tbuckley/cabot-search huggingface dataset:
Permissiveness of kupffer cells for simian immunodeficiency virus (SIV) and morphological changes in the liver of rhesus monkeys at different periods of SIV infection
Authors: Yury Persidsky, Anne-Marie Steffan, Jean-Louis Gendrault, Bruno Hurtrel, Stefan Berger, Cathy Royer, Hans-Jochen Stutte, Elizabeth Muchmore, Anne-Marie Aubertin, André Kirn
Journal: Hepatology (1995)

The pathogenesis of liver injury, which remains unclear in the course of human immunodeficiency virus infection, can be investigated in simian immunodeficiency virus-infected macaques, which develop an immunodeficiency disease resembling human acquired immune deficiency syndrome (AIDS). We studied the livers of 21 monkeys infected with simian immunodeficiency virus (SIVmac251) for 4 days to 39 months and detected viral antigens in Kupffer cells, macrophages, and lymphocytes in 65% of the livers tested. Virus-containing cells were present in 5 out of 9 livers tested as early as 4 days postinoculation. The number of positive cells as well as their content in viral proteins substantially increased in sinusoidal cells with the progression of the disease. Morphological features and double immunolabeling indicated that Kupffer cells constituted the predominant cell type containing viral antigens. The presence of multinucleated giant cells displaying the ultrastructural features of resident liver macrophages was another sign of the productive infection of Kupffer cells in vivo, which was attested by the observation of budding, immature, and mature SIV particles. Kupffer cell hyperplasia and hypertrophy were evident and appeared to be related to the development of SIV infection, because a close correlation was found between antigenemia and the surface area occupied by these cells. The Kupffer cells contained apoptotic lymphocytes, indicating that resident liver macrophages could play a role in the uptake of such cells from the blood. The production of tumor necrosis factor alpha (TNF alpha) and, possibly, interferon-alpha by Kupffer cells, the expression of vascular adhesion molecule-1, (VCAM-1), intralobular and periportal inflammation, and the proliferation and expansion of bile duct cells were other signs of liver involvement in SIV infection.
European drugs agency clashes with scientists over safety of GLP-1 drugs
Authors: D. Cohen
Journal: BMJ (2013)

Despite concerns raised by some scientists that a particular class of antidiabetes drugs known as glucagon-like peptide-1 (GLP-1) based drugs may have adverse effects on the pancreas, the European Medicines Agency has said that it had no new concerns about the drugs on the basis of the “presently available data.” 

These drugs, which are also called incretin mimetics, are of two types: GLP-1 agonists, such as exenatide, liraglutide, and lixisenatide; and dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin and saxagliptin.

A recent BMJ investigation found evidence indicating a potential risk of unwanted effects of the GLP-1 based drugs on the pancreas.1 This evidence included unpublished evidence of increases in size and abnormal changes in animal pancreases, raised pancreatic enzyme concentrations in humans, and pancreatitis in early clinical trials.

The investigation also highlighted safety signals for pancreatic cancer from the adverse reporting database from three different agencies.

However, after its own investigation of “presently available” non-clinical and clinical data, the European drug regulator said that the evidence did “not confirm recent concerns over an increased risk of pancreatic adverse …
Apoptosis Imaging for Monitoring DR5 Antibody Accumulation and Pharmacodynamics in Brain Tumors Noninvasively
Authors: Thomas G. Weber, Franz Osl, Anja Renner, Thomas Pöschinger, Stefanie Galbán, Alnawaz Rehemtulla, Werner Scheuer
Journal: Cancer Research (2014)

High-grade gliomas often possess an impaired blood-brain barrier (BBB), which allows delivery of large molecules to brain tumors. However, achieving optimal drug concentrations in brain tumors remains a significant hurdle for treating patients successfully. Thus, detailed investigations of drug activities in gliomas are needed. To investigate BBB penetration, pharmacodynamics, and tumor retention kinetics of an agonistic DR5 antibody in a brain tumor xenograft model, we utilized a noninvasive imaging method for longitudinal monitoring of apoptosis induction. Brain tumors were induced by intracranial (i.c.) implantation of a luciferase-expressing tumor cell line as a reporter. To quantify accumulation of anti-DR5 in brain tumors, we generated a dosage-response curve for apoptosis induction after i.c. delivery of fluorescence-labeled anti-DR5 at different dosages. Assuming 100% drug delivery after i.c. application, the amount of accumulated antibody after i.v. application was calculated relative to its apoptosis induction. We found that up to 0.20% to 0.97% of antibody delivered i.v. reached the brain tumor, but that apoptosis induction declined quickly within 24 hours. These results were confirmed by three-dimensional fluorescence microscopy of antibody accumulation in explanted brains. Nonetheless, significant antitumor efficacy was documented after anti-DR5 delivery. We further demonstrated that antibody penetration was facilitated by an impaired BBB in brain tumors. These imaging methods enable the quantification of antibody accumulation and pharmacodynamics in brain tumors, offering a holistic approach for assessment of central nervous system-targeting drugs.
TEST OF GLOMERULAR EFFICIENCY-Reply
Authors: Edward J. Stieglitz
Journal: JAMA (1935)

<h3>To the Editor:—</h3> In reply to this note we wish to state that the reference to Leschke was unknown to us and failure to mention his work of 1914 entirely unintentional. It should be pointed out that prior to the work of E. K. Marshall Jr. (<i>Am. J. Physiol.</i><b>94</b>:1 [July] 1930), J. G. Edwards (<i>Am. J. Physiol.</i><b>95</b>:493 [Nov.] 1930) and of Gersh and Stieglitz (<i>Anat. Rec.</i><b>58</b>:349 [March] 1934) there was no convincing evidence that ferrocyanide salts were excreted solely through the renal glomeruli. The earlier experimental work of Biberfeld and of Basler is discussed in some detail in the paper by Gersh and Stieglitz, to which reference is made in our clinical report inThe Journal. The clinical application of sodium ferrocyanide as a significant test of glomerular efficiency was dependent on the experimental proof of the route and method of its renal elimination.
Anti-idiotypic antibodies to anti-PDC-E2 in primary biliary cirrhosis and normal subjects
Authors: Qiao-yi Chen, Merrill J. Rowley, Ian R. Mackay
Journal: Hepatology (1999)

Anti-idiotypic antibodies may regulate the immune system and influence pathogenic autoimmunity. We investigated idiotype-anti-idiotype interactions in sera of patients with primary biliary cirrhosis (PBC), normal subjects and animals immunized with pyruvate dehydrogenase complex (PDC) or its derivatives. IgG autoantibody to the E2 subunit of PDC (PDC-E2) was derived by affinity-purification from sera of 12 patients with PBC, and F(ab)2 was prepared (anti-PDC-E2-F[ab]2). This was used as a reactant by enzyme-linked immunosorbent assay (ELISA) with sera from patients with PBC, normal subjects, or immunized animals. Results were that IgG antibody to anti-PDC-E2-F(ab)2 was detectable at low concentration in 12 PBC sera (mean optical density [OD] +/- SD: 1.02 +/- 0.26), and also in 19 normal sera (mean OD +/- SD: 0.97 +/- 0. 35) using a serum dilution of 1:20; background OD was 0.09 to 0.10, whereas antisera from animals immunized with PDC or PDC-E2 were nonreactive. There was a significant inverse correlation (r = -.59, P =.04) between the levels of anti-PDC-E2 in PBC sera (but not normal sera), and anti-idiotypic antibody reactive with anti-PDC-E2-F(ab)2. Anti-idiotypic antibody existed as a complex with anti-PDC-E2, because the removal of anti-PDC-E2 from serum resulted in decreased reactivity to anti-PDC-E2-F(ab)2. Reactivity between PDC-E2 and anti-PDC-E2 from PBC serum was not inhibited by normal sera, indicating that anti-idiotypic antibody from normal sera with anti-PDC-E2 reacts with the framework of F(ab) rather than the paratope. The conclusions are that PBC and normal sera contain IgG class anti-idiotypic antibodies to anti-PDC-E2, the characteristic autoantibody in PBC. Anti-PDC-E2 in immunized animals does not contain an idiotype cross-reactive with human anti-PDC-E2. Anti-idiotypic antibody in PBC is complexed with anti-PDC-E2 and in part accounts for immune complexes demonstrable in PBC. Anti-idiotypic antibody in PBC may regulate levels of anti-PDC-E2.
Transneuronal propagation of mutant huntingtin contributes to non–cell autonomous pathology in neurons
Authors: Eline Pecho-Vrieseling, Claus Rieker, Sascha Fuchs, Dorothee Bleckmann, Maria Soledad Esposito, Paolo Botta, Chris Goldstein, Mario Bernhard, Ivan Galimberti, Matthias Müller, Andreas Lüthi, Silvia Arber, Tewis Bouwmeester, Herman van der Putten, Francesco Paolo Di Giorgio
Journal: Nature Neuroscience (2014)
Older Patients: Safe Behind the Wheel?
Authors: Anita Slomski
Journal: JAMA (2010)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Treatment of Goiter and Thyroid Nodules with Thyroid
Authors: E. B. Astwood
Journal: JAMA (1960)

The effectiveness of orally administered thyroid substance in the treatment of simple goiter was noted 70 years ago, but its justification awaited the modern discovery of the relation of the thyroid to the thyrotropic hormone of the hypophysis. The present analysis of 230 cases of simple goiter demonstrates the value of thyroid U.S.P., which was given in single daily doses, usually of 180 mg. at the outset. This amount caused mild symptoms of overdosage in 16% of the patents and in some cases it had to be increased in order to obtain the desired regression. Thyroid nodules and simple goiter were reduced in size or disappeared in about two-thirds of the cases. This corroborates the older clinical observations as well as the underlying theory and indicates that simple goiter is essentially a benign process.
Explanations shift attitudes to animal experiments
Authors: R. Woodman
Journal: BMJ (1999)

Attitudes on animal experimentation shift dramatically when people are told about the potential medical benefits, according to results of a major new poll.

Sixty four per cent of a representative sample of 2009 people in Britain aged 15 years and over disagreed with the view that scientists should be allowed to conduct any experiment on animals, and only 24%agreed. However, when told that animal experiments might hasten development of treatments for life threatening diseases, such as leukaemia and AIDS, there was a huge …
PES1 promotes breast cancer by differentially regulating ERα and ERβ
Authors: Long Cheng, Jieping Li, Yongjian Han, Jing Lin, Chang Niu, Zhichao Zhou, Bin Yuan, Ke Huang, Jiezhi Li, Kai Jiang, Hao Zhang, Lihua Ding, Xiaojie Xu, Qinong Ye
Journal: Journal of Clinical Investigation (2012)

The initiation of breast cancer is associated with increased expression of tumor-promoting estrogen receptor α (ERα) protein and decreased expression of tumor-suppressive ERβ protein. However, the mechanism underlying this process is unknown. Here we show that PES1 (also known as Pescadillo), an estrogen-inducible protein that is overexpressed in breast cancer, can regulate the balance between ERα and ERβ. We found that PES1 modulated many estrogen-responsive genes by enhancing the transcriptional activity of ERα while inhibiting transcriptional activity of ERβ. Consistent with this regulation of ERα and ERβ transcriptional activity, PES1 increased the stability of the ERα protein and decreased that of ERβ through the ubiquitin-proteasome pathway, mediated by the carboxyl terminus of Hsc70-interacting protein (CHIP). Moreover, PES1 transformed normal human mammary epithelial cells and was required for estrogen-induced breast tumor growth in nude mice. Further analysis of clinical samples showed that expression of PES1 correlated positively with ERα expression and negatively with ERβ expression and predicted good clinical outcome in breast cancer. Our data demonstrate that PES1 contributes to breast tumor growth through regulating the balance between ERα and ERβ and may be a better target for the development of drugs that selectively regulate ERα and ERβ activities.
Troglitazone Reduces Plasma Leptin Concentration but Increases Hunger in NIDDM Patients
Authors: Hiroyuki Shimizu, Takahumi Tsuchiya, Noriyuki Sato, Yohnosuke Shimomura, Isao Kobayashi, Masatomo Mori
Journal: Diabetes Care (1998)

OBJECTIVE Troglitazone, which improves peripheral insulin resistance of experimental diabetic animals and diabetic patients, affects ob gene expression in the adipose tissue of rodents. The present study was undertaken to examine a hypothesis that clinical administration of troglitazone may reduce circulating leptin levels and affect eating behavior in NIDDM patients. RESEARCH DESIGN AND METHODS Troglitazone was administered at a dosage of 200 mg twice daily for 12 weeks in 20 poorly controlled NIDDM patients. Chronological changes in glycemic control, serum lipids, immunoreactive leptin (IRL) levels, and BMI were measured. Body fat weight was also assessed by bioelectric impedance. RESULTS Troglitazone significantly decreased fasting plasma glucose, serum immunoreactive insulin, and HbA1c levels. Serum levels of IRL and triglyceride were significantly reduced by troglitazone administered for 4, 8, and 12 weeks. Troglitazone administration significantly increased the BMI in NIDDM patients, and two-thirds of the patients complained of increased hunger after the start of troglitazone administration. CONCLUSIONS Troglitazone significantly reduces circulating leptin levels at clinical doses. It may affect the eating behavior of poorly controlled NIDDM patients through the improvement of glycemic control and/or the reduction of circulating leptin.
Cigarette packs to feature graphic images
Authors: Bob Burton
Journal: BMJ (2004)

The Australian government is proposing that by mid-2005 every packet of cigarettes andtobacco sold there will feature graphic images of smoking related diseases over half the front and rear panels.

The proposals emulate those adopted in Canada, which introduced graphic warnings covering half each pack in January 2001, and Brazil, which introduced similar images in February 2002. Unveiling the proposed changes for public comment the parliamentary secretary for health, Trish Worth, pointed to the success of the changes in Canada, which have resulted in a 3% reduction in tobacco consumption.

Australians currently …
Mind over matter in the postinfective irritable bowel
Authors: D A DROSSMAN
Journal: Gut (1999)

Although macromolecular synthesis inhibitors have been demonstrated to prevent neuronal apoptosis in a number of paradigms, their mechanisms of protection remains unclear. Recently, we found that neuronal death resulting from cystine deprivation, glutathione loss, and oxidative stress is apoptotic and is prevented by inhibitors of macromolecular synthesis. We now report that protection is associated with enhanced availability of acid-soluble cyst(e)ine and restoration of cellular glutathione levels. N-acetylcysteine, an agent that delivers exogenous cysteine intracellularly and raises glutathione, is also protective, while buthionine sulfoximine, an inhibitor of glutathione synthesis, prevents protection by inhibitors of macromolecular synthesis. These results suggest that protection provided by these agents, in this paradigm, derives from shunting of the amino acid cysteine from global protein synthesis into the formation of the antioxidant glutathione.
Evaluation of the effect of nifedipine upon myocardial perfusion and contractility using cardiac magnetic resonance imaging and tissue Doppler echocardiography in systemic sclerosis
Authors: O Vignaux
Journal: Annals of the Rheumatic Diseases (2005)

Primary myocardial involvement due to microcirculation impairment is common in systemic sclerosis (SSc). Cardiovascular magnetic resonance imaging (MRI) and tissue Doppler echocardiography (TDE) were recently shown to be more sensitive than conventional methods for the respective assessment of myocardial perfusion and contractility. Previous studies have suggested that dihydropyridine-type calcium channel blockers mitigate both myocardial perfusion and function abnormalities.To investigate the effects of nifedipine on myocardial perfusion by MRI and on contractility by TDE, in patients with SSc.18 patients with SSc without clinical heart failure and with normal pulmonary arterial pressure (14 women, 4 men; mean (SD) age 59 (9) years; mean (SD) disease duration 7 (4) years, 10 with diffuse and 8 with limited cutaneous forms) were prospectively evaluated. The MRI perfusion index, determined from time-intensity curves, and systolic and diastolic strain rate determined by TDE were assessed at baseline, after a 72 hour vasodilator washout period, and after 14 days of oral treatment with nifedipine 60 mg/day.Nifedipine treatment led to a significant increase in the MRI perfusion index (mean (SD) 0.26 (0.07) v 0.19 (0.05) at baseline, p = 0.0003) and in systolic and diastolic strain rate (2.3 (0.6) v 1.5 (0.4) s(-1) at baseline, p = 0.0002, and 4.2 (1.6) v 3.0 (1.2) at baseline, p = 0.0003, respectively).Fourteen days of treatment with nifedipine simultaneously improves myocardial perfusion and function, as evaluated by highly sensitive and quantitative methods.
Tumour necrosis factor blockade induces an anti-inflammatory growth hormone signalling pathway in experimental colitis
Authors: X Han, N Benight, B Osuntokun, K Loesch, S J Frank, L A Denson
Journal: Gut (2006)

Background: Neutralisation of tumour necrosis factor α (TNFα)restores systemic growth hormone function in patients with Crohn's disease, and induces mucosal healing. Anabolic effects of growth hormone depend on activation of the STAT5 transcription factor. Although it has recently been reported that both administration of growth hormone and neutralisation of TNFα reduce mucosal inflammation in experimental colitis, whether this involved activation of STAT5 in the gut is not known. Aim: To determine whether TNFα blockade in colitis up regulates a growth hormone:STAT5 signalling pathway in the colon. Methods: Interleukin 10-deficient mice and wild-type controls received growth hormone or anti-TNFα antibody, and T84 human colon carcinoma cells were treated with TNFα or growth hormone. Activation and expression of STAT5b, peroxisome proliferator-activated receptor gamma (PPARγ), NFκB/IκB and growth hormone receptor were determined. Results: Growth hormone activated STAT5b and up regulated expression of PPARγ in normal mouse colon; inflamed colon was partially resistant to this. Chronic administration of growth hormone, nevertheless, significantly reduced activation of colonic NFκB (p = 0.028). Neutralisation of TNFα rapidly increased abundance of growth hormone receptor, activation of STAT5 and abundance of PPARγ in the colon, but reduced activation of NFκB in colitis. Growth hormone activated STAT5, and directly reduced TNFα activation of NFκB, in T84 cells. Conclusions: Reduced activation of colonic STAT5 and expression of PPARγ may contribute to persistent mucosal inflammation in colitis. Up regulation of STAT5 and PPARγ, either through neutralisation of TNFα or chronic administration of growth hormone, may exert an anti-inflammatory effect in inflammatory bowel disease.
Ophthalmic Manifestations of Systemic Vascular Disease
Authors: James D. Kingham
Journal: JAMA (1975)

Rather than an ophthalmic text, this book is volume 3 in a series,<i>Major Problems in Internal Medicine</i>. Its purpose is to serve as an introduction to the relationship of the eye to vascular and systemic disease. Those who have read David Cogan's two books on neurology of the visual system will be familiar with the format of this volume. The early chapters include an introduction to the physical examination of the eye and incorporate discussions on signs and symptoms, significance of fundus signs, visual field abnormalities, and fundus signs of systemic vascular disease. Later chapters consider specific vascular entities, such as occlusive arterial disease, occlusive venous disease, vasculitis, and finally, neuro-ophthalmic complications of intracranial vascular disease. Of course, each chapter, as in Cogan's previous books, includes a summary. Although modestly referred to as an introductory treatise, this book covers a plethora of ocular conditions. To cover so much in
Targeting depressive symptoms is unlikely to help
Authors: J. C. Coyne
Journal: BMJ (2010)

Ritchie and colleagues urge moving from observational epidemiology to public health interventions to reduce dementia and propose reducing depressive symptoms.1 This is a poor example except as an opportunity to reflect on the pitfalls of inferring modifiable risk from correlation.

Depressive symptoms are related to a host of antecedent and cross sectional correlates ranging …