tbuckley/cabot-search huggingface dataset:
The role of hip abductor and external rotator muscle strength in the development of exertional medial tibial pain: a prospective study
Authors: Ruth Verrelst, Tine Marieke Willems, Dirk De Clercq, Philip Roosen, Lennert Goossens, Erik Witvrouw
Journal: British Journal of Sports Medicine (2013)

To prospectively identify proximal risk factors contributing to the development of exertional medial tibial pain (EMTP).Data were prospectively collected on healthy female students in physical education, who were freshmen in 2010-2011 and 2011-2012. 95 female students, aged 18.15 ± 0.84, were tested at the beginning of their first academic year. Testing included isokinetic hip strength measurements of the abductors, adductors, internal rotators and external rotators. The follow-up of the individulas was assessed using a weekly online questionnaire and a 3-monthly retrospective control questionnaire. EMTP was diagnosed by an experienced MD (Doctor of Medicine). Cox regression analysis was used to identify the potential risk factors for the development of EMTP.21 individuals were diagnosed with EMTP during follow-up. The results of this study identified that decreased hip abductor concentric strength is a predictive parameter for the development of EMTP in females. More specifically, total work (p=0.010) and average power (p=0.045) for concentric abduction strength were found to be significant predictors for this lower leg overuse injury.Hip abductor weakness is a significant predictor for EMTP in women. Preventive screening methods for EMTP should therefore include this proximal contributing factor.
Sensitivity of the Supraventricular Pacemakers to Acetylcholine in Acute Hypoxemia
Authors: C. CALLEBAUT, S. RODBARD, L. N. KATZ
Journal: Circulation (1950)

Severe hypoxemia enhances the effect of endogenous and exogenous acetylcholine to depress the supraventricular pacemakers and conduction pathways, as shown in experiments on dogs.
Enlarging Residual Mass After Treatment of a Nonseminomatous Germ Cell Tumor: Growing Teratoma Syndrome or Cancer Recurrence?
Authors: Nicolas Aide, François Comoz, Emmanuel Sevin
Journal: Journal of Clinical Oncology (2007)

of myeloid malignancies and in de novo MDS it has been reported to be associated with a high rate of transformation to AML and a poor prognosis. 7This abnormality has been previously described in a case of secondary myelodysplasia. 8In conclusion, we report what is to our knowledge a previously unrecognised risk of prolonged survival with fotemustine, secondary acute leukemia.
Diabetes, Depression, and Death
Authors: Hillary R. Bogner, Knashawn H. Morales, Edward P. Post, Martha L. Bruce
Journal: Diabetes Care (2007)

We sought to test our a priori hypothesis that depressed patients with diabetes in practices implementing a depression management program would have a decreased risk of mortality compared with depressed patients with diabetes in usual-care practices.We used data from the multisite, practice-randomized, controlled Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT), with patient recruitment from May 1999 to August 2001, supplemented with a search of the National Death Index. Twenty primary care practices participated from the greater metropolitan areas of New York City, New York; Philadelphia, Pennsylvania; and Pittsburgh, Pennsylvania. In all, 584 participants identified though a two-stage, age-stratified (aged 60-74 or >or=75 years) depression screening of randomly sampled patients and classified as depressed with complete information on diabetes status are included in these analyses. Of the 584 participants, 123 (21.2%) reported a history of diabetes. A depression care manager worked with primary care physicians to provide algorithm-based care. Vital status was assessed at 5 years.After a median follow-up of 52.0 months, 110 depressed patients had died. Depressed patients with diabetes in the intervention category were less likely to have died during the 5-year follow-up interval than depressed diabetic patients in usual care after accounting for baseline differences among patients (adjusted hazard ratio 0.49 [95% CI 0.24-0.98]).Older depressed primary care patients with diabetes in practices implementing depression care management were less likely to die over the course of a 5-year interval than depressed patients with diabetes in usual-care practices.
Effects of tripotassium dicitrato bismuthate (TDB) tablets or cimetidine in the treatment of duodenal ulcer.
Authors: I Hamilton, B W Worsley, H J O'Connor, A T Axon
Journal: Gut (1983)

Forty patients with duodenal ulcer were randomly allocated to treatment with either tripotassium dicitrato bismuthate tablets or cimetidine for six weeks. Endoscopically confirmed healing of the ulcer occurred in 80% treated with tripotassium dicitrato bismuthate tablets and in 85% treated with cimetidine. Symptomatic improvement was also similar in the two groups. Treatment with cimetidine was associated with an increase in pH of gastric aspirate during treatment and increased numbers of bacteria were isolated from the gastric aspirate during treatment, while the pH and bacterial flora of gastric aspirate did not change during tripotassium dicitrato bismuthate treatment. Serum and urinary bismuth levels rose during treatment with tripotassium dicitrato bismuthate and urinary excretion remained raised two weeks after cessation of treatment. Tripotassium dicitrato bismuthate tablets appear to be as effective as cimetidine in the treatment of duodenal ulcer without the potentially undesirable effects of a reduction in gastric acid secretion.
Renal sodium retention complicating alcoholic liver disease: Relation to portosystemic shunting and liver function
Authors: William G. Rector, Frederick Lewis, Alastair D. Robertson, Gregory T. Everson
Journal: Hepatology (1990)

The aim of this study was to determine whether liver function and portosystemic shunting are related to renal sodium retention in alcoholic liver disease. Twenty-three studies were performed; 10 patients had ascites. Liver function was assessed from the plasma elimination rates of antipyrine, caffeine and stable isotopes of cholic acid, the latter administered both orally [2,2,4,4-2H] and intravenously [24-13C]. Portosystemic shunt fraction was calculated as the ratio of the intravenous and oral clearances of the isotopes of cholic acid. Portosystemic shunt fraction was similar in patients with and without ascites (61% ± 16% vs. 64% ± 11%) and unrelated to urinary sodium excretion in patients with ascites (r = −0.145). Patients with ascites had significantly lower elimination rates of all administered compounds as compared with patients without ascites (antipyrine = 0.012 ± 0.007 vs. 0.031 ± 0.016/hr, p &lt; 0.001; caffeine = 0.014 ± 0.013 vs. 0.061 ± 0.041/hr, p &lt; 0.002; intravenous cholic acid = 1.355 ± 0.442 vs. 2.284 ± 0.885/hr, p = 0.005; orally administered cholic acid = 2.178 ± 0.841 vs. 4.056 ± 1.837/hr, p = 0.007). However, urinary sodium excretion in patients with ascites was not related to the elimination constants of these compounds (r = 0.360, 0.319, 0.067, -0.073, respectively). Ascites complicating alcoholic liver disease is associated with impaired liver function but not the extent of portosystemic shunting. (Hepatology 1990;12:455-459).
Smoking Is Associated With Reduced Risk of Autoimmune Diabetes in Adults Contrasting With Increased Risk in Overweight Men With Type 2 Diabetes
Authors: Bahareh Rasouli, Valdemar Grill, Kristian Midthjell, Anders Ahlbom, Tomas Andersson, Sofia Carlsson
Journal: Diabetes Care (2012)

To investigate the association between smoking habits and risk of autoimmune diabetes in adults and of type 2 diabetes.We used data from the three surveys of the Nord-Trøndelag Health Study, spanning 1984-2008 and including a cohort of 90,819 Norwegian men (48%) and women (52%) aged ≥20 years. Incident cases of diabetes were identified by questionnaire and classified as type 2 diabetes (n = 1,860) and autoimmune diabetes (n = 140) based on antibodies to glutamic decarboxylase (GADA) and age at onset of diabetes. Hazard ratios (HRs) adjusted for confounders were estimated by Cox proportional hazards regression models.The risk of autoimmune diabetes was reduced by 48% (HR 0.52 [95% CI 0.30-0.89]) in current smokers and 58% in heavy smokers (0.42 [0.18-0.98]). The reduced risk was positively associated with number of pack-years. Heavy smoking was associated with lower levels of GADA (P = 0.001) and higher levels of C-peptide (964 vs. 886 pmol/L; P = 0.03). In contrast, smoking was associated with an increased risk of type 2 diabetes, restricted to overweight men (1.33 [1.10-1.61]). Attributable proportion due to an interaction between overweight and heavy smoking was estimated to 0.40 (95% CI 0.23-0.57).In this epidemiological study, smoking is associated with a reduced risk of autoimmune diabetes, possibly linked to an inhibitory effect on the autoimmune process. An increased risk of type 2 diabetes was restricted to overweight men.
Effects of Fructose vs Glucose on Regional Cerebral Blood Flow in Brain Regions Involved With Appetite and Reward Pathways
Authors: Kathleen A. Page, Owen Chan, Jagriti Arora, Renata Belfort-DeAguiar, James Dzuira, Brian Roehmholdt, Gary W. Cline, Sarita Naik, Rajita Sinha, R. Todd Constable, Robert S. Sherwin
Journal: JAMA (2013)

<h3>Importance</h3>Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety.<h3>Objective</h3>To study neurophysiological factors that might underlie associations between fructose consumption and weight gain.<h3>Design, Setting, and Participants</h3>Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded, random-order, crossover design.<h3>Main Outcome Measures</h3>Relative changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion. Secondary outcomes included whole-brain analyses to explore regional CBF changes, functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses, and hormone responses to fructose and glucose ingestion.<h3>Results</h3>There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion (−5.45 vs 2.84 mL/g per minute, respectively; mean difference, 8.3 mL/g per minute [95% CI of mean difference, 1.87-14.70]; P = .01). Glucose ingestion (compared with baseline) increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus but not the striatum. Regional CBF within the hypothalamus, thalamus, insula, anterior cingulate, and striatum (appetite and reward regions) was reduced after glucose ingestion compared with baseline (P &lt; .05 significance threshold, family-wise error [FWE] whole-brain corrected). In contrast, fructose reduced regional CBF in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex (P &lt; .05 significance threshold, FWE whole-brain corrected). In whole-brain voxel-level analyses, there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons. Fructose vs glucose ingestion resulted in lower peak levels of serum glucose (mean difference, 41.0 mg/dL [95% CI, 27.7-54.5]; P &lt; .001), insulin (mean difference, 49.6 μU/mL [95% CI, 38.2-61.1]; P &lt; .001), and glucagon-like polypeptide 1 (mean difference, 2.1 pmol/L [95% CI, 0.9-3.2]; P = .01).<h3>Conclusion and Relevance</h3>In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels.
Identification of novel synergistic targets for rational drug combinations with PI3 kinase inhibitors using siRNA synthetic lethality screening against GBM
Authors: Y.-W. Kim, T. J. Liu, D. Koul, N. Tiao, A. H. Feroze, J. Wang, G. Powis, W. K. A. Yung
Journal: Neuro-Oncology (2011)

Several small molecules that inhibit the PI3 kinase (PI3K)-Akt signaling pathway are in clinical development. Although many of these molecules have been effective in preclinical models, it remains unclear whether this strategy alone will be sufficient to interrupt the molecular events initiated and maintained by signaling along the pathways because of the activation of other pathways that compensate for the inhibition of the targeted kinase. In this study, we performed a synthetic lethality screen to identify genes or pathways whose inactivation, in combination with the PI3K inhibitors PX-866 and NVPBEZ-235, might result in a lethal phenotype in glioblastoma multiforme (GBM) cells. We screened GBM cells (U87, U251, and T98G) with a large-scale, short hairpin RNA library (GeneNet), which contains 43 800 small interfering RNA sequences targeting 8500 well-characterized human genes. To decrease off-target effects, we selected overlapping genes among the 3 cell lines that synergized with PX-866 to induce cell death. To facilitate the identification of potential targets, we used a GSE4290 dataset and The Cancer Genome Atlas GBM dataset, identifying 15 target genes overexpressed in GBM tissues. We further analyzed the selected genes using Ingenuity Pathway Analysis software and showed that the 15 genes were closely related to cancer-promoting pathways, and a highly interconnected network of aberrations along the MYC, P38MAPK, and ERK signaling pathways were identified. Our findings suggest that inhibition of these pathways might increase tumor sensitivity to PX-866 and therefore represent a potential clinical therapeutic strategy.
Profiling Cytochrome <i>P</i>450 Expression in Ovarian Cancer: Identification of Prognostic Markers
Authors: Diane Downie, Morag C.E. McFadyen, Patrick H. Rooney, Margaret E. Cruickshank, David E. Parkin, Iain D. Miller, Colin Telfer, William T. Melvin, Graeme I. Murray
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The cytochromes P450 are a multigene family of enzymes with a central role in the oxidative metabolism of a wide range of xenobiotics, including anticancer drugs and biologically active endogenous compounds. The purpose of this study was to define the cytochrome P450 profile of ovarian cancer and identify novel therapeutic targets and establish the prognostic significance of expression of individual cytochrome P450s in this type of cancer. Experimental Design: Immunohistochemistry for a panel of 23 cytochrome P450s and cytochrome P450 reductase was done on an ovarian cancer tissue microarray consisting of 99 primary epithelial ovarian cancers, 22 peritoneal metastasis, and 13 normal ovarian samples. The intensity of immunoreactivity in each sample was established by light microscopy. Results: In primary ovarian cancer, several P450s (CYP1B1, CYP2A/2B, CYP2F1, CYP2R1, CYP2U1, CYP3A5, CYP3A7, CYP3A43, CYP4Z1, CYP26A1, and CYP51) were present at a significantly higher level of intensity compared with normal ovary. P450 expression was also detected in ovarian cancer metastasis and CYP2S1 and P450 reductase both showed significantly increased expression in metastasis compared with primary ovarian cancer. The presence of low/negative CYP2A/2B (log rank = 7.06, P = 0.008) or positive CYP4Z1 (log rank = 6.19, P = 0.01) immunoreactivity in primary ovarian cancer were each associated with poor prognosis. Both CYP2A/2B and CYP4Z1 were also independent markers of prognosis. Conclusions: The expression profile of individual P450s has been established in ovarian cancer. Several P450s show increased expression in ovarian cancer and this provides the basis for developing P450-based therapeutics in ovarian cancer. Expression of CYP2A/2B or CYP4Z1 in primary ovarian cancer were independent markers of prognosis.
Phospholipid antibodies in alcoholic liver disease
Authors: Antonio Chedid, Kurmanadha R. Chadalawada, Timothy R. Morgan, Thomas E. Moritz, Charles L. Mendenhall, James B. Hammond, Peter W. Emblad, Doris C. Cifuentes, Joanne W. H. Kwak, Alice Gilman-Sachs, Kenneth D. Beaman
Journal: Hepatology (1994)

Alcoholic liver injury has been reported to be directed preferentially against the proteins of the cell membrane, sparing the phospholipids. However, antiphospholipid antibodies against certain cell membrane phospholipids are known to be associated with a variety of diseases. We undertook this investigation to determine whether antiphospholipid antibodies were present in the serum of patients with alcoholic liver disease. We investigated seventy long-term alcoholic patients (> 80 gm ethanol/day for > 1 yr) and 8 normal nonalcoholic controls by means of enzyme-linked immunosorbent assay to determine whether serum antibodies were generated against the following membrane phospholipids: phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol (cardiolipin) and phosphatidic acid. Group 1 comprised alcoholic patients with normal liver function (n = 13), group 2 comprised alcoholic patients with abnormal liver function (n = 16), group 3 comprised patients with alcoholic hepatitis or cirrhosis (n = 41) and group 4 comprised nonalcoholic controls (n = 8). The antibody prevalence was 15% in group 1, 31% in group 2, 81% in group 3 and 0% in group 4. In group 3, 20 of 41 patients had antibodies against several cell membrane phospholipids (i.e., phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidic acid, cardiolipin and phosphatidylinositol). The antiphosphatidylethanolamine isotype was IgA or IgM in 25 of 41 of these patients. Both IgA (p < 0.01) and IgM (p < 0.008) antiphosphatidylethanolamine correlated significantly with disease severity. Antiphospholipid antibodies in alcoholic patients seem to reflect disease progression and correlate significantly with disease severity.
Effect of β‐Globin gene cluster haplotype on the hematological and clinical features of sickle cell anemia
Authors: R. F. Rieder, S. Safaya, P. Gillette, S. Fryd, H. Hsu, J. G. Adams, M. H. Steinberg
Journal: American Journal of Hematology (1991)

Abstract In 113 black American adults with sickle cell anemia (HbSS), we examined nine polymorphic restriction sites, including the Xmnl site 5' to the G γ gene, to see whether haplotype is related to the level of HbF and the proportion of G γ chains or if it influences the hematological and clinical features of the disease. Seventy‐five percent of the patients were homozygous or heterozygous for the Benin (no. 19) or Central African Republic (Bantu, no.20) haplotypes; 13.3% were homozygous fo heterozygous for the Senegal (no.3) haplotype, while 11.5% had other genotypes. Of the subjects, 14.2% were either homozygous or heteroxygous for the Xmnl restriction site 5' to the G γ gene. We found no effect of haplotype on HbF levels. The level of G γ chains was 60.5% ± 17.0% in individuals with other haplotypes. Subjects with the Xmnl site 5' to the G γ gene had G γ globin levels of 59.5% ± 16.7% while those lacking that site had an average of 47.2% ± 12.1%. There were no significant differences among these groups in hemoglobin concentration, packed cell volume, mean cell volume, or haplotype 3 and the 5' G γ Xmnl site were associated with increased G γ chains, there was no effect on HbF level or other hematological and clinical features that might reflect disease severity. It is likelu that determinants unrelated to haplotype, linked or unlinked to the β‐globin gene cluster, are the major effectors of differences in the levels of HbF in American patients with sickle cell anemia.
Upregulation of miR-142-3p in Peripheral Blood Mononuclear Cells of Operationally Tolerant Patients with a Renal Transplant
Authors: Richard Danger, Annaïck Pallier, Magali Giral, Marc Martínez-Llordella, Juan José Lozano, Nicolas Degauque, Alberto Sanchez-Fueyo, Jean-Paul Soulillou, Sophie Brouard
Journal: Journal of the American Society of Nephrology (2012)

Achieving drug-free tolerance or successfully using only small doses of immunosuppression is a major goal in organ transplantation. To investigate the potential mechanisms by which some kidney transplant recipients can achieve operational tolerance, we compared the expression profiles of microRNA in peripheral blood mononuclear cells of operationally tolerant patients with those of stable patients treated with conventional immunosuppression. B cells from operationally tolerant patients overexpressed miR-142-3p. The expression of miR-142-3p was stable over time and was not modulated by immunosuppression. In Raji B cells, overexpression of miR-142-3p modulated nearly 1000 genes related to the immune response of B cells, including potential miR-142-3p targets and molecules previously identified in the blood of operationally tolerant patients. Furthermore, our results suggested that a negative feedback loop involving TGF-β signaling and miR-142-3p expression in B cells may contribute to the maintenance of tolerance. In summary, miR-142-3p expression in peripheral blood mononuclear cells correlates with operational tolerance. Whether upregulation of miR-142-3p modulates inflammatory responses to promote tolerance or is a result of this tolerance state requires further study.
Expression of C5a-like biological activities by the fifth component of human complement (C5) upon limited digestion with noncomplement enzymes without release of polypeptide fragments.
Authors: R A Wetsel, W P Kolb
Journal: The Journal of Experimental Medicine (1983)

Experimental conditions required for the expression of maximum C5 activation upon limited trypsin hydrolysis were determined to be 0.008 mol of trypsin/mol C5 in a reaction mixture containing 1 mg C5/ml veronal-buffered saline incubated at 37 degrees C for 30 min. Employing these optimal incubation conditions, the primary or preferred site of trypsin hydrolysis of the C5 alpha-chain resulted in the production of C5 alpha 1 (molecular weight, 90,000) and C5 alpha 5 (molecular weight, 25,000) fragments that remained disulfide bonded to the modified C5 molecule (C5'try). Detailed structural-functional analyses clearly indicated the trypsin-mediated conversion of the C5 alpha-chain to C5 alpha 1 and C5 alpha 5 was responsible for the acquisition of neutrophil lysosomal enzyme-releasing and chemotactic activities. Gel filtration column chromatography under physiological ionic strength, pH 7.4, or in the presence of 0.2% SDS further demonstrated that at least 90% of the total recoverable C5a-like biological activity was mediated by the 210,000 molecular weight forms of trypsin-modified C5. Other physiologically relevant, noncomplement protease enzymes (alpha-thrombin, plasmin, and elastase) also activated C5 to express C5a-like reactivities. Analysis of alpha-thrombin-induced, C5 alpha-chain cleavage events by SDS-polyacrylamide slab gel electrophoresis indicated that the mechanism of alpha-thrombin-activation of C5 is similar to that described for trypsin. Reconciliation of this novel mechanism of C5 activation by trypsin with previously published results, and a discussion of the biological significance of noncomplement enzyme-mediated activation of C5 as it might relate to inflammatory processes in vivo, was presented.