tbuckley/cabot-search huggingface dataset:
Replacement of the Muscle-Specific Sarcoplasmic Reticulum Ca <sup>2+</sup> -ATPase Isoform SERCA2a by the Nonmuscle SERCA2b Homologue Causes Mild Concentric Hypertrophy and Impairs Contraction-Relaxation of the Heart
Authors: Mark Ver Heyen, Stephane Heymans, Gudrun Antoons, Thomas Reed, Muthu Periasamy, Bonaventure Awede, Jean Lebacq, Peter Vangheluwe, Mieke Dewerchin, Desiré Collen, Karin Sipido, Peter Carmeliet, Frank Wuytack
Journal: Circulation Research (2001)

The cardiac sarco(endo)plasmic reticulum Ca(2+)-ATPase gene (ATP2A2) encodes the following two different protein isoforms: SERCA2a (muscle-specific) and SERCA2b (ubiquitous). We have investigated whether this isoform specificity is required for normal cardiac function. Gene targeting in mice successfully disrupted the splicing mechanism responsible for generating the SERCA2a isoform. Homozygous SERCA2a(-/-) mice displayed a complete loss of SERCA2a mRNA and protein resulting in a switch to the SERCA2b isoform. The expression of SERCA2b mRNA and protein in hearts of SERCA2a(-/-) mice corresponded to only 50% of wild-type SERCA2 levels. Cardiac phospholamban mRNA levels were unaltered in SERCA2a(-/-) mice, but total phospholamban protein levels increased 2-fold. The transgenic phenotype was characterized by a approximately 20% increase in embryonic and neonatal mortality (early phenotype), with histopathologic evidence of major cardiac malformations. Adult SERCA2a(-/-) animals (adult phenotype) showed a reduced spontaneous nocturnal activity and developed a mild compensatory concentric cardiac hypertrophy with impaired cardiac contractility and relaxation, but preserved beta-adrenergic response. Ca(2+) uptake levels in SERCA2a(-/-) cardiac homogenates were reduced by approximately 50%. In isolated cells, relaxation and Ca(2+) removal by the SR were significantly reduced. Comparison of our data with those obtained in mice expressing similar cardiac levels of SERCA2a instead of SERCA2b indicate the importance of the muscle-specific SERCA2a isoform for normal cardiac development and for the cardiac contraction-relaxation cycle.
Dietary Modification of Thyroxine Deiodination in Rat Liver is Not Mediated by Hepatic Sulfhydryls
Authors: Laurence A. Gavin, Francis A. McMahon, M. Moeller
Journal: Journal of Clinical Investigation (1980)

The enzymatic deiodination of thyroxine (T(4)) is thiol dependent. Fasting (72 h) depresses hepatic T(4) deiodination and lowers the hepatic content of nonprotein sulfhydryls (NP-SH) and reduced glutathione (GSH). It has been proposed that the fasting effect may be mediated through these alterations in hepatic sulfhydryls. To test the importance of tissue (hepatic) thiol content in the modification of T(4) deiodination consequent to dietary manipulation, we examined the sequential deiodination of T(4) to 3,5,3'-triiodothyronine (T(3)) (5'-deiodination) and 3,3',5-triiodothyronine (reverse T(3), rT(3)) (5-deiodination) in liver homogenates without added thiol from groups of rats fed Purina lab chow (P) (a protein-rich diet), glucose alone (G), or glucose plus cysteine (G(c)) for 72 h or fasted (F) for the same period. The initial rate of each reaction was compared to the tissue concentrations of NP-SH and GSH. Dietary manipulation induced significant changes in hepatic deiodination of T(4) to T(3) and rT(3) and sulfhydryl content. There was a marked dissociation between the rate of each reaction and hepatic NP-SH and GSH levels. T(4) deiodination by the alternative pathways was significantly higher (P < 0.01) in G > P > F. In contrast both hepatic NP-SH and GSH concentrations were greater (P < 0.05) in P > F > G. The lack of a relationship between these parameters was further emphasized on analysis of tissue from rats fed G(c). Despite the clearcut (P < 0.01) increase in hepatic NP-SH and GSH consequent to G(c) feeding, there was no alteration in iodothyronine deiodination compared to the group fed glucose alone. These data indicate that the effects of diet on T(4) monodeiodination in liver are not mediated by changes in the tissue level of sulfhydryl compounds but rather involve alterations in the concentrations of the deiodinases.
One-Hour Plasma Glucose Identifies Insulin Resistance and β-Cell Dysfunction in Individuals With Normal Glucose Tolerance
Authors: Melania Manco, Simona Panunzi, David P. Macfarlane, Alain Golay, Olle Melander, Thomas Konrad, John R. Petrie, Geltrude Mingrone
Journal: Diabetes Care (2010)

Some individuals with normal glucose tolerance (NGT) exhibit a 1-h excursion of plasma glucose during oral glucose tolerance testing as high as that of individuals with impaired glucose tolerance (IGT). The aim of this study was to characterize their metabolic phenotype.A total of 1,205 healthy volunteers (aged 29-61 years) underwent assessment of 1) oral glucose tolerance and 2) insulin sensitivity (standardized euglycemic-hyperinsulinemic clamp), as part of the Relationship between Insulin Sensitivity and Cardiovascular Risk (RISC) study.One-hour plasma glucose correlated better than 2-h plasma glucose with total insulin secretion (r = 0.43), beta-cell glucose sensitivity (r = -0.46), and beta-cell rate sensitivity (r = -0.18). Receiver operating characteristic analysis identified 8.95 mmol/l as the best cutoff value for prediction of IGT from 1-h plasma glucose (sensitivity 77% and specificity 80%). Participants with NGT with 1-h plasma glucose >8.95 mmol/l had larger waist circumference, higher BMI, lower insulin sensitivity, higher fasting glucose, and higher insulin secretion than their counterparts with 1-h plasma glucose <or=8.95 mmol/l (P < 0.001 for all comparisons). Moreover, they exhibited lower beta-cell glucose sensitivity (P < 0.001), beta-cell rate sensitivity (P < 0.001), and potentiation factor (P = 0.026). When compared with conventionally defined IGT, they were not different in waist circumference and BMI, hepatic insulin extraction, beta-cell glucose sensitivity, beta-cell rate sensitivity, and potentiation factor but did have greater insulin sensitivity along with reduced basal (P = 0.001) and total insulin secretion (P = 0.002).Higher values of 1-h plasma glucose may identify an intermediate condition between NGT and IGT characterized by greater insulin resistance, reduced beta-cell glucose sensitivity, and reduced beta-cell rate sensitivity.
ICOS and Bcl6-dependent pathways maintain a CD4 T cell population with memory-like properties during tuberculosis
Authors: Albanus O. Moguche, Shahin Shafiani, Corey Clemons, Ryan P. Larson, Crystal Dinh, Lauren E. Higdon, C.J. Cambier, James R. Sissons, Alena M. Gallegos, Pamela J. Fink, Kevin B. Urdahl
Journal: The Journal of Experimental Medicine (2015)

Immune control of persistent infection with Mycobacterium tuberculosis (Mtb) requires a sustained pathogen-specific CD4 T cell response; however, the molecular pathways governing the generation and maintenance of Mtb protective CD4 T cells are poorly understood. Using MHCII tetramers, we show that Mtb-specific CD4 T cells are subject to ongoing antigenic stimulation. Despite this chronic stimulation, a subset of PD-1+ cells is maintained within the lung parenchyma during tuberculosis (TB). When transferred into uninfected animals, these cells persist, mount a robust recall response, and provide superior protection to Mtb rechallenge when compared to terminally differentiated Th1 cells that reside preferentially in the lung-associated vasculature. The PD-1+ cells share features with memory CD4 T cells in that their generation and maintenance requires intrinsic Bcl6 and intrinsic ICOS expression. Thus, the molecular pathways required to maintain Mtb-specific CD4 T cells during ongoing infection are similar to those that maintain memory CD4 T cells in scenarios of antigen deprivation. These results suggest that vaccination strategies targeting the ICOS and Bcl6 pathways in CD4 T cells may provide new avenues to prevent TB.
Screening elderly cancer patients for disabilities: evaluation of study of osteoporotic fractures (SOF) index and comprehensive geriatric assessment (CGA)
Authors: A. Luciani, L. Dottorini, N. Battisti, C. Bertuzzi, S. Caldiera, I. Floriani, S. Zonato, D. Ferrari, P. Foa
Journal: Annals of Oncology (2012)
Clonal analysis of F1 hybrid helper T cells. I-A subregion-encoded hybrid determinants restrict the activity of keyhole limpet hemocyanin-specific helper T cells.
Authors: J F Sproviero, M J Imperiale, M Zauderer
Journal: The Journal of Experimental Medicine (1981)

Clonal expansion of isolated precursors to helper T cells was induced in limiting dilution cultures of keyhole limpet hemocyanin (KLH)-primed F1 hybrid lymph node cells. Progeny of each isolated precursor was tested for helper activity by transfer to independent cultures with hapten-primed B cells of either parental or F1 hybrid origin. The major histocompatibility complex (MHC) restriction specificity of each F1 hybrid helper T clone was determined. To assess the contribution of I-A and I-E subregion-encoded genes to the expression of these restriction elements, helper T cell cultures derived from F1 hybrids between strains with recombinant H-2 haplotypes were analyzed. Parental and unique F1 hybrid MHC determinants that are encoded entirely within the I-A subregion were found to restrict the activity of KLH-specific helper T cells.
Differentiation from precursors in athymic nude mouse bone marrow of unusual spontaneously cytolytic cells showing anti-self-H-2 specificity and bearing T cell markers.
Authors: J Reimann, R G Miller
Journal: The Journal of Experimental Medicine (1983)

We describe an in vitro limiting dilution culture system that supports growth and differentiation of nylon wool nonadherent bone marrow cells from athymic nude mice. Cells were seeded at low cell numbers (5-120 cells per 20-microliter microculture well) in the absence of added filler or feeder cells but in the presence of conditioned medium. Microwells positive for growth appeared to contain a single clone of cells that adhered together to form a tight cluster referred to here as a colony. A fraction of colonies contained cells that expressed an unusual spontaneous cytolytic activity. They lysed syngeneic or semisyngeneic Con A blast or tumor cell targets but seldom lysed H-2-incompatible Con A blast or tumor target cells, even in a lectin-facilitated assay. A large fraction of colonies contained lymphoid cells that expressed the T cell markers Thy-1 and Lyt-1. Colonies expressing spontaneous cytolytic activity and also containing cells with Thy-1+ and/or Lyt-1+ markers could be grown from nylon wool nonadherent nude marrow cells depleted rigorously by cell sorting of cells expressing either of these markers. Expression of Thy-1 and spontaneous cytolytic activity in a particular colony was significantly correlated. Short-term lines established from cytolytic colonies with T cell markers maintained both characteristics. The cytolytic effector cells observed in these cultures may represent an early stage in the development of the T cell repertoire.
Risk Factors for Breast Cancer for Women Aged 40 to 49 Years
Authors: Heidi D. Nelson
Journal: Annals of Internal Medicine (2012)

Background: Identifying risk factors for breast cancer specific to women in their 40s could inform screening decisions. Purpose: To determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor. Data Sources: MEDLINE (January 1996 to the second week of November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter of 2011), Scopus, reference lists of published studies, and the Breast Cancer Surveillance Consortium. Study Selection: English-language studies and systematic reviews of risk factors for breast cancer in women aged 40 to 49 years. Additional inclusion criteria were applied for each risk factor. Data Extraction: Data on participants, study design, analysis, follow-up, and outcomes were abstracted. Study quality was rated by using established criteria, and only studies rated as good or fair were included. Results were summarized by using meta-analysis when sufficient studies were available or from the best evidence based on study quality, size, and applicability when meta-analysis was not possible. Data from the Breast Cancer Surveillance Consortium were analyzed with proportional hazards models by using partly conditional Cox regression. Reference groups for comparisons were set at U.S. population means. Data Synthesis: Sixty-six studies provided data for estimates. Extremely dense breasts on mammography or first-degree relatives with breast cancer were associated with at least a 2-fold increase in risk for breast cancer. Prior breast biopsy, second-degree relatives with breast cancer, or heterogeneously dense breasts were associated with a 1.5- to 2.0-fold increased risk; current use of oral contraceptives, nulliparity, and age 30 years or older at first birth were associated with a 1.0- to 1.5-fold increased risk. Limitations: Studies varied by measures, reference groups, and adjustment for confounders, which could bias combined estimates. Effects of multiple risk factors were not considered. Conclusion: Extremely dense breasts and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk for breast cancer in women aged 40 to 49 years. Identification of these risk factors may be useful for personalized mammography screening. Primary Funding Source: National Cancer Institute.
A genetic association study of the IGF-1 gene and radiological osteoarthritis in a population-based cohort study (the Rotterdam study)
Authors: I Meulenbelt, C Bijkerk, H S Miedema, F C Breedveld, A Hofman, H A Valkenburg, H A P Pols, P E Slagboom, C M van Duijn
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> A genetic association study was performed to investigate whether radiographical osteoarthritis (ROA) was associated with specific genotypes of the insulin-like growth factor I (IGF-1) gene. <h3>METHODS</h3> Subjects aged 55–65 years were selected from a population-based study of which ROA at the knee, hip, spine, and hand was assessed. Genotypes were determined of a polymorphism in the promoter region of the IGF-1 gene. <h3>RESULTS</h3> The IGF-1 locus was significantly associated with the presence of ROA (overall adjusted OR for heterozygous subjects = 1.9, 95% CI 1.2, 3.1 and for homozygous subjects 3.6, 95% CI 0.8, 16.2). <h3>CONCLUSION</h3> These results suggest that variation at the IGF-1 locus is associated with ROA development and may play a part in ROA pathogenesis. To confirm these findings replication in another population-based sample is needed.
Prevalence and Trends in Obesity and Severe Obesity Among Children in the United States, 1999-2012
Authors: Asheley Cockrell Skinner, Joseph A. Skelton
Journal: JAMA Pediatrics (2014)

<h3>Importance</h3> Childhood obesity is the focus of public health efforts and accurate estimates of the prevalence and severity of obesity are needed for policy decisions and directions for future research. <h3>Objective</h3> To examine the prevalence of obesity and severe obesity over time for 14 years of the continuous National Health and Nutrition Examination Survey, 1999 to 2012, and to examine differences in the trends by age, race/ethnicity, and sex. <h3>Design, Setting, and Participants</h3> Representative sample (N = 26 690) of children in the United States, ages 2 to 19 years, in repeated cross-sections of the National Health and Nutrition Examination Survey, 1999 to 2012. <h3>Main Outcomes and Measures</h3> Prevalence of overweight (body mass index [BMI] ≥ 85th percentile), obesity (BMI ≥ 95th percentile for age and sex), class 2 obesity (BMI ≥ 120% of the 95th percentile or BMI ≥ 35), and class 3 obesity (BMI ≥ 140% of the 95th percentile or BMI ≥ 40). <h3>Results</h3> From 2011 to 2012, 17.3% (95% CI, 15.3-19.3) of children in the United States aged 2 to 19 years were obese. Additionally, 5.9% (95% CI, 4.4-7.4) of children met criteria for class 2 obesity and 2.1% (95% CI, 1.6-2.7) met criteria for class 3 obesity. Although these rates were not significantly different from 2009 to 2010, all classes of obesity have increased over the last 14 years. <h3>Conclusions and Relevance</h3> Nationally representative data do not show any significant changes in obesity prevalence in the most recently available years, although the prevalence of obesity may be stabilizing. Continuing research is needed to determine which, if any, public health interventions can be credited with this stability. Unfortunately, there is an upward trend of more severe forms of obesity and further investigations into the causes of and solutions to this problem are needed.
Further cases of unusual triggers of sneezing
Authors: Mahmood F Bhutta, Harold Maxwell
Journal: Journal of the Royal Society of Medicine (2009)

We agree entirely with Richard Smith and colleagues that competing interests beyond the financial are important, and appreciate their contribution to the debate. 1 As we state in our recent editorial, 2 PLoS Medicine takes all potential competing interests seriously.We accept that financial competing interests are easier to define and judge, but our editorial also outlines our position that more leadership and better policy are needed in the area of
HISTOPLASMOSIS AND SARCOIDOSIS
Authors: HAROLD L. ISRAEL
Journal: Annals of Internal Medicine (1967)

Letters and Comments1 February 1967HISTOPLASMOSIS AND SARCOIDOSISHAROLD L. ISRAEL, M.D.HAROLD L. ISRAEL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-66-2-450 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: An erroneous quotation by J. G. Guckian and J. E. Perry in "Granulomatous Hepatitis" (Ann. Intern. Med. 65: 1081, 1966) deserves correction. They state:Israel and associates . . . reported 22 patients with histoplasmosis who were originally thought to have sarcoidosis. Only four had a positive skin test, and none had positive Histoplasma complement-fixation tests or positive culture. The diagnoses were made by the identification of the organisms in tissues.Actually we reported one case in which histoplasmosis simulated sarcoidosis. In an effort to ascertain the frequency of this phenomenon, we surveyed 22 patients with typical... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 302 S. 19th St., Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1967Volume 66, Issue 2Page: 450-450KeywordsHepatitis EHepatitis G virusHistoplasmosisSarcoidosisSkin tests Issue Published: 1 February 1967 PDF downloadLoading ...
Inhibition of lactation with oestrogens.
Authors: C. K. Vartan
Journal: BMJ (1969)

therefore be estimated to be well in excess of 400.This compares with the present number of 349 consultants in England and Wales, and indicates the probability of expan- sion rather than contraction in the specialty.Of the 349 consultants in diseases of the chest, 242 (nearly 70%) are stated to be over the age of 50, and only two below the age of 40.This peculiar age-distribution is consequent upon the contraction in the specialty which followed the decline of tuberculosis.But other respiratory diseases continue unabated, or even increasing in relative importance; and, unless recruitment to training in the specialty is expanded, within 15 years there will be a grave deficiency of consultant physicians trained in chest diseases.It is therefore to be hoped that the Ministry's gloomy assessment of prospects will not discourage recruitment to training in what appears likely to be an expanding specialty.-Weare, etc.,
Altered profile of human gut microbiome is associated with cirrhosis and its complications
Authors: Jasmohan S. Bajaj, Douglas M. Heuman, Phillip B. Hylemon, Arun J. Sanyal, Melanie B. White, Pamela Monteith, Nicole A. Noble, Ariel B. Unser, Kalyani Daita, Andmorgan R. Fisher, Masoumeh Sikaroodi, Patrick M. Gillevet
Journal: Journal of Hepatology (2013)
TOXIN AND ANTITOXIN OF AND PROTECTIVE INOCULATION AGAINST BACILLUS WELCHII
Authors: Carroll G. Bull, Ida W. Pritchett
Journal: The Journal of Experimental Medicine (1917)

Five cultures of Bacillus welchii have been studied and compared Four came from infected wounds in the western theatre of war, and one was obtained from a personal article of clothing. Each culture possesses the essential characteristics ascribed to that group of bacteria. The infectious processes caused by the five cultures in rabbits, guinea pigs, and pigeons, are local in character; and very few or no bacilli enter or are found in the general blood stream during life or immediately after death. Glucose broth cultures, injected intravenously, are fatal to rabbits. Death occurs, almost immediately or after a few hours. Agglutinative bacterial emboli have been ruled out as the cause of death, as has been an acid intoxication. The fluid part of the culture acts in the same manner as the full culture and irrespective of neutralization with sodium hydroxide. The full cultures and supernatant fluid are hemolytic when injected directly into the circulation of rabbits and pigeons, and the acute death produced may be ascribed to a massive destruction of red corpuscles. The passage of the fluid portion of glucose broth cultures through Berkefeld filters reduces materially the hemolytic and poisonous effects. Cultures of the Welch bacilli in plain broth to which sterile pigeon or rabbit muscle is added are highly toxic, and the toxicity is not noticeably diminished by Berkefeld filtration. The filtrates are hemolytic when injected intravenously and inflaming and necrotizing when injected subcutaneously and intramuscularly. The local lesions produced in the breast muscles of the pigeon closely resemble those caused by infection with the bacilli. The toxicity of these filtrates is not affected by neutralization with sodium hydroxide, but is materially reduced by heating to 62°C. and entirely removed by heating to 70°C. for 30 minutes. Successive injections of carefully graded doses of this toxic filtrate in pigeons and rabbits give rise to active immunity. The blood taken from the immunized rabbits is capable of neutralizing the toxic filtrate in vivo and in vitro. The filtrate has therefore been designated as toxin and the immune serum as antitoxin. The antitoxin neutralizes the toxin in multiple proportions. Hence the latter would seem to possess the properties of an exotoxin. Moreover, it neutralizes the hemolytic as well as the locally .injurious toxic constituent. Antitoxic serum prepared from a given culture of Bacillus welchii is neutralizing for the toxins yielded by the other four cultures of that microorganism. The antitoxin is protective and curative against infection with the spore and the vegetative stages of Bacillus welchii in pigeons. The limits of the protective and curative action are now under investigation.