tbuckley/cabot-search huggingface dataset:
Insulin Autoimmune Syndrome Associated With Benign Monoclonal Gammopathy: Evidence for Monoclonal Insulin Autoantibodies
Authors: Taro Wasada, Yoko Eguchi, Sumiko Takayama, Kenshi Yao, Yukimasa Hirata, Sadao Ishii
Journal: Diabetes Care (1989)

A 64-yr-old man with benign monoclonal gammopathy developed recurrent episodes of severe hypoglycemia but lacked evidence of insulinoma or exogenous insulin administration. The patient's plasma was found to contain anti-insulin antibodies and large amounts of extractable insulin (1110 μU/ml), which was identified as human insulin by high-performance liquid chromatography (HPLC). The anti-insulin antibodies consisted solely of IgG and A-light chains. Scatchard analysis of these antibodies revealed an almost straightline relationship, with markedly low affinity and high capacity. An immune complex made of 125l-labeled insulin and the patient's antibodies emerged in a molecular-sieve HPLC as almost a single peak, suggesting a homogeneous antibody population. In addition, the patient's M protein was separately shownto be the IgG and λ–light-chain type. We suggest that the insulin autoantibodies responsible for the spontaneous hypoglycemia in this patient are monoclonal and of M protein origin.
Neuromuscular and vascular hamartoma of small bowel
Authors: S S E Fernando, V J Mcgovern
Journal: Gut (1982)

Two examples of a hitherto undescribed hamartomatous condition of the small intestine are presented. They consist of fascicles of smooth muscle derived from the muscularis mucosae, bundles of unmyelinated nerve fibres with scattered ganglion cells, and haemangiomatous vessels, occurring focally within a segment of the intestine, and causing stenosis.
Inducible Nitric Oxide Synthase Attenuates Endothelium-Dependent Renal Microvascular Vasodilation
Authors: ATSUHIRO ICHIHARA, MATSUHIKO HAYASHI, L. GABRIEL NAVAR, TAKAO SARUTA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Previous studies have demonstrated that inducible nitric oxide synthase (iNOS) plays a key pathophysiologic role during sepsis. The present study was designed to delineate the consequences of iNOS activation on renal microvascular function. Male Sprague-Dawley rats were given intraperitoneal injections of lipopolysaccharide (LPS; 4 mg/kg) at 16 h and 4 h before experimentation. Afferent and efferent arteriolar diameters from LPS-treated and control rats were assessed in vitro with the use of the blood perfused juxtamedullary nephron technique. Basal afferent and efferent arteriolar diameters of LPS-treated rats averaged 19.7 ± 0.9 ( n = 7) and 18.3 ± 1.0 μm ( n = 5), respectively, and were similar to those of control rats (20.8 ± 0.3 [ n = 6] and 18.4 ± 0.6 μm [ n = 6], respectively). Superfusion with the selective iNOS inhibitor S,S ′-(1,3-phenylenebis[1,2-ethanediyl]) bisisothiourea (PBIT), at the doses of 0.01, 0.1, and 1 μM, significantly decreased afferent and efferent arteriolar diameters in a dose-dependent manner, whereas afferent or efferent arteriolar diameters of control rats were not altered in response to the same doses of PBIT. In the second series of experiments, superfusion with 10 μM acetylcholine (ACh) significantly increased afferent and efferent arteriolar diameters of LPS-treated rats by 14.9 ± 1.6% ( n = 9) and 6.6 ± 1.1% ( n = 6), respectively. The ACh-induced afferent and efferent arteriolar dilator responses were inhibited by superfusion with the nonselective NOS inhibitor N ω -nitro-L-arginine (100 μM). However, afferent and efferent arteriolar dilator responses to ACh were significantly enhanced during selective iNOS inhibition with 1 μM PBIT (40.1 ± 0.7% and 25.2 ± 1.3%, respectively). These results suggest that activation of iNOS by LPS increases the influence of nitric oxide on afferent and efferent arteriolar tone and impairs endothelium-dependent nitric oxide effects.
Lung function and mortality in the United States: data from the First National Health and Nutrition Examination Survey follow up study
Authors: D M Mannino
Journal: Thorax (2003)

A study was undertaken to define the risk of death among a national cohort of US adults both with and without lung disease.Participants in the first National Health and Nutrition Examination Survey (NHANES I) followed for up to 22 years were studied. Subjects were classified using a modification of the Global Initiative for Chronic Obstructive Lung Disease criteria for chronic obstructive pulmonary disease (COPD) into the following mutually exclusive categories using the forced expiratory volume in 1 second (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC ratio, and the presence of respiratory symptoms: severe COPD, moderate COPD, mild COPD, respiratory symptoms only, restrictive lung disease, and no lung disease. Proportional hazard models were developed that controlled for age, race, sex, education, smoking status, pack years of smoking, years since quitting smoking, and body mass index.A total of 1301 deaths occurred in the 5542 adults in the cohort. In the adjusted proportional hazards model the presence of severe or moderate COPD was associated with a higher risk of death (hazard ratios (HR) 2.7 and 1.6, 95% confidence intervals (CI) 2.1 to 3.5 and 1.4 to 2.0), as was restrictive lung disease (HR 1.7, 95% CI 1.4 to 2.0).The presence of both obstructive and restrictive lung disease is a significant predictor of earlier death in long term follow up.
High Levels of B-Cell Activating Factor in Patients with Active Chronic Graft-Versus-Host Disease
Authors: Stefanie Sarantopoulos, Kristen E. Stevenson, Haesook T. Kim, Nazmim S. Bhuiya, Corey S. Cutler, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Recent studies suggest that donor B cells as well as T cells contribute to immune pathology in patients with chronic graft-versus-host disease (GVHD). B-cell activating factor (BAFF) promotes survival and differentiation of activated B cells. Thus, we tested whether BAFF correlated with chronic GVHD disease activity and time of onset after allogeneic hematopoietic stem cell transplantation (HSCT). Experimental Design: Patients who had undergone allogeneic HSCT between 1994 and 2005 for hematologic malignancies were studied. ELISA was used to measure plasma BAFF levels and flow cytometry was used to assess BAFF receptor expression on B cells in patients with or without chronic GVHD. Results: In 104 patients, BAFF levels were significantly higher in patients with active chronic GVHD compared with those without disease (P = 0.02 and 0.0004, respectively). Treatment with high-dose prednisone (≥30 mg/d) was associated with reduced BAFF levels in patients with active chronic GVHD (P = 0.0005). Serial studies in 24 patients showed that BAFF levels were high in the first 3 months after HSCT but subsequently decreased in 13 patients who never developed chronic GVHD. In contrast, BAFF levels remained elevated in 11 patients who developed chronic GVHD. Six-month BAFF levels ≥10 ng/mL were strongly associated with subsequent development of chronic GVHD (P &amp;lt; 0.0001). Following transplant, plasma BAFF levels correlated inversely with BAFF receptor expression on B cells (P = 0.01), suggesting that soluble BAFF affected B cells through this receptor. Conclusion: These results suggest that elevated BAFF levels contribute to B-cell activation in patients with active chronic GVHD.
Cholera toxin subunit B inhibits IL-12 and IFN- production and signaling in experimental colitis and Crohn's disease
Authors: E M Coccia
Journal: Gut (2005)

<b>Background and aims:</b> Cholera toxin B subunit (CT-B) is a powerful modulator of immune responses. The authors have previously demonstrated that oral administration of recombinant CT-B (rCT-B) is able to prevent and cure the Crohn's disease (CD)-like trinitrobenzene sulfonic acid (TNBS) mediated colitis. In this study they extended their observations and examined if rCT-B interferes with the molecular signaling underlying the Th1 type response both in TNBS colitis and in ex vivo human CD explants. <b>Methods:</b> TNBS treated mice were fed with rCT-B, and IFN-γ and IL-12 production by colonic lamina propria mononuclear cells (LPMC) was examined by ELISA. In vitro culture of mucosal explants from CD patients and non-inflammatory bowel disease controls, pre-incubated with rCT-B, were examined for IFN-γ and IL-12 production by ELISA and semiquantitative reverse transcription polymerase chain reactions. STAT-1, -4, -6 activation and T-bet expression were examined following rCT-B treatment by western blotting both in TNBS treated mice and in human mucosal explants. <b>Results:</b> rCT-B significantly reduced IL-12 and IFN-γ secretion by LPMC from TNBS treated mice. Consistent with this, rCT-B inhibited both STAT-4 and STAT-1 activation and downregulated T-bet expression. Inhibition of Th1 signaling by CT-B associated with no change in IL-4 synthesis and expression of active STAT-6 indicating that rCT-B does not enhance Th2 cell responses. Moreover, in vitro treatment of CD mucosal explants with rCT-B resulted in reduced secretion of IL-12/IFN-γ and inhibition of STAT-4/STAT-1 activation and T-bet expression. <b>Conclusions:</b> These studies indicate that CT-B inhibits mucosal Th1 cell signaling and suggest that rCT-B may be a promising candidate for CD therapy.
Tissue Redox Activity as a Hallmark of Carcinogenesis: From Early to Terminal Stages of Cancer
Authors: Rumiana Bakalova, Zhivko Zhelev, Ichio Aoki, Tsuneo Saga
Journal: Clinical Cancer Research (2013)

Abstract Purpose: The study aimed to clarify the dynamics of tissue redox activity (TRA) in cancer progression and assess the importance of this parameter for therapeutic strategies. Experimental Design: The experiments were carried out on brain tissues of neuroblastoma-bearing, glioma-bearing, and healthy mice. TRA was visualized in vivo by nitroxide-enhanced MRI on anesthetized animals or in vitro by electron paramagnetic resonance spectroscopy on isolated tissue specimens. Two biochemical parameters were analyzed in parallel: tissue total antioxidant capacity (TTAC) and plasma levels of matrix metalloproteinases (MMP). Results: In the early stage of cancer, the brain tissues were characterized by a shorter-lived MRI signal than that from healthy brains (indicating a higher reducing activity for the nitroxide radical), which was accompanied by an enhancement of TTAC and MMP9 plasma levels. In the terminal stage of cancer, tissues in both hemispheres were characterized by a longer-lived MRI signal than in healthy brains (indicating a high-oxidative activity) that was accompanied by a decrease in TTAC and an increase in the MMP2/MMP9 plasma levels. Cancer progression also affected the redox potential of tissues distant from the primary tumor locus (liver and lung). Their oxidative status increased in both stages of cancer. Conclusions: The study shows that tissue redox balance is very sensitive to the progression of cancer and can be used as a diagnostic marker of carcinogenesis. The study also suggests that the noncancerous tissues of a cancer-bearing organism are susceptible to oxidative damage and should be considered a therapeutic target. Clin Cancer Res; 19(9); 2503–17. ©2013 AACR.
A Danish Diabetes Risk Score for Targeted Screening
Authors: Charlotte Glümer, Bendix Carstensen, Annelli Sandbæk, Torsten Lauritzen, Torben Jørgensen, Knut Borch-Johnsen
Journal: Diabetes Care (2004)

OBJECTIVE—To develop a simple self-administered questionnaire identifying individuals with undiagnosed diabetes with a sensitivity of 75% and minimizing the high-risk group needing subsequent testing. RESEARCH DESIGN AND METHODS—A population-based sample (Inter99 study) of 6,784 individuals aged 30–60 years completed a questionnaire on diabetes-related symptoms and risk factors. The participants underwent an oral glucose tolerance test. The risk score was derived from the first half and validated on the second half of the study population. External validation was performed based on the Danish Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION) pilot study. The risk score was developed by stepwise backward multiple logistic regression. RESULTS—The final risk score included age, sex, BMI, known hypertension, physical activity at leisure time, and family history of diabetes, items independently and significantly (P &amp;lt; 0.05) associated with the presence of previously undiagnosed diabetes. The area under the receiver operating curve was 0.804 (95% CI 0.765–0.838) for the first half of the Inter99 population, 0.761 (0.720–0.803) for the second half of the Inter99 population, and 0.803 (0.721–0.876) for the ADDITION pilot study. The sensitivity, specificity, and percentage that needed subsequent testing were 76, 72, and 29%, respectively. The false-negative individuals in the risk score had a lower absolute risk of ischemic heart disease compared with the true-positive individuals (11.3 vs. 20.4%; P &amp;lt; 0.0001). CONCLUSIONS—We developed a questionnaire to be used in a stepwise screening strategy for type 2 diabetes, decreasing the numbers of subsequent tests and thereby possibly minimizing the economical and personal costs of the screening strategy.
THE EFFECT OF POTASSIUM IN NEPHRECTOMIZED RATS WITH HYPOKALEMIC ALKALOSIS
Authors: Jack Orloff, Thomas J. Kennedy, Robert W. Berliner
Journal: Journal of Clinical Investigation (1953)

On the basis of balance studies conducted on rats recovering from hypokalemic alkalosis, Cooke, Segar, Cheek, Coville and Darrow (1) have con- cluded that a shift of hydrogen ions into muscle cells in exchange for potassium is the basis of the extracellular alkalosis.This thesis received further support from the studies of Black and Milne (2) on the development of hypokalemic alkalosis in man.
Dose Finding and Early Efficacy Study of Gemcitabine Plus Capecitabine in Combination With Bevacizumab Plus Erlotinib in Advanced Pancreatic Cancer
Authors: Naureen Starling, David Watkins, David Cunningham, Janet Thomas, Janine Webb, Gina Brown, Karen Thomas, Jacqui Oates, Ian Chau
Journal: Journal of Clinical Oncology (2009)

This study evaluated safety and efficacy of chemotherapy (gemcitabine plus capecitabine) plus bevacizumab/erlotinib in advanced pancreatic cancer because dual epidermal growth factor receptor/vascular endothelial growth factor blockade has a rational biologic basis in this malignancy.Patients with untreated, unresectable, locally advanced or metastatic pancreatic carcinoma were enrolled onto one of the following four sequential dose levels (DLs) of escalating capecitabine doses (days 1 to 21): DL1, 910 mg/m(2); DL2, 1,160 mg/m(2); DL3, 1,400 mg/m(2); or DL4, 1,660 mg/m(2). Doses of coadministered gemcitabine (1,000 mg/m(2) on days 1, 8, and 15), bevacizumab (5 mg/kg on days 1 and 15), and erlotinib (100 mg/d) every 28 days (up to six cycles) were fixed. Using a 3+3 study design, dose-limiting toxicity (DLT) was assessed in cycle 1. Results Twenty assessable patients were enrolled (DL1, n = 8; DL2, n = 3; DL3, n = 6; and DL4, n = 3); 97 cycles were administered. Median age was 63 years (range, 33 to 77 years), and male-to-female ratio was 10:10. Performance status was 0 and 1 in two and 17 patients, respectively; and nine and 11 patients had locally advanced and metastatic disease, respectively. DLT occurred in one patient at DL1 (grade 3 epistaxis) and two patients at DL4 (grade 3 diarrhea and grade 3 skin rash > 7 days). Common grade 3 and 4 toxicities (10% to 20%) were diarrhea, hand-foot syndrome, stomatitis, and skin rash. Grade 3 lethargy and grade 3 or 4 neutropenia occurred in 40% and 45% of patients, respectively. No GI perforation, grade 3 GI hemorrhage/hypertension, or pneumonitis occurred. Ten partial responses were observed. Median overall and progression-survival times (all patients) were 12.5 and 9.0 months, respectively.The maximum-tolerated dose of capecitabine was 1,660 mg/m(2). The recommended capecitabine dose in this cytotoxic doublet/biologic doublet regimen is 1,440 mg/m(2); this regimen is under evaluation in an ongoing phase II study.
Associations of Dietary Fiber With Glucose Metabolism in Nondiabetic Relatives of Subjects With Type 2 Diabetes
Authors: Katriina Ylönen, Carola Saloranta, Carina Kronberg-Kippilä, Leif Groop, Antti Aro, Suvi M. Virtanen
Journal: Diabetes Care (2003)

OBJECTIVE—To study cross-sectional associations of dietary fiber intake with insulin resistance, insulin secretion, and glucose tolerance in a population at high risk for type 2 diabetes. RESEARCH DESIGN AND METHODS—The subjects consisted of 248 male and 304 female adult nondiabetic relatives of patients with type 2 diabetes. Dietary intake was measured by means of two 3-day food records. Associations of total, water-insoluble, and water-soluble fiber with measures of glucose metabolism based on an oral glucose tolerance test, were analyzed by multiple linear regression analysis adjusting for sex, age, length of education, physical activity, BMI, waist-to-hip ratio, systolic blood pressure, and serum triglyceride and HDL cholesterol concentrations. The homeostasis model assessment insulin resistance index, the incremental 30-min serum insulin concentration divided by the incremental 30-min glucose concentration, and fasting and 2-h glucose concentrations were the outcome variables. RESULTS—The dietary intake of total as well as water-insoluble and water-soluble fiber was inversely associated with insulin resistance: −0.17 (0.07), P = 0.012; −0.15 (0.07), P = 0.024; and −0.14 (0.07), P = 0.049 [regression coefficients (SE)]. Fiber variables were unrelated to insulin secretion and plasma glucose concentrations. CONCLUSIONS—The results support evidence that a high intake of dietary fiber is associated with enhanced insulin sensitivity and therefore may have a role in the prevention of type 2 diabetes.
Loss of the Transmembrane but not the Soluble Kit Ligand Isoform Increases Testicular Germ Cell Tumor Susceptibility in Mice
Authors: Jason D. Heaney, Man-Yee J. Lam, Megan V. Michelson, Joseph H. Nadeau
Journal: Cancer Research (2008)

Several genetic variants act as modifiers of testicular germ cell tumor (TGCT) susceptibility in the 129/Sv mouse model of human pediatric TGCTs. One such modifier, the Steel locus, encodes the transmembrane-bound and soluble ligand of the kit receptor. Some (Sl and SlJ) but not all (Sld) mutations of the Steel locus increase TGCT incidence in heterozygous mutant mice. Because Sl and SlJ are large deletions that affect multiple transcripts and Sld is an intragenic deletion of the kit ligand (Kitl) from which only the soluble protein is produced, it was uncertain whether Kitl or a neighboring gene is a modifier of TGCT susceptibility. We tested the effect of the small Steel grizzle-belly (Slgb) deletion on TGCT susceptibility to determine whether Kitl is a TGCT modifier gene. An increase in TGCT incidence was observed in Slgb/+ heterozygotes, and fine mapping of the deletion breakpoints revealed that Kitl is the only conventional gene deleted by the mutation, suggesting that Kitl is the TGCT modifier gene at the Steel locus. Additionally, we propose that soluble KITL in Sld/+ heterozygous mutant mice complements a dosage effect of transmembrane-associated kit ligand on TGCT susceptibility and that the kit receptor (Kit) is haplosufficient for primordial germ cell development.
NAPOLI-1: Randomized Phase 3 Study of MM-398 (NAL-IRI), with or Without 5-Fluorouracil and Leucovorin, Versus 5-Fluorouracil and Leucovorin, in Metastatic Pancreatic Cancer Progressed on or Following Gemcitabine-Based Therapy
Authors: D. Von Hoff, C.P. Li, A. Wang-Gillam, G. Bodoky, A. Dean, G. Jameson, T. Macarulla, K.H. Lee, D. Cunningham, J.F. Blanc, R. Hubner, C.F. Chiu, G. Schwartsmann, J. Siveke, F. Braiteh, V. Moyo, B. Belanger, N. Dhindsa, E. Bayever, L.T. Chen
Journal: Annals of Oncology (2014)
Blood Viscosity in Subjects With Normoglycemia and Prediabetes
Authors: Concetta Irace, Claudio Carallo, Faustina Scavelli, Maria Serena De Franceschi, Teresa Esposito, Agostino Gnasso
Journal: Diabetes Care (2013)

Blood viscosity (BV) is higher in diabetic patients and might represent a risk factor for the development of insulin resistance and type 2 diabetes. However, data in subjects with normal glucose or prediabetes are missing. In the current study, we evaluated the relationship between BV and blood glucose in subjects with normal glucose or prediabetes.Enrolled subjects were divided into three groups according to blood glucose: group A (n = 74), blood glucose <90 mg/dL; group B (n = 96), blood glucose ranging from 90 to 99 mg/dL; and group C (n = 94), blood glucose ranging from 100 to 125 mg/dL. BV was measured at 37°C with a cone-plate viscometer at shear rates ranging from 225 to 22.5 s(-1).Blood pressure, blood lipids, fibrinogen, and plasma viscosity were similar in the three groups. BMI and waist circumference were significantly increased in group C. Hematocrit (P < 0.05) and BV (P between 0.01 and 0.001) were significantly higher in groups B and C compared with group A. Blood glucose was significantly and inversely correlated with HDL cholesterol and directly with BMI, waist, hematocrit (r = 0.134), and BV (from 225 s(-1) to 22.5 s(-1); r ranging from 0.162 to 0.131). BV at shear rate 225 s(-1) was independently associated with blood glucose.The current study shows a direct relationship between BV and blood glucose in nondiabetic subjects. It also suggests that, even within glucose values considered completely normal, individuals with higher blood glucose levels have increased BV comparable with that observed in subjects with prediabetes.
Interaction between birth complications and early maternal rejection in predisposing individuals to adult violence: specificity to serious, early-onset violence
Authors: A Raine, P Brennan, S A Mednick
Journal: American Journal of Psychiatry (1997)

The authors previously reported that birth complications interact with early maternal rejection in predisposing individuals to violence at age 18 years. This study extended the follow-up period for violent offending from 18 years to 34 years, thus increasing the sample of violent offenders threefold and allowing more detailed analyses on onset and type of violence, the form of maternal rejection, and the effect of maternal mental illness.Complications in the births of 4,269 males in Denmark, maternal rejection of these individuals before the age of 1 year, and their histories of criminal offenses at age 34 years were assessed.The biosocial interaction previously observed held for violent but not nonviolent crime, was specific to more serious forms of violence and not threats of violence, held for early-onset but not late-onset violence, and was not accounted for by psychiatric illness in the mothers. Being reared in a public care institution in the first year of life and the mother's attempt to abort the fetus were the key aspects of maternal rejection that interacted with birth complications in predisposing a subject to violence.These findings 1) indicate that the mechanisms underlying early-onset, serious violence differ from those for less serious, late-onset violence, 2) implicate very early factors in the development of violence, 3) highlight the potential importance of integrating psychosocial with biological factors in understanding and preventing violence, and 4) suggest that interventions to reduce birth complications and maternal rejection may help reduce violence.