tbuckley/cabot-search huggingface dataset:
Bacteriophage control of antiphagocytic determinants in group A streptococci.
Authors: J G Spanier, P P Cleary
Journal: The Journal of Experimental Medicine (1980)

At least two genes have been shown to be required for the expression of the antiphagocytic M protein molecule in group A streptococci. Evidence for phage involvement in the expression of M protein is that: (a) M- cultures of bacteria can be converted to the M+ state (resistant to phagocytosis) upon lysogenization with appropriate bacteriophages; (b) without those bacteriophages the M- recipient culture could not be detected to revert to the M+ state, even under our most stringent selective conditions; and (c) stable M+ lysogens cured of their bacteriophages returned to the M- state. Immunochemical analysis of lysogenically converted M+ strains demonstrated that they contain precipitating and antiphagocytic determinants of the parental M-76 strain (CS110) rather than M-12 determinants expressed by the phage donor strain. This information strongly suggests that the M- strain CS112 possesses the structural gene for M protein, but that it remains predominantly unexpressed. Quantitation of the M antigen produced by these strains supports the observation that the M- phage-recipient strain possesses a small amount of extractable M antigen and that phage activates its synthesis by some unknown mechanism. Various possibilities to account for the phage requirement in M protein synthesis and its role in the transition between M+ and M- states are discussed.
Reduced Monoamine Oxidase Activity in Blood Platelets from Bipolar Depressed Patients
Authors: DENNIS L. MURPHY, RICHARD WEISS
Journal: American Journal of Psychiatry (1972)

Cellular monoamine oxidase (MAO) activity measured in blood platelets is significantly (45 percent) lower in depressed patients with a history of mania (bipolar patients) than in nonbipolar depressed patients and normal controls of similar age and sex. This difference in MAO activity may be related to other biological and psychological characteristics of these patients that suggest that bipolar patients constitute a specific subgroup among patients with affective disorders.
Coronary Blood Flow Assessment After Successful Angioplasty for Acute Myocardial Infarction Predicts the Risk of Long-Term Cardiac Events
Authors: Alain P. Furber, Fabrice Prunier, Hoang Cuong Phan Nguyen, Stéphane Boulet, Stéphane Delépine, Philippe Geslin
Journal: Circulation (2004)

Background— Analysis of coronary flow velocity (CFV) in the recanalized infarct-related coronary artery (IRA) with a Doppler guidewire is useful for predicting recovery of regional left ventricular function, in-hospital complications, and survival. We postulated that the CFV pattern after IRA reperfusion for acute myocardial infarction (AMI) would predict long-term adverse cardiac events. Methods and Results— Sixty-eight consecutive patients with a first AMI underwent CFV measurement with a Doppler guidewire after successful reopening of the IRA by coronary angioplasty. At the end of follow-up, 3.8±1.7 years after AMI, 44 of the 65 surviving patients (67.7%) were free of long-term cardiac events. Univariate analysis showed that the following factors were predictive of an end point combining cardiac death, recurrent MI, and congestive heart failure: hypertension, age ≥65 years, time from onset of chest pain to PTCA ≥6 hours, peak creatine kinase &gt;4000 IU/L, ejection fraction ≤50%, proximal left anterior descending artery occlusion, resting average peak velocity ≤10 cm/s, average systolic peak velocity ≤5 cm/s, a rapid diastolic deceleration time (≤600 ms), and early retrograde systolic flow. In the final multivariate model, only age ≥65 years (OR, 3.6; 95% CI, 1.1 to 11.8; P =0.03), time to PTCA ≥6 hours (OR, 2.9; 95% CI, 1.0 to 8.3; P =0.04), and a rapid diastolic deceleration time (OR, 5.4; 95% CI, 1.5 to 19.3; P =0.01) were independent predictors. Conclusions— The CFV pattern appears to be an accurate predictor of long-term cardiac events in patients having undergone successful reopening of the IRA after AMI, identifying a subset of at-risk patients.
ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor
Authors: Zhiming Yang, Yu-Jia Chang, I-Chen Yu, Shuyuan Yeh, Cheng-Chia Wu, Hiroshi Miyamoto, Diane E Merry, Gen Sobue, Lu-Min Chen, Shu-Shi Chang, Chawnshang Chang
Journal: Nature Medicine (2007)
The Structure and Function of the Endothelial Glycocalyx Layer
Authors: Sheldon Weinbaum, John M. Tarbell, Edward R. Damiano
Journal: Annual Review of Biomedical Engineering (2007)

Over the past decade, since it was first observed in vivo, there has been an explosion in interest in the thin (∼500 nm), gel-like endothelial glycocalyx layer (EGL) that coats the luminal surface of blood vessels. In this review, we examine the mechanical and biochemical properties of the EGL and the latest studies on the interactions of this layer with red and white blood cells. This includes its deformation owing to fluid shear stress, its penetration by leukocyte microvilli, and its restorative response after the passage of a white cell in a tightly fitting capillary. We also examine recently discovered functions of the EGL in modulating the oncotic forces that regulate the exchange of water in microvessels and the role of the EGL in transducing fluid shear stress into the intracellular cytoskeleton of endothelial cells, in the initiation of intracellular signaling, and in the inflammatory response.
Curcumin Targets Breast Cancer Stem–like Cells with Microtentacles That Persist in Mammospheres and Promote Reattachment
Authors: Monica S. Charpentier, Rebecca A. Whipple, Michele I. Vitolo, Amanda E. Boggs, Jana Slovic, Keyata N. Thompson, Lekhana Bhandary, Stuart S. Martin
Journal: Cancer Research (2013)

Abstract Cancer stem–like cells (CSC) and circulating tumor cells (CTC) have related properties associated with distant metastasis, but the mechanisms through which CSCs promote metastasis are unclear. In this study, we report that breast cancer cell lines with more stem-like properties display higher levels of microtentacles (McTN), a type of tubulin-based protrusion of the plasma cell membrane that forms on detached or suspended cells and aid in cell reattachment. We hypothesized that CSCs with large numbers of McTNs would more efficiently attach to distant tissues, promoting metastatic efficiency. The naturally occurring stem-like subpopulation of the human mammary epithelial (HMLE) cell line presents increased McTNs compared with its isogenic non–stem-like subpopulation. This increase was supported by elevated α-tubulin detyrosination and vimentin protein levels and organization. Increased McTNs in stem-like HMLEs promoted a faster initial reattachment of suspended cells that was inhibited by the tubulin-directed drug, colchicine, confirming a functional role for McTNs in stem cell reattachment. Moreover, live-cell confocal microscopy showed that McTNs persist in breast stem cell mammospheres as flexible, motile protrusions on the surface of the mammosphere. Although exposed to the environment, they also function as extensions between adjacent cells along cell–cell junctions. We found that treatment with the breast CSC-targeting compound curcumin rapidly extinguished McTN in breast CSC, preventing reattachment from suspension. Together, our results support a model in which breast CSCs with cytoskeletal alterations that promote McTNs can mediate attachment and metastasis but might be targeted by curcumin as an antimetastatic strategy. Cancer Res; 74(4); 1250–60. ©2013 AACR.
Effects of intermittent pressure loading on the development of ventricular hypertrophy in the cat.
Authors: M L Marcus, D L Eckberg, J L Braxmeier, F M Abboud
Journal: Circulation Research (1977)

Although the effects of persistent pressure loading on the development of ventricular hypertrophy have been studied extensively, the effects of intermittent pressure loading have not been examined. To study the effects of intermittent pressure loading we subjected the right ventricle of cats to intermittent pulmonary artery constriction over a 2-week period. Two intermittent pressure loading schedules were employed. The first consisted of a right ventricular systolic pressure of 60 mm Hg for 3.5 days and normal right ventricular pressure for 3.5 days; and the second consisted of a right ventricular systolic pressure of 60 mm Hg for 2.3 days and normal right ventricular pressure for 4.7 days. The intermittent pressure-loaded cats were compared with normal unoperated controls, sham-operated controls, and cats with persistent right ventricular pressure load for either 1-week or 1- to 2-month duration. The data indicate that intermittent pressure loading caused significant right ventricular hypertrophy. Since significant residual ventricular hypertrophy was present in both intermittent pressure loading groups, regression of ventricular hypertrophy involves a slower process than the progression of hypertrophy.
Cell-Specific Antigens and Immunoglobulin Synthesis of Murine Myeloma Cells and Their Variants&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. Hyman, P. Ralph, S. Sarkar
Journal: JNCI Journal of the National Cancer Institute (1972)

Myeloma variants fall into several classes with respect to immunoglobulin secretion, surface antigens, and leukemia virus group-specific antigens. Variants that do not synthesize immunoglobulin have greatly reduced amounts of histocompatibility antigen and Gross leukemia antigen and no detectable plasma-cell-specific antigen.
Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma
Authors: C.M. Nutting, C.M.L. van Herpen, A.B. Miah, S.A. Bhide, J.-P. Machiels, J. Buter, C. Kelly, D. de Raucourt, K.J. Harrington
Journal: Annals of Oncology (2009)
Tauroursodeoxycholic acid inserts the apical conjugate export pump, Mrp2, into canalicular membranes and stimulates organic anion secretion by protein kinase C–dependent mechanisms in cholestatic rat liver
Authors: Ulrich Beuers, Manfred Bilzer, Anila Chittattu, Gerd A. Kullak-Ublick, Dietrich Keppler, Gustav Paumgartner, Frank Dombrowski
Journal: Hepatology (2001)

Ursodeoxycholic acid (UDCA) exerts anticholestatic effects by undefined mechanisms. Previous work suggested that UDCA stimulates biliary exocytosis via Ca ++ – and protein kinase C (PKC)–dependent mechanisms. Therefore, the effect of taurine–conjugated UDCA (TUDCA) was studied in the experimental model of taurolithocholic acid (TLCA)–induced cholestasis on bile flow, hepatobiliary exocytosis, distribution of PKC isoforms, and density of the apical conjugate export pump, Mrp2, in canalicular membranes. Isolated perfused rat livers were preloaded with horseradish peroxidase (HRP), a marker of vesicular exocytosis, and were perfused with bile acids or dimethylsulfoxide (control) only. PKC isoform distribution and membrane density of Mrp2 were studied using immunoblotting and immunoelectron–microscopic techniques. Biliary secretion of the Mrp2 substrate, 2,4–dinitrophenyl– S –glutathione (GS–DNP), was studied in the presence or absence of the PKC inhibitor, bisindolylmaleimide I (BIM–I; 1 μmol/L). TLCA (10 μmol/L) impaired bile flow by 51%; biliary secretion of HRP and GS–DNP by 46% and 95%, respectively; membrane binding of the Ca ++ –sensitive α–isoform of PKC by 32%; and density of Mrp2 in the canalicular membrane by 79%. TUDCA (25 μmol/L) reversed the effects of TLCA on bile flow, secretion of HRP and GS–DNP, and distribution of α–PKC. TUDCA reduced membrane binding of ε–PKC and increased Mrp2 density 4–fold in canalicular membranes of cholestatic hepatocytes. BIM–I inhibited the effect of TUDCA on GS–DNP secretion in cholestatic livers by 49% without affecting secretion in controls. In conclusion, TUDCA may enhance the secretory capacity of cholestatic hepatocytes by stimulation of exocytosis and insertion of transport proteins into apical membranes via PKC–dependent mechanisms. (Hepatology 2001;33:1206–1216.)
Prevention of Recurrent Foot Ulcers With Plantar Pressure–Based In-Shoe Orthoses: The CareFUL Prevention Multicenter Randomized Controlled Trial
Authors: Jan S. Ulbrecht, Timothy Hurley, David T. Mauger, Peter R. Cavanagh
Journal: Diabetes Care (2014)

To assess the efficacy of in-shoe orthoses that were designed based on shape and barefoot plantar pressure in reducing the incidence of submetatarsal head plantar ulcers in people with diabetes, peripheral neuropathy, and a history of similar prior ulceration.Single-blinded multicenter randomized controlled trial with subjects randomized to wear shape- and pressure-based orthoses (experimental, n = 66) or standard-of-care A5513 orthoses (control, n = 64). Patients were followed for 15 months, until a study end point (forefoot plantar ulcer or nonulcerative plantar forefoot lesion) or to study termination. Proportional hazards regression was used for analysis.There was a trend in the composite primary end point (both ulcers and nonulcerative lesions) across the full follow-up period (P = 0.13) in favor of the experimental orthoses. This trend was due to a marked difference in ulcer occurrence (P = 0.007) but no difference in the rate of nonulcerative lesions (P = 0.76). At 180 days, the ulcer prevention effect of the experimental orthoses was already significant (P = 0.003) when compared with control, and the benefit of the experimental orthoses with respect to the composite end point was also significant (P = 0.042). The hazard ratio was 3.4 (95% CI 1.3-8.7) for the occurrence of a submetatarsal head plantar ulcer in the control compared with experimental arm over the duration of the study.We conclude that shape- and barefoot plantar pressure-based orthoses were more effective in reducing submetatarsal head plantar ulcer recurrence than current standard-of-care orthoses, but they did not significantly reduce nonulcerative lesions.
A Dynamic De-Escalating Dosing Strategy to Determine the Optimal Biological Dose for Antiangiogenic Drugs
Authors: Urban Emmenegger, Robert S. Kerbel
Journal: Clinical Cancer Research (2005)

The concept and application of antiangiogenic therapy for the treatment of cancer has been on a long roller coaster ride. After years of promising, and sometimes exciting, preclinical studies, the first antiangiogenic drug clinical trials began in the early 1990s with the fumagillin analogue, TNP-
Ophthalmic Manifestations of Infections Caused by the USA300 Clone of Community-Associated Methicillin-Resistant Staphylococcus aureus
Authors: Tina Rutar, Henry F. Chambers, J. Brooks Crawford, Francoise Perdreau-Remington, Orin M. Zwick, Michael Karr, Jennifer J. Diehn, Kimberly P. Cockerham
Journal: Ophthalmology (2006)
Blocking of bronchoscopic endobronchial valve in the complex surgical treatment of patients with pulmonary tuberculosis
Authors: Denis Krasnov, Vladimir Krasnov, Nikolai Grishchenko, Tymofei Beschetniy, Dmytrii Skvortsov, Mikhail Reykhrud, Sergei Skluev
Journal: European Respiratory Journal (2012)

A randomized study of osteoplastic thoracoplasty (OT), supplemented with bronchoscopic lung by blocking the affected part in the complex treatment of patients with pulmonary tuberculosis category CV + MBT +.  A new strategy for treating patients with epidemiologically dangerous, most of whom standard chemotherapy regimens are not effective anti-TB drugs, pulmonary resection is contraindicated. The combination of OT and a new bronchoscopic method to block endobronchial valve (EBV) has a higheffect and preserves lung.  Scope and purpose: Evaluate and analyze the impact of bronchoscopic after blocking OT in the combined treatment. According to the existing hypothesis, additional installation endobronchial valve increases the number of patients who can not get close cavities (CV-) and bacterial termination (MBT-).  Methods: We compared the efficacy of blocking the affected part of bronchoscopic lung after OT in patients with advanced pulmonary tuberculosis category CV + MBT + patients that OT was performed without installing an endobronchial valve. Effectiveness of the control points were CV-and MBT-. Estimated risk ratio. A total of 291 patients were involved, of whom 158 fulfilled OT after bronchoscopic block (main group), 133 continued treatment without having to install EBV (comparison group). EBV production company Medlung Inc., Barnaul, Russia.  Results: The proposed complex surgical treatment tactics can increase the effectiveness of remedial measures: the main group more frequently observed cessation of bacterial isolation (RR = 1,43, 95% CI = 1.33 - 1.52), the closure of decay cavities (RR = 1,49, 95% CI = 1.39 - 1.59).
Altered Tissue Degradation and Distribution of Atrial Natriuretic Peptide in Patients With Idiopathic Dilated Cardiomyopathy and Its Relationship With Clinical Severity of the Disease and Sodium Handling
Authors: Giorgio Iervasi, Aldo Clerico, Sergio Berti, Alessandro Pilo, Andrea Biagini, Romano Bianchi, Luigi Donato
Journal: Circulation (1995)

Background Atrial natriuretic peptide (ANP) has been suggested to play an important role in heart failure, preserving cardiorenal homeostasis through maintenance of the sodium balance and inhibition of the detrimental effects of the neurohormonal vasoconstrictor system. The current study was designed to investigate whether there is a disturbed renewal and distribution of ANP in patients with idiopathic dilated cardiomyopathy (IDC) with differing clinical severity of disease. Methods and Results We used a tracer method to perform a cross-sectional study of 15 IDC patients with differing clinical severity (New York Heart Association functional class I to III), prospectively divided into two groups according to their functional class (group 1, classes I and II; group 2, classes II-III and III). Eleven normotensive, nonobese male volunteers also were studied as a control group. Main ANP kinetic parameters were derived from the disappearance curve of the labeled hormone after the bolus injection of [ 125 I]-labeled ANP. A high-performance liquid chromatography technique was used to separate the radiolabeled hormone in each plasma sample. Patients in group 1 showed higher ANP metabolic clearance rate (MCR) (2731.9±726.2 mL · min −1 · m −2 ) than patients of group 2 (1718.4±621.2 mL · min −1 · m −2 ) and control subjects (1873.1±551.2 mL · min −1 · m −2 ). ANP disposal (MCR) positively correlated with biological hormonal effect (urinary sodium excretion) both in control subjects and in patients. In IDC patients of both groups, however, MCR values were always higher (approximately doubled) than the values found in control subjects at the corresponding sodium excretion. This finding indicates that a reduced ANP biological activity is associated with hormone degradation in patients. Moreover, patients of group 2 showed significantly higher ANP production rates (395.6±183.8 ng · min −1 · m −2 ) than group 1 (166.0±139.0 ng · min −1 · m −2 ) and control subjects (130.7±105.4 ng · min −1 · m −2 ) despite a marked reduction in sodium excretion. Patients with IDC showed a progressive reduction in the total distribution volume (group 1, 19.8±5.8 L/m 2 ; group 2, 12.7±6.9 L/m 2 ; control subjects, 27.0±11.6 L/m 2 ) of the hormone; this probably was due to a reduction in exchanges of ANP with peripheral tissues. Conclusions Our study demonstrates a markedly altered degradation and distribution of ANP in patients with IDC, even in those at the early stage of clinical disease (classes I and II, group 1) who have ANP plasma levels in the normal range.
Ursodeoxycholic acid inhibits hepatic cystogenesis in experimental models of polycystic liver disease
Authors: Patricia Munoz-Garrido, José J.G. Marin, María J. Perugorria, Aura D. Urribarri, Oihane Erice, Elena Sáez, Miriam Úriz, Sarai Sarvide, Ainhoa Portu, Axel R. Concepcion, Marta R. Romero, María J. Monte, Álvaro Santos-Laso, Elizabeth Hijona, Raúl Jimenez-Agüero, Marco Marzioni, Ulrich Beuers, Tatyana V. Masyuk, Nicholas F. LaRusso, Jesús Prieto, Luis Bujanda, Joost P.H. Drenth, Jesús M. Banales
Journal: Journal of Hepatology (2015)
RENAL AUTOEXPLANTATION AND PROTECTION AGAINST RENOPRIVAL HYPERTENSIVE CARDIOVASCULAR DISEASE AND HEMOLYSIS *
Authors: E. E. Muirhead, J. A. Stirman, F. Jones
Journal: Journal of Clinical Investigation (1960)

METHODS Explantation proceduresGroup I: Whole kidney explanted to peritoneum.In 8 dogs the whole kidney was explanted to the peritoneum under sodium pentobarbital anesthesia as follows. 1)The left kidney was removed through an anterior midline ab- dominal incision.2) The renal capsule was stripped and
Cholesteryl Ester Transfer Protein Inhibition, High-Density Lipoprotein Raising, and Progression of Coronary Atherosclerosis
Authors: Stephen J. Nicholls, E. Murat Tuzcu, Danielle M. Brennan, Jean-Claude Tardif, Steven E. Nissen
Journal: Circulation (2008)

Despite favorable effects on high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol, the cholesteryl ester transfer protein inhibitor torcetrapib failed to slow atherosclerosis progression and increased mortality. We investigated the relationship between lipid changes and progression of coronary atherosclerosis.Intravascular ultrasound was performed at baseline and follow-up in 910 participants randomized to torcetrapib/atorvastatin or atorvastatin monotherapy. The relationship between changes in lipoprotein levels and the primary intravascular ultrasound end point, change in percent atheroma volume, was investigated. Compared with atorvastatin monotherapy, torcetrapib raised HDL-C by 61%, lowered low-density lipoprotein cholesterol by 20%, raised serum sodium (0.44+/-0.14 mmol/L, P=0.02), and lowered serum potassium (0.11+/-0.02 mmol/L, P<0.0001). Despite substantial increases in HDL-C, no effect was found of torcetrapib on percent atheroma volume. In torcetrapib-treated patients, an inverse relationship was observed between changes in HDL-C and percentage atheroma volume (r=-0.17, P<0.001). Participants with regression had greater increases in HDL-C (mean+/-SE, 62.9+/-37.4% versus 54.0+/-39.1%, P=0.002). Compared with the lowest quartile, torcetrapib-treated patients in the highest quartile of HDL-C change showed the least progression (-0.31+/-0.27 versus 0.88+/-0.27%, P=0.001). The highest on-treatment HDL-C quartile showed significant regression of percent atheroma volume (-0.69+/-0.27%, P=0.01). In multivariable analysis, changes in HDL-C levels independently predicted the effect on atherosclerosis progression (P=0.001).The majority of torcetrapib-treated patients demonstrated no regression of coronary atherosclerosis. Regression was only observed at the highest HDL-C levels. Torcetrapib raised serum sodium and lowered potassium, consistent with an aldosterone-like effect, which may explain the lack of favorable effects in the full study cohort. Accordingly, other cholesteryl ester transfer protein inhibitors, if they lack this off-target toxicity, may successfully slow atherosclerosis progression.