tbuckley/cabot-search huggingface dataset:
Injury and biomechanical perspectives on the rugby scrum: a review of the literature
Authors: Grant Trewartha, Ezio Preatoni, Michael E England, Keith A Stokes
Journal: British Journal of Sports Medicine (2014)

As a collision sport, rugby union has a relatively high overall injury incidence, with most injuries being associated with contact events. Historically, the set scrum has been a focus of the sports medicine community due to the perceived risk of catastrophic spinal injury during scrummaging. The contemporary rugby union scrum is a highly dynamic activity but to this point has not been well characterised mechanically. In this review, we synthesise the available research literature relating to the medical and biomechanical aspects of the rugby union scrum, in order to (1) review the injury epidemiology of rugby scrummaging; (2) consider the evidence for specific injury mechanisms existing to cause serious scrum injuries and (3) synthesise the information available on the biomechanics of scrummaging, primarily with respect to force production. The review highlights that the incidence of acute injury associated with scrummaging is moderate but the risk per event is high. The review also suggests an emerging acknowledgement of the potential for scrummaging to lead to premature chronic degeneration injuries of the cervical spine and summarises the mechanisms by which these chronic injuries are thought to occur. More recent biomechanical studies of rugby scrummaging confirm that scrum engagement forces are high and multiplanar, but can be altered through modifications to the scrum engagement process which control the engagement velocity. As the set scrum is a relatively 'controlled' contact situation within rugby union, it remains an important area for intervention with a long-term goal of injury reduction.
Topical steroids and bacterial infection
Authors: J.A. SAVIN
Journal: British Journal of Dermatology (1976)

Journal Article Topical steroids and bacterial infection Get access J.A. SAVIN J.A. SAVIN Department of Dermatology, The Royal Infirmary, Edinburgh EH3 9YW Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 94, Issue s12, 1 March 1976, Pages 125–128, https://doi.org/10.1111/j.1365-2133.1976.tb02281.x Published: 01 March 1976
Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction- a novel mechanism for maintaining vascular function
Authors: Ying Shao, Zhongjian Cheng, Xinyuan Li, Valeria Chernaya, Hong Wang, Xiao-feng Yang
Journal: Journal of Hematology & Oncology (2014)

Endothelial dysfunction is a pathological status of the vascular system, which can be broadly defined as an imbalance between endothelium-dependent vasoconstriction and vasodilation. Endothelial dysfunction is a key event in the progression of many pathological processes including atherosclerosis, type II diabetes and hypertension. Previous reports have demonstrated that pro-inflammatory/immunoeffector cytokines significantly promote endothelial dysfunction while numerous novel anti-inflammatory/immunosuppressive cytokines have recently been identified such as interleukin (IL)-35. However, the effects of anti-inflammatory cytokines on endothelial dysfunction have received much less attention. In this analytical review, we focus on the recent progress attained in characterizing the direct and indirect effects of anti-inflammatory/immunosuppressive cytokines in the inhibition of endothelial dysfunction. Our analyses are not only limited to the importance of endothelial dysfunction in cardiovascular disease progression, but also expand into the molecular mechanisms and pathways underlying the inhibition of endothelial dysfunction by anti-inflammatory/immunosuppressive cytokines. Our review suggests that anti-inflammatory/immunosuppressive cytokines serve as novel therapeutic targets for inhibiting endothelial dysfunction, vascular inflammation and cardio- and cerebro-vascular diseases.
Mutations in antiquitin in individuals with pyridoxine-dependent seizures
Authors: Philippa B Mills, Eduard Struys, Cornelis Jakobs, Barbara Plecko, Peter Baxter, Matthias Baumgartner, Michèl A A P Willemsen, Heymut Omran, Uta Tacke, Birgit Uhlenberg, Bernhard Weschke, Peter T Clayton
Journal: Nature Medicine (2006)
Repair of Tobacco Carcinogen-Induced DNA Adducts and Lung Cancer Risk: a Molecular Epidemiologic Study
Authors: None Qingyi Wei
Journal: JNCI Journal of the National Cancer Institute (2000)

Only a fraction of cigarette smokers develop lung cancer, suggesting that people differ in their susceptibility to this disease. We investigated whether differences in DNA repair capacity (DRC) for repairing tobacco carcinogen-induced DNA damage are associated with differential susceptibility to lung cancer.From August 1, 1995, through April 30, 1999, we conducted a hospital-based, case-control study of 316 newly diagnosed lung cancer patients and 316 cancer-free control subjects matched on age, sex, and smoking status. DRC was measured in cultured lymphocytes with the use of the host-cell reactivation assay with a reporter gene damaged by a known activated tobacco carcinogen, benzo[a]pyrene diol epoxide. Statistical tests were two-sided.Overall, lower DRC was observed in case patients than in control subjects (P:<.001) and was associated with a greater than twofold increased risk of lung cancer. Compared with the highest DRC quartile in the control subjects and after adjustment for age, sex, pack-years of smoking, family history of cancer, and other covariates, reduced DRC was associated with increased risk of lung cancer in a dose-dependent fashion (odds ratio [OR] = 1.8 with 95% confidence interval [CI] = 1.1-3.1, OR = 2.0 with 95% CI = 1.2-3.4, and OR = 4. 3 with 95% CI = 2.6-7.2 for the second, third, and fourth quartiles, respectively; P:(trend)<.001). Case patients who were younger at diagnosis (<60 years old), female, or lighter smokers or who reported a family history of cancer exhibited the lowest DRC and the highest lung cancer risk among their subgroups, suggesting that these subgroups may be especially susceptible to lung cancer.The results provide evidence that low DRC is associated with increased risk of lung cancer. The findings from this hospital-based, case-control study should be validated in prospective studies.
Effects of intravascular cryotherapy on vessel wall repair in a balloon-injured rabbit iliac artery model
Authors: A Cheema
Journal: Cardiovascular Research (2003)

Although the application of cold energy, cryotherapy, has been shown to cause selective damage to cellular components with preservation of matrix structure resulting in less fibrosis in a variety of tissues, the effects of intravascular cryotherapy on vessel wall repair after balloon angioplasty are unknown. We sought to characterize the effects of cryotherapy application on vessel wall repair after balloon angioplasty and study the relationship between collagen accumulation in the vessel wall and late lumen loss as assessed by serial intravascular ultrasound.The immediate, early (72 h) and late (10 weeks) effects of three intravascular cryotherapy application time periods (60, 120 and 240 s) after iliac artery balloon angioplasty ('cryotherapy') were compared with balloon angioplasty alone ('control') in 59 rabbits. Arterial lumen area was measured by intravascular ultrasound immediately after the procedure, at 72 h and at 10 weeks. Collagen content was calculated separately for intima and media/adventitia layers and correlated with late lumen loss.Cryotherapy produced average vessel wall temperature of -26 degrees C (range, -20 to -45 degrees C) and resulted in significantly larger lumen cross-sectional area (CSA) immediately after application (5.74+/-1.18 vs. 4.14+/-0.75 mm(2), P=0.008) but was not different than control arteries at 10 weeks. At 72 h, there was extensive cell loss in the medial and adventitial layers accompanied by increased macrophage infiltration in cryotherapy treated arteries compared to control. At 10 weeks, intimal hyperplasia was increased 2-fold in cryotherapy treated arteries. Collagen content was increased 2-fold in the medial/adventitial layers, and nearly 3-fold in the intima of cryotherapy treated arteries. Collagen content in arterial intima (P=0.01) as well as media/adventitia (P=0.005) positively correlated with late lumen loss. Foci of chondro- and osseous metaplasia and calcification were evident at the medial-adventitial junction in cryotherapy treated arteries at 10 weeks.Intravascular cryotherapy induced early arterial wall cell loss and late intimal hyperplasia, vascular fibrosis and chondro- and osseous metaplastic changes with no late beneficial effects on lumen area compared to balloon angioplasty alone. Collagen accumulation in all three layers of the vessel wall contributes to the development of late inward remodeling after balloon angioplasty.
Conjunctival involvement in the autoimmune blistering dermatoses: a clinical and histopathological study
Authors: Peggy Frith, V. Venning, F. Wojnarowska, P. Millard, A. Bron
Journal: British Journal of Dermatology (1987)

Journal Article Conjunctival involvement in the autoimmune blistering dermatoses: a clinical and histopathological study Get access Peggy Frith, Peggy Frith Oxford Eye Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar V. Venning, V. Venning Department of Dermatology, Slade Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar F. Wojnarowska, F. Wojnarowska Department of Dermatology, Slade Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar P. Millard, P. Millard Department of Histopathology, John Radcliffe Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar A. Bron A. Bron Oxford Eye Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue s32, 1 June 1987, Page 19, https://doi.org/10.1111/j.1365-2133.1987.tb12001.x Published: 01 June 1987
Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: reanalysis of West African studies
Authors: Peter Aaby, Henrik Jensen, Badara Samb, Badara Cisse, Morten Sodemann, Marianne Jakobsen, Anja Poulsen, Amabelia Rodrigues, Ida Maria Lisse, Francois Simondon, Hilton Whittle
Journal: The Lancet (2003)
Representation is space-variant
Authors: Giorgio Bonmassar, Eric L. Schwartz
Journal: Behavioral and Brain Sciences (1998)

Under shift, caused for example by eye movement, or by relative movement of the subject or object of perception, the cortical representation undergoes very large changes in “size” and “shape.” Space-variance of cortical representation rules out models that fundamentally require linear interpolation between shifted patterns (e.g., Edelman's model) or rigid shift of an invariant retinal stimulus corresponding to shift at the cortex (e.g., the shifter theory of van Essen). Recently, a computational solution of “quasi-shift” invariance for space-variant mappings has been constructed (Bonmassar &amp; Schwartz 1997a; 1997b).
Discrepancies between FISH and immunohistochemistry for assessment of the ALK status are associated with ALK ‘borderline’-positive rearrangements or a high copy number: a potential major issue for anti-ALK therapeutic strategies
Authors: M.I. Ilie, C. Bence, V. Hofman, E. Long-Mira, C. Butori, L. Bouhlel, S. Lalvée, J. Mouroux, M. Poudenx, J. Otto, C.H. Marquette, P. Hofman
Journal: Annals of Oncology (2014)
Influenza subunit vaccine: antibody responses to one and two doses of vaccine and length of response, with particular reference to the elderly.
Authors: J S MacKenzie
Journal: BMJ (1977)

Antibody responses to subunit influenza vaccine prepared against A2/England/42/72 (h3n2) were studied in 69 volunteers aged 60 and over and 231 aged 59 and below over 12 months in 1973 and 1974. After two doses of vaccine seroconversion frequencies and geometric mean haemagglutination-inhibition (HI) titres were higher in the elderly, but no differences were observed between the two groups in the length of their responses. Sixteen (23%) of the elderly volunteers seroconverted only after receiving a second dose of vaccine or seroconverted twice after receiving both doses of vaccine. It was considered justifiable, therefore, to recommend the continuation of a two-dose schedule for patients in a high-risk category. Within 30 weeks of vaccination 87 (29%) volunteers had considerably reduced HI titres (less than 48), which might indicate potential susceptibility to influenza during an epidemic, and the number had risen to 132 (44%) by 50 weeks. It was suggested that high-risk patients should receive annnual vaccination two to four months before the possible epidemic period.
Smad1 Protects Cardiomyocytes From Ischemia-Reperfusion Injury
Authors: Mitsuru Masaki, Masahiro Izumi, Yuichi Oshima, Yoshikazu Nakaoka, Tadashi Kuroda, Ryusuke Kimura, Shoko Sugiyama, Kazuo Terai, Masafumi Kitakaze, Keiko Yamauchi-Takihara, Ichiro Kawase, Hisao Hirota
Journal: Circulation (2005)

We previously reported that bone morphogenetic protein 2 (BMP2) protected against apoptosis of serum-deprived cardiomyocytes via induction of Bcl-xL through the Smad1 pathway. To investigate whether Smad1 signaling promotes cell survival in the adult heart, we subjected transgenic mice with cardiac-specific overexpression of smad1 gene (Smad1TG) to ischemia-reperfusion (I/R) injury.The effects of BMP2 or adenovirus-mediated transfection of smad1 on cardiomyocyte survival in hypoxia-reoxygenation were examined using rat neonatal cardiomyocytes. BMP2 and Smad1 each significantly promoted survival and diminished apoptotic death of cardiomyocytes during hypoxia-reoxygenation. Interestingly, Smad1 was found to be activated during I/R in normal mouse heart. To examine physiological and pathological roles of Smad1 in I/R, we generated Smad1TG using the alpha-myosin heavy chain gene promoter. Phosphorylation of Smad1 was found in all smad1 transgene-positive mouse hearts. To examine whether Smad1 prevents injury of cardiomyocytes in vivo, we subjected Smad1TG and age-matched wild-type mice (WT) to I/R injury induced by 1 hour of ligation of the left coronary artery and 1 hour of reperfusion. TUNEL and DNA ladder analyses showed that Smad1TG had significantly smaller myocardial infarctions and fewer apoptotic deaths of cardiomyocytes than did WT. Interestingly, increased expression of Bcl-xL and beta-catenin was more remarkable whereas caspase3 was less activated in Smad1TG heart than in that of WT.These findings suggest that the Smad1 signaling pathway plays a role in cardioprotection against I/R injury.
Effect of Phosphate Depletion on Magnesium Homeostasis in Rats
Authors: Wilhelm J. Kreusser, Kiyoshi Kurokawa, Enrique Aznar, Ellen Sachtjen, Shaul G. Massry
Journal: Journal of Clinical Investigation (1978)

The effects of phosphate depletion on magnesium (Mg) homeostasis were evaluated in rats fed a diet containing 0.03% phosphorus for periods up to 8 wk. Plasma phosphorus fell significantly (P < 0.01) from 10.1±0.27 (SE) to 5.0±0.54 mg/100 ml within 1 day and continued to fall gradually to a level of 1.2±0.21 mg/100 ml by the end of the 8th wk. A significant (P < 0.01) increment in urinary Mg excretion (UMgV) from 46±2.7 to 126±24 μeq/24 h occurred during the 1st day of phosphate depletion; UMgV reached a peak of 300±24 μeq/24 h by the 3rd day and remained high ranging between 150-300 μeq/24 h, thereafter. The magnitude of the magnesuria was related to the degree of hypophosphatemia and was not affected by lowering the calcium intake and reducing the hypercalciuria. The concentration of plasma Mg fell significantly (P < 0.01) from 1.2±0.02 to 0.79±0.10 meq/liter by the 1st day of the study and remained low throughout.
Significant Biological Role of Sp1 Transactivation in Multiple Myeloma
Authors: Mariateresa Fulciniti, Samir Amin, Puru Nanjappa, Scott Rodig, Rao Prabhala, Cheng Li, Stephane Minvielle, Yu-tzu Tai, Pierfrancesco Tassone, Herve Avet-Loiseau, Teru Hideshima, Kenneth C. Anderson, Nikhil C. Munshi
Journal: Clinical Cancer Research (2011)

The transcription factor specificity protein 1 (Sp1) controls number of cellular processes by regulating the expression of critical cell cycle, differentiation, and apoptosis-related genes containing proximal GC/GT-rich promoter elements. We here provide experimental and clinical evidence that Sp1 plays an important regulatory role in multiple myeloma (MM) cell growth and survival.We have investigated the functional Sp1 activity in MM cells using a plasmid with Firefly luciferase reporter gene driven by Sp1-responsive promoter. We have also used both siRNA- and short hairpin RNA-mediated Sp1 knockdown to investigate the growth and survival effects of Sp1 on MM cells and further investigated the anti-MM activity of terameprocol (TMP), a small molecule that specifically competes with Sp1-DNA binding in vitro and in vivo.We have confirmed high Sp1 activity in MM cells that is further induced by adhesion to bone marrow stromal cells (BMSC). Sp1 knockdown decreases MM cell proliferation and induces apoptosis. Sp1-DNA binding inhibition by TMP inhibits MM cell growth both in vitro and in vivo, inducing caspase-9-dependent apoptosis and overcoming the protective effects of BMSCs.Our results show Sp1 as an important transcription factor in myeloma that can be therapeutically targeted for clinical application by TMP.
Molecular Mechanisms of Epidermal Growth Factor Receptor (EGFR) Activation and Response to Gefitinib and Other EGFR-Targeting Drugs
Authors: Mayumi Ono, Michihiko Kuwano
Journal: Clinical Cancer Research (2006)

Abstract The epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, including EGFR, HER2/erbB2, and HER3/erbB3, is an attractive target for antitumor strategies. Aberrant EGFR signaling is correlated with progression of various malignancies, and somatic tyrosine kinase domain mutations in the EGFR gene have been discovered in patients with non–small cell lung cancer responding to EGFR-targeting small molecular agents, such as gefitinib and erlotinib. EGFR overexpression is thought to be the principal mechanism of activation in various malignant tumors. Moreover, an increased EGFR copy number is associated with improved survival in non–small cell lung cancer patients, suggesting that increased expression of mutant and/or wild-type EGFR molecules could be molecular determinants of responses to gefitinib. However, as EGFR mutations and/or gene gains are not observed in all patients who respond partially to treatment, alternative mechanisms might confer sensitivity to EGFR-targeting agents. Preclinical studies showed that sensitivity to EGFR tyrosine kinase inhibitors depends on how closely cell survival and growth signalings are coupled with EGFR, and also with HER2 and HER3, in each cancer. This review also describes a possible association between EGFR phosphorylation and drug sensitivity in cancer cells, as well as discussing the antiangiogenic effect of gefitinib in association with EGFR activation and phosphatidylinositol 3-kinase/Akt activation in vascular endothelial cells.
T Cell–Mediated Hypersensitivity Reactions to Drugs
Authors: Rebecca Pavlos, Simon Mallal, David Ostrov, Soren Buus, Imir Metushi, Bjoern Peters, Elizabeth Phillips
Journal: Annual Review of Medicine (2014)

The immunological mechanisms driving delayed hypersensitivity reactions (HSRs) to drugs mediated by drug-reactive T lymphocytes are exemplified by several key examples and their human leukocyte antigen (HLA) associations: abacavir and HLA-B*57:01, carbamazepine and HLA-B*15:02, allo-purinol and HLA-B*58:01, and both amoxicillin-clavulanate and nevirapine with multiple class I and II alleles. For HLA-restricted drug HSRs, specific class I and/or II HLA alleles are necessary but not sufficient for tissue specificity and the clinical syndrome. Several models have been proposed to explain the immunopathogenesis of severe T cell-mediated drug HSRs, and our increased understanding of the risk factors and mechanisms involved in the development of these reactions will further the development of sensitive and specific strategies for preclinical screening that will lead to safer and more cost-effective drug design.
Alcohol Consumption in Relation to Metabolic Regulation, Inflammation, and Adiponectin in 64-Year-Old Caucasian Women
Authors: Linda Englund Ögge, Gerhard Brohall, Carl Johan Behre, Caroline Schmidt, Björn Fagerberg
Journal: Diabetes Care (2006)

OBJECTIVE— The aims of this study were to examine alcohol drinking patterns in women with type 2 diabetes, impaired glucose tolerance (IGT), and normal glucose tolerance (NGT) and to investigate whether alcohol intake was associated with improved insulin sensitivity, decreased biomarkers of inflammation, and increased adiponectin levels and if these effects were limited to dysmetabolic women. RESEARCH DESIGN AND METHODS— From a cohort of 64-year-old Caucasian women, 209 with type 2 diabetes, 205 with IGT, and 186 with NGT were recruited. Alcohol consumption and medication use were assessed by questionnaires. Anthropometric data were collected, and blood glucose, insulin, HDL cholesterol, triglycerides, C-reactive protein, white blood cell count, and serum adiponectin were measured. RESULTS— Compared with the NGT group, alcohol consumption was lower in the IGT group and lowest in the diabetes group. Mean alcohol intakes of &amp;gt;9.2 and ≥3–9 g/day were positively associated with adiponectin and insulin sensitivity (homeostasis model assessment [HOMA]), respectively, independently of obesity, metabolic control, and other confounders. Alcohol intake correlated negatively with inflammatory markers, although this did not remain after adjustment for HOMA and waist circumference. The inverse associations between alcohol consumption and factors related to the metabolic syndrome such as HOMA, waist circumference, and inflammatory markers were more obvious among women with diabetes and IGT than in healthy women. CONCLUSIONS— In these women, moderate alcohol consumption showed beneficial associations with the prevalence of type 2 diabetes, IGT, insulin sensitivity, and serum adiponectin. There is a need to clarify whether adiponectin may be a mechanistic link and also to clarify the clinical implications of these observations.