tbuckley/cabot-search huggingface dataset:
DISTRIBUTION OF THE Rh FACTOR IN AMERICAN INDIANS
Authors: Karl Landsteiner, Alexander S. Wiener, G. Albin Matson
Journal: The Journal of Experimental Medicine (1942)

Erythrocytes from 120 full blooded American Indians and 155 Indians of mixed ancestry were tested for the Rh agglutinogen. Only a single blood among the full blooded Indians appeared to lack this factor, and in the Indians known not to be full blooded, the distribution of this (and other) blood properties was found to be intermediate between that for whites and pure Indians according to expectation. A variant of Rh demonstrable by a special human serum was more than twice as frequent in full blooded Indians as in white individuals.
Analysis of Published Criteria for Clinically Inactive Disease in a Large Juvenile Dermatomyositis Cohort Shows That Skin Disease Is Underestimated
Authors: Beverley Almeida, Raquel Campanilho‐Marques, Katie Arnold, Clarissa A. Pilkington, Lucy R. Wedderburn, Kiran Nistala
Journal: Arthritis & Rheumatology (2015)

Objective The Pediatric Rheumatology International Trials Organisation (PRINTO) recently published criteria for classification of patients with juvenile dermatomyositis (DM) as having clinically inactive disease. The criteria require that at least 3 of 4 conditions be met, i.e., creatine kinase level ≤150 units/liter, Childhood Myositis Assessment Scale score ≥48, Manual Muscle Testing in 8 muscles score ≥78, and physician's global assessment of overall disease activity (PGA) ≤0.2. The present study was undertaken to test these criteria in a UK cohort of patients with juvenile DM. Methods We assessed 1,114 patient visits for the 4 items in the PRINTO criteria for clinically inactive disease. Each visit was analyzed to determine whether skin disease was present. The Disease Activity Score (DAS) for juvenile DM was determined in 59 patients. Results At 307 of the 1,114 visits, clinically inactive disease was achieved based on the 3 muscle criteria (but with a PGA of &gt;0.2); rash was present at 65.8% of these visits and nailfold capillary abnormalities at 35.2%. When PGA ≤0.2 was one of the 3 criteria that were met, the frequency of skin signs was significantly lower (rash in 23.1% and nailfold capillary abnormalities in 8.7%). If PGA was considered an essential criterion for clinically inactive disease (P‐CID), patients with active skin disease were less likely to be categorized as having clinically inactive disease (a median DAS skin score of 0 [of a possible maximum of 9] in visits where the PGA was ≤0.2, versus a median DAS skin score of 4 in patients meeting the 3 muscle criteria [with a PGA of &gt;0.2]; P &lt; 0.001). Use of the P‐CID led to improvements in the positive predictive value and the positive likelihood ratio (85.4% and 11.0, respectively, compared to 72.9% and 5.1 with the current criteria). Conclusion There was a high frequency of skin disease among patients with juvenile DM who did not meet the PGA criterion for inactive disease but met the other 3 criteria. Incorporating PGA as an essential criterion for clinically inactive disease helps prevent the misclassification of patients with active skin disease.
Thyrotropin-releasing Hormone Stimulation of Adrenocorticotropin Production by Mouse Pituitary Tumor Cells in Culture
Authors: Marvin C. Gershengorn, Carlos O. Arevalo, Elizabeth Geras, Mario J. Rebecchi
Journal: Journal of Clinical Investigation (1980)

ACTH-producing mouse pituitary tumor cells in culture (AtT-20/NYU-1 cells) were found to have binding sites for thyrotropin-releasing hormone (TRH). These putative receptors bound TRH with high affinity; the apparent equilibrium dissociation constant was 3.7 nM. The affinity of the receptors for a series of TRH analogues was similar to those previously reported for TRH-receptor interactions on thyrotropic and mammotropic cells in culture. Like some human pituitary tumors in situ, AtT-20/NYU-1 cells were found to produce the alpha subunit of the glycoprotein hormones (alpha). Alpha accumulation in the medium was constant (3.1 ng/mg cell protein per h) and was not affected by TRH. In contrast, TRH increased the amount of ACTH accumulated in the medium from AtT-20/NYU-1 cells to 190 and 420% of control at 1 and 24 h, respectively. TRH induced a dose-dependent increase in ACTH release during a 30-min incubation; half-maximal stimulation occurred at ∼0.1 nM. TRH had no effect on ACTH release in vitro from anterior pituitary cells derived from normal rats. Because TRH stimulates release of ACTH in some untreated patients with Cushing's disease and Nelson's syndrome as well as pathological states associated with pituitary tumors (but not in normal subjects), AtT-20/NYU-1 cells may serve as an important in vitro model for human pituitary ACTH-secreting adenomas. Moreover, these findings suggest that the primary abnormality in Cushing's disease and Nelson's syndrome, allowing TRH stimulation of ACTH release, may be intrinsic to neoplastic adrenocorticotrophs rather than in neuroregulation of ACTH release.
Effects of a Monounsaturated Fatty Acid–Enriched Hypocaloric Diet on Cardiovascular Risk Factors in Obese Patients With Type 2 Diabetes
Authors: Barry Gumbiner, Cecilia C Low, Peter D Reaven
Journal: Diabetes Care (1998)

OBJECTIVE To determine whether the lipoprotein response to weight loss in obese patients with type 2 diabetes can be improved by modifying the macronutrient composition of the commonly prescribed low-fat, high-carbohydrate (CHO) hypocaloric diet. RESEARCH DESIGN AND METHODS Nine obese patients with type 2 diabetes were treated with a monounsaturated fatty acid (MUFA)-enriched weight-reducing formula diet and compared with eight obese patients with type 2 diabetes treated with a low-fat, high-CHO weight-reducing formula diet. Weight loss ensued for 6 weeks, followed by 4 weeks of refeeding using isocaloric formulas enriched with MUFA or CHO, respectively. Fasting blood samples were obtained to measure plasma lipoproteins and LDL susceptibility to oxidation (measured as lag time: time required to induce in vitro formation of conjugated dienes). RESULTS At baseline, there were no differences between the groups in plasma lipids, lipoproteins, or LDL susceptibility to oxidation. Weight loss was similar between the groups. Dieting resulted in decreases in total plasma cholesterol, LDL, HDL, triglycerides, and apolipoproteins A and B (P &amp;lt; 0.05), but the MUFA group manifested a greater decrease in total cholesterol, triglycerides, and apolipoprotein B and a smaller decrease in HDL and apolipoprotein A than the CHO group (P &amp;lt; 0.05). Improvements in these parameters were sustained during refeeding. After dieting, lag time was prolonged in the MUFA group (208 ± 10 min) compared with the CHO group (146 ± 11 min; P &amp;lt; 0.05). Lag time was prolonged further during refeeding in the MUFA group (221 ± 13 min, P = 0.10), while the CHO group remained unchanged (152 ± 9 min, P &amp;lt; 0.05). Lag time correlated strongly with the oleic acid content of LDL after dieting and refeeding (r = 0.74 and r = 0.93, respectively; both P &amp;lt; 0.001). CONCLUSIONS Macronutrient content is an important determinant of the lipoprotein response to weight loss in obese patients with type 2 diabetes. MUFA-enriched hypocaloric diets potentiate the beneficial effects of weight loss to ameliorate cardiovascular risk factors in obese patients with type 2 diabetes.
Long-Term Therapy for Chronic Bacteriuria in Men
Authors: RICHARD B. FREEMAN
Journal: Annals of Internal Medicine (1975)

Response to therapy, renal function, and mortality were analyzed in a prospective study of 249 men with bacteriuria followed for up to 10 years. All patients received initial organism-specific antibiotic therapy followed by 2 years of continuous treatment with sulfamethizole, nitrofurantoin, methenamine mandelate, or placebo. Continuous therapy with active drugs delayed recurrence of bacteriuria and reduced acute clinical exacerbations of infection. Patients with pure Escherichia coli bacteriuria, normal intravenous pyelogram, no previous therapy, and a normal prostate had a good prognosis with short-term antibiotic therapy alone. The presence of prostatic or upper urinary tract calculi, pyelonephritic scars, or mixed or enterococcal infections predicted a poor bacteriologic prognosis. In the absence of severe urologic disease or concomitant noninfectious renal disease no patients with persistent bacteriuria developed renal failure. Continuous antibiotic therapy is of value in selected male patients with bacteriuria in reducing recurrence and acute clinical exacerbations of urinary tract infection.
Regulation of G Protein–Coupled Receptor Signaling by Scaffold Proteins
Authors: Randy A. Hall, Robert J. Lefkowitz
Journal: Circulation Research (2002)

The actions of many hormones and neurotransmitters are mediated through stimulation of G protein–coupled receptors. A primary mechanism by which these receptors exert effects inside the cell is by association with heterotrimeric G proteins, which can activate a wide variety of cellular enzymes and ion channels. G protein–coupled receptors can also interact with a number of cytoplasmic scaffold proteins, which can link the receptors to various signaling intermediates and intracellular effectors. The multicomponent nature of G protein–coupled receptor signaling pathways makes them ideally suited for regulation by scaffold proteins. This review focuses on several specific examples of G protein–coupled receptor-associated scaffolds and the roles they may play in organizing receptor-initiated signaling pathways in the cardiovascular system and other tissues.
The measurement and importance of red cell survival
Authors: Robert S. Franco
Journal: American Journal of Hematology (2008)

The measurement of red blood cell survival in the circulation has progressed from the original differential agglutination technique of Ashby to current isotopic and flow cytometric methods. While occasionally useful in the clinic, these methods find widespread use in a number of important research areas, including the evaluation of new red cell storage media in transfusion medicine and studies of the pathophysiology of sickle cell disease and diabetes. In this review, measurement techniques are placed in historical perspective and examined for relative merits and suitable application.
Cholestatic liver injury secondary to artemisinin
Authors: Shiva Kumar
Journal: Hepatology (2015)

1Center for Liver Disease & Transplantation, Aurora St. Luke's Medical Center, Milwaukee, Wisconsin, USA, and Digestive Disease InstituteCleveland Clinic Abu DhabiAbu DhabiUnited Arab Emirates *Address reprint requests to: Shiva Kumar, M.D., M.S., Digestive Disease Institute, Cleveland Clinic Abu Dhabi, PO Box 112412, Abu Dhabi, United Arab Emirates. E‐mail: [email protected]; Fax: +971 2 410 8374.
Effects of Rest Interval on the Release of Calcium From the Sarcoplasmic Reticulum in Isolated Guinea Pig Ventricular Myocytes
Authors: Cesare M. N. Terracciano, Ruby U. Naqvi, Kenneth T. MacLeod
Journal: Circulation Research (1995)

Abstract Guinea pig cardiac myocytes were loaded with the fluorescent dye indo 1, and cell contraction was measured by a video edge-detection system. Ca 2+ was released from the sarcoplasmic reticulum (SR) by rapidly cooling the myocytes or by rapid application of 10 mmol/L caffeine. Estimates of the amount of Ca 2+ released from the SR after different rest intervals (ie, under different loading conditions) were obtained by measuring the current evoked by rapid application of 10 mmol/L caffeine, which we call Na + /Ca 2+ exchange current. This current is completely inhibited by removal of extracellular Na + and Ca 2+ or by application of 5 mmol/L Ni 2+ . SR Ca 2+ release after rest intervals of 5 to 120 seconds (assuming cell volume to be 30×10 −12 L) was estimated to be 57.8±5.7 to 25.7±4.5 μmol/L accessible cell volume, respectively, equivalent to 23 to 10 μmol/kg wet wt, respectively. There was an exponential decline in Ca 2+ released from the SR after rest intervals of 2 to 120 seconds (rate constant, 0.029 s −1 ; t 1/2 , 24 seconds); thereafter, there remained a portion (56%) of Ca 2+ releasable to caffeine application. We found a similar exponential decay (rate constant, 0.020 s −1 ; t 1/2 , 35 seconds) of the size of rapid cooling contractures with increasing rest intervals. The time to peak of the Na + /Ca 2+ exchange current in the presence of caffeine slowed at long rest intervals, ie, at smaller SR loads. A decrease in SR load of 50% increased the time to peak of the exchange current by 213±37% (n=6). The rate of generation of a rapid cooling contracture was faster after short rest intervals and was associated with a faster rise in the corresponding increase in indo 1 fluorescence. A decrease in SR load of 50% decreased the rate of cell shortening to 34±5% and decreased the rate of change in fluorescence to 54±2% (n=5).
Early onset of somatic mutation in immunoglobulin VH genes during the primary immune response.
Authors: N S Levy, U V Malipiero, S G Lebecque, P J Gearhart
Journal: The Journal of Experimental Medicine (1989)

The dynamics of somatic mutation in Ig variable genes was investigated in order to define a population of B cells undergoing mutation. BALB/cJ mice were injected with PC-KLH, and splenic RNA was prepared 5, 7, and 13 d later. The mRNA was annealed to gamma constant region primers to make cDNA transcripts encoding VH genes. 103 cDNA clones corresponding to 18 different genes from the VH7183, VH3660, and VHS107 subfamilies were sequenced to identify mutation. VH genes had a low level of mutation on day 5 after immunization and accumulated more mutation by day 7 at a rate of 10(-3) mutations per nucleotide per generation. However, by day 13, the number of mutations per gene did not increase, and most of the substitutions encoded replacement amino acid changes that were clustered in the hypervariable regions, indicating that the mutational process was less active during the second week and that antigen selection had occurred. The data are consistent with a developmentally regulated mechanism in which mutation is activated during the first week of the primary immune response for a limited time period, after which selection acts to preserve the beneficial mutants.
Incidence of probable occupational asthma and changes in airway calibre and responsiveness in apprentice welders
Authors: M. El-Zein, J-L. Malo, C. Infante-Rivard, D. Gautrin
Journal: European Respiratory Journal (2003)

The majority of cross-sectional studies have shown a higher prevalence of ventilatory impairment in welders while only few longitudinal studies were able to detect chronic effects on spirometry or bronchial responsiveness. The aim of the study was to determine the incidence of probable occupational asthma (OA), bronchial obstruction and hyperresponsiveness among 286 students entering an apprenticeship programme in the welding profession. This epidemiological prospective cohort study consisted of a baseline assessment survey and two follow-up assessments. A respiratory symptom questionnaire was administered at each visit. Spirometry and methacholine bronchial challenge test results, conducted once prior to onset of exposure and later after an average of 15 months of apprenticeship, were available for 194 subjects. The incidence of probable OA was ∼3% (6 of 194). The incidence of bronchial hyperresponsiveness, defined as a ≥3.2‐fold decrease in the provocative concentration causing a 20% fall in the forced expiratory volume in one second from baseline to the end of the study was 11.9%. A statistically significant difference was found between the baseline and end of study for the lung function values. In particular, the forced expiratory volume per cent predicted had significantly dropped by 8.4% on average. The significance of these early pulmonary function changes in relation to possible chronic effects of exposure to welding fumes and gases remains to be explored.
Collaborative Care Intervention Targeting Violence Risk Behaviors, Substance Use, and Posttraumatic Stress and Depressive Symptoms in Injured Adolescents
Authors: Douglas Zatzick, Joan Russo, Sarah Peregrine Lord, Christopher Varley, Jin Wang, Lucy Berliner, Gregory Jurkovich, Lauren K. Whiteside, Stephen O’Connor, Frederick P. Rivara
Journal: JAMA Pediatrics (2014)

Violence and injury risk behaviors, alcohol and drug use problems, and posttraumatic stress disorder (PTSD) and depressive symptoms occur frequently among adolescents presenting to acute care medical settings after traumatic physical injury.To test the effectiveness of a stepped collaborative care intervention targeting this constellation of risk behaviors and symptoms in randomly sampled hospitalized adolescents with and without traumatic brain injury.A pragmatic randomized clinical trial was conducted at a single US level I trauma center. Participants included 120 adolescents aged 12 to 18 years randomized to intervention (n = 59) and control (n = 61) conditions.Stepped collaborative care intervention included motivational interviewing elements targeting risk behaviors and substance use as well as medication and cognitive behavioral therapy elements targeting PTSD and depressive symptoms.Adolescents were assessed at baseline before randomization and 2, 5, and 12 months after injury hospitalization. Standardized instruments were used to assess violence risk behaviors, alcohol and drug use, and PTSD and depressive symptoms.The investigation attained more than 95% adolescent follow-up at each assessment point. At baseline, approximately one-third of the participants endorsed the violence risk behavior of carrying a weapon. Regression analyses demonstrated that intervention patients experienced significant reductions in weapon carrying compared with controls during the year after injury (group × time effect, F3,344 = 3.0; P = .03). At 12 months after the injury, 4 (7.3%) intervention patients vs 13 (21.3%) control patients reported currently carrying a weapon (relative risk, 0.31; 95% CI, 0.11-0.90). The intervention was equally effective in reducing the risk of weapon carrying among injured adolescents with and without traumatic brain injury. Other treatment targets, including alcohol and drug use problems and high levels of PTSD and depressive symptoms, occurred less frequently in the cohort relative to weapon carrying and were not significantly affected by the intervention.Collaborative care intervention reduced the risk of adolescent weapon carrying during the year after the injury hospitalization. Future investigation should replicate this preliminary observation. If the finding is replicated, orchestrated investigative and policy efforts could systematically implement and evaluate screening and intervention procedures targeting youth violence prevention at US trauma centers.clinicaltrials.gov identifier: NCT00619255.
Functional bowel disorders and functional abdominal pain
Authors: W G Thompson, G F Longstreth, D A Drossman, K W Heaton, E J Irvine, S A Muller-Lissner
Journal: Gut (1999)

The Rome diagnostic criteria for the functional bowel disorders and functional abdominal pain are used widely in research and practice. A committee consensus approach, including criticism from multinational expert reviewers, was used to revise the diagnostic criteria and update diagnosis and treatment recommendations, based on research results. The terminology was clarified and the diagnostic criteria and management recommendations were revised. A functional bowel disorder (FBD) is diagnosed by characteristic symptoms for at least 12 weeks during the preceding 12 months in the absence of a structural or biochemical explanation. The irritable bowel syndrome, functional abdominal bloating, functional constipation, and functional diarrhea are distinguished by symptom-based diagnostic criteria. Unspecified FBD lacks criteria for the other FBDs. Diagnostic testing is individualized, depending on patient age, primary symptom characteristics, and other clinical and laboratory features. Functional abdominal pain (FAP) is defined as either the FAP syndrome, which requires at least six months of pain with poor relation to gut function and loss of daily activities, or unspecified FAP, which lacks criteria for the FAP syndrome. An organic cause for the pain must be excluded, but aspects of the patient’s pain behavior are of primary importance. Treatment of the FBDs relies upon confident diagnosis, explanation, and reassurance. Diet alteration, drug treatment, and psychotherapy may be beneficial, depending on the symptoms and psychological features.
Type I interferon dependence of plasmacytoid dendritic cell activation and migration
Authors: Carine Asselin-Paturel, Géraldine Brizard, Karine Chemin, Andre Boonstra, Anne O'Garra, Alain Vicari, Giorgio Trinchieri
Journal: The Journal of Experimental Medicine (2005)

Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration.
Osteopontin Deficiency Protects against Airway Remodeling and Hyperresponsiveness in Chronic Asthma
Authors: Davina C M Simoes, Georgina Xanthou, Kalomira Petrochilou, Vily Panoutsakopoulou, Charis Roussos, Christina Gratziou
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Osteopontin (OPN) is a cytokine that is upregulated in epithelial cells and macrophages in the lungs of mice during chronic allergen challenge and airway remodeling and also in lungs of patients with asthma. However, it remains unclear whether OPN has an in vivo effect on lung remodeling in allergic asthma. Based on its ability to induce smooth muscle and fibroblast proliferation and migration we hypothesize that OPN regulates lung remodeling and also affects subsequent airway hyperresponsiveness (AHR).Study the role of OPN in airway remodeling using OPN-knockout (KO) mice and a reversal approach administering recombinant mouse OPN (rOPN) in KO mice before challenge.A chronic allergen-challenge model of airway remodeling with OPN KO mice, KO mice treated with rOPN, and human bronchial smooth muscle were used.OPN deficiency protected mice against ova-induced AHR, which was associated with lower collagen and mucus production, gob-5 mRNA expression, submucosal cell area infiltration, and proliferation. Administration of rOPN to KO mice, just at the final five allergen challenges, exacerbated AHR and all the remodeling characteristics measured. In addition, rOPN increased the expression of IL-13 and pro-matrix metalloproteinase-9 in the lungs. Moreover, we demonstrated that rOPN induces proliferation of human BSM through binding to its alpha(v)beta3 integrin receptor and activation of PI3K/Akt downstream signaling pathway.We conclude that OPN deficiency protects against remodeling and AHR. Thus our data reveal OPN as a novel therapeutic target for airway remodeling and associated AHR in chronic asthma.