tbuckley/cabot-search huggingface dataset:
Inhibition of Rho-Associated Kinase Results in Suppression of Neointimal Formation of Balloon-Injured Arteries
Authors: Naoki Sawada, Hiroshi Itoh, Koji Ueyama, Jun Yamashita, Kentaro Doi, Tae-Hwa Chun, Mayumi Inoue, Ken Masatsugu, Takatoshi Saito, Yasutomo Fukunaga, Satsuki Sakaguchi, Hiroshi Arai, Nobuhisa Ohno, Masashi Komeda, Kazuwa Nakao
Journal: Circulation (2000)

Rho-associated kinase (ROCK), an effector of small GTPase Rho, regulates vascular tone via a calcium sensitization mechanism and plays a key role in the pathogenesis of hypertension. However, its role in vascular growth remains unclear.Y-27632, a specific ROCK inhibitor, and the overexpression of dominant-negative ROCK suppressed the mitogen-induced DNA synthesis of cultured vascular smooth muscle cells (VSMCs), which indicates the essential role of ROCK in the control of VSMC proliferation in vitro. Y-27632 also suppressed the chemotaxis of VSMCs. Male Wistar rats were systemically given Y-27632 (35 to 70 mg. kg(-1). day(-1)) through an intraperitoneal infusion. The neointimal formation of balloon-injured carotid arteries was significantly suppressed in Y-27632-treated rats (intima/media ratio, 0.22+/-0.02) compared with vehicle-treated rats (intima/media ratio, 0.92+/-0.21) or hydralazine-treated rats with a similar blood pressure decrease (intima/media ratio, 1.03+/-0.15). The phosphorylation of myosin phosphatase and myosin light chain was elevated in injured arteries in a Y-27632-sensitive manner, indicating the augmentation of ROCK activity in neointimal formation. The downregulation of the cyclin-dependent kinase inhibitor p27(kip1) in injured vessels was reversed by Y-27632 treatment, reflecting the antiproliferative effect of ROCK inhibition in vivo.We conclude that ROCK plays a key role in the process of neointimal formation after balloon injury. Thus, the inhibition of ROCK may be a potential therapeutic strategy for treating vascular proliferative disorders and hypertension.
Functional variants of antioxidant genes in smokers with COPD and in those with normal lung function
Authors: R P Young
Journal: Thorax (2006)

<b>Objective.</b> To implement and assess a task-based learning exercise that prompts pharmacy students to integrate their understanding of different disciplines. <b>Design.</b> Master of pharmacy (MPharm degree) students were provided with simulated information from several preclinical science and from clinical trials and asked to synthesize this into a marketing authorization application for a new drug. Students made a link to pharmacy practice by creating an advice leaflet for pharmacists. <b>Assessment.</b> Students' ability to integrate information from different disciplines was evaluated by oral examination. In 2 successive academic years, 96% and 82% of students demonstrated an integrated understanding of their proposed new drug. Students indicated in a survey that their understanding of the links between different subjects improved. <b>Conclusion.</b> Simulated drug discovery provides a learning environment that emphasizes the connectivity of the preclinical sciences with each other and the practice of pharmacy.
Letter: Death from asthma.
Authors: R B Woodward
Journal: BMJ (1976)

in its longest diameter was the only lesion detected.No evidence was found by which the latter could be aetiologically linked to the hydrops.In particular, there were no "vuln- erable" blood vessels of the placenta that might have been obstructed by the tumour, nor was this excessively vascular, so that an arteriovenous shunt effect was unlikely.Explanations such as protein sequestration by the tumour or unduly rapid increase in the vascular bed are within the realms of speculation.This association has not been reported before so far as I am aware (although Macafee et al; mention a case of mediastinal teratoma associated with hydrops) and I should be grateful to hear from any of your readers who know of a similar observation.
Risk Factors for Frequent and Severe Hypoglycemia in Type 1 Diabetes
Authors: Catherine Allen, Tamara LeCaire, Mari Palta, Kathleen Daniels, Melissa Meredith, Donn J. D’Alessio
Journal: Diabetes Care (2001)

OBJECTIVE—To determine the risk of frequent and severe hypoglycemia and the associated demographic and clinical risk factors. RESEARCH DESIGN AND METHODS—Demographic and diabetes self-management factors were measured in 415 subjects followed prospectively for 4–6.5 years of type 1 diabetes duration as participants in a population-based incident cohort. Blood samples were collected up to three times yearly to test glycosylated hemoglobin (GHb) levels. Reports of frequent (2–4 times/week) and severe (lost consciousness) hypoglycemia as well as other diabetes self-management data were collected by questionnaires. RESULTS—Frequent hypoglycemia was common (33 and 35% of participants reported this on the 4- and 6.5-year questionnaires, respectively), whereas severe hypoglycemia occurred much less often. Better glycemic control (odds ratio [OR] 1.3 per 2% decrease in GHb, 95% CI 1.1–1.5) and more frequent self-monitored blood glucose (1.5 per blood glucose check, 1.3–1.7) were independently related to frequent hypoglycemia. The association of frequent hypoglycemia with intensive insulin therapy increased with age. Better glycemic control (1.5 per 2% decrease in GHb, 1.2–2.0) and older age were related to severe hypoglycemic reactions. No sociodemographic factors other than age increased the risk of hypoglycemia. CONCLUSIONS—Frequent hypoglycemia was common in a population representing the full range of glycemic control in the community. Intensive insulin management and blood glucose monitoring independently predicted frequent but not severe hypoglycemia. This information may be useful for updating patients such that minor changes in diabetes management might decrease the daily burden of this condition while maintaining intensive insulin therapy.
Effect of adenosine receptors stimulation on generation of CD1alowCD14+CD209+ cells in patients with bronchial asthma
Authors: Ksenia Yuryeva, Sergey Ryzhov, Julia Yakovleva, Elena Korotkaya, Konstantin Goremykin, Evgeniy Kulikov, Alexey Sazonov
Journal: European Respiratory Journal (2011)

Background: Increased concentration of adenosine have been found in bronchoalveolar lavage, blood and exhaled breath condensate of patients with BA (Spicuzza et al, Eur J Pharmacol. 2006;533:77-88). Adenosine skews dendritic cell (DC9s) differentiation toward cell population characterized by CD1alowCD14+CD209+ antigenic phenotype and high expression of proinflammatory cytokines (Novitskiy et al, Blood 2008;112:1822-31).  Aim: To investigate effects of adenosine receptors (AdoR9s) stimulation during initial time period of DC9s differentiation from peripheral blood (PB) monocytes in patients with bronchial asthma.  Methods: PB monocytes were received from 32 subjects diagnosed with BA and 19 healthy volunteers and cultured in DC-differentiation medium in the absence or presence of AdoR9s agonist NECA (30μM) for 38 hours. Cell surface expression of CD1a, CD14 and CD209 was analyzed by FACS.  Results: We have found that stimulation of AdoR9s results in higher yield of CD1alowCD14+CD209+ cells in patients with BA compare to healthy volunteers (8.22% ±1.72% and 3.43%±0.83%, in BA patients and healthy volunteers respectively; p  Conclusion: Our study indicates the role of adenosine regulation of DC9s differentiation in BA. The heterogeneity in responses to AdoR9s stimulation may be used as a basis for individual BA treatment development.
Liver Scanning in Patients With Suspected Abdominal Tumor
Authors: Henry J. Fee
Journal: JAMA (1974)

Despite technical advances, the number of patients with hepatic metastases not visualized by liver scanning remains high; more important, there is a significant incidence of false-positive reports. Preoperative scans of 70 patients with a high probability of abdominal tumor were compared with the incidence of hepatic metastases found at laparotomy. The overall accuracy of the liver scan was 84%; there were 13% false-positive and 23% false-negative results. Thus, the chance for error is too high to determine the existence of hepatic metastases on the results of liver scanning alone. (<i>JAMA</i>230:1675-1677, 1974)
Phase II Evaluation of Imatinib Mesylate in the Treatment of Recurrent or Persistent Epithelial Ovarian or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study
Authors: Russell J. Schilder, Michael W. Sill, Roger B. Lee, Tanya J. Shaw, Mary K. Senterman, Andres J. Klein-Szanto, Zoe Miner, Barbara C. Vanderhyden
Journal: Journal of Clinical Oncology (2008)

Purpose This phase II trial assessed the activity and tolerability of an oral dose of imatinib mesylate 400 mg twice daily in patients with recurrent or persistent epithelial ovarian or primary peritoneal carcinoma. The association between the expression of certain markers and clinical outcome was investigated. Patients and Methods Primary measure of clinical efficacy was progression-free survival (PFS) at 6 months. Mutational analysis of KIT, immunohistochemistry (IHC) and enzyme-linked immunosorbent assay for markers (KIT, platelet-derived growth factor [PDGF] receptor [-R], AKT2, phosphorylated AKT [p-AKT], stem cell factor [SCF], and PDGF) were performed. Results Fifty-six eligible patients were evaluated. Nine patients were progression free for at least 6 months including one complete responder. The median PFS and survival were 2 and 16 months, respectively. The most common grade 3 and 4 toxicities were neutropenia, GI, dermatologic effects, pain, and electrolyte disturbances. At least one target of imatinib (KIT, PDGFR-α, or PDGFR-β) was expressed in all tumors, and most tumors expressed all three receptors. Higher expression of p-AKT and PDGFR-β were associated with shorter PFS, and higher IHC scores (% immunopositive cells × staining intensity) of SCF and p-AKT were associated with decreased overall survival. No sequence mutations were detected in the KIT gene. Higher pretreatment plasma concentrations of PDGF-AB, PDGF-BB, and vascular endothelial growth factor (VEGF) were individually associated with shorter PFS and survival. Conclusion Imatinib mesylate was well tolerated but had minimal single-agent activity in patients with recurrent ovarian or primary peritoneal carcinoma. No marker was identified that would predict activity of imatinib; however, tumor p-AKT and plasma VEGF levels were associated with poor outcome.
Mechanism of Enhancement by Angiotensin II of Sympathetic Adrenergic Transmission in the Guinea Pig
Authors: Christopher Bell
Journal: Circulation Research (1972)

An electrophysiological analysis was made of the mechanism underlying the potentiation by angiotensin II of responses to adrenergic nervous stimulation of the isolated vas deferens and the uterine artery of the guinea pig. Concentrations of angiotensin II up to 5 x 10 -7 g/ml did not affect resting muscle cell membrane potential, cause spontaneous transmitter release, or increase transmitter release induced by single nerve stimuli. The time courses of excitatory junction potentials were not increased, indicating that the neuronal mechanism for transmitter inactivation was not inhibited. Angiotensin II did, however, increase the degree of facilitation of successive excitatory junction potentials during repetitive low-frequency nerve stimulation, leading to greater depolarization of the muscle cells than under control conditions. That this enhancement of facilitation was the primary mechanism underlying potentiation of transmission by angiotensin II was supported by the finding that the potentiation of mechanical responses to nerve stimulation decreased markedly as the frequency of stimulation was raised over the range where facilitation is replaced by summation as the major factor in depolarizing the muscle cells to firing threshold (2-6 pulses/sec). This mechanism of action of angiotensin II means that its potentiating effect on transmission is relatively specific for the low frequencies of nervous activity which are thought to be important in tonic cardiovascular control.
Risk of high-grade cervical intraepithelial neoplasia during follow-up in HPV-positive women according to baseline p16-INK4A results: a prospective analysis of a nested substudy of the NTCC randomised controlled trial
Authors: Francesca Carozzi, Anna Gillio-Tos, Massimo Confortini, Annarosa Del Mistro, Cristina Sani, Laura De Marco, Salvatore Girlando, Stefano Rosso, Carlo Naldoni, Paolo Dalla Palma, Manuel Zorzi, Paolo Giorgi-Rossi, Nereo Segnan, Jack Cuzick, Guglielmo Ronco
Journal: The Lancet Oncology (2012)
Psychoanalysis and Neuropsychiatry—A Look at Their Interface
Authors: LEO RANGELL
Journal: American Journal of Psychiatry (1970)

To study the impact of the current external barrage on man's nervous and mental functioning, neurology, psychiatry, and psychoanalysis, along with the entire spectrum of the behavioral sciences, must collaborate and each contribute its own unique approach. The author describes the relationship between psychoanalysis and many of the therapeutic "advances" appearing periodically that extract a piece of psychoanalytic theory or technique and make it into a "new" and whole explanatory system.
Testicular tumor as the first manifestation of B‐lymphoid blastic crisis in a case of Ph‐positive chronic myelogenous leukemia
Authors: Junko H. Ohyashiki, Kazuma Ohyashiki, Hirofumi Shimizu, Makoto Miki, Nobuhiro Kimura, Shigeo Mori, Kouji Fujisawa, Jun‐Ichi Akatsuka, Keisuke Toyama
Journal: American Journal of Hematology (1988)

Abstract We report an 8‐year‐old boy with Ph‐positive chronic myelogenous leukemia (CML) who showed a testicular tumor as the first manifestation of blastic crisis. Pathological examination of the excised testis revealed marked infiltration of immature cells, whereas bone marrow remained in the chronic phase. Immunohistochemical and molecular examinations disclosed the immature cells to have B‐lymphocyte surface determinants and immunoglobulin JH rearrangement. DNA obtained from the testis and peripheral blood cells showed similarly rearranged bcr configurations, indicating that infiltrating cells in the testis originated from the CML clone. Bone marrow showed B‐lymphoid blastic crisis 4 months after testicular involvement.
ErbB3-Dependent Motility and Intravasation in Breast Cancer Metastasis
Authors: Chengsen Xue, Fubo Liang, Radma Mahmood, Magalis Vuolo, Jeffrey Wyckoff, Hong Qian, Kun-Lin Tsai, Mimi Kim, Joseph Locker, Zhong-Yin Zhang, Jeffrey E. Segall
Journal: Cancer Research (2006)

Abstract A better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density. Enhanced metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with stronger chemotaxis and invasion responses to heregulin β1. Suppression of ErbB3 expression reduced both intravasation and metastasis. A human breast cancer tumor tissue microarray showed a significant association between ErbB3 and ErbB2 expression and metastasis independent of tumor size. These results indicate that ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to metastasis through enhancing tumor cell invasion and intravasation in vivo and that ErbB-directed therapies may be useful for the inhibition of invasion independent of effects on tumor growth. (Cancer Res 2006; 66(3): 1418-26)
Internalization of <i>Leishmania mexicana</i> Complex Amastigotes via the Fc Receptor Is Required to Sustain Infection in Murine Cutaneous Leishmaniasis
Authors: Peter E. Kima, Stephanie L. Constant, Lynn Hannum, Maria Colmenares, Karen S. Lee, Ann M. Haberman, Mark J. Shlomchik, Diane McMahon-Pratt
Journal: The Journal of Experimental Medicine (2000)

We show here that maintenance of Leishmania infections with Leishmania mexicana complex parasites (Leishmania amazonensis and Leishmania pifanoi) is impaired in the absence of circulating antibody. In these studies, we used mice genetically altered to contain no circulating antibody, with and without functional B cells. This experimental design allowed us to rule out a critical role for B cell antigen presentation in Leishmania pathogenesis. In addition, we show that mice lacking the common gamma chain of Fc receptors (FcgammaRI, FcepsilonRI, and FcgammaRIII) are similarly refractory to infection with these parasites. These observations establish a critical role for antibody in the pathogenesis associated with infection by members of the L. mexicana complex.
UK stroke performance still improving after 12 years of scrutiny
Authors: A. O'Dowd
Journal: BMJ (2011)

Patients experiencing a stroke are getting better care in the UK after more than 12 years of scrutiny, according to the latest and final National Sentinel Stroke Audit.

More needs to be done, however, to continue the steady improvement since the first audit was published in 1998, says the National Sentinel Stroke Audit 2010: Round 7 published on 12 May.

The new audit, which looked at the process of stroke care for 11 353 patients admitted to hospitals between 1 April and 30 June 2010, in England, Wales, and Northern Ireland, found that 88% of patients spent some time on a stroke unit—a rise from 74% in 2008—where patients have better outcomes than those admitted to general wards.

About two thirds of patients spent more than 90% of their hospital stay …
Comparison of Mitotic Index, In Vitro Bromodeoxyuridine Labeling, and MIB-1 Assays to Quantitate Proliferation in Breast Cancer
Authors: Ann D. Thor, Shuqing Liu, Dan H. Moore II, Susan M. Edgerton
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To investigate the hypothesis that in vitro bromodeoxyuridine (BrDu) labeling might be superior to MIB-1 immunostaining for prognostic value, because it more selectively labels cells during the S phase. METHODS: Four hundred eighty-six patients with breast cancers (59% lymph node-negative, 41% lymph node-positive) surgically excised between 1988 and 1993 (median follow-up, 62 months) were evaluated for cellular proliferation using prospective in vitro BrDu uptake assays, retrospective mitotic indices, and MIB-1 labeling. RESULTS: MIB-1, BrDu labeling, and mitotic index–derived proliferation data were highly correlated. Each was similarly associated with most other markers of prognosis, although these relationships were not identical. By univariate analysis, nodal status was the most significant prognostic variable for all patients. Higher BrDu labeling index, MIB-1 immunolabeling, and mitotic index were also associated with shortened disease-free survival (DFS) and disease-specific survival for the entire patient group, as well as for node-negative patients. The association between cellular proliferation and survival was much weaker for node-positive patients. Multivariate models confirmed that nodal status, tumor size, and proliferation data predicted survival in all patients as well as those with node-negative disease, although MIB-1 was somewhat more closely associated with outcome than mitotic index or in vitro BrDu data. For patients with T1N0M0 disease (n = 172), the only significant predictors of DFS were proliferation rate (mitotic index or MIB-1) and tumor grade. CONCLUSIONS: Proliferation rate predicts recurrence and survival in breast cancer. This effect is more pronounced in node-negative patients. In vitro BrDu data are not superior to MIB-1 and mitotic counting.
A National Survey of End-of-life Care for Critically Ill Patients
Authors: THOMAS J. PRENDERGAST, MICHAEL T. CLAESSENS, JOHN M. LUCE
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

In some intensive care units (ICUs), fewer patients who die now undergo attempts at cardiopulmonary resuscitation (CPR), and many more have life support actively withdrawn prior to death than did a decade ago. To determine the frequency of withdrawal of life support, we contacted every American postgraduate training program with significant clinical exposure to critical care medicine, asking them prospectively to classify patients who died into one of five mutually exclusive categories. We received data from 131 ICUs at 110 institutions in 38 states. There were 6,303 deaths, of which 393 patients were brain dead. Of the remaining 5,910 patients who died, 1,544 (23%) received full ICU care including failed cardiopulmonary resuscitation (CPR); 1,430 (22%) received full ICU care without CPR; 797 (10%) had life support withheld; and 2,139 (38%) had life support withdrawn. There was wide variation in practice among ICUs, with ranges of 4 to 79%, 0 to 83%, 0 to 67%, and 0 to 79% in these four categories, respectively. Variation was not related to ICU type, hospital type, number of admissions, or ICU mortality. We conclude that limitation of life support prior to death is the predominant practice in American ICUs associated with critical care training programs. There is wide variation in end-of-life care, and efforts are needed to understand practice patterns and to establish standards of care for patients dying in ICUs.
Role of Hypoxia-Inducible Factor (HIF)-1α versus HIF-2α in the Regulation of HIF Target Genes in Response to Hypoxia, Insulin-Like Growth Factor-I, or Loss of von Hippel-Lindau Function: Implications for Targeting the HIF Pathway
Authors: Veronica A. Carroll, Margaret Ashcroft
Journal: Cancer Research (2006)

Abstract Overexpression of hypoxia-inducible factors (HIF), HIF-1α and HIF-2α, leads to the up-regulation of genes involved in proliferation, angiogenesis, and glucose metabolism and is associated with tumor progression in several cancers. However, the contribution of HIF-1α versus HIF-2α to vascular endothelial growth factor (VEGF) expression and other HIF-regulated target genes under different conditions is unclear. To address this, we used small interfering RNA (siRNA) techniques to knockdown HIF-1α and/or HIF-2α expression in response to hypoxia, insulin-like growth factor (IGF)-I, or renal carcinoma cells expressing constitutively high basal levels of HIF-1α and/or HIF-2α due to loss of von Hippel-Lindau (VHL) function. We found that HIF-1α primarily regulates transcriptional activation of VEGF in response to hypoxia and IGF-I compared with HIF-2α in MCF-7 cells. We also observed a reciprocal relationship between HIF-1α and HIF-2α expression in hypoxia in these cells: HIF-2α siRNA enhanced HIF-1α–mediated VEGF expression in MCF-7 cells in response to hypoxia, which could be completely blocked by cotransfection with HIF-1α siRNA. In contrast, in renal carcinoma cells that constitutively express HIF-1α and HIF-2α due to loss of VHL function, we found that high basal VEGF, glucose transporter-1, urokinase-type plasminogen activator receptor, and plasminogen activator inhibitor-1 expression was predominantly dependent on HIF-2α. Finally, we showed that a newly identified small-molecule inhibitor of HIF-1, NSC-134754, is also able to significantly decrease HIF-2α protein expression and HIF-2α–regulated VEGF levels in renal carcinoma cells. Our data have important implications for how we target the HIF pathway therapeutically. (Cancer Res 2006; 66(12): 6264-70)