tbuckley/cabot-search huggingface dataset:
Human Leukocyte Antigen and Season of Birth in Japanese Patients With Schizophrenia
Authors: Kaori Narita, Tsukasa Sasaki, Rie Akaho, Yuji Okazaki, Ichiro Kusumi, Tadafumi Kato, Ohiko Hashimoto, Rimmei Fukuda, Tsukasa Koyama, Katsuhisa Matsuo, Yuriko Okabe, Shinichiro Nanko, Hirohiko Hohjoh, Katsushi Tokunaga
Journal: American Journal of Psychiatry (2000)

Five Japanese studies, to the authors' knowledge, without exception, have consistently shown an increased frequency of human leukocyte antigen (HLA)-DR1 in patients with schizophrenia. This suggests an association between HLA-DR1 and schizophrenia in the Japanese population. The mechanism of the association is unknown; however, prenatal infections may be involved. The present study explored factors, including winter birth, that might correlate with this mechanism. Age at onset and gender were also studied.Factors were compared between Japanese patients with schizophrenia with and in those without HLA-DR1 (N=60 and N=307, respectively).A significantly higher incidence of births in February and March was observed in patients with (31.7%) than those without (15. 6%) HLA-DR1. No association was found between the presence of HLA-DR1 and other variables.Although this result is preliminary, it may suggest an interaction between HLA and winter birth in the development of schizophrenia in the Japanese population.
Low-Density Lipoprotein Cholesterol in Patients with Stable Coronary Heart Disease — Is It Time to Shift Our Goals?
Authors: Bertram Pitt
Journal: New England Journal of Medicine (2005)

The evidence of the effectiveness of statins in the treatment of stable coronary heart disease (CHD) continues to grow. Large-scale, randomized, secondary-prevention trials involving patients with CHD have shown that statins reduce the clinical consequences of atherosclerosis, including death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina pectoris and heart failure, as well as the need for coronary revascularization. Current guidelines recommend a low-density lipoprotein (LDL) cholesterol level of less than 100 mg per deciliter (2.6 mmol per liter) as the goal for patients with stable CHD and a goal of 70 mg per deciliter (1.8 . . .
Multiple Myeloma in the Older Adult: Better Prospects, More Challenges
Authors: Tanya M. Wildes, Ashley Rosko, Sascha A. Tuchman
Journal: Journal of Clinical Oncology (2014)

Multiple myeloma (MM) is disproportionately diagnosed in older adults; with the aging of the population, the number of older adults diagnosed with MM will increase by nearly 80% in the next two decades. Duration of survival has improved dramatically over the last 20 years, but the improvements in older adults have not been as great as those in younger adults with MM.In this article, we address treatment approaches in older adults who are eligible for and those ineligible for high-dose therapy with autologous stem-cell transplantation as well as supportive care considerations and the potential role for geriatric assessment in facilitating decision making for older adults with MM.The evidence from recent studies demonstrates that combinations of novel and conventional antimyeloma agents result in improved response rates and, in some cases, improved progression-free and overall survival. However, some older adults are particularly vulnerable to toxicities of therapy and discontinuation of therapy and, consequently, they have poorer survival. In addition, older adults may prioritize other outcomes of therapy, such as quality of life, over more conventional end points such as disease response and duration of survival. Geriatric assessment can facilitate risk-stratification of older adults at greater risk for adverse events from therapy and aid in personalizing therapy for vulnerable or frail older adults.Survival in older adults with MM is improving with novel therapeutics, but efficacy must be balanced with risk of toxicity of therapy and maintenance of quality of life. Novel instruments such as geriatric assessment tools may facilitate these aims.
Fortnightly review: Bladder cancer
Authors: A. P M van der Meijden
Journal: BMJ (1998)

Bladder cancer is the fifth most common malignancy in Europe and the fourth most common malignancy in the United States. About 75% of patients with bladder cancer are men. The most established risk factors for bladder cancer are cigarette smoking and occupational exposure to certain carcinogens. About 80% of bladder tumours are confined to the bladder mucosa, the so called superficial tumours, and 20% invade the muscle layer. The management and prognosis of the two types of cancer are completely different: superficial tumours are fairly benign, and invasive tumours are highly malignant.
Acidification Prevents Endothelial Cell Apoptosis by Axl Activation
Authors: Daniela D’Arcangelo, Carlo Gaetano, Maurizio C. Capogrossi
Journal: Circulation Research (2002)

Prior studies have shown that acidification due to hypercarbia protects endothelial cells from serum deprivation–induced apoptosis. However, the mechanism(s) responsible for the antiapoptotic effect of acidification is still unclear. cDNA array screening was performed on human umbilical vein endothelial cells cultured in a bicarbonate medium equilibrated either with 5% CO 2 (pH 7.4) or with 20% CO 2 (pH 7.0). Tyrosine kinase receptor Axl expression was 3.3-fold higher after 6 hours at pH 7.0 compared with pH 7.4; this modulation was confirmed by reverse transcriptase–polymerase chain reaction (3.0±0.9-fold, P &lt;0.03; n=3), Northern blot (3.6±0.1-fold, P &lt;0.0003; n=3), and Western blot (10±1.8-fold, P &lt;0.004; n=3). In a time-course study, both Northern and Western blot analyses showed that the most marked difference in Axl expression between pH 7.4 and pH 7.0 occurred after 24 to 48 hours. Furthermore, Axl phosphorylation was enhanced at pH 7.0. Axl ligand, the survival factor growth arrest–specific gene 6 product (Gas6), was released into the conditioned medium, and by Western blot analysis, similar amounts of protein were found at pH 7.0 and 7.4. Full-length Axl cDNA overexpression reduced serum deprivation–induced apoptosis by 64.4±11.9% in human umbilical vein endothelial cells cultured at pH 7.4 compared with mock-transfected cells ( P &lt;0.0004). Furthermore, overexpression of either soluble Axl or antisense Gas6 mRNA partially reverted the protective effect of acidification, increasing ≈2.5-fold the number of apoptotic cells at pH 7.0 (control 19.3±2.7%, soluble Axl 48.9±9.7%, P &lt;0.001; antisense Gas6 49.3±14.3%, P &lt;0.03). In conclusion, Gas6/Axl signaling may play an important role in endothelial cell survival during acidification. The full text of this article is available at http://www.circresaha.org.
SPI-CI and SPI-6 cooperate in the protection from effector cell–mediated cytotoxicity
Authors: Michael Bots, Ingrid G. M. Kolfschoten, Sandra A. Bres, Mirjam T. G. A. Rademaker, Guido M. de Roo, Margreet Krüse, Kees L. M. C. Franken, Michael Hahne, Christopher J. Froelich, Cornelis J. M. Melief, Rienk Offringa, Jan Paul Medema
Journal: Blood (2004)
Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial
Authors: Anders Widmark, Olbjørn Klepp, Arne Solberg, Jan-Erik Damber, Anders Angelsen, Per Fransson, Jo-Åsmund Lund, Ilker Tasdemir, Morten Hoyer, Fredrik Wiklund, Sophie D Fosså
Journal: The Lancet (2008)
X-linked inheritance of Fanconi anemia complementation group B
Authors: Amom Ruhikanta Meetei, Marieke Levitus, Yutong Xue, Annette L Medhurst, Michel Zwaan, Chen Ling, Martin A Rooimans, Patrick Bier, Maureen Hoatlin, Gerard Pals, Johan P de Winter, Weidong Wang, Hans Joenje
Journal: Nature Genetics (2004)
PTU-003 Paracentesis: UK Trainees’ Practice, Experience and Attitudes
Authors: C Shekhar, A Ramakrishnan, L C Claridge
Journal: Gut (2013)

<h3>Introduction</h3> Abdominal paracentesis is considered a relatively safe procedure<sup>1</sup> but serious life threatening complications are known tooccur<sup>2</sup> and practise guidelines often differ between centres. Moreover, in many European countries gastroenterologists are trained in the use of abdominal ultrasound and utilise this when inserting paracentesis catheters. <h3>Aim :</h3> To obtain a snapshot of current UK trainee practise and experience of paracentesis and its complications. <h3>Methods</h3> A cross sectional survey of current UK gastroenterology trainees was conducted over a 3 week period (Dec 2012-Jan 2013). <h3>Results</h3> 88 trainees completed the survey. 75% (76/88) of respondents have more than 3 yrs’ experience in gastroenterology at registrar level. 42% (37/88) report having performed or supervised &gt; 100 procedures and a further 42% have performed &gt; 50 procedures. 28.7% (26/88) have witnessed serious complications; 14.9% (13/88) report significant haemorrhage requiring blood transfusion, 16.1% (14/88) have encountered bowel perforation and 9%(6/88) attribute a patient’s death to a paracentesis. Only 10.2% (9/88) of trainees routinely take informed written consent. 22.7% (20/88) state that their unit has no formal consent policy for paracentesis. 63% (48/88) of trainees exclusively use suprapubic ‘Bonnano’ catheters despite the fact that this product is unlicensed for use as a paracentesis catheter. The majority of trainees (78.4%) estimate a failure rate requiring ultrasound guided catheter placement of &lt; 10%. However, 23.9% (21/88) state that when this is required patients routinely wait longer than 2 days. 73.9% (65/88) report that radiology colleagues are unwilling to insert catheters in patients with INR &gt; 1.5 without administration of fresh frozen plasma. 80.7% (71/88) of trainees believe training in abdominal ultrasonography should be part of the gastroenterology curriculum and 62.5% (55/88) feel that this would improve the safety and efficiency of paracentesis. <h3>Conclusion</h3> The number of UK trainees reporting serious adverse events due to paracentesis is higher than expected. It is therefore of concern that few trainees are taking written consent for this procedure. The majority of trainees are still using the unlicensed ‘Bonnano’ catheter despite the availability of licenced products such as the ‘Safe-T-Centesis ‘and ‘Neo-Hydro’ drainage kits. The majority of UK gastroenterology trainees express a desire to be trained in abdominal ultrasonography and believe this would improve the safety of paracentesis. <h3>Disclosure of Interest</h3> None Declared <h3>References</h3> Runyon BA. Arch Intern Med. 1986 v; 146(11):2259–61. Pache I, Bilodeau M. Aliment Pharmacol Ther.2005 Mar 1; 21(5):525–9.
Serum cholesterol precursor sterols in coeliac disease: effects of gluten free diet and cholestyramine.
Authors: M Vuoristo, T A Miettinen
Journal: Gut (1986)

Enhanced biliary secretion and high faecal excretion of cholesterol are associated with increased cholesterol synthesis in coeliac disease. We have further investigated cholesterol synthesis in coeliac disease by determining the concentrations of faecal steroids and cholesterol precursors in serum, with and without a gluten free diet and while taking cholestyramine. The levels of unesterified methyl sterols and free and esterified lathosterol, but not those of squalene and desmosterol, were increased in proportion to the level of cholesterol synthesis, as measured with the sterol balance technique. Serum esterified methyl sterol concentrations were also slightly higher but, unlike free methyl sterols or lathosterol, they were not significantly correlated with cholesterol synthesis. The gluten free diet decreased the level of cholesterol synthesis, and the levels of lathosterol and free methyl sterols. There was less decrease in the concentration of esterified methyl sterols, and an insignificant decrease in the concentrations of squalene and desmosterol. Cholestyramine lowered the serum cholesterol concentration and increased that of serum free methyl sterols less in the patients than in the controls, and the increase was proportionate to increase of cholesterol elimination (or synthesis). The increase of serum free methyl sterols per unit of the increase of cholesterol elimination (or synthesis) was three times higher in the bile acid malabsorption caused by cholestyramine than in the cholesterol malabsorption caused by gluten enteropathy. On the other hand, the decrease in the level of serum cholesterol relative to the increase in cholesterol elimination (or synthesis) was higher in cholesterol malabsorption due to coeliac disease than in cholestyramine induced bile acid malabsorption. Effective secretion of newly synthesised and/or absorbed cholesterol directly into the bile could be a factor in the marked decrease of the serum cholesterol concentration in coeliac disease.
Plasma levels of progastrin but not amidated gastrin or glycine extended gastrin are elevated in patients with colorectal carcinoma
Authors: R K Siddheshwar
Journal: Gut (2001)

<h3>BACKGROUND</h3> The relationship between plasma gastrin levels and colorectal cancer is controversial. When confounding factors which increase plasma gastrin levels are taken into account, it has been shown that gastrin levels are not elevated in patients with colorectal cancer. However, these studies only measured amidated gastrin. Total gastrin (which includes unprocessed, partially processed, and mature forms of gastrin) has been shown to be elevated in patients with colorectal cancer. <h3>AIMS</h3> The aim of this study was to determine whether fasting plasma levels of progastrin, amidated gastrin, or glycine extended gastrin are elevated in patients with colorectal cancer or colorectal polyps compared with controls. <h3>METHODS</h3> Progastrin, amidated gastrin, and glycine extended gastrin were estimated by radioimmunoassay using the following antibodies: L289, 109–21, and L2. Blood samples were analysed for <i>Helicobacter pylori</i> by an enzyme linked immunosorbent assay. <h3>RESULTS</h3> Median progastrin levels were significantly higher in the cancer group (27.5 pmol/l) than in the polyp (⩽15 pmol/l) or control (⩽15 pmol/l) group (p=0.0001). There was no difference in median levels of amidated gastrin between groups. Median levels of amidated gastrin were significantly higher in <i>H pylori</i> positive patients (19 pmol/l) than in <i>H pylori</i> negative patients (8 pmol/l) (p=0.0022). Median plasma progastrin levels were significantly higher for moderately dysplastic polyps (38 pmol/l) compared with mildly dysplastic (15 pmol/l) and severely dysplastic (15 pmol/l) polyps (p=0.05). <h3>CONCLUSIONS</h3> Plasma levels of progastrin, but not amidated gastrin or glycine extended gastrin, are significantly elevated in patients with colorectal cancer compared with those with colorectal polyps or controls, irrespective of their <i>H pylori</i>status. We conclude that measuring plasma progastrin levels in patients with colorectal cancer is warranted.
Standardizing Factors in Electrocardiography
Authors: JAMES A. CRONVICH, JOHN P. CONWAY, GEORGE E. BURCH
Journal: Circulation (1950)

Modifications in recorder standardization are required to correct inherent scalar differences among potential differences measured in a given electrocardiographic reference frame. In the frontal plane, agreement between the resultant vectors calculated from unipolar limb lead measurements and from standard lead measurements can be obtained by standardizing the galvanometer for recording the unipolar limb lead potentials at √3 cm. per millivolt. A method for calculating this "standardizing factor" and similar factors for other reference frames is presented and applied to calculations for the equilateral tetrahedron, the isosceles tetrahedron, and the cube.
Amputations at the London Hospital, 1852–1857
Authors: D D C Howat
Journal: Journal of the Royal Society of Medicine (2001)

Mr Chaloner (August 2001 JRSM, pp. 409-412), commenting on the use of chloroform in the Crimean War, suggests that the wounded who were transported to Scutari to have operations performed there would have been less likely to die as a result of anaesthesia than those who were operated upon in the field soon after their injuries, because they would be less likely to be hypovolaemic (if they survived the journey) and better able to withstand the depressive effects of chloroform.

In the official report the figures for the administration of chloroform are poor and only a few deaths are recorded1. One young soldier having a minor operation became violent and almost certainly died of cardiac arrest due to ventricular fibrillation.

In the French Army—more than ten times the size of the British Army—no deaths due to anaesthesia were reported in 25 000 cases; careful instructions about its administration were issued2. Since the time of Larrey, it was the custom to perform amputations as soon after injury as possible, because a recently wounded soldier fared better. The ambulances volantes allowed operations to be performed at or near to the front line. In the British Army, just over 1500 received chloroform3. At the beginning of the war there were no ambulances. For this and other reasons, amputations were not always performed as quickly and there is no evidence that the army surgeons received specific instructions in the use of chloroform.

The transport to Scutari, which took several days, could well have increased the chances of hypovolaemic shock and infection, and therefore of death, before or soon after arrival, as Mr Chaloner suggests.
HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome
Authors: J.D. Carpten, C.M. Robbins, A. Villablanca, L. Forsberg, S. Presciuttini, J. Bailey-Wilson, W.F. Simonds, E.M. Gillanders, A.M. Kennedy, J.D. Chen, S.K. Agarwal, R. Sood, M.P. Jones, T.Y. Moses, C. Haven, D. Petillo, P.D. Leotlela, B. Harding, D. Cameron, A.A. Pannett, A. Höög, H. Heath, L.A. James-Newton, B. Robinson, R.J. Zarbo, B.M. Cavaco, W. Wassif, N.D. Perrier, I.B. Rosen, U. Kristoffersson, P.D. Turnpenny, L.-O. Farnebo, G.M. Besser, C.E. Jackson, H. Morreau, J.M. Trent, R.V. Thakker, S.J. Marx, B.T. Teh, C. Larsson, M.R. Hobbs
Journal: Nature Genetics (2002)
Short chain fatty acid rectal irrigation for left-sided ulcerative colitis: a randomised, placebo controlled trial.
Authors: R I Breuer, K H Soergel, B A Lashner, M L Christ, S B Hanauer, A Vanagunas, J M Harig, A Keshavarzian, M Robinson, J H Sellin, D Weinberg, D E Vidican, K L Flemal, A W Rademaker
Journal: Gut (1997)

BACKGROUND: Short chain fatty acid (SCFA) deficiency is associated with colitis in animals and humans, and the mucosal metabolism of these compounds is decreased in ulcerative colitis. AIMS: To assess the efficacy of topical SCFA treatment in ulcerative colitis. PATIENTS AND METHODS: 103 patients with distal ulcerative colitis were entered into a six week, double-blind, placebo controlled trial of rectal SCFA twice daily; patients who were unchanged on placebo were offered SCFA in an open-label extension trial. RESULTS: Of the 91 patients completing the trial, more patients in the SCFA treated than in the placebo treated group improved (33% v 20%, p = 0.14, NS). Those on SCFA also had larger, but statistically non-significant, reductions in every component of their clinical and histological activity scores. In patients with a relatively short current episode of colitis (&lt; 6 months, n = 42), more responded to SCFA than to placebo (48% v 18%, p = 0.03). These patients also had larger, but statistically non-significant, decreases in their clinical activity index (p = 0.08 v placebo). Every patient who improved used at least five of six of the prescribed rectal SCFA irrigations, whereas only 37% who did not improve were as compliant. In the open-label extension trial, 65% improved on SCFA; these patients also had significant reductions (p &lt; 0.02) in their clinical and histological activity scores. CONCLUSIONS: Although SCFA enemas were not of therapeutic value in this controlled trial, the results suggest efficacy in subsets of patients with distal ulcerative colitis including those with short active episodes. Prolonged contact with rectal mucosa seems to be necessary for therapeutic benefit.
ANTIGEN-REACTIVE CELLS IN NORMAL, IMMUNIZED, AND TOLERANT MICE
Authors: W. D. Armstrong, E. Diener, G. R. Shellam
Journal: The Journal of Experimental Medicine (1969)

The numbers of antigen-reactive cells (ARC) responding to a purified protein, the polymer of S. adelaide flagellin, have been assayed in cell populations derived from several lymphoid tissues of mice. The assay, which employs the cell transfer into lethally irradiated mice, indicates that there is a response of ARC in bone marrow in the absence of thymus cells. This suggests that the immune response to this protein antigen is not thymus dependent. The presence of relatively large numbers of ARC in Peyer's patches argues for their direct participation in the immune response in the adult mouse. The kinetics of ARC and antibody-forming cells in the early primary response employing the transfer system is described. The numbers of ARC declined during the first 2 days of the immune response, but by day 6 had increased to about five times the number in unprimed spleen cells. The rise is believed to be a result of the primary injection of antigen and therefore may be described as memory; however, these experiments have not been able to further elucidate any specific qualities of the "memory cell." Tolerance induction in C(57)BL/Brad mice produced by repeated injections of a cyanogen bromide digest of the antigen is described. The ARC or its precursor is shown to be the site of the lesion of tolerance by direct investigation.
Successful Production of Pseudotyped rAAV Vectors Using a Modified Baculovirus Expression System
Authors: Erik Kohlbrenner, George Aslanidi, Kevin Nash, Stanislav Shklyaev, Martha Campbell-Thompson, Barry J. Byrne, Richard O. Snyder, Nicholas Muzyczka, Kenneth H. Warrington, Sergei Zolotukhin
Journal: Molecular Therapy (2005)

Scalable production of rAAV vectors remains a major obstacle to the clinical application of this prototypical gene therapy vector. A recently developed baculovirus-based production protocol (M. Urabe et al., 2002, Hum. Gene Ther. 13, 1935-1943) found limited applications due to the system's design. Here we report a detailed analysis of the stability of the original baculovirus system components BacRep, BacVP, and transgene cassette-containing BacGFP. All of the baculovirus helpers analyzed were prone to passage-dependent loss-of-function deletions resulting in considerable decreases in rAAV titers. To alleviate the instability and to extend the baculovirus platform to other rAAV serotypes, we have modified both Rep- and Cap-encoding components of the original system. The modifications include a parvoviral phospholipase A2 domain swap allowing production of infectious rAAV8 vectors in vivo. Alternatively, an infectious rAAV8 (or rAAV5) vector incorporating the AAV2 VP1 capsid protein in a mosaic vector particle with AAV8 capsid proteins was produced using a novel baculovirus vector. In this vector, the level of AAV2 VP1 expression is controlled with a "riboswitch," a self-cleaving ribozyme controlled by toyocamycin in the "ON" mode. The redesigned baculovirus system improves our capacity for rAAV manufacturing by making this production platform more applicable to other existing serotypes.