tbuckley/cabot-search huggingface dataset:
FATE OF MYCOBACTERIUM TUBERCULOSIS IN MOUSE TISSUES AS DETERMINED BY THE MICROBIAL ENUMERATION TECHNIQUE
Authors: Robert M. McCune, Ralph Tompsett
Journal: The Journal of Experimental Medicine (1956)

Observations are presented on the behavior of populations of tubercle bacilli in the tissues of mice during the administration of antimicrobial drugs. The behavior of the populations during therapy with any particular drug was different depending upon whether the tubercle bacilli were subsisting in the lung or in the spleen. Moreover, the pattern of microbial behavior was distinctive and predictable for each drug studied. Changes in the size of the populations of tubercle bacilli in the tissues appeared to be a more sensitive reflection of drug influence than microscopic study of the number and character of the tuberculous lesions. Nevertheless, in untreated animals, pulmonary lesions evolved and progressed steadily to a fatal outcome despite the fact that the populations of tubercle bacilli had stabilized at a relatively high census early in the course of therapy. The uniform persistence of tubercle bacilli in the spleen throughout prolonged drug administration was demonstrated with every drug or multiple drug regimens except for pyrazinamide when accompanied by isoniazid. Cultures of the bacilli which survived in the tissues despite antimicrobial therapy were highly susceptible to the drugs employed when tested in vitro. Thus the survival of the tubercle bacilli in the tissues represented microbial persistence rather than drug resistance. When pyrazinamide and isoniazid were administered together, it was not possible to detect the microorganisms in the spleen or lungs of treated animals. A detailed investigation of this apparent abolition of microbial persistence forms the subject of an accompanying report.
Interferon (IFN) Consensus Sequence-binding Protein, a Transcription Factor of the IFN Regulatory Factor Family, Regulates Immune Responses In Vivo through Control of Interleukin 12 Expression
Authors: Nathalia A. Giese, Lucia Gabriele, T. Mark Doherty, Dennis M. Klinman, Lekidelu Tadesse-Heath, Christina Contursi, Suzanne L. Epstein, Herbert C. Morse
Journal: The Journal of Experimental Medicine (1997)

Mice with a null mutation of the gene encoding interferon consensus sequence-binding protein (ICSBP) develop a chronic myelogenous leukemia-like syndrome and mount impaired responses to certain viral and bacterial infections. To gain a mechanistic understanding of the contributions of ICSBP to humoral and cellular immunity, we characterized the responses of control and ICSBP-/- mice to infection with influenza A (flu) and Leishmania major (L. major). Mice of both genotypes survived infections with flu, but differed markedly in the isotype distribution of antiflu antibodies. In sera of normal mice, immunoglobulin (Ig)G2a antibodies were dominant over IgG1 antibodies, a pattern indicative of a T helper cell type 1 (Th1)-driven response. In sera of ICSBP-/- mice, however, IgG1 antibodies dominated over IgG2a antibodies, a pattern indicative of a Th2-driven response. The dominance of IgG1 and IgE over IgG2a was detected in the sera of uninfected mice as well. A seeming Th2 bias of ICSBP-deficient mice was also uncovered in their inability to control infection with L. major, where resistance is known to be dependent on IL-12 and IFN-gamma as components of a Th1 response. Infected ICSBP-deficient mice developed fulminant, disseminated leishmaniasis as a result of failure to mount a Th1-mediated curative response, although T cells remained capable of secreting IFN-gamma and macrophages of producing nitric oxide. Compromised Th1 differentiation in ICSBP-/- mice could not be attributed to hyporesponsiveness of CD4(+) T cells to interleukin (IL)-12; however, the ability of uninfected and infected ICSBP-deficient mice to produce IL-12 was markedly impaired. This indicates that ICSBP is a deciding factor in Th responses governing humoral and cellular immunity through its role in regulating IL-12 expression.
Imatinib mesylate attenuates fibrosis in coxsackievirus b3-induced chronic myocarditis
Authors: Carola Leipner, Katja Grün, Andreas Müller, Elisabeth Buchdunger, Laura Borsi, Hartwig Kosmehl, Alexander Berndt, Tobias Janik, Andrea Uecker, Michael Kiehntopf, Frank-D. Böhmer
Journal: Cardiovascular Research (2008)

Coxsackievirus B3 (CVB3)-induced chronic myocarditis in mice is accompanied by severe fibrosis and by sustained elevation of platelet-derived growth factor (PDGF)-A, -B, and -C levels in the cardiac tissue. To test if PDGF stimulation of resident fibroblasts causally contributes to fibrosis, we employed inhibition of PDGF receptor signalling with the orally available kinase inhibitor Imatinib.Chronic myocarditis was induced by CVB3 infection of major histocompatibility complex (MHC) class II knockout (B6Aa(0)/Aa(0)) mice. The mice were treated with 100 mg/kg Imatinib or vehicle, respectively, twice daily for 34 days. Expression of PDGF-C and of inflammatory cytokines were analysed by semi-quantitative RT-PCR. PDGFalpha receptor phosphorylation was detected by immunoblotting of cardiac tissue extracts and in situ by immunohistochemistry. Fibrosis formation was analysed by Sirius-Red staining and hydroxyproline (HP) determination. Fibronectin, and tenascin expression was analysed by RT-PCR and immunohistochemistry. Matrix metalloproteinase (MMP) activity was assessed with collagen, synthetic peptides, and gelatine as substrates. Imatinib significantly inhibited the myocarditis-related PDGFalpha receptor activation in the heart tissue. The virus titres in the hearts, inflammatory infiltrations, and elevated PDGF levels were unaffected by the Imatinib treatment. A significant attenuation of fibrosis occurred in Imatinib-treated animals. The Sirius Red-stained fibrotic area was reduced from 5.30 +/- 0.50 to 3.21 +/- 0.35%, and the HP content was reduced from 362 +/- 43 to 238 +/- 32 microMol/10 mg dry weight vs. 190 +/- 27 in uninfected controls. The expression of fibronectin, EIIIA+ fibronectin, and tenascin C were likewise reduced. The diminished matrix protein deposition was not caused by elevated MMP activity, since MMP activity was not changed or even reduced under Imatinib.The data suggest a causal role for elevated PDGF expression and PDGF receptor activity in the pathogenesis of cardiac fibrosis.
Comprehensive mutational profiling in advanced systemic mastocytosis
Authors: Juliana Schwaab, Susanne Schnittger, Karl Sotlar, Christoph Walz, Alice Fabarius, Markus Pfirrmann, Alexander Kohlmann, Vera Grossmann, Manja Meggendorfer, Hans-Peter Horny, Peter Valent, Mohamad Jawhar, Martina Teichmann, Georgia Metzgeroth, Philipp Erben, Thomas Ernst, Andreas Hochhaus, Torsten Haferlach, Wolf-Karsten Hofmann, Nicholas C. P. Cross, Andreas Reiter
Journal: Blood (2013)
Mechanical Remodeling of the Left Atrium After Loss of Atrioventricular Synchrony
Authors: Paul B. Sparks, Harry G. Mond, Jitendra K. Vohra, Anthony G. Yapanis, Leeanne E. Grigg, Jonathan M. Kalman
Journal: Circulation (1999)

Background —Tachycardia-mediated mechanical remodeling of the atrium is considered central to the pathogenesis of thromboembolism associated with chronic atrial fibrillation. Whether atrial mechanical remodeling also occurs in response to atrial stretch induced by chronic asynchronous ventricular pacing in patients with permanent pacemakers is unknown. Methods and Results —The study design was a prospective randomized comparison between 21 patients paced chronically in the VVI mode and 11 patients paced chronically in the DDD mode for 3 months. Left atrial appendage (LAA) function and the presence of spontaneous echo contrast (SEC) were determined with transesophageal echocardiography (TEE) within 24 hours of pacemaker implantation and after 3 months. The VVI patients were then programmed to DDD and underwent a third TEE after DDD pacing for an additional 3 months. After chronic VVI pacing, LAA velocity decreased from 82.4±29.0 to 42.1±25.4 cm/s ( P &lt;0.01), LAA fractional area change decreased from 74.9±17.2% to 49.8±22.0% ( P &lt;0.01), and 4 patients (19%) developed left atrial SEC ( P &lt;0.05). With the reestablishment of chronic AV synchrony, LAA velocity increased to 61.6±18.5 cm/s ( P &lt;0.01), LAA fractional area change increased to 76.4±18.1% ( P &lt;0.01), and SEC resolved. In the 11 patients undergoing chronic DDD pacing, no significant changes in LAA velocity (baseline, 86.0±28.8 cm/s versus 3 months, 79.6±14.9 cm/s) or LAA fractional area change (baseline, 76.2±19.4% versus 72.5±15.7%) were demonstrated, and SEC did not develop. Conclusions —Chronic loss of AV synchrony induced by VVI pacing is associated with mechanical remodeling of the left atrium, which may reverse after the reestablishment of AV synchrony with DDD pacing. This process may be partly responsible for the higher incidence of thromboembolism observed in patients undergoing VVI pacing compared with AV sequential pacing.
Seafood Safety Hot Line
Authors: Stuart L. Nightingale
Journal: JAMA (1995)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Biochemistry and Physiology of Bone, vol 3; Development and Growth
Authors: Reginald R. Cooper
Journal: JAMA (1972)

The rapidly expanding insight into bone structure and biodynamics, resulting from the interaction of various research disciplines, necessitates continued transmittal of information. In fulfilling such a task, this new volume assumes its rightful place along with its two predecessors in this series. This treatise consists of 12 chapters, each a distinct monograph by one or more world-renowned authors with extensive experience and intense interest in the respective subjects. The reader can therefore select from among these according to his desires, but should not expect an elementary, coordinated, complete text on bone physiology. He can expect to find each topic discussed in light of opinions espoused by the particular writer. Several chapters describing osteogenesis, bone growth, and bone turnover summarize well-established concepts and integrate these with others gained by the use of modern research methods. Other sections review bone repair and transplantation. Outstanding expositions on cell dynamics of bone, action of
559 THE OUTCOME OF LIVER TRANSPLANTATION FOR BUDD-CHIARI SYNDROME – A SINGLE CENTER EXPERIENCE
Authors: U. Ołdakowska-Jedynak, M. Ziarkiewicz, J. Dwilewicz-Trojaczek, M. Tomaniak, P. Nyckowski, K. Zieniewicz, R. Paluszkiewicz, W.W. Jędrzejczak, M. Krawczyk
Journal: Journal of Hepatology (2011)
Serotonin and Angiotensin Receptors in Cardiac Fibroblasts Coregulate Adrenergic-Dependent Cardiac Hypertrophy
Authors: Fabrice Jaffré, Philippe Bonnin, Jacques Callebert, Haythem Debbabi, Vincent Setola, Stéphane Doly, Laurent Monassier, Bertrand Mettauer, Burns C. Blaxall, Jean-Marie Launay, Luc Maroteaux
Journal: Circulation Research (2008)

By mimicking sympathetic stimulation in vivo, we previously reported that mice globally lacking serotonin 5-HT 2B receptors did not develop isoproterenol-induced left ventricular hypertrophy. However, the exact cardiac cell type(s) expressing 5-HT 2B receptors (cardiomyocytes versus noncardiomyocytes) involved in pathological heart hypertrophy was never addressed in vivo. We report here that mice expressing the 5-HT 2B receptor solely in cardiomyocytes, like global 5-HT 2B receptor–null mice, are resistant to isoproterenol-induced cardiac hypertrophy and dysfunction, as well as to isoproterenol-induced increases in cytokine plasma-levels. These data reveal a key role of noncardiomyocytes in isoproterenol-induced hypertrophy in vivo. Interestingly, we show that primary cultures of angiotensinogen null adult cardiac fibroblasts are releasing cytokines on stimulation with either angiotensin II or serotonin, but not in response to isoproterenol stimulation, demonstrating a critical role of angiotensinogen in adrenergic-dependent cytokine production. We then show a functional interdependence between AT 1 Rs and 5-HT 2B receptors in fibroblasts by revealing a transinhibition mechanism that may involve heterodimeric receptor complexes. Both serotonin- and angiotensin II–dependent cytokine production occur via a Src/heparin-binding epidermal growth factor–dependent transactivation of epidermal growth factor receptors in cardiac fibroblasts, supporting a common signaling pathway. Finally, we demonstrate that 5-HT 2B receptors are overexpressed in hearts from patients with congestive heart failure, this overexpression being positively correlated with cytokine and norepinephrine plasma levels. Collectively, these results reveal for the first time that interactions between AT 1 and 5-HT 2B receptors coexpressed by noncardiomyocytes are limiting key events in adrenergic agonist-induced, angiotensin-dependent cardiac hypertrophy. Accordingly, antagonists of 5-HT 2B receptors might represent novel therapeutics for sympathetic overstimulation-dependent heart failure.
Positive Approaches to Continuing Medical Education in Community Hospitals
Authors: Norman S. Stearns
Journal: New England Journal of Medicine (1967)

THE Postgraduate Medical Institute, established in 1953 under the sponsorship of the Massachusetts Medical Society, was designed to encourage and, at least in part, to provide for the continuing education of physicians.1 The Institute believes that community hospitals will be the primary focus of continuing education activity for physicians in the future. It is expected that practitioners will continue to educate themselves by reading and by attendance at society meetings and formal courses. Such individual efforts, however, will truly be recognized and rewarded in the hospital setting and particularly in hospitals with meaningful education programs of their own.The present . . .
Effect of Losartan, a Type 1 Angiotensin II Receptor Antagonist, on Bronchial Hyperresponsiveness to Methacholine in Patients with Bronchial Asthma
Authors: SHIGEHARU MYOU, MASAKI FUJIMURA, YUMIE KAMIO, YOSHIHISA ISHIURA, KAZUYOSHI KURASHIMA, HIDEKI TACHIBANA, TATSUKI HIROSE, TAKUMA HASHIMOTO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

It is unclear whether angiotensin II receptors are involved in bronchial hyperresponsiveness in asthmatic patients. We examined the effect of losartan, a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in eight patients with stable asthma. Bronchial responsiveness to methacholine, assessed as the concentration of methacholine producing a 20% fall in FEV1 (PC20-FEV1) and a 35% fall in standardized partial expiratory flow at 40% of FVC (PC35-PEF40), was measured on two occasions 2 wk apart. Losartan (50 mg once a day) or a placebo was orally administered for 1 wk before methacholine provocation test in a double-blind, randomized, crossover fashion. Although the PC20-FEV1 values after placebo (2.037 [geometric standard error of the mean, GSEM = 0.210] mg/ml) and losartan (2.098 [GSEM, 0.239] mg/ml) were identical (p = 0.840), the geometric mean PC35-PEF40 values significantly (p = 0.034) increased from 0.258 (GSEM, 0.156) mg/ml with placebo to 0.456 (GSEM, 0.186) mg/ml with losartan. We conclude that AT1 receptors are involved in bronchial hyperresponsiveness in asthmatic patients. This is the first report demonstrating the involvement of AT1 receptors in bronchial asthma.
Identification of Neurotransmitter Receptor Genes Under Significantly Relaxed Selective Constraint by Orthologous Gene Comparisons Between Humans and Rodents
Authors: Hisakazu Iwama, Takashi Gojobori
Journal: Molecular Biology and Evolution (2002)

Neurotransmitter receptors (neuroreceptors) are classified into two types, G protein–coupled receptors (GPCRs) and ligand-gated ion channels. The former occupies a small part of the large GPCR superfamily, whereas the latter consists of three superfamilies. In these superfamilies, humans and rodents share almost the same set of neuroreceptor genes. This neuroreceptor gene set is good material to examine the degree of selective constraint exerted on each member gene of a given superfamily. If there are any neuroreceptor genes under the degree of selective constraint that is very different from that of the other member genes, they may have influenced the functional features characteristic of human neural activities. With the aim of identifying such neuroreceptor genes, we collected sequence data of orthologous neuroreceptor genes for humans, mice, and rats by database searches. This data set included ortholog pairs for 141 kinds of neuroreceptor genes, which covered almost the whole set of neuroreceptor genes known to be expressed in the human brain. The degree of selective constraint was estimated by computing the ratio (dN/dS) of the number of nonsynonymous substitutions to that of synonymous substitutions. We found that the dN/dS ratio ranged widely and its distribution fitted a gamma distribution. In particular, we found that four neuroreceptor genes are under the significantly relaxed selective constraint. They are an ionotropic glutamate receptor subunit NMDA-2C, two GABAA receptor subunits, i.e., GABAA-ϵ and GABAA-𝛉, and a dopamine receptor D4. Interestingly, these neuroreceptors have been reported to be associated with cognitive abilities such as memory and learning, and responsiveness to novel stimuli. These cognitive abilities can influence the behavioral features of an individual. Thus, it suggests that the relaxed-constraint neuroreceptor genes have evolved, assuring that the nervous system responds to a variety of stimuli with proper flexibility.
Measles Reimmunization in Children Seronegative After Initial Immunization
Authors: Gregory A. Poland
Journal: JAMA (1997)

To evaluate the success of measles reimmunization in children without measles antibody after the initial dose of measles vaccine.A prospective clinical trial in Olmsted County, Minnesota, and Northern Newfoundland and Labrador in Canada.A total of 130 healthy white, Innu, and Inuit schoolchildren. All subjects had received the post-1980 Moraten measles vaccine 4 to 11 years earlier.Children previously identified as measles antibody seronegative or equivocal after 1 dose of measles vaccine were entered into the trial and reimmunized. Measles antibody was measured a minimum of 6 weeks later using a whole-virus IgG measles-specific enzyme-linked immunoassay (EIA).Of the 130 children reimmunized, 106 (81.5%) became measles antibody seropositive, but 24 children (18.5%) remained seronegative. Younger age at initial immunization (<13 months vs > or = 13 months) was significantly associated with lack of seropositive antibody levels following reimmunization (odds ratio, 3.9; 95% confidence interval, 1.5-9.7). In addition, antibody levels after reimmunization were significantly reduced with increasing time since initial immunization (P=.001).After 2 doses of measles vaccine, 98.2% of all subjects in this study were seropositive for measles antibody, despite the fact that almost 20% of children did not have measurable antibodies 4 to 11 years following a first dose. These findings suggest that the current public health policy recommending a 2-dose measles immunization strategy, with the second dose given at school entry, will provide high levels of immunity in the community.
miRNA Profiling of Endocrine-Resistant Breast Tumours.
Authors: A. Larionov, D. Faratian, H. Caldwell, A. Sims, A. Fawkes, L. Murphy, L. Renshaw, J. Dixon, J. Dixon
Journal: Cancer Research (2009)

Abstract RationalemiRNAs are a relatively recently discovered class of molecules with major implications in cellular biology, including tumorigenesis; yet little is known about their possible involvement in the development of endocrine resistance in breast cancer. The aim of this study was to identify sub-groups of endocrine-resistant tumours with distinctive miRNA profiles.Methods and ResultsFrozen biopsies were obtained from a series of 51 breast cancers, which were either progressing primary tumours, local recurrences or contra-lateral breast lesions developed while patients received endocrine treatment. Hormonal treatment included aromatase inhibitors or tamoxifen, most of the patients reached post-menopausal age, miRNA profiles were obtained using Illumina DASL® Sentrix Array Matrix.Un-supervised hierarchical clustering split 51 studied endocrine resistant tumours into two major groups, distinctive in their miRNA profiles. Several of miRNAs discriminating between the clusters have already been implemented in breast cancer (mir7, mir10a, mir205, mir206, mir 210). Most of the other miRNAs associated with the main tumour clusters are yet to be studied in relation to breast cancer biology (e.g. mir192, mir625, mir941, mir145 and mir512 among others). The miRNA-based tumour clusters were not clearly associated with a specific treatment or type of resistance. The miRNAs most clearly able to discriminate between tumours resistant to AIs and Tamoxifen included mir186, mir196a, mir196b and miR-594:9.1 (p&amp;lt;0.05, fold change &amp;gt;1.2).DiscussionThe results show heterogeneity of miRNA profiles in endocrine resistant breast cancers, for the first time suggesting that endocrine resistant tumours can be split into two major molecular sub-groups basing on their miRNA profiles. The results suggest that (i) miRNA-mediated gene expression regulation may be involved in the mechanisms of endocrine resistance and (ii) miRNA profiling allows different molecular sub-classes of endocrine-resistant tumours to be distinguished. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5130.
Multiple Foci of Increased Accumulation of Ga-67 Citrate in a Horseshoe Kidney
Authors: TERRI GLASS, SYDNEY HEYMAN
Journal: Clinical Nuclear Medicine (1991)

In the proper clinical setting, Ga-67 citrate appears to be a highly valuable radionuclide which may be used to differentiate an infectious process in the kidney from nephroblastomatosis. The authors present the case of a 7- year-old boy with multiple well-circumscribed foci of intense Ga-67 citrate accumulation in a horseshoe kidney. After a 2-week course of antibiotic therapy, the kidney showed significant improvement.