tbuckley/cabot-search huggingface dataset:
Inhibition of Versican Synthesis by Antisense Alters Smooth Muscle Cell Phenotype and Induces Elastic Fiber Formation In Vitro and in Neointima After Vessel Injury
Authors: Robert Huang, Mervyn J. Merrilees, Kathleen Braun, Brent Beaumont, Joan Lemire, Alexander W. Clowes, Aleksander Hinek, Thomas N. Wight
Journal: Circulation Research (2005)

The proteoglycan versican is implicated in several atherogenic events, including stimulation of vascular smooth muscle cell (VSMC) growth and migration, retention of lipoproteins, and promotion of thrombogenesis. A high content of intimal versican also correlates with a low content of elastin, suggesting an inhibitory role for versican in elastogenesis. To determine whether reduced production of versican can be used to enhance elastogenesis, we transduced Fischer rat VSMC (FRSMC) with a versican antisense sequence using the retroviral vector LXSN. Stable expression of versican antisense (LVaSN) significantly reduced versican production, induced a flattened morphology, reduced cell proliferation and migration, increased tropoelastin synthesis, increased elastin binding protein (S-Gal/EBP), and increased deposition of elastic fibers in long-term cultures. Add-back of chondroitin sulfate chains, or versican, decreased S-Gal/EBP and elastic fiber formation. LVaSN cells seeded into balloon catheter-injured rat carotid arteries formed neointimae containing low levels versican, increased amounts of S-Gal/EBP, and increased elastin deposits 7 days postinjury. At 4 weeks, neointimae formed from LVaSN cells were highly structured and contained multiple layers of elastic fibers and lamellae. These results indicate a central role for versican and its constituent chondroitin sulfate chains in controlling cell phenotype, elastogenesis, and intimal structure.
Autotoxicity of Nitric Oxide in Airway Disease
Authors: Tod A. Flak, William E. Goldman
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Though nitric oxide (NO) plays a role in many normal pulmonary functions and is involved in inflammatory and immune responses, it also has cytopathologic potential if not tightly controlled. In Bordetella pertussis infection, NO mediates the respiratory epithelial pathology that is a hallmark of the pertussis syndrome. Tracheal cytotoxin (TCT) released by B. pertussis triggers the production of an inducible NO synthase (iNOS) within tracheal epithelial cells, which produce the NO ultimately responsible for their destruction. The induction of iNOS is most likely due to the cytokine interleukin-1, which is generated intracellularly in response to TCT; this cytokine, like TCT, can reproduce the pathology caused by B. pertussis infection. Similar epithelial destruction is observed in asthma, but the precise mechanism of damage remains incompletely defined. It is possible that NO induced by proinflammatory cytokines in the asthmatic respiratory epithelium plays a central role in the observed epithelial damage in asthma as it does in pertussis.
Long-term outcome of the repair of 50 mm long median nerve defects in rhesus monkeys with marrow mesenchymal stem cells-containing, chitosan-based tissue engineered nerve grafts
Authors: Nan Hu, Hong Wu, Chengbin Xue, Yanpei Gong, Jian Wu, Zhaoqun Xiao, Yumin Yang, Fei Ding, Xiaosong Gu
Journal: Biomaterials (2012)
Rapid nontranscriptional activation of endothelial nitric oxide synthase mediates increased cerebral blood flow and stroke protection by corticosteroids
Authors: Florian P. Limbourg, Zhihong Huang, Jean-Christophe Plumier, Tommaso Simoncini, Masayuki Fujioka, Jan Tuckermann, Günther Schütz, Michael A. Moskowitz, James K. Liao
Journal: Journal of Clinical Investigation (2002)

Many cellular responses to corticosteroids involve the transcriptional modulation of target genes by the glucocorticoid receptor (GR). A rapid, non-nuclear effect of GR was found to mediate neuroprotection. High-dose corticosteroids (20 mg/kg intraperitoneally), given within 2 hours of transient cerebral ischemia, acutely increased endothelial nitric oxide synthase (eNOS) activity, augmented regional cerebral blood flow (CBF) by 40% to 50%, and reduced cerebral infarct size by 32%. These neuroprotective effects of corticosteroids were abolished by the GR antagonist RU486 and by inhibition of phosphatidylinositol 3-kinase (PI3K), and were absent in eNOS–/– mice. To determine the mechanism by which GR activated eNOS, we measured the effect of corticosteroids on PI3K and the protein kinase Akt. In a ligand-dependent manner, GR activated PI3K and Akt in vitro and in vivo caused NO-dependent vasodilation, which was blocked by cotreatment with RU486 or the PI3K inhibitor LY294002 but not by transcriptional inhibitors. Indeed, a mutant GR, which cannot dimerize and bind to DNA, still activated PI3K and Akt in response to corticosteroids. These findings indicate that non-nuclear GR rapidly activates eNOS through the PI3K/Akt pathway and suggest that this mechanism mediates the acute neuroprotective effects of corticosteroids through augmentation of CBF.
Beverage Use and Risk for Kidney Stones in Women
Authors: Gary C. Curhan, Walter C. Willett, Frank E. Speizer, Meir J. Stampfer
Journal: Annals of Internal Medicine (1998)

Background: An increase in fluid intake is routinely recommended for patients who have had kidney stones to decrease the likelihood of recurrence. However, data on the effect of particular beverages on stone formation in women are limited. Objective: To examine the association between the intake of 17 beverages and risk for kidney stones in women. Design: Prospective cohort study with 8 years of follow-up. Setting: United States. Participants: 81 093 women in the Nurses' Health Study who were 40 to 65 years of age in 1986 and had no history of kidney stones. Measurements: Beverage use and diet were assessed in 1986 and 1990 with a validated, self-administered food-frequency questionnaire. The main outcome measure was incident symptomatic kidney stones. Results: During 553 081 person-years of follow-up over an 8-year period, 719 cases of kidney stones were documented. After risk factors other than fluid intake were controlled for, the relative risk for stone formation for women in the highest quintile of total fluid intake compared with women in the lowest quintile was 0.62 (95% CI, 0.48 to 0.80). Inclusion of consumption of specific beverages in the multivariate model significantly added to prediction of risk for kidney stones (P < 0.001). In a multivariate model that adjusted simultaneously for the 17 beverages and other possible risk factors, risk for stone formation decreased by the following amount for each 240-mL (8-oz) serving consumed daily: 10% (CI, 5% to 15%) for caffeinated coffee, 9% (CI, 2% to 15%) for decaffeinated coffee, 8% (CI, 1% to 15%) for tea, and 59% (CI, 32% to 75%) for wine. In contrast, a 44% (CI, 9% to 92%) increase in risk was seen for each 240-mL serving of grapefruit juice consumed daily. Conclusions: An increase in total fluid intake can reduce risk for kidney stones, and the choice of beverage may be meaningful.
NICE guidance recommends fewer but earlier antenatal check ups
Authors: S. Mayor
Journal: BMJ (2003)

Healthy women with uncomplicated pregnancies should have fewer but more informative antenatal check ups, says new evidence based guidance, published last week, on the routine care of pregnant women.

The guidance, from the National Institute for Clinical Excellence, recommends that healthy women should typically be offered 10 appointments during first pregnancies and seven during subsequent pregnancies, rather than the current average of around 14.

The guidance, which applies to the NHS in England and Wales, suggests that appointments—although fewer—should start earlier in pregnancy. Most women currently see a doctor at around 12 weeks, but the guidance says that seeing a health professional earlier, at around …
Effect of Wheat Fiber and Vitamins C and E on Rectal Polyps in Patients With Familial Adenomatous Polyposis
Authors: J. J. DeCosse, H. H. Miller, M. L. Lesser
Journal: JNCI Journal of the National Cancer Institute (1989)

Over a 4-year period in a chemoprevention trial on large bowel neoplasia, 58 patients with familial adenomatous polyposis were treated with 4 g of ascorbic acid (vitamin C)/day plus 400 mg of alpha-tocopherol (vitamin E)/day alone or with a grain fiber supplement (22.5 g/day). In this randomized, double-blind, placebo-controlled study, we determined the effects of these supplements on rectal polyps in these patients. Analysis by intent to treat suggested that the high-fiber supplement had a limited effect. Analysis adjusted for patient compliance showed a stronger benefit from the high-fiber supplement during the middle 2 years of the trial. The results provide evidence for inhibition of benign large bowel neoplasia by grain fiber supplements in excess of 11 g/day in this study population. The findings are consistent with the hypothesis that dietary grain fiber and total dietary fat act as competing variables in the genesis of large bowel neoplasia.
924 CF102 INDUCES APOPTOSIS OF LIVER CANCER WHILE PREVENTING APOPTOSIS IN LIVER INFLAMMATION: A NEW APPROACH TO TREAT LIVER DISEASES
Authors: S. Cohen, S.M. Stemmer, G. Zozulya, A. Ochaion, R. Patoka, F. Barer, S. Bar Yehuda, L. Rath-Wolfson, P. Fishman
Journal: Journal of Hepatology (2010)
Abstract 5472: Class III beta-tubulin in castration resistant human prostate cancer
Authors: Stephane Terry, Guillaume Ploussard, Pascale Maillé, Yves Allory, Nathalie Nicolaiew, Pascale Soyeux, Laurence Kheuang, Stephane Culine, Ralph Buttyan, Alexandre de la Taille, Francis Vacherot
Journal: Cancer Research (2010)

Abstract BACKGROUND: Class III β-tubulin (βIII-tubulin) is expressed in tissues of neuronal lineage but it is also expressed in several human malignancies including non small cell lung carcinoma, breast and ovarian cancer. Overexpression of βIII-tubulin in these tumors is associated with an unfavorable outcome and resistance to taxane-based therapies. βIII-tubulin deregulation however is still poorly documented in prostate cancer. Previously, we reported that βIII-tubulin expression is increased in prostate cancer (PCa) cells by androgen ablation. Here we sought to better characterize the contribution of βIII-tubulin to castration resistant PCa, the stage of the tumor most responsible for mortality from PCa. METHODS: βIII-tubulin expression was assayed by immunohistochemistry in prostate tumors obtained from patients with castration resistant PCa. Protein expression was scored as null (0), weak (1), moderate (2) and strong (3) and considered significant when the score was 2 or more in more than 10% of cancer cells. Consecutive sections were also immunostained for neuroendocrine biomarkers, neuron specific enolase (NSE) and chromogranin A (CgA). An androgen independent (AI) variant of LNCaP cells (AI-LNCaP) was assessed for the effects of docetaxel treatment on βIII-tubulin expression. Finally, DU145 cells stably overexpressing βIII-tubulin were tested for their sensitivity to docetaxel relative to control vector-transfected cells. RESULTS: 24/40 specimens of castration resistant tumors were found to express significant levels of βIII-tubulin. In 6 out of 22 cases analyzed, regions of the tumor positively co-stained for both βIII tubulin and NSE, however none of 8 evaluated cases showed co-staining for βIII-tubulin and CgA. AI-LNCaP cells treated with 5 to 10 nM docetaxel showed a time dependent increase in βIII-tubulin expression. DU145 cells stably overexpressing βIII-tubulin were found to be more resistant to docetaxel than the parental counterpart with a 2-fold increase in the IC50. CONCLUSION: Our data indicate that βIII-tubulin is expressed in the majority of castration resistant prostate tumors. Although βIII-tubulin immunostaining of prostate tumor cells sometimes coincides with staining for neuroendocrine markers, most βIII-tubulin positive tumor cells examined did not show coincidental staining so increased βIII-tubulin expression may occur independently of NE differentiation. Regardless, our in vitro studies support a role for βIII-tubulin in the emergence of doxetaxel resistance by androgen independent human PCa cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5472.
Cytogenetic correlates of TET2 mutations in 199 patients with myeloproliferative neoplasms
Authors: Kebede Hussein, Omar Abdel‐Wahab, Terra L. Lasho, Daniel L. Van Dyke, Ross L. Levine, Curtis A. Hanson, Animesh Pardanani, Ayalew Tefferi
Journal: American Journal of Hematology (2009)
Angina pectoris-like pain provoked by intravenous adenosine in healthy volunteers.
Authors: C Sylven, B Beermann, B Jonzon, R Brandt
Journal: BMJ (1986)

In a study to characterise the chest pain induced by adenosine this agent was given as a bolus into a peripheral vein to six healthy volunteers (five men) aged 30-44. On the first day the maximum tolerable dose was determined in each case. On the second day three doses of adenosine (one third, two thirds, and the full maximum tolerable dose) and three doses of saline were given single blind in randomised order. Thereafter aminophylline 5 mg/kg was given and the procedure repeated in a different randomised order. On the third day between two thirds and the full maximum tolerable dose was given followed by 10 mg dipyridamole intravenously and a second injection of the same dose of adenosine. Heart rate and atrioventricular blocks were recorded by electrocardiography. One minute after each dose of adenosine the chest pain was scored. The maximum tolerable dose of adenosine ranged from 10.6 to 37.1 mg. All subjects experienced uneasy central chest pain provoking anxiety. The pain radiated to the shoulders, ulnar aspect of the arms, epigastric area, back, and into the throat. The pain began about 20 seconds after the injection and lasted 10-15 seconds. Increasing the dose of adenosine increased the intensity of the pain. Administration of aminophylline reduced the pain significantly. Second degree heart block was recorded in five of the six subjects during the time that the pain was experienced. After aminophylline no block was observed. Dipyridamole increased the intensity of pain. The duration of second degree heart block increased in four of the subjects, and in two of these third degree heart block occurred. These findings suggest that adenosine released from the myocardium during ischaemia induces angina pectoris by stimulating theophylline sensitive receptors.
Attributes of a Rejected Manuscript
Authors: John D. Archer
Journal: JAMA (1975)

The Journalattempts to publish valid, readable manuscripts of interest and value to a general medical audience. Some editorial decisions are relatively easy. These involve submissions of obviously outstanding quality that conform toJournalformat or, alas, those of little or no merit. More often, however, editorial priorities are less easily set. Since we can publish only a small fraction of the manuscripts we receive, we must reject, although reluctantly, a substantial number of evident merit, on the basis of excessive length or narrow interest. Once such fairly clear-cut decisions are made, we must select among the many others competing for space inThe Journalpages. Our numerous expert consultants are of indispensable help in many of these selections. Ultimately, however, the editorial staff must make the decisions. It is interesting to examine certain characteristics common among the rejected ranks and likely absent from the accepted. In general, one or
James Nelson Montgomery
Authors: M. Inman
Journal: BMJ (2003)

Former consultant paediatrician Plymouth (b Belfast 1922; q Queen's University, Belfast, 1945; DCH, MD, FRCP), died from multiple myeloma on 1 May 2003.​2003.




Figure 1




Following two years in the Royal Air Force and jobs in Manchester and London, Nelson Montgomery became the longest serving resident assistant physician at Great Ormond Street. A Fulbright scholarship took him to the Boston Children's Hospital, and then he returned to St Mary's as a senior registrar. Monty boasted that he obtained his consultant post without a single publication to his name, but he was an excellent teacher of the young senior house officers, and he exchanged extra tuition for the diploma in child health for digging in his vegetable patch. He retired in 1983. He leaves a wife, Bridget; three children; and a grandson.
The Isolation of Hypertensin from the Circulating Blood of Normal Dogs with Experimental Renal Hypertension by Dialysis in an Artificial Kidney
Authors: LEONARD T. SKEGGS, JOSEPH R. KAHN, NORMAN P. SHUMWAY
Journal: Circulation (1951)

Hypertensin has been dialyzed out of the circulating blood of dogs by means of an artificial kidney and a new method has been devised for its recovery from the dialyzate. More hypertensin was recovered from the dialyzate obtained from dogs with experimental renal hypertension than from normal animals.
Model for End-Stage Liver Disease Score Predicts Left Ventricular Assist Device Operative Transfusion Requirements, Morbidity, and Mortality
Authors: Jennifer C. Matthews, Francis D. Pagani, Jonathan W. Haft, Todd M. Koelling, David C. Naftel, Keith D. Aaronson
Journal: Circulation (2010)

The Model for End-Stage Liver Disease (MELD) predicts events in cirrhotic subjects undergoing major surgery and may offer similar prognostication in left ventricular assist device candidates with comparable degrees of multisystem dysfunction.Preoperative MELD scores were calculated for subjects enrolled in the University of Michigan Health System (UMHS) mechanical circulatory support database. Univariate and multiple regression analyses were performed to investigate the ability of patient characteristics, laboratory data (including MELD scores), and hemodynamic measurements to predict total perioperative blood product exposure and operative mortality. The ability of preoperative MELD scores to predict operative mortality was evaluated in subjects enrolled in the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS), and results were compared with those from the UMHS cohort. The mean+/-SD MELD scores for the UMHS (n=211) and INTERMACS (n=324) cohorts were 13.7+/-6.1 and 15.2+/-5.8, respectively, with 29 (14%) and 19 (6%) perioperative deaths. In the UMHS cohort, median total perioperative blood product exposure was 74 units (25th and 75th percentiles, 44 and 120 units). Each 5-unit MELD score increase was associated with 15.1+/-3.8 units (beta+/-SE) of total perioperative blood product exposure. Each 10-unit increase in total perioperative blood product exposure increased the odds of operative death (odds ratio, 1.05; 95% confidence interval, 1.01 to 1.10). Odds ratios, measuring the ability of MELD scores to predict perioperative mortality, were 1.5 (95% confidence interval, 1.1 to 2.0) and 1.5 (95% confidence interval, 1.1 to 2.1) per 5 MELD units for the UMHS and INTERMACS cohorts, respectively. When MELD scores were dichotomized as >or=17 and <17, risk-adjusted Cox proportional-hazard ratios for 6-month mortality were 2.5 (95% confidence interval, 1.2 to 5.3) and 2.5 (95% confidence interval, 1.1 to 5.4) for the UMHS and INTERMACS cohorts, respectively.The MELD score identified left ventricular assist device candidates at high risk for perioperative bleeding and mortality.
T‐γ large granular lymphocyte leukemia associated with amegakaryocytic thrombocytopenic purpura, Sjögren's syndrome, and polyglandular autoimmune syndrome type II, with subsequent development of pure red cell aplasia
Authors: David Ergas, Alexander Tsimanis, Mordechai Shtalrid, Chen Duskin, Alain Berrebi
Journal: American Journal of Hematology (2002)

Abstract We present a female patient with T‐γ LGL leukemia, who was followed for the last 20 years. Over these years she developed several autoimmune disorders, including Sjögren's syndrome, Hashimoto's thyroiditis, premature ovarian failure (compatible with type II autoimmune polyglandular syndrome), amegakaryocytic thrombocytopenic purpura, and finally pure red cell aplasia. PCR analysis confirmed rearrangement for TCR γ. This case emphasizes the complex association of LGL leukemia with autoimmune disorders. Am. J. Hematol. 69:132–134, 2002. © 2002 Wiley‐Liss, Inc.
A 38 year old woman with hypotensive shock at the onset of menstruation: case outcome
Authors: S. Serrano Villar, J. Perez-Somarriba, T. Sainz Costa, S. Winstanley, T. Santillana Lopez, L. Escribano Mora, B. Orejas Gonzalez
Journal: BMJ (2009)

Four weeks ago ( BMJ 2009;338:b6, doi:10.1136/bmj.b6) we presented the case of Mrs Barroso who presented with serious hypotensive shock triggered by the onset of menstruation. All investigations were negative, except for retroperitoneal fibrosis and periaortic adenopathies found on computed tomography ( BMJ 2009;338:b246, doi:10.1136/bmj.b246).

Subsequently, we measured her serum tryptase concentration, which was 30 μg/l (normal range <12 μg/l. Tryptase is an endoprotease exclusively present in mast cells; hence it is a sensitive marker of conditions in which mast cells are implicated, such as anaphylaxis and mastocytosis.

A bone marrow biopsy sample showed normocellularity and multifocal aggregates of abnormal spindle shaped mast cells (figs 1⇓, 2⇓, and 3⇓). Mutation of codon …
Abrupt Withdrawal of Isosorbide 5-Mononitrate (Imdur®) after Long Term Treatment in Stable Angina Pectoris
Authors: N. Rehnqvist, G. Olsson, J. Engvall, U. Rosenqvist, G. Nyberg, A. Aberg, G. Ulvenstam, A. Uusitalo, O. Keyriläinen, R. Härkönen, B. Nilsson
Journal: Drugs (1987)
Remodeling of Axonal Connections Contributes to Recovery in an Animal Model of Multiple Sclerosis
Authors: Martin Kerschensteiner, Florence M. Bareyre, Bigna S. Buddeberg, Doron Merkler, Christine Stadelmann, Wolfgang Brück, Thomas Misgeld, Martin E. Schwab
Journal: The Journal of Experimental Medicine (2004)

In multiple sclerosis (MS), inflammation in the central nervous system (CNS) leads to damage of axons and myelin. Early during the clinical course, patients can compensate this damage, but little is known about the changes that underlie this improvement of neurological function. To study axonal changes that may contribute to recovery, we made use of an animal model of MS, which allows us to target inflammatory lesions to the corticospinal tract (CST), a major descending motor pathway. We demonstrate that axons remodel at multiple levels in response to a single neuroinflammatory lesion as follows: (a) surrounding the lesion, local interneurons show regenerative sprouting; (b) above the lesion, descending CST axons extend new collaterals that establish a “detour” circuit to the lumbar target area, whereas below the lesion, spared CST axons increase their terminal branching; and (c) in the motor cortex, the distribution of projection neurons is remodeled, and new neurons are recruited to the cortical motor pool. Behavioral tests directly show the importance of these changes for recovery. This paper provides evidence for a highly plastic response of the motor system to a single neuroinflammatory lesion. This framework will help to understand the endogenous repair capacity of the CNS and to develop therapeutic strategies to support it.