAK transplant recipients compared with diabetic recipients of kidney transplants alone from the time of the kidney as well as the pancreas transplants. PAK recipients now enjoy >80% graft survival at 1 yr. This improvement in outcome results from better immunosuppression, good matching, and close posttransplant monitoring for rejection.
Prognostic significance of nucleolar organizer regions in hepatocellular carcinoma
Authors: Koichi Shimizu, Ryohei Izumi, Toru Ii, Keiichi Muraoka, Tetsuya Inoue, Wataru Fukushima, Koya Sakamoto, Takashi Tani, Tetsuo Hashimoto, Masao Yagi, Itsuo Miyazaki, Akitaka Nonomura
Journal: Hepatology (1995)

It has been suggested that the number of argyrophilic nucleolar organizer regions (AgNORs) correlates with cellular activity and the aggressiveness of malignancy. The mean number of AgNORs per nucleus may, therefore, be a prognostic factor for hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic significance of the number of AgNORs in HCC. The silver-staining technique was applied to surgically resected specimens to indicate AgNORs. Eighty-nine of the specimens were of HCC, 23 were of normal liver adjacent to HCC, and 32 were of cirrhotic liver adjacent to HCC. The number of AgNORs of HCC (mean +/- SD, 3.26 +/- 1.23) was significantly higher than those of normal liver (1.37 +/- 0.13) and cirrhotic liver (1.49 +/- 0.14). The number of AgNORs was significantly correlated with serum alpha-fetoprotein level, tumor size, portal vein invasion, and Edmondson-Steiner histological grade. In patients undergoing curative resection, the survival rate of those with a high number (> 3.04) of AgNORs was significantly worse than that of those with a low number (< or = 3.04) of AgNORs. Multivariate analysis showed that the number of AgNORs was a significant prognostic indicator in patients without portal vein invasion, and portal vein invasion was the only significant variable when all patients undergoing curative resection were assessed together. The results of this study suggest that the number of AgNORs is useful as an indicator of the grade of malignancy and as a predictor of the prognosis of patients with HCC who do not have portal vein involvement.
Effect of RasGAP N2 Fragment–Derived Peptide on Tumor Growth in Mice
Authors: David Michod, Alessandro Annibaldi, Stephan Schaefer, Christine Dapples, Bertrand Rochat, Christian Widmann
Journal: JNCI Journal of the National Cancer Institute (2009)

Peptides that interfere with the natural resistance of cancer cells to genotoxin-induced apoptosis may improve the efficacy of anticancer regimens. We have previously reported that a cell-permeable RasGAP-derived peptide (TAT-RasGAP 317–326 ) specifically sensitizes tumor cells to genotoxin-induced apoptosis in vitro. Here, we examined the in vivo stability of a protease-resistant D -form of the peptide, RI·TAT-RasGAP 317–326 , and its effect on tumor growth in nude mice bearing subcutaneous human colon cancer HCT116 xenograft tumors. After intraperitoneal injection, RI·TAT-RasGAP 317–326 persisted in the blood of nude mice for more than 1 hour and was detectable in various tissues and subcutaneous tumors. Tumor-bearing mice treated daily for 7 days with RI·TAT-RasGAP 317–326 (1.65 mg/kg body weight) and cisplatin (0.5 mg/kg body weight) or doxorubicin (0.25 mg/kg body weight) displayed reduced tumor growth compared with those treated with either genotoxin alone (n = 5–7 mice per group; P = .004 and P = .005, respectively; repeated measures analysis of variance [ANOVA, two-sided]). This ability of the RI·TAT-RasGAP 317–326 peptide to enhance the tumor growth inhibitory effect of cisplatin was still observed at peptide doses that were at least 150-fold lower than the dose lethal to 50% of mice. These findings provide the proof of principle that RI·TAT-RasGAP 317–326 may be useful for improving the efficacy of chemotherapy in patients.
A NEW METHOD OF FITTING ARTIFICIAL LEG SOCKETS
Authors: E. M. Little
Journal: BMJ (1925)

T IBsJ water down one it is quite easy to determine whether the two cannulas lie in the same or in separate cavities.Such precautions are by no means fanciful, and I have met with cases of canalicular optie neuritis where the sinus infection (lid not torrespond with the retinal defects until further careful exploration revealed such irregularities as I have (loscribed, and which had very neally led to the source of the very serious ocular defect beinig missed and the patient nirelieved.' LITERATURE.
Receptors for IgG: subclass specificity of receptors on different mouse cell types and the definition of two distinct receptors on a macrophage cell line.
Authors: C H Heusser, C L Anderson, H M Grey
Journal: The Journal of Experimental Medicine (1977)

To evaluate subclass specificity and aggregate size requirements of IgG receptors on mouse cells, we measured binding of radiolabeled monomeric and BDB-aggregated mouse myeloma proteins fractionated into various sizes by means of gel filtration. Monomers, tetramers, and high molecular weight (approximately 10(7) daltons) aggregates were used. The various cells and cell lines studied could be segregated into three patterns of reactivity: (a) Macrophage and macrophage-like cell lines bound monomer IgG2a preferentially; high molecular weight IgG aggregates bound as follows: IgG1 = IgG2b = IgG2a. (b) Lymphoid lines D2N and S49 showed no capacity to bind monomer IgG2a; high molecular weight aggregates bound as follows: IgG1 = IgG2b less than IgG2a. (c) Other Thy-1-positive lymphoid cell lines (EL4 and L5178) and normal T and B cells showed no capacity to bind monomer IgG; high molecular weight IgG aggregates bound to a lesser extent than to cells of the first two categories in the following manner: IgG1 less than IgG2b greater than or equal to IgG2a. The variable pattern of reactivity of the macrophage-like cell lines with monomer and aggregated IgG suggested that two distinct receptors for IgG were present: one capable of binding IgG2a and another capable of binding all aggregates. Further evidence for this hypothesis was obtained by analysis of the inhibitory capacity of different IgG subclasses on the binding of aggregated IgG and monomer IgG2a to P388 cells. Inhibition of monomer IgG2a binding was effected only by monomer or aggregated IgG2a, whereas inhibition of binding of aggregated IgG1 or IgG2b was noted with aggregates of all three subclasses with some preferential inhibition by monomer IgG2b being observed. Furthermore, monomer IgG2b binding was preferentially inhibitable by monomer IgG2b. It is postulated from these data that two receptor sites are present on this macrophage-like cell line, one reactive with aggregates of all three subclasses as well as monomer IgG2b, and another receptor specific for monomer IgG2a which also binds aggregated IgG2a. Support of this concept was obtained by trypsinization experiments in which the binding of monomer IgG2a was markedly decreased by trypsin treatment of cells, whereas the binding of aggregated IgG2b was unaffected by this treatment.
Effect of forward shoulder posture on pulmonary capacities of females
Authors: Ali Ghanbari, Farahnaz Ghaffarinejad, Farshid Mohammadi, Mojdeh Khorrami, Sobhan Sobhani
Journal: British Journal of Sports Medicine (2007)

Objective: To evaluate if forward shoulder posture (FSP) would alter pulmonary capacities. Design and setting: A blinded, controlled design was used. Subjects: 40 female subjects with FSP recruited from university students. Methods and main outcome measurements: Saggital plane postural alignment of the shoulder was measured. A camera was utilized to send photo signals of the reflective markers to a computer equipped with the ability to convert this information into a file of three-dimensional coordinates. The angle formed by a line connecting C7 to the acromion process was measured and it provides FSP degree. Vital capacity (VC), Forced vital capacity (FVC) and expiratory residual volume (ERV) were recorded. Results: There was significant correlation between FSP values and VC (p=.009), FVC (p=.004) and ERV (p=.005). A distinct decrease in VC, FVC and ERV was seen with increasing FSP degrees (p&lt;.05). Conclusion: There was significant correlation between FSP and respiratory values. The respiratory values are decreased subsequent to increasing FSP degrees.
Rheumatic Fever in Airmen: Stigma Analysis with Some Controlled Observations on Convalescent Depression and Arthralgias
Authors: C. Ounsted
Journal: Annals of the Rheumatic Diseases (1950)

Glover (1946) has traced the steady decline of acute rheumatism in the British armed forces over the last hundred years.The disease has become at once less common and less severe.Recent papers from English sources confirm this trend.Copeman (1944) reported 42 cases, only two of whom showed evidence of carditis, and Reynell described 25 consecutive cases, all with a mild course.Canadian and American reports showed, however, that among their troops severe forms of rheumatic fever were common.Ferguson (1943) reported 243 cases, 27 per cent. of whom had cardiac damage, and 6 per cent.a rheumatoid syndrome.Griffith (1946) found, among 1,046 American servicemen with the disease, 119 cases of rheumatic pneumonitis and 52 examples of the " acute fulminating " type.The aim of this small study was to analyse the manifestations of acute rheumatism as'they were seen in young British airmen stationed in the Midlands of England between December, 1946, and June, 1948, and from this analysis to make a picture of the form this protean disease took in our particular community.Cases There were 35 cases of rheumatic fever and nine cases of chronic rheumatic heart disease admitted to our general hospital during this period.These 44 cases formed 0 * 58 per cent. of the 7,560 total admissions to hospital.The long period of bed-rest required gave these patients an importance greater than their numbers suggest.In fact, they accounted for approximately 20 per cent. of the bed-days occupied in the medical unit.Aetiology.-Thepatients were non-commissioned officers and airmen, the great preponderance being freshly enlisted conscripts.There was an emphasis on the younger age-group slightly disproportionate to the age distribution among the airmen in our region.Twenty-six of the patients had less than a year's service.Twelve months was roughly half the period of service at that time.(Quinn (1947) showed that rheumatic servicemen were likely to manifest their disease during their first year with the forces.)The disease did not occur in epidemic form, and admissions were spread smoothly over the winter months.Cases were drawn from widely separated stations, the distribution being even from one to another.Features of the Disease.-For the purposes of this study the features of the disease have been divided into three groups.
Function of the anal sphincters in spinal man.
Authors: B Frenckner
Journal: Gut (1975)

Eight patients with traumatic transverse lesions of the spinal cord and eight healthy controls were examined with respect to the function of the anal sphincters. Continuous recordings of anal pressure and electromyograms from the striated sphincter muscles were obtained during gradual rectal distension by means of an air-filled balloon. The patients were more prone than the controls to display a cessation of all electrical activity from the striated muscles in response to rectal distension and they also exhibited a less pronounced inflation reflex. It is concluded that upon rectal distension in normal man the striated muscles are stimulated by a cerebral centre at an unconscious level as well as by a low centre of the spinal cord. The former accounts for an augmented inflation reflex and maintained or increased electrical activity when rectal distension is substantial. The smooth internal sphincter was found to be independent of cerebral influence at rest as well as during rectal distension.
Potentiation by hypercholesterolemia of the induction of aortic intramural synthesis of plasminogen activator inhibitor type 1 by endothelial injury.
Authors: H Sawa, B E Sobel, S Fujii
Journal: Circulation Research (1993)

Accumulation of plasminogen activator inhibitor type 1 (PAI-1) in the arterial wall may accelerate atherogenesis by inhibiting fibrinolysis, diminishing proteolysis of extracellular matrix proteins, or modifying migration of vascular smooth muscle cells. Increased intramural expression of the PAI-1 gene is induced by thrombosis. To determine whether it occurs also in response to a sustained mechanical insult to endothelium, hypercholesterolemia, or both, rabbits were subjected to sustained aortic injury induced by implantation of indwelling polyethylene tubing, to hyperlipidemia induced by cholesterol and peanut oil feeding over a period of 8 weeks, or both. Sustained vascular injury alone did not increase plasma PAI-1. However, hypercholesterolemia with or without mechanically induced vascular injury increased plasma PAI-1 twofold. The expression of PAI-1 mRNA in aorta (Northern blots) was significantly increased when vascular injury was combined with hyperlipidemia. In situ hybridization showed that the increase with mechanical injury alone occurred in endothelial cells covering the neointima (positive for factor VIII and thrombomodulin), in abnormally differentiated vascular smooth muscle cells (positive for embryonic myosin heavy chain), and in macrophages (positive for the RAM-11 anti-macrophage antibody). Qualitatively similar but much more marked increases in PAI-1 gene expression were seen when arterial injury was accompanied by hypercholesterolemia. Neither vitronectin, known to stabilize PAI-1, nor vitronectin mRNA increased in liver. However, immunocytochemistry and Western blots demonstrated marked aortic accumulation of vitronectin protein with hyperlipidemia, particularly in subendothelial fibrotic regions, accompanied by increased neointimal vitronectin mRNA as shown by in situ hybridization. These results suggest that increased synthesis and stabilization of vascular PAI-1 may potentiate accumulation of extracellular matrix, thereby accelerating atherosclerosis.
Some of the challenges in drug development for irritable bowel syndrome
Authors: E A MAYER
Journal: Gut (2001)

If one accepts the concept that enhanced perception of visceral stimuli plays an important role in the pathophysiology of irritable bowel syndrome (IBS) and other functional gastrointestinal disorders (and not everybody does!1 2), identification of drugs which can normalise this enhanced perception should be a major effort in the search for effective IBS medications. Enhanced perception of different physiologically occurring gut stimuli can result from numerous mechanisms, including such fundamentally different but possibly interrelated processes as changes in sensory transmission (in the periphery or centrally), alterations in endogenous pain modulation, or even changes in gut directed attentional mechanisms.3Any of these mechanisms alone or in combination could produce some of the most prevalent clinical manifestations of visceral hypersensitivity in IBS: sensations of abdominal fullness (in the absence of excessive distension), abdominal pain (in the absence of detectable tissue injury), sigmoid tenderness during palpation or during endoscopic examination, or the sensation of incomplete rectal evacuation (in the absence of a full rectum).

Based on several studies in the rat, demonstrating that acute mucosal inflammation can produce sensitisation of primary afferents as well as dorsal horn neurones thereby resulting in acute visceral hyperalgesia,3 the concept of targeting and testing candidate drugs for their visceroanalgesic potential has been widely accepted as a worthwhile endeavour by industry and academia alike.4 The strategies pursued by optimists in this field are variations of the following sequence: (1) identify receptors or ion channels on visceral afferent neurones; (2) select compounds targeted at these membrane proteins; (3) evaluate candidate compounds for their ability to reduce behavioural responses of the rat or other rodents to colorectal distension (ideally in the normal colon and following some type of acute sensitisation); (4) evaluate if the compound has visceroanalgesic properties on …
Early Alveolar Epithelial Dysfunction Promotes Lung Inflammation in a Mouse Model of Hermansky-Pudlak Syndrome
Authors: Elena N. Atochina-Vasserman, Sandra R. Bates, Peggy Zhang, Helen Abramova, Zhenguo Zhang, Linda Gonzales, Jian-Qin Tao, Bernadette R. Gochuico, William Gahl, Chang-Jiang Guo, Andrew J. Gow, Michael F. Beers, Susan Guttentag
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: The pulmonary phenotype of Hermansky-Pudlak syndrome (HPS) in adults includes foamy alveolar type 2 cells, inflammation, and lung remodeling, but there is no information about ontogeny or early disease mediators.Objectives: To establish the ontogeny of HPS lung disease in an animal model, examine disease mediators, and relate them to patients with HPS1.Methods: Mice with mutations in both HPS1/pale ear and HPS2/AP3B1/pearl (EPPE mice) were studied longitudinally. Total lung homogenate, lung tissue sections, and bronchoalveolar lavage (BAL) were examined for phospholipid, collagen, histology, cell counts, chemokines, surfactant protein D (SP-D), and S-nitrosylated SP-D. Isolated alveolar epithelial cells were examined for expression of inflammatory mediators, and chemotaxis assays were used to assess their importance. Pulmonary function test results and BAL from patients with HPS1 and normal volunteers were examined for clinical correlation.Measurements and Main Results: EPPE mice develop increased total lung phospholipid, followed by a macrophage-predominant pulmonary inflammation, and lung remodeling including fibrosis. BAL fluid from EPPE animals exhibited early accumulation of both SP-D and S-nitrosylated SP-D. BAL fluid from patients with HPS1 exhibited similar changes in SP-D that correlated inversely with pulmonary function. Alveolar epithelial cells demonstrated expression of both monocyte chemotactic protein (MCP)-1 and inducible nitric oxide synthase in juvenile EPPE mice. Last, BAL from EPPE mice and patients with HPS1 enhanced migration of RAW267.4 cells, which was attenuated by immunodepletion of SP-D and MCP-1.Conclusions: Inflammation is initiated from the abnormal alveolar epithelial cells in HPS, and S-nitrosylated SP-D plays a significant role in amplifying pulmonary inflammation.
“Renalism”
Authors: Glenn M. Chertow, Sharon-Lise T. Normand, Barbara J. McNeil
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Higher risk patients (including the elderly) receive more conservative therapy for cardiovascular diseases, even though the relative benefits of therapy tend to be greater. The perceived risk of radiocontrast-associated nephrotoxicity may influence the provision of coronary angiography and subsequent revascularization, especially among individuals with chronic kidney disease (CKD). The aim of this study was to determine whether there is excessive variation in the provision of coronary angiography after acute myocardial infarction on the basis of the presence of CKD and whether there is an association between angiography and mortality. Elderly (age 65 to 89 yr) individuals with acute myocardial infarction from the Cooperative Cardiovascular Project were classified by the presence or absence of CKD (defined as a baseline serum creatinine of 1.5 to 5.0 mg/dl). In CKD patients, the propensity to undergo coronary angiography was determined and the effect of coronary angiography on mortality was estimated using multivariable logistic regression and stratification. Mortality was significantly higher with CKD (52.6 versus 26.4%). Fewer patients with CKD underwent coronary angiography (25.2 versus 46.8%) despite the observation that a similar proportion of patients were deemed appropriate for angiography by standard, published criteria. When limiting the analysis to CKD patients who are considered appropriate, the multivariable estimate of the odds of death associated with coronary angiography was 0.58 (95% confidence interval, 0.50 to 0.67). With adjustment using propensity scores, the odds ratio averaged across propensity score quintiles was 0.62 (95% confidence interval, 0.54 to 0.70). Results were qualitatively similar when patients were stratified by CKD stage IV (estimated GFR <30 ml/min per 1.73 m2). There is a large relative decrease in utilization of coronary angiography among patients with CKD. Alteration in practice because of an aversion to the risk of radiocontrast-associated nephrotoxicity (“renalism”) is inappropriate, even if the true relative benefit of invasive strategies is a fraction of what is estimated here.