tbuckley/cabot-search huggingface dataset:
Racial and Ethnic Differences in Utilization of Mental Health Services Among High-Risk Youths
Authors: Ann F. Garland, Anna S. Lau, May Yeh, Kristen M. McCabe, Richard L. Hough, John A. Landsverk
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: Racial and ethnic disparities in mental health service use have been identified as a major public health problem. However, the extent to which these disparities may be accounted for by other confounding sociodemographic or clinical predictors of service use (e.g., family income, functional impairment, caregiver strain) is relatively unexplored, especially for youth services. The goal of this study was to test for racial/ethnic disparities in use of a variety of outpatient, inpatient, and informal mental health services among high-risk youths, with the effects of other predictive factors controlled. METHOD: Participants were 1,256 youths ages 6–18 years who received services in a large, publicly funded system of care (including the child welfare, juvenile justice, special education, alcohol and drug abuse, and mental health service sectors). Youths and caregivers were interviewed with established measures of mental health service use, psychiatric diagnoses, functional impairment, caregiver strain, and parental depression. RESULTS: Significant racial/ethnic group differences in likelihood of receiving any mental health service and, specifically, formal outpatient services were found after the effects of potentially confounding variables were controlled. Race/ethnicity did not exert a significant effect on the use of informal or 24-hour-care services. CONCLUSIONS: Racial/ethnic disparities in service use remain a public health problem.
Exendin(9-39)amide is an antagonist of glucagon-like peptide-1(7-36)amide in humans.
Authors: J Schirra, K Sturm, P Leicht, R Arnold, B Göke, M Katschinski
Journal: Journal of Clinical Investigation (1998)

The gastrointestinal hormone, glucagon-like peptide-1(7-36)amide (GLP-1) is released after a meal. The potency of synthetic GLP-1 in stimulating insulin secretion and in inhibiting glucagon secretion indicates the putative physiological function of GLP-1. In vitro, the nonmammalian peptide, exendin(9-39)amide [ex(9-39)NH2], is a specific and competitive antagonist of GLP-1. This in vivo study examined the efficacy of ex(9-39)NH2 as an antagonist of exogenous GLP-1 and the physiological role of endogenous GLP-1. Six healthy volunteers underwent 10 experiments in random order. In each experiment, a 30-min period of euglycemia was followed by an intravenous infusion of glucose for 150 min that established a stable hyperglycemia of 8 mmol/liter. There was a concomitant intravenous infusion of one of the following: (1) saline, (2) GLP-1 (for 60 min at 0.3 pmol . kg-1 . min-1 that established physiological postprandial plasma levels, and for another 60 min at 0.9 pmol . kg-1 . min-1 to induce supraphysiological plasma levels), (3-5) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 + GLP-1, (6-8) ex(9-39)NH2 at 30, 60, or 300 pmol . kg-1 . min-1 + saline, (9 and 10) GIP (glucose-dependent insulinotropic peptide; for 60 min at 0.8 pmol . kg-1 . min-1, with saline or ex(9-39)NH2 at 300 pmol . kg-1 . min-1). Each volunteer received each of these concomitant infusions on separate days. ex(9-39)NH2 dose-dependently reduced the insulinotropic action of GLP-1 with the inhibitory effect declining with increasing doses of GLP-1. ex(9-39)NH2 at 300 pmol . kg-1 . min-1 blocked the insulinotropic effect of physiological doses of GLP-1 and completely antagonized the glucagonostatic effect at both doses of GLP-1. Given alone, this load of ex(9-39)NH2 increased plasma glucagon levels during euglycemia and hyperglycemia. It had no effect on plasma levels of insulin during euglycemia but decreased plasma insulin during hyperglycemia. ex(9-39)NH2 did not alter GIP-stimulated insulin secretion. These data indicate that in humans, ex(9-39)NH2 is a potent GLP-1 antagonist without any agonistic properties. The pancreatic A cell is under a tonic inhibitory control of GLP-1. At hyperglycemia, the B cell is under a tonic stimulatory control of GLP-1.
Medical Supplies Donated to Hospitals in Bosnia and Croatia, 1994-1995
Authors: Markus Michael
Journal: JAMA (1996)

<h3>Objective.</h3> —To evaluate access to and distribution and quality of medical supplies donated by humanitarian aid organizations to hospitals and health services during the war in Bosnia and Croatia. <h3>Design.</h3> —Retrospective survey of 68 representatives of hospitals and field hospitals regularly caring for inpatients between May 1994 and April 1995. <h3>Setting.</h3> —Three study areas: the Republic and Federation of Bosnia-Herzegovina, Republika Srpska (part of Bosnia-Herzegovina controlled by Bosnian Serbs), and Republika Srpska Krajina (part of Croatia controlled by Croatian Serbs during the study period). <h3>Participants.</h3> —Of 68 hospital representatives, 44 completed the survey (65% response rate). Respondents did not include representatives from 11 hospitals and field hospitals that could not be contacted because of operational obstacles resulting from the ongoing war. <h3>Results.</h3> —Lack of supplies was reported as an important limitation by 62% (26/42) of respondents, followed by lack of staff and security, physical isolation, and lack of infrastructure. Antibiotics were mentioned by 76% (32/42) of respondents as the unavailable drug or item most urgently needed. The majority of drug and medical supplies used to treat patients had been supplied by 5 humanitarian aid organizations. The frequency with which respondents mentioned their "own means" (eg, from the ministry of health or respective municipalities) was relatively low (9%), reflecting the high degree of dependency on humanitarian aid. All respondents rated the quality of donated supplies and the working relationship with the donating organization as "very good" or "satisfactory"; 93% (41/44) of respondents indicated that the donated supplies were appropriate. Six of 44 respondents preferred to receive supplies as part of assembled kits; 70% (31/44) preferred to receive such assistance as loose supplies according to demand. <h3>Conclusion.</h3> —During war, access and security are beyond the control of humanitarian agencies. Assistance coordination, however, must be provided. Although a consensus on policies and objectives between different humanitarian organizations is difficult to reach, satisfactory complementarity can be achieved. The systematic and continuous gathering of information at the recipient and user level, beginning at the early phase of the conflict, is recommended to maintain appropriate assistance.
Identification of uniquely expressed transcription factors in highly purified B‐cell lymphoma samples
Authors: Ulrika Andréasson, Patrik Edén, Carsten Peterson, Carl‐Magnus Högerkorp, Mats Jerkeman, Niels Andersen, Mattias Berglund, Christer Sundström, Richard Rosenquist, Carl A.K. Borrebaeck, Sara Ek
Journal: American Journal of Hematology (2010)

Transcription factors (TFs) are critical for B-cell differentiation, affecting gene expression both by repression and transcriptional activation. Still, this information is not used for classification of B-cell lymphomas (BCLs). Traditionally, BCLs are diagnosed based on a phenotypic resemblance to normal B-cells; assessed by immunohistochemistry or flow cytometry, by using a handful of phenotypic markers. In the last decade, diagnostic and prognostic evaluation has been facilitated by global gene expression profiling (GEP), providing a new powerful means for the classification, prediction of survival, and response to treatment of lymphomas. However, most GEP studies have typically been performed on whole tissue samples, containing varying degrees of tumor cell content, which results in uncertainties in data analysis. In this study, global GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). The identified transcription factors influence both the global and specific gene expression of the BCLs and have possible implications for diagnosis and treatment.
CDK6 kinase activity is required for thymocyte development
Authors: Miaofen G. Hu, Amit Deshpande, Nicolette Schlichting, Elisabeth A. Hinds, Changchuin Mao, Marei Dose, Guo-fu Hu, Richard A. Van Etten, Fotini Gounari, Philip W. Hinds
Journal: Blood (2011)
Selective suppression of an early step in human B cell activation by cyclosporin A.
Authors: A Muraguchi, J L Butler, J H Kehrl, R J Falkoff, A S Fauci
Journal: The Journal of Experimental Medicine (1983)

The effect of cyclosporin A (CsA), a fungal metabolite with immunosuppressive properties, on the induction of human B cell proliferation and differentiation, has been described. CsA had a selective inhibitory effect on the activation phase of the cell cycle vs. the proliferation phase following preactivation of the cells. Cell enlargement and RNA synthesis of small resting B cells triggered by anti-mu were inhibited by addition of CsA (5-500 ng/ml). The inhibitory effect of CsA was found only when the drug was added within 24 h of initiation of culture. In marked contrast, once small B cells were activated by anti-mu, the resulting large, activated B cells could be induced to initiate DNA synthesis by incubation with B cell growth factor (BCGF), and addition of CsA (1-1,000 ng/ml) to the culture did not suppress this BCGF-induced B cell proliferation. Addition of CsA to cultures of B cells which had been preactivated with Staphylococcus aureus Cowan strain I (SAC) and were already proliferating did not suppress B cell differentiation factor (BCDF)-induced differentiation of these cells. Thus, these data indicate that CsA can be used as a pharmacologic tool to dissect out human B cell responses into two distinct steps: (a) the initial activation step induced by anti-Ig, which is characterized by cell enlargement, RNA synthesis, and expression of receptors for BCGF; and (b) the proliferative step induced by BCGF in these preactivated B cells that undergo DNA synthesis and can then go on to differentiate in the presence of BCDF. In this regard, CsA selectively suppresses an early step of human B cell activation and has little inhibitory effect on the subsequent factor-dependent proliferation and differentiation.
Hemodynamics and antianginal effects of high dose oral isosorbide dinitrate after chronic use.
Authors: D T Danahy, W S Aronow
Journal: Circulation (1977)

In a randomized, double-blind, crossover study, 19 patients with angina were exercised 2 min after 0.4 mg sublingual nitroglycerin and after sublingual placebo and before and 1, 3, and 5 hours after oral isosorbide dinitrate (ISDN) and oral placebo. After initial testing, patients took the dose of ISDN they had had during the study (mean dose 29 mg) for a mean period of 5.6 months before retesting using the same protocol. Compared to placebo, exercise time after sublingual nitroglycerin increased 56% (P less than 0.001) initially and 51% (P less than 0.001) at retest. Compared to placebo, exercise time increased 58% (P less than 0.05) initially and 58% (P less than 0.005) at retest 1 hour after ISDN, 38% (P less than 0.05) initially and 27% (P less than 0.005) at retest 3 hours after ISDN, and 13% (NS) initially and 21% (P less than 0.02) at retest five hours after ISDN. The mean exericse times initially and at retest were not significantly different. Hemodynamic changes (decrease in systolic blood pressure and increase in heart rate) at 15 min persisted through 300 min after ISDN during both initial testing and during retesting. However, these changes were significantly less during retesting. We conclude that a partial tolerance to the hemodynamic effects of the drug develops after chronic use of high dose oral ISDN but that the antianginal efficacy of both sublingual nitroglycerin and oral ISDN is unimpaired.
Peripheral insulin resistance predicts liver damage in nondiabetic subjects with nonalcoholic fatty liver disease
Authors: Chiara Rosso, Lavinia Mezzabotta, Melania Gaggini, Federico Salomone, Roberto Gambino, Andrea Marengo, Francesca Saba, Ester Vanni, Ramy Younes, Chiara Saponaro, Emma Buzzigoli, Gian Paolo Caviglia, Maria Lorena Abate, Antonina Smedile, Mario Rizzetto, Maurizio Cassader, Amalia Gastaldelli, Elisabetta Bugianesi
Journal: Hepatology (2015)

Surrogate indexes of insulin resistance and insulin sensitivity are widely used in nonalcoholic fatty liver disease (NAFLD), although they have never been validated in this population. We aimed to validate the available indexes in NAFLD subjects and to test their ability to predict liver damage also in comparison with the NAFLD fibrosis score. Surrogate indexes were validated by the tracer technique (6,6-D2 -glucose and U-(13) C-glucose) in the basal state and during an oral glucose tolerance test. The best-performing indexes were used in an independent cohort of 145 nondiabetic NAFLD subjects to identify liver damage (fibrosis and nonalcoholic steatohepatitis). In the validation NAFLD cohort, homeostasis model assessment of insulin resistance, insulin to glucose ratio, and insulin sensitivity index Stumvoll had the best association with hepatic insulin resistance, while peripheral insulin sensitivity was most significantly related to oral glucose insulin sensitivity index (OGIS), insulin sensitivity index Stumvoll, and metabolic clearance rate estimation without demographic parameters. In the independent cohort, only oral glucose tolerance test-derived indexes were associated with liver damage and OGIS was the best predictor of significant (≥F2) fibrosis (odds ratio = 0.76, 95% confidence interval 0.61-0.96, P = 0.0233) and of nonalcoholic steatohepatitis (odds ratio = 0.75, 95% confidence interval 0.63-0.90, P = 0.0021). Both OGIS and NAFLD fibrosis score identified advanced (F3/F4) fibrosis, but OGIS predicted it better than NAFLD fibrosis score (odds ratio = 0.57, 95% confidence interval 0.45-0.72, P < 0.001) and was also able to discriminate F2 from F3/F4 (P < 0.003).OGIS is associated with peripheral insulin sensitivity in NAFLD and inversely associated with an increased risk of significant/advanced liver damage in nondiabetic subjects with NAFLD.
Ataxia-telangiectasia mutated kinase regulates ribonucleotide reductase and mitochondrial homeostasis
Authors: Jana S. Eaton, Z. Ping Lin, Alan C. Sartorelli, Nicholas D. Bonawitz, Gerald S. Shadel
Journal: Journal of Clinical Investigation (2007)

Ataxia-telangiectasia mutated (ATM) kinase orchestrates nuclear DNA damage responses but is proposed to be involved in other important and clinically relevant functions. Here, we provide evidence for what we believe are 2 novel and intertwined roles for ATM: the regulation of ribonucleotide reductase (RR), the rate-limiting enzyme in the de novo synthesis of deoxyribonucleoside triphosphates, and control of mitochondrial homeostasis. Ataxia-telangiectasia (A-T) patient fibroblasts, wild-type fibroblasts treated with the ATM inhibitor KU-55933, and cells in which RR is inhibited pharmacologically or by RNA interference (RNAi) each lead to mitochondrial DNA (mtDNA) depletion under normal growth conditions. Disruption of ATM signaling in primary A-T fibroblasts also leads to global dysregulation of the R1, R2, and p53R2 subunits of RR, abrogation of RR-dependent upregulation of mtDNA in response to ionizing radiation, high mitochondrial transcription factor A (mtTFA)/mtDNA ratios, and increased resistance to inhibitors of mitochondrial respiration and translation. Finally, there are reduced expression of the R1 subunit of RR and tissue-specific alterations of mtDNA copy number in ATM null mouse tissues, the latter being recapitulated in tissues from human A-T patients. Based on these results, we propose that disruption of RR and mitochondrial homeostasis contributes to the complex pathology of A-T and that RR genes are candidate disease loci in mtDNA-depletion syndromes.
In Vivo Priming of Cd4 T Cells That Produce Interleukin (Il)-2 but Not IL-4 or Interferon (Ifn)-γ, and Can Subsequently Differentiate into IL-4–Or IFN-γ–Secreting Cells
Authors: Xiaowen Wang, Tim Mosmann
Journal: The Journal of Experimental Medicine (2001)

The differentiation of antigen-stimulated naive CD4 T cells into T helper (Th)1 or Th2 effector cells can be prevented in vitro by transforming growth factor (TGF)-β and anti–interferon (IFN)-γ. These cells proliferate and synthesize interleukin (IL)-2 but not IFN-γ or IL-4, and can differentiate into either Th1 or Th2 cells. We have now used two-color Elispots to reveal substantial numbers of primed cells producing IL-2 but not IL-4 or IFN-γ during the Th1- or Th2-biased immune responses induced by soluble proteins or with adjuvants. These cells were CD4+CD44high and were present during immediate and long-term immune responses of normal mice. Naive T cell receptor for antigen (TCR) transgenic (DO11.10) T cells were primed in vivo after adoptive transfer into normal hosts and FACS® cloned under conditions that did not allow further differentiation. After clonal proliferation, aliquots of each clone were cultured in Th1- or Th2-inducing conditions. Many in vivo–primed cells were uncommitted, secreting IL-2 but not IL-4 or IFN-γ at the first cloning step, but secreting either IL-4 or IFN-γ after differentiation in the appropriate conditions. These in vivo-primed, uncommitted, IL-2–producing cells may constitute an expanded pool of antigen-specific cells that provide extra flexibility for immune responses by differentiating into Th1 or Th2 phenotypes later during the same or subsequent immune responses.
Immunoglobulins and complement components in synovial fluid of patients with acute rheumatic fever.
Authors: M Svartman, E V Potter, T Poon-King, D P Earle
Journal: Journal of Clinical Investigation (1975)

Three components of complement and six other serum proteins were assayed in synovial fluid and serum samples from 25 patients with acute rheumatic fever in Trinidad. The resulting data indicate a relative decrease in both early and late components of complement within the synovial fluids which suggests local activation by immune complexes. Such activation of complement within the joint spaces may play a primary role in development of the inflammatory arthritis of acute rheumatic fever.
Venous Thromboembolism in Patients With Colorectal Cancer: Incidence and Effect on Survival
Authors: Allison Alcalay, Ted Wun, Vijay Khatri, Helen K. Chew, Danielle Harvey, Hong Zhou, Richard H. White
Journal: Journal of Clinical Oncology (2006)

Purpose To describe the incidence and outcomes associated with venous thromboembolism (VTE) among patients with colorectal cancer. Methods This was a retrospective analysis of all colorectal cancer patients diagnosed in California between 1993 and 1995 and 1997 to 1999. Principal outcomes were incident symptomatic VTE events and death. Associations between specific risk factors and principal outcomes were analyzed using Cox proportional hazards models. Results Among 68,142 colorectal cancer patients, 50% were women, mean age was 70 ± 15 years, and approximately 70% underwent a major operation. The 2-year cumulative incidence of VTE was 2,100 patients (3.1%), with an incidence rate that decreased significantly over time from 5.0% (events/100 patient-years) in months 0 to 6 to 1.4% during months 7 to 12 to 0.6% during the second year. Significant predictors of VTE included metastatic stage (hazard ratio [HR] = 3.2; 95% CI, 2.8 to 3.8) and three or more comorbid conditions (HR = 2.0; 95% CI, 1.7 to 2.3). The risk of VTE was significantly reduced among Asians/Pacific Islanders (HR = 0.4; 95% CI, 0.3 to 0.5.) and patients who underwent an abdominal operation (HR = 0.4; 95% CI, 0.3 to 0.4). In risk-adjusted models, VTE was a significant predictor of death within 1 year of cancer diagnosis among patients with local- (HR = 1.8; 95% CI, 1.4 to 2.3) or regional-stage disease (HR = 1.5; 95% CI, 1.3 to 1.8) but not among patients with metastatic disease (HR = 1.1; 95% CI, 1.0 to 1.2). Conclusion The incidence of VTE among colorectal cancer patients was highest in the first 6 months after diagnosis and decreased rapidly thereafter. Metastatic disease and the number of medical comorbidities were the strongest predictors of VTE. Incident VTE reduced survival among patients with local or regional disease, suggesting that, in these patients, VTE may reflect the presence of a biologically more aggressive cancer.
The Heart of Children with Steroid-Resistant Nephrotic Syndrome
Authors: Yaacov Frishberg, Sofia Feinstein, Choni Rinat, Rachel Becker-Cohen, Israela Lerer, Annick Raas-Rothschild, Benjamin Ferber, Amiram Nir
Journal: Journal of the American Society of Nephrology (2005)

Mutations in the gene NPHS2 encoding podocin are responsible for a recessive form of steroid-resistant nephrotic syndrome (SRNS). The common phenotype is of massive proteinuria in early childhood that tends to progress to end-stage renal failure. Extrarenal manifestations have not been described. Twenty-two children with SRNS from six unrelated Arab families were found to be homozygous for the R138X mutation in NPHS2. Eighteen patients underwent cardiac evaluation at diagnosis of SRNS while they had normal BP and preserved renal function. Cardiac anomalies were detected in 16 (89%) children: Left ventricular hypertrophy in eight, pulmonary stenosis in six, discrete subaortic stenosis in two, and Ebstein anomaly and ventricular septal defect in one each. The remaining four affected individuals were assessed only once they had end-stage renal failure. They had severe left ventricular hypertrophy and experienced repeated episodes of heart failure. Two control groups were equally evaluated. The first consisted of 37 siblings without nephrotic syndrome, of whom only one carrier had a cardiac defect (P < 0.001). None of the second group, which included 22 children with persistent nephrotic syndrome as a result of other causes, had a cardiac anomaly (P < 0.001). Cardiac disorders in homozygotes for mutations in NPHS2 cannot be attributed to an association by chance or to a state of persistent nephrotic syndrome. Because human podocin mRNA is expressed in fetal heart, it is speculated that it may have a role in normal cardiac development. Cardiac evaluation is recommended at the time of diagnosis of SRNS due to mutations in podocin.
MicroSAGE is highly representative and reproducible but reveals major differences in gene expression among samples obtained from similar tissues
Authors: Seth Blackshaw, Winston Patrick Kuo, Peter J. Park, Motokazu Tsujikawa, Jenny M Gunnersen, Hamish S Scott, Wee-Ming Boon, Seong-Seng Tan, Constance L. Cepko
Journal: Genome biology (2003)