tbuckley/cabot-search huggingface dataset:
Lymphocytotoxic antibodies in systemic lupus erythematosus: studies of their temperature dependence, binding characteristics, and specificity in vitro.
Authors: P W Peake, J D Greenstein, V Timmermans, L Gavrilovic, J A Charlesworth
Journal: Annals of the Rheumatic Diseases (1988)

The lymphocytotoxicity of 33 lupus sera was tested against purified helper/inducer (OKT4) and cytotoxic/suppressor (OKT8) subsets of T lymphocytes at 15 degrees C and 37 degrees C in vitro. There was significantly less killing of both OKT4 and OKT8 cells at 37 degrees C (p less than 0.001 and p less than 0.01) and the ratio of OKT4/OKT8 cell killing at 15 degrees C (1.39 (0.73); mean (SD] was different from that observed at 37 degrees C (0.79 (0.42)) (p less than 0.001). OKT4 killing was greater than OKT8 killing in 21 out of 33 sera at 15 degrees C, while 22 of these sera showed predominantly OKT8 cytotoxicity at 37 degrees C. The relation between the OKT4/OKT8 cell ratio and OKT4/OKT8 serum killing was examined in 22 patients at both temperatures: a significant inverse correlation was observed at 37 degrees C (r = -0.53; p = 0.015) but not at 15 degrees C (p greater than 0.05). The addition of metabolic and cytoskeletal inhibitors increased cytotoxicity at 37 degrees C, but not IgM surface binding. A Scatchard binding analysis of the reaction at 15 degrees C showed that large numbers of antibody molecules were bound to both subsets, with a low average dissociation constant of less than or equal to 6 x 10(-8) mol/l, and electrophoretic blotting indicated that the target surface antigens varied in type and number among individual lymphocytotoxic sera. The demonstration of temperature dependent, tight binding between lymphocytotoxic antibody and variable antigens on the T cell surface emphasises the potential for this phenomenon to affect lymphocyte function in vivo in patients with systemic lupus erythematosus.
Therapeutic Assessment of Cytochrome C for the Prevention of Obesity Through Endothelial Cell-targeted Nanoparticulate System
Authors: Md. Nazir Hossen, Kazuaki Kajimoto, Hidetaka Akita, Mamoru Hyodo, Taichi Ishitsuka, Hideyoshi Harashima
Journal: Molecular Therapy (2013)

Because the functional apoptosis-initiating protein, cytochrome C (CytC) is rapidly cleared from the circulation (t1/2 (half-life): 4 minutes), it cannot be used for in vivo therapy. We report herein on a hitherto unreported strategy for delivering exogenous CytC as a potential and safe antiobesity drug for preventing diet-induced obesity, the most common type of obesity in humans. The functional activity of CytC encapsulated in prohibitin (a white fat vessel-specific receptor)-targeted nanoparticles (PTNP) was evaluated quantitatively, as evidenced by the observations that CytC-loaded PTNP causes apoptosis in primary adipose endothelial cells in a dose-dependent manner, whereas CytC alone did not. The delivery of a single dose of CytC through PTNP into the circulation disrupted the vascular structure by the targeted apoptosis of adipose endothelial cells in vivo. Intravenous treatment of CytC-loaded PTNP resulted in a substantial reduction in obesity in high-fat diet (HFD) fed wild-type (wt) mice, as evidenced by the dose-dependent prevention of the percentage of increase in body weight and decrease in serum leptin levels. In addition, no detectable hepatotoxicity was found to be associated with this prevention. Thus, the finding highlights the promising potential of CytC for use as an antiobesity drug, when delivered through a nanosystem.
Body Mass Index and Risk of Lung Cancer Among Never, Former, and Current Smokers
Authors: Llewellyn Smith, Louise A. Brinton, Margaret R. Spitz, Tram Kim Lam, Yikyung Park, Albert R. Hollenbeck, Neal D. Freedman, Gretchen L. Gierach
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundAlthough obesity has been directly linked to the development of many cancers, many epidemiological studies have found that body mass index (BMI)—a surrogate marker of obesity—is inversely associated with the risk of lung cancer. These studies are difficult to interpret because of potential confounding by cigarette smoking, a major risk factor for lung cancer that is associated with lower BMI.
In vitro targeting and imaging the translocator protein TSPO 18-kDa through G(4)-PAMAM–FITC labeled dendrimer
Authors: Nunzio Denora, Valentino Laquintana, Antonio Lopalco, Rosa Maria Iacobazzi, Angela Lopedota, Annalisa Cutrignelli, Giuliano Iacobellis, Cosimo Annese, Mariafrancesca Cascione, Stefano Leporatti, Massimo Franco
Journal: Journal of Controlled Release (2013)
Assessment of work performance in asthma for determination of cardiorespiratory fitness and training capacity.
Authors: C J Clark, L M Cochrane
Journal: Thorax (1988)

In view of the lack of objective information on work performance in asthma, a progressive incremental exercise test was carried out in 44 subjects with mild to moderate asthma and 64 normal, healthy subjects matched for habitual activity, to compare cardiorespiratory fitness and to determine the relative contribution of airflow obstruction to exercise limitation. The two groups achieved similar maximum heart rates (mean (SD) 176(12) and 175(10) beats/min). After allowance for confounding factors the asthmatic subjects had a lower maximum oxygen consumption (VO2 max) (by 199 ml min-1) than control subjects. Having asthma also accounted for a significant reduction in anaerobic threshold (125 ml min-1) and oxygen pulse (0.805 ml/beat). There was no correlation of FEV1 with VO2 max, anaerobic threshold, or oxygen pulse either before or after bronchodilator. The dyspnoea index (VE/MVV%) was increased in the asthmatic subjects at peak exercise, but was less than 60% in all subjects at a workload that produced 75% of the predicted maximum heart rate. Thus the asthmatic subjects had a maximum heart rate similar to that of normal subjects but the low VO2 max, anaerobic threshold, and oxygen pulse suggest suboptimal fitness, which was not directly due to airflow obstruction. All had sufficient ventilatory reserve to allow toleration of training at a work intensity adequate to permit improvements in cardiovascular fitness.
Is there a regeneration stimulator substance in the effluent from perfused partially hepatectomized livers?
Authors: Rosemary van Hoorn-Hickman, Del Kahn, Jewel Green, Heather A. Macleod, John Terblanche
Journal: Hepatology (1981)

An attempt was made to transfer a stimulator substance from the perfusate of partially hepatectomized perfused livers to the portal stump of portacaval-shunted pig recipients. Blood was either cross-circulated with recipients during perfusion or was given by exchange transfusion after 4 hr perfusion. There was an increase in thymidine kinase activity and mitotic indices in biopsies from portacaval-shunted recipients whether perfusions were performed 2 or 4 days after partial hepatectomy. Blood perfused through intact livers did not enhance the regenerative response of portacaval-shunted pigs; in fact it appeared to suppress the normal small response. Approximately 10% of the portacaval-shunted recipients died acutely when perfusate was infused into the portal stump. This did not occur if saline or unperfused blood was used suggesting that some toxic substance accumulated during liver perfusion. In end-stage fulminant hepatic failure, use of blood perfused through a partially hepatectomized animal liver may provide the regenerative stimulus which often appears to be lacking.
γ-Glutamyltransferase as a Risk Factor for Cardiovascular Disease Mortality
Authors: Elfriede Ruttmann, Larry J. Brant, Hans Concin, Günter Diem, Kilian Rapp, Hanno Ulmer
Journal: Circulation (2005)

Background— There is evidence from recent studies that γ-glutamyltransferase (GGT) is likely to be associated with cardiovascular disease (CVD). However, few studies to date with sufficient sample size and follow-up investigated the association of GGT with CVD mortality. Methods and Results— The relation of GGT to the risk of death from CVD was examined in a cohort of 163 944 Austrian adults that was monitored for up to 17 years. To evaluate GGT as an independent predictor, Cox proportional hazards models were calculated, which adjusted for established risk factors. In both men and women, high GGT was significantly ( P &lt;0.001) associated with total mortality from CVD, showing a clear dose-response relationship. Adjusted hazard ratios (95% CI) per log GGT increase were 1.66 (1.40 to 1.98) in men and 1.64 (1.36 to 1.97) in women. In men, subgroup analyses showed that high GGT was positively associated with incident fatal events of chronic forms of coronary heart disease ( P =0.009), congestive heart failure ( P &lt;0.001), and hemorrhagic ( P =0.01) and ischemic stroke ( P &lt;0.001). No significant associations were observed for acute myocardial infarction ( P =0.16). In women, hazard ratios suggested associations in all subgroups; however, for hemorrhagic and ischemic stroke they were not statistically significant ( P =0.09 and P =0.07, respectively). In addition, subgroup analyses stratified by age revealed a stronger relationship of GGT in younger participants. Hazard ratios for total CVD were 2.03 (1.53 to 2.69) in men and 2.60 (1.53 to 4.42) in women younger than 60 years. Conclusions— This study demonstrates in a large, prospectively observed cohort that GGT is independently associated with cardiovascular mortality.
Increased Prevalence of Congenital Heart Defects in Monozygotic and Dizygotic Twins
Authors: Anne Maria Herskind, Dorthe Almind Pedersen, Kaare Christensen
Journal: Circulation (2013)

Background— Smaller studies and many case series reports indicate that congenital heart defects may be more common in monochorionic twins than in dichorionic twins and singletons. Methods and Results— We investigated congenital heart defect occurrence in all twins and 5% of all singletons born in Denmark in 1977–2001 and followed through 2006 by linking the Danish Twin Registry and Statistics Denmark registers including the National Medical Birth Register and the Danish National Patient Register. Among 41 525 twin individuals, a total of 584 twins (1.4%) had a congenital heart defect registered in the Danish National Patient Register, whereas the corresponding numbers for singletons were 648 of 74 473 (0.87%; P &lt;0.001; ie, a 63% [95% confidence interval, 45–82%] increased risk for congenital heart defect for twins). Patent ductus arteriosus and coarctation of aorta occurred &gt;3 times as often in twins as in singletons, at 3.9 (95% confidence interval, 2.6–5.8) and 3.1 (95% confidence interval, 1.5–6.4), respectively. The increased occurrence in twins was also found in sensitivity analyses including only inpatients or only surgically treated cases regardless of whether preterm patent ductus arteriosus was included. We were not able to demonstrate a higher risk for congenital heart defect among monozygotic twins compared with dizygotic twins, and the congenital heart defect occurrence was also increased in dizygotic twins, who are all dichorionic. Conclusions— Congenital heart defect is more common in twins than in singletons, and the increased occurrence is not restricted to monochorionic twins. Intrauterine surveillance and a postnatal comprehensive cardiac assessment for both twins may be considered regardless of chorionicity and zygosity.
Inspiratory Muscle Relaxation Rate Slows during Exhaustive Treadmill Walking in Patients with Chronic Heart Failure
Authors: PHILIP D. HUGHES, NICHOLAS HART, CARL-HUGO HAMNEGÅRD, MALCOLM GREEN, ANDREW J. S. COATS, JOHN MOXHAM, MICHAEL I. POLKEY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Exercise intolerance is a feature of chronic heart failure (CHF). We hypothesized that excessive loading of the respiratory muscle pump might contribute to exertional breathlessness. One marker of excessive muscle-loading is slowing of maximum relaxation rate (MRR) and, therefore, to test our hypothesis, we investigated the effect of exhaustive treadmill walking on inspiratory muscle MRR in patients with CHF. We studied eight stable patients with mild-moderate CHF walking on a treadmill until termination because of severe dyspnea. Inspiratory muscle MRR was determined from esophageal pressure (Pes) change during submaximal sniffs (Sn) before and immediately after exercise to a mean (SD) minute ventilation of 77 (18) L/min. For comparison, nine healthy subjects performed a similar protocol; exercise was terminated either by severe dyspnea or when minute ventilation reached 100 L/min. There were no significant differences in terms of heart rate, respiratory rate, tidal volume, or inspiratory duty cycle at cessation of exercise. The mean slowing of Sn Pes MRR in the first minute after termination of exercise in the CHF group was 22.4% and in the normal control group it was 2.8% (p < 0.01). Our data show that slowing of inspiratory muscle relaxation rate occurs in patients with CHF walking to severe breathlessness. We conclude that severe loading of the inspiratory muscles is a feature of exertional dyspnea in CHF.
Selective hepatobiliary transport defect for organic anions and neutral steroids in mutant rats with hereditary-conjugated hyperbilirubinemia
Authors: Peter L. M. Jansen, Geny M. M. Groothuis, Wilbert H. M. Peters, Dirk F. M. Meijer
Journal: Hepatology (1987)

Mutant rats (TM rats) with abnormal hepatic excretory function were used to study biliary transport of dibromosulfophthalein, ouabain, tributylmethyl ammonium, cholate and taurocholate. In whole animals, dibromosulfophthalein and ouabain clearance is reduced to 7 and 37% of normal, respectively, due to severely impaired excretion from liver to bile. Initial uptake rates of these agents are relatively little affected. In the isolated perfused liver preparation, dibromosulfophthalein is retained within liver and perfusion medium, and the 60-min recovery on bile is reduced to 1.5 vs 75% in normal controls. Biliary excretion of cholate, taurocholate and the quaternary ammonium cation, [ 14 C]tributylmethyl ammonium, is not impaired. These results provide evidence for a selective defect of organic anion and neutral steroid transport in TM rats and confirm that multiple pathways exist for the hepatobiliary excretion of organic anions, neutral steroids, bile acids and cations. Bile flow in whole animals and in the isolated perfused liver is reduced to 50 and 30% of normal, respectively. This suggests that a normal function of the excretory systems for organic anions and neutral steroids is important for the maintenance of normal bile flow.
Creutzfeldt-Jakob disease: Do patients have viremia?
Authors: William Check
Journal: JAMA (1978)

Evidence has been obtained for the presence of infectious virus in the blood of guinea pigs with experimental Creutzfeldt-Jakob disease. If these results are replicated in humans with this type of spongiform encephalopathy, it could explain both systemic spread of the disease and raise a warning about transmissibility (through blood transfusions, for instance) during the long, symptomless period of incubation. The work was reported recently by Elias and Laura Manuelidis, both MDs and professors of neurology and pathology at the Yale University School of Medicine. In 1975 these investigators were the first to transmit Creutzfeldt-Jakob disease to laboratory rodents using human biopsy material from patients with the disease. In the current experiments reported in the June 2, 1978, issue of<i>Science</i>, they used brain tissue from guinea pigs that had been inoculated originally with material derived from the brain of a patient with Creutzfeldt-Jakob disease. This guinea-pig brain tissue was
Histologic Type, Organ of Origin, and Wnt Pathway Status: Effect on Gene Expression in Ovarian and Uterine Carcinomas
Authors: Kerby A. Shedden, Malti P. Kshirsagar, Donald R. Schwartz, Rong Wu, Hongfeng Yu, David E. Misek, Samir Hanash, Hidetaka Katabuchi, Lora Hedrick Ellenson, Eric R. Fearon, Kathleen R. Cho
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Ovarian and uterine carcinomas manifest several differentiation patterns resembling those seen in nonneoplastic epithelia of the gynecologic tract. Specific oncogene and tumor suppressor gene defects have been associated with particular differentiation patterns in carcinomas arising in either the uterus or ovary. For instance, ovarian and uterine carcinomas with endometrioid differentiation frequently show β-catenin mutations. Whereas type of differentiation is considered in the treatment of uterine carcinomas, it does not presently contribute to decisions about treatment of ovarian carcinomas. A widely accepted view is that the accumulation of specific gene defects and gene expression changes underlies phenotypic traits of cancers, including their response to treatment. Experimental Design: Using oligonucleotide microarrays to assess gene expression in 103 primary ovarian and uterine carcinomas, we sought to address whether organ of origin or type of differentiation (histotype; endometrioid versus serous) had a more substantial effect on gene expression patterns. Results: We found that effects on gene expression due to organ of origin and histotype are similar in magnitude and are parallel in that organ effects are similar in the two histotypes and histotype effects are similar in the two organs. In addition, ovarian and uterine endometrioid adenocarcinomas with β-catenin defects show a common gene expression signature largely distinct from that seen in tumors lacking such defects. Conclusions: Our results illustrate how organ of origin, type of differentiation, and specific molecular defects all contribute to gene expression in the most common types of ovarian and uterine cancers. The findings also imply gene expression data will be of value for stratifying ovarian cancer patients for new treatment approaches.
Hypoxia-Inducible Factor-1 Promotes Pancreatic Ductal Adenocarcinoma Invasion and Metastasis by Activating Transcription of the Actin-Bundling Protein Fascin
Authors: Xiao Zhao, Song Gao, He Ren, Wei Sun, Huan Zhang, Jianwei Sun, Shengyu Yang, Jihui Hao
Journal: Cancer Research (2014)

Because of the early onset of local invasion and distant metastasis, pancreatic ductal adenocarcinoma (PDAC) is the most lethal human malignant tumor, with a 5-year survival rate of less than 5%. In this study, we investigated the role of fascin, a prometastasis actin-bundling protein, in PDAC progression, invasion, and the molecular mechanisms underlying fascin overexpression in PDAC. Our data showed that the expression levels of fascin were higher in cancer tissues than in normal tissues, and fascin overexpression correlated with the PDAC differentiation and prognosis. Fascin overexpression promoted PDAC cell migration and invasion by elevating matrix metalloproteinase-2 (MMP-2) expression. Fascin regulated MMP-2 expression through protein kinase C and extracellular signal-regulated kinase. Importantly, our data showed that hypoxia induced fascin overexpression in PDAC cells by promoting the binding of hypoxia-inducible factor-1 (HIF-1) to a hypoxia response element on the fascin promoter and transactivating fascin mRNA transcription. Intriguingly, HIF-1α expression levels in PDAC patient specimens significantly correlated with fascin expression. Moreover, immunohistochemistry staining of consecutive sections demonstrated colocalization between HIF-1α and fascin in PDAC specimens, suggesting that hypoxia and HIF-1α were responsible for fascin overexpression in PDAC. When ectopically expressed, fascin was able to rescue PDAC cell invasion after HIF-1α knockdown. Our results demonstrated that fascin is a direct target gene of HIF-1. Our data suggested that the hypoxic tumor microenvironment in PDAC might promote invasion and metastasis by inducing fascin overexpression, and fascin might be targeted to block PDAC progression.
A functional promoter polymorphism in <i>monocyte chemoattractant protein–1</i> is associated with increased susceptibility to pulmonary tuberculosis
Authors: Pedro O. Flores-Villanueva, Jorge A. Ruiz-Morales, Chang-Hwa Song, Ludmila M. Flores, Eun-Kyeong Jo, Marta Montaño, Peter F. Barnes, Moises Selman, Julio Granados
Journal: The Journal of Experimental Medicine (2005)

We examined the distribution of single nucleotide polymorphisms (SNPs) in nitric oxide synthase 2A, monocyte chemoattractant protein–1 (MCP-1), regulated on activation, normal T cell expressed and secreted, and macrophage inflammatory protein–1α genes in tuberculosis patients and healthy controls from Mexico. The odds of developing tuberculosis were 2.3- and 5.4-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Cases of homozygous GG had the highest plasma levels of MCP-1 and the lowest plasma levels of IL-12p40, and these values were negatively correlated. Furthermore, stimulation of monocytes from healthy carriers of the genotype GG with Mycobacterium tuberculosis antigens yielded higher MCP-1 and lower IL-12p40 concentrations than parallel experiments with monocytes from homozygous AA. Addition of anti–MCP-1 increased IL-12p40 levels in cultures of M. tuberculosis–stimulated monocytes from homozygous GG, and addition of exogenous MCP-1 reduced IL-12p40 production by M. tuberculosis–stimulated monocytes from homozygous AA. Furthermore, we could replicate our results in Korean subjects, in whom the odds of developing tuberculosis were 2.8- and 6.9-fold higher in carriers of MCP-1 genotypes AG and GG than in homozygous AA. Our findings suggest that persons bearing the MCP-1 genotype GG produce high concentrations of MCP-1, which inhibits production of IL-12p40 in response to M. tuberculosis and increases the likelihood that M. tuberculosis infection will progress to active pulmonary tuberculosis.