tbuckley/cabot-search huggingface dataset:
Biochemical and Cellular Effects of Direct Maxacalcitol Injection into Parathyroid Gland in Uremic Rats
Authors: Kazuhiro Shiizaki, Shigeo Negi, Ikuji Hatamura, Toshifumi Sakaguchi, Fumie Saji, Ken Kunimoto, Masahide Mizobuchi, Ikuo Imazeki, Akira Ooshima, Tadao Akizawa
Journal: Journal of the American Society of Nephrology (2004)

The most important etiological factors of resistance to medical treatments for secondary hyperparathyroidism are the decreased contents of the vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in parathyroid cells and a severely swollen parathyroid gland (PTG) as a result of hyperplasia. The effects of direct maxacalcitol (OCT) injection into PTG in terms of these factors were investigated in this study. The PTG of Sprague-Dawley rats that were 5/6 nephrectomized and fed a high-phosphate diet were treated by a direct injection of OCT (DI-OCT) or vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (PTH), Ca(2+), and phosphorus levels, in VDR and CaSR expression levels in parathyroid cells, and in Ca(2+)-PTH curves were examined. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA electrophoresis for PTG. DI-OCT markedly decreased serum intact PTH level, and a significant difference in this level between DI-OCT and DI-vehicle was observed. However, serum Ca(2+) and phosphorus levels did not changed markedly in both groups. The upregulations of both VDR and CaSR, the clear shift to the left downward in the Ca(2+)-PTH curve, and the induction of apoptosis after DI-OCT were observed. These findings were not observed in the DI-vehicle-treated rats. Moreover, these effects of DI-OCT were confirmed by the DI-OCT into one PTG and DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce simultaneous VDR and CaSR upregulations and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH levels in very severe secondary hyperparathyroidism.
Priming after a Fractional Dose of Inactivated Poliovirus Vaccine
Authors: Sonia Resik, Alina Tejeda, Roland W. Sutter, Manuel Diaz, Luis Sarmiento, Nilda Alemañi, Gloria Garcia, Magilé Fonseca, Lai Heng Hung, Anna-Lea Kahn, Anthony Burton, J. Mauricio Landaverde, R. Bruce Aylward
Journal: New England Journal of Medicine (2013)

To reduce the costs of maintaining a poliovirus immunization base in low-income areas, we assessed the extent of priming immune responses after the administration of inactivated poliovirus vaccine (IPV).
Education and the metabolic syndrome in women.
Authors: S P Wamala, J Lynch, M Horsten, M A Mittleman, K Schenck-Gustafsson, K Orth-Gomér
Journal: Diabetes Care (1999)

OBJECTIVE: The main objective was to examine the association between the metabolic syndrome and socioeconomic position (as indicated by education) among women. RESEARCH DESIGN AND METHODS: The study sample comprised healthy women (aged 30-65 years) in Sweden who were representative of the general population in a metropolitan area. Socioeconomic position was measured by educational level (mandatory [&amp;lt; or = 9 years], high school, or college/university). The metabolic syndrome was defined as the presence of two or more of the following components: 1) fasting plasma glucose level &amp;gt; or = 7.0 mmol/l; 2) arterial blood pressure &amp;gt; or = 160/90 mmHg; 3) fasting plasma triglycerides &amp;gt; or = 1.7 mmol/l and/or HDL cholesterol &amp;lt; 1.0 mmol/l; and 4) central obesity (waist-to-hip ratio &amp;gt; 0.85 and/or BMI &amp;gt; 30 kg/m2). RESULTS: After adjustment for age, the risk ratio for the presence of the metabolic syndrome comparing the lowest (&amp;lt; or = 9 years) with the highest (college/university) education was 2.7 (95% CI 1.1-6.8). This association persisted after controlling for menopausal status, family history of diabetes, and behavioral risk factors. CONCLUSIONS: Low education is associated with increased risk for metabolic syndrome in middle-aged women. These findings show that not only are women with low socioeconomic position at increased risk for individual risk factors that are associated with cardiovascular disease and type 2 diabetes, they are also at increased risk for the metabolic clustering of risk factors.
SURVIVAL IN PATIENTS WITH MODERATE OR SEVERE MITRAL REGURGITATION AT HIGH RISK FOR SURGERY TREATED WITH AND WITHOUT THE MITRACLIP: A PROPENSITY MATCHED COMPARISON
Authors: Eric J. Velazquez, Chithra Sangli, Hussein Al-Khalidi, Paul Grayburn, Joseph Massaro, Susanna Stevens, Ted Feldman, Mitchell Krucoff
Journal: Journal of the American College of Cardiology (2012)
Smoking Initiation in the United States: A Role for Worksite and College Smoking Bans
Authors: John P. Pierce, Millie Naquin, Elizabeth Gilpin, Gary Giovino, Sherry Mills, Steven Marcus
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Smoking Initiation in the United States: A Role for Worksite and College Smoking Bans Get access John P. Pierce, John P. Pierce Search for other works by this author on: Oxford Academic PubMed Google Scholar Millie Naquin, Millie Naquin Search for other works by this author on: Oxford Academic PubMed Google Scholar Elizabeth Gilpin, Elizabeth Gilpin Search for other works by this author on: Oxford Academic PubMed Google Scholar Gary Giovino, Gary Giovino Search for other works by this author on: Oxford Academic PubMed Google Scholar Sherry Mills, Sherry Mills Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven Marcus Steven Marcus Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 14, 17 July 1991, Pages 1009–1013, https://doi.org/10.1093/jnci/83.14.1009 Published: 17 July 1991 Article history Received: 23 July 1990 Revision received: 08 April 1991 Accepted: 12 April 1991 Published: 17 July 1991
Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets
Authors: Ying-Jun Chang, Xiang-Yu Zhao, Lan-Ping Xu, Xiao-Hui Zhang, Yu Wang, Wei Han, Huan Chen, Feng-Rong Wang, Xiao-Dong Mo, Yuan-Yuan Zhang, Ming-Rui Huo, Xiao-Su Zhao, Kong Y, Kai-Yan Liu, Xiao-Jun Huang
Journal: Journal of Hematology & Oncology (2015)

Small studies suggest an association of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) with primary graft failure (GF) following haploidentical stem cell transplantation, but primary graft rejection (GR) was not discriminated from primary poor graft function (PGF). In this study, we aimed to determine the association of DSAs with primary GF, including GR and PGF, in patients who underwent unmanipulated haploidentical blood and marrow transplantation. A total of 345 subjects were prospectively recruited and randomly selected as training group (n = 173) and validation group (n = 172). Patient plasma/serum was screened. For HLA antibody positive samples with a median fluorescent intensity (MFI) >500, DSAs were further tested using a LABScreen Single Antigen Kit (One Lambda). A total of 342 patients (99.1 %) achieved sustained myeloid engraftment. The median times to neutrophil engraftment and platelet engraftment were 13 days (range, 8–28 days) and 18 days (range, 6–330 days), respectively. The cumulative incidence of primary GF was 6.4 ± 1.3 % and included GR (0.9 ± 0.5 %) and PGF (5.5 ± 1.2 %). Of the 345 cases tested, 39 (11.3 %) were DSA positive. Multivariate models showed that DSAs (MFI ≥ 10,000) were correlated to primary GR (P < 0.001) and that DSAs (MFI ≥ 2000) were strongly associated with primary PGF (P = 0.005). All patients were classified into three groups for analysis. Group A included cases that were DSA negative and those with a DSA MFI <2000 (n = 316), group B included cases with a 2000 ≤ MFI < 10,000 (n = 19), and group C included cases with a MFI ≥10,000 (n = 10). The DSAs were associated with an increased incidence of the primary GF (3.2 vs. 31.6 vs. 60 %, for groups A, B, and C, respectively, P < 0.001), transplant-related mortality (TRM) rate (17.2 vs. 14.7 vs. 33.3 %, for groups A, B, and C, respectively, P = 0.022), and inferior overall survival (OS, 77.3 vs. 85.3 vs. 44.4 %, for groups A, B, and C, respectively, P = 0.015). The primary GF was independently associated with a higher incidence of TRM (P < 0.001), inferior disease-free survival (P < 0.001), and OS (P < 0.001). The findings confirmed the effect of DSAs on primary GF, including GR and PGF, and survival. Our results suggest incorporating DSAs in the algorithm for haploidentical donor selection.
An assessment of the value of Ag NOR staining in the identification of dysplastic and other borderline melanocytic naevi
Authors: RONA M. MACKIE, S.I. WHITE, MORAG M. SEYWRIGHT, H. YOUNG
Journal: British Journal of Dermatology (1989)

One hundred and six melanocytic lesions were studied to determine the value of the so called Ag NOR technique in differentiating dysplastic naevi, Spitz naevi and spindle cell naevi of Reed from malignant melanoma and from 'banal' compound or intradermal naevi. In 79 cases Ag NOR counts were possible. The banal naevi (36) had a mean count of 1.54, (SD 0.3), and the unequivocally malignant superficial spreading melanomas (13), lentigo maligna melanomas (4) and secondary melanomas (4) had a mean count overall of 3.9 (SD 1.59). For dysplastic naevi (16) the mean Ag NOR count was 1.63 (SD 0.36) and for Spitz and spindle cell naevi (in toto 6) the figure was 1.72 (SD 0.55). The difference in Ag NOR counts between all types of naevi and all types of melanoma was highly statistically significant, but there was no difference between banal naevi and dysplastic, Spitz, and spindle cell naevi. Correlation of Ag NOR counts between three independent observers was good. This technique may, therefore, be a useful adjunct in separating true melanoma from borderline melanocytic naevi.
FDA questions use of aspirin for primary prevention of stroke and heart attack
Authors: M. McCarthy
Journal: BMJ (2014)

Aspirin should not be routinely used for the primary prevention of heart attack or stroke in patients with no history of cardiovascular disease, the US Food and Drug Administration has concluded.

“The FDA has reviewed the available data and does not believe the evidence supports the general use of aspirin for primary prevention of a heart attack or stroke,” it said in a statement posted online last week.1

“In fact, there are serious risks associated with the use of aspirin, including increased …
An Evaluation of Colchicine as an Alternative to Inhaled Corticosteriods in Moderate Asthma
Authors: JAMES E. FISH, STEPHEN P. PETERS, CHRISTOPHER V. CHAMBERS, STEPHEN J. McGEADY, KENNETH R. EPSTEIN, HOMER A. BOUSHEY, REUBEN M. CHERNIACK, VERNON M. CHINCHILLI, JEFFREY M. DRAZEN, JOHN V. FAHY, SUZANNE S. HURD, ELLIOT ISRAEL, STEPHEN C. LAZARUS, ROBERT F. LEMANSKE, RICHARD J. MARTIN, ELIZABETH A. MAUGER, CHRISTINE SORKNESS, STANLEY J. SZEFLER
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Colchicine demonstrates an array of anti-inflammatory properties of potential relevance to asthma. However, the efficacy of colchicine as an alternative to inhaled corticosteroid therapy for asthma is unknown. Five centers participated in a controlled trial testing the hypothesis that in patients with moderate asthma needing inhaled corticosteroids for control, colchicine provides therapeutic benefit as measured by maintenance of control when inhaled steroids are discontinued. Subjects were stabilized on triamcinolane acetonide (800 μ g daily) and then enrolled in a 2-wk run-in during which all subjects took both colchicine (0.6 mg/twice a day) and triamcinolone. At the end of the run-in, all subjects discontinued triamcinolone and were randomized to continued colchicine (n = 35) or placebo (n = 36) for a 6-wk double-blind treatment period. The treatment groups were similar in terms of disease severity. After corticosteroid withdrawal, 60% of colchicine-treated and 56% of placebo-treated subjects were considered treatment failures as defined by preset criteria. No significant difference in survival curves was found between treatment groups (log rank = 0.38). Other measures, including changes in FEV1, peak expiratory flow, symptoms, rescue albuterol use, and quality of life scores, also did not differ between groups. Of note, subjects failing treatment had significantly greater methacholine responsiveness at baseline than did survivors (PC20, 0.81 ± 1.38 versus 2.11 ± 2.74 mg/ml; p = 0.01). An analysis of treatment failures suggested that the criteria selected for failure reflected a clinically meaningful but safe level of deterioration. We conclude that colchicine is no better than placebo as an alternative to inhaled corticosteroids in patients with moderate asthma. Additionally, we conclude that the use of treatment failure as the primary outcome variable in an asthma clinical trial where treatment is withdrawn is feasible and safe under carefully monitored conditions.
Baseline characteristics in the Modification of Diet in Renal Disease Study.
Authors: T Greene, J J Bourgoignie, V Habwe, J W Kusek, L G Snetselaar, J M Soucie, M E Yamamoto
Journal: Journal of the American Society of Nephrology (1993)

The Modification of Diet in Renal Disease Study is randomized, multicenter, clinical trial designed to determine the effects of three levels of dietary control of protein and phosphorus and two levels of blood pressure control on the rate of decline of kidney function among persons with chronic renal disease. Study participants were assigned to one of two studies, Study A or Study B, depending on their GFR just before randomization. Within each study, participants were randomly allocated to one of two levels of blood pressure control and to one of two dietary interventions according to separate 2 x 2 factorial designs. A total of 840 men and women aged 18 to 70 were randomized. This report summarizes the demographic, biochemical, and clinical characteristics of the randomized participants at the time of entry into the trail, overviews the protocol and purposes of the baseline period before randomization, and evaluates the balance among the treatment intervention groups within Studies A and B at the time of randomization. Major indicators of renal function were found to be well balanced among the treatment groups. Selected baseline characteristics of participants in the Modification of Diet in Renal Disease Study are compared with those of other renal clinical trials and with those of new cases of treated ESRD reported in the United States Renal Data System.
Prednisone-dependent asthma: inflammatory indices in induced sputum
Authors: MM Pizzichini, E Pizzichini, L Clelland, A Efthimiadis, I Pavord, J Dolovich, FE Hargreave
Journal: European Respiratory Journal (1999)

The kinetics of changes in inflammatory indices in induced sputum from eight prednisone dependent asthmatics whose minimum clinical maintenance and exacerbation doses were known were investigated. The study began on the last day of a course of 30 mg prednisone daily for one week. Thereafter, the daily prednisone was reduced in a structured way to below the maintenance dose. This treatment was continued until a clinical exacerbation occurred. Prednisone 30 mg daily was then given again for one week. The mean duration of prednisone reduction was 7.4 weeks and the median dose was 7.5 mg x day(-1). Increases in sputum eosinophils preceded increases in blood eosinophils by 4 weeks and worsening of symptoms and forced expiratory volume in one second by 6 weeks. The clinical exacerbation was also accompanied by sputum neutrophilia and increases in sputum eosinophil cationic protein (ECP), fibrinogen and interleukin (IL)-5. Treatment with prednisone suppressed median sputum eosinophilia (from 16.3 to 0%, p&lt;0.001), decreased sputum ECP (from 7,480 to 700 microg x L(-1), p = 0.01), but did not improve neutrophil numbers, fibrinogen or IL-5. The results show that the reduction of prednisone treatment in prednisone-dependent asthmatics evokes a severe airway eosinophilic inflammatory response. Clinical and blood indices deteriorate later than those in sputum suggesting that sputum examination may be useful to identify the minimum regular dose of prednisone required in these patients.
Bone Marrow–Derived Cells Do Not Contribute Significantly to Collagen I Synthesis in a Murine Model of Renal Fibrosis
Authors: Candice Roufosse, George Bou-Gharios, Evangelia Prodromidi, Catherine Alexakis, Rosemary Jeffery, Sarah Khan, William R. Otto, Julia Alter, Richard Poulsom, H. Terence Cook
Journal: Journal of the American Society of Nephrology (2006)

Interstitial fibroblasts play a central role in kidney fibrosis. Their origin is debated, with recent data indicating a contribution of bone marrow (BM)-derived cells to the expanded population of interstitial cells after kidney damage in animals and humans. This study investigated whether these BM-derived cells would respond appropriately to a fibrotic drive by producing collagen. A transgenic mouse that expresses both luciferase and beta-galactosidase reporter molecules under the control of a 17-kb promoter and enhancer element of the gene encoding the alpha2 chain of the collagen I was used. Male transgenic BM was transplanted into female wild-type C57BL/6 mice (n=14), and unilateral ureteric obstruction was performed later to induce renal fibrosis. In the obstructed kidney of the BM-chimeric female mice, a mean of 8.6% of smooth muscle actin-positive interstitial cells were Y chromosome positive. Increased collagen I mRNA in the obstructed kidney was detected by in situ hybridization. No luciferase activity was detected by enzyme assays in tissue homogenates of BM recipients, and very few luciferase mRNA transcripts were seen, mainly in tubular cells. beta-Galactosidase activity was not a useful reporter molecule because it could not be distinguished from enhanced endogenous beta-galactosidase activity in the obstructed kidney. These results indicate that BM-derived interstitial cells do not make a significant contribution to collagen I synthesis in the context of renal injury.
Cisplatin Hypersensitivity of Testicular Germ Cell Tumors Is Determined by High Constitutive Noxa Levels Mediated by Oct-4
Authors: Matthias Gutekunst, Thomas Mueller, Andrea Weilbacher, Michael A. Dengler, Jens Bedke, Stephan Kruck, Moshe Oren, Walter E. Aulitzky, Heiko van der Kuip
Journal: Cancer Research (2013)

Abstract Testicular germ cell tumors (TGCT) are considered a paradigm of chemosensitive tumors. Embryonal carcinoma cells represent the pluripotent entity of TGCTs and are characterized by expression of Oct-4, a key regulator of pluripotency and a determinant of their inherent hypersensitivity to cisplatin. However, the mechanisms underlying this Oct-4–mediated sensitivity are poorly understood. We previously showed that p53 is a major player in cisplatin hypersensitivity and therefore investigated whether Oct-4 may directly affect p53 activity. Despite a significant decrease in sensitivity, depletion of Oct-4 neither did alter cisplatin-induced transactivation of p53 target genes nor its subcellular localization. These data indicate that, rather than directly modulating p53 activity, Oct-4 provides a cellular context that augments the proapoptotic activity of p53. As mitochondrial priming by the Bcl-2 family is a known determinant of chemosensitivity, we compared the constitutive levels of these proteins in Oct-4–positive and -depleted cells. We identified Noxa as the only Bcl-2 family protein to be highly correlated with Oct-4 status and cisplatin sensitivity. Compared with differentiated cells, constitutive Noxa levels were significantly higher in Oct-4–positive cell lines and cancer patient samples. Furthermore, RNA interference–mediated knockdown of Oct-4 resulted in reduced Noxa transcript, in an almost complete loss of constitutive Noxa protein and decreased cisplatin hypersensitivity to a similar extent as did Noxa depletion. In conclusion, our study indicates that Noxa is a central determinant of hypersensitivity to cisplatin. Oct-4–dependent high constitutive levels of this BH3-only protein prime embryonal carcinoma cells to undergo rapid and massive apoptosis in response to p53 activation. Cancer Res; 73(5); 1460–9. ©2012 AACR.
Mouse Mammary Tumor Virus: New Tumor Virus or Just a Rumor Virus?
Authors: V. Brower
Journal: JNCI Journal of the National Cancer Institute (2009)

W hen German microbiologist Harald zur Hausen, M.D., D.Sc., hypothesized in 1974 that human papillomavirus (HPV) played a central role in causing cervical cancer, few took him seriously. But in 1983 he discovered HPV-16, and a year later, HPV-18 in tumors of cervical cancer patients — findings that led eventually to the first preventive cancer vaccine and, for zur Hausen, last year’s Nobel prize for medicine. Spurred by the clinical success of HPV research and the discovery of additional viruses implicated in cancer, scientists continue to hunt for other cancer-causing viruses. One leading contender, the mouse mammary tumor virus (MMTV), is a retrovirus that causes breast cancer in mice. Having found molecular evidence of its presence in human breast tumors, researchers are now investigating a possible causal link. “Among ‘rumor viruses, ’ perhaps the strongest case exists for MMTV in breast cancer,” said David Griffi ths, Ph.D., of Scotland’s Moredun Research Institute in Penicuik. Currently 15% – 25% of cancers are virally linked, with six viruses considered cofactors in or causes of human cancer: HPV in cervical cancer, hepatitis B and C in liver cancer, Epstein – Barr virus in Burkitt lymphoma and nasopharyngeal cancer, human T-cell lymphotropic virus type 1 in adult T-cell leukemia virus, and human herpesvirus 8 in Kaposi sarcoma. In addition to MMTV, other candidate viruses include simian virus 40 in mesothelioma, brain cancer, and lymphoma; cytomegalovirus in glioma; bovine leukemia virus in breast cancer and leukemia; Epstein – Barr virus in breast cancer; HPV in breast and prostate cancer; and xenotropic murine leukemia – related virus in prostate cancer. Proving a causal link is diffi cult and time consuming ( see JNCI News, 2004;96:256 – 7), and the MMTV hypothesis has gone in and out of favor over the last few decades. “In 1964, the NCI established its virus – cancer program, which focused on retroviruses after the discovery of [bovine leukemia virus] and other animal viruses, but 12 – 13 years of studies yielded nothing defi nitive,” said Gertrude Buehring, Ph.D., associate professor of virology at the University of California, Berkeley. “By the early 1980s, most everyone thought that the book was closed,” she said. In addition, the discovery of human immunodefi ciency virus in the mid-1980s diverted funding from MMTV research, according to Walter Gunzburg, Ph.D., professor of virology at the Veterinary University of Vienna. The NCI is not currently funding internal research of MMTV or other rumor viruses, but it does support external research on proven virus – cancer connections.