tbuckley/cabot-search huggingface dataset:
Targeting physical activity in a low socioeconomic status population: observations from the Norwegian “Romsås in Motion” study
Authors: A K Jenum, C A N Lorentzen, Y Ommundsen
Journal: British Journal of Sports Medicine (2008)

To summarise the main results of a community-based study on physical activity promotion - "Romsås in Motion".The study assessed changes in physical activity, body mass and psychosocial mediators of physical activity from a pseudo-experimental cohort study involving two districts with low socioeconomic status in Oslo, Norway. In 2000, baseline investigation included 2950 30-67-year-olds - 48% of those invited. At follow-up in 2003 we measured 1776 subjects (67% of those eligible). A set of theoretically informed strategies targeting individuals, groups and the environment were implemented, tailored towards groups with different psychosocial readiness for change. Net changes (the difference between changes in the intervention and control districts) and results of mediation analyses related to the effect of the intervention are reported.The increase in physical activity measured by two questionnaires was 9.5% (p = 0.008) and 8.1% (p = 0.02), respectively. The proportion who increased their body mass was reduced by 50% compared with the control district. Participation in walking and aerobic exercise groups, having seen the "Walk the stairs" poster and used the walk path, were particularly effective intervention components. The most promising psychosocial mediators of forward transition in stages of change were physical activity identity, perceived control, support from friends and family, and self-efficacy when facing psychological barriers.Through a theoretically informed, low-cost, population-based intervention programme an increase in physical activity levels and a reduced weight gain were observed. Mediation findings regarding forward transition in stages of change enhance our understanding of psychosocial mechanisms of behaviour change, and may prove helpful in guiding implementation and evaluation of future interventions.
Clinical, Immunological and Genetic Spectrum Of Novel BTK Gene Mutations In X-Linked Agammaglobulinemia Patients and Female Carriers
Authors: Regan Pyle, John B. Hagan, Amanda Martinez, Avni Y. Joshi, Thomas Boyce, Gerald W. Volcheck, Yesim Yilmaz-Demirdag, Sami L. Bahna, Roshini S. Abraham
Journal: Journal of Allergy and Clinical Immunology (2014)
HIC1 Modulates Prostate Cancer Progression by Epigenetic Modification
Authors: Jianghua Zheng, Jinglong Wang, Xueqing Sun, Mingang Hao, Tao Ding, Dan Xiong, Xiumin Wang, Yu Zhu, Gang Xiao, Guangcun Cheng, Meizhong Zhao, Jian Zhang, Jianhua Wang
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Prostate cancer is the second leading cause of cancer deaths among men in Western counties, which has also occurred in Chinese male with markedly increasing incidence in recent years. Although the mechanism underlying its progression still remains unclear, epigenetic modifications are important ethological parameters. The purpose of this study is to determine the methylation status and function of hypermethylatioted in cancer 1 (HIC1) in prostate cancer progression. Experimental Design: The methylation status of HIC1 promoter was assayed in cell lines, tissues, and plasma of patients with prostate cancer by using methylation-specific PCR and bisulfate sequencing PCR. The ability of HIC1 to regulate proliferation, migration, and invasion was assessed by MTT, scratch-healing assay, and reconstituted extracellular matrices in porous culture chambers. Tumorigenesis, metastases, and bone destruction were analyzed in mice bearing prostate cancer cells restoring HIC1 by using Xenogen IVIS with radiographic system and small-animal positron emission tomography computed tomographic images. Microarrays were searched for genes that had correlated expression with HIC1 mRNA. Reporter gene assays were used to determine whether HIC1 affected the expression of CXCR7, and chromatin immunoprecipitation was used to determine whether HIC1 bound to CXCR7 promoters. All P values were determined using 2-sided tests. Results: The methylation status of 11 CpG sites within HIC1 promoter was abundantly methylated in cell lines, tissues, and plasma of patients with prostate cancer compared with those of respective normal controls. Restoring HIC1 expression in prostate cancer cells markedly inhibited proliferation, migration, and invasion and induced the apoptosis in these cells. Moreover, mice bearing prostate cancer–restoring HIC1 cells had a marked effect on reducing tumor growth, multiple tissue metastases, and bone destruction. Notably, we also identified that the chemokine receptor CXCR7 is a direct downstream target gene of HIC1. Finally, we showed that CXCR7 promoter in prostate cancer cells is negatively regulated by HIC1, which may be responsible for prostate cancer progression. Conclusions: Our data show for the first time that hypermethylation of HIC1 promoter results in loss of its repressive function, responsible for prostate cancer progression and invasion. These findings suggest that therapies targeting epigenetic events regulating HIC1 expression may provide a more effective strategy for prostate cancer treatment. Clin Cancer Res; 19(6); 1400–10. ©2012 AACR.
Efficacy of low-dose alpha interferon therapy in HBV-related chronic liver disease in Asian Indians: a randomized controlled trial
Authors: Shiv K. Sarin, R.C. Guptan, Varsha Thakur, Shailaja Malhotra, Veena Malhotra, Kakoli Banerjee, Pramod Khandekar
Journal: Journal of Hepatology (1996)
Significance of Multifocality in Ductal Carcinoma In Situ: Outcomes of Women Treated With Breast-Conserving Therapy
Authors: Eileen Rakovitch, Jean-Philippe Pignol, Wedad Hanna, Steven Narod, Jacqueline Spayne, Sharon Nofech-Mozes, Carole Chartier, Lawrence Paszat
Journal: Journal of Clinical Oncology (2007)

Purpose There is concern that women with multifocal ductal carcinoma in situ (DCIS; confined to one quadrant) who are treated with breast-conserving surgery face a high risk of local recurrence; therefore, many are treated with mastectomy. The objective of this study is to evaluate the significance of multifocality and the outcomes of women with multifocal DCIS treated with breast-conserving therapy. Methods The records of patients treated with breast-conserving surgery for DCIS between 1982 and 2000 were reviewed. Multivariate analyses were performed to evaluate the effects of multifocality and other prognostic factors on the rate of local recurrence. Results Of 615 cases of DCIS reviewed, 310 (41%) received breast-conserving surgery and 305 (40%) received breast-conserving surgery plus radiation (n = 260 with multifocality, n = 314 without multifocality, and n = 31 focality unreported). On multivariate analysis, multifocality (hazard ratio [HR] = 1.80; 95% CI, 1.15 to 2.80; P = .01), radiation treatment (HR = 0.46; 95% CI, 0.29 to 0.74; P = .001), margin width 4 mm or smaller (HR = 1.74; 95% CI, 1.03 to 2.92; P = .04), and high nuclear grade (HR = 1.65; 95% CI, 1.02 to 2.65; P = .04) were associated with risk of local recurrence. The detrimental effect of multifocality was limited to women who did not receive radiotherapy; the local recurrence–free survival rate at 10 years was 59% for women with multifocal disease and 80% for women without multifocality (P = .02). Among women treated with breast-conserving surgery plus radiation, there was no difference in 10-year local recurrence–free survival (80% v 87%; P = .35). There was no association between multifocality and the development of invasive recurrence. Conclusion Multifocality is a significant predictor of local recurrence in women who receive breast-conserving surgery for DCIS without radiotherapy; however, low recurrence rates can be achieved if adjuvant radiation is administered.
Bayesian Statistical Methods in Public Health and Medicine
Authors: Ruth D. Etzioni, Joseph B. Kadane
Journal: Annual Review of Public Health (1995)

This article reviews the Bayesian statistical approach to the design and analysis of research studies in the health sciences. The central idea of the Bayesian method is the use of study data to update the state of knowledge about a quantity of interest. In study design, the Bayesian approach explicitly incorporates expressions for the loss resulting from an incorrect decision at the end of the study. The Bayesian method also provides a flexible framework for the monitoring of sequential clinical trials. We present several examples of Bayesian methods in practice including a study of disease progression in AIDS, a comparison of two therapies in a clinical trial, and a case-control study investigating the link between dietary factors and breast cancer.
Joint Effects of C-Reactive Protein and Glycated Hemoglobin in Predicting Future Cardiovascular Events of Patients With Advanced Atherosclerosis
Authors: Martin Schillinger, Markus Exner, Jasmin Amighi, Wolfgang Mlekusch, Schila Sabeti, Helmut Rumpold, Oswald Wagner, Erich Minar
Journal: Circulation (2003)

C-reactive protein (CRP) and glycohemoglobin (HbA1c) are established risk factors for the development of cardiovascular disease. We investigated the joint effects of these parameters on cardiovascular outcome of patients with advanced atherosclerosis.We studied 454 patients with advanced atherosclerosis (median age, 69 years; 264 male). Cardiovascular risk profile, high-sensitivity CRP (hs-CRP), and HbA1c were obtained at baseline, and patients were followed for a median of 21 months (interquartile range, 13 to 26) for the occurrence of major adverse cardiovascular events (MACE) (myocardial infarction, percutaneous coronary interventions, coronary artery bypass graft, carotid revascularization, stroke, and death). We observed 166 MACE in 128 patients (28%). Cumulative event-free survival rates at 6, 12, and 24 months were 91%, 85%, and 73%, respectively. Adjusted hazard ratios for the occurrence of MACE according to increasing quartiles of hs-CRP and HbA1c were 1.35 (P=0.31), 1.90 (P=0.026) and 2.13 (P=0.007), and 1.40 (P=0.26), 1.81 (P=0.059), and 2.36 (P=0.023), respectively, compared with the lowest quartiles. Considering both parameters jointly, we found that patients with hs-CRP >0.44 mg/dL and HbA1c >6.2% (upper quartiles) were at highest risk for MACE, with each parameter adding to the prognostic information of the other.Inflammation, indicated by hs-CRP, and hyperglycemia, indicated by HbA1c, jointly contribute to the cardiovascular risk of patients with advanced atherosclerosis. Patients with both hs-CRP and HbA1c in the upper quartiles (>0.44 mg/dL and >6.2%, respectively) are at particularly high risk for poor cardiovascular outcome.
<i>CCR</i> 20th Anniversary Commentary: Immune-Related Response Criteria—Capturing Clinical Activity in Immuno-Oncology
Authors: Axel Hoos, Jedd D. Wolchok, Rachel W. Humphrey, F. Stephen Hodi
Journal: Clinical Cancer Research (2015)

Abstract To evaluate antitumor responses to chemotherapeutic agents, investigators would typically rely upon Response Evaluation Criteria in Solid Tumors (RECIST) or modified WHO criteria, which do not comprehensively capture responses with immunotherapeutic agents. In the December 1, 2009, issue of Clinical Cancer Research, Wolchok and colleagues reported their development of novel criteria, designated “Immune-related Response Criteria” (irRC), designed to better capture the response patterns observed with immunotherapies. Broad use of the irRC since then has allowed for a more comprehensive evaluation of immunotherapies in clinical trials, indicating that their concepts can be used in conjunction with either RECIST or WHO, and has shown irRC to be a powerful tool for improved clinical investigation. Clin Cancer Res; 21(22); 4989–91. ©2015 AACR. See related article by Wolchok et al., Clin Cancer Res 2009;15(23) December 1, 2009;7412–20
Effect of inhaled nitric oxide on hemodynamics and VA/Q inequalities in patients with chronic obstructive pulmonary disease.
Authors: J Moinard, G Manier, O Pillet, Y Castaing
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Nitric oxide (NO) has been reported to be an endothelium-derived relaxing factor, and hypoxic pulmonary vasoconstriction seems to be enhanced by inhibitors of endothelially dependent vascular relaxation. We examined the circulatory effects of inhalation of 15 ppm NO in air in 14 hypoxic patients suffering from chronic obstructive pulmonary disease (COPD). Of these patients 4 breathed 100% O2 before NO. The effects of NO inhalation on pulmonary gas exchange were also studied in 12 of these patients using the multiple inert gas elimination technique, 3 of whom breathed air, 100% O2, and 15 ppm NO in air in succession. Under baseline conditions, both mean +/- SD pulmonary artery pressure and pulmonary vascular resistance were increased (Ppa = 24.3 +/- 10.4 mm Hg and PVR = 3.3 +/- 1.1 mm Hg/L/min, respectively). Although the pulmonary circulatory effects were not immediate, with no detectable changes after 1 min NO inhalation, Ppa and PVR fell significantly (-19.1 +/- 10.5%, p < 0.02 and -29.3 +/- 15.1%, p < 0.02, respectively) after 10 min NO inhalation. Moreover, the extent of the NO-induced reduction in Ppa was found to depend on the level of baseline pulmonary arterial hypertension. No systemic circulatory effects were observed. The mean VA/Q ratio and the dispersion of ventilation and blood flow distributions were not altered by NO inhalation, although there was a significantly higher percentage of ventilation (7.3 +/- 7.3%, p < 0.05) in poorly and unperfused areas (VA/Q > 10).(ABSTRACT TRUNCATED AT 250 WORDS)
The Gap Between the Physiological and Therapeutic Roles of Mesenchymal Stem Cells
Authors: Umberto Galderisi, Antonio Giordano
Journal: Medicinal Research Reviews (2014)

Abstract Several investigators have cultivated marrow stromal cells and have identified a population of mesenchymal stem cells (MSCs). These cells expand extensively in vitro and exhibit multilineage differentiation potential. The lack of MSC‐specific markers impedes identification of MSC functions. Further in vivo studies of these cells may elucidate the nature of MSCs. Although the nature of MSCs remains unclear, nonclonal stromal cultures are used as a source of putative MSCs for therapeutic purposes. Preclinical studies and clinical trials assumed that transplanted MSCs exert their effects through their differentiation properties or through the release of molecules that restore tissue functions and modulate immune cells. These studies reported contradictory results and failed to meet expectations. Thus, it is important to note that current protocols for MSC therapy are primarily based on the use of in vitro expanded nonclonal MSCs. Clearly defining the physiological features of in situ MSCs and the in vitro and in vivo properties of nonclonal cultures of stromal cells, which are often misidentified as pure stem cell cultures, may explain the reported failures of MSC therapy. This review will address these issues.
Synovitis of small joints: sonographic guided diagnostic and therapeutic approach
Authors: W. Grassi, G. Lamanna, A. Farina, C. Cervini
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> The aim of this pictorial essay is to describe the sonographic guided approach to investigation and local injection therapy of a small joint in a patient with psoriatic arthritis (PA). <h3>METHODS</h3> Sonographic pictures are obtained using a high frequency ultrasonography apparatus equipped with a 13-MHz transducer. <h3>RESULTS</h3> Ultrasonography allows a careful morphostructural assessment of soft tissue involvement in PA patients. Sonographic findings include joint cavity widening, capsular thickening, synovial proliferation, synovial fluid changes, tendon sheath widening. Ultrasound guided placement of the needle within the joint and injection of corticosteroid under sonographic control can be easily performed. <h3>CONCLUSIONS</h3> High frequency ultrasonography is a quick and safe procedure that allows a useful diagnostic and therapeutic approach in patients with arthritis of small joints.
Revalidation: a view from Africa
Authors: Andrew R Potter
Journal: BMJ (2005)

S ooner or later, if I want to remain licensed to practise medicine in the United Kingdom, I must undergo the revalidation process. As my practice in sub-Saharan tropical Africa is different from that of my UK colleagues, I wonder whether the criteria for revalidation will be identical.

I work in a charity hospital without mains electricity or water, 15 km outside the large northern town of Parakou in temperatures ranging from 26°C to 40°C. Our diesel generator allows us to enjoy cool air only in the operating theatre. In the outpatients area I sweat, along with everyone else. An unrelentingly hot, humid working environment is not conducive to the General Medical Council's ideal of constant politeness and in-depth discussions of treatment options with my patients.

Our target population is the rural community of farmers and cattle herders, most of whom exist in grinding poverty. They still live in houses of mud and wattle with thatched roofs. Their lives are dominated by the agricultural seasons: hoeing, sowing, weeding, and harvesting. Most do …
Laminin α5 Chain Metastasis- and Angiogenesis-Inhibiting Peptide Blocks Fibroblast Growth Factor 2 Activity by Binding to the Heparan Sulfate Chains of CD44
Authors: Suguru Hibino, Masahiko Shibuya, Matthew P. Hoffman, Jean A. Engbring, Rydhwana Hossain, Mayumi Mochizuki, Shoji Kudoh, Motoyoshi Nomizu, Hynda K. Kleinman
Journal: Cancer Research (2005)

Abstract Recently, we reported that the laminin α5 synthetic peptide A5G27 (RLVSYNGIIFFLK, residues 2,892-2,904) binds to the CD44 receptor of B16-F10 melanoma cells via the glycosaminoglycans on CD44 and inhibits tumor cell migration, invasion, and angiogenesis in a dominant-negative manner. Here, we have identified the potential mechanism of A5G27 activity using WiDr human colorectal carcinoma cells. WiDr cells bound to the laminin A5G27 peptide via the heparin-like and chondroitin sulfate B glycosaminoglycan side chains of CD44. Cell binding to fibroblast growth factor (FGF2) was blocked by laminin peptide A5G27 but not by either a scrambled version of this peptide or by another laminin peptide known to bind cell surface proteoglycans. FGF2 signaling involving tyrosine phosphorylation was also blocked by laminin peptide A5G27 but was not affected by peptide controls. Finally, we have shown that peptide A5G27 directly blocks FGF2 binding to heparin. Peptide A5G27 has sequence homology to a region on FGF2 that binds heparin and the FGF receptor and is important in FGF2 central cavity formation. We conclude that peptide A5G27 inhibits metastasis and angiogenesis by blocking FGF2 binding to the heparan sulfate side chains of CD44 variant 3, thus decreasing FGF2 bioactivity.
Identification of pancreas necrosis in severe acute pancreatitis: imaging procedures versus clinical staging.
Authors: S Block, W Maier, R Bittner, M Buchler, P Malfertheiner, H G Beger
Journal: Gut (1986)

One hundred and five of 395 patients with acute pancreatitis were surgically treated in our clinic from 1981 to 1984. Ninety three of these patients were examined with contrast enhanced computed tomography and/or ultrasound and were clinically assessed according to Ranson's objective criteria before operation. At operation, 77 patients showed necrotising pancreatitis and 16 showed biliary acute interstitial pancreatitis. Ninety per cent of the cases with extensive and 79% of those with minor necroses of the pancreas had been demonstrated with contrast enhanced computed tomography. Ultrasound failed to be diagnostic in 24% of the patients due to meteorism; the sensitivity of the diagnostic studies for pancreatic necrosis was 73% regardless of the extent of the process. Using the early objective signs, seven patients with acute interstitial pancreatitis were classified as having a severe attack, whereas 30 patients with necrotising pancreatitis were categorised as mild attacks. We conclude that the contrast enhanced computed tomography is an aid in deciding on conservative or surgical treatment in a case of acute pancreatitis. Ultrasound does not appear to be an adequate method for determining pancreatic necrosis. The early objective signs fail to sufficiently identify the necrotising form of acute pancreatitis.
Myelin Oligodendrocyte Glycoprotein–specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis
Authors: Estelle Bettelli, Maria Pagany, Howard L. Weiner, Christopher Linington, Raymond A. Sobel, Vijay K. Kuchroo
Journal: The Journal of Experimental Medicine (2003)

Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (&amp;gt;30%) of MOG-specific TCR transgenic mice spontaneously develop isolated optic neuritis without any clinical nor histological evidence of experimental autoimmune encephalomyelitis (EAE). Optic neuritis without EAE could also be induced in these mice by sensitization with suboptimal doses of MOG. The predilection of these mice to develop optic neuritis is associated with higher expression of MOG in the optic nerve than in the spinal cord. These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis.
Chromosomal organization of the human major histocompatibility complex class I gene family.
Authors: B H Koller, D E Geraghty, R DeMars, L Duvick, S S Rich, H T Orr
Journal: The Journal of Experimental Medicine (1989)

17 HLA class I genes have been isolated from the genome of B-lymphoblastoid cell line 721. Sequence analysis and transfection studies indicate that three genes, in addition to those encoding the HLA-A, -B, and -C antigens can direct the synthesis of a class I alpha protein (4, 5, 21). Using gene-specific DNA probes to analyze the presence of restriction fragment-length polymorphisms within a large pedigree and in panel of HLA deletion mutant cell lines, we show here that two of these genes, designated HLA-G and HLA-F, are located on the short arm of chromosome 6 telomeric to the HLA-A locus. The third expressed non-A, -B, and -C class I gene, HLA-E, is located between HLA-A and HLA-C (4). In addition, the remaining 11 class I pseudogenes and gene fragments are localized relative to established markers on chromosome 6p.