tbuckley/cabot-search huggingface dataset:
Premature Expression of T Cell Receptor (Tcr)αβ Suppresses Tcrγδ Gene Rearrangement but Permits Development of γδ Lineage T Cells
Authors: Kathleen Terrence, Christian P. Pavlovich, Errin O. Matechak, B.J. Fowlkes
Journal: The Journal of Experimental Medicine (2000)

The T cell receptor (TCR)γδ and the pre-TCR promote survival and maturation of early thymocyte precursors. Whether these receptors also influence γδ versus αβ lineage determination is less clear. We show here that TCRγδ gene rearrangements are suppressed in TCRαβ transgenic mice when the TCRαβ is expressed early in T cell development. This situation offers the opportunity to examine the outcome of γδ versus αβ T lineage commitment when only the TCRαβ is expressed. We find that precursor thymocytes expressing TCRαβ not only mature in the αβ pathway as expected, but also as CD4−CD8− T cells with properties of γδ lineage cells. In TCRαβ transgenic mice, in which the transgenic receptor is expressed relatively late, TCRγδ rearrangements occur normally such that TCRαβ+CD4−CD8− cells co-express TCRγδ. The results support the notion that TCRαβ can substitute for TCRγδ to permit a γδ lineage choice and maturation in the γδ lineage. The findings could fit a model in which lineage commitment is determined before or independent of TCR gene rearrangement. However, these results could be compatible with a model in which distinct signals bias lineage choice and these signaling differences are not absolute or intrinsic to the specific TCR structure.
Depression and Diabetes
Authors: Anne Engum, Arnstein Mykletun, Kristian Midthjell, Are Holen, Alv A. Dahl
Journal: Diabetes Care (2005)

OBJECTIVE—The purpose of this study was to investigate factors associated with depression in type 1 and type 2 diabetes and test whether these differ from factors associated with depression in the nondiabetic population. RESEARCH DESIGN AND METHODS—In an unselected population study comprising 60,869 individuals, potential sociodemographic, lifestyle, and clinical factors were investigated in participants with and without diabetes. The associations between hyperglycemia and depression in types 1 and 2 diabetes were also studied. The levels of depression were self-rated by using the Hospital Anxiety and Depression Scale. RESULTS—Several factors were correlated with depression in types 1 and 2 diabetes. However, these factors were not different from those of the nondiabetic population. Comorbid chronic somatic diseases were associated with depression in type 2 but not type 1 diabetes. In type 2 diabetes, those without comorbidity had the same odds of depression as the nondiabetic population with no chronic somatic diseases. No significant associations were found for hyperglycemia in relation to depression in type 1 and type 2 diabetes. CONCLUSIONS—Type 2 diabetes without other chronic somatic diseases did not increase the risk of depression. Factors associated with depression in type 1 and type 2 diabetes were shared with the nondiabetic population.
Molecular Pathways: Translational Potential of Deubiquitinases as Drug Targets
Authors: Pádraig D'Arcy, Stig Linder
Journal: Clinical Cancer Research (2014)

Abstract The ubiquitin proteasome system (UPS) is the main system for controlled protein degradation and a key regulator of fundamental cellular processes. The dependency of cancer cells on a functioning UPS coupled with the clinical success of bortezomib for the treatment of multiple myeloma have made the UPS an obvious target for drug development. Deubiquitinases (DUB) are components of the UPS that encompass a diverse family of ubiquitin isopeptidases that catalyze the removal of ubiquitin moieties from target proteins or from polyubiquitin chains, resulting in altered signaling or changes in protein stability. Increasing evidence has implicated deregulation of DUB activity in the initiation and progression of cancer. The altered pattern of DUB expression observed in many tumors can potentially serve as a clinical marker for predicting disease outcome and therapy response. The finding of DUB overexpression in tumor cells suggests that they may serve as novel targets for the development of anticancer therapies. Several specific and broad-spectrum DUB inhibitors are shown to have antitumor activity in preclinical in vivo models with low levels of systemic toxicity. Future studies will hopefully establish the clinical potential for DUB inhibitors as a strategy to treat cancer. Clin Cancer Res; 20(15); 3908–14. ©2014 AACR.
Long-Term Nasogastric Feeding Tube
Authors: Vernon O. Lundmark
Journal: JAMA (1969)

<h3>To the Editor:—</h3> About 20 years ago, at the annual meeting of the Washington State Medical Society, I described a cellophane tubing sold by the Visking Company, the diameter of which approximated that of the common Levin tube. This tube was filled with melted butter as an obturator, chilled, and passed before the butter could melt. The result was a pliable nonirritating tube which permitted feeding without the problems of the Levin tube. The Penrose tube described seems unduly complex, and I think our "butter tube" has definite advantages. It has been used in the Northwest by many men and found extremely valuable. I have kept it in place as long as four months.
Phase I Trial of 5-Day Continuous Venous Infusion of Oxaliplatin at Circadian Rhythm-Modulated Rate Compared With Constant Rate
Authors: Jean-Pierre Caussanel, Francis Lévi, Silvano Brienza, Jean-Louis Misset, Moshe Itzhaki, René Adam, Gérard Milano, Bernard Hecquet, Georges Mathé
Journal: JNCI Journal of the National Cancer Institute (1990)

The toxic effects and tissue uptake of both cisplatin and oxaliplatin—[(1 R , 2 R )-1,2-cyclohexanediamine- N,N ′] [oxalato(2-)- O,O ′]platinum—were previously shown to vary similarly according to dosing time in mice. A 4-hour infusion of cisplatin resulted in fewer side effects and allowed administration of higher doses at 16 hours than at 4 hours in patients with cancer. We hypothesized that the continuous venous infusion of oxaliplatin for 5 days would be less toxic and would deliver a higher dose to the patient if the drug were infused at a circadian rhythm-modulated rate (peak at 16 hr; schedule B) rather than at a constant rate (schedule A). We tested this hypothesis in a randomized phase I trial. We escalated the dose of oxaliplatin to the patient by 25 mg/m 2 per course. Courses were repeated every 3 weeks. An external, multichannel, programmable-in-time pump was used for the infusions. Toxicity was assessable for 94 courses in 23 patients (12 patients with breast carcinoma, nine with hepatocellular carcinoma, and two with cholangiocarcinoma). The incidence of neutropenia of World Health Organization grades II–IV and the incidence of distal paresthesias were 10 or more times higher ( P ≤ .05) with schedule A than with schedule B. In addition, vomiting was 55% higher ( P = .15) with schedule A than with schedule B. Furthermore, with schedule B, the mean dose of oxaliplatin ( P ≤ .001) and its maximum tolerated dose ( P = .06) could be increased by 15% over those doses with schedule A. An objective response was achieved in two of the 12 patients with previously treated breast cancer. We recommend that the dose of oxaliplatin for phase II trials be 175 mg/m 2 , delivered according to the circadian rhythm-modulated rate. [J Natl Cancer inst 82:1046–1050, 1990]
Reviews, Notes, and Listings: Cardiology: The Artificial Heart: Prototypes, Policies, and Patients
Authors: James B. Young
Journal: Annals of Internal Medicine (1993)

Literature of Medicine15 March 1993Reviews, Notes, and Listings: Cardiology: The Artificial Heart: Prototypes, Policies, and PatientsJames B. Young, MDJames B. Young, MDBaylor College of Medicine, Houston, TX 77030.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-118-6-199303150-00035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Artificial Heart: Prototypes, Policies, and PatientsFirst edition. John R. Hogness and Malin VanAntwerp; eds. 298 pages. Washington, D.C.: National Academy Press; 1991. $29.95.The allure of mechanical circulatory support systems (MCSS) sparks debate among social and clinical scientists. A totally implantable artificial heart has become the Holy Grail for many, and assessment of federal support for their pilgrimage is required. This text considers the challenge and is admirably edited. It should be studied by everyone interested in “big ticket,” sophisticated, highly focused health care technology.This book contains a careful analysis of government's liaison with MCSS industry as well as of ... Author, Article, and Disclosure InformationAffiliations: Baylor College of Medicine, Houston, TX 77030. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 March 1993Volume 118, Issue 6Page: 478KeywordsHealth careHeartLife expectancyQuality of lifeScientists ePublished: 15 August 2000 Issue Published: 15 March 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effects of Chromium and Yeast Supplements on Carbohydrate and Lipid Metabolism in Diabetic Men
Authors: Michael B Rabinowitz, Harvey C Gonick, Seymour R Levin, Mayer B Davidson
Journal: Diabetes Care (1983)

Diabetes mellitus has been shown to develop as a consequence of chromium (Cr) deficiency in experimental animals and in humans sustained by prolonged total parenteral nutrition. Prior limited trials in humans had indicated that Cr supplements, in either inorganic or organic form, may improve carbohydrate utilization. We report here a clinical double-blind, random crossover trial of inorganic Cr trichloride, a brewer's yeast that contained Cr as glucose tolerance factor (GTF), a brewer's yeast extract without GTF, and a placebo. Forty-three outpatient diabetic men received three of these supplements for 4 mo each. Subgroups included 21 ketosis-prone men; 7 ketosis-resistant, nonobese men; and 15 ketosis-resistant obese men. Chromium levels were followed pre- and posttreatment in hair, red blood cells, plasma, and urine. Response of carbohydrate metabolism to treatment was assessed in terms of change in insulin requirements, fasting plasma glucose, plasma cholesterol, and triglycerides, as well as change in plasma glucose, glucagon, and insulin or C-peptide levels in response to a standard meal. In some men, these parameters were also measured after i.v. tolbutamide. Both the inorganic and organic oral Cr supplements increased measurable body pools of Cr in hair and red blood cells by about 25%. However, fasting plasma glucose and lipids and the glucose response to either the standard meal or to tolbutamide were not significantly altered by any of the treatments. Despite this lack of effect on carbohydrate levels, the ketosis-resistant subgroups demonstrated a significant increase in postprandial insulin after treatment with the brewer's yeast that contained GTF.
Good Law from Tragic Facts — Congress, the FDA, and Preemption
Authors: George J. Annas
Journal: New England Journal of Medicine (2009)

In Wyeth v. Levine, the U.S. Supreme Court ruled that the approval of a drug by the Food and Drug Administration (FDA) did not prohibit injured patients from filing state civil lawsuits against pharmaceutical companies alleging failure to provide adequate warning about the drug's dangers.
Onset of Cardiac Function During Early Mouse Embryogenesis Coincides With Entry of Primitive Erythroblasts Into the Embryo Proper
Authors: Rui Ping Ji, Colin K.L. Phoon, Orlando Aristizábal, Kathleen E. McGrath, James Palis, Daniel H. Turnbull
Journal: Circulation Research (2003)

When cardiac function and blood flow are first established are fundamental questions in mammalian embryogenesis. The earliest erythroblasts arise in yolk sac blood islands and subsequently enter the embryo proper to initiate circulation. Embryos staged 0 to 30 somites (S) were examined in utero with 40- to 50-MHz ultrasound biomicroscopy (UBM)-Doppler, to determine onset of embryonic heartbeat and blood flow and to characterize basic physiology of the very early mouse embryonic circulation. A heartbeat was first detected at 5 S, and blood vascular flow at 7 S. Heart rate, peak arterial velocity, and velocity-time integral showed progressive increases that indicated a dramatically increasing cardiac output from even the earliest stages. In situ hybridization revealed an onset of the heartbeat coincident with the appearance of yolk sac-derived erythroblasts in the embryo proper at 5 S. Early maturation of the circulation follows a tightly coordinated program.
An Address on OBSERVATION, CO-ORDINATION OF KNOWLEDGE, AND JUDGEMENT
Authors: W. Russell
Journal: BMJ (1927)

as to reduce what had been a polycythaemia to figures which wvere just above those of a normal blood count.Four years before this event Dr. George Graham helped nie in givilng her continuous inhalations of oxygen.We demion- strated that the blood state of these patients is not improved by this measure.Haematuria due to Hexamine.In this series there is only one case of hexamine haema- turia.I think there was no doubt about the causationl.It was a case of acute encephalitis.A post-mnortem exam- ination was made eventually.The patient had been given only a moderate dose-20 grainis every six hours-and at the end of the third day there was a profuse haematuria.Unclassified Cases.There were five unclassified cases, and I have already said that I feel s'ure that one or perhaps two of them wouild be put down as " essential liaematuria " by those who consider that there is a gtroup of cases to which we might give that provisional label.One of these unclassified cases was a patient with aneurysm of the thoracic aorta; she had a profuse haematuria four days before death.The seconld of the ulclassified cases miight possibly he regarded as a case of calculus or iephrolitliiasis.Then there was the case of a boy of 18 whom Mr. Ogier Ward sent to me from St. Peter's.I failed to miake a diagnosis, but Mr. Ball was able to say that the blood came from one kidney onlv, and not from both.We know that in some of these cases of haematuria without obvious cause it is one side olnly tllat bleeds.That is lno guarantee, however, that if niephrectoiny is performed on tllat kidney the other one may iiot start a similar condition.But perhaps the most typical case of wlhat is termed " essenitial haemliaturia " was that of a maii of 33 (looking up the literature I find that the cases coming into this loose group of haematurias are generally between 20 and 40 years of age), a cycle maker, wlho, in 1921, passed blood in his urine.He was examinied witlh the cystoscope with- out anything abnormal being found.In November of that year lhe had a certain dull, not acute, pain, but nothing was dolne, because again nothing further was found.In January, 1922, he had a short attack of haematuria with no other symptoms.When he presented himself at the hospital a third time the left kidney was explored, but
Behavioral and neurological toxicity of polybrominated biphenyls in rats and mice.
Authors: H A Tilson, P A Cabe, C L Mitchell
Journal: Environmental Health Perspectives (1978)

Male, albino rats of the F-344/N strain and mice of the B6C3F1 strain were dosed by gavage, 5 days per week for a toal of 22 doses with 0.03--30 mg/kg of FireMaster FF-1, 0.168-16.8 Mg/kg of 2,4,5,2',4',5'-hexabromobiphenyl (HBB), or corn oil vehicle. A battery of tests was administered at the end of repeated dosing (30 day examination) and 30 days after dosing ceased (60 day test). FF-1 and, to a much lesser extent, HBB decreased body weight and performance on a variety of tests designed to detect neuromuscular dysfunction. Included in these tests were activity in the open field, forelimb grip strength, and muscular reflexes. Visual placement responses were also decreased in some animals, while hypothermia was observed in others. Emotionally, as measured by the number of defecations and urinations in the open field, was not affected by exposure to either compound. At the end of 30 day test, mice were less affected by exposure to these polybrominated biphenyls (PBBs) than rats; rats tended to worsen during the 30 days of no dosing, while mice tended to improve. These experiments indicate that oral dosing with levels of PBBs below those required to produce signs of acute toxicity produced behavioral or neurological toxicity when given repeatedly.
Nurses taking on junior doctors' work: a confusion of accountability
Authors: S. Dowling, R. Martin, P. Skidmore, L. Doyal, A. Cameron, S. Lloyd
Journal: BMJ (1996)

The number of hospital based posts in which nurses take over clinical work previously done by junior doctors is growing. Accountability for the scope of such new roles and the standards of practice which apply to them are still unclear. When analysed together and compared, the regulations arising from the professional bodies (GMC and UKCC), civil law concerning certain wrongs to patients, and employment law are sometimes contradictory and hard to interpret. The resulting uncertainties about appropriate management for clinical roles evolving between the professions, coupled with an increasingly litigious public, put the nurses and consultants involved at risk of complaints and of disciplinary and legal action. Drawing on our current research into changing clinical roles at the medical-nursing interface, we suggest strategies to reduce risk. Doctors and nurses should be equal partners in planning and managing these new posts, patients should be informed adequately about the nature of the postholder's role and training, significant changes in the work of such postholders should be formally acknowledged by the employer and relevant insurers, individuals taking up new roles should have access to legal advice and support to cover legal risk, and national regulatory bodies need to work together to harmonise their codes of practice in relation to changing clinical roles between the professions.
MALARIA CONTRACTED IN FLANDERS
Authors: J. McG. H. Reid, H. E. Humphrys
Journal: BMJ (1915)

r'IHE fol1o1w-ina cases were admitted to a general hospital from various; parts of thle front: CASFE I had liv-ed in Hull all his life and never pzreviously left Engfland.He came out to France in Julv feeling v-er fit,-but on Auglust 28tlh hiad pains in the head, followed next day by shivering iits.This continued every secondl day, and he was admitted to lhospital on September 9th.The blood, examined the following dav, showed the presence of a typical benign tertian parasite.lie said.that lie had never been near Indian troops, btit thiat lle was encamped beside a river.CASE II hiad live(d in Londonandhad never been out of England before.Oni AugLust 29th he had an operation for appendicitis, which was followed tiree days after by shivering attacks.He bliad been in excellent lhealth before.He had niever been in close proximiiity to Indian troops, but said there wvas a small pondlnear where he was billeted.The blood film showedl benign tertian.CASEI III had l ived in Suiffolk and had niever previouslvy been- ou-t of Eniland.He said that lhe had attacks of shiv-ering two onithis ago in Franlce, but did not report sick.Oni Augu"st 24th he agtain hlad )ad shivers, wvhich occurred every other day.He said.that hle was in close contact with Indian troops.The blood slhowed benigrn tertian.CASE iv belonged to Fifeshire.He had never previously left Scotlanld.He came to' France in May feeling very fit and was only in contact with Indian troops one day.He had shivering attacks and vomiting a mnonth ago.These attacks had con- tinued ever since andl occurred at night.He was admitted on August 28th; the blootl filim showed benign tertian.CASE V lived in Staffordshire, and had never beeni ouit of Eng- land befoi:e.He was in close contact with Indian troops for thiee monthis.He was taken ill with shiivering attackls and lheadachie on Septemiiber 5ti; the shivering attacks occurred every day.The bloodl film slhowed benign tertian.
Phase 2 study of the combination of merimepodib with peginterferon-α2b, and ribavirin in nonresponders to previous therapy for chronic hepatitis C
Authors: Patrick Marcellin, Yves Horsmans, Frederik Nevens, Jean-Didier Grange, Jean-Pierre Bronowicki, Denis Vetter, Susan Purdy, Varun Garg, Leif Bengtsson, Lindsay McNair, John Alam
Journal: Journal of Hepatology (2007)
Trimethadione Nephrosis Treated with Cortisone and Nitrogen Mustard
Authors: Richard C. Talamo, John D. Crawford
Journal: New England Journal of Medicine (1963)

TRIMETHADIONE,§ an anticonvulsant commonly used in the treatment of petit-mal epilepsy, is known to produce nephrotoxicity in human beings and animals.1 Sixteen cases of nephrotic syndrome that followed its use have been reported in the literature. Although many of the clinical and laboratory findings are similar to those of idiopathic nephrosis this entity differs by its frequent response to discontinuation of trimethadione medication and by its refractoriness to steroid therapy.2 The patient to be discussed acquired severe nephrotic syndrome while taking trimethadione and showed no response to withdrawal of medication or steroid therapy. Combined use of cortisone and nitrogen . . .
A New Remedy for Whooping Cough.
Authors: Frederick T. Wright
Journal: JAMA (1900)

Calumet, Mich., Sept. 24, 1900. <h3>To the Editor:</h3> —In the<i>Berliner Klinische Wochenschrift</i>for Dec. 11, 1899, appeared an article by Dr. Max Heim, of Düsseldorf, in which he recounted such successful results in the treatment of pertussis with a new remedy, "antitussin," that I was impelled to obtain a small amount of the remedy for trial. The results of this trial are, I think, sufficiently interesting to be worthy the notice of those who may not have seen Dr. Heim's original article or any abstract of it. It is an ointment, consisting of 5 parts difluordiphenyl, 10 parts of vaselin and 85 parts of lanolin, and is administered by inunction. The back, chest or abdomen of the patient is thoroughly washed with warm soap and water and rubbed dry with a rough towel. On the skin thus prepared the ointment is applied, a small portion at a time, and
Impact of chronic graft-versus-host disease on the health status of hematopoietic cell transplantation survivors: a report from the Bone Marrow Transplant Survivor Study
Authors: Christopher J. Fraser, Smita Bhatia, Kirsten Ness, Andrea Carter, Liton Francisco, Mukta Arora, Pablo Parker, Stephen Forman, Daniel Weisdorf, James G. Gurney, K. Scott Baker
Journal: Blood (2006)