tbuckley/cabot-search huggingface dataset:
Pathogenesis of the mucosal hyperplasia in self-filling blind loops of rat jejunum: a morphometric study in germ free animals.
Authors: H Menge, C T Germer, R Stossel, G Simes, H Hahn, E O Riecken
Journal: Gut (1987)

Bacterial overgrowth and high intraluminal concentrations of deconjugated bile acids are thought to be responsible for mucosal hyperplasia in self-filling blind loops of rat jejunum. To investigate this hypothesis further we have assessed the three dimensional architecture of these loops created in germ free animals without or with di- or mono-association of different bacterial species. It was found that mucosal hyperplasia develops in the absence of any bacterial contamination and that bacterial association does not lead to a more pronounced mucosal proliferation. This implies that other mechanisms provoke this morphological phenomenon. Increased bulk contents in these loops or immunological events are probably the most likely explanation.
US House passes bill to protect health providers who won't provide abortions
Authors: Janice Hopkins Tanne
Journal: BMJ (2004)

A “conscience” clause attached to the House of Representatives' 2005 appropriations bill for the Departments of Labor, Health and Human Services, and Education protects healthcare providers that will not provide abortions or refer patients for abortions.

The broad amendment, introduced by Dr Dave Weldon, a Florida Republican, says that funds in the bill may not be made available to a federal, state, or local programme that “subjects any institutional or individual health care entity to discrimination on the basis that the health care entity does not provide, pay for, provide coverage of, or refer for abortions.” An entity is “an individual physician or other health care professional, a hospital, a provider-sponsored organisation, a health maintenance organisation, a health insurance plan, or any other kind of health care facility, …
Enteric neuronal plasticity and a reduced number of interstitial cells of Cajal in hypertrophic rat ileum
Authors: E Ekblad, R Sjuve, A Arner, F Sundler
Journal: Gut (1998)

Background —Partial obstruction of the ileum causes a notable hypertrophy of smooth muscle cells and enteric neurones in the proximally located intestine. Aims —To study the expression of neuromessengers in the hypertrophic ileum of rat as little is known about neuromessenger plasticity under these conditions. To investigate the presence of interstitial cells of Cajal (ICC) in hypertrophic ileum. Methods —Ileal hypertrophy was induced by circumferential application of a strip of plastic film for 18–24 days. Immunocytochemistry, in situ hybridisation, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, and ethidium bromide staining were used to investigate the number of enteric neurones expressing neuropeptides and nitric oxide synthase, and the frequency of ICC. Results —In the hypertrophic ileum several neuronal populations showed changes in their expression of neuromessengers. Myenteric neurones expressing vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide, and galanin were notably increased in number. In submucous ganglia the number of VIP immunoreactive neurones decreased while those expressing VIP mRNA increased. NADPH diaphorase positive submucous neurones increased dramatically while the number of neuronal type nitric oxide synthase expressing ones was unchanged. The number of ICC decreased notably in hypertrophic ileum. Conclusion —Enteric neurones change their levels of expression of neuromessengers in hypertrophic ileum. ICC are also affected. The changes are presumably part of an adaptive response to the increased work load.
Use of Hormone Replacement Therapy and the Risk of Colorectal Cancer
Authors: Gad Rennert, Hedy S. Rennert, Mila Pinchev, Ofer Lavie, Stephen B. Gruber
Journal: Journal of Clinical Oncology (2009)

Purpose Estrogen/progestin replacement therapy is prescribed to women in menopause for purposes of postmenopausal symptom control or prevention of hormone deficiency–related diseases such as osteoporosis. Such treatments have formerly been shown to be associated with lower colorectal cancer risk in an as yet unknown mechanism. Patients and Methods The Molecular Epidemiology of Colorectal Cancer study was a population-based case-control study in northern Israel of patients with colorectal cancer who were diagnosed between 1998 and 2006, and age-, sex-, clinic-, and ethnicity-matched population controls. Use of hormone replacement therapy (HRT) was assessed using a structured interview and validated by studying prescription records in a subset of patients for whom they were available. Results Two thousand four hundred sixty peri/postmenopausal women were studied from among 2,648 patients with colorectal cancer and 2,566 controls. The self-reported use of HRT was associated with a significantly reduced relative risk of colorectal cancer (odds ratio [OR], 0.67; 95% CI, 0.51 to 0.89). This association remained significant after adjustment for age, sex, use of aspirin and statins, sports activity, family history of colorectal cancer, ethnic group, and level of vegetable consumption (OR, 0.37; 95% CI, 0.22 to 0.62). Statistically significant interactions were seen between use of HRT and use of aspirin and involvement in sports activity. Using pharmacy data, only users of combined oral preparations demonstrated a significant negative association with colorectal cancer. Conclusion The use of oral HRT was associated with a 63% relative reduction in the risk of colorectal cancer in postmenopausal women after adjustment for other known risk factors. This effect was not found in aspirin users and women with intensive sports participation.
Selenium and the Course of Mild Graves' Orbitopathy
Authors: Claudio Marcocci, George J. Kahaly, Gerasimos E. Krassas, Luigi Bartalena, Mark Prummel, Matthias Stahl, Maria Antonietta Altea, Marco Nardi, Susanne Pitz, Kostas Boboridis, Paolo Sivelli, George von Arx, Maarten P. Mourits, Lelio Baldeschi, Walter Bencivelli, Wilmar Wiersinga
Journal: New England Journal of Medicine (2011)

We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given sodium selenite (100 μg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy–specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score.
Inhibition of Protein Kinase CK2 Reduces <i>Cyp24a1</i> Expression and Enhances 1,25-Dihydroxyvitamin D3 Antitumor Activity in Human Prostate Cancer Cells
Authors: Wei Luo, Wei-Dong Yu, Yingyu Ma, Mikhail Chernov, Donald L. Trump, Candace S. Johnson
Journal: Cancer Research (2013)

Vitamin D has broad range of physiological functions and antitumor effects. 24-Hydroxylase, encoded by the CYP24A1 gene, is the key enzyme for degrading many forms of vitamin D including the most active form, 1,25D(3). Inhibition of CYP24A1 enhances 1,25D(3) antitumor activity. To isolate regulators of CYP24A1 expression in prostate cancer cells, we established a stable prostate cancer cell line PC3 with CYP24A1 promoter driving luciferase expression to screen a small molecular library for compounds that inhibit CYP24A1 promoter activity. From this screening, we identified, 4,5,6,7-tetrabromobenzimidazole (TBBz), a protein kinase CK2 selective inhibitor as a disruptor of CYP24A1 promoter activity. We show that TBBz inhibits CYP24A1 promoter activity induced by 1,25D(3) in prostate cancer cells. In addition, TBBz downregulates endogenous CYP24A1 mRNA level in TBBz-treated PC3 cells. Furthermore, siRNA-mediated CK2 knockdown reduces 1,25D(3)-induced CYP24A1 mRNA expression in PC3 cells. These results suggest that CK2 contributes to 1,25D(3)-mediated target gene expression. Finally, inhibition of CK2 by TBBz or CK2 siRNA significantly enhances 1,25D(3)-mediated antiproliferative effect in vitro and in vivo in a xenograft model. In summary, our findings reveal that protein kinase CK2 is involved in the regulation of CYP24A1 expression by 1,25D(3) and CK2 inhibitor enhances 1,25D(3)-mediated antitumor effect.
TrkC Binds to the Bone Morphogenetic Protein Type II Receptor to Suppress Bone Morphogenetic Protein Signaling
Authors: Wook Jin, Chohee Yun, Hae-Suk Kim, Seong-Jin Kim
Journal: Cancer Research (2007)

Abstract TrkC, a member of the tropomyosin-related kinase (Trk) family of neurotrophin receptors, is implicated in the growth and survival of human cancer tissues. TrkC is also a potent oncoprotein expressed in tumors derived from multiple cell lineages, and functions as an active protein tyrosine kinase by neurotrophin-3 (NT-3). We previously reported that TrkC plays an essential role in tumor growth and metastasis in a murine cancer cell line. Here, we report that expression of TrkC suppresses bone morphogenetic protein 2 (BMP-2)–induced Smad1 phosphorylation and transcriptional activation. In the highly metastatic CT26 murine colon cancer cell line, which expresses endogenous TrkC, silencing TrkC expression by small interfering RNA significantly enhanced BMP-2–induced Smad1 phosphorylation and restored BMP-2 growth inhibitory activity. In contrast, expression of TrkC in RIE-1 cells, in which TrkC is not expressed, completely suppressed BMP-2 transcriptional activation. Furthermore, we showed that TrkC directly binds to the BMP type II receptor (BMPRII), thereby preventing it from interacting with the BMPRI. This activity requires a functional TrkC protein tyrosine kinase, and the BMPRII seems to be a direct target of TrkC. Our findings provide evidence for a previously unknown mechanism by which TrkC, a neuronal receptor, can block BMP tumor-suppressor activity. [Cancer Res 2007;67(20):9869–77]
Modeling Genomic Diversity and Tumor Dependency in Malignant Melanoma
Authors: William M. Lin, Alissa C. Baker, Rameen Beroukhim, Wendy Winckler, Whei Feng, Jennifer M. Marmion, Elisabeth Laine, Heidi Greulich, Hsiuyi Tseng, Casey Gates, F. Stephen Hodi, Glenn Dranoff, William R. Sellers, Roman K. Thomas, Matthew Meyerson, Todd R. Golub, Reinhard Dummer, Meenhard Herlyn, Gad Getz, Levi A. Garraway
Journal: Cancer Research (2008)

The classification of human tumors based on molecular criteria offers tremendous clinical potential; however, discerning critical and "druggable" effectors on a large scale will also require robust experimental models reflective of tumor genomic diversity. Here, we describe a comprehensive genomic analysis of 101 melanoma short-term cultures and cell lines. Using an analytic approach designed to enrich for putative "driver" events, we show that cultured melanoma cells encompass the spectrum of significant genomic alterations present in primary tumors. When annotated according to these lesions, melanomas cluster into subgroups suggestive of distinct oncogenic mechanisms. Integrating gene expression data suggests novel candidate effector genes linked to recurrent copy gains and losses, including both phosphatase and tensin homologue (PTEN)-dependent and PTEN-independent tumor suppressor mechanisms associated with chromosome 10 deletions. Finally, sample-matched pharmacologic data show that FGFR1 mutations and extracellular signal-regulated kinase (ERK) activation may modulate sensitivity to mitogen-activated protein kinase/ERK kinase inhibitors. Genetically defined cell culture collections therefore offer a rich framework for systematic functional studies in melanoma and other tumors.
Treatment of primary HIV-1 infection with cyclosporin A coupled with highly active antiretroviral therapy
Authors: G. Paolo Rizzardi, Alexandre Harari, Brunella Capiluppi, Giuseppe Tambussi, Kim Ellefsen, Donatella Ciuffreda, Patrick Champagne, Pierre-Alexandre Bart, Jean-Philippe Chave, Adriano Lazzarin, Giuseppe Pantaleo
Journal: Journal of Clinical Investigation (2002)

Primary HIV-1 infection causes extensive immune activation, during which CD4+ T cell activation supports massive HIV-1 production. We tested the safety and the immune-modulating effects of combining cyclosporin A (CsA) treatment with highly active antiretroviral therapy (HAART) during primary HIV-1 infection. Nine adults with primary HIV-1 infection were treated with CsA along with HAART. At week 8, all patients discontinued CsA but maintained HAART. Viral replication was suppressed to a comparable extent in the CsA + HAART cohort and in 29 control patients whose primary infection was treated with HAART alone. CsA restored normal CD4+ T cell levels, both in terms of percentage and absolute numbers. The increase in CD4+ T cells was apparent within a week and persisted throughout the study period. CsA was not detrimental to virus-specific CD8+ or CD4+ T cell responses. At week 48, the proportion of IFN-γ–secreting CD4+ and CD4+CCR7– T cells was significantly higher in the CsA + HAART cohort than in the HAART-alone cohort. In conclusion, rapid shutdown of T cell activation in the early phases of primary HIV-1 infection can have long-term beneficial effects and establish a more favorable immunologic set-point. Appropriate, immune-based therapeutic interventions may represent a valuable complement to HAART for treating HIV infection.
Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99–06): a randomised trial
Authors: Thierry Facon, Jean Yves Mary, Cyrille Hulin, Lotfi Benboubker, Michel Attal, Brigitte Pegourie, Marc Renaud, Jean Luc Harousseau, Gaëlle Guillerm, Carine Chaleteix, Mamoun Dib, Laurent Voillat, Hervé Maisonneuve, Jacques Troncy, Véronique Dorvaux, Mathieu Monconduit, Claude Martin, Philippe Casassus, Jérôme Jaubert, Henry Jardel, Chantal Doyen, Brigitte Kolb, Bruno Anglaret, Bernard Grosbois, Ibrahim Yakoub-Agha, Claire Mathiot, Hervé Avet-Loiseau
Journal: The Lancet (2007)
Adhesion of Gastric Carcinoma Cells to Peritoneum Mediated by α3β1 Integrin (VLA-3)
Authors: Hironori Takatsuki, Shinya Komatsu, Rikio Sano, Yoshikazu Takada, Tsutomu Tsuji
Journal: Cancer Research (2004)

Abstract The interaction between gastric carcinoma cells and the peritoneal lining is a key step in peritoneal dissemination. In this study, we examined the roles of the β1 family of integrin receptors in the adhesion of such cells to the peritoneum. The adhesion of several gastric carcinoma cell lines to peritonea excised from mice was inhibited most by an anti-α3 integrin antibody and to a lesser extent by an anti-α2 integrin antibody. In the peritoneal implantation of NUGC-4 human gastric carcinoma cells in athymic mice, treatment of the cells with anti-α2 or anti-α3 integrin antibody reduced the number of disseminated nodules; suppression by the anti-α3 integrin antibody was stronger than that by the anti-α2 integrin antibody. The cDNAs to human α2 and α3 integrins were introduced into K562 leukemic cells, which were positive for the integrin β1 subunit but negative for the α2 or α3 subunit. The α3 integrin-transfected cells adhered to excised peritoneum and to a monolayer of peritoneal mesothelial cells more firmly than did the α2 integrin-transfected cells or the mock transfectant. Reverse transcription-PCR was used to analyze the expression of laminin-5 and laminin-10/11, which have been reported to serve as high-affinity ligands for α3β1 integrin. mRNA for these laminin isoforms was found in mesothelial cells from the diaphragm and parietal peritoneum. These results strongly suggest that α3β1 integrin plays an essential role in mediating the initial attachment of cancer cells to the peritoneum, leading to the formation of peritoneal metastasis.
Diagnostic imaging: orthopaedics
Authors: C Milne
Journal: British Journal of Sports Medicine (2006)

Edited by D Stoller, P Tirman, M Bredella. Published by Elsevier, 2004, hard cover, A$412.50, £175.35 (approx), €254.50 (approx), $307.62 (approx), ISBN 0721629202

Every once in a while, a very special reference work is published. This is one such example. The publishers announce in their blurb that they are proud to present “a precedent-setting image and graphics-packed series that …represents the textbook of the twenty first century!”. I think they have delivered.

The book is split into nine sections. The first six of these cover all of the major joints, via a regional approach. Major muscle groups—for example, hamstrings—are included in the chapter relating to an adjacent joint. The final three chapters are concerned with bone marrow, bone tumours, and soft tissue tumours. There is no chapter on spinal problems; this must …
Quitlines and Nicotine Replacement for Smoking Cessation: Do We Need to Change Policy?
Authors: John P. Pierce, Sharon E. Cummins, Martha M. White, Aimee Humphrey, Karen Messer
Journal: Annual Review of Public Health (2012)

In the past 20 years, public health initiatives on smoking cessation have increased substantially. Randomized trials indicate that pharmaceutical cessation aids can increase success by 50% among heavier smokers who seek help, and use of these aids has increased markedly. Quitlines provide a portal through which smokers can seek assistance to quit and are promoted by tobacco control programs. Randomized trials have demonstrated that telephone coaching following a quitline call can also increase quitting, and a combination of quitlines, pharmaceutical aids and physician monitoring can help heavier smokers to quit. While quit attempts have increased, widespread dissemination of these aids has not improved population success rates. Pharmaceutical marketing strategies may have reduced expectations of the difficulty of quitting, reducing success per attempt. Some policies actively discourage unassisted smoking cessation despite the documented high success rates of this approach. There is an urgent need to revisit public policy on smoking cessation.
Metabolic Signatures Uncover Distinct Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma
Authors: Pilar Caro, Amar U. Kishan, Erik Norberg, Illana A. Stanley, Bjoern Chapuy, Scott B. Ficarro, Klaudia Polak, Daniel Tondera, John Gounarides, Hong Yin, Feng Zhou, Michael R. Green, Linfeng Chen, Stefano Monti, Jarrod A. Marto, Margaret A. Shipp, Nika N. Danial
Journal: Cancer Cell (2012)
Risk of Subsequent Fracture After Low-Trauma Fracture in Men and Women
Authors: Jacqueline R Center, Dana Bliuc, Tuan V Nguyen, John A Eisman
Journal: JAMA (2007)

ContextThere are few published long-term data on absolute risk of subsequent fracture (refracture) following initial low-trauma fracture in women and fewer in men.ObjectiveTo examine long-term risk of subsequent fracture following initial osteoporotic fracture in men and women.Design, Setting, and ParticipantsProspective cohort study (Dubbo Osteoporosis Epidemiology Study) in Australia of 2245 community-dwelling women and 1760 men aged 60 years or older followed up for 16 years from July 1989 through April 2005.Main Outcome MeasureIncidence of first (initial) fracture and incidence of subsequent fracture according to sex, age group, and time since first fracture. Relative risk was determined by comparing risk of subsequent fracture with risk of initial fracture.ResultsThere were 905 women and 337 men with an initial fracture, of whom 253 women and 71 men experienced a subsequent fracture. Relative risk (RR) of subsequent fracture in women was 1.95 (95% confidence interval [CI], 1.70-2.25) and in men was 3.47 (95% CI, 2.68-4.48). As a result, absolute risk of subsequent fracture was similar in women and men and at least as great as the initial fracture risk for a woman 10 years older. Thus, women and men aged 60 to 69 years had absolute refracture rates of 36/1000 person-years (95% CI, 26-48/1000) and 37/1000 person-years (95% CI, 23-59/1000), respectively. The increase in absolute fracture risk remained for up to 10 years, by which time 40% to 60% of surviving women and men experienced a subsequent fracture. All fracture locations apart from rib (men) and ankle (women) resulted in increased subsequent fracture risk, with highest RRs following hip (RR, 9.97; 95% CI, 1.38-71.98) and clinical vertebral (RR, 15.12; 95% CI, 6.06-37.69) fractures in younger men. In multivariate analyses, femoral neck bone mineral density, age, and smoking were predictors of subsequent fracture in women and femoral neck bone mineral density, physical activity, and calcium intake were predictors in men.ConclusionAfter an initial low-trauma fracture, absolute risk of subsequent fracture was similar for men and women. This increased risk occurred for virtually all clinical fractures and persisted for up to 10 years.
Validation of the Gail et al. Model of Breast Cancer Risk Prediction and Implications for Chemoprevention
Authors: B. Rockhill, D. Spiegelman, C. Byrne, D. J. Hunter, G. A. Colditz
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Women and their clinicians are increasingly encouraged to use risk estimates derived from statistical models, primarily that of Gail et al., to aid decision making regarding potential prevention options for breast cancer, including chemoprevention with tamoxifen. Methods: We evaluated both the goodness of fit of the Gail et al. model 2 that predicts the risk of developing invasive breast cancer specifically and its discriminatory accuracy at the individual level in the Nurses' Health Study. We began with a cohort of 82 109 white women aged 45–71 years in 1992 and applied the model of Gail et al. to these women over a 5-year follow-up period to estimate a 5-year risk of invasive breast cancer. All statistical tests were two-sided. Results: The model fit well in the total sample (ratio of expected [E] to observed [O] numbers of cases = 0.94; 95% confidence interval [CI] = 0.89 to 0.99). Underprediction was slightly greater for younger women (<60 years), but in most age and risk factor strata, E/O ratios were close to 1.0. The model fit equally well (E/O ratio = 0.93; 95% CI = 0.87 to 0.99) in a subset of women reporting recent screening (i.e., within 1 year before the baseline); among women with an estimated 5-year risk of developing invasive breast cancer of 1.67% or greater, the E/O ratio was 1.04 (95% CI = 0.96 to 1.12). The concordance statistic, which indicates discriminatory accuracy, for the Gail et al. model 2 when used to estimate 5-year risk was 0.58 (95% CI = 0.56 to 0.60). Only 3.3% of the 1354 cases of breast cancer observed in the cohort arose among women who fell into age–risk strata expected to have statistically significant net health benefits from prophylactic tamoxifen use. Conclusions: The Gail et al. model 2 fit well in this sample in terms of predicting numbers of breast cancer cases in specific risk factor strata but had modest discriminatory accuracy at the individual level. This finding has implications for use of the model in clinical counseling of individual women.
Testosterone and dominance: Between-population variance and male energetics
Authors: Richard G. Bribiescas
Journal: Behavioral and Brain Sciences (1998)

The testosterone–dominance model is noteworthy but should incorporate the ecological factors that often underlie variability in basal testosterone. This is evident in the ethnic testosterone differences discussed in the target article (sect. 8). The significance of acute changes in testosterone levels in response to competition is also poorly understood. Significant metabolic effects have been reported, suggesting that other physiological explanations should be explored, independent of potential behavioral or social factors.