tbuckley/cabot-search huggingface dataset:
Toenail Selenium and Incidence of Type 2 Diabetes in U.S. Men and Women
Authors: Kyong Park, Eric B. Rimm, David S. Siscovick, Donna Spiegelman, JoAnn E. Manson, J. Steven Morris, Frank B. Hu, Dariush Mozaffarian
Journal: Diabetes Care (2012)

Compelling biological pathways suggest that selenium (Se) may lower onset of type 2 diabetes mellitus (T2DM), but very few studies have evaluated this relationship, with mixed results. We examined the association between toenail Se and incidence of T2DM.We performed prospective analyses in two separate U.S. cohorts, including 3,630 women and 3,535 men, who were free of prevalent T2DM and heart disease at baseline in 1982-1983 and 1986-1987, respectively. Toenail Se concentration was quantified using neutron activation analysis, and diabetes cases were identified by biennial questionnaires and confirmed by a detailed supplementary questionnaire. Hazard ratios of incident T2DM according to Se levels were calculated using Cox proportional hazards.During 142,550 person-years of follow-up through 2008, 780 cases of incident T2DM occurred. After multivariable adjustment, the risk of T2DM was lower across increasing quintiles of Se, with pooled relative risks across the two cohorts of 1.0 (reference), 0.91 (95% CI 0.73-1.14), 0.78 (0.62-0.99), 0.72 (0.57-0.91), and 0.76 (0.60-0.97), respectively (P for trend = 0.01). Results were similar excluding the few individuals (4%) who used Se supplements. In semiparametric analyses, the inverse relationship between Se levels and T2DM risk appeared to be linear.At dietary levels of intake, individuals with higher toenail Se levels are at lower risk for T2DM. Further research is required to determine whether varying results in this study versus prior trials relate to differences in dose, source, statistical power, residual confounding factors, or underlying population risk.
Expression of Angiotensinogen mRNA and Protein in Angiotensin II-Dependent Hypertension
Authors: HIROYUKI KOBORI, LISA M. HARRISON-BERNARD, L. GABRIEL NAVAR
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Chronic elevations in circulating angiotensin II (AngII) levels produce sustained hypertension and increased intrarenal AngII contents through multiple mechanisms, which may include sustained or increased local production of AngII. This study was designed to test the hypothesis that chronic AngII infusion increases renal angiotensinogen mRNA and protein levels, thus contributing to the increase in intrarenal AngII levels. AngII (80 ng/min) was infused subcutaneously for 13 d into Sprague-Dawley rats, using osmotic minipumps. Control rats underwent sham operations. By day 12, systolic arterial BP increased to 184 ± 3 mmHg in AngII-treated rats, whereas values for sham-treated rats remained at control levels (125 ± 1 mmHg). Plasma renin activity was markedly suppressed (0.2 ± 0.1 versus 5.3 ± 1.2 ng AngI/ml per h); however, renal AngII contents were significantly increased in AngII-treated rats (273 ± 29 versus 99 ± 18 fmol/g). Western blot analyses of plasma and liver protein using a polyclonal anti-angiotensinogen antibody demonstrated two specific immunoreactive bands, at 52 and 64 kD, whereas kidney tissue exhibited one band, at 52 kD. Densitometric analyses demonstrated that AngII infusion did not alter plasma (52- or 64-kD), renal (52-kD), or hepatic (52-kD) angiotensinogen protein levels; however, there was a significant increase in hepatic expression of the highly glycosylated 64-kD angiotensinogen protein, of almost fourfold (densitometric value/control value ratios of 3.79 ± 1.16 versus 1.00 ± 0.35). Renal and hepatic expression of angiotensinogen mRNA, which was examined by semiquantitative reverse transcription-PCR, was significantly increased in AngII-treated rats, compared with shamtreated rats (kidney, densitometric value/glyceraldehyde-3-phosphate dehydrogenase mRNA value ratios of 0.82 ± 0.11 versus 0.58 ± 0.04; liver, densitometric value/glyceraldehyde-3-phosphate dehydrogenase mRNA value ratios of 2.34 ± 0.07 versus 1.32 ± 0.15). These results indicate that increases in circulating AngII levels increase intrarenal angiotensinogen mRNA levels, which may contribute to the sustained renal AngII-generating capacity that paradoxically occurs in AngII-treated hypertensive rats.
Characterisation of the cell type-specificity of collagenase 3 mRNA expression in comparison with membrane type 1 matrix metalloproteinase and gelatinase A in the synovial membrane in rheumatoid arthritis
Authors: P K Petrow
Journal: Annals of the Rheumatic Diseases (2002)

Objective: To study the pattern and cell type-specificity of collagenase 3, membrane-type 1 matrix metalloproteinase (MT1-MMP), and gelatinase A mRNA expression in the synovial membrane in rheumatoid arthritis (RA). Methods: The mRNA expression of collagenase 3, MT1-MMP, and gelatinase A was characterised by northern blot analysis, reverse transcriptase-polymerase chain reaction, and in situ hybridisation. In situ hybridisation was performed in combination with the immunohistochemical detection of cell type-specific antigens. Results: Synovial membrane specimens from 19 of 21 patients with RA expressing collagenase 3 mRNA were positive for MT1-MMP and gelatinase A mRNA. In control samples from patients without destructive inflammatory joint diseases collagenase 3 mRNA was not expressed and only in two of seven cases was a coexpression of MT1-MMP and gelatinase A mRNA detected. Fibroblast-like cells of the synovial membrane were found to be the predominant source of collagenase 3, MT1-MMP, and gelatinase A mRNA expression in lining and sublining layers as well as at the synovial membrane-cartilage interface. Additionally, the expression of MT1-MMP mRNA was detected in endothelial cells. Collagenase 3 mRNA expression was found in about 5% of CD68 positive macrophages. Conclusions: Collagenase 3 mRNA is expressed simultaneously with MT1-MMP and gelatinase A mRNA in fibroblast-like cells of the synovial membrane in RA. These results suggest (<i>a</i>) a broad extracellular proteolytic potential of fibroblast-like cells and (<i>b</i>) an important role of cell surface associated procollagenase 3 activation by MT1-MMP and gelatinase A for cartilage degradation by invading fibroblast-like cells.
Antiinflammatory Effects of CD95 Ligand (FasL)-induced Apoptosis
Authors: Yakun Gao, John M. Herndon, Hui Zhang, Thomas S. Griffith, Thomas A. Ferguson
Journal: The Journal of Experimental Medicine (1998)

Apoptosis is critical to homeostasis of multicellular organisms. In immune privileged sites such as the eye, CD95 ligand (FasL)-induced apoptosis controls dangerous inflammatory reactions that can cause blindness. Recently, we demonstrated that apoptotic cell death of inflammatory cells was a prerequisite for the induction of immune deviation after antigen presentation in the eye. In this report, we examine the mechanism by which this takes place. Our results show that Fas- mediated apoptosis of lymphoid cells leads to rapid production of interleukin (IL)-10 in these cells. The apoptotic cells containing IL-10 are responsible for the activation of immune deviation through interaction with antigen-presenting cells (APC). In support of this, we found that apoptotic cells from IL-10+/+ animals fed to APC in vitro promote Th2 cell differentiation, whereas apoptotic IL-10−/− cells, as well as nonapoptotic cells, favor Th1 induction. Thus, apoptotic cell death and tolerance are linked through the production of an antiinflammatory cytokine to prevent dangerous and unwanted immune responses that might compromise organ integrity.
Measuring the activity of the disease in patients with cutaneous lupus erythematosus
Authors: A. Parodi, C. Massone, M. Cacciapuoti, M.G. Aragone, P. Bondavalli, G. Cattarini, A. Rebora
Journal: British Journal of Dermatology (2000)

The Systemic Lupus Activity Measure (SLAM) is a system proposed by rheumatologists to measure disease activity in their patients with systemic lupus erythematosus (LE). It involves scoring a group of clinical symptoms and laboratory findings, the maximum possible score being 84. In systemic LE, the mid-point is between 9 and 12. We applied SLAM to 176 patients with cutaneous LE. Ninety-seven had localized discoid LE (L-DLE), 59 had disseminated discoid LE (D-DLE) and 20 had subacute cutaneous LE (SCLE). Eighty-five patients had low activity disease (0-4 points), 72 mildly active disease (5-9 points), 15 moderately active disease (10-14 points) and only four had very active disease (>/= 15 points). The most frequent lesions in patients who scored more than 10 points were photosensitivity, cicatricial alopecia, Raynaud's phenomenon and oral ulcers. Fifty patients were followed up for more than 5 years (mean follow-up 9 years). Nine of these had an increased SLAM score. Seven had L-DLE, one D-DLE and one SCLE. Seven of the 50 patients had photosensitivity, five cicatricial alopecia, five non-cicatricial alopecia, two Raynaud's phenomenon and two oral ulcers. Three patients who started with L-DLE evolved to D-DLE. The SLAM system is useful in the monitoring of disease activity in patients with cutaneous LE. Over time, even L-DLE patients may develop active disease. Photosensitivity, alopecia, oral ulcers and Raynaud's phenomenon seem to herald a worse prognosis.
Anterior Cingulate, Gyrus Rectus, and Orbitofrontal Abnormalities in Elderly Depressed Patients: An MRI-Based Parcellation of the Prefrontal Cortex
Authors: Martina Ballmaier, Arthur W. Toga, Rebecca E. Blanton, Elizabeth R. Sowell, Helen Lavretsky, Jeffrey Peterson, Daniel Pham, Anand Kumar
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: To examine structural abnormalities in subregions of the prefrontal cortex in elderly patients with depression, the authors explored differences in gray matter, white matter, and CSF volumes by applying a parcellation method based on magnetic resonance imaging (MRI). METHOD: Twenty-four elderly patients with major depression and 19 group-matched comparison subjects were studied with high-resolution MRI. Cortical surface extraction, tissue segmentation, and cortical parcellation methods were applied to obtain volume measures of gray matter, white matter, and CSF in seven prefrontal subregions: the anterior cingulate, gyrus rectus, orbitofrontal cortex, precentral gyrus, superior frontal cortex, middle frontal cortex, and inferior frontal cortex. RESULTS: Highly significant bilateral volume reductions in gray matter were observed in the anterior cingulate, the gyrus rectus, and the orbitofrontal cortex. Depressed patients also exhibited significant bilateral white matter volume reductions and significant CSF volume increases in the anterior cingulate and the gyrus rectus. Finally, the depressed group showed significant CSF volume reductions in the orbitofrontal cortex relative to the comparison subjects. None of the other regions examined revealed significant structural abnormalities. CONCLUSIONS: The prominent bilateral gray matter deficits in the anterior cingulate and the gyrus rectus as well as the orbitofrontal cortex may reflect disease-specific modifications of elderly depression. The differential pattern of abnormalities detected in the white matter and CSF compartments imply that distinct etiopathological mechanisms might underlie the structural cortical changes in these regions.
Alcohol and Affect: A Psychopharmacological Study
Authors: DEMMIE MAYFIELD, DAVID ALLEN
Journal: American Journal of Psychiatry (1967)

To investigate the influence of alcohol upon affective state, an intoxicating dose was administered intravenously to three groups—alcoholic patients, severely depressed patients, and control subjects. Using the Clyde Mood Scale to measure each subject's affect before and after alcohol infusion, the authors found that alcohol does alter affect, primarily in a palliative rather than euphoriant way. The alcoholics derived the least benefit from alcohol intoxication in terms of affective improvement, while the depressed patients improved dramatically.
Mucolipidosis II and III. The genetic relationships between two disorders of lysosomal enzyme biosynthesis.
Authors: O T Mueller, N K Honey, L E Little, A L Miller, T B Shows
Journal: Journal of Clinical Investigation (1983)

The genetic relationships between the multiple variants of mucolipidosis II (I-cell disease) and mucolipidosis III (pseudo-Hurler polydystrophy) were investigated with a sensitive genetic complementation analysis procedure. These clinically distinct disorders have defects in the synthesis of a recognition marker necessary for the intracellular transport of acid hydrolases into lysosomes. Both disorders are associated with an inherited deficiency of a uridine diphosphate-N-acetyl-glucosamine: lysosomal enzyme precursor N-acetyl-glucosamine-phosphate transferase activity. We had previously shown that both disorders are genetically heterogeneous. Complementation analysis between mucolipidosis II and III fibroblasts indicated an identity of mucolipidosis II with one of the three mucolipidosis III complementation groups (ML IIIA), suggesting a close genetic relationship between these groups. The presence of several instances of complementation within this group suggested an intragenic complementation mechanism. Genetic complementation in heterokaryons resulted in increases in N-acetyl-glucosamine-phosphate transferase activity, as well as in the correction of lysosomal enzyme transport. This resulted in increases in the intracellular levels of several lysosomal enzymes and in the correction of the abnormal electrophoretic mobility pattern of intracellular beta-hexosaminidase. The findings demonstrate that a high degree of genetic heterogeneity exists within these disorders. N-acetyl-glucosamine-phosphate transferase is apparently a multicomponent enzyme with a key role in the biosynthesis and targeting of lysosomal enzymes.
No Rosetta Stone for a Sense–Antisense Origin of Aminoacyl tRNA Synthetase Classes
Authors: Tom A. Williams, Kenneth H. Wolfe, Mario A. Fares
Journal: Molecular Biology and Evolution (2008)

Aminoacyl tRNA synthetases (aaRS) are crucial enzymes that join amino acids to their cognate tRNAs, thereby implementing the genetic code. These enzymes fall into two unrelated structural classes whose evolution has not been explained. The leading hypothesis, proposed by Rodin and Ohno, is that the two classes originated as a pair of sense-antisense genes encoded on opposite strands of a single DNA molecule. This unusual idea obtained its main support from reports of a "Rosetta stone": a locus where genes for heat shock protein 70 (HSP70) and an Nicotinamide adenine dinulecotide-specific glutamate dehydrogenase (NAD-GDH), which are structurally homologous to the two classes of aaRS, overlap extensively on complementary DNA strands. This remarkable locus was first characterized in the oomycete Achlya klebsiana and has since been reported in many other species. Here we present evidence that the open reading frames on the antisense strand of HSP70 genes are spurious, and we identify a more probable candidate for the gene encoding the oomycete NAD-GDH enzyme. These results cast extensive doubt on the Rosetta Stone argument.
Abnormalities of Neurohormonal and Cardiac Autonomic Nervous Activities Relate Poorly to Functional Status in Fontan Patients
Authors: Hideo Ohuchi, Hisashi Takasugi, Hiroyuki Ohashi, Osamu Yamada, Ken Watanabe, Toshikatsu Yagihara, Shigeyuki Echigo
Journal: Circulation (2004)

Background— Impaired cardiac autonomic nervous activities and increased neurohumoral activities (CANA, NHA) characterize Fontan patients. However, the clinical significance of these changes is not clearly understood. Our purpose was to clarify the clinical significance of the CANA and NHA in stable Fontan patients. Methods and Results— We divided 22 atriopulmonary connection (APC) and 75 total cavopulmonary connection (TCPC) patients into 4 subgroups according to New York Heart Association (NYHA) class (1.8±0.6) and measured various CANA and NHA indices. All NHA indices were elevated in the symptomatic patients ( P &lt;0.001). Natriuretic peptides were higher in the APC than in the TCPC patients, and the hemodynamics showed no correlation with brain natriuretic peptide in the APC patients. Low arterial oxygen saturation and impaired hemodynamics greatly influenced all elevated NHA indices ( P &lt;0.01), except for plasma renin activity, in the TCPC patients. Impaired CANA indices did not relate to NYHA class, although surgeries were associated with lower heart rate variability. In addition to poor correlation between NHA and CANA, age and ventricular morphology had no impact on all CANA and NHA indices, except for high norepinephrine in right ventricular Fontan patients. Conclusions— Although symptomatic Fontan patients exhibit higher NHA, CANA is not related to either NYHA class or NHA. APC itself is responsible for higher natriuretic peptides, and arterial oxygen desaturation has a great impact on elevated NHA in the TCPC patients. These characteristics of the NHA and CANA differ from those of heart failure patients with biventricular physiology.
Significance of 19-norandrosterone in athletes’ urine samples
Authors: C Ayotte
Journal: British Journal of Sports Medicine (2006)

Nandrolone and other 19-norsteroid potent anabolic steroids have been prohibited in sports for 30 years. The detection of the main urinary metabolite—19-norandrosterone—in amounts greater than 2 ng/ml constitutes an adverse analytical finding. The presence in nutritional sport supplements of steroids not listed on the label has undoubtedly resulted in positive tests, but inadvertent consumption of meat containing residues of hormonal treatment should not realistically cause apprehension. Although highly improbable, athletes should prudently avoid meals composed of pig offal in the hours preceding the test since the consumption of edible parts of a non-castrated pig, containing 19-nortestosterone, has been shown to results in the excretion of 19-norandrosterone in the following hours. Norsteroid metabolites are formed during pregnancy and excreted as minor metabolites of norethisterone, and minute amounts have been identified in some male and female samples when using more sensitive techniques of detection. Whereas exercise does not seem to be a significant factor in 19-norandrosterone excretion, some rare urine samples were found to be a suitable medium for in situ 19-demethylation of urinary metabolites.
Lipocytes and transitional cells in alcoholic liver disease: A morphometric study
Authors: Ki M. Mak, Charles S. Lieber
Journal: Hepatology (1988)

Lipocytes and transitional cells in alcoholic liver disease were analyzed by quantitative morphometry in liver biopsy specimens of 17 alcoholic patients. In fatty livers, 93% of the perisinusoidal cells were lipocytes with a volume of lipid droplets occupying more than 20% of the individual cell volume. In fatty livers with perivenular fibrosis, 83% of the cells were lipocytes and 17% were transitional cells with lipid droplets of less than 20% of the cell volume. In cirrhosis, 45% of the cells were lipocytes and 55% of the cells were transitional cells. Thus, the process of hepatic fibrosis was associated with a shift from lipocytes to transitional cells. The percentage of transitional cells (expressed as total perisinusoidal cells) was 5.1% in fatty livers, 16.5% in fatty livers with perivenular fibrosis (not significantly different when compared to fatty livers) and 59.7% in cirrhotic livers (p &lt; 0.025) when compared to fatty livers or fatty livers with perivenular fibrosis). The number of transitional cells per 100 hepatocytes was estimated to be 0.5 in fatty livers, 1.3 in fatty livers with perivenular fibrosis and 2.1 in cirrhotic livers. The appearance of transitional cells was associated with a corresponding decrease in the number of lipocytes, supporting the hypothesis that transitional cells were derived from lipocytes. In comparison to lipocytes, the surface area of transitional cells (as measured by digitized morphometry) was 30 to 46% smaller (p &lt; 0.01). When expressed as the percentage of the total cell area, the lipid droplet compartment in transitional cells was 34% smaller (p &lt; 0.001) than that in lipocytes, whereas the nonlipid cytoplasmic and nuclear compartments in transitional cells were 18 to 20% (p &lt; 0.01) and 15% (p &lt; 0.05) larger than those in lipocytes, respectively. The rough endoplasmic reticulum in transitional cells became better developed than that in lipocytes, but only at the cirrhotic stage, confirmed by quantitative morphometry. We found a significantly higher collagen score in the Disse space surrounding transitional cells in fatty livers with perivenular fibrosis or cirrhosis compared to that of lipocytes. In two cases of alcoholic hepatitis with cirrhosis, virtually all perisinusoidal cells exhibited structural features and morphometric values comparable to those of transitional cells in the livers without hepatitis. In the liver of one nonalcoholic subject, perisinusoidal cells exhibited structural features and morphometric values comparable to those of lipocytes in the livers of alcoholics.
Impact of Expression of Human Epidermal Growth Factor Receptors EGFR and ERBB2 on Survival in Stage II/III Gastric Cancer
Authors: Masanori Terashima, Koji Kitada, Atsushi Ochiai, Wataru Ichikawa, Issei Kurahashi, Shinichi Sakuramoto, Hitoshi Katai, Takeshi Sano, Hiroshi Imamura, Mitsuru Sasako
Journal: Clinical Cancer Research (2012)

EGF receptor (EGFR) and HER2 positivity are considered to be negative prognostic factors in gastric cancer. Biomarker analysis was conducted to evaluate the impact of EGFR and HER2 expression on the outcome of patients enrolled in the Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC), a randomized controlled trial comparing postoperative adjuvant S-1 therapy with surgery alone in 1,059 patients with stage II/III gastric cancer.Formalin-fixed, paraffin-embedded surgical specimens were retrospectively examined in 829 patients (78.3%). The effects of EGFR and HER2 positivity on survival were analyzed on the basis of the 5-year survival data from the study. EGFR positivity was defined as an immunohistochemistry (IHC) score of 3+, and HER2 positivity as an IHC score of 3+ or an IHC score of 2+ with a positive dual-color in situ hybridization status.EGFR and HER2 were positive in 75 (9.0%) and 113 (13.6%) patients, respectively. The overall and relapse-free survival rates were significantly lower in EGFR-positive patients than in EGFR-negative patients, whereas they were similar in HER2-positive and HER2-negative patients. Multivariate analysis showed that EGFR positivity correlated with poor outcomes [HR = 1.504; 95% confidence interval (CI) = 1.020-2.149; P = 0.040]. Treatment with S-1 improved survival compared with surgery alone, irrespective of EGFR and HER2 status.EGFR positivity, but not HER2 positivity, was associated with poor patient outcomes after curative resection of stage II/III gastric cancer. There was no interaction between S-1 and EGFR or HER2 status with respect to survival outcome.