tbuckley/cabot-search huggingface dataset:
Depressed Fatty Acid and Acetate Oxidation and Other Metabolic Defects in Homogenates from Hearts of Hamsters with Hereditary Cardiomyopathy
Authors: K. JOE KAKO, MAUREEN J. THORNTON, H. ALEXANDER HEGGTVEIT
Journal: Circulation Research (1974)

Metabolic changes in heart homogenate of Syrian hamsters with hereditary cardiomyopathy (BIO 14.6 strain) were examined. Oxidation of labeled fatty acids and acetate by myopathic homogenates was severely depressed; CO 2 production from labeled acetate was only one-fifteenth of the control value, and butyrate oxidation was suppressed to one-fourth of the control value. Although the addition of carnitine enhanced the oxidation of palmitate and octanoate by homogenates from both healthy and cardiomyopathic hamsters, the magnitude of the depression of oxidation (60-80%) in the myopathic homogenates was not influenced by carnitine. No change occurred in the rate of formation of palmitoyl-CoA from palmitoyl- l -carnitine or in the activity of acyl-CoA synthetases; similarly, the one-step oxidation of [1- 14 C]pyruvate, [1- 14 C]α-ketoglutarate, and succinate was unimpaired in cardiomyopathy, and the oxidation of [2- 14 C]pyruvate and [U- 14 C]α-ketoglutarate was maintained at a relatively high level (63-71% of control). In contrast, oxidation of [1, 4- 14 C]- and [2, 3- 14 C]succinate and [1- 14 C]acetyl-CoA by the myopathic homogenates was depressed to only 40% of the control values. The mechanism responsible for these defects in substrate oxidation by tissue homogenates from cardiomyopathic hearts has not been elucidated; however, significant increases in the activities of two of five hydrolytic enzymes indicate the possible involvement of lysosomes. Ventricular RNA and DNA, the ratio of RNA to DNA and the ratio of heart weight to body weight were all significantly increased, but myocardial water and triglyceride content and esterification of [1- 14 C]palmitate into neutral lipids showed no significant change.
Prognosis of Carcinoid Heart Disease
Authors: Jacob E. Møller, Patricia A. Pellikka, Alain M. Bernheim, Hartzell V. Schaff, Joseph Rubin, Heidi M. Connolly
Journal: Circulation (2005)

Background— The long-term prognosis of patients who develop carcinoid heart disease and the effect of cardiac surgery on outcome are not well established. Methods and Results— In this retrospective study, we identified 200 patients with carcinoid syndrome referred for echocardiography in whom the diagnosis of carcinoid heart disease was confirmed. Patients were divided into 3 groups of similar size according to the date from first diagnosis of carcinoid heart disease. Group A comprised patients diagnosed from 1981 through June 1989; group B, diagnosed July 1989 through May 1995; and group C, June 1995 through 2000. The end point was all-cause mortality. Median survival was significantly lower in group A (1.5 years, 95% CI 1.1 to 1.9 years) compared with groups B (3.2, 95% CI 1.3 to 5.1 years) and C (4.4, 95% CI 2.4 to 7.1 years; P =0.009). In a multivariate model adjusted for treatment and clinical characteristics, the risk of death in groups B (hazard ratio 0.67, 95% CI 0.46 to 0.99, P =0.04) and C (hazard ratio 0.61, 95% CI 0.39 to 0.92, P =0.006) was significantly reduced relative to group A. Cardiac surgery was performed in 87 patients. When cardiac surgery was included as a time-dependent covariate in a multivariate analysis, it was associated with a risk reduction of 0.48 (95% CI 0.31 to 0.73, P &lt;0.001), whereas the time period of diagnosis was no longer significant. Conclusions— The prognosis of patients with recognized carcinoid heart disease has improved over the past 2 decades at our institution. This change in survival may be related to valve replacement surgery.
Psychiatric Disorders Among Offspring of Depressed Mothers: Associations With Paternal Psychopathology
Authors: Naomi R Marmorstein, Stephen M Malone, William G Iacono
Journal: American Journal of Psychiatry (2004)

The association between maternal depression and offspring dysfunction is well documented; however, little attention has been paid to psychopathology in the partners of these depressed mothers or to how paternal psychopathology might influence the relationship between maternal depression and offspring dysfunction. The purpose of this study was to explore whether major depression and/or antisocial behavior tended to occur more frequently among partners of depressed mothers (compared to partners of nondepressed mothers) and to examine how these paternal disorders related to offspring psychopathology.Participants were drawn from the Minnesota Twin Family Study, a community-based study of twins and their parents. Depressed and nondepressed mothers, their partners (the biological fathers of the twins), and their 17-year-old offspring were included. Structured interviews were used to assess participants for the presence of major depression, conduct disorder, and adult antisocial behavior.Depressed mothers tended to partner with antisocial fathers. Depression in mothers and antisocial behavior in fathers were both significantly and independently associated with offspring depression and conduct disorder. No interactions of the parental diagnoses with each other or with the gender of the offspring were found.Many offspring of depressed mothers experience the additional risk of having an antisocial father. The implications of these findings for risk among the offspring of depressed mothers are discussed.
DEFINITION OF DRUNKENNESS
Authors: E. R. Fothergill
Journal: BMJ (1928)

<h3>ABSTRACT</h3> <h3>BACKGROUND</h3> Obesity is linked to a higher incidence of Alzheimer’s disease (AD). Studies show that plasma amyloid-β (Aβ) dyshomeostasis, particularly 42/40 ratio indicates heightened risk of developing AD. However, the relationship between body mass index (BMI) and circulating plasma Aβ have not been extensively studied. <h3>OBJECTIVE</h3> We hypothesised that people with a high BMI have altered plasma Aβ homeostasis compared with people with a lower BMI. We also tested whether lowering BMI by calorie-restriction normalises plasma concentrations of Aβ. <h3>METHODS</h3> The plasma concentrations of Aβ40, Aβ42 and Aβ42/40 ratio were measured in 106 participants who were classified as either lean, overweight, and obese, based on their BMI. 12 overweight/obese participants from the cohort of 106 individuals, were thereafter subjected to a 12-week calorie-restriction weight-loss program. We then tested whether the decreased BMI shows any correlation with plasma Aβ levels. <h3>RESULTS</h3> Obese participants showed significantly lower mean plasma Aβ42/40 ratio compared to lean (17.54%, <i>p</i>&lt;0.0001) and overweight participants (11.76%, <i>p</i>&lt;0.0001). The weight-loss regimen decreased BMI by an average of 4.148%, and was associated with a 6.5% decrease in plasma Aβ40 (<i>p</i>=0.0425). However, weight loss showed negligible correlations with plasma Aβ40, Aβ42 and Aβ42/40 ratio. <h3>CONCLUSION</h3> Obesity is associated with aberrant plasma Aβ homeostasis which may be associated with an increased risk for AD. Weight-loss shows some influence of Aβ, but further studies are required to elucidate the underlying mechanisms of how obesity induces plasma Aβ dyshomeostasis and the complete effect of weight-loss on Aβ metabolism.
S1P1 receptor directs the release of immature B cells from bone marrow into blood
Authors: Maria L. Allende, Galina Tuymetova, Bridgin G. Lee, Eliana Bonifacino, Yun-Ping Wu, Richard L. Proia
Journal: The Journal of Experimental Medicine (2010)

S1P1 receptor expression is required for the egress of newly formed T cells from the thymus and exit of mature T and B cells from secondary lymphoid organs. In this study, we deleted the expression of the S1P1 receptor gene (S1pr1) in developing B cells in the bone marrow. Although B cell maturation within the bone marrow was largely normal in the B cell–specific S1pr1 knockout (B-S1pr1KO) mice, their newly generated immature B cells appeared in the blood at abnormally low numbers as compared with control mice. In the bone marrow of B-S1pr1KO mice, immature B cells in contact with the vascular compartment displayed increased apoptosis as compared with control mice. Forced expression of CD69, a negative regulator of S1P1 receptor expression, in developing bone marrow B cells also reduced the number of immature B cells in the blood. Attenuation of CXCR4 signaling, which is required for the proper retention of developing B cells in bone marrow, did not release immature B cells into the blood of B-S1pr1KO mice as effectively as in control mice. Our results indicate that the S1P1 receptor provides a signal necessary for the efficient transfer of newly generated immature B cells from the bone marrow to the blood.
The Structure and Organization of Lamprin Genes: Multiple-Copy Genes with Alternative Splicing and Convergent Evolution with Insect Structural Proteins
Authors: Paul Robson, Glenda M. Wright, John H. Youson, Fred W. Keeley
Journal: Molecular Biology and Evolution (2000)

Lamprin is a unique structural protein which forms the extracellular matrix of several cartilaginous structures found in the lamprey. Lamprin is noncollagenous in nature but shows sequence similarities to elastins and to insect structural proteins. Here, we characterize the structure and organization of lamprin genes, demonstrating the presence of multiple similar but not identical copies of the lamprin gene in the genome of the lamprey. In at least one species of lamprey, Lampetra richardsoni, the multiple gene copies are arranged in tandem in the genome in a head-to-tail orientation. Lamprin genes from Petromyzon marinus contain either seven or eight exons, with exon 4 being alternatively spliced in all genes, resulting in a total of six different lamprin transcripts. All exon junctions are of class 1,1. An unusual feature of the lamprin gene structure is the distribution of the 3′ untranslated region sequence among multiple exons. A TATA box and cap sequence have been identified in upstream sequences in close proximity to the transcription start site, but no CAAT box could be identified. Sequence and gene structure comparisons between lamprins, elastins, and insect structural proteins suggest that the regions of sequence similarity are the result of a process of convergent evolution.
DST Studies in Psychotic Depression: A Meta-Analysis
Authors: J C Nelson, J M Davis
Journal: American Journal of Psychiatry (1997)

OBJECTIVE: Although hypersecretion of cortisol has frequently been reported in psychotic depression, the findings have been mixed. The authors performed a meta-analysis of the existing studies to determine the significance of differences in nonsuppression of cortisol across studies. METHOD: Fourteen studies that compared dexamethasone suppression test (DST) results in psychotic and nonpsychotic patients were examined, and a Mantel-Haenszel meta-analysis was performed. For comparison purposes, 19 studies of the DST with respect to melancholic/nonmelancholic and inpatient/outpatient distinctions were similarly reviewed. RESULTS: This analysis indicated a highly significant probability that a greater rate of cortisol nonsuppression occurs in psychotic depression. The nonsuppression rate was substantially higher in patients with psychotic depression (64%) than in nonpsychotic patients (41%). In the 19 studies of melancholia, nonsuppression was less frequent (36%), and when inpatient/outpatient status was controlled, melancholic depression was not significantly associated with nonsuppression. In nonmelancholic outpatients with major depression, the nonsuppression rate was low (12%). CONCLUSIONS: Among patients with major depression, psychotic depression is the subtype that is most closely associated with nonsuppression of cortisol on the DST. Hypercortisolemia is usually present in psychotic depression and may be important in understanding the pathophysiology of this syndrome. (Am J Psychiatry 1997; 154:1497–1503)
Association Between Sulfotransferase 1A1 Genotype and Survival of Breast Cancer Patients Receiving Tamoxifen Therapy
Authors: S. Nowell
Journal: JNCI Journal of the National Cancer Institute (2002)

Background: Human sulfotransferase 1A1 (SULT1A1) catalyzes the sulfation of a variety of phenolic and estrogenic compounds, including 4-hydroxytamoxifen (4-OH TAM), the active metabolite of tamoxifen. A functional polymorphism in exon 7 of the SULT1A1 gene (SULT1A1*2) has been described that generates an enzyme that has approximately twofold lower activity and is less thermostable than that of the common allele SULT1A1*1. We investigated the hypothesis that that high sulfation activity would increase the elimination of 4-OH TAM by examining whether the presence of this polymorphism affects the efficacy of tamoxifen therapy. Methods: We examined the relationship between the SULT1A1*2 allele and survival in a cohort of 337 women with breast cancer who received tamoxifen (n = 160) or who did not (n = 177). SULT1A1 genotype was determined by restriction fragment polymorphism analysis. Patient survival was evaluated according to SULT1A1 genotype using Kaplan–Meier survival functions. Hazard ratios (HRs) were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided. Results: Among tamoxifen-treated patients, those who were homozygous for the SULT1A1*2 low-activity allele had approximately three times the risk of death (HR = 2.9, 95% confidence interval [CI] = 1.1 to 7.6) as those who were homozygous for the common allele or those who were heterozygous (SULT1A1*1/*2). Among patients who did not receive tamoxifen, there was no association between survival and SULT1A1 genotype (HR = 0.7, 95% CI = 0.3 to 1.5). Conclusions: Sulfation of 4-OH TAM provides a previously unanticipated benefit, possibly due to alterations in the bioavailability of the active metabolite or to undefined estrogen receptor-mediated events. These data alternatively suggest that variability in the metabolism of tamoxifen may affect its efficacy.
Lymphocyte transformation induced by autologous cells. IV. Human T-lymphocyte proliferation induced by autologous or allogeneic non-T lymphocytes.
Authors: M M Kuntz, J B Innes, M E Weksler
Journal: The Journal of Experimental Medicine (1976)

An autologous mixed lymphocyte reaction was demonstrated between T and non-T lymphocytes. Sheep erythrocyte rosetting was used to separate human lymphocytes into T and non-T lymphoid preparations. Non-T lymphocytes stimulated the proliferation of autologous T lymphocytes. The cell in this preparation that was most stimulatory had the characteristics of a K lymphocyte. The allogeneic mixed lymphocyte reaction was also shown to reflect the proliferation of T lymphocytes stimulated by allogeneic non-T lymphocytes. Proliferation of T lymphocytes in the allogeneic mixed lymphocyte culture probably reflects a response to both foreign histocompatibility determinants and determinants present on non-T lymphocytes. It is suggested that the proliferative response of T lymphocytes to autologous non-T lymphocytes may be a step in the process by which T lymphocytes regulate immunity.
Substance P binding in normal neonatal foreskin
Authors: P. ARENBERGER, R.O. LEDER, A. ABRAHAM, J-K. CHANG, E.M FARBER
Journal: British Journal of Dermatology (1995)

The distribution of binding sites for NTE-biotinyl-[Arg3]-substance P (SPB) was demonstrated in neonatal foreskin using a conjugate of streptavidin with horseradish peroxidase. The observed binding is reversible, and may be abrogated by either the non-peptide substance P receptor antagonist, CP-96,345, or by unlabelled substance P. The generalized epidermal distribution and focal dermal localization of SPB binding suggest that although NK-1 receptors are abundant in human neonatal foreskin, neuromodulatory mechanisms may play a significant role in epidermal physiology.
Does reduced-intensity allogeneic transplantation confer a survival advantage to patients with poor prognosis chronic lymphocytic leukaemia? A case–control retrospective analysis
Authors: J. Delgado, S. Pillai, N. Phillips, S. Brunet, G. Pratt, J. Briones, R. Lovell, R. Martino, J. Ewing, A. Sureda, D.W. Milligan, J. Sierra
Journal: Annals of Oncology (2009)
Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation
Authors: Daigo Hashimoto, Andrew Chow, Melanie Greter, Yvonne Saenger, Wing-Hong Kwan, Marylene Leboeuf, Florent Ginhoux, Jordi C. Ochando, Yuya Kunisaki, Nico van Rooijen, Chen Liu, Takanori Teshima, Peter S. Heeger, E. Richard Stanley, Paul S. Frenette, Miriam Merad
Journal: The Journal of Experimental Medicine (2011)

Acute graft-versus-host disease (GVHD) results from the attack of host tissues by donor allogeneic T cells and is the most serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Host antigen-presenting cells are thought to control the priming of alloreactive T cells and the induction of acute GVHD after allo-HCT. However, whereas the role of host DC in GVHD has been established, the contribution of host macrophages to GVHD has not been clearly addressed. We show that, in contrast to DC, reducing of the host macrophage pool in recipient mice increased donor T cell expansion and aggravated GVHD mortality after allo-HCT. We also show that host macrophages that persist after allo-HCT engulf donor allogeneic T cells and inhibit their proliferation. Conversely, administration of the cytokine CSF-1 before transplant expanded the host macrophage pool, reduced donor T cell expansion, and improved GVHD morbidity and mortality after allo-HCT. This study establishes the unexpected key role of host macrophages in inhibiting GVHD and identifies CSF-1 as a potential prophylactic therapy to limit acute GVHD after allo-HCT in the clinic.
Positron Emission Tomography Use and Stage Migration in Lung Cancer: A False Sense of Accomplishment?
Authors: Natasha B. Leighl
Journal: Journal of Clinical Oncology (2012)

Stage migration is an evolutionary hazard in oncology. Over a quartercenturyago,Feinbergetal 1 demonstratedthattheuseofnovel imaging techniques to detect occult metastases (radionuclide scanning, computed tomography [CT] and ultrasonography) shifted patients with early-stage lung cancer into higher stages and artificially inflated survival rates. This is because patients who are upstaged have a worse prognosis than others in the early-stage group to which they wereinitiallyassigned,yetabetterprognosisthanthoseinthehigher
B-Type Natriuretic Peptide and Ischemia in Patients With Stable Coronary Disease
Authors: Kirsten Bibbins-Domingo, Maria Ansari, Nelson B. Schiller, Barry Massie, Mary A. Whooley
Journal: Circulation (2003)

In patients with symptoms of heart failure, elevations in B-type natriuretic peptide (BNP) accurately identify ventricular dysfunction. However, BNP levels are not specific for ventricular dysfunction in patients who do not have overt symptoms of heart failure, suggesting that other cardiac processes such as myocardial ischemia may also cause elevations in BNP.To determine whether BNP elevations are associated with myocardial ischemia, we measured plasma BNP levels before performing exercise treadmill testing with stress echocardiography in outpatients with stable coronary disease. Of the 355 participants, 113 (32%) had inducible ischemia. Compared with participants in the lowest BNP quartile (0 to 16.4 pg/mL), those in the highest quartile of BNP (> or =105 pg/mL) had double the risk of inducible ischemia (adjusted relative risk, 2.0; 95% CI, 1.2 to 2.6; P=0.008). The relation between elevated BNP levels and inducible ischemia was especially evident in the 206 participants who had a history of myocardial infarction (adjusted relative risk, 2.6; 95% CI, 1.5 to 3.7, P=0.002) and was absent in those without a history of myocardial infarction (adjusted relative risk, 1.0; 95% CI, 0.3 to 2.2; P=0.9). This association between BNP levels and inducible ischemia remained strong after adjustment for measures of systolic and diastolic dysfunction.Elevated levels of BNP are independently associated with inducible ischemia among outpatients with stable coronary disease, particularly among those with a history of myocardial infarction. The observed association between BNP levels and ischemia may explain why tests for BNP are not specific for ventricular dysfunction among patients with coronary disease.
Impact factors: no totum pro parte by skewness of citation
Authors: T Opthof
Journal: Cardiovascular Research (2004)

with a high impact factor obtain this high value by frequent citation of only a limited number of their papers and, on the other hand, journals with low impact factors publish many papers that remain uncited [1].Thus, mere publication of a paper in a given journal cannot be regarded as a quality marker of that particular paper [2], it just means that the authors have 'succeeded in surviving' the review process of that journal.Seglen [3] has analyzed that 50% of the obtained citations are accumulated by only 15% of the contents of a journal.In addition, the most frequently cited 50% of the contents obtain almost all citations (90%).These numbers were based on an analysis of three biochemical journals (Biochimica Biophysica Acta, Biochemical Journal and Journal of Biochemical Chemistry) and have later been confirmed for two cardiovascular journals (Circulation Research and Cardiovascular Research) [4].Both analyses applied to recently published papers [3,4].It is not known whether these data vary over time and whether or not they depend on impact itself.
Exercise Training for Heart Failure
Authors: Andrew J. S. Coats
Journal: Circulation (1999)

e have known for many years of the benefits of an exercise component in cardiac rehabilitation.It was initially thought that significant left ventricular impairment was a contraindication to participation in such programs.3][4] It was not until the late 1980s, however, that the first reports of training patients with a history of chronic heart failure (CHF) emerged. 5,6Pioneering work from Duke University showed a significant enhancement in exercise capacity and ancillary physiological benefits, including reduced lactate production, improved use of ventilatory reserve, and increased leg blood flow during progressive exercise. 5,6This was quickly followed by the first prospective controlled trial of exercise training in CHF, an 11-patient crossover study of home-based exercise training using a cycle ergometer for 8 weeks versus a similar period of activity restriction. 7The result was an improvement in exercise capacity and an improvement in questionnaire-based heart failure-related symptoms.The era of training as a treatment of heart failure had begun.
Congenital erythroleukemia: A case report with morphological, immunophenotypic, and cytogenetic findings
Authors: Randy R. Allan, Louis D. Wadsworth, Dagmar K. Kalousek, Bonnie G. Massing
Journal: American Journal of Hematology (1989)

Abstract We report a lethal case of congenital erythroleukemia presenting on the first day of life with peripheral blast cells and a leukemic infiltrate in the placenta. Although initial bone marrow examination did not fulfill the French‐American‐British (FAB) cooperative group criteria for acute myelogenous leukemia (AML), including M6, a malignant clone was confirmed by cytogenetic analysis: 49,XX,+8,+19,+21. Evolution to erythroleukemia (M6) occurred over a two‐month period. The diagnosis of erythroleukemia was supported by immunophenotyping employing an antibody to glycophorin A. The clinical course was complicated by liver failure of unknown etiology. Comparison to previously reported cases of early childhood erythroleukemia is made.