tbuckley/cabot-search huggingface dataset:
Beneficial effects of long-term selective endothelin type A receptor blockade in canine experimental heart failure
Authors: G W Moe, A Albernaz, G O Naik, M Kirchengast, D J Stewart
Journal: Cardiovascular Research (1998)

Objectives: We examined the effects of chronic type A endothelin receptor (ETA) blockade in a dog model of pacing-induced cardiomyopathy. Methods: Eight dogs received an ETA antagonist, LU 135252 (50 mg/kg orally daily) and nine dogs received a matching placebo starting at day three of pacing and continued for the remainder of the three weeks of pacing. Results: In the placebo group, the mean pulmonary artery pressure and left ventricular end diastolic pressure increased from 16±3 and 8±2 mmHg, respectively, at baseline to 40±11 and 34±7 mmHg, respectively, at two weeks (both p<0.001 versus baseline). Cardiac output declined from 3.5±0.7 to 1.9±0.6 l/min (p<0.001). In the treatment group, LU 135252 attenuated the increase in mean pulmonary artery and left ventricular end diastolic pressure (16±3 and 9±1 mmHg at baseline to 29±3 and 27±3 mmHg, respectively, at two weeks (p<0.001), and the decline in cardiac output (3.2±0.3 to 2.6±0.8 l/min, p<0.01; p<0.05 versus placebo for the three parameters). Systemic and pulmonary vascular resistance increased only in the placebo group. Left ventricular end-diastolic volume increased to a similar degree. However, LU 135252 attenuated the increase in plasma norepinephrine level (placebo, 1.2±0.5 to 3.7±1.9 pmol/l; treatment, 0.8±0.3 to 2.4±0.6 pmol/l; both p<0.001 versus baseline; p<0.05 versus placebo). Conclusion: Our results suggest that endothelin-1 plays a role in the hemodynamic perturbations in canine pacing-induced cardiomyopathy. The favourable hemodynamic effects without concomitant aggravation of neurohormonal activation suggests that ETA receptor blockade may be beneficial in the treatment of heart failure.
Bony Immunology: 1st Annual International Conference on Osteoimmunology Crete, Greece, May 28–June 2, 2006
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

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Bone loss after ovariectomy is comparable in the presence (left) or absence (right) of T cells.

ERBEN Low estrogen—during menopause in women or induced by ovary removal in rodents—causes osteoporosis. Roberto Pacifici (Emory University School of Medicine, Atlanta,
Platelets as Cellular Effectors of Inflammation in Vascular Diseases
Authors: Matthew T. Rondina, Andrew S. Weyrich, Guy A. Zimmerman
Journal: Circulation Research (2013)

Platelets are chief effector cells in hemostasis. In addition, they are multifaceted inflammatory cells with functions that span the continuum from innate immune responses to adaptive immunity. Activated platelets have key thromboinflammatory activities in a variety of vascular disorders and vasculopathies. Recently identified inflammatory and immune activities provide insights into the biology of these versatile blood cells that are directly relevant to human vascular diseases.
Correlations between histological type, clinical behaviour, and prognosis in thymoma.
Authors: C Ricci, E A Rendina, E O Pescarmona, F Venuta, R Di Tolla, L P Ruco, C D Baroni
Journal: Thorax (1989)

Seventy four cases of thymoma were reclassified into three histological categories--cortical (30), medullary (9), and mixed (34) (the remaining patient had an intrathymic thymoma)--for an investigation of the relation between histological type, clinical behaviour, and long term prognosis. There were significant differences between the histological types in the frequency of myasthenia gravis and of the different tumour stages, the mean age of the patients, and prognosis. Myasthenia gravis occurred more commonly in patients with cortical (33%) and mixed thymoma (35%) than in patients with medullary thymoma (11%). Five, 10, 15, and 20 year actuarial survival was 100% for medullary thymoma; 85%, 76%, 65% and 65% respectively for mixed thymoma; and 52%, 45%, 45%, and 45% for cortical thymoma. Medullary thymoma is a benign tumour arising late in life and there was no mortality in this series after surgery alone. Cortical thymoma usually presented in middle age and must be regarded as malignant; mortality was 50% at five years despite a multidisciplinary approach, with surgery and postoperative radiotherapy in all patients and chemotherapy in selected cases. Mixed thymoma had a better prognosis than cortical thymoma, but must be regarded as potentially malignant. One third of the total patients had died by 10 years despite radical tumour resection.
Helper T cells induced by an immunopurified herpes simplex virus type I (HSV-I) 115 kilodalton glycoprotein (gB) protect mice against HSV-I infection.
Authors: W L Chan, M L Lukig, F Y Liew
Journal: The Journal of Experimental Medicine (1985)

Three herpes simplex virus type I (HSV-I) glycoproteins of apparent molecular masses 103, 63, and 115 kD have been purified using virus-specific monoclonal antibodies (mAb) G8D1, C2D2, and T157, respectively. Both G8D1 and C2D2 neutralize HSV-I in vitro and passively protect CBA mice against HSV-I infection in vivo, whereas T157 is neither neutralizing nor passively protective. However, mice given a single subcutaneous injection of 30 micrograms 115 kD glycoprotein in saline were completely protected against lethal challenges of HSV-I administered intraperitoneally or in the footpad 7 d after immunization. In contrast, mice similarly immunized with 103 or 63 kD glycoproteins were only partially protected. The prophylactic immunity was correlated with an early induction of specific antibody, which became even more evident 3 d after virus challenge. There was a remarkable similarity in antibody isotype distribution between the responses to 115 kD glycoprotein and to heat-inactivated intact HSV-I. However, the prechallenge sera from 115 kD glycoprotein hyperimmunized mice were again neither virus-neutralizing nor passively protective. All three glycoproteins induced only low levels of delayed-type hypersensitivity (DTH). Pretreatment of mice with cyclophosphamide significantly enhanced DTH to 115 kD and 103 kD glycoproteins in the absence of antibody, but failed to confer significant immunity, indicating that DTH alone is insufficient for protection. Splenic and lymph node Ig- (B cell-depleted) cells from mice protectively immunized with 115 kD glycoprotein could adoptively transfer effective protection and enhance a virus neutralizing antibody response in normal recipients challenged with a lethal dose of HSV-I. Both the protection and the ability to enhance neutralizing antibody were diminished when the cells were treated with mAb GK 1.5 and complement. These results therefore demonstrate that the 115 kD glycoprotein, though not apparently containing accessible epitopes for the induction of virus-neutralizing antibody, possesses determinants capable of activating helper T cells. These L3T4+ cells confer strong protective immunity by enhancing protective antibody upon challenge infection, probably through associative help.
PRELIMINARY CLINICAL REPORTS
Authors: Nathan S. Kline, Gunther M. Jacob
Journal: American Journal of Psychiatry (1955)

780 This is a preliminary report of combined reserpine-chlorpromazine therapy on more than 250 disturbed psychotic patients. The following dosage plan was evolved: The patient was started on 3 mg. reserpine and 25 mg. chiorpromazine orally once a day. After 10 days the chlorpromazine was increased to 25 mg. b.i.d. At the end of 3 to 4 weeks, if the patient was not showing satisfactory progress, the dose of chlorpromazine was increased to 50 mg. b.i.d., reserpine remaining at 3 mg. daily. After another 3 to 4 weeks, if the patient’s progress was still unsatisfactory, 5 mg. reserpine intramuscularly was added to the oral regimen. This was continued for io days. If the patient then showed signs of responding to therapy, intramuscular medication was gradually withdrawn, but the oral medication remained unchanged until the close of therapy. If, however, after 10 days of intramuscular injections, the patient was not showing an adequate response, the intramuscular dose was raised to 10 mg. and was continued until the response was adequate; then intramuscular injections were gradually withdrawn, leaving only the oral medication. Treatment lasted a minimum of 3 months. If at the outset the patient was extremely disturbed, and an early quieting effect was necessary, the patient was started on 5 mg. reserpine intramuscularly, and 3 mg. reserpine and 25 mg. chlorpromazine orally once a day. After 10 days the chiorpromazine was increased to b.i.d., and, if the patient’s progress was satisfactory, the intramuscular injections were gradually withdrawn; if progress was still unsatisfactory, the injections were continued for another 10 days. Then, if necessary, the intramuscular dose was raised to iO mg. After improvement was sufficient to discontinue this initial course of intramuscular reserpine injections, the subsequent dosage was the same as outlined in the preceding paragraph. In a previous paper by Barsa and Kline, “Use of Reserpine in Disturbed Psychotic Patients,” 1 Barsa distinguished 3 stages in the course of treatment with reserpine alone: the sedative period (sedative effect of the drug predominant) ; the turbulent period (behavior and symptoms grow worse); and the integrative period, in which the patient’s personality is gradually integrated and the delusions and hallucinations disappear. In combined reserpine-chlorpromazine therapy, too, the patient usually passed through these 3 stages, except that as a rule the turbulent period was not so severe or protracted as in uncombined reserpine therapy. Chlorpromazine seemed to have a definite potentiating effect on reserpine. Many cases that did not respond adequately to reserpine alone, did respond to the combined therapy. In the majority of cases it was possible to achieve satisfactory results without the need of intramuscular injections. Furthermore, the course of therapy was less stormy and less distressing to the patient because of the milder and shorter turbulent period.
Individual income, income distribution, and self rated health in Japan: cross sectional analysis of nationally representative sample
Authors: K. Shibuya, H. Hashimoto, E. Yano
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess the effects on self rated health of individual income and income distribution in Japan. <b>Design:</b> Cross sectional analysis. Data collected on household income, self rated health, and other sociodemographic characteristics at the individual level from comprehensive survey of the living conditions of people on health and welfare in a nationally representative sample from each prefecture. <b>Setting:</b> Prefectures in Japan. <b>Participants:</b> 80 899 people aged &gt;15 years with full records in survey. <b>Main outcome measures:</b> Dichotomous variable for self rated health of each respondent (0 if excellent, very good or good; 1 if fair or poor). <b>Results:</b> Inequality in income at the prefecture level measured by the Gini coefficient was comparable with that in other industrialised countries. Unadjusted odds ratios show a 14% increased risk (odds ratio 1.14, 95% confidence interval 1.02 to 1.27) in reporting poor or fair health for individuals living in prefectures with higher inequality in income. After adjustment, individual income was more strongly associated with self rated health than income inequality. Additional inclusion of regional effects showed that median income at the prefecture level was inversely related to self rated health. <b>Conclusions:</b> Individual income, probably relative to the median prefecture income, has a stronger association with self rated health than income inequality at the prefecture level. <h3>What is already known on this topic</h3> Contrary to the common perception of an egalitarian society, income inequality in Japan has increased rapidly since the late 1980s, though life expectancy continues to increase Individual level studies, exclusively carried out in the United States to assess the independent effects of income inequality on health, have had mixed results <h3>What this study adds</h3> Individual income levels, probably relative to regional median income, may have more influence on an individual9s perceived health than regional income inequality in Japan
Oxidative Stress by Monoamine Oxidase Mediates Receptor-Independent Cardiomyocyte Apoptosis by Serotonin and Postischemic Myocardial Injury
Authors: Pascale Bianchi, Oxana Kunduzova, Emanuela Masini, Claudie Cambon, Daniele Bani, Laura Raimondi, Marie-Helene Seguelas, Silvia Nistri, Wilson Colucci, Nathalie Leducq, Angelo Parini
Journal: Circulation (2005)

Background— Serotonin (5-hydroxytryptamine [5-HT]), released by activated platelets during cardiac ischemia, is metabolized by the mitochondrial enzyme monoamine oxidase A (MAO-A). Because hydrogen peroxide is one of the byproducts of 5-HT degradation by MAO-A, we investigated the potential role of reactive oxygen species generated by MAOs in 5-HT-dependent cardiomyocyte death and post-ischemia-reperfusion cardiac damage. Methods and Results— Treatment of isolated adult rat cardiomyocytes with 5-HT induced intracellular oxidative stress and cell apoptosis. The apoptotic cascade triggered by 5-HT involves release of cytochrome c, upregulation of proapoptotic Bax protein, and downregulation of antiapoptotic Bcl-2 protein. These effects were prevented by inhibition of amine transporter or MAO, antioxidants, or iron chelation. In contrast, cardiomyocyte apoptosis was only slightly affected by the 5-HT 2B receptor antagonist SB 206553. In vivo, inhibition of MAO-A largely reduced myocardial ultrastructural damage induced by 30 minutes of ischemia followed by 60 minutes of reperfusion in the rat heart. Cardioprotective effects of MAO inhibitors were associated with the prevention of postischemic oxidative stress, neutrophil accumulation, and mitochondrial-dependent cell death and were not reverted by SB 206553. Administration of MAO-A inhibitors during ischemia was still effective in preventing cardiac damage. Conclusions— Our results supply the first direct evidence that oxidative stress induced by MAO is responsible for receptor-independent apoptotic effects of 5-HT in cardiomyocytes and postischemic myocardial injury. These findings provide new insight into the mechanisms of 5-HT action in the heart and may constitute the basis for novel therapies.
β-Mannosylceramide Activates Type I Natural Killer T Cells to Induce Tumor Immunity without Inducing Long-Term Functional Anergy
Authors: Jessica J. O'Konek, Shingo Kato, Satomi Takao, Liat Izhak, Zheng Xia, Petr Illarionov, Gurdyal S. Besra, Masaki Terabe, Jay A. Berzofsky
Journal: Clinical Cancer Research (2013)

Most studies characterizing antitumor properties of invariant natural killer T (iNKT) cells have used the agonist, α-galactosylceramide (α-GalCer). However, α-GalCer induces strong, long-lasting anergy of iNKT cells, which could be a major detriment for clinical therapy. A novel iNKT cell agonist, β-mannosylceramide (β-ManCer), induces strong antitumor immunity through a mechanism distinct from that of α-GalCer. The objective of this study was to determine whether β-ManCer induces anergy of iNKT cells.Induction of anergy was determined by ex vivo analysis of splenocytes from mice pretreated with iNKT cell agonists as well as in the CT26 lung metastasis in vivo tumor model.β-ManCer activated iNKT cells without inducing long-term anergy. The transience of anergy induction correlated with a shortened duration of PD-1 upregulation on iNKT cells activated with β-ManCer, compared with α-GalCer. Moreover, whereas mice pretreated with α-GalCer were unable to respond to a second glycolipid stimulation to induce tumor protection for up to 2 months, mice pretreated with β-ManCer were protected from tumors by a second stimulation equivalently to vehicle-treated mice.The lack of long-term functional anergy induced by β-ManCer, which allows for a second dose to still give therapeutic benefit, suggests the strong potential for this iNKT cell agonist to succeed in settings where α-GalCer has failed.
Late exercise training improves non-uniformity of transmural myocardial function in rats with ischaemic heart failure
Authors: Younss Aït Mou, Cyril Reboul, Lucas Andre, Alain Lacampagne, Olivier Cazorla
Journal: Cardiovascular Research (2008)

The exercise-induced beneficial mechanisms after long-term myocardial infarction (MI) are incompletely understood. The present study evaluated the effect of treadmill exercise training (5 weeks), started at a late stage of heart failure (HF) (13 weeks post-MI), on rat left ventricle remodelling and dysfunction of the regional global and cellular contractile functions.In vivo echocardiography confirmed that sub-endocardial (ENDO) layers contract more (+86%) and faster (+50%) than the sub-epicardial (EPI) layers. This gradient was lost in MI rats due to a predominant reduction in the ENDO layer contractility. Exercise partially restored the amplitude and velocity of ENDO contraction, resulting in a partial recovery of the pump function indexed by the aortic blood-flow velocity time integral. At the cellular level, MI impaired ENDO contractile properties by reducing cell shortening (10-7%), calcium transient, and myofilament Ca(2+) sensitivity. These alterations were normalized by exercise. Sarcoplasmic reticulum Ca(2+)-ATPase (SERCA)2a expression and myosin light chain (MLC)-2 phosphorylation in ENDO cells were significantly reduced after MI and were restored by exercise. The EPI layer was only slightly reduced in vivo without cellular alterations.This study shows that exercise performed at a late stage after MI restored a transmural non-uniformity of myocardium lost during HF. Recoveries of Ca(2+) homeostasis and myofilament function of cardiomyocytes contribute to this beneficial effect.
Time course of changes in the mechanical properties of the canine right and left ventricles during hypertrophy caused by pressure overload.
Authors: I Mirsky, M M Laks
Journal: Circulation Research (1980)

We developed a mathematical model of the right and left ventricles to determine whether there is a change in the mechanical properties of muscle during the hypertrophy process resulting from pulmonary arterial banding. Pressure-volume data were obtained from 10 normal dog hearts and 8 dog hearts in which the pulmonary artery was banded for periods of 2--40 weeks. These data were applied to the model, and the time course of wall stress and muscle stiffness was quantified for both ventricles. The results demonstrate that (1) myocardial stiffness is increased in pressure-overload hypertrophy (2) normal right and left ventricular muscle exhibits similar mechanical properties and (3) the relationships between wall stresses and the volume/mass ratios to the period of banding are biphasic. We concluded that (1) increase in muscle stiffness is due to several factors. In the early stages of hypertrophy, it may be predominantly due to fibrosis and, in the later stages, to substantial increases in muscle mass. (2) The progressive increase in muscle stiffness concomitant with the increase in muscle mass may be due to the presence of myocardial cellular projections and fibrosis. (3) The appropriate timing for surgical/medical intervention should take place before low volume:mass ratios and, hence, low wall stresses are attained.
Closing gaps in the human genome using sequencing by synthesis
Authors: Manuel Garber, Michael C Zody, Harindra M Arachchi, Aaron Berlin, Sante Gnerre, Lisa M Green, Niall Lennon, Chad Nusbaum
Journal: Genome biology (2009)

The most recent release of the finished human genome contains 260 euchromatic gaps (excluding chromosome Y). Recent work has helped explain a large number of these unresolved regions as 'structural' in nature. Another class of gaps is likely to be refractory to clone-based approaches, and cannot be approached in ways previously described. We present an approach for closing these gaps using 454 sequencing. As a proof of principle, we closed all three remaining non-structural gaps in chromosome 15.
Regulation of Smooth Muscle α-Actin Expression In Vivo Is Dependent on CArG Elements Within the 5′ and First Intron Promoter Regions
Authors: Christopher P. Mack, Gary K. Owens
Journal: Circulation Research (1999)

Abstract —The aims of the present studies were to define sufficient promoter sequences required to drive endogenous expression of smooth muscle (SM) α-actin and to determine whether regulation of SM α-actin expression in vivo is dependent on CArG (CC(A/T) 6 GG) cis elements. Promoter deletions and site directed mutagenesis techniques were used to study gene regulation in transgenic mice as well as in smooth muscle cell (SMC) cultures. Results demonstrated that a Lac Z transgene that contained 547 bp of the 5′ rat SM α-actin promoter was sufficient to drive embryonic expression of SM α-actin in the heart and in skeletal muscle but not in SMCs. Transient transfections into SMC cultures demonstrated that the conserved CArG element in the first intron had significant positive activity, and gel shift analyses demonstrated that the intronic CArG bound serum response factor. A transgene construct from −2600 through the first intron (p2600Int/Lac Z) was expressed in embryos and adults in a pattern that closely mimicked endogenous SM α-actin expression. Expression in adult mice was completely restricted to SMCs and was detected in esophagus, stomach, intestine, lung, and nearly all blood vessels, including coronary, mesenteric, and renal vascular beds. Mutation of CArG B completely inhibited expression in all cell types, whereas mutation of the intronic CArG selectively abolished expression in SMCs, which suggests that it may act as an SMC-specific enhancer-like element. Taken together, these results provide the first in vivo evidence for the importance of multiple CArG cis elements in the regulation of SM α-actin expression.
Physical activity/fitness peaks during perimenopause and BMI change patterns are not associated with baseline activity/fitness in women: a longitudinal study with a median 7-year follow-up
Authors: Xuemei Sui, Jiajia Zhang, Duck-chul Lee, Timothy S Church, Wenbin Lu, Junxiu Liu, Steven N Blair
Journal: British Journal of Sports Medicine (2012)

Objective To assess the age-associated longitudinal trends in cardiorespiratory fitness (CRF), leisure-time physical activity (PA), and body mass index (BMI) across the lifespan in a cohort of adult women. Methods The sample included 1467 women from the Aerobics Center Longitudinal Study who were 30–79 years old at baseline and had 3–22 health examinations between 1971 and 2006. CRF was quantified by maximal Balke treadmill exercise tests. The total metabolic equivalent-minutes/week of self-reported PA and measured BMI (kg/m 2 ) were calculated. Results The overall pattern of CRF decreased over time. After age 60 years, fitness level tended to decline rapidly. Women at age 50 had the highest PA level, which decreased after age 50 and plateaued at age 60. The overall pattern of BMI increased with age. However, after age 60 years the rate of increase in BMI became much slower. Adjusting for smoking, health status, and the individual exposures of CRF, PA and BMI did not influence the observed associations. Women who did not meet current PA recommendation or those who were low fit at baseline had a higher BMI throughout adulthood than their more active or fit peers, but the trajectory of BMI was unassociated with baseline activity or fitness levels. Conclusion We concluded that the age-related longitudinal patterns in physical activity and fitness are not linear. Baseline activity and fitness levels are associated with BMI status during adulthood, but do not affect BMI change trajectory.