tbuckley/cabot-search huggingface dataset:
Regulation of apoptotic signaling pathways in hepatocytes<i>in vivo</i>
Authors: Hartmut Jaeschke, Mary Lynn Bajt
Journal: Hepatology (2003)

The mitochondrial pathway is critical for the efficient execution of death receptor–initiated apoptosis in certain cell types. Questions remain as to why the mitochondria are required in that scenario. We investigated the molecular events that determined the need for the mitochondria by using an in vivo model of anti–Fas–induced hepatocyte apoptosis. In wild–type mice, Fas stimulation resulted in normal activation of caspase–3, with the generation of the active p19–p12 complex. In bid –deficient mice, caspase–3 activation was arrested after the initial cleavage at Asp 175 . This allowed the generation of the p12 small subunit, but the p20 large subunit could not be further processed to the p19 subunit. The p20–p12 complex generated by Fas stimulation in bid –deficient hepatocytes was inactive, arresting the death program. Failure of p20/p12 caspase–3 to mature and to exhibit activity was because of the inhibition by the inhibitor–of–apoptosis proteins (IAPs), such as XIAP, and also to a low caspase–8 activity. This block could be overcome in wild–type mice by two mechanisms. Smac was released from mitochondria early following Fas activation and was competitively bound to the IAPs to reverse their effects. XIAP could also be cleaved, and this occurred later and was likely mediated by enhanced caspase activities. Both mechanisms were dependent on Bid and thus were not operative in bid –deficient hepatocytes. In conclusion, mitochondrial activation by Bid is required for reversing the IAP inhibition through Smac release. It is also required for the alternative activation of caspases through cytochrome c release, as demonstrated previously. Together, these events ensure a successful progression of the death program initiated by the death receptor activation in the hepatocyte.
To Ablate or Not to Ablate?
Authors: Karen L. Sherman, David J. Bentrem
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
The Effect of <b> <i>Ipomoea batatas </i> </b>(Caiapo) on Glucose Metabolism and Serum Cholesterol in Patients With Type 2 Diabetes
Authors: Bernhard H. Ludvik, Katja Mahdjoobian, Werner Waldhaeusl, Astrid Hofer, Rudolf Prager, Alexandra Kautzky-Willer, Giovanni Pacini
Journal: Diabetes Care (2002)

There is considerable and growing interest in neutraceutical products for the treatment of diabetes (1). Recently, it has been shown that caiapo, the extract of white-skinned sweet potato ( Ipomoea batatas ), improves glycemic control in rodents by reducing insulin resistance (2). The aim of our study was to assess the effect of caiapo on glucose metabolism and its tolerability and mode of action in male Caucasian type 2 diabetic patients in a randomized, double-blind prospective study in parallel groups controlled with placebo.

A total of 18 male type 2 diabetic patients (age: 58 ± 8 years; weight: 88 ± 3 kg; BMI: 27.7 ± 2.7 kg/m2; means ± SEM) treated by diet alone were randomized to receive placebo or 2 (low dose) or 4 g (high dose) caiapo (four tablets each containing 168 or 336 mg powdered white-skinned sweet potato [ I. batatas ], respectively) before breakfast, lunch, and dinner for 6 weeks. The study protocol was approved by the Ethics Committee of the University of Vienna, and informed consent was obtained from all patients before inclusion into the study. Safety parameters (hematology and blood chemistry, including hepatic enzymes and urinanalysis) were controlled before and at the end of the study, and patients were asked to report any adverse events. Patients were seen weekly during the 6-week trial, and fasting blood glucose was measured. Each subject underwent a frequently sampled intravenous glucose tolerance test (FSIGT) …
The Goulstonian Lectures ON THE NATURE OF ARTERIO-SCLEROSIS: Delivered before the Royal College of Physicians of London
Authors: G. Evans
Journal: BMJ (1923)

TRTIw BRIMI resting; to maintain this attitude the nerve meclianisms must have in them a nucleus wlhich may have been expanded into that elaborate mechanism which serves the needs of orthograde apes.SCOLIOSIS.In none of the orthograde forms is such a continuous and urgent demand made on the postural spinal mechanism as is the case in man.In man only is the whole weiglht of the suprasacral part of the body supported erect on the spine over long intervals.The demuand on this neuro-muscular postural mechanism is, I think, even greater in thc sitting than in the standing posture, particularly if we sit leaning, forwards in writing and reading.Sitting bolt upriglht is particularly exhausting, more especially for young people in whom growth of vertebrae and of spinal muscles is pro- ceeding apace.The muscles which act on the short levers of the spine yield first, while the muscles which act on the long costal levers can still keep on.We rest tlhese exhausted short spinal muscles by, allowing the vertebrae to rotate until the articular processes begin to lock ard the transverse processes rest upon the necks of the long costal levers.Herein lies the beginning of lateral curvature or scoliosis.If the habit becomes fixed, then come the de formities of chest, vertebrae, and spine with which orthopaedic surgeons are only too familiar.It is not true, how- ever, to say that our spines are not perfectly adapted to the upright posture; it would be more accurate to say that human spines were not evolved to witlhstand the monotonous and trying postures entailed by modern education and by many modern industries.
Outpatient management of diabetic children.
Authors: G. W. Chance
Journal: BMJ (1969)

Diabetes mellitus affects about one per 1,000 children of school age. Few would disagree with the view that admission to hospital is essential for initial treatment and education of the child and parents. Views on the outpatient management of the diabetic child differ, however. Recommended regimens range from those in which insulin is given three times daily, together with a rigid diet in which all items are weighed, to those in which any limitation is rejected and regarded as a threat to the child's psyche. Neither of these extremes appears satisfactory and by using an intermediate approach much may be achieved without incurring psychological problems. The long-term effects of an acceptable and stable outpatient course are often underestimated. It will influence the attitude of the child and the parents to the condition and will set the pattern for the whole of the child's life. At a children's hospital it is beneficial for both care and morale for diabetic children to attend a special clinic; at the same time it is of great educational benefit to those looking after them. In smaller departments paediatricians will often find it useful to set aside a special clinic period at which the diabetic children may be supervised personally and where they may learn that there are others who are similarly affected.
Tyranny of Standards
Authors: Harold F. Hamit
Journal: JAMA (1975)

To the Editor.—  In their COMMENTARY (231:709, 1975), Fifer and Aldrich deplored the fact that labeling information supplied by manufacturers often lags far behind known benefits and actual usage of a given medication. But I think that they failed to emphasize sufficiently that the wording of package inserts, advertising, and other information regarding the use of this drug is rigidly controlled by officials of the Food and Drug Administration (FDA). The manufacturers of Xylocaine (lidocaine) probably were quite aware of its value in controlling cardiac arrhythmias, and the manufacturers of Valium (diazepam) probably had ample evidence that it is the drug of choice for status epilepticus long before FDA officials allowed them to say so in their package inserts and promotional information. Warnings against the use of Valium for convulsive disorders most likely were included in the package inserts at the insistence of FDA officials and under at least implied
Intestinal Bypass and Zinc
Authors: GEORGE MEYER
Journal: Annals of Internal Medicine (1979)

Letters1 February 1979Intestinal Bypass and ZincGEORGE MEYER, M.D.GEORGE MEYER, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-90-2-278_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The recent observations of decreased zinc and copper levels in patients after intestinal bypass procedures in the absence of skin lesions seems, at first glance, to be an observation in search of a disease (1). However, the finding strengthens a suspicion that low zinc levels in these patients may add to the protein deficiency that develops in the postoperative period. Because zinc deficiency may alter the senses of taste and smell, it seems likely that, in some cases, dysosmia (perverted smell) and dysgeusia (perverted taste) may develop, leading to avoidance of certain foods with subsequent protein deficiency...References1. ATKINSONDAHMSBRAYJACOBSANDSTEAD RWGRH: Plasma zinc and copper in obesity and after intestinal bypass. Ann Intern Med 89:491-493, 1978 LinkGoogle Scholar2. HENKINSCHECHTERHOYEMATTERN RPRC: Idiopathic hypogeusia with dysgeusia, hyposmia, and dysosmia. JAMA 217:434-440, 1971 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHair and plasma zinc levels following exclusion of biliopancreatic secretions from functioning gastrointestinal tract in humansClinical observations and immunologic abnormalities following bowel bypass surgeryZinc Deficiency and Intestinal Bypass ProceduresJOHN A. GAROFALO, M.D., ELLIOT STRONG, M.D., ROBERT A. GOOD, PH.D., M.D. 1 February 1979Volume 90, Issue 2Page: 278-278KeywordsFoodLesionsSmellTasteZinc Issue Published: 1 February 1979 PDF downloadLoading ...
WT1 Induces Apoptosis through Transcriptional Regulation of the Proapoptotic Bcl-2 Family Member Bak
Authors: Debra J. Morrison, Milton A. English, Jonathan D. Licht
Journal: Cancer Research (2005)

Abstract Wilms' tumor or nephroblastoma is believed to arise from embryonic nephrogenic rests of multipotent cells that fail to terminally differentiate into epithelium and continue to proliferate. The WT1 tumor suppressor gene, a transcription factor controlling the mesenchymal-epithelial transition in renal development, is mutated in 10% to 15% of Wilms' tumors. This potentially explains the disordered differentiation and proliferation program of a subset of Wilms' tumors. To elucidate the role of mutations of WT1 in the etiology of Wilms' tumor, we used an inducible cellular system for expressing wild-type and tumor-derived missense mutant WT1 proteins. Expression of wild-type WT1, but not mutant proteins, blocked cellular proliferation and DNA synthesis and rapidly induced apoptosis. We showed that wild-type WT1 induced transcription of one of the seven studied proapoptotic genes, Bak. Furthermore, WT1 protein bound to specific DNA-binding sites located in the Bak promoter and Bak was critical to WT1-mediated apoptosis, as overexpression of VDAC2, a specific Bak inhibitor, attenuated WT1-mediated cell death. These data support the hypothesis that Wilms' tumors arise, in part, because WT1 mutant proteins fail to promote programmed cell death during kidney development.
TCT-789 Optimizing plugs size for transcatheter paravalvular leak closure with Amplatzer Vascular Plug III devices
Authors: Grzegorz Smolka, Piotr Pysz, Ewa Peszek-Przybyla, Przemyslaw Zurek, Zbigniew Gasior, Andrzej Ochala
Journal: Journal of the American College of Cardiology (2012)
S100A4 is expressed at site of invasion in rheumatoid arthritis synovium and modulates production of matrix metalloproteinases
Authors: L Senolt, M Grigorian, E Lukanidin, B Simmen, B A Michel, K Pavelka, R E Gay, S Gay, M Neidhart
Journal: Annals of the Rheumatic Diseases (2006)

The metastasis-associated protein S100A4 promotes the progression of cancer by regulating the remodelling of the extracellular matrix. The expression of S100A4 in vivo is shown and the functional role of S100A4 in the pathogenesis of osteoarthritis and rheumatoid arthritisis is explored. The expression of S100A4 in rheumatoid arthritis, osteoarthritis and normal synovial tissues was determined by immunohistochemistry. The expression of matrix metalloproteinase (MMP) mRNA was measured in rheumatoid arthritis and osteoarthritis synovial fibroblasts treated and untreated with S100A4 oligomer by real-time polymerase chain reaction. Levels of released MMPs were confirmed by ELISA in cell culture supernatants. S100A4 protein was expressed in rheumatoid arthritis and osteoarthritis synovial tissues, in contrast with normal synovium. S100A4 up regulated MMP-3 mRNA in rheumatoid arthritis synovial fluid, with a peak after 6 h. This resulted in release of MMP-3 protein. MMP-1, MMP-9 and MMP-13 mRNA were also up regulated in synovial fluid, but with different kinetics. MMP-14 mRNA showed no change. Thus, S100A4 protein is expressed in synovial tissues of patients with rheumatoid arthritis and osteoarthritis in contrast with healthy people. It induces the expression and release of MMP-3 and other MMPs from synovial fluid. The data suggest that S100A4-producing cells could be involved in the pathogenesis of osteoarthritis and rheumatoid arthritis, including pannus formation and joint destruction.
Clinical risk factors for development of nonlymphoma cancer post-heart and heart-lung transplantation: analysis of 30-year follow-up in 1,026 patients
Authors: Shao-Zhou Gao, Mark G. Perlroth, Jose G. Montoya, Joan L. Miller, Sue DiMiceli, Bill Brown, Phillip E. Oyer, John S. Schroeder
Journal: Journal of the American College of Cardiology (2002)
Jejunal manometry in distal subacute mechanical obstruction: significance of prolonged simultaneous contractions.
Authors: M Camilleri
Journal: Gut (1989)

The aim of this study is to assess the value of jejunal manometry in the diagnosis of subacute mechanical obstruction distal to the proximal small bowel. In a retrospective review of 850 manometric tracings carried out in patients with unexplained nausea, vomiting, abdominal pain or altered bowel movements, 16 tracings were identified with features suggestive of mechanical obstruction: prolonged simultaneous contractions (PC) and postprandial clustered contractions (CC). Three patients had CC lasting less than 20 minutes: none proved to have mechanical obstruction. Among seven patients with CC lasting more than 30 minutes, three had proven mechanical obstruction, one probable adhesion obstruction, and in three no obstruction was found. All three patients with PC and three with mixed PC and CC had mechanical obstruction. The obstructed intestine manifests a variety of pressure profiles in the proximal jejunum: PC, CC, or mixed patterns. Prolonged simultaneous contractions are suggestive of distal subacute bowel obstruction; CC lasting over 30 minutes are less specific, whereas CC lasting less than 20 minutes are not associated with obstruction.
The Uromodulin C744G mutation causes MCKD2 and FJHN in children and adults and may be due to a possible founder effect
Authors: M.T.F. Wolf, B.B. Beck, F. Zaucke, A. Kunze, J. Misselwitz, J. Ruley, T. Ronda, A. Fischer, F. Eifinger, C. Licht, E. Otto, B. Hoppe, F. Hildebrandt
Journal: Kidney International (2007)
Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2–3 years of tamoxifen: a retrospective analysis of the Intergroup Exemestane Study
Authors: J Sven D Mieog, James P Morden, Judith M Bliss, R Charles Coombes, Cornelis JH van de Velde
Journal: The Lancet Oncology (2012)
Sildenafil Improves Exercise Hemodynamics and Oxygen Uptake in Patients With Systolic Heart Failure
Authors: Gregory D. Lewis, Justine Lachmann, Janice Camuso, John J. Lepore, Jordan Shin, Maryann E. Martinovic, David M. Systrom, Kenneth D. Bloch, Marc J. Semigran
Journal: Circulation (2006)

Heart failure (HF) is frequently associated with dysregulation of nitric oxide-mediated pulmonary vascular tone. Sildenafil, a type 5 phosphodiesterase inhibitor, lowers pulmonary vascular resistance in pulmonary hypertension by augmenting intracellular levels of the nitric oxide second messenger, cyclic GMP. We tested the hypothesis that a single oral dose of sildenafil (50 mg) would improve exercise capacity and exercise hemodynamics in patients with chronic systolic HF through pulmonary vasodilation.Thirteen patients with New York Heart Association class III HF underwent assessment of right heart hemodynamics, gas exchange, and first-pass radionuclide ventriculography at rest and with cycle ergometry before and 60 minutes after administration of 50 mg of oral sildenafil. Sildenafil reduced resting pulmonary arterial pressure, systemic vascular resistance, and pulmonary vascular resistance, and increased resting and exercise cardiac index (P<0.05 for all) without altering mean arterial pressure, heart rate, or pulmonary capillary wedge pressure. Sildenafil reduced exercise pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary vascular resistance/systemic vascular resistance ratio, which indicates a selective pulmonary vasodilator effect with exercise. Peak VO2 increased (15+/-9%) and ventilatory response to CO2 output (VE/VCO2 slope) decreased (16+/-5%) after sildenafil treatment. Improvements in right heart hemodynamics and exercise capacity were confined to patients with secondary pulmonary hypertension (rest pulmonary arterial pressure >25 mm Hg).The present study shows that in patients with systolic HF, type 5 phosphodiesterase inhibition with sildenafil improves peak VO2, reduces VE/VCO2 slope, and acts as a selective pulmonary vasodilator during rest and exercise in patients with HF and pulmonary hypertension.
Wegener's granulomatosis presenting with granulomatous facial erythematous papules and plaques mimicking granulomatous rosacea
Authors: M. Steinhoff, J. Steinhoff-Georgieva, C.C. Geilen, C. Assaf
Journal: British Journal of Dermatology (2006)

Conflicts of interest: none declared. Sir, A 70‐year‐old woman presented in 2003 with erythematous skin lesions that had developed on both cheeks within 2 months (Fig. 1a). She had a history of B‐cell chronic lymphocytic leukaemia (B‐CLL) in stage Binet C that was diagnosed in 1996. After seven courses of the chimeric anti‐CD20 antibody rituximab and interleukin‐2, followed by six courses of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) chemotherapy, the patient had been in partial remission since 1998. At presentation, she was being given immunoglobulin infusions by our haematologists every other week because of secondary humoral deficiency. The initial skin biopsy revealed perivascular and perifollicular granulomatous infiltrates compatible with granulomatous rosacea. However, systemic dapsone and tetracycline combined with topical metronidazole 2% twice daily for 6 weeks failed to ameliorate the patient's clinical condition. Moreover, she developed new skin lesions on the right thigh and suffered from increasing nasal obstruction. Nasal endoscopy revealed extensive haemorrhagic crusts and necrosis as well as septal perforation. An endonasal biopsy demonstrated a granulomatous inflammatory reaction with extensive necrosis. A third biopsy, taken from the right thigh, was the first to reveal clear signs of granulomatous vasculitis (Fig. 1b). The clinical symptoms pointed to Wegener's granulomatosis (WG). The patient was fully staged by computed tomographic scan, but no further sites of disease manifestation could be found. Repeated serological analyses were negative for classic antineutrophil cytoplasmic antibodies (c‐ANCA). Serological tests were also negative for perinuclear ANCA, anticardiolipin antibodies and syphilis. The white blood cell count (2·34 × 109 L−1; normal 4·0–10·0 × 109), IgM (< 0·17 g L−1; normal 0·4–2·3) and IgA (0·39 g L−1; normal 0·7–4·0) were decreased, whereas C‐reactive protein (10 mg L−1; normal < 6) and erythrocyte sedimentation rate (32 mm in the first hour; normal < 25) were slightly elevated. Angiotensin‐converting enzyme, haemoglobin and IgG were found to be normal. Renal involvement was excluded by urinalysis. A nasal smear detected oxacillin‐resistant Staphylococcus aureus.
Who can pay for innovative medicines?
Authors: Stefaan Decramer, Marc Decramer
Journal: European Respiratory Journal (2013)

Innovative medicines are of vital importance to the patients affected with one of the many acute or chronic illnesses, for which current treatments are often suboptimal. In particular chronic non-communicable diseases are becoming more prevalent, and this is even seen as a real crisis requiring United Nations action [1, 2]. It is widely known that, although the investments of the pharmaceutical industry in research and development (R&D) have increased substantially in the past decade, the number of innovative medicines that were registered with the US Food and Drug Administration and the European Medicines Agency has decreased over the same time period [3, 4]. A prime example is the respiratory field in which only nine new drugs have been developed over the past 40 years, four of which were for one particular disease, i.e. primary pulmonary hypertension [5]. Despite R&D spending at a high of 18% of revenues, the R&D productivity of the big pharmaceutical companies declined by 20% between 2001 and 2007 [6]. The innovation pipeline remains anaemic. A further thread is that shareholders are not willing …
Observations on the epidemiology of appendicitis.
Authors: D J Ashley
Journal: Gut (1967)

EDITORIAL COMMENT During a study of the epidemiology of appendicitis it was found that acute appendicitis is equally common in men and in women.Appendicectomy for non-acute appendicitis is commoner in women, and it is suggested that these patients are suffering from pain originating in the genital organs.Acute appendicitis in Wales is equally common amongst the Welsh and non-Welsh population.Appendicectomy for non-acute appendicitis is commoner in people of Welsh origin.Acute appendicitis is commoner in the spring but there is no seasonal variation in the case of appendicectomy for non-acute conditions.