tbuckley/cabot-search huggingface dataset:
Role of cGMP-kinase II in the control of renin secretion and renin expression.
Authors: C Wagner, A Pfeifer, P Ruth, F Hofmann, A Kurtz
Journal: Journal of Clinical Investigation (1998)

To investigate the roles of the cGMP-dependent protein kinases (cGKs) in the control of the renin system, we studied the regulation of renin in cGKI- or cGKII-deficient mice in vivo and in vitro. Renal renin mRNA levels both under stimulatory (low-salt diet plus ramipril) and inhibitory (high-salt diet) conditions were not different between wild-type and cGKI-/- mice, but were significantly elevated in cGKII-/- mice under all experimental conditions. In primary cultures of renal juxtaglomerular cells (JG) established from wild-type, cGKI-/-, and cGKII-/- mice, the adenylate cyclase activator forskolin stimulated renin secretion similarly in all genotypes tested. 8-bromo-cGMP attenuated basal and forskolin-stimulated renin secretion in cultures from wild-type and cGKI-/-, but had no effect in cells isolated from cGKII-/- mice. Activation of cGKs by 8-bromo-cGMP decreased renin secretion from the isolated perfused rat kidney, independent of prestimulation by beta-adrenoreceptor activation, macula densa inhibition, reduced perfusion pressure, or by a nominally calcium-free perfusate. Taken together, these findings suggest that activation of cGKII has a general inhibitory effect on renin secretion from renal JG cells.
VENEREAL DISEASES: Prophylactic and Abortive Treatment
Authors: E. B. Turner
Journal: BMJ (1918)

cated mlan would almost infallibly fail in the minutiae of the protective process, and therefore becomiie infected.If a mnani, as is very probable in some circumstances, incuirs the risk of infection three or four times in a few hours, it is very improbable that before eachl performnance hle is likely again satisfactorily to protect limlself.
MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A
Authors: Carmen Urbich, David Kaluza, Timo Frömel, Andrea Knau, Katrin Bennewitz, Reinier A. Boon, Angelika Bonauer, Carmen Doebele, Jes-Niels Boeckel, Eduard Hergenreider, Andreas M. Zeiher, Jens Kroll, Ingrid Fleming, Stefanie Dimmeler
Journal: Blood (2011)
NON-INVASIVE CHARACTERIZATION OF CHRONIC MYOCARDIAL INFARCTIONS USING T1 MAPPING BASED CARDIOVASCULAR MAGNETIC RESONANCE AT 3T WITHOUT EXOGENOUS CONTRAST AGENTS
Authors: Avinash Kali, Ivan Cokic, Richard Tang, Hsin-Jung Yang, Behzad Sharif, Eduardo Marban, Debiao Li, Daniel Berman, Rohan Dharmakumar
Journal: Journal of the American College of Cardiology (2014)
Abstract 404: Regulation of NKG2D expression and NKG2D-positive T cell tumor-specific trafficking by doxorubicin and IL-12 <i>in vivo</i>
Authors: Jiemiao Hu, Shiguo Zhu, Xueqing Xia, Wayne M. Yokoyama, Shulin Li
Journal: Cancer Research (2012)

Abstract IL-12 and doxorubicin treatment are known to polarize anti-tumor immune response and induce tumor cell death, respectively, when each is administered alone. IL-12 treatment can boost NKG2D receptor expression on immune cells, enhancing NK cell cytotoxicity against different tumor cell lines. However, IL-12 treatment alone can only modestly increase expression of NKG2D receptor. In tumor immuno-surveillance, it is important to create an environment in which spleen cells constitutively express the NKG2D receptor thereby triggering NKG2D-dependent tumor cell death. In an earlier study, we found that coadministration of the anti-neoplastic drug doxorubicin and IL-12 greatly boosted anti-tumor efficacy. This increased anti-tumor efficacy was associated with a substantial increase in immune cell infiltration at tumor sites, but the underlying mechanism by which the increased number of immune cells was trafficked into the tumors remains largely unknown. This report demonstrates that doxorubicin plus IL-12 treatment induces the higher expression of NKG2D receptor in CD8 T cells than IL-12 treatment alone, resulting in an increased infiltration of NKG2D-positive CD8 T cells, and leading to an NKG2D-dependent tumor growth inhibition in vivo. These in vivo observations are in agreement with our in vitro result, in which the encounter between NKG2D receptor-positive effector cells and NKG2D ligand-positive tumor cells yields an NKG2D-dependent tumor cell death as determined by cytolytic activity assay. Blocking the NKG2D receptor by using neutralization antibody impaired doxorubicin plus IL-12 treatment-mediated tumor eradication in vivo and effector cell-mediated tumor cell death in vitro. Together, the evidence links the higher IL-12 plus doxorubicin treatment-induced NKG2D expression to greater CD8 T cell infiltration into tumors, tumor cell death, and anti-tumor efficacy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 404. doi:1538-7445.AM2012-404
A New Doctor in the House
Authors: Steven Z. Pantilat
Journal: JAMA (1999)

The traditional patient-primary care physician (PCP) relationship provides many ethical protections for patients, including confidentiality, shared medical decision making, and respect for patient autonomy. Hospitalist models, which introduce a purposeful discontinuity of care, threaten these protections and raise certain ethical concerns. We analyze 2 cases that explore ethical issues arising in hospitalist systems and suggest ways to ensure ethical protection for patients. The first case examines how hospitalization can disrupt the patient-PCP relationship and raise ethical issues regarding confidentiality. In the second case, we discuss decision making when the patient's goals and preferences for care change as a result of hospitalization. Effective hospitalist systems provide a model for a trusting patient-physician relationship. Although the hospitalist must take responsibility for inpatient management, the PCP has a key role in addressing important issues in the hospital and providing care after discharge. As hospitalists assume control of inpatient care, they must also provide ethical protections to patients to supplement those currently vested in the patient-PCP relationship. An approach that keeps the patient's best interests foremost, defines a clear role for the PCP, and takes advantage of the expertise and availability of hospitalists will best serve patients and physicians.
Accumulation of multiple T-cell clonotypes in the liver of primary biliary cirrhosis
Authors: M Ohmoto
Journal: Hepatology (1997)

The histological hallmark of primary biliary cirrhosis (PBC) is the destruction of the interlobular and septal bile ducts accompanied by a dense accumulation of lymphocytes; this constellation of features is termed chronic nonsuppurative destructive cholangitis. To analyze the T cells responsible for bile duct destruction, the T-cell receptor (TCR) Vβ repertoire was studied in liver biopsy specimens, and also in peripheral blood lymphocytes (PBL) obtained from seven patients with PBC in the early stage (Scheuer's stage I or II). The complementary DNA (cDNA) of each TCR Vβ1-20 chain was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were examined by single-strand conformation polymorphism (SSCP) analysis. On the RT-PCR/SSCP analysis, a leukemic cell line, HPB-ALL, showed bands in TCR Vβ 5.2 and Vβ 6, indicating clonal expansion with distinct TCR. In the PBL from healthy subjects, the PCR products were amplified from many TCR Vβ and were shown as smears on SSCP, suggesting that PBL consist of diverse T-cell clones. In PBC, many TCR Vβ products were amplified by RT-PCR in both liver tissues and PBL, and no biased expression of a particular Vβ was observed. SSCP analysis revealed multiple bands in most Vβ chains, suggesting the presence of selected but multiple T-cell clones. Both the number and types of Vβ showing clonal expansion were heterogeneous in the PBC patients. A comparative RT-PCR SSCP analysis of each TCR Vβ between tissue lymphocytes and PBL revealed the presence of some identical T-cell clones in both the PBC liver and the PBL. These results suggest that T cells infiltrating the liver in PBC consist of multiple clonotypes and that T-cell clones accumulated in the liver are also present in PBL.
Contrast-enhanced intraoperative ultrasonography for vascular imaging of hepatocellular carcinoma: Clinical and biological significance
Authors: Kota Sato, Shinji Tanaka, Yusuke Mitsunori, Kaoru Mogushi, Mahmut Yasen, Arihiro Aihara, Daisuke Ban, Takanori Ochiai, Takumi Irie, Atsushi Kudo, Noriaki Nakamura, Hiroshi Tanaka, Shigeki Arii
Journal: Hepatology (2012)

Abstract Abnormal tumor vascularity is one of the typical features of hepatocellular carcinoma (HCC). In this study, the significance of contrast-enhanced intraoperative ultrasonography (CEIOUS) images of HCC vasculature was evaluated by clinicopathological and gene expression analyses. We enrolled 82 patients who underwent curative hepatic resection for HCC with CEIOUS. Clinicopathological and gene expression analyses were performed according to CEIOUS vasculature patterns. CEIOUS images of HCC vasculatures were classified as reticular HCC or thunderbolt HCC. Thunderbolt HCC was significantly correlated with higher alpha-fetoprotein levels, tumor size, histological differentiation, portal vein invasion, and tumor-node-metastasis stage, and these patients demonstrated a significantly poorer prognosis for both recurrence-free survival ( P = 0.0193) and overall survival ( P = 0.0362) compared with patients who had reticular HCC. Gene expression analysis revealed that a rereplication inhibitor geminin was significantly overexpressed in thunderbolt HCCs ( P = 0.00326). In vitro knockdown of geminin gene reduced significantly the proliferation of human HCC cells. Immunohistochemical analysis confirmed overexpression of geminin protein in thunderbolt HCC ( P &lt; 0.0001). Multivariate analysis revealed geminin expression to be an independent factor in predicting poor survival in HCC patients ( P = 0.0170). Conclusion : CEIOUS vascular patterns were distinctly identifiable by gene expression profiling associated with cellular proliferation of HCC and were significantly related to HCC progression and poor prognosis. These findings might be clinically useful as a determinant factor in the postoperative treatment of HCC.
Influence of chronobiological variation in the risk of acute aortic dissection on in-hospital mortality
Authors: Rajendra H. Mehta, Roberto Manfredini, Francesca Portaluppi, Stuart Hutchison, Jeanna V. Cooper, Marc Penn, Eduardo Bossone, Arturo Evangelista, Kim A. Eagle, Christoph A. Nienaber
Journal: Journal of the American College of Cardiology (2003)
Theory of mind and other domain-specific hypotheses
Authors: C. M. Heyes
Journal: Behavioral and Brain Sciences (2001)

The commentators do not contest the target article's claim that there is no compelling evidence of theory of mind in primates, and recent empirical studies further support this view. If primates lack theory of mind, they may still have other behavior control mechanisms that are adaptive in complex social environments. The Somatic Marker Mechanism (SMM) is a candidate, but the SMM hypothesis postulates a much weaker effect of natural selection on social cognition than the theory of mind hypothesis (on inputs to cognitive mechanisms, not on the mechanisms themselves), and there is currently no evidence that it is specific to social stimuli or to primates. "Two Guesser" training would make the goggles test too chauvinistic, and in its current form the goggles problem could not be solved by physical matching because, while wearing goggles, an individual cannot see itself seeing.
Mild hypertension: a clinical trial conducted in hospital general practice.
Authors: H E Joesbury, C A Phillips, R T Garrett, E Wilkes, A J Smith
Journal: BMJ (1976)

To compare findings in a hospital trial of hypotensive drugs with those in a general practice trial several patients with mild hypertension were studied at the same time in hospital and in general practice. They received bendrofluazide and potassium chloride or bendrofluazide, potassium chloride, and reserpine according to a double-blind crossover protocol, and blood biochemical values were studied over eight weeks and six months. When reserpine was withdrawn from nine women they followed a modified protocol comparing bendrofluazide and potassium chloride with potassium chloride alone. The blood pressure values measured by the general practitioners were similar to those measured in hospital. Both the diuretic alone and the diuretic with reserpine produced significant falls in blood pressures. Although plasma renin activity increased on diuretic treatment, continued treatment did not produce a further increase, and levels gradually declined towards normal.
Bismuth Nephrotoxicity
Authors: Joyce D. Gryboski, Samuel P. Gotoff
Journal: New England Journal of Medicine (1961)

A CASE of renal poisoning by bismuth thioglycollate is reported to re-emphasize the nephrotoxicity of bismuth compounds in the pediatric age group.Case ReportA 7 1/2-year-old boy was transferred to the Pediatric Service of the Grace—New Haven Community Hospital because of severe azotemia. Eight days previously he had been given 30 mg. of bismuth thioglycollate§ intramuscularly for the treatment of small warts over the dorsal surfaces of both hands. Two hours later he began to vomit, and on the following day he was given a phosphorated carbohydrate solution,¶ without significant improvement. Intermittent vomiting persisted for the next week and . . .
A Successful Case of Caesarean Section
Authors: F. A. Mouillot
Journal: BMJ (1890)

catheter is next introduced into the Eustachian orifice under guidance of the rhinoscopic mirror.The handle of the catheter is then moved towards the opposite angle of the mouth, and perhaps slightly depressed, the beak of the instrument being introduced well into the tube by a slight onward and upward movement of the whole instrument.Inflation can now be made with the bag in the ordinary way.The opposite tube can of course be catheter- ised without removing the instrument from the nasopharynx.My catheter, being only curved in one plane, differs from that of Cutter, of Boston, in which the terminal portion of the instrument is movable, and also from those suggested by Stork and Kessel, who, according to Politzer, recommend that the instrument should be bent to one side as well as somewhat backwards.I agree with
Magnetic Resonance Imaging–targeted Biopsy May Enhance the Diagnostic Accuracy of Significant Prostate Cancer Detection Compared to Standard Transrectal Ultrasound-guided Biopsy: A Systematic Review and Meta-analysis
Authors: Ivo G. Schoots, Monique J. Roobol, Daan Nieboer, Chris H. Bangma, Ewout W. Steyerberg, M.G. Myriam Hunink
Journal: European Urology (2014)
PRE-HOSPITAL FIBRINOLYSIS FOLLOWED BY URGENT PERCUTANEOUS INTERVENTION WITHIN THE FIRST TWO HOURS OF STEMI ARE ASSOCIATED WITH A SIGNIFICANT REDUCTION IN MICROVASCULAR OBSTRUCTION AND INFARCT SIZE
Authors: Colin M. Barker, Lisa Torres, Daniel Maland, Eugene Stautberg, John Ledoux, Catalin Loghin, Troy Weirick, Ali Denktas, H. Vernon Anderson, Stefano Sdringola, Richard W. Smalling
Journal: Journal of the American College of Cardiology (2010)
REVERSE REMODELING OF LEFT ATRIUM AFTER CATHETER ABLATION OF ATRIAL FIBRILLATION IN EARLY AND ADVANCED STAGES OF LEFT ATRIAL STRUCTURAL REMODELING BY DELAYED ENHANCEMENT-MRI
Authors: Suman Kuppahally, Nazem Akoum, Troy Badger, Nathan S. Burgon, Dennis Parker, Thomas S. Haslam, Rob MacLeod, Eugene Kholmovski, Chris McGann, Nassir F. Marrouche
Journal: Journal of the American College of Cardiology (2010)
The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression
Authors: Dirk Baumjohann, Robin Kageyama, Jonathan M Clingan, Malika M Morar, Sana Patel, Dimitri de Kouchkovsky, Oliver Bannard, Jeffrey A Bluestone, Mehrdad Matloubian, K Mark Ansel, Lukas T Jeker
Journal: Nature Immunology (2013)
Referral, Utilization, and Staffing Patterns of a Mental Health Service in a Prepaid Group Practice Program in New York
Authors: SIDNEY S. GOLDENSOHN, RAYMOND FINK, SAM SHAPIRO
Journal: American Journal of Psychiatry (1969)

The authors describe a psychiatric demonstration program in a prepaid group practice plan. Among adults aged 15 and older, the average annual consultation rate was 11 per 1,000 enrollees and the treatment rate 7.5 per 1,000. Treatment visits in one year averaged 14.2 services; patients treated by psychiatrists had fewer average visits than those of social workers. It was noted that family doctors in the medical group altered their referral practices following two years of contact with the mental health service.
Cellular electrophysiological changes during ischemia in isolated, coronary-perfused cat ventricle with healed myocardial infarction.
Authors: S Kimura, A L Bassett, J S Cameron, H Huikuri, P L Kozlovskis, R J Myerburg
Journal: Circulation (1988)

Cellular electrophysiological consequences of acute ischemia superimposed on healed myocardial infarction were studied in isolated, coronary-perfused cat left ventricles 2-4 months after ligation of multiple distal tributaries of the left anterior descending and circumflex coronary arteries. Oxygenated Tyrode's solution was perfused through the left anterior descending and circumflex coronary arteries, and the preparations were superfused with Tyrode's solution gassed with 95% N2-5% CO2. Transmembrane action potentials were recorded from the endocardial cells in normal and infarcted zones. There were no significant differences in measured action potential variables and refractory periods between cells in the normal and infarcted zones before acute ischemia. When coronary perfusion was discontinued ("ischemia"), resting potential, action potential amplitude, and action potential duration were reduced, and the refractory period was shortened progressively in cells of the normal zone. However, the action potential changes were less prominent, and the refractory period was unchanged in cells in the infarcted zone. As a result, there were significant differences in resting membrane potential, action potential amplitude, action potential duration, and refractory period between cells in the normal and infarcted zones at 10 minutes of ischemia. These differences became larger as the ischemic period was prolonged. Spontaneous rapid ventricular activity was observed during the last 20-30 minutes of ischemia in four of eight preparations with healed myocardial infarction, whereas no spontaneous rapid ventricular activity was recorded in any of six normal heart preparations. Our data suggest that superimposition of acute ischemia on healed myocardial infarction produces electrophysiological inhomogeneities that may enhance arrhythmogenesis.
Abstract 466: Synthetic triterpenoids target cell migration and cell adhesion via GSK3β
Authors: Ciric To, Gianni M. Di Guglielmo
Journal: Cancer Research (2012)

Abstract Synthetic triterpenoids are a class of anti-tumor compounds that target various cellular functions including apoptosis, growth inhibition, anti-inflammation and cytoprotection. Previously, we have shown that triterpenoids also inhibit cell migration and the objective of our current study is to examine the molecular mechanisms. Since cellular adhesion dynamics play a critical role in cell migration, we investigated the effects of triterpenoids on focal adhesion morphology. Using immunofluorescence microscopic analysis of focal adhesion markers, paxillin and Focal Adhesion Kinase (FAK), we found that cells that were treated with synthetic triterpenoids possessed enlarged focal adhesions. Interestingly, numerous focal adhesion related proteins including IQGAP1, paxillin, FAK and Glycogen Synthase Kinase 3 (GSK3) were identified as drug-binding proteins using pull down and mass spectrometry approaches. Therefore, we investigated if triterpenoids target these proteins and affect cell adhesion turnover to inhibit cell migration. We found that focal adhesion re-establishment was altered by triterpenoids while pre-existing focal adhesions remained largely unaffected. To further explore the underlying mechanism of triterpenoids on GSK3β dependent cell adhesion dynamics, we analyzed GSK3β activity. We found that triterpenoids stimulate the phosphorylation of GSK3β at serine 9, however, both FAK and paxillin phosphorylation was largely unaffected by the triterpenoids. In parallel studies, we observed that focal adhesion staining was enlarged with cells that were treated with the GSK3β inhibitors, lithium chloride and SB216763. In addition, GSK3β inhibition affected the localization of not only GSK3β but also IQGAP1, an important scaffolding protein involved in cell polarity. From our results, we postulate that synthetic triterpenoids may affect cell migration by targeting GSK3β, which in turns, inhibits its activity and displaces its localization from the leading edge. More importantly, GSK3β inhibition by the triterpenoids and by GSK3β inhibitors also lead to the displacement of IQGAP1 from the leading edge, which further suggests that triterpenoids may act via a GSK3β mechanism to affect focal adhesions and cell migration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 466. doi:1538-7445.AM2012-466