tbuckley/cabot-search huggingface dataset:
The Neuroendocrine-Derived Peptide Parathyroid Hormone–Related Protein Promotes Prostate Cancer Cell Growth by Stabilizing the Androgen Receptor
Authors: John DaSilva, Daniel Gioeli, Michael J. Weber, Sarah J. Parsons
Journal: Cancer Research (2009)

Abstract During progression to an androgen-independent state following androgen ablation therapy, prostate cancer cells continue to express the androgen receptor (AR) and androgen-regulated genes, indicating that AR is critical for the proliferation of hormone-refractory prostate cancer cells. Multiple mechanisms have been proposed for the development of AR-dependent hormone-refractory disease, including changes in expression of AR coregulatory proteins, AR mutation, growth factor–mediated activation of AR, and AR protein up-regulation. The most prominent of these progressive changes is the up-regulation of AR that occurs in &amp;gt;90% of prostate cancers. A common feature of the most aggressive hormone-refractory prostate cancers is the accumulation of cells with neuroendocrine characteristics that produce paracrine factors and may provide a novel mechanism for the regulation of AR during advanced stages of the disease. In this study, we show that neuroendocrine-derived parathyroid hormone–related protein (PTHrP)–mediated signaling through the epidermal growth factor receptor (EGFR) and Src pathways contributes to the phenotype of advanced prostate cancer by reducing AR protein turnover. PTHrP-induced accumulation of AR depended on the activity of Src and EGFR and consequent phosphorylation of the AR on Tyr534. PTHrP-induced tyrosine phosphorylation of AR resulted in reduced AR ubiquitination and interaction with the ubiquitin ligase COOH terminus of Hsp70-interacting protein. These events result in increased accumulation of AR and thus enhanced growth of prostate cancer cells at low levels of androgen. [Cancer Res 2009;69(18):7402–11]
Challenges of genetic counseling in patients with autosomal dominant diseases, such as the hyper-IgE syndrome (STAT3-HIES)
Authors: Benedikt D. Spielberger, Cristina Woellner, Gregor Dueckers, Julie Sawalle-Belohradsky, Beate Hagl, Katja Anslinger, Birgit Bayer, Kathrin Siepermann, Tim Niehues, Bodo Grimbacher, Bernd H. Belohradsky, Ellen D. Renner
Journal: Journal of Allergy and Clinical Immunology (2012)
Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances11The PAcing THerapies in Congestive Heart Failure (PATH-CHF) study was supported by a grant from the Guidant Corporation (St. Paul, Minnesota). Drs. Pochet, Salo, Kramer and Spinelli have corporate appointments with Guidant Corp.
Authors: Christoph Stellbrink, Ole-Alexander Breithardt, Andreas Franke, Stefan Sack, Patricia Bakker, Angelo Auricchio, Thierry Pochet, Rod Salo, Andrew Kramer, Julio Spinelli
Journal: Journal of the American College of Cardiology (2001)
Decreased B cell activating factor receptor expression on peripheral lymphocytes associated with increased disease activity in primary Sjogren's syndrome and systemic lupus erythematosus
Authors: J. Sellam, C. Miceli-Richard, J.-E. Gottenberg, M. Ittah, F. Lavie, C. Lacabaratz, N. Gestermann, A. Proust, O. Lambotte, X. Mariette
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To analyse B cell activating factor (BAFF) receptor (BAFF-R) expression on peripheral lymphocytes from patients with primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). <b>Patients and methods:</b> Peripheral blood mononuclear cells from 20 patients with pSS, 19 patients with SLE and 15 controls were examined by flow cytometry to investigate BAFF-R mean fluorescence intensity (MFI) on lymphocytes. BAFF-R mRNA level from isolated blood B cells of nine patients with pSS and eight controls was assessed by real-time quantitative reverse transcription-PCR. BAFF serum level was determined by ELISA. <b>Results:</b> In all subjects, BAFF-R was expressed on all naïve CD27− and memory CD27+ B-cells and was present on &lt;0.5% of T cells. The expression of BAFF-R on B cells was significantly decreased in patients with pSS as compared with controls (MFI = 7.8 vs 10.6, p = 0.001), and was intermediate in patients with SLE (MFI = 9.5). Serum BAFF level was inversely correlated with BAFF-R MFI (p = 0.007), but not because of competition between endogenous BAFF (at observed concentrations in patients) and the monoclonal antibody (11C1) detecting BAFF-R. BAFF-R mRNA levels did not differ between patients with pSS and controls (p = 0.48). BAFF-R MFI decreased after overnight culture with recombinant human BAFF (from 32.5 to 25.4, p = 0.03). Contrary to the serum BAFF level, BAFF-R expression was correlated with extraglandular involvement in pSS and SLE Disease Activity Index. <b>Conclusions:</b> BAFF-R expression is reduced on peripheral B cells of patients with pSS and SLE. This down-regulation occurs through a post-transcriptional mechanism and could be the consequence of chronic increase in BAFF. BAFF-R levels on B cells could be a novel activity biomarker in autoimmune diseases.
Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial
Authors: Simon J Griffin, Knut Borch-Johnsen, Melanie J Davies, Kamlesh Khunti, Guy EHM Rutten, Annelli Sandbæk, Stephen J Sharp, Rebecca K Simmons, Maureen van den Donk, Nicholas J Wareham, Torsten Lauritzen
Journal: The Lancet (2011)
A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C
Authors: M.-L. Yu, C.-Y. Dai, J.-F. Huang, N.-J. Hou, L.-P. Lee, M.-Y. Hsieh, C.-F. Chiu, Z.-Y. Lin, S.-C. Chen, M.-Y. Hsieh, L.-Y. Wang, W.-Y. Chang, W.-L. Chuang
Journal: Gut (2006)

The recommended treatment for patients infected with hepatitis C virus genotype 2 (HCV2) is pegylated interferon (peginterferon) and ribavirin for 24 weeks.To assess whether a shorter 16-week treatment is as effective as a standard 24-week treatment.Patients with HCV2 infection were randomised in a 1:2 ratio to either 16 weeks (n = 50) or 24 weeks (n = 100) of treatment with peginterferon alpha-2a (180 mug/week) and weight-based ribavirin 1000-1200 mg/day, with a 24-week follow-up period. A rapid virological response (RVR) was defined as seronegative for HCV RNA at 4 weeks of treatment, and the primary end point, sustained virological response (SVR), as seronegative for HCV RNA at the 24-week follow-up.The rate of RVR and SVR was 86% (43/50, 95% confidence interval (CI) 76% to 96%) and 94% (47/50, CI 87% to 100%), respectively, in the 16-week group, which was comparable to 87% (87/100, CI 80% to 94%) and 95% (95/100, CI 91% to 99%) in the 24-week group. Patients with RVR had a significantly higher SVR rate than patients without RVR in both 16-week (100% vs 57%, p = 0.015) and 24-week groups (98% vs 77%, p = 0.002). Multivariate analysis showed that RVR and age were independent factors associated with SVR. Both treatment arms were equally well tolerated. The incidence of alopecia was significantly higher in the 24-week group (49%) than in the 16-week group (20%, p = 0.001).16 weeks and 24 weeks of peginterferon treatment with weight-based ribavirin at a dose of 1000-1200 mg/day provided equal efficacy in patients with HCV2 who achieved RVR at 4 weeks.
Clinical Manifestations of Toxic Shock Syndrome
Authors: P. Joan Chesney
Journal: JAMA (1981)

Twenty-two women aged 13 to 44 years (mean, 22 years) with toxic shock syndrome (TSS) were hospitalized in Madison, Wis, between Aug 1, 1977, and Sept 1, 1980. Disease onset occurred during menses in 21 patients; all recovered. Notable sequelae included vocal cord paralysis and impaired finger sensation in two patients and recurrent disease in three. Coagulase-positive staphylococci were grown from the cervix or vagina in 11 of 12 women cultured. Previously undescribed features included vulvar cellulitis, hypocalcemia, hypophosphatemia, hypocholesterolemia, hyponatremia, lymphocytopenia, hypoferrinemia, and late convalescent hair and nail loss. Patients requiring dopamine hydrochloride had worse renal function, longer hospitalizations, and higher total serum bilirubin levels, and clinical onset earlier in menses. Originally reported in children, TSS now appears to be primarily a disease of menstruating women in whom recurrences are possible. (<i>JAMA</i>1981;246:741-748)
GSK3β Promotes Apoptosis after Renal Ischemic Injury
Authors: Zhiyong Wang, Andrea Havasi, Jonathan Gall, Ramon Bonegio, Zhijian Li, Haiping Mao, John H. Schwartz, Steven C. Borkan
Journal: Journal of the American Society of Nephrology (2010)

The mechanism by which the serine-threonine kinase glycogen synthase kinase-3beta (GSK3beta) affects survival of renal epithelial cells after acute stress is unknown. Using in vitro and in vivo models, we tested the hypothesis that GSK3beta promotes Bax-mediated apoptosis, contributing to tubular injury and organ dysfunction after acute renal ischemia. Exposure of renal epithelial cells to metabolic stress activated GSK3beta, Bax, and caspase 3 and induced apoptosis. Expression of a constitutively active GSK3beta mutant activated Bax and decreased cell survival after metabolic stress. In contrast, pharmacologic inhibition (4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione [TDZD-8]) or RNA interference-mediated knockdown of GSK3beta promoted cell survival. Furthermore, RNA interference-mediated knockdown of Bax abrogated the cell death induced by constitutively active GSK3beta. In a cell-free assay, TDZD-8 inhibited the phosphorylation of a peptide containing the Bax serine(163) site targeted by stress-activated GSK3beta. In rats, TDZD-8 inhibited ischemia-induced activation of GSK3beta, Bax, and caspase 3; ameliorated tubular and epithelial cell damage; and significantly protected renal function. Taken together, GSK3beta-mediated Bax activation induces apoptosis and tubular damage that contribute to acute ischemic kidney injury.
Activation of Estrogen Receptor-α by the Anion Nitrite
Authors: David J. Veselik, Shailaja Divekar, Sivanesan Dakshanamurthy, Geoffrey B. Storchan, Jasmine M.A. Turner, Kelly L. Graham, Li Huang, Adriana Stoica, Mary Beth Martin
Journal: Cancer Research (2008)

Abstract In this study, the ability of nitrite and nitrate to mimic the effects of estradiol on growth and gene expression was measured in the human breast cancer cell line MCF-7. Similar to estradiol, treatment of MCF-7 cells with either 1 μmol/L nitrite or 1 μmol/L nitrate resulted in ∼4-fold increase in cell growth and 2.3-fold to 3-fold increase in progesterone receptor (PgR), pS2, and cathepsin D mRNAs that were blocked by the antiestrogen ICI 182,780. The anions also recruited estrogen receptor-α (ERα) to the pS2 promoter and activated exogenously expressed ERα when tested in transient cotransfection assays. To determine whether nitrite or nitrate was the active anion, diphenyleneiodonium was used to inhibit oxidation/reduction reactions in the cell. The ability of diphenyleneiodonium to block the effects of nitrate, but not nitrite, on the induction of PgR mRNA and the activation of exogenously expressed ERα suggests that nitrite is the active anion. Concentrations of nitrite, as low as 100 nmol/L, induced a significant increase in PgR mRNA, suggesting that physiologically and environmentally relevant doses of the anion activate ERα. Nitrite activated the chimeric receptor Gal-ER containing the DNA-binding domain of GAL-4 and the ligand-binding domain of ERα and blocked the binding of estradiol to the receptor, suggesting that the anion activates ERα through the ligand-binding domain. Mutational analysis identified the amino acids Cys381, His516, Lys520, Lys529, Asn532, and His547 as important for nitrite activation of the receptor. [Cancer Res 2008;68(10):3950–8]
Cryoimmunoglobulinemia in rheumatoid arthritis. Significance in serum of patients with rheumatoid vasculitis.
Authors: M Weisman, N Zvaifler
Journal: Journal of Clinical Investigation (1975)

Cryogloculins were examined in a standardized manner in an unselected group of 35 patients with rheumatoid arthritis (RA) and 8 patients with RA complicated by cutaneous vasuclitis and neuropathy. Optimum conditions for detection and characterization of cryoglobulins were established; the proportion of resolubilized to total precipitable protein remained constant in an individual patient under these conditions. All 8 vascultis patients and 9 of 35 other patients with RA exhibited cryoglobulins; total protein and immunoglobin content were significantly higher in the cryoglobulins of patients with vasculitis. Immunoglobulins G and M constituted two-thirds and three-quarters of the total protein in the cryoglobulins from uncomplicated rheumatoid and vasculitis patients, respectively. Serum antiglobulin titers were higher, and serum C3 levels were lower, in vasculitis patients compared to rheumatoid patients without vasclitis. Anti-gamma globulin activity was detected in all cryoglobulins from vasculitis patients. Cryoglobulin IgG and IgM were polyclonal. Density gradient analyses demonstrated the majority of the cryoglobulin activity to reside in the 19S IgM fraction. There was no evidence of a light weight (8S) IgM. A monoclonal rheumatoid factor did not detect 7S-ANTI-7S complexes in the cryoprecipitates, but acid eluates from some cryoglobulins absorbed with insoluble IgG revealed an antiglobulin of the IgG class. Serial studies performed on vasculitis patients treated with cyclophosphamide disclosed a relationship between clinical evidence of vasculitis and the presence of cryoglobulins. The antigen (IgG) and antibody (largely IgM rheumatoid factor) nature of these cryglobulins is presented as evidence that the widespread vascular complications of RA are mediated, at least in part, by circulating immune complexes.
Light and Scanning Electron Microscopy of Exfoliated Bladder Epithelial Cells in Rats Fed N -[ 4-(5-Nitro-2-furyl)-2-thiazolyl]formamide 2 3
Authors: J. B. Jacobs, M. Arai, S. M. Cohen, G. H. Friedell
Journal: JNCI Journal of the National Cancer Institute (1976)

Urine specimens obtained periodically from weanling male F344 rats fed 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) for 25 weeks followed by control diet for an additional 35 weeks, were examined by light microscopy (LM) and scanning electron microscopy (SEM). LM revealed red blood cells and atypical transitional cells in the urine at 25 and 43 weeks, when microinvasive transitional cell carcinoma was present. Malignant transitional cells were seen in the urine by LM at 60 weeks, when muscle invasion was present in histologic sections. However, SEM showed pleomorphic microvilli on exfoliated urothelial cells as early as 10 weeks after the beginning of FANFT administration, and the microvilli became increasingly pleomorphic as the bladder lesions progressed to muscle invasion at 60 weeks. Noninvasive tumors were present in histologic sections of rat bladders examined at the end of 10 weeks of FANFT administration. The numerous microvilli on exfoliated bladder tumor cells were in sharp contrast to the peaked micro ridges of normal exfoliated superficial cells.
Whole genome and global expression profiling of Dupuytren's disease: systematic review of current findings and future perspectives
Authors: B Shih, S Watson, A Bayat
Journal: Annals of the Rheumatic Diseases (2012)

<h3></h3> Dupuytren9s disease (DD) is a common fibroproliferative disorder affecting the palmar fascia, which may lead to permanent contracture of the affected digit. Profiling studies investigating DD at whole-genomic, transcriptomic and proteomic levels have been carried out, from which large numbers of candidate genes potentially involved in DD have been reported. This review focuses on identifying genes reported by multiple studies or validated by multiple experimental techniques, as well as signalling pathways suggested to contribute to DD. Meta-analysis was also carried out on three microarray datasets. Twenty-one genes were found to be reported as dysregulated in multiple gene expression microarrays, seven of which have been further validated by other experimental methods. Sixty-four genes determined to be dsyregulated by meta-analysis correlate to those reported by published microarray studies. In addition, several pathways have been proposed to be involved in DD by whole-genome or global expression profiling. Further investigation in these genes and pathways, and correlating them to genotypes or environmental factors for DD, may aid in further elucidation of mechanisms involved in DD pathogenesis.
Influence of culturing on the survival of major histocompatibility complex- compatible and -incompatible thyroid grafts in rats
Authors: ST Bartlett, AS Jennings, C Yu, A Naji, CF Barker, WK Silvers
Journal: The Journal of Experimental Medicine (1983)

Culturing Fischer thyroid fragments promotes their survival in major histocompatibility complex (MHC) -incompatible ACI rats but not in MHC- compatible Lewis animals.
SPONTANEOUS RECOVERY FROM NUTRITIONAL MACROCYTIC ANEMIA IN YOUNG SWINE FOLLOWING INITIAL ESTRUS
Authors: Susan Gower Smith, Raymond Reiser, George T. Harrell
Journal: Journal of Clinical Investigation (1941)

Spontaneous recovery from a severe macrocytic anemia produced experimentally in young swine by a prolonged partial deficiency of the vitamin B-complex has not been reported previously.The present communication deals with such a study.or combination of synthetic factors has proven effective as the extrinsic factor.Due to the varied hematopoietic response of different species to the same treatment, any study involving anemia demands care in the selection of TABLE I Correlation of age, sex, weight, diet and performance of all the animals Weight Time* un-Time* un-
Incomplete Left Bundle-Branch Block
Authors: S. SERGE BAROLD, JOSEPH W. LINHART, FRANK J. HILDNER, ONKAR S. NARULA, PHILIP SAMET
Journal: Circulation (1968)

Rate-dependent intermittent incomplete and complete left bundle-branch block (LBBB) is described in a patient without other evidence of heart disease. Continuous electrocardiographic tracings revealed QRS complexes intermediate in configuration between normal conduction and complete LBBB during the transitional phase from normal to abnormal conduction. This provided an opportunity to study the various grades of incomplete LBBB in man. During the incomplete LBBB phase, the morphology of the QRS complexes bore a close resemblance to the QRS form in the Wolff-Parkinson-White syndrome (type B). The differences between these two entities are emphasized.
Bilateral targeted lung denervation in patients with COPD in a single procedure
Authors: Arschang Valipour, Christophe Pison, Romain Kessler, Gaetan Deslee
Journal: European Respiratory Journal (2014)

Background: Acetylcholine derived from parasympathetic nerves is a well-validated pharmacologic target to treat patients with COPD. Unfortunately, long-term compliance with inhaled bronchodilators is poor. Targeted lung denervation (TLD) is a novel bronchoscopic therapy for COPD that ablates parasympathetic pulmonary nerves along the main bronchi.

Aim: Demonstrate feasibility and safety of treating both lungs in a single TLD procedure.

Methods: A prospective, multicenter, study of patients with COPD (FEV1/FVC 15% reversible to ipratropium) was performed evaluating safety and feasibility of TLD ([NCT01716598][1]) using a lung denervation system (Holaira, Inc., USA). Patients underwent bilateral TLD in a single procedure following baseline assessment off and on tiotropium and repeat assessment at 30 and 90 days after TLD.

Results: Fifteen patients (47% male, age 63.2±4.0 yrs) underwent TLD at 15 watts. TLD was technically successful 100% of the time. Procedure time was 46±11 minutes per lung. At baseline off tiotropium, FEV1 and 6MWT distance were 0.77±0.24 liters (l) & 354±139 meters (m) respectively; at baseline on tiotriopium 1.09±0.22 l & 406±111 m; 30 days following TLD off tiotropium 1.09±0.32 l & 369±126 m; and 90-days 1.02±0.32 liters & 409±108 m. There were no procedural complications. Six respiratory adverse events, 1 serious adverse event (tachycardia at 85 days, now stable) and no hospitalizations occurred within 90 days of TLD.

Conclusion: TLD delivered to both lungs in a single procedure is feasible and safe with few 90-day respiratory related adverse events. TLD improves FEV1 and 6MWT distance similarly to inhaled long-acting muscarinic antagonists.

 [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01716598&atom=%2Ferj%2F44%2FSuppl_58%2F1775.atom
Use of F-18 Fluorodeoxyglucose Positron Emission Tomography With Dual-Phase Imaging to Identify Intraductal Papillary Mucinous Neoplasm
Authors: Masayoshi Saito, Takeshi Ishihara, Motohisa Tada, Toshio Tsuyuguchi, Rintaro Mikata, Yuji Sakai, Katsunobu Tawada, Harutoshi Sugiyama, Jo Kurosawa, Masayuki Otsuka, Yoshitaka Uchida, Katsuhiro Uchiyama, Masaru Miyazaki, Osamu Yokosuka
Journal: Clinical Gastroenterology and Hepatology (2012)
Introductory Address Delivered at the Opening of St. Mary's Hospital Medical School, October 2nd, 1865
Authors: C. H. Jones
Journal: BMJ (1865)

GE ENrLESIEN,-The time-honoured custom of pre- facingnt of each session of imedip study by agn a4de,ss, delivered by one of the'teachers of each qchool, has much, I think, to commeid it to our approval; artd one of its advant-ages gIab b:e this -that itaf fokds us an opportunity of reviewing our position, an4 setti4ng before our minds the chief fea- tures of ithe changing scene.It seems to be a natural tendency implanted in us all to portion out the time given to us, and to pause at the end of various periods, and cQnsider more or less closely what our prooress has Ebeen, and what our prospects appear.The wise man, deeply conscious of.thevalue of time, will be ever desirous thus to pause and ,con- sider his ways; and even the most heedlosa and un- thinking can hardly avoid some reflection as the stream of time, which is bearing him on, turns, and opens before him, s it were, anQther of its long reaches.Wisely is it ordered, no doubt, that the year- returning JYLCWTos, our natal day,and the; coma- imencement of set" priodss of labour, should thus in- vite us to salutary thoghts;;which may become the spring of renewed and improved action.ei It M-ils to my lot to*day.to be: the one who is dep:ited by' the staff of St., Mary's to greet again the friends 'and older studntas of the hospital and school, and to held -,out th, right hand of-welcome to the younger, who come to s, now for, the first time.To each and all of these, and through them, perhaps, to others' around As, I mi,t strive.to say. a few words.AAd when I think.that,hmsany speaking, it is -extretnely i- .probableth&ti I shal ever have the like opportuknity again, I oannot but feel anxious that I may-be able to say sqmething which shall have voice-toi the heart.