tbuckley/cabot-search huggingface dataset:
Ethnic Differences in β-Cell Functional Reserve and Clinical Features in Patients With Ketosis-Prone Diabetes
Authors: Mario R. Maldonado, Max E. Otiniano, Rebekah Lee, Lucille Rodriguez, Ashok Balasubramanyam
Journal: Diabetes Care (2003)

Diabetic ketoacidosis (DKA) has been reported in subjects who lack the clinical characteristics of type 1 diabetes (1–3). In a preliminary analysis of the “types” of diabetes in patients presenting with DKA, we found that Hispanic patients had a significantly higher proportion with type 2 diabetes when compared with Caucasians and African Americans (1).

We performed a prospective analysis to compare demographic and clinical characteristics among ketosis-prone indigent subjects belonging to these three ethnic groups. We interviewed 271 consecutive patients at the time of admission for DKA over a 3-year period. Fasting serum C-peptide and …
Comprehensive, Quantitative Mapping of T Cell Epitopes in Gluten in Celiac Disease
Authors: Jason A. Tye-Din, Jessica A. Stewart, James A. Dromey, Tim Beissbarth, David A. van Heel, Arthur Tatham, Kate Henderson, Stuart I. Mannering, Carmen Gianfrani, Derek P. Jewell, Adrian V. S. Hill, James McCluskey, Jamie Rossjohn, Robert P. Anderson
Journal: Science Translational Medicine (2010)

Celiac disease is a genetic condition that results in a debilitating immune reaction in the gut to antigens in grain. The antigenic peptides recognized by the T cells that cause this disease are incompletely defined. Our understanding of the epitopes of pathogenic CD4+ T cells is based primarily on responses shown by intestinal T-cells in vitro to hydrolysates or polypeptides of gluten, the causative antigen. A protease-resistant 33-amino acid peptide from wheat α-gliadin is the immunodominant antigen, but little is known about the spectrum of T cell epitopes in rye and barley or the hierarchy of immunodominance and consistency of recognition of T-cell epitopes in vivo. We induced polyclonal gluten-specific T cells in the peripheral blood of celiac patients by feeding them cereal and performed a comprehensive, unbiased analysis of responses to all celiac toxic prolamins, a class of plant storage protein. The peptides that stimulated T cells were the same among patients who ate the same cereal, but were different after wheat, barley and rye ingestion. Unexpectedly, a sequence from ω-gliadin (wheat) and C-hordein (barley) but not α-gliadin was immunodominant regardless of the grain consumed. Furthermore, T cells specific for just three peptides accounted for the majority of gluten-specific T cells, and their recognition of gluten peptides was highly redundant. Our findings show that pathogenic T cells in celiac disease show limited diversity, and therefore suggest that peptide-based therapeutics for this disease and potentially other strongly HLA-restricted immune diseases should be possible.
ELECTRICAL TREATMENT OF MUSCLES IN "TRENCH FEET."
Authors: G. M. Levick
Journal: BMJ (1918)

1(a handful of sodium or potassium carbonate) are added; on subsequent mornings the cresol is omitted.After the mtorniing bath, and again in tlle evening, the following ointment is applied to all affected parts from the neck downwards, excepting the genitals; A Chrysarobin..X.. ...... gr. 10Acid. salicylic ....
Characterization of childhood acute lymphoblastic leukemia xenograft models for the preclinical evaluation of new therapies
Authors: Natalia L. M. Liem, Rachael A. Papa, Christopher G. Milross, Michael A. Schmid, Mayamin Tajbakhsh, Seoyeon Choi, Carole D. Ramirez, Alison M. Rice, Michelle Haber, Murray D. Norris, Karen L. MacKenzie, Richard B. Lock
Journal: Blood (2004)
Pooled Analysis of Phosphatidylinositol 3-Kinase Pathway Variants and Risk of Prostate Cancer
Authors: Stella Koutros, Fredrick R. Schumacher, Richard B. Hayes, Jing Ma, Wen-Yi Huang, Demetrius Albanes, Federico Canzian, Stephen J. Chanock, E. David Crawford, W. Ryan Diver, Heather Spencer Feigelson, Edward Giovanucci, Christopher A. Haiman, Brian E. Henderson, David J. Hunter, Rudolf Kaaks, Laurence N. Kolonel, Peter Kraft, Loïc Le Marchand, Elio Riboli, Afshan Siddiq, Mier J. Stampfer, Daniel O. Stram, Gilles Thomas, Ruth C. Travis, Michael J. Thun, Meredith Yeager, Sonja I. Berndt
Journal: Cancer Research (2010)

The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking, and may affect prostate carcinogenesis. Thus, we explored the association between single-nucleotide polymorphisms (SNP) in PI3K genes and prostate cancer. Pooled data from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium were examined for associations between 89 SNPs in PI3K genes (PIK3C2B, PIK3AP1, PIK3C2A, PIK3CD, and PIK3R3) and prostate cancer risk in 8,309 cases and 9,286 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. SNP rs7556371 in PIK3C2B was significantly associated with prostate cancer risk [OR(per allele), 1.08 (95% CI, 1.03-1.14); P(trend) = 0.0017] after adjustment for multiple testing (P(adj) = 0.024). Simultaneous adjustment of rs7556371 for nearby SNPs strengthened the association [OR(per allele), 1.21 (95% CI, 1.09-1.34); P(trend) = 0.0003]. The adjusted association was stronger for men who were diagnosed before the age of 65 years [OR(per allele), 1.47 (95% CI, 1.20-1.79); P(trend) = 0.0001] or had a family history [OR(per allele) = 1.57 (95% CI, 1.11-2.23); P(trend) = 0.0114], and was strongest in those with both characteristics [OR(per allele) = 2.31 (95% CI, 1.07-5.07), P-interaction = 0.005]. Increased risks were observed among men in the top tertile of circulating insulin-like growth factor-I (IGF-I) levels [OR(per allele) = 1.46 (95% CI, 1.04-2.06); P(trend) = 0.075]. No differences were observed with disease aggressiveness (Gleason grade >or=8 or stage T(3)/T(4) or fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially for familial, early-onset disease, which may be attributable to IGF-dependent PI3K signaling.
Coronary Artery Findings After Left-Sided Compared With Right-Sided Radiation Treatment for Early-Stage Breast Cancer
Authors: Candace R. Correa, Harold I. Litt, Wei-Ting Hwang, Victor A. Ferrari, Lawrence J. Solin, Eleanor E. Harris
Journal: Journal of Clinical Oncology (2007)

To compare the incidence and distribution of coronary artery disease after left-sided versus right-sided irradiation in patients treated with breast conservation for early-stage breast cancer who subsequently underwent cardiac stress testing and/or catheterization for cardiovascular symptoms.The medical records of 961 stage I-II breast cancer patients treated from 1977 to 1995 at the University of Pennsylvania with conventional tangential beam radiation treatment (RT) were screened for cardiac stress tests and catheterizations performed after RT. The results of these tests were analyzed by laterality of RT and compared with baseline cardiovascular risk.At diagnosis, patients with left-sided and right-sided breast cancer had the same estimated 10-year risk (both 7%) of developing coronary artery disease. At a median time of 12 years post-RT (range, 2 to 24 years), 46 patients with left-sided and 36 patients with right-sided breast cancer (total, N = 82) had undergone cardiac stress testing. A statistically significant higher prevalence of stress test abnormalities was found among left (27 of 46; 59%) versus right-side irradiated patients (three of 36; 8%; P = .001). Furthermore, 19 of 27 of left-sided abnormalities (70%) were in the left anterior descending artery territory. Thirteen left-side irradiated patients also underwent cardiac catheterization revealing 12 of 13 with coronary stenoses (92%) and eight of 13 with coronary stenoses (62%) solely in the left anterior descending artery.Patients treated with left-sided radiation as a component of breast conservation have an increased risk of late, radiation-associated coronary damage. Treatment with modern radiation techniques may reduce the risk of cardiac injury.
Tob1 is a constitutively expressed repressor of liver regeneration
Authors: Karen J. Ho, Nhue L. Do, Hasan H. Otu, Martin J. Dib, Xianghui Ren, Keiichi Enjyoji, Simon C. Robson, Ernest F. Terwilliger, Seth J. Karp
Journal: The Journal of Experimental Medicine (2010)

How proliferative and inhibitory signals integrate to control liver regeneration remains poorly understood. A screen for antiproliferative factors repressed after liver injury identified transducer of ErbB2.1 (Tob1), a member of the PC3/BTG1 family of mito-inhibitory molecules as a target for further evaluation. Tob1 protein decreases after 2/3 hepatectomy in mice secondary to posttranscriptional mechanisms. Deletion of Tob1 increases hepatocyte proliferation and accelerates restoration of liver mass after hepatectomy. Down-regulation of Tob1 is required for normal liver regeneration, and Tob1 controls hepatocyte proliferation in a dose-dependent fashion. Tob1 associates directly with both Caf1 and cyclin-dependent kinase (Cdk) 1 and modulates Cdk1 kinase activity. In addition, Tob1 has significant effects on the transcription of critical cell cycle components, including E2F target genes and genes involved in p53 signaling. We provide direct evidence that levels of an inhibitory factor control the rate of liver regeneration, and we identify Tob1 as a crucial check point molecule that modulates the expression and activity of cell cycle proteins.
T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase
Authors: Mark W. Musch, Lane L. Clarke, Daniel Mamah, Lara R. Gawenis, Zheng Zhang, William Ellsworth, David Shalowitz, Navdha Mittal, Petros Efthimiou, Ziad Alnadjim, Steve D. Hurst, Eugene B. Chang, Terrence A. Barrett
Journal: Journal of Clinical Investigation (2002)

Inflammatory bowel disease (IBD) is associated with mucosal T cell activation and diarrhea. We found that T cell activation with anti-CD3 mAb induces profound diarrhea in mice. Diarrhea was quantified by intestinal weight-to-length (wt/l) ratios, mucosal Na+/K+-ATPase activity was determined and ion transport changes were measured in Ussing chambers. Anti-CD3 mAb increased jejunal wt/l ratios by more than 50% at 3 hours, returning to base line after 6 hours. Fluid accumulation was significantly reduced in TNF receptor-1 (TNFR-1–/–), but not IFN-γ knockout mice. Anti-CD3 mAb decreased mucosal Na+/K+-ATPase activity, which was blocked by anti-TNF mAb and occurred to a lesser degree in TNFR-1–/– mice. Neither α nor β subunits of Na+/K+-ATPase decreased in abundance at 3 hours. Intestinal tissue from anti-CD3–treated mice exhibited increased permeability to mannitol at 1 hour and decreases in electroneutral Na+ absorption, Na+-dependent glucose absorption, and cAMP-stimulated anion secretion at 3 hours. Furthermore, enteral fluid accumulation was observed in CFTR–/– mice, indicating a minor role of active anion secretion. These data suggest that diarrhea in IBD is due to TNF-mediated malabsorption rather than to secretory processes. T cell activation induces luminal fluid accumulation by increasing mucosal permeability and reducing epithelial Na+/K+-ATPase activity leading to decreased intestinal Na+ and water absorption.
The Relation Between Eating Disorders and Components of Perfectionism
Authors: Cynthia M. Bulik, Federica Tozzi, Charles Anderson, Suzanne E. Mazzeo, Steve Aggen, Patrick F. Sullivan
Journal: American Journal of Psychiatry (2003)

OBJECTIVE: The authors’ goal was to explore the relation between perfectionism and psychopathology, including eating disorders. METHOD: Using logistic regression, the authors calculated odds ratios for the associations between perfectionism subscale scores and psychiatric disorders in 1,010 female twins who completed the Multidimensional Perfectionism Scale and participated in diagnostic interviews. RESULTS: Elevated concern over mistakes was associated with anorexia and bulimia nervosa but not with other psychiatric disorders. Doubts about actions was associated with eating and anxiety disorders. Multivariable models confirmed that higher scores on the subscales for concern over mistakes and doubts about actions were most strongly associated with eating disorders. CONCLUSIONS: The aspect of perfectionism captured by scores on a subscale measuring concern over mistakes may be particularly associated with eating disorders and not generically predictive of psychopathology.
Transformation of human lymphocytes in vitro by autologous and allogeneic rheumatoid synovial fluids.
Authors: T.D Kinsella
Journal: Annals of the Rheumatic Diseases (1976)

To assess the possible participation of cellular immune mechanisms in the pathogenesis of rheumatoid arthritis (RA) in vitro studies of the blastogenicity of rheumatoid and non-rheumatoid synovial fluids for human peripheral blood lymphocytes were conducted. In autologous cultures it was found that 13 of 19 rheumatoid fluids induced significant lymphocyte blastogenesis, whereas only 1 of 13 nonrheumatoid fluids induced such a response. In allogeneic cultures rheumatoid fluids induce significant blastogenesis of RA lymphocytes in 18 of 23 experiments, and of non-RA lymphocytes in 8 of 18 experiments. By contrast, nonrheumatoid fluids induced significant blastogenesis of RA lymphocytes in 2 of 13 experiments, and of non-RA lymphocytes in 1 of 14 experiments. The blastogenicity of fluids was found to correlate significantly with the presence therein of immunofluorescent intracellular inclusions of immunoglobulin and complement. These studies support the concept that the presence of immune complexes in the majority of rheumatoid synovial fluids might render the latter blastogenic for human lymphocytes in vivo, thereby perpetuating rheumatoid synovitis.
The<i>T</i><sub>L,NO</sub>/<i>T</i><sub>L,CO</sub>ratio in pulmonary function test interpretation
Authors: J. Michael B. Hughes, Ivo van der Lee
Journal: European Respiratory Journal (2012)

The transfer factor of the lung for nitric oxide ( T L,NO ) is a new test for pulmonary gas exchange. The procedure is similar to the already well-established transfer factor of the lung for carbon monoxide ( T L,CO ). Physiologically, T L,NO predominantly measures the diffusion pathway from the alveoli to capillary plasma. In the Roughton–Forster equation, T L,NO acts as a surrogate for the membrane diffusing capacity ( D M ). The red blood cell resistance to carbon monoxide uptake accounts for ∼50% of the total resistance from gas to blood, but it is much less for nitric oxide. T L,NO and T L,CO can be measured simultaneously with the single breath technique, and D M and pulmonary capillary blood volume ( V c ) can be estimated. T L,NO , unlike T L,CO , is independent of oxygen tension and haematocrit. The T L,NO / T L,CO ratio is weighted towards the D M / V c ratio and to α; where α is the ratio of physical diffusivities of NO to CO (α=1.97). The T L,NO / T L,CO ratio is increased in heavy smokers, with and without computed tomography evidence of emphysema, and reduced in the voluntary restriction of lung expansion; it is expected to be reduced in chronic heart failure. The T L,NO / T L,CO ratio is a new index of gas exchange that may, more than derivations from them of D M and V c with their in-built assumptions, give additional insights into pulmonary pathology.
Scavenger cells with Gram-positive bacterial lipoteichoic acid infiltrate around the damaged interlobular bile ducts of primary biliary cirrhosis
Authors: Koichi Tsuneyama, Kenichi Harada, Naoko Kono, Katsushi Hiramatsu, Yoh Zen, Yoshiko Sudo, M.Eric Gershwin, Mamoru Ikemoto, Hiroyuki Arai, Yasuni Nakanuma
Journal: Journal of Hepatology (2001)
Phase II trial of vorinostat in combination with bortezomib in recurrent glioblastoma: a north central cancer treatment group study
Authors: B. B. Friday, S. K. Anderson, J. Buckner, C. Yu, C. Giannini, F. Geoffroy, J. Schwerkoske, M. Mazurczak, H. Gross, E. Pajon, K. Jaeckle, E. Galanis
Journal: Neuro-Oncology (2011)

Vorinostat, a histone deacetylase (HDAC) inhibitor, has shown evidence of single-agent activity in glioblastoma (GBM), and in preclinical studies, we have demonstrated significant synergistic cytotoxicity between HDAC inhibitors and proteasome inhibitors in GBM cell lines. We therefore conducted a phase II trial to evaluate the efficacy of vorinostat in combination with the proteasome inhibitor bortezomib in patients with recurrent GBM. Vorinostat was administered at a dose of 400 mg daily for 14 days of a 21-day cycle, and bortezomib was administered at a dose of 1.3 mg/m2 intravenously on days 1, 4, 8, and 11 of the cycle. A total of 37 patients were treated, and treatment was well tolerated: grade 3, 4 nonhematologic toxicity occurred in 30% of patients and consisted mainly of fatigue (14%) and neuropathy (5%); grade 3, 4 hematologic toxicity occurred in 37% of patients and consisted of thrombocytopenia (30%), lymphopenia (4%), and neutropenia (4%). The trial was closed at the predetermined interim analysis, with 0 of 34 patients being progression-free at 6 months. One patient achieved a partial response according to the Macdonald criteria. The median time to progression for all patients was 1.5 months (range, 0.5–5.6 months), and median overall survival (OS) was 3.2 months. Patients who had received prior bevacizumab therapy had a shorter time to progression and OS, compared with those who had not. On the basis of the results of this phase II study, further evaluation of the vorinostat-bortezomib combination in GBM patients in this dose and schedule is not recommended.
Individual lung blood flow during unilateral hypoxia: effects of inhaled nitric oxide
Authors: K Hambraeus-Jonzon, L Bindslev, C Frostell, G Hedenstierna
Journal: European Respiratory Journal (1998)

We hypothesized that the diversion of blood away from a hypoxic lung to the opposite oxygenated lung can be enhanced by inhaling nitric oxide (NO) into the oxygenated lung. We measured individual lung blood flow when 50 ppm NO was selectively inhaled to: a hyperoxic lung during contralateral hypoxia; a normoxic lung during bilateral normoxia; and a hyperoxic lung during bilateral hyperoxia. Twenty two patients with healthy lungs were studied during intravenous anaesthesia. The lungs were separately and synchronously ventilated. The relative perfusion of each lung was assessed by the inert gas elimination technique. Unilateral hypoxic (inspiratory oxygen fraction (FI,O2) 0.05) ventilation during contralateral hyperoxia reduced the perfusion of the hypoxic lung from a mean (SD) of 47 (9)% of cardiac output (Q'), to 30 (7)% (p<0.001) of Q'. NO inhalation to the hyperoxic lung increased its blood flow from 70 (7)% to 75 (6)% (p<0.05) of Q', and reduced the blood flow to the hypoxic lung to 25 (6)% (p<0.05). Unilateral NO inhalation during bilateral normoxia or hyperoxia had no effect on pulmonary blood flow distribution. Nitric oxide inhalation to a hyperoxic lung increases the perfusion to this lung by redistribution of blood flow if the opposite lung is hypoxic.
Development of both human connective tissue-type and mucosal-type mast cells in mice from hematopoietic stem cells with identical distribution pattern to human body
Authors: Naotomo Kambe, Hidefumi Hiramatsu, Mika Shimonaka, Hisanori Fujino, Ryuta Nishikomori, Toshio Heike, Mamoru Ito, Kimio Kobayashi, Yoshito Ueyama, Norihisa Matsuyoshi, Yoshiki Miyachi, Tatsutoshi Nakahata
Journal: Blood (2003)
STUDIES ON INFLUENZA IN THE PANDEMIC OF 1957-1958. II. PULMONARY COMPLICATIONS OF INFLUENZA*†
Authors: Donald B. Louria, Herbert L. Blumenfeld, John T. Ellis, Edwin D. Kilbourne, David E. Rogers
Journal: Journal of Clinical Investigation (1959)

ASCVD, arteriosclerotic heart disease; CO, coronary occlusion; AS, aortic stenosis; Al, aortic insufficiency.Where pulmonary symptoms blended with initial influenza symptoms the interval has been listed as <1.Cough, chest pain, dyspnea and cyanosis are graded in severity from 0 to + + +.RLL.right lower
Clinical Management Factors Contribute to the Decision for Contralateral Prophylactic Mastectomy
Authors: Tari A. King, Rita Sakr, Sujata Patil, Inga Gurevich, Michelle Stempel, Michelle Sampson, Monica Morrow
Journal: Journal of Clinical Oncology (2011)

Purpose To determine whether increasing rates of contralateral prophylactic mastectomy (CPM) are due to recognition of risk factors for contralateral breast cancer (CBC) or treatment factors related to the index lesion. Methods From 1997 to 2005, 2,965 patients with stage 0 to III primary unilateral breast cancer underwent mastectomy at Memorial Sloan-Kettering Cancer Center. Patients who did and did not undergo CPM within 1 year of treatment for their index cancer were compared to identify independent predictors of CPM. Results The rate of CPM was 13.8% (n = 407), increasing from 6.7% in 1997 to 24.2% in 2005 (P &lt; .0001). Patients with BRCA mutations or prior mantle radiation (n = 52) accounted for 13% of those having CPM. The rate of CPM by surgeon varied from 1% to 26%. Multivariate logistic regression adjusting for surgeon-identified white race (odds ratio [OR] = 3.3), immediate reconstruction (OR = 3.3), family history of breast cancer (OR = 2.9), magnetic resonance imaging (MRI) at diagnosis (OR = 2.8), age younger than 50 years (OR = 2.2), noninvasive histology (OR = 1.8), and prior attempt at breast conversation (OR = 1.7) to be independent predictors of CPM. Conclusion These data suggest that increasing use of CPM is not associated with increased recognition of patients at high risk for CBC. Treatment factors, such as immediate reconstruction, preoperative MRI, and unsuccessful attempts at breast conservation, are associated with increased rates of CPM. Efforts to optimize breast conservation, minimize unnecessary tests, and improve patient education about the low risk of CBC may help to curb this trend.
Promotion of Colorectal Cancer Invasion and Metastasis through Activation of NOTCH–DAB1–ABL–RHOGEF Protein TRIO
Authors: Masahiro Sonoshita, Yoshiro Itatani, Fumihiko Kakizaki, Kenji Sakimura, Toshio Terashima, Yu Katsuyama, Yoshiharu Sakai, M. Mark Taketo
Journal: Cancer Discovery (2014)

Abstract We have recently identified a metastasis suppressor gene for colorectal cancer: AES/Aes, which encodes an endogenous inhibitor of NOTCH signaling. When Aes is knocked out in the adenomatous epithelium of intestinal polyposis mice, their tumors become malignant, showing marked submucosal invasion and intravasation. Here, we show that one of the genes induced by NOTCH signaling in colorectal cancer is DAB1/Dab1. Genetic depletion of DAB1 suppresses cancer invasion and metastasis in the NOTCH signaling–activated mice. DAB1 is phosphorylated by ABL tyrosine kinase, which activates ABL reciprocally. Consistently, inhibition of ABL suppresses cancer invasion in mice. Furthermore, we show that one of the targets of ABL is the RAC/RHOGEF protein TRIO, and that phosphorylation at its Tyr residue 2681 (pY2681) causes RHO activation in colorectal cancer cells. Its unphosphorylatable mutation TRIO Y2681F reduces RHOGEF activity and inhibits invasion of colorectal cancer cells. Importantly, TRIO pY2681 correlates with significantly poorer prognosis of patients with colorectal cancer after surgery. Significance: These results indicate that TRIO pY2681 is one of the downstream effectors of NOTCH signaling activation in colorectal cancer, and can be a prognostic marker, helping to determine the therapeutic modality of patients with colorectal cancer. Cancer Discov; 5(2); 198–211. ©2014 AACR. See related commentary by Kranenburg, p. 115 This article is highlighted in the In This Issue feature, p. 97