tbuckley/cabot-search huggingface dataset:
T-type calcium channels are involved in hypoxic pulmonary hypertension
Authors: Marc Chevalier, Guillaume Gilbert, Etienne Roux, Philipe Lory, Roger Marthan, Jean-Pierre Savineau, Jean-François Quignard
Journal: Cardiovascular Research (2014)

Pulmonary hypertension (PH) is the main disease of pulmonary circulation. Alteration in calcium homeostasis in pulmonary artery smooth muscle cells (PASMCs) is recognized as a key feature in PH. The present study was undertaken to investigate the involvement of T-type voltage-gated calcium channels (T-VGCCs) in the control of the pulmonary vascular tone and thereby in the development of PH.Experiments were conducted in animals (rats and mice) kept 3-4 weeks in either normal (normoxic) or hypoxic environment (hypobaric chamber) to induce chronic hypoxia (CH) PH. In vivo, chronic treatment of CH rats with the T-VGCC blocker, TTA-A2, prevented PH and the associated vascular hyperreactivity, pulmonary arterial remodelling, and right cardiac hypertrophy. Deletion of the Cav3.1 gene (a T-VGCC isoform) protected mice from CH-PH. In vitro, patch-clamp and PCR experiments revealed the presence of T-VGCCs (mainly Cav3.1 and Cav3.2) in PASMCs. Mibefradil, NNC550396, and TTA-A2 inhibited, in a concentration-dependent manner, T-VGCC current, KCl-induced contraction, and PASMC proliferation.The present study demonstrates that T-VGCCs contribute to intrapulmonary vascular reactivity and is implicated in the development of hypoxic PH. Specific blockers of T-VGCCs may thus prove useful for the therapeutic management of PH.
Immunohistochemical characterization of keratin expression in clear cell acanthoma
Authors: T. OHNISHI, S. WATANABE
Journal: British Journal of Dermatology (1995)

The nature of clear cell acanthoma has not been clarified, although many hypotheses have been proposed, including a benign neoplasm derived from epidermis or the acrosyringium, or a non-specific dermatosis. In this study, seven cases of clear cell acanthoma were analysed by immunohistochemical techniques, using various monoclonal antikeratin antibodies, and antibodies against filaggrin, involucrin and epithelial membrane antigen. Different immunoreactivities were noted between clear cell acanthoma and a normal eccrine gland, including the acrosyringium. Immunoreactivities of clear cell acanthoma were almost identical to those of normal epidermis, although some antibodies gave a different staining pattern between clear cell acanthoma and normal epidermis. The expression of cytokeratins in psoriatic epidermis has been reported to change as a result of abnormal differentiation or maturation. Clear cell acanthoma showed a similar staining pattern to inflammatory dermatoses such as psoriasis vulgaris, lichen planus and discoid lupus erythematosus. We speculate that clear cell acanthoma is a localized form of inflammatory dermatosis rather than a neoplasm.
Cerebral Perfusion Abnormalities in Therapy???resistant Epilepsy in Mentally Retarded Pediatric Patients
Authors: H M ABDEL-DAYEM, M K NAWAZ, M M HASSOON, M ABDEL-RAHMAN, O E OLOFSSON
Journal: Clinical Nuclear Medicine (1991)

Thirteen mentally retarded pediatric patients aged 4 to 13 years with therapy-resistant epilepsy underwent Tc-99m HMPAO brain perfusion SPECT studies. The results (abnormal in 12 of the 13 patients) were compared with EEG results in 12 of the 13 patients (abnormal in all 12) and x-ray CT in 11 of the 13 patients (normal in 9). Patients with spikes on EEG had foci of increased uptake on HMPAO. This study confirms that HMPAO is sensitive in detecting perfusion abnormalities and localizing epileptic foci in this group of patients.
The strength of primary care systems
Authors: J. L. Haggerty, J.-F. Levesque, W. Hogg, S. Wong
Journal: BMJ (2013)

Stronger systems improve population health but require higher levels of spending

A recent article in Health Affairs by Kringos and colleagues seems destined to take its place alongside other seminal studies that support the importance of investing in a strong system of primary care for a well functioning health system, better population health, and perhaps even greater health equity.1 2 3

The team of researchers from the Netherlands Institute for Health Research used statistical databases and government reports from 31 European countries to measure the strength of five primary care dimensions—structure, access, coordination, continuity, and comprehensiveness. They looked at the association between each dimension and healthcare spending, patient perceived quality of care, potentially avoidable admissions to hospital, population health, and health inequality according to socioeconomic status.

They found that population health was better in countries that had a strong primary care structure and robust mechanisms to support coordination and comprehensiveness. The strength of primary care systems was measured by the density of primary care providers and the quality of their work environment. Stronger systems were associated with lower rates of avoidable admissions to hospital and fewer potential years of life lost …
Legionella wadsworthii Species Nova: A Cause of Human Pneumonia
Authors: PAUL H. EDELSTEIN
Journal: Annals of Internal Medicine (1982)

A new species of Legionella that caused pneumonia in a patient with chronic lymphocytic leukemia has been characterized. The name Legionella wadsworthii species nova is proposed for this bacterium. The type strain is Wadsworth 81-716A (American Type Culture Collection 33877). The new species differs phenotypically from L. pneumophila in that the predominant cellular fatty acid is methyl-12-methyltetradecanoic acid (a-15:0) rather than methyl-14-methylpentadecanoic acid (i-16:0), and in its failure to react with L. pneumophila antiserum. The clinical illness caused by L. wadsworthii was not apparently different from that seen with other legionella infections, except for prolonged fever and slow resolution of pulmonary infiltrates.
A surgeon with AIDS. Lack of evidence of transmission to patients
Authors: B. Mishu
Journal: JAMA (1990)

In January 1989 [corrected], the media reported the identity of a surgeon who was recently diagnosed with the acquired immunodeficiency syndrome (AIDS). Concern about surgeon-to-patient transmission of human immunodeficiency virus (HIV) persisted despite reassurances from health authorities. Therefore, HIV antibody testing was offered to the surgeon's patients. We identified 2160 patients operated on since 1982; none had been reported to Tennessee's AIDS registry. A total of 264 had already died; none were reported to have died of AIDS or other HIV-related diseases. Of the 1896 patients remaining, we contacted 1652; 616 (37%) were tested. Only one (an intravenous drug user) was HIV antibody positive, and his medical history suggested that he may already have had AIDS at the time of his surgery. These results support the concept that the risks to patients operated on by HIV-infected surgeons are most likely quite low and support recommendations for the individualized assessment of HIV-infected health care workers.The authors attempted to notify and to offer HIV antibody testing to all patients who had been operated on by a Tennessee surgeon with AIDS during the seven years prior to his diagnosis. They found no evidence of HIV transmission to patients from the surgeon. Six hundred and sixteen former patients were screened for HIV; only one, an intravenous drug user, tested positive for HIV antibody. None of 2,160 former patients appeared on the Tennessee AIDS registry. None of 264 deceased patients were reported to have died of AIDS or of AIDS-related diseases. Mishu, et al. argue that their findings support the conclusion that risks to patients operated on by HIV-positive surgeons are probably quite low, and that each instance of a HIV-infected health worker should be assessed individually.
Primary care trusts should give local people a voice, says report
Authors: Z. Kmietowicz
Journal: BMJ (2002)

Primary care trusts are at risk of losing touch with the concerns of their local communities and becoming distant, corporate bodies that work in isolation from the people they serve, warns a report from an independent health service think tank.

Although it has been general health policy for the last 10 years to involve local people in planning and developing health services, primary care organisations (primary care trusts and primary care groups) have struggled to implement public involvement, says the …
THE ETIOLOGY AND TREATMENT OF ANEMIA IN PREGNANCY
Authors: MAURICE B. STRAUSS
Journal: JAMA (1934)

Numerous workers 1 have established the existence of a distinct lowering of the hemoglobin concentration in the blood of normal pregnant women. The nature of this physiologic anemia and of recovery therefrom has remained confused because seldom have intensive studies been made of the blood of normal women month by month from early pregnancy through and after the puerperium. Such studies 2 show a steady decline in both hemoglobin and red blood cells from early in pregnancy until the end of the second trimester, after which either no further change or a slight rise occurs. However, observations indicate that within ten days of parturition normal women who have had no significant defects of diet or gastric secretion during pregnancy show an abrupt rise of both hemoglobin and red blood cells to essentially the levels held at the beginning of pregnancy. Correlation of these data with known changes of blood volume
COMP-Ang1 stimulates HIF-1α–mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment
Authors: Seock-Won Youn, Sae-Won Lee, Jaewon Lee, Han-Kyul Jeong, Jung-Won Suh, Chang-Hwan Yoon, Hyun-Jae Kang, Hak-Zoo Kim, Gou-Young Koh, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Blood (2011)
Enprostil and ranitidine in prevention of duodenal ulcer relapse: one year double blind comparative trial.
Authors: K Lauritsen, T Havelund, L S Laursen, P Bytzer, J Kjaergaard, J Rask-Madsen
Journal: BMJ (1987)

One hundred and forty two patients with duodenal ulcer who after a short term study had relief of pain and healed ulcers proved endoscopically were allocated at random to double blind maintenance treatment with enprostil (a synthetic dehydroprostaglandin E2) 35 micrograms or ranitidine 150 mg at bedtime for up to 12 months. Patients were monitored every third month and examined by endoscopy at three, six, and 12 months, or more often if warranted. The cumulative relapse rates in the enprostil group at three, six, and 12 months were 37% (25/67), 56% (37/66), and 62% (41/66), respectively. The corresponding rates in the ranitidine group were 8% (6/71), 19% (13/69), and 29% (20/69). These differences were highly significant and further enhanced by life table analysis adjusting for withdrawals and by an "intention to treat" analysis in which absence of proof of non-recurrence was counted as failure, more patients in the enprostil group having been withdrawn because of adverse events or recorded as non-compliant with the protocol. Enprostil 35 micrograms at bedtime cannot be recommended for preventing relapse of duodenal ulcer. Furthermore, the results challenge the clinical relevance of using so called "cytoprotection" for preventing recurrence.
Cardiac epinephrine synthesis and ischemia-induced myocardial epinephrine release
Authors: Y KUROKO, T YAMAZAKI, N TOKUNAGA, T AKIYAMA, H KITAGAWA, K ISHINO, S SANO, H MORI
Journal: Cardiovascular Research (2007)

Phenylethanolamine-N-methyltransferase (PNMT), the enzyme that synthesizes epinephrine (EPI) from norepinephrine (NE) in the adrenal gland, is present in extra-adrenal tissues including heart. Ischemia evokes an excessive NE accumulation in the myocardial interstitial spaces. Therefore, cardiac PNMT activity with high NE levels may contribute to cardiac EPI synthesis and release evoked by ischemia.We measured dialysate EPI levels in the left ventricle of anesthetized rabbits using a cardiac microdialysis technique. The dialysate EPI level served as an index of the myocardial interstitial EPI level. Locally administered NE-induced dialysate EPI responses were measured. The left circumflex coronary artery was occluded for 60 min and the dialysate EPI and NE levels in the ischemic region were measured. Coronary occlusion-induced EPI responses were compared with and without administration of a PNMT inhibitor (SKF29661) in the presence and absence of desipramine (catecholamine transport blocker).Local administration of NE (250, 2500 ng/ml) increased the EPI levels to 734+/-125 and 2088+/-367 pg/ml respectively. These increases in dialysate EPI were suppressed by the PNMT inhibitor. Acute myocardial ischemia significantly increased the EPI levels to 3607+/-1069 pg/ml in the ischemic region, and these were suppressed by the PNMT inhibitor (1417+/-581 pg/ml). The pretreatment with desipramine suppressed ischemia-induced EPI release, which did not differ with (725+/-155 pg/ml) and without administration of a PNMT inhibitor (743+/-172 pg/ml).The cardiac PNMT in the left ventricle is capable of synthesizing EPI with markedly elevated NE levels in the myocardial interstitial space.
Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). IV. Distinct H-2-linked Ir genes control antibody responses to different HBsAg determinants on the same molecule and map to the I-A and I-C subregions.
Authors: D R Milich, G G Leroux-Roels, R E Louie, F V Chisari
Journal: The Journal of Experimental Medicine (1984)

We have previously demonstrated that the murine humoral immune responses to the group-specific a and subtype-specific d/y determinants of hepatitis B surface antigen (HBsAg) are controlled by H-2-linked immune response (Ir) genes. High responder (H-2d,q), intermediate responder (H-2a greater than b greater than k) and nonresponder (H-2f,s) haplotypes have been identified (8, 9). The kinetics and specificity of in vivo antibody production after HBsAg immunization in congeneic, H-2-recombinant strains was analyzed to further define relevant Ir genes and their influence on the immune response to distinct antigenic determinants. These studies indicate that the humoral anti-HBs response is regulated by at least two Ir genes, one in the I-A subregion (Ir-HBs-1) and one in the I-C subregion (Ir-HBs-2) of the murine H-2 complex. Ir-HBs-1 regulates the primary responses to all HBsAg determinants, whereas the influence of Ir-HBs-2 is determinant specific, affecting the responses to the d or y determinants. The anti-a response is regulated exclusively by Ir-HBs-1. Strains possessing only the Ir-HBs-2 gene [B10.S(9R) and B10.HTT] produce no anti-a response and a subtype-specific antibody response is detected only after secondary or tertiary immunization. In contrast, the influence of Ir-HBs-2 in the presence of Ir-HBs-1 is detected upon primary immunization and is additive rather than exclusive. There is also suggestive evidence that the presence of the Ek molecule, at least in the context of I-Ak, may have a suppressive influence on the anti-HBs response. Additionally, HBsAg-specific, T cell proliferative responses were H-2 restricted and the kinetics and specificity of T cell proliferative responses paralleled in vivo antibody production. These data indicate that, although the I-A subregion exerts a dominant influence, distinct Ir-HBs genes, mapping in separate I subregions, control immune responses to alternate HBsAg determinants on the same protein molecule.
Interleukin-6–Deficient Mice Resist Development of Autoimmune Myocarditis Associated With Impaired Upregulation of Complement C3
Authors: Urs Eriksson, Michael O. Kurrer, Nicole Schmitz, Stephan C. Marsch, Adriano Fontana, Hans-Pietro Eugster, Manfred Kopf
Journal: Circulation (2003)

Interleukin (IL)-6 regulates various aspects of the immune response. In the context of heart diseases, it has been recognized as a prognostic factor for dilated cardiomyopathy, which often results from myocarditis.Using IL-6-deficient mice, we studied the role of IL-6 in a model of autoimmune myocarditis resulting from immunization with a peptide derived from cardiac alpha-myosin. Prevalence and severity of myocarditis were markedly reduced in the absence of IL-6. CD4+ T cells from immunized IL-6-deficient mice proliferated poorly on restimulation with specific antigen in vitro and did not mediate disease on adoptive transfer into IL-6-competent RAG-2-deficient mice, which otherwise lack B cells and T cells. Production of complement C3, a crucial factor for the development of myocarditis, was strongly upregulated in IL-6+/+ but not in IL-6-deficient mice after immunization.Our results demonstrate that IL-6 is required for the expansion of autoimmune CD4+ T cells and the pathogenesis of autoimmune myocarditis, possibly by upregulation of complement C3.
Common variants at ten loci modulate the QT interval duration in the QTSCD Study
Authors: Arne Pfeufer, Serena Sanna, Dan E. Arking, Martina Müller, Vesela Gateva, Christian Fuchsberger, Georg B. Ehret, Marco Orr, Cristian Pattaro, Anna Köttgen, Siegfried Perz, Gianluca Usala, Maja Barbalic, Man Li, Benno Pütz, Angelo Scuteri, Ronald J. Prineas, Moritz F. Sinner, Christian Gieger, Samer S. Najjar, W. H Linda Kao, Thomas W. Mühleisen, Mariano Dei, Christine Happle, Stefan Möhlenkamp, Laura Crisponi, Raimund Erbel, Karl Heinz Jöckel, Silvia Naitza, Gerhard Steinbeck, Fabio Marroni, Andrew A. Hicks, Edward Lakatta, Bertram Müller-Myhsok, Peter P. Pramstaller, H. Erich Wichmann, David Schlessinger, Eric Boerwinkle, Thomas Meitinger, Manuela Uda, Josef Coresh, Stefan Kääb, Gonçalo R. Abecasis, Aravinda Chakravarti
Journal: Nature Genetics (2009)
Ca <sup>2+</sup> as a Mediator of Ischemic Preconditioning
Authors: Hiroshi Miyawaki, Muhammad Ashraf
Journal: Circulation Research (1997)

Abstract We tested the hypothesis that elevation of [Ca 2+ ] i during ischemic preconditioning (IPC) stimulates protein kinase C (PKC), which confers the protection against the ischemic injury. Langendorff-perfused rat hearts were subjected to 40-minute global ischemia followed by 30-minute reperfusion (I/R). In preconditioned groups, hearts were subjected to either IPC, consisting of 5-minute global ischemia and 10-minute reperfusion, or high-Ca 2+ preconditioning (HCPC), ie, the 5-minute perfusion of higher Ca 2+ perfusate (2.3 mmol/L Ca 2+ ) followed by 10-minute perfusion of normal perfusate (1.8 mmol/L Ca 2+ ), and then were subjected to I/R. A significant functional recovery and decreased lactate dehydrogenase release were observed in HCPC and IPC hearts compared with ischemic control hearts. ATP contents of preconditioned hearts were significantly higher than those of the ischemic control hearts. The cell structure in preconditioned hearts was preserved better than that in the ischemic control hearts. Furthermore, the activation and translocation of PKC from cytoplasm to sarcolemma were observed in the preconditioned hearts. Verapamil administered during IPC significantly attenuated the salutary effects of IPC. Administration of chelerythrine, a specific PKC inhibitor, completely abolished the HCPC- and IPC-induced cardioprotection. The translocation of PKC by IPC was blocked by verapamil or chelerythrine. Immunohistochemical study using rabbit polyclonal antibody against PKC isoforms indicated that stress induced by IPC or HCPC evoked the translocation of PKCα and PKCδ to the cell membrane. Translocation of PKC isoforms was attenuated by the treatment with verapamil or chelerythrine. These results demonstrate that (1) a transient increase in [Ca 2+ ] i during IPC is an important trigger for the activation of PKC, which is responsible for cardioprotection; (2) the elevation of [Ca 2+ ] i during IPC, at least partly, resulted from Ca 2+ entry via voltage-dependent Ca 2+ channel; and (3) activation and translocation of PKCα and PKCδ occur during IPC and HCPC and may be important in preconditioning.
Background potassium current active during the plateau of the action potential in guinea pig ventricular myocytes.
Authors: P H Backx, E Marban
Journal: Circulation Research (1993)

Background outward K+ currents in guinea pig ventricular myocytes were characterized over a broad range of membrane potentials, including those corresponding to the plateau of the action potential. The background current that is blocked by 1 mM Ba2+ (IK,p) activates within 5 msec at positive potentials, does not inactivate, and deactivates very rapidly on repolarization. IK,p is insensitive to Cl- channel blockers, internal or external [Cl-], dihydropyridines, and sulfonylureas. In contrast, the delayed rectifier K+ current (IK) was not completely blocked even by 30 mM Ba2+. Ba(2+)-sensitive current density increased progressively from 0.16 +/- 0.04 pA/pF at 0 mV to 0.52 +/- 0.21 pA/pF at +80 mV (n = 13, mean +/- SEM). The background current remains present when [K+]o is reduced to 0 mM, which suppresses the inward rectifier K+ current (IK1). These and other features suggest that IK,p is generated by K+ channels that are distinct from IK1 or IK. The kinetics and voltage dependence of IK,p render it capable of modulating both the height and duration of the cardiac action potential.
Jejunal diverticular bleeding treated with hemoclips at double-balloon enteroscopy
Authors: S. Eun, J. Kim, B. Ko, J. Cho, J. Lee, M. Lee, C. Shim
Journal: Endoscopy (2009)

An 80-year-old man was referred for evaluation of melena and hematochezia. The initial esophagogastroduodenoscopy, a colonoscopy, and a computed tomographic scan all failed to identify the source of the bleeding. Double-balloon enteroscopy was performed using the oral approach (EN-450T5/20; Fujinon Co. Ltd., Saitama, Japan). A blood clot adhering to a jejunal diverticulum was found 20 cm distal to the ligament of Treitz and linear submucosal vessels could be traced proximal to the bleeding point ([Fig. 1]). Two endoclips (Resolution Clip; Boston Scientific Co., Natick, Massachusetts, USA) were deployed on the feeding vessels. A blood clot was removed with tripod grasping forceps and the diverticulum was gently irrigated with water. We were then able to confirm that the bleeding had stopped ([Fig. 2], [Video 1]). The patient had no further episodes of bleeding during his hospital stay and was discharged.