tbuckley/cabot-search huggingface dataset:
A Role for the Clock Gene <i>Per1</i> in Prostate Cancer
Authors: Qi Cao, Sigal Gery, Azadeh Dashti, Dong Yin, Yan Zhou, Jiang Gu, H. Phillip Koeffler
Journal: Cancer Research (2009)

Abstract Circadian rhythms regulate diverse physiologic processes, including homeostatic functions of steroid hormones and their receptors. Perturbations of these rhythms are associated with pathogenic conditions, such as depression, diabetes, and cancer. Androgens play an important role in both normal development and carcinogenesis of the prostate. In the present study, we investigated a potential role for the core clock factor Per1 in the pathogenesis of prostate cancer. Serum-shocked synchronized prostate cancer cells displayed disrupted circadian rhythms compared with the normal prostate tissue. Using Oncomine to perform a meta-analysis of microarray expression studies, we found that Per1 is down-regulated in human prostate cancer samples compared with normal prostates. Reporter assays showed that Per1 inhibited transactivation of the androgen receptor (AR) both in 293T cells overexpressing the AR and in the prostate cancer cell line LNCaP. Forced expression of Per1 in LNCaP cells diminished the expression of known androgen-sensitive genes following stimulation with dihydrotestosterone. We showed that Per1 physically interacted with AR; in addition, we found that Per1 itself is regulated by androgens in prostate cancer cells. Overexpression of Per1 in prostate cancer cells resulted in significant growth inhibition and apoptosis. Our results support the emerging role of circadian genes as key players in malignant transformation. Further elucidating the connections between clock genes and the AR pathway could benefit the development of new therapeutic strategies for prostate cancer as well as provide insights into chronotherapy as a way to optimize current therapies. [Cancer Res 2009;69(19):7619–25]
Therapeutic effect of cytotoxic T lymphocyte antigen 4/immunoglobulin on a murine model of primary biliary cirrhosis
Authors: Amy Dhirapong, Guo-Xiang Yang, Steven Nadler, Weici Zhang, Koichi Tsuneyama, Patrick Leung, Stuart Knechtle, Aftab A. Ansari, Ross L. Coppel, Fu-Tong Liu, Xiao-Song He, Eric M. Gershwin
Journal: Hepatology (2012)

Collectively, the data in both humans and murine models of human primary biliary cirrhosis (PBC) suggest that activated T cells, particularly CD8 T cells, play a critical role in biliary cell destruction. Under physiological conditions, T-cell activation involves two critical signals that involve the major histocompatibility complex and a set of costimulatory molecules, which include a receptor on T cells termed cytotoxic T lymphocyte antigen 4 (CTLA-4). Germane to the studies reported herein, signaling by CTLA-4 has the potential to modulate costimulation and induce inhibitory signals. In this study, we have taken advantage of our well-defined murine model of PBC, in which mice are immunized with 2-octynoic acid coupled to bovine serum albumin (2OA-BSA), leading to the production of high-titer antimitochondrial autoantibodies (AMAs) and portal cellular infiltrates. To investigate the potential of CTLA-4-Ig (immunoglobulin) as an immunotherapeutic agent, we treated mice both before and after induction of autoimmune cholangitis. First, we demonstrate that CTLA-4-Ig treatment, begun 1 day before 2OA-BSA immunization, completely inhibits the manifestations of cholangitis, including AMA production, intrahepatic T-cell infiltrates, and bile duct damage. However, and more critically, treatment with CTLA-4-Ig, initiated after the development of autoimmune cholangitis in previously immunized mice, also resulted in significant therapeutic benefit, including reduced intrahepatic T-cell infiltrates and biliary cell damage, although AMA levels were not altered. Conclusion: These data suggest that an optimized regimen with CTLA-4-Ig has the potential to serve as an investigative therapeutic tool in patients with PBC.
Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan.
Authors: Y Kurokawa, S Takayama, Y Konishi, Y Hiasa, S Asahina, M Takahashi, A Maekawa, Y Hayashi
Journal: Environmental Health Perspectives (1986)

Long-term in vivo carcinogenicity tests of potassium bromate (KBrO3), sodium hypochlorite (NaClO), and sodium chlorite (NaClO2) have been conducted in Japan from 1977 to 1985. In these investigations, groups of approximately 50 male and 50 female F344 rats or B6C3F1 mice were given solutions of the compounds as their drinking water ad libitum at two dose levels determined on the basis of preliminary 13-week tests. Control animals were given distilled water. The carcinogenic potential of KBrO3 was tested by administering doses of 500 or 250 ppm to rats for 110 weeks. Significantly elevated incidences of renal cell tumors in males and females and mesotheliomas of the peritoneum in males as compared to controls were observed. When female mice were given KBrO3 at doses of 1000 or 500 ppm for 78 weeks, no significant differences in tumor incidences between experimental and control groups were apparent. NaClO was administered to male and female rats, respectively, at doses of 1000 or 500 ppm and 2000 or 1000 ppm for 104 weeks. In mice, NaClO was given at doses of 1000 or 500 ppm to either sex for 103 weeks. The incidences of tumors in NaClO-treated and control animals of both sexes were not significantly different in both rat and mouse studies. NaClO2 was given to rats of both sexes at a dose of 600 or 300 ppm for 85 weeks. No statistically significant differences were observed in the incidences of tumor formation between NaClO2-treated and control groups of both sexes. NaClO2 was administered to mice at a concentration of 500 or 250 ppm for 85 weeks. In males, the combined incidences of hyperplastic nodules and hepatocellular carcinomas of the liver in a low-dose group, and adenomas and adenocarcinomas of the lung in a high-dose group, were marginally increased compared to controls (p less than 0.05). However, these incidences in treated males were within the range of values of historical control data in our program. We concluded that KBrO3 was carcinogenic in rats of both sexes. NaClO was not carcinogenic in either rats and or mice under the conditions of the present studies. Although NaClO2 was shown to be noncarcinogenic in rats, the results for mice were evaluated as inconclusive. Also the results of two-stage mouse skin carcinogenesis using KBrO3, NaClO, and NaClO2 are presented. The necessity for further testing of oxidant chemicals to determine potential carcinogenic and/or promoting effects is suggested in view of the recently proposed role of active oxygen species in carcinogenesis.
A case of esophagorespiratory fistula successfully managed with a new technique for esophagoscopic closure
Authors: B. Odemis, M. Kekilli, M. Ibis, M. Arhan, Y. Beyazit, N. Sasmaz
Journal: Endoscopy (2009)

Fistulas between the esophagus and the tracheobronchial tree are rarely seen in adults. Malignancy is the most common cause of these fistulas, and these generally have a poor prognosis. Benign causes of such fistulas are iatrogenic (i. e. intubation, sclerotherapy, and surgery), infections, inflammatory conditions, and corrosive ingestion. Bronchoesophageal fistulas of benign origin are rare but have a favorable outcome with appropriate treatment [1] [2] [3]. We report here the case of a patient with an esophagorespiratory fistula (ERF) who was managed successfully with a new technique for esophagoscopic closure.
Screening Patients With Type 2 Diabetes for Active Tuberculosis in Communities of China
Authors: Wenjing Zhao, Lizheng Shi, Vivian A. Fonseca, Jiang He, Decheng Shao, Jie Zhao, Qingmei Chen, Aitian Yin
Journal: Diabetes Care (2013)

Patients with diabetes mellitus (DM) are at higher risk of tuberculosis (TB) (1), especially in China, where there is a high burden of both diseases (2). Comorbidity of DM and TB (DM + TB) results in higher probabilities of treatment failure, multidrug resistance, and death (3). In China, epidemiologic information for DM + TB is limited, and effective tools to identify cases of DM + TB are not available. Therefore, this cross-sectional, observational pilot study aimed to identify the prevalence, risk factors, and clinical symptoms of TB in patients with DM.

A stratified-cluster random sampling method was used to enroll patients with diagnosed type 2 DM who were ≥25 years of age in randomly selected villages in two sampling sites/counties (Ningyang and Yishui in the Shandong Province) from May to July 2012. Diagnostic criteria of DM followed the guidelines of World Health Organization (4). TB screening guidelines were recommended …
Glucose-induced fibronectin and collagen type III expression in renal fibroblasts can occur independent of TGF-β1
Authors: Suzanne Lam, Nicole A.M. Verhagen, Frank Strutz, Johan W. van der Pijl, Mohamed R. Daha, Cees van Kooten
Journal: Kidney International (2003)

Glucose-induced fibronectin and collagen type III expression in renal fibroblasts can occur independent of TGF-β1. <h3>Background</h3> Various renal cell types have been shown to contribute to the excessive matrix deposition observed in diabetic nephropathy. The present study examined the effect of high ambient glucose and transforming growth factor-β1 (TGF-β1) on matrix production by human renal fibroblasts. <h3>Methods</h3> Human renal fibroblasts (TK173) were used to examine the effects of high glucose and TGF-β1 on fibronectin and collagen type III expression. Stable transfectants were generated of TK173 cells expressing a dominant negative TGF-β type II receptor. Matrix components were measured in enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). <h3>Results</h3> Fibronectin secretion by renal fibroblasts was increased upon exposure to high glucose, but with delayed kinetics compared to TGF-β1-induced fibronectin. Exposure to high glucose resulted in an increased secretion of latent TGF-β1. However, treatment with neutralizing pan-specific anti-TGF-β antibodies could not attenuate the effects of glucose. Furthermore, collagen type III was up-regulated by high glucose, but not by TGF-β1. Importantly, fibroblasts expressing a dominant negative TGF-β type II receptor were defective in TGF-β1-induced fibronectin production, whereas glucose-induced fibronectin and collagen type III were unaffected. <h3>Conclusions</h3> These data show that in renal fibroblasts exposure to high glucose can increase matrix production independent of endogenous TGF-β1. Although glucose activation is accompanied by an increased production of latent TGF-β1, which can have an important role in vivo, the data suggest involvement of alternative growth factors in the mechanism by which hyperglycemic conditions can modulate matrix accumulation in diabetic nephropathy.
Oral GS-5806 Activity in a Respiratory Syncytial Virus Challenge Study
Authors: John P. DeVincenzo, Richard J. Whitley, Richard L. Mackman, Cecilia Scaglioni-Weinlich, Lisa Harrison, Eric Farrell, Stephen McBride, Robert Lambkin-Williams, Robert Jordan, Yan Xin, Srini Ramanathan, Thomas O’Riordan, Sandra A. Lewis, Xiaoming Li, Seth L. Toback, Shao-Lee Lin, Jason W. Chien
Journal: New England Journal of Medicine (2014)

Respiratory syncytial virus (RSV) is a common cause of infant hospitalizations and is increasingly recognized as a cause of considerable morbidity and mortality. No accepted antiviral treatment exists.We conducted a double-blind, placebo-controlled study of GS-5806, an oral RSV-entry inhibitor, in healthy adults who received a clinical challenge strain of RSV intranasally. Participants were monitored for 12 days. At the time of a positive test for RSV infection or 5 days after inoculation, whichever occurred first, participants were randomly assigned to receive GS-5806 or placebo in one of seven sequential cohorts. Cohorts 1 to 4 received a first dose of 50 mg of GS-5806 and then 25 mg daily for the next 4 days, cohort 5 received a first dose of 50 mg and then 25 mg daily for the next 2 days, cohort 6 received one 100-mg dose, and cohort 7 received a first dose of 10 mg and then 5 mg daily for the next 4 days. Dose selection for cohorts 5, 6, and 7 occurred after an interim analysis of data for cohorts 1 to 4. The primary end point was the area under the curve (AUC) for the viral load, which was assessed after administration of the first dose through the 12th day after inoculation. Secondary end points were mucus weight and symptom scores.Among the 54 participants in cohorts 1 to 4 who were infected with RSV, active treatment was associated with a lower viral load (adjusted mean, 250.7 vs. 757.7 log10 plaque-forming-unit equivalents [PFUe] × hours per milliliter; P<0.001), lower total mucus weight (mean, 6.9 g vs. 15.1 g; P=0.03), and a lower AUC for the change from baseline in symptom scores (adjusted mean, -20.2 vs. 204.9 × hours; P=0.005). The results were similar in cohorts 5, 6, and 7. Adverse events, including low neutrophil counts and increased levels of alanine aminotransferase, were more common among participants receiving GS-5806.Treatment with GS-5806 reduced the viral load and the severity of clinical disease in a challenge study of healthy adults. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01756482.).
Identifying sentinel node could reduce surgery in breast cancer
Authors: H. Bower
Journal: BMJ (1997)

The spread of cancer into the axilla in patients with breast cancer can be accurately predicted from the health of a single node, Italian oncologists have claimed after encouraging results from research into a new technique that could save thousands of women from unnecessary surgery.

Using a new radiographic procedure to find a “sentinel” node in the armpit, researchers from the European Institute of Oncology in Milan correctly assessed the …
Autoimmunity in Concurrent Myasthenia Gravis and Pemphigus Erythematosus
Authors: Ernst H. Beutner
Journal: JAMA (1968)

A patient with myasthenia gravis, a malignant thymoma, and pemphigus erythematosus was found to have antibodies to the cross striations of skeletal muscle, to the intercellular areas of stratified squamous epithelium, and to nuclei as revealed by indirect immunofluorescence. Somewhat comparable observations have been made in other cases. The concurrence of these rare immunologic derangements point to some common underlying mechanisms.
Influence of Age on the Hemodynamic Response to Exercise
Authors: STEVO JULIUS, ANTOON AMERY, LEIGH S. WHITLOCK, JAMES CONWAY
Journal: Circulation (1967)

Respiratory and hemodynamic measurements were made on 54 sedentary subjects during progressive exercise on a bicycle ergometer up to the point of maximal voluntary effort. The age range of the group was from 18 to 68 years. The maximum tolerated exercise, as indicated by the highest achieved level of oxygen consumption (V o o2 ), diminished with age. Older subjects had a lower resting cardiac output (Q) than normal subjects, but an identical increase in Q with V o o2 . There was no evidence of flattening of this curve as the older subjects approached highest exercise loads. Consequently, the arteriovenous oxygen difference did not increase abnormally on high loads, and the cardiac response to exercise in older subjects appeared to be adequate. The relationship between inspired air volume and heart rate with V o o2 at submaximal loads was not influenced by age. Systolic pressure increased progressively with exercise and showed a greater change in older subjects. Total peripheral resistance at rest increased with age; but with increasing exercise, this difference progressively diminished.
Medallion-like dermal dendrocyte hamartoma: the main diagnostic pitfall is congenital atrophic dermatofibrosarcoma
Authors: M. Marque, D. Bessis, F. Pedeutour, V. Viseux, B. Guillot, S. Fraitag-Spinner
Journal: British Journal of Dermatology (2008)

Medallion-like dermal dendrocyte hamartoma is a newly described and rare clinical and pathological entity. This congenital, round, erythematous and atrophic lesion in the thoracic area is histologically characterized by a CD34+ dermal and hypodermal spindle-cell infiltration. We describe the clinical, histopathological, cytological and molecular features of three cases of dermal dendrocyte hamartoma. In all the cases, atrophic congenital dermatofibrosarcoma protuberans (DFSP) was the first histological diagnosis. In one case, wide surgery had been performed on the basis of the clinical and histological presentation. The histological pattern was similar in all the cases: epidermal atrophy and a spindle to ovoid cell proliferation in the dermis and in the subcutaneous fat. Immunochemical staining for CD34 and factor XIIIa was positive. Cytogenetic and molecular studies were performed; no chromosomal abnormality nor translocation t(17;22)(q22;q13) was observed. Fluorescence in situ hybridization analysis did not reveal the DFSP fusion gene COL1A1-PDGFB. We observed that the main diagnostic pitfall of medallion-like dermal dendrocyte hamartoma is atrophic congenital DFSP due to clinical and histological similarities. We emphasize that molecular studies to eliminate the t(17;22)(q22;q13) translocation of DFSP may provide determinant elements for diagnosis in order to avoid unnecessary mutilating surgery.
Prevalence and Characteristics of Systolic Blood Pressure Thresholds in Individuals 60 Years or Older
Authors: Daichi Shimbo, Rikki M. Tanner, Paul Muntner
Journal: JAMA Internal Medicine (2014)

Carlos J. Rodriguez, MD, MPH; Katrina Swett, MS; Sunil K. Agarwal, MD, PhD; Aaron R. Folsom, MD, MPH; Ervin R. Fox, MD, MPH; Laura R. Loehr, MD, PhD; Hanyu Ni, PhD, MPH; Wayne D. Rosamond, PhD; Patricia P. Chang, MD, MHS
The Retirement of Professor Austin Flint.
Authors: Samuel Alexander
Journal: JAMA (1906)

New York City, July 17, 1906. <h3>To the Editor:</h3> —Cornell University Medical College has suffered a serious loss in the retirement this year of its distinguished professor of physiology, Dr. Austin Flint. The many practitioners who, in their student days, came under his instruction in the former Bellevue Hospital Medical College, and later in Cornell, should be interested in this brief note of farewell. A man who, up to the present time, has been a vigorous and effective teacher, and who, in his seventieth year, has issued a new edition of his work on physiology, revised and in every respect up to date, must be intellectually still in his prime. The university, having fixed an age limit to the employment of its instructors, was unable longer to reap the advantages of Dr. Flint's services. The loss will fall heavily on the present and future students, for as a teacher the
1113 HCV infection is an independent risk factor for insulin resistance in non-diabetic subjects: results from the third national health and nutrition examination survey (NHANES III)
Authors: S LIANGPUNSAKUL, P PANDYA, P KWO, N CHALASANI
Journal: Hepatology (2003)

To better understand relationships between perineural invasion (PNI) and radical prostatectomy outcomes, we examined whether PNI was independently associated with adverse pathologic features and worse survival outcomes after radical prostatectomy.PNI is a routinely reported pathologic parameter for prostate biopsy specimens. We identified 3226 patients undergoing radical prostatectomy for clinically localized prostate cancer at our institution between 1994 and 2010. We used multivariable logistic regression models to examine whether PNI was independently associated with extraprostatic extension, seminal vesicle invasion, and surgical margin status. We used Kaplan-Meier methods and the log-rank test to assess disease-free, prostate cancer-specific, and overall survival according to PNI status. Cox proportional hazards modeling was used to evaluate relationships between PNI and survival outcomes.PNI was identified in the prostate biopsy specimen in 20% of patients who underwent radical prostatectomy. Patients with PNI were more likely to have adverse pathologic features, including extraprostatic extension, seminal vesicle invasion, and positive surgical margins. Patients with PNI had shorter disease-free, cancer-specific, and overall survival (all log-rank P <.001). After adjustment for adverse pathologic features at radical prostatectomy, PNI was independently associated with disease-free survival (adjusted hazard ratio, 1.45; 95% confidence interval, 1.09-1.92) and overall survival (hazard ratio, 1.57; 95% confidence interval, 1.13-2.18).PNI was independently associated with adverse pathologic features and worse survival outcomes after radical prostatectomy. For these reasons, PNI on prostate biopsy specimens should be considered in prostate cancer treatment decision making and clinical care.
Clinical Outcomes After Implantation of a Centrifugal Flow Left Ventricular Assist Device and Concurrent Cardiac Valve Procedures
Authors: Carmelo Milano, Francis D. Pagani, Mark S. Slaughter, Duc Thinh Pham, David R. Hathaway, Mary V. Jacoski, Kevin B. Najarian, Keith D. Aaronson
Journal: Circulation (2014)

Cardiac valve procedures are commonly performed concurrently during implantation of left ventricular assist devices, but the added procedural risk has not been studied in detail.Data from patients receiving the HeartWare Ventricular Assist Device in the ADVANCE bridge to transplant (BTT) trial and continued access protocol were reviewed. Of 382 consecutive patients who completed follow-up between August 2008 and June 2013 (mean time on support 389 days, median 271 days), 262 (68.6%) underwent isolated HeartWare Ventricular Assist Device implantation, 75 (19.6%) a concurrent valve procedure, and 45 (11.8%) concurrent nonvalvular procedures. Of the concurrent valve procedures, 56 were tricuspid, 13 aortic, and 6 mitral. Survival was similar between groups (79% for concurrent valve procedures and 85% for HeartWare Ventricular Assist Device only at 1 year; P=0.33). Concurrent valve procedures were also associated with increased unadjusted early right heart failure (RHF). A multivariable analysis for death and RHF (121 total events) identified female sex (odds ratio=2.0 [95% confidence interval, 1.2-3.3; P=0.0053]) and preimplant tricuspid regurgitation severity (odds ratio=2.9 [95% confidence interval, 1.8-4.8, P<0.0001]) as independent predictors while concurrent tricuspid valve procedures (TVP) were not predictors. Furthermore, patients with significant preimplant tricuspid regurgitation who did not receive a TVP experienced an increased rate of late RHF compared with those who received TVP (0.19 versus 0.05 events per patient-year, respectively; P=0.024).Compared with HeartWare Ventricular Assist Device alone, survival was equivalent for the concurrent valve procedure group. Tricuspid regurgitation severity was the most important predictor of increased postoperative RHF, and concurrent TVP was not an independent predictor of RHF overall. Concurrent TVP may reduce the rate of late RHF for patients with significant preimplant tricuspid insufficiency.http://www.clinicaltrials.gov. Unique identifier: NCT00751972.
Sex and Aging
Authors: John H.J. Bancroft
Journal: New England Journal of Medicine (2007)

Human beings are living longer, women more so than men. Among people 85 years of age and older, there are 4 men for every 10 women.1 What happens to sexuality in older age?In this issue of the Journal, Lindau et al.2 report the results of a community-based survey assessing sexual activity and problems among 3005 men and women 57 to 85 years of age. Among participants with a spousal or other intimate relationship, the proportion who reported being sexually active decreased steadily across the age groups and was uniformly lower among women; in the subgroup of respondents who were . . .