tbuckley/cabot-search huggingface dataset:
Some factors affecting prognosis in pemphigus vulgaris and pemphigoid
Authors: J.A. SAVIN
Journal: British Journal of Dermatology (1981)

The records of twenty‐eight patients dying with pemphigus vulgaris, and forty‐two with pemphigoid, have been examined for factors affecting the length of their survival. Age at onset of the disease is important, old patients dying significantly more quickly than young ones. A short pre‐treatment phase signifies a fulminating course in pemphigus vulgaris but not in pemphigoid.
Sera from patients with the acquired immunodeficiency syndrome inhibit production of interleukin-2 by normal lymphocytes.
Authors: J P Siegel, J Y Djeu, N I Stocks, H Masur, E P Gelmann, G V Quinnan
Journal: Journal of Clinical Investigation (1985)

We studied the effects of sera from patients with the acquired immunodeficiency syndrome (AIDS) on interleukin-2 (IL-2) production to help elucidate the mechanism of immunodeficiency. Compared with sera from healthy controls, sera from AIDS patients suppressed phytohemagglutinin (PHA)-induced IL-2 production by normal blood mononuclear cells. Sera from homosexual contacts of AIDS patients and from adults with acute cytomegalovirus infection generally lacked this suppressive activity. The effect of the AIDS sera could not be attributed to absence of a stimulatory or nutritive factor, to inactivation of IL-2, to inhibition of the IL-2 assay, nor to increased turnover of IL-2. The suppressive effect of the sera was not mediated by radiosensitive or T8 antigen-bearing suppressor cells or by increased prostaglandin production or decreased interleukin-1 production. The sera acted directly on the groups of cells that produce IL-2, T cells and large granular lymphocytes; suppression occurred at an early, probably pretranslational, stage. When cells were incubated with AIDS sera and then washed, the suppressive effect persisted. The sera did not cause direct or complement-mediated cytotoxic effects on normal mononuclear cells nor did they suppress PHA-induced interferon production, nor proliferation of T lymphoblasts or lymphocyte lines. The suppressive effect was not mediated by interferon, cortisol, immunoglobulin G or M, or immune complexes. The activity was stable at pH 3, pH 10, and 60 degrees C; inactivated at 100 degrees C; and not ether extractable. Because IL-2 plays a central role in the development of many immune responses, the serum factor(s) that inhibits IL-2 production could contribute significantly to the immunodeficiency of AIDS.
A4.6 TGF-β is a potent inducer of nerve growth factor in articular cartilage via the ALK5-SMAD2/3 pathway. Potential role in OA related pain?
Authors: EN Blaney Davidson, APM van Caam, EL Vitters, MB Bennink, E Thijssen, WB van den Berg, MI Koenders, PLEM van Lent, FAJ van de Loo, PM van der Kraan
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Pain is the main problem for patients with OA. Pain is linked to inflammation, but in OA a subset of patients suffer from pain without inflammation, indicating an alternative source of pain. NGF inhibition very efficiently blocks pain during OA, but the exact source of NGF is unclear. NGF is elevated in animal models of OA with cartilage damage without inflammation. TGF-beta is released from cartilage upon damage. We investigated whether TGF-beta could contribute to NGF expression in the joint and which signalling route is involved. <h3>Materials and methods</h3> Murine and human chondrocyte cell lines, primary bovine and human chondrocytes, and cartilage explants from bovine metacarpal joints and human OA joints were stimulated with TGF-β1 and/or IL-1β as a positive control for NGF induction. We analysed NGF expression on mRNA level with QPCR and stained human OA cartilage for NGF immunohistochemically. Cultures were additionally pre-incubated with inhibitors for TAK1 (oxozeaenol), Smad2/3 (SB-505124) or Smad1/5/8 (LDN-193189) signalling to identify the TGF-β pathway inducing NGF. <h3>Results</h3> TGF-beta consistently induced NGF expression at higher levels than IL-1 in all of our experimental models: murine, bovine and human origin, in cell lines, primary chondrocytes and explant cultures. We initially expected TAK1 to be dominant and pivotal in NGF induction due to involvement in both IL-1 and TGF-beta signalling. TAK1 inhibition consistently reduced (but not blocked) TGF-β-induced NGF whereas it fully blocked IL-1β-induced NGF expression. In contrast, ALK5-Smad2/3 inhibition fully blocked TGF-β-induced NGF expression. Blocking the Smad1/5/8 pathway did not affect NGF expression. Human OA primary chondrocytes had a large variation in basal NGF levels (mRNA and histology). TGF-β consistently induced a higher level of NGF induction than IL-1 in these chondrocytes despite variable basal levels of NGF when stimulating human OA cartilage explants with TGF-beta, NGF expression increased, which could be fully blocked by inhibiting ALK5-Smad2/3 signalling. <h3>Conclusions</h3> This is the first time that it is shown that TGF-β induces NGF expression in (primary) chondrocytes. Moreover, we found that TGF-beta consistently induced NGF at higher levels than IL-1. In addition, IL-1-induced NGF could be fully abrogated by TAK1 inhibition, but this only reduced TGF-beta-induced NGF expression. In contrast blocking signalling via ALK5-Smad2/3 fully abrogated the TGF-beta-induced NGF expression. Clearly, our data show that there are sources of NGF other than inflammation in the joint and that this should be taken into account when studying pain in OA.
Hepatitis B virus variants in patients receiving lamivudine treatment with breakthrough hepatitis evaluated by serial viral loads and full-length viral sequences
Authors: Chun-Jen Liu, Pei-Jer Chen, Ming-Yang Lai, Jia-Horng Kao, Ding-Shinn Chen
Journal: Hepatology (2001)

Both viral loads and genome variations have been implicated in the pathogenesis of acute exacerbation of chronic hepatitis B. Hepatitis B exacerbation in patients receiving lamivudine treatment represented a unique setting to clarify their importance. Three organ recipients with posttransplantation hepatitis B exacerbation and 3 patients with chronic hepatitis B were studied. All received lamivudine treatment and their alanine aminotransferase (ALT) levels and hepatitis B virus (HBV) loads were regularly followed. Full-length genomic sequences before and during lamivudine treatment were determined in patients who had breakthrough of serum HBV DNA or elevation of serum ALT. Breakthrough of serum HBV DNA occurred after 6 to 15 months of lamivudine treatment in all. A rapid increase of viral load accompanying the emergence of tyrosine-methionine-aspartate-aspartate (YMDD) variant was followed by hepatitis B exacerbation in each patient. The mean number of nucleotide and amino acid substitutions per genome pair was equivalent in immunosuppressed or immunocompetent patients (6.3 vs. 6.3 for nucleotide, P &gt; .05; 6.0 vs. 6.7 for amino acid, P &gt; .05). Changes of nucleotide and amino acid beyond the YMDD motif were distributed along the whole HBV genome but none occurred within the known B-cell epitopes and human leukocyte antigen class I- or II-restricted T-cell epitopes. Our results suggest that a resurgence of viral load rather than changes of the known immunogenic viral epitopes is more closely associated with the development of hepatitis B exacerbation after the emergence of YMDD variants in patients receiving lamivudine treatment. (Hepatology 2001;34:583-589.)
Echocardiographic findings in systemic amyloidosis: Spectrum of cardiac involvement and relation to survival
Authors: Luis Cueto-Garcia, Guy S. Reeder, Robert A. Kyle, Douglas L. Wood, James B. Seward, James Naessens, Kenneth P. Offord, Philip R. Greipp, William D. Edwards, A. Jamil Tajik
Journal: Journal of the American College of Cardiology (1985)
Bile salt export pump expression: Can immunohistochemistry in isolation mislead?
Authors: A. S. Knisely
Journal: Hepatology (2013)

Moghadamrad et al.1 describe a woman with gallstones, intrahepatic cholestasis, and normal-range serum gamma-glutamyl transpeptidase activity; a single identifiable mutation in ABCB11 (encoding bile salt export pump, BSEP); and reduced expression by centrilobular hepatocytes of immunohistochemically demonstrable BSEP. They propose that the single-copy mutation found in ABCB11, c.221T>C/p.Ile74Arg, underlay cholestatic liver disease in their patient. I should like to believe them, but in my opinion their findings, as presented, do not adequately support their proposal. Predicted pathogenicity of the c.221T>C mutation is not addressed and, regrettably, findings using appropriate immunohistochemical controls are not supplied. Immunohistochemically assessed expression of other canalicular transporters, homologs of BSEP such as the products of ABCB4 (multidrug resistance protein 3, MDR3) and ABCC2 (Dubin-Johnson protein/multidrug resistance-associated protein 2, MRP2), should have been described to permit the reader to judge if a generalized debility of adenosine triphosphate-binding cassette transporter expression, affecting centrilobular hepatocytes in particular, might have led nonspecifically to the abnormality of BSEP expression presented. The authors might also have discussed the possibility that mutation in genes with products that specifically modulate expression of wild-type BSEP, as reported for ATP8B1 through farnesoid X receptor,2 contributed to the decreased BSEP expression that they report. I caution investigators against reliance on immunohistochemical studies in which expression of an individual protein is assessed in isolation. I shall welcome information from Moghadamrad et al. on the predicted pathogenicity of the p.Ile74Arg substitution mutation in ABCB11, on results of immunostaining for MDR3 and MRP2 in their patient's liver-biopsy specimen, and on results of sequencing in their patient of genes with products that affect BSEP expression. A.S. Knisely, M.D. King's College Hospital Institute of Liver Studies London, UK
Delhi's government asks private hospitals why they aren't providing free care to the poor
Authors: M. Chaudhuri
Journal: BMJ (2012)

The High Court in Delhi has written to 10 leading private hospitals asking them to explain why they have not complied with an order passed a decade ago that they must treat a proportion of poor patients free of charge.

On 15 November 2002 the government of the National Capital Territory gave some 43 hospitals in Delhi land at minimal costs with the proviso that at least 10% of beds be reserved for poor people, who would be given free treatment when admitted as inpatients, and that 25% of patients would get free drugs …
PWE-164 Utilizing Integrative Genomic Analysis and Proteomics to Decipher the Biology and Therapeutic Potential of Trim44 in Oesophageal Adenocarcinoma and Breast Cancer
Authors: J C Ong, N Shannon, J Skehel, K Wang, O M Rueda, C E Walker, R Hardwick, C Caldas, R C Fitzgerald
Journal: Gut (2013)

<h3>Introduction</h3> The incidence of oesophageal adenocarcinoma (OAC) has quadrupled in the last 30 years and outcomes remain poor. We have previously identified TRIM44 as an independent prognostic gene commonly amplified in OAC and breast cancer. However, the exact biology of TRIM44 and its role in epithelial cancers remain unclear <h3>Methods</h3> Gene set enrichment analysis (GSEA) was performed on gene expression microarray data of oesophageal (n = 146) and breast cancers (METABRIC, n = 1980) to identify signalling pathways activated by TRIM44 amplification and overexpression. Mass spectrometry was used to identify binding partners of TRIM44 in both endogenous and overexpression settings. Validation of the mass spectrometry results were performed using reciprocal co-immunoprecipitations experiments <h3>Results</h3> GSEA performed on OAC samples identified 14 pathway signatures that were significantly enriched with TRIM44 overexpression. To validate these results, GSEA was performed on the METABRIC dataset and this revealed that the PI3K-AKT-mTOR signalling was the only pathway out of the 14 identified signatures to be significantly overenriched in samples with TRIM44 amplification in OAC and breast cancer (p &lt; 0.05). Mass spectrometry of immunoprecipitated TRIM44 identified 2 novel binding partners of TRIM44 -- a ring finger protein associated with activation of c-jun and a tumour metastatic gene shown to directly activate the PI3K-AKT-mTOR signalling pathway. Validation of these two binding partners was successfully performed with endogenous co-immunoprecipitation of TRIM44 in HSC-39, a cell line with high level amplifications of TRIM44; demonstrating that both binding partners associate with TRIM44 in the endogenous setting. <h3>Conclusion</h3> Integrative genomic analysis and GSEA provided an insight into the pathways activated by TRIM44. The mTOR pathway was consistently associated with TRIM44 amplification and overexpression. A proteomics approach identified two potential mechanistic explanations how TRIM44 activates the mTOR pathway. Clinically, these findings open up the possibilities of using mTOR inhibitors or peptides disrupting TRIM44 protein interactions to treat TRIM44 amplified tumours. <h3>Disclosure of Interest</h3> None Declared.
Hypercoagulability and Fibrinolysis: An Experimental Study.
Authors: Daniel Deykin
Journal: Annals of Internal Medicine (1968)

s1 May 1968Hypercoagulability and Fibrinolysis: An Experimental Study.Daniel Deykin, M.D., Thomas P. Ashford, M.D., Peter SilversmithDaniel Deykin, M.D.Search for more papers by this author, Thomas P. Ashford, M.D.Search for more papers by this author, Peter SilversmithSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-68-5-1167_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe clinical syndrome of accelerated intravascular coagulation and simultaneously occurring fibrinolysis is being recognized with increasing frequency. The pathogenesis of the fibrinolytic component of this syndrome remains obscure. The present experiments were undertaken to determine whether activation of the intrinsic coagulation sequence in vivo could itself elicit fibrinolysis. Transient and intense hypercoagulability was produced in anesthetized rabbits by the infusion of normal thrombin-free human serum (1 ml/kg) into the marginal ear veins. Blood samples were drawn before and at intervals after the infusion of serum. The time of onset of coagulation and the rate of fibrin polymerization were determined by... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Massachusetts PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1968Volume 68, Issue 5Page: 1167-1167KeywordsBloodFibrinFibrinolysisPathogenesisRabbitsVeins ePublished: 1 December 2008 Issue Published: 1 May 1968 PDF downloadLoading ...
2008 DOSE-RANGING, THREE-DAY MONOTHERAPY STUDY OF THE HCV NS3 PROTEASE INHIBITOR GS-9256
Authors: E.J. Lawitz, T.C. Marbury, B.D. Vince, N. Grunenberg, M. Rodriguez-Torres, M.P. De Micco, J.N. Tarro, M.J. Shelton, S. West, J. Zong, A. Bae, K. Wong, H.-M. Mo, D. Oldach, W. Delaney, F. Rousseau
Journal: Journal of Hepatology (2010)
The Transparency of the Cornea: A Symposium Organized by the Council for International Organizations of Medical Sciences, Established Under the Joint Auspices of UNESCO and WHO
Authors: Daniel Snydacker
Journal: JAMA (1960)

Of all the remarkable structures of the vertebrate anatomy, truly one of the most remarkable is the cornea. Though the eye may be the "window of the soul" and the cornea is surely the window of the eye, remarkably little concerning the physiology of the cornea is known. The papers which constitute this symposium held in 1958 summarize the current thinking in regard to the anatomy of the cornea, the reasons for its transparency, its metabolism, and the abnormalities of its metabolism which take place in various dystrophies. The clinician should find the section dealing with corneal grafting particularly interesting. The reasons for the success or failure of the graft are presented in a lucid manner. The discussions which took place after each paper are included and are of particular interest. Sir Stewart Duke-Elder, who moderated the symposium, has an admirable knack of keeping the discussions on the track and
Yes, even human brown fat is on fire!
Authors: Barbara Cannon, Jan Nedergaard
Journal: Journal of Clinical Investigation (2012)

That adult humans possess brown fat is now accepted - but is the brown fat metabolically active? Does human brown fat actually combust fat to release heat? In this issue of the JCI, Ouellet et al. demonstrate that metabolism in brown fat really is increased when adult humans are exposed to cold. This boosts the possibility that calorie combustion in brown fat may be of significance for our metabolism and, correspondingly, that the absence of brown fat may increase our proneness to obesity - provided that brown fat becomes activated not only by cold but also through food-related stimuli.
Burn-Out: The High Cost of High Achievement
Authors: Phil Gunby
Journal: JAMA (1981)

What is burn-out? You can get a lot of opinions, including the view (perhaps a semantic argument in some instances) that there is no such thing. In the terms of this book, it is often a condition in which likely-to-succeed persons begin "exhibiting signs of something amiss between themselves and their environment." Clinical psychologist Freudenberger says he has experienced it himself; that what is happening is not just something inside the persons affected. No, suggest the authors, "much had to be attributed to the times we live in, the swift acceleration of change, the depersonalization of neighborhoods, schools, and work situations." In any case, whatever burn-out is or is not, it is a much-discussed subject these days, and physicians may want to examine as many viewpoints as possible. This book, of course, offers one of them.
Rights and Health Care — Beyond Equity and Efficiency
Authors: Charles Fried
Journal: New England Journal of Medicine (1975)

Abstract Economic analysis in general has difficulty accommodating the concept of rights. The economic analysis of health care in particular proposes triage as the model of a rational delivery system, with no place for traditional ethical limits and obligations. Familiar arguments based on resource constraints do not prove that rights cannot reasonably be recognized. Nor are rights in general and rights in medical care in particular adequately respected by attending to considerations of just distribution or equity. Rights in medical care are different from rights to medical care, and must be respected in any decent, advanced society. That such rights may be overridden in emergencies does not mean that respect for rights is not a constraint upon the pursuit of equity and efficiency. (N Engl J Med 293:241–245, 1975)
Differential Diagnosis of RSR' and Dominant R Wave Patterns in Right Chest Leads
Authors: Marcio M. Menendez
Journal: JAMA (1966)

Dominant R waves or RSR' patterns in right precordial leads frequently present problems in differential diagnosis. Either may be a normal variant or an indication of heart disease. <h3>RSR' Variants</h3> Variants of the RSR' pattern are common in normal children and not uncommon in young adults. The normal R' wave is attributed to late activation of the crista supraventricularis. It is often difficult to distinguish normal from abnormal and one of the knottiest problems is the RSR' complex in lead V<sub>1</sub>or V<sub>2</sub>that casts suspicion on the otherwise normal patient and her tracing (Figure,<i>d</i>). Some general rules are helpful:<sup>1</sup> An R' wave is probably normal in V2 if it is not found in V1; it is probably normal in V1 if not present in V3R or a low V1. An R' wave is probably abnormal if it is associated with a primary R
Single L-type Ca2+ channel regulation by cGMP-dependent protein kinase type I in adult cardiomyocytes from PKG I transgenic mice
Authors: Frank Schröder, Gunnar Klein, Beate Fiedler, Michaela Bastein, Nicole Schnasse, Anja Hillmer, Sandra Ames, Stepan Gambaryan, Helmut Drexler, Ulrich Walter, Suzanne M Lohmann, Kai C Wollert
Journal: Cardiovascular Research (2003)

Objective: Calcium entry via the L-type Ca2+ channel (LTCC) is crucial for excitation–contraction (EC) coupling and activation of Ca2+-dependent signal transduction pathways in cardiac myocytes. Both nitric oxide (NO), signaling via cGMP, and acetylcholine, signaling via the muscarinic receptor, have been identified as negative regulators of β-adrenoreceptor-stimulated LTCC activity in cardiac myocytes. Methods: To examine the potential role of cGMP-dependent protein kinase type I (PKG I) in the inhibitory effects of NO/cGMP and the muscarinic receptor on LTCC activity, we generated transgenic (TG) mice overexpressing PKG I selectively in cardiac myocytes under the control of the α-myocin heavy chain promoter. Single LTCC-gating properties were assessed in isolated ventricular myocytes from adult wild-type (WT) and PKG I transgenic (TG) mice. Results: Basal LTCC activity (peak average current, mean open probability, mean availability) was significantly decreased by the nitric oxide donor DEA-NO (0.1 μmol/l) and the cGMP-analog 8-Br-cGMP (1 mmol/l) in TG but not in WT cardiac myocytes. Conversely, muscarinic (carbachol, 1 μmol/l) stimulation had no significant effect on basal LTCC activity in either WT or TG cardiac myocytes. β-Adrenergic stimulation with isoproterenol (1 μmol/l) increases single LTCC activity in WT and TG cardiac myocytes to the same extent. The inhibitory effects of DEA-NO and 8-Br-cGMP on isoproterenol activation of the LTCC current were significantly enhanced in TG as compared to WT cardiac myocytes. By contrast, carbachol inhibition of isoproterenol-stimulated single LTCC activity was not enhanced in TG cardiac myocytes. Conclusion: Transgenic overexpression of PKG I augments NO/cGMP inhibition but not muscarinic inhibition of single LTCC activity, indicating that PKG I is a downstream target for NO/cGMP, but not the muscarinic receptor in adult cardiac myocytes.
Androgen Receptor Signaling Fuels DNA Repair and Radioresistance in Prostate Cancer
Authors: Jiri Bartek, Martin Mistrik, Jirina Bartkova
Journal: Cancer Discovery (2013)

Abstract Summary: Successful treatment by genotoxic modalities including radiotherapy is commonly hampered by treatment resistance in advanced cancers. Two new studies now reveal that androgen receptor signaling transcriptionally upregulates a large subset of DNA repair genes, thereby enhancing the repair capacity and promoting radioresistance of prostate cancer. These results provide a mechanistic rationale for a combined treatment by ionizing radiation and androgen deprivation therapy. Cancer Discov; 3(11); 1222–4. ©2013 AACR. See related article by Polkinghorn et al., p. 1245 See related article by Goodwin et al., p. 1254
FOREIGN BODIES IN STOMACH
Authors: E. Raymond Hildreth
Journal: JAMA (1934)

This case is reported because of its general interest and to add it to the literature on the curiosities of medicine. M. H. L., a woman, aged 46, married, was admitted to the State Hospital at Central Islip, Feb. 10, 1932. The diagnosis was involution melancholia with suicidal tendencies. Sept. 6, 1933, she vomited and complained of constipation. A large hard mass was palpable in the upper left quadrant of the abdomen. Liquid petrolatum and enemas were administered daily, with little appreciable effect on the mass. September 11, a roentgenogram showed a mass of what appeared to be metallic spoons in the stomach. September 12, a laparotomy was performed. An incision was made in the upper anterior surface of the stomach and the following objects were removed: forty-eight teaspoons, one teaspoon handle, three bolts, one nut, one prune pit, one button, one small piece of glass, two pieces of spring