tbuckley/cabot-search huggingface dataset:
Acinar heterogeneity of fatty acid binding protein expression in the livers of male, female and clofibrate-treated rats
Authors: Nathan M. Bass, Mary E. Barker, Joan A. Manning, Albert L. Jones, Robert K. Ockner
Journal: Hepatology (1989)

Liver fatty acid binding protein may play a role in the intracellular transport and compartmentation of long-chain fatty acid metabolism. The distribution of liver fatty acid binding protein in the hepatic acinus was determined by means of immunocytochemistry as well as by measurement of liver fatty acid binding protein in cellular protein selectively released from zone 1 and zone 3 cells by means of anterograde and retrograde liver perfusion with digitonin. In untreated male rats, specific immunocytochemical staining for liver fatty acid binding protein showed a declining portal-to-central hepatocellular gradient in intensity, consistent with the portal-to-central ratio of liver fatty acid binding protein abundance measured in effluents from digitonin-perfused livers of 1.6:1. Female and clofibrate-treated male rats, in both of which hepatic synthesis and abundance of liver fatty acid binding protein are greater than in untreated males, differed as well in the pattern of acinar expression of this protein. In females, periportal concentrations of liver fatty acid binding protein determined from the effluent of livers perfused anterograde with digitonin were similar to male values, whereas liver fatty acid binding protein concentration in pericentral hepatocytes determined from the effluent of retrograde perfused livers was increased, resulting in a marked attenuation of the portal-to-central gradient of this protein; this was also apparent on immunocytochemistry. Clofibrate-treated rats, in contrast, displayed a panacinar increase in liver fatty acid binding protein with maintenance of the portal-to-central ratio observed in untreated males. We conclude that there exists a declining portal-to-central gradient in liver fatty acid binding protein cellular abundance in the hepatic acinus of untreated male rats. Furthermore, the increased synthesis and abundance of liver fatty acid binding protein in female and clofibrate-treated male rats results in two different alterations in the acinar expression of this protein, i.e. a pericentral increase (female) or a panlobular increase (clofibrate). Elucidation of the relationship between the zonation of hepatic fatty acid metabolism and the acinar expression of liver fatty acid binding protein should provide a more detailed understanding of the function of this protein.
Difference between Sexes in Dispersion of Intelligence
Authors: J. A. F. Roberts
Journal: BMJ (1945)

foundations of biological knowledge!So it must remain until we develop a wider and deeper consciousness of what con- stitutes ordered knowledge, and by what cycle of thought it is to be achieved.Yet to feel some discontent with medicine as we find it does not imply any lack of pride in its achievements, nor any diminished sense of privilege in seeking to serve it.If one is a critic, it is, I trust, in the spirit expressed by Milton when he says, " For he who freely magnifies what hath been nobly done, and fears not to declare as freely what might be done better, gives ye the best covenant of his fidelity."
LIGAND RECOGNITION BY αβ T CELL RECEPTORS
Authors: Mark M. Davis, J. Jay Boniface, Ziv Reich, Daniel Lyons, Johannes Hampl, Bernhard Arden, Yueh-hsiu Chien
Journal: Annual Review of Immunology (1998)

While still incomplete, the first data concerning the biochemistry of T cell receptor-ligand interactions in cell-free systems seem to have considerable predictive value regarding whether a T cell response is strong or weak or suppressive. This data will help considerably in elucidating the mechanisms behind T cell responsiveness. Also of great interest are the first structures of T cell receptor molecules and, particularly, TCR-ligand complexes. These appear to confirm earlier suggestions of a fixed orientation for TCR engagement with peptide/MHC and should form the basis for understanding higher oligomers, evidence for which has also just emerged. We conclude with an analysis of the highly diverse CDR3 loops found in all antigen receptor molecules and suggest that such regions form the core of both TCR and antibody specificity.
Effect of isoniazid on antigen-specific interferon-γ secretion in latent tuberculosis
Authors: Martha Torres, Lourdes García-García, Pablo Cruz-Hervert, Heinner Guio, Claudia Carranza, Leticia Ferreyra-Reyes, Sergio Canizales, Susana Molina, Elizabeth Ferreira-Guerrero, Norma Téllez, Rogelio Montero-Campos, Guadalupe Delgado-Sánchez, Norma Mongua-Rodriguez, Jose Sifuentes-Osornio, Alfredo Ponce-de Leon, Eduardo Sada, Douglas B. Young, Robert J. Wilkinson
Journal: European Respiratory Journal (2014)

Treatment of persons with latent tuberculosis (TB) infection at greatest risk of reactivation is an important component of TB control and elimination strategies. Biomarkers evaluating the effectiveness of treatment of latent TB infection have not yet been identified. This information would enhance control efforts and assist the evaluation of new treatment regimes. We designed a two-group, two-arm, randomised clinical study of tuberculin skin test-positive participants: 26 with documented contact with TB patients and 34 with non-documented contact. Participants in each group were randomly assigned to the immediate- or deferred-isoniazid treatment arms. Assays of in vitro interferon (IFN)-γ secretion in response to recombinant Rv1737 and overlapping synthetic peptide pools from various groups of immunodominant proteins were performed. During isoniazid therapy, a significant increase from baseline in the proportion of IFN-γ responders to the 10-kDa culture filtrate protein, Rv2031, Rv0849, Rv1986, Rv2659c, Rv2693c and the recombinant Rv1737 protein was observed (p⩽0.05). The peptide pool of Rv0849 and Rv1737 recombinant proteins induced the highest percentage of IFN-γ responders after isoniazid therapy. The in vitro IFN-γ responses to these proteins might represent useful markers to evaluate changes associated with treatment of latent TB infection.
Aggravation of cardiac myofibroblast arrhythmogeneicity by mechanical stress
Authors: Teddy Grand, Nicolò Salvarani, Florian Jousset, Stephan Rohr
Journal: Cardiovascular Research (2014)

AimsMyofibroblasts (MFBs) as appearing in the myocardium during fibrotic remodelling induce slow conduction following heterocellular gap junctional coupling with cardiomyocytes (CMCs) in bioengineered tissue preparations kept under isometric conditions. In this study, we investigated the hypothesis that strain as developed during diastolic filling of the heart chambers may modulate MFB-dependent slow conduction.
Three-Year Outcomes of Bariatric Surgery vs Lifestyle Intervention for Type 2 Diabetes Mellitus Treatment
Authors: Anita P. Courcoulas, Steven H. Belle, Rebecca H. Neiberg, Sheila K. Pierson, Jessie K Eagleton, Melissa A. Kalarchian, James P. DeLany, Wei Lang, John M. Jakicic
Journal: JAMA Surgery (2015)

Questions remain about the role and durability of bariatric surgery for type 2 diabetes mellitus (T2DM).To compare the remission of T2DM following surgical and nonsurgical treatments.In this 3-arm randomized clinical trial conducted at the University of Pittsburgh Medical Center from October 1, 2009, to June 26, 2014, in Pittsburgh, Pennsylvania, outcomes were assessed 3 years after treating 61 obese participants aged 25 to 55 years with T2DM. Analysis was conducted with an intent-to-treat population.Participants were randomized to either an intensive lifestyle weight loss intervention for 1 year followed by a low-level lifestyle intervention for 2 years or surgical treatments (Roux-en-Y gastric bypass [RYGB] or laparoscopic adjustable gastric banding [LAGB]) followed by low-level lifestyle intervention in years 2 and 3.Primary end points were partial and complete T2DM remission and secondary end points included diabetes medications and weight change.Body mass index (calculated as weight in kilograms divided by height in meters squared) was less than 35 for 26 participants (43%), 50 (82%) were women, and 13 (21%) were African American. Mean (SD) values were 100.5 (13.7) kg for weight, 47.3 (6.6) years for age, 7.8% (1.9%) for hemoglobin A1c level, and 171.3 (72.5) mg/dL for fasting plasma glucose level. Partial or complete T2DM remission was achieved by 40% (n = 8) of RYGB, 29% (n = 6) of LAGB, and no intensive lifestyle weight loss intervention participants (P = .004). The use of diabetes medications was reduced more in the surgical groups than the lifestyle intervention-alone group, with 65% of RYGB, 33% of LAGB, and none of the intensive lifestyle weight loss intervention participants going from using insulin or oral medication at baseline to no medication at year 3 (P < .001). Mean (SE) reductions in percentage of body weight at 3 years were the greatest after RYGB at 25.0% (2.0%), followed by LAGB at 15.0% (2.0%) and lifestyle treatment at 5.7% (2.4%) (P < .01).Among obese participants with T2DM, bariatric surgery with 2 years of an adjunctive low-level lifestyle intervention resulted in more disease remission than did lifestyle intervention alone.clinicaltrials.gov Identifier: NCT01047735.
A STUDY OF THE ELIMINATION OF PHENOLSULPHONEPHTHALEIN IN VARIOUS EXPERIMENTAL LESIONS OF THE KIDNEY
Authors: A. B. Eisenbrey
Journal: The Journal of Experimental Medicine (1911)

The study of a variety of experimental renal lesions in the dog demonstrates that the phenolsulphonephthalein test of Rowntree and Geraghty is one of the most satisfactory and at the same time most delicate methods of estimating the functional activity of the kidney. The elimination of the test dye is decreased in so-called spontaneous nephritis and in experimental nephritis due to potassium chromate, uranium nitrate, cantharidin, diphtheria toxin, and arsenic, and in those lesions caused by snake venom, hemolytic serum, prolonged renal anemia, and extensive reduction of the kidney substance. Its elimination is not' diminished, but is increased, in the presence of the renal lesion caused by nephrotoxic immune serum, and for this discrepancy no explanation is at hand. The test is a reliable method of demonstrating improvement in the functional activity of the kidney, as is shown in our study of spontaneous nephritis. The increased elimination of the dye occurring after small doses of various irritants, which is frequently characteristic of the early stages of a severe nephritis, and which is seen also several days after unilateral nephrectomy, would appear to have an important relation to the problem of kidney function; and although probably not of clinical importance, it is worthy of further study as a phase of renal activity.
Neonatal Diabetes Caused by Pancreatic Agenesia
Authors: Alessandro Salina, Lorenzo Pasquali, Concetta Aloi, Francesca Lugani, Giuseppe d'Annunzio, Renata Lorini
Journal: Diabetes Care (2010)

Permanent neonatal diabetes (PND) is an extremely rare condition. Few cases of PND caused by pancreas-development failure have been described, and only a few genetic causes have been identified so far (1).

We describe a boy with PND caused by pancreas agenesis, currently age 7 years. He is the first child of healthy, unrelated parents. He was born at 35 weeks of gestation, with severe intrauterine growth restriction (weight 1,620 g; length 45 cm). In the first day of life he developed severe hyperglycemia, and neonatal diabetes was diagnosed and treated with insulin, initially intravenously and then subcutaneously. Atrial septal defect was diagnosed in absence of …
Norepinephrine Stores and Contractile Force of Papillary Muscle from the Failing Human Heart
Authors: CHARLES A. CHIDSEY, EDMUND H. SONNENBLICK, ANDREW G. MORROW, EUGENE BRAUNWALD
Journal: Circulation (1966)

The relation between cardiac norepinephrine concentration and the functional state of the myocardium was studied in left ventricular papillary muscles removed from patients with congestive heart failure at the time of mitral valve replacement. Myocardial function was assessed by determining the maximum isometric active tension that the papillary muscle could develop in an in vitro system, and by measuring the increase in active tension in response to the norepinephrine-releasing sympathomimetic amine, tyramine. The norepinephrine concentration averaged 0.36 µg./Gm. in 17 muscles. In eight of these a response to tyramine was observed with a 21-per cent increase in active tension, and the norepinephrine concentrations averaged 0.53 µg./Gm.; in the other six muscles tested with tyramine no positive inotropic response was observed, and the norepinephrine concentration was significantly lower, averaging 0.16 µg./Gm. The maximum active tension in 17 muscles averaged 1.78 Gm./mm. 2 , and a significant positive correlation between the maximum tension and the norepinephrine concentration of the individual muscles was observed. In the eight muscles responding to tyramine, the maximum tension observed, 2.34 Gm./mm. 2 , was significantly greater than that observed in the six muscles unresponsive to tyramine, 0.64 Gm./mm. 2 It is concluded that norepinephrine depletion appears to be associated with defective myocardial function although no causal relationship between these two abnormalities has been established.
Progressive nodular histiocytosis in a child with a hypothalamic tumour
Authors: S.J. Beswick, J.M.W. Kirk, K. Bradshaw, D.S.A. Sanders, C. Moss
Journal: British Journal of Dermatology (2002)

We report a 13-year-old girl with multiple cutaneous histiocytic lesions, precocious puberty, growth hormone deficiency and a hypothalamic tumour. We conclude that she has progressive nodular histiocytosis, but this case illustrates the difficulty in differentiating the type II histiocytoses.
Alcohol drinking and non-Hodgkin lymphoma risk: a systematic review and a meta-analysis
Authors: I. Tramacere, C. Pelucchi, M. Bonifazi, V. Bagnardi, M. Rota, R. Bellocco, L. Scotti, F. Islami, G. Corrao, P. Boffetta, C. La Vecchia, E. Negri
Journal: Annals of Oncology (2012)
A Multifactorial Signature of DNA Sequence and Polycomb Binding Predicts Aberrant CpG Island Methylation
Authors: Michael T. McCabe, Eva K. Lee, Paula M. Vertino
Journal: Cancer Research (2008)

Abstract Aberrant CpG island methylation is associated with transcriptional silencing of regulatory genes in human cancer. Although most CpG islands remain unmethylated, a subset accrues aberrant methylation in cancer via unknown mechanisms. Previously, we showed that CpG islands differ in their intrinsic propensity towards hypermethylation. We developed a classifier (PatMAn) based on the frequencies of seven DNA sequence patterns that discriminated methylation-prone (MP) and methylation-resistant (MR) CpG islands. Here, we report on the genome-wide application and direct testing of PatMAn in cancer. Although trained on data from a cell culture model of de novo methylation involving the overexpression of DNMT1, PatMAn accurately predicted CpG islands at increased risk of hypermethylation in cancer cell lines and primary tumors. Analysis of CpG islands predicted to be MP revealed a strong association with embryonic targets of polycomb-repressive complex 2 (PRC2), indicating that PatMAn predicts not only aberrant methylation, but also PRC2 binding. A second classifier (SUPER-PatMAn) that integrates the seven PatMAn DNA patterns with SUZ12 enriched regions as a marker of PRC2 occupancy showed improved performance (prediction accuracy, 81–88%). In addition to many non-PRC2 targets, SUPER-PatMAn identified a subset of PRC2 targets that were more likely to be hypermethylated in cancer. Genome-wide, CpG islands predicted to be MP were enriched in genes known to undergo hypermethylation in cancer, genes functioning in transcriptional regulation, and components of developmental pathways. These findings show that hypermethylation of certain gene loci is controlled in part by an underlying susceptibility influenced by both local sequence context and trans-acting factors. [Cancer Res 2009;69(1):282–91]
Genetic Testing in Families With Hereditary Nonpolyposis Colon Cancer
Authors: C Lerman, C Hughes, B J Trock, R E Myers, D Main, A Bonney, M R Abbaszadegan, A E Harty, B A Franklin, J F Lynch, H T Lynch
Journal: JAMA (1999)

ContextGenetic testing for hereditary nonpolyposis colon cancer (HNPCC) is available, but the rates of acceptance of testing or barriers to participation are not known.ObjectiveTo investigate rates and predictors of utilization of genetic testing for HNPCC.DesignCohort study conducted between July 1996 and July 1998.SettingHereditary nonpolyposis colon cancer family registry.ParticipantsAdult male and female members (n=208) of 4 extended HNPCC families contacted for a baseline telephone interview.InterventionsFamily education and individual genetic counseling.Main Outcome MeasureParticipant acceptance of HNPCC test results.ResultsOf the 208 family members, 90 (43%) received test results and 118 (57%) declined. Of 139 subjects (67%) who completed a baseline telephone interview, 84 (60%) received test results and 55 (40%) declined. Of the 84 subjects who received test results, 35 (42%) received information indicating that they had HNPCC-associated mutations and 49 (58%) that they did not. Test acceptors had higher education levels (odds ratio [OR], 3.74; 95% confidence interval [CI], 2.49-5.61) and were more likely to have participated in a previous genetic linkage study (OR, 4.30; 95% CI, 1.84-10.10). The presence of depression symptoms significantly reduced rates of HNPCC test use (OR, 0.34; 95% CI, 0.17-0.66). Although rates of test use were identical among men and women, the presence of depression symptoms resulted in a 4-fold decrease in test use among women (OR, 0.25; 95% CI, 0.08-0.80) and a smaller, nonsignificant reduction among men (OR, 0.49; 95% CI, 0.19-1.27).ConclusionsDespite having significantly elevated risks of developing colon cancer, a relatively small proportion of HNPCC family members are likely to use genetic testing. Barriers to test acceptance may include less formal education and the presence of depression symptoms, especially among women. Additional research is needed to generalize these findings to different clinical settings and racially diverse populations.
Alkaline phosphatase isoenzyme activities in rheumatoid arthritis: hepatobiliary enzyme dissociation and relation to disease activity.
Authors: S Aida
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--Hyperphosphatasaemia has been observed occasionally in patients with rheumatoid arthritis (RA), and it has been suggested that the serum alkaline phosphatase (ALP) level is related to the activity of the disease. Therefore, the relationship between serum ALP and RA was studied. METHODS--The serum activities of hepatobiliary enzymes (ALP isoenzymes, gamma-glutamyltranspeptidase (GTP), leucine aminopeptidase (LAP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT)), immunoglobulins, RA haemagglutinin test (RAHA), C reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were observed in 288 patients with rheumatoid arthritis. RESULTS--Serum biliary ALP (ALP1) activity was detected in 31.6% of the patients. In patients positive for ALP1 the respective values of total ALP (ALPt) (p &lt; 0.001), liver ALP (ALP2) (p &lt; 0.001), bone ALP (ALP3) (p &lt; 0.05), gamma-GTP (p &lt; 0.001), LAP (p &lt; 0.001), immunoglobulins IgG (p &lt; 0.01), IgA (p &lt; 0.01), and IgM (p &lt; 0.01), RAHA (p &lt; 0.001), CRP (p &lt; 0.001), ESR (p &lt; 0.001), and articular index (p &lt; 0.001) were significantly higher than in patients who did not have ALP1. Significant Spearman9s rank correlations (rs) were demonstrated between serum ALP2 level and the respective values of ALPt (rs = 0.9128, p &lt; 0.001), ALP1 (rs = 0.4443, p &lt; 0.001), ALP3 (rs = 0.5898, p &lt; 0.001), gamma-GTP (rs = 0.2903, p &lt; 0.001), LAP (rs = 0.3093, p &lt; 0.001), IgA (rs = 0.2299, p &lt; 0.01), IgM (rs = 0.1773, p &lt; 0.05), RAHA (rs = 0.2420, p &lt; 0.01), CRP (rs = 0.3532, p &lt; 0.001), ESR (rs = 0.4006, p &lt; 0.001). the articular index (rs = 0.4006, p &lt; 0.001). However, no significant difference or correlation was noted for either AST or ALT. In many patients who showed abnormal hyperphosphatasaemia, hepatobiliary enzyme dissociation was observed: levels of ALPt (in 12.8%), ALP1 (in 31.6%), ALP2 (18.8%), gamma-GTP (in 4.3%), and LAP (in 19.3%) were abnormally high, but both AST and ALT were within normal limits. CONCLUSION--These findings are considered to be characteristic of RA, and suggest the existence of latent or subclinical hepatobiliary involvement and an association between the expansion of hepatobiliary involvement and the mechanism of disease activation. Thus measurement of the serum levels of ALP and its isoenzymes in RA is considered to be important.
Interventions for Depression Symptoms Among Adolescent Survivors of War and Displacement in Northern Uganda
Authors: Paul Bolton, Judith Bass, Theresa Betancourt, Liesbeth Speelman, Grace Onyango, Kathleen F. Clougherty, Richard Neugebauer, Laura Murray, Helen Verdeli
Journal: JAMA (2007)

Prior qualitative work with internally displaced persons in war-affected northern Uganda showed significant mental health and psychosocial problems.To assess effect of locally feasible interventions on depression, anxiety, and conduct problem symptoms among adolescent survivors of war and displacement in northern Uganda.A randomized controlled trial from May 2005 through December 2005 of 314 adolescents (aged 14-17 years) in 2 camps for internally displaced persons in northern Uganda.Locally developed screening tools assessed the effectiveness of interventions in reducing symptoms of depression and anxiety, ameliorating conduct problems, and improving function among those who met study criteria and were randomly allocated (105, psychotherapy-based intervention [group interpersonal psychotherapy]; 105, activity-based intervention [creative play]; 104, wait-control group [individuals wait listed to receive treatment at study end]). Intervention groups met weekly for 16 weeks. Participants and controls were reassessed at end of study.Primary measure was a decrease in score (denoting improvement) on a depression symptom scale. Secondary measures were improvements in scores on anxiety, conduct problem symptoms, and function scales. Depression, anxiety, and conduct problems were assessed using the Acholi Psychosocial Assessment Instrument with a minimum score of 32 as the lower limit for clinically significant symptoms (maximum scale score, 105).Difference in change in adjusted mean score for depression symptoms between group interpersonal psychotherapy and control groups was 9.79 points (95% confidence interval [CI], 1.66-17.93). Girls receiving group interpersonal psychotherapy showed substantial and significant improvement in depression symptoms compared with controls (12.61 points; 95% CI, 2.09-23.14). Improvement among boys was not statistically significant (5.72 points; 95% CI, -1.86 to 13.30). Creative play showed no effect on depression severity (-2.51 points; 95% CI, -11.42 to 6.39). There were no statistically different improvements in anxiety in either intervention group. Neither intervention improved conduct problem or function scores.Both interventions were locally feasible. Group interpersonal psychotherapy was effective for depression symptoms among adolescent girls affected by war and displacement. Other interventions should be investigated to assist adolescent boys in this population who have symptoms of depression.clinicaltrials.gov Identifier: NCT00280319.