tbuckley/cabot-search huggingface dataset:
Stable expression of manganese superoxide dismutase (MnSOD) in insulinoma cells prevents IL-1beta- induced cytotoxicity and reduces nitric oxide production.
Authors: H E Hohmeier, A Thigpen, V V Tran, R Davis, C B Newgard
Journal: Journal of Clinical Investigation (1998)

The fact that insulin-producing islet beta-cells are susceptible to the cytotoxic effects of inflammatory cytokines represents a potential hinderance to the use of such cells for transplantation therapy of insulin-dependent diabetes mellitus (IDDM). In the current study, we show that IL-1beta induces destruction of INS-1 insulinoma cells, while having no effect on a second insulinoma cell line RIN1046-38 and its engineered derivatives, and that this difference is correlated with a higher level of expression of manganese superoxide dismutase (MnSOD) in the latter cells. Stable overexpression of MnSOD in INS-1 cells provides complete protection against IL-1beta-mediated cytotoxicity, and also results in markedly reduced killing when such cells are exposed to conditioned media from activated human or rat PBMC. Further, overexpression of MnSOD in either RIN- or INS-1-derived lines results in a sharp reduction in IL-1beta-induced nitric oxide (NO) production, a finding that correlates with reduced levels of the inducible form of nitric oxide synthase (iNOS). Treatment of INS-1 cells with L-NMMA, an inhibitor of iNOS, provides the same degree of protection against IL-1beta or supernatants from LPS-activated rat PBMC as MnSOD overexpression, supporting the idea that MnSOD protects INS-1 cells by interfering with the normal IL-1beta-mediated increase in iNOS. Because NO and its derivatives have been implicated as critical mediators of beta-cell destruction in IDDM, we conclude that well regulated insulinoma cell lines engineered for MnSOD overexpression may be an attractive alternative to isolated islets as vehicles for insulin replacement in autoimmune diabetes.
Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin
Authors: I I Raad, H A Hanna, M Boktour, Y Jiang, H A Torres, C Afif, D P Kontoyiannis, R Y Hachem
Journal: Leukemia (2007)
The Royal Commission and the Morale of the Medical Profession
Authors: John Lister
Journal: New England Journal of Medicine (1976)

The Royal Commission set up last year to consider "the best use and management of the financial and manpower resources of the National Health Service" is proceeding with its work. From the outset the chairman, Sir Alec Merrison, made it clear that he and his colleagues would welcome the views of individuals as well as official bodies who thought they had relevant advice to offer. He also indicated that he intended to interpret his brief widely and that he would not hesitate to include in his review any aspect of the working of the National Health Service (NHS) that might . . .
Matrix-Dependent Mechanism of Neutrophil-Mediated Release and Activation of Matrix Metalloproteinase 9 in Myocardial Ischemia/Reperfusion
Authors: Merry Lindsey, Kyle Wedin, Michael D. Brown, Christopher Keller, Alida J. Evans, James Smolen, Alan R. Burns, Roger D. Rossen, Lloyd Michael, Mark Entman
Journal: Circulation (2001)

Background —A key component of reperfusion of myocardial infarction is an immediate inflammatory response, which enhances tissue repair. Matrix turnover is crucial to tissue repair, and matrix metalloproteinases (MMPs) are key enzymes involved in matrix degradation. The hypothesis tested is that one inflammation-based effector of tissue repair is the secretion and activation of MMP-9 by infiltrating neutrophils. Methods and Results —Cardiac lymph and tissue were assayed for latent and active MMP-2 and MMP-9 by zymography and immunochemistry. Dual-labeling immunofluorescence determined the cellular source of MMP-9 protein. Isolated canine neutrophils were incubated with preischemic and postischemic cardiac lymph in the presence and absence of collagen-fibronectin pads, and the supernatants were assayed for latent and active MMP-9. MMP-9 increased during the first hours of reperfusion in both lymph supernatants and myocardial extracts, and this increase was of neutrophil origin. MMP-9 in the cardiac lymph remained latent but was activatable. In contrast, MMP-9 in the myocardium was in both latent and active forms. In situ zymography demonstrated that activated MMP-9 surrounded the infiltrated neutrophils. When postischemic cardiac lymph was incubated with neutrophils in vitro, MMP-9 secretion and activation occurred only in the presence of a collagen-fibronectin substrate; preischemic cardiac lymph did not induce significant secretion or activation. Conclusions —Infiltrating neutrophils are an early source of MMP-9 after reperfusion, and a portion of MMP-9 in the myocardium is active. Infiltrating neutrophils may localize MMP-9 activation by secreting MMP-9 and as a source of activating proteases.
Bullous fixed drug eruption due to paracetamol with an unusual immunofluorescence pattern
Authors: None Hern, None Harman, None Clement, None Black
Journal: British Journal of Dermatology (1998)

Journal Article Bullous fixed drug eruption due to paracetamol with an unusual immunofluorescence pattern Get access S. Hern, S. Hern St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K., Search for other works by this author on: Oxford Academic Google Scholar K. Harman, K. Harman St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K., Search for other works by this author on: Oxford Academic Google Scholar M. Clement, M. Clement Department of Dermatology, Orpington Hospital, Orpington, Kent BR6 9JU, U.K. Search for other works by this author on: Oxford Academic Google Scholar M.M. Black M.M. Black St John's Institute of Dermatology, St Thomas' Hospital, London SE1 7EH, U.K., Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 6, 1 December 1998, Pages 1129–1131, https://doi.org/10.1046/j.1365-2133.1998.2576o.x Published: 01 December 1998
Heterogeneous Tumor Evolution Initiated by Loss of pRb Function in a Preclinical Prostate Cancer Model
Authors: Reginald Hill, Yurong Song, Robert D. Cardiff, Terry Van Dyke
Journal: Cancer Research (2005)

Abstract Because each change in the evolution of a cancer is predicated on the effects of previous events, a full understanding of selective changes and their effect on tumor progression can only be understood in the context of appropriate initiating events. Here, we define the effect of pRb function inactivation in prostate epithelium on both the initiation of prostate cancer and the establishment of selective pressures that lead to diminished Pten function and tumor evolution. Using genetically engineered mice, we show that inactivation of the pRb family proteins (Rb/p107/p130) induces epithelial proliferation and apoptosis and is sufficient to produce prostatic intraepithelial neoplasia (PIN) lesions. Over time, adenocarcinomas develop in all mice with no evidence of neuroendocrine tumors. Apoptosis is dependent on Pten function and not p53, unlike other epithelial cell types tested previously. Consequently, Pten hemizygosity reduces apoptosis by 50%, accelerating progression to adenocarcinomas with heterogeneous composition. Heterogeneity is associated with concurrent Pten haploinsufficiency and focal selective progression to complete Pten loss, which yields distinct tumor properties. Given that this analysis models the apparent timing of highly penetrant events in human prostate cancer, observed effects may recapitulate the natural evolution of prostate cancer development.
IDIOPATHIC NEUTROPENIA IN HOMOSEXUAL MEN
Authors: R.M. Minchinton, I. Frazer, J. Van Der Lelie, J.M.A. Lange, J. Goudsmit, S.A. Danner, C.M. Van der Plas-Van Dalen, J.J.E. Vos, A.E.G.Kr Von Dem Borne
Journal: The Lancet (1985)
Therapy for Cytomegalovirus Retinitis: Still No Silver Lining
Authors: Lucy H. Y. Young
Journal: JAMA (1996)

CYTOMEGALOVIRUS (CMV) retinitis is the leading cause of visual loss in acquired immunodeficiency syndrome (AIDS), occurring in about one third of patients with AIDS. Without treatment, the disease is relentless, eventually leading to complete destruction of the retina. In the past decade, many therapeutic options have been used, but the major breakthrough in the management of this devastating disorder took place with the availability of ganciclovir and foscarnet. However, as both agents are unable to eliminate CMV from the infected retina, lifelong therapy is required. Unfortunately, despite treatment with good compliance, reactivation develops in virtually all patients over time. It is also the general impression that the relapse of the retinitis or development of new lesions takes place in increasingly shorter intervals, indicating that the disease becomes harder to control as immune status of the patient worsens. See also p 142. The current management of newly diagnosed CMV retitinis is
Decamethonium Iodide as a Curarizing Agent in General Anaesthesia
Authors: A. R. Ellerker
Journal: BMJ (1950)

The reasons why medical boards failed to diagnose and exclude these cases from service are discussed, with special reference to the importance of the position and type of the apex beat in diagnosis.Increased disablement from a purely medical point of view occurred in only 34% of the total.It was caused by recurrent rheumatic fever, bacterial endocarditis, auricular fibrillation, angina of effort, and the occurrence of emboli or cardiac failure.The importance of radiological examination of the heart and the potential value of mass radiography are discussed.I wish to thank Sir John Parkinson for his helpful criticism.My thanks are also due to Dr.
Services for the mentally handicapped.
Authors: N Gordon
Journal: BMJ (1980)

intermediate social and economic conditions, has a similar prevalence of gall stones at necropsy to that found in several English towns.However, the death rate from ischaemic heart disease in Scotland was 260o greater for males under 60 and 60%, greater for females in the same age group.We do not have sufficient information to analyse statistically the relationship between gall stones and ischaemic heart disease, but these figures suggest that the negative correlation described by Dr Barker does not apply to this region.
Playing the Odds
Authors: Joel Stein
Journal: JAMA Pediatrics (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Three Hundred Cases of Diffuse Ulcerative Colitis Treated by Total Colectomy and Ileo-rectal Anastomosis
Authors: S. O. Aylett
Journal: BMJ (1966)

In 1953 a preliminary report on the surgical treatment of diffuse ulcerative colitis by total colectomy and ileo-rectal anastomosis was published by the author in this journal. Since that time many interim reviews have been recorded (Aylett, 1960, 1963, 1964), but it would seem appropriate now that well over 300 cases have been subjected to this type of procedure that the experience gained and the lessons learned during the treatment of the first 300 patients in this series, operated upon between March 1952 and March 1965, should be detailed. Before our first attempts to retain the rectum and to re establish intestinal continuity it had become apparent that the ulcerative changes present in this disease were by no means irreversible. Repeated sigmoidoscopic examinations carried out on patients who had responded to medical treatment showed conclusively that the previously existing ulcers could become covered with new-formed epithelium, and biopsy material con firmed microscopically this macroscopic observation. It was also noted that these changes followed and did not precede the alleviation of the patient's toxaemia and ill-health. It appeared that if the toxaemia associated with the disease could be overcome?and in the chronic as well as the acute and fulminating cases it is severe?the regenerative processes inherent in the intestinal mucosa were adequate to recover areas of ulc?ration and permit the intestine once again to fulfil its normal physiological function. In those cases which failed to respond to medical treatment it was possible that, if excision of the vast bulk of the source of this toxaemia?that is, the excision of the whole of the colon and the uppermost part of the rectum?was undertaken, then the consequent relief of the toxaemia would be such that the ulcerative processes in the rectum remaining would heal as the patient recovered health. Thus a permanent ileostomy would be avoided and a normal route of intestinal evacuation estab lished. This theoretical basis of the operation of total colec tomy and ileo-rectal anastomosis has been amply established in practice, and, except in a very small minority of patients to be discussed later, experience has shown that pan proctocolectomy with the formation of a permanent ileostomy is an unnecessary disability to inflict upon a patient requiring surgery for the cure of ulcerative colitis.
Age dependent hypergastrinaemia in children with Helicobacter pylori gastritis--evidence of early acquisition of infection.
Authors: W A McCallion, J E Ardill, K B Bamford, S R Potts, V E Boston
Journal: Gut (1995)

Acute Helicobacter pylori associated gastritis causes achlorhydria, a powerful stimulus to gastrin secretion. If H pylori infection is acquired primarily in early childhood, then the degree of hypergastrinaemia in seropositive children should be age dependent. Anti-Helicobacter antibodies and fasting gastrin concentrations were measured in 439 children aged 4 to 13 years attending hospital for routine day case surgery not connected with any gastrointestinal disorder. Thirty per cent were seropositive for H pylori. There was an inverse relationship between the fasting gastrin concentration and age; the mean fasting gastrin in children aged 4-5 years, 155 ng/l, was significantly higher than that seen in children aged 12-13 years, 90 ng/l. The more noticeable hypergastrinaemia seen in young children with H pylori associated gastritis may reflect achlorhydria associated with acute H pylori infection and suggests that this is primarily acquired in early childhood.
Outcomes with various drug eluting or bare metal stents in patients with diabetes mellitus: mixed treatment comparison analysis of 22 844 patient years of follow-up from randomised trials
Authors: S. Bangalore, S. Kumar, M. Fusaro, N. Amoroso, A. J. Kirtane, R. A. Byrne, D. O. Williams, J. Slater, D. E. Cutlip, F. Feit
Journal: BMJ (2012)

<b>Objectives</b> To evaluate the efficacy and safety of currently used drug eluting stents compared with each other and compared with bare metal stents in patients with diabetes. <b>Design</b> Mixed treatment comparison meta-analysis. <b>Data sources and study selection</b> PubMed, Embase, and CENTRAL were searched for randomised clinical trials, until April 2012, of four durable polymer drug eluting stents (sirolimus eluting stents, paclitaxel eluting stents, everolimus eluting stents, and zotarolimus eluting stents) compared with each other or with bare metal stents for the treatment of de novo coronary lesions and enrolling at least 50 patients with diabetes. <b>Primary outcomes</b> Efficacy (target vessel revascularisation) and safety (death, myocardial infarction, stent thrombosis). <b>Results</b> From 42 trials with 22 844 patient years of follow-up, when compared with bare metal stents (reference rate ratio 1) all of the currently used drug eluting stents were associated with a significant reduction in target vessel revascularisation (37% to 69%), though the efficacy varied with the type of stent (everolimus eluting stents∼sirolimus eluting stents&gt;paclitaxel eluting stents∼zotarolimus eluting stent&gt;bare metal stents). There was about an 87% probability that everolimus eluting stents were the most efficacious compared with all others, though there were limited usable data for the zotarolimus eluting Resolute stent in patients with diabetes. Moreover, there was no increased risk of any safety outcome (including very late stent thrombosis) with any drug eluting stents compared with bare metal stents. There was about a 62% probability that the everolimus eluting stent was the safest stent for the outcome of "any" stent thrombosis. <b>Conclusions</b> Among patients with diabetes treated with coronary stents all currently available drug eluting stents were efficacious without compromising safety compared with bare metal stents. There were relative differences among the drug eluting stents, such that the everolimus eluting stent was the most efficacious and safe.
THE NATURE OF ILEOCOLITIS FROM AN ETIOLOGIC POINT OF VIEW
Authors: C. G. GRULEE
Journal: JAMA (1913)

The term "ileocolitis," while originally a pathologic designation, has become distinctly clinical. No one, I think, will assert that all cases which show the clinical manifestations of ileocolitis are necessarily combined with the pathologic lesions which the term implies, and certainly not with the severe pathologic lesions which are commonly associated with it. It seems to me that the term ileocolitis conveys to the mind of most persons the clinical picture which follows in from twenty-four to forty-eight hours the acute stage of intoxication of alimentary origin. This period represents a symptom-complex which is more or less regular. The stools, while not so frequent as during the acute stage, contain much mucus and often blood. The temperature ranges usually between 99 and 101 F., prostration is great and the tolerance for food is markedly reduced. It is this stage of acute attacks of summer diarrhea which offer so much difficulty
316. Production of Adenoviral Vectors in an Academic cGMP Facility
Authors: M.F. Medina, J. Rudy, U. Sankar, D. Chong, R. Foley, J. Gauldie
Journal: Molecular Therapy (2006)

Vectors used for early-phase clinical trials (Phase I-II) are required to be manufactured in a facility that at a minimum complies with cGMP (current good manufacturing practices) requirements on premises and equipment. Such facilities are mostly prevalent in academic institutions that provide support to in-house researchers as they embark on clinical testing of their vectors in humans. There are several advantages to establishment of an in-house facility for producing these vectors, such as increased accessibility to information or documentation essential for clinical trial applications. Disadvantages include the high costs associated with compliance to regulatory requirements with respect to establishment of facility, equipment, raw materials and training of personnel.
Turbulent/Viscous Interactions Control Doppler/Catheter Pressure Discrepancies in Aortic Stenosis
Authors: Edward G. Cape, Michael Jones, Izumi Yamada, Michael D. VanAuker, Lilliam M. Valdes-Cruz
Journal: Circulation (1996)

Background Despite good correlation between Doppler and catheter pressure drops in numerous reports, it is well known that Doppler tends to apparently overestimate pressure drops obtained by cardiac catheterization. Neither (1) simplification of the Bernoulli equation nor (2) pressure recovery effects can explain this dilemma when taken alone. This study addressed the hypothesis that a Reynolds number–based approach, which characterizes (1) and (2), provides a first step toward better agreement of catheter and Doppler assessments of pressure drops. Methods and Results Doppler and catheter pressure drops were studied in an in vitro model designed to isolate the proposed Reynolds number effect and in a sheep model with varying degrees of stenosis. Doppler pressure drops in vitro correlated with the directly measured pressure drop for individual valves ( r =.935, .960, .985, .984, .989, and .975) but with markedly different slopes and intercepts. A Bland-Altman type plot showed no useful pattern of discrepancy. The Reynolds number was successful in collapsing the data into the profile proposed in the hypothesis. Parallel results were found in the animal model. Conclusions Apparent overestimation of net pressure drop by Doppler is due to pressure recovery effects, and these effects are countered by both viscous effects and inertial/turbulent effects. Only by reconciliation of discrepancies by use of a quantity such as Reynolds number that embodies the relative importance of competing factors can the noninvasive and invasive methods be connected. This study shows that a Reynolds number–based approach accomplishes this goal both in the idealized in vitro setting and in a biological system.
Controlled Clinical Trials-Reply
Authors: K. Lance Gould
Journal: JAMA (1983)

In Reply.—  I thank Dr Spodick for his supporting view with regard to my editorial inThe Journal. Although we agree on most points, I would reiterate my criticisms of large, multicentered, randomized clinical trials for reperfusion therapy in cases of acute myocardial infarction, which make such trials frequently uninterpretable and, therefore, a waste of limited research funds.   1. Preselection, medical-surgical crossovers, data attrition, and, finally different characteristics of randomized groups despite randomization make the final data questionable in many if not most such trials.  2. Mortality is a remote and non-specific end point that provides little insight into mechanisms or actual effects of therapy. That is, the therapy may benefit the problem for which it was intended, but other factors of selection or side effects, which may be investigated or solved as separate problems, obscure these benefits by increasing mortality nonspecifically.  3. In our experience, admission left ventricular ejection