tbuckley/cabot-search huggingface dataset:
Oxidized Phospholipids, Lp(a) Lipoprotein, and Coronary Artery Disease
Authors: Sotirios Tsimikas, Emmanouil S. Brilakis, Elizabeth R. Miller, Joseph P. McConnell, Ryan J. Lennon, Kenneth S. Kornman, Joseph L. Witztum, Peter B. Berger
Journal: New England Journal of Medicine (2005)

Lp(a) lipoprotein binds proinflammatory oxidized phospholipids. We investigated whether levels of oxidized low-density lipoprotein (LDL) measured with use of monoclonal antibody E06 reflect the presence and extent of obstructive coronary artery disease, defined as a stenosis of more than 50 percent of the luminal diameter.Levels of oxidized LDL and Lp(a) lipoprotein were measured in a total of 504 patients immediately before coronary angiography. Levels of oxidized LDL are reported as the oxidized phospholipid content per particle of apolipoprotein B-100 (oxidized phospholipid:apo B-100 ratio).Measurements of the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels were skewed toward lower values, and the values for the oxidized phospholipid:apo B-100 ratio correlated strongly with those for Lp(a) lipoprotein (r=0.83, P<0.001). In the entire cohort, the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels showed a strong and graded association with the presence and extent of coronary artery disease (i.e., the number of vessels with a stenosis of more than 50 percent of the luminal diameter) (P<0.001). Among patients 60 years of age or younger, those in the highest quartiles for the oxidized phospholipid:apo B-100 ratio and Lp(a) lipoprotein levels had odds ratios for coronary artery disease of 3.12 (P<0.001) and 3.64 (P<0.001), respectively, as compared with patients in the lowest quartile. The combined effect of hypercholesterolemia and being in the highest quartiles of the oxidized phospholipid:apo B-100 ratio (odds ratio, 16.8; P<0.001) and Lp(a) lipoprotein levels (odds ratio, 14.2; P<0.001) significantly increased the probability of coronary artery disease among patients 60 years of age or younger. In the entire study group, the association of the oxidized phospholipid:apo B-100 ratio with obstructive coronary artery disease was independent of all clinical and lipid measures except one, Lp(a) lipoprotein. However, among patients 60 years of age or younger, the oxidized phospholipid:apo B-100 ratio remained an independent predictor of coronary artery disease.Circulating levels of oxidized LDL are strongly associated with angiographically documented coronary artery disease, particularly in patients 60 years of age or younger. These data suggest that the atherogenicity of Lp(a) lipoprotein may be mediated in part by associated proinflammatory oxidized phospholipids.
HUMAN T CELL RESPONSES AGAINST MELANOMA
Authors: Thierry Boon, Pierre G. Coulie, Benoît J. Van den Eynde, Pierre van der Bruggen
Journal: Annual Review of Immunology (2005)

Many antigens recognized by autologous T lymphocytes have been identified on human melanoma. Melanoma patients usually mount a spontaneous T cell response against their tumor. But at some point, the responder T cells become ineffective, probably because of a local immunosuppressive process occurring at the tumor sites. Therapeutic vaccination of metastatic melanoma patients with these antigens is followed by tumor regressions only in a small minority of the patients. The T cell responses to the vaccines show correlation with the tumor regressions. The local immunosuppression may be the cause of the lack of vaccination effectiveness that is observed in most patients. In patients who do respond to the vaccine, the antivaccine T cells probably succeed in reversing focally this immunosuppression and trigger a broad activation of other antitumor T cells, which proceed to destroy the tumor.
Autophagy Protects the Proximal Tubule from Degeneration and Acute Ischemic Injury
Authors: Tomonori Kimura, Yoshitsugu Takabatake, Atsushi Takahashi, Jun-ya Kaimori, Isao Matsui, Tomoko Namba, Harumi Kitamura, Fumio Niimura, Taiji Matsusaka, Tomoyoshi Soga, Hiromi Rakugi, Yoshitaka Isaka
Journal: Journal of the American Society of Nephrology (2011)

Autophagy is a bulk protein degradation system that likely plays an important role in normal proximal tubule function and recovery from acute ischemic kidney injury. Using conditional Atg5 gene deletion to eliminate autophagy in the proximal tubule, we determined whether autophagy prevents accumulation of damaged proteins and organelles with aging and ischemic renal injury. Autophagy-deficient cells accumulated deformed mitochondria and cytoplasmic inclusions, leading to cellular hypertrophy and eventual degeneration not observed in wildtype controls. In autophagy-deficient mice, I/R injury increased proximal tubule cell apoptosis with accumulation of p62 and ubiquitin positive cytoplasmic inclusions. Compared with control animals, autophagy-deficient mice exhibited significantly greater elevations in serum urea nitrogen and creatinine. These data suggest that autophagy maintains proximal tubule cell homeostasis and protects against ischemic injury. Enhancing autophagy may provide a novel therapeutic approach to minimize acute kidney injury and slow CKD progression.
Association between mycobacterial genotypes and disease progression in Mycobacterium avium pulmonary infection
Authors: T Kikuchi, A Watanabe, K Gomi, T Sakakibara, K Nishimori, H Daito, S Fujimura, R Tazawa, A Inoue, M Ebina, Y Tokue, M Kaku, T Nukiwa
Journal: Thorax (2009)

<h3>Background:</h3> Non-tuberculous mycobacterial lung disease, most commonly caused by <i>Mycobacterium avium</i> infection, tends to show variable disease progression, and significant disease predictors have not been adequately established. <h3>Methods:</h3> Variable numbers of tandem repeats (VNTR) were evaluated in 16 mycobacterial interspersed repetitive unit (MIRU) loci from <i>M avium</i> isolates cultured from respiratory specimens obtained from 2005 to 2007. Specifically, the association between VNTR profiles and disease progression was assessed. <h3>Results:</h3> Among the 37 subjects who provided positive respiratory cultures for <i>M avium</i> during the 2005–6 period, 15 subjects were treated within 10 months following a microbiological diagnosis of progressive <i>M avium</i> lung disease. Nine subjects underwent long-term follow-up (&gt;24 months) without treatment for stable <i>M avium</i> lung disease. Based on a neighbour-joining cluster analysis used to classify <i>M avium</i>-positive subjects according to the VNTR profile, subjects with progressive versus stable lung disease were found to be grouped together in distinct clusters. Further analysis using logistic regression modelling showed that disease progression was significantly associated with the genetic distance of the <i>M avium</i> isolate from an appropriately selected reference (age-adjusted odds ratio 1.95; 95% confidence interval 1.16 to 3.30; p = 0.01 for the most significant model). A best-fit model could be used to predict the progression of <i>M avium</i> lung disease when subjects from the 2005–6 period were combined with those from 2007 (p = 0.003). <h3>Conclusion:</h3> Progressive lung disease due to <i>M avium</i> infection is associated with specific VNTR genotypes of <i>M avium</i>.
A TEST OF CONNECTIVE TISSUE STATE AND REACTIVITY IN COLLAGEN DISEASES*
Authors: Daniel M. Laskin, Milton B. Engel, Norman R. Joseph, Victor E. Pollak
Journal: Journal of Clinical Investigation (1961)

In the group of conditions known as  diseases there are often morphological changes in discrete areas of the connective tissue. For example, fibrinoid degeneration of the collagen fibers and changes in the ground substance may be seen in the subcutaneous nodules of rheumatoid arthritis and in the skin lesions of lupus erythematosus. These lesions are not well understood. The more generalized alterations in the connective tissue are even more difficult to demonstrate and remain poorly defined. Using an in vivo electrometric method, we have previously determined certain physicochemical properties of normal mammalian connective tissue which are related to its amphoteric colloidal structure (1-5). Since these properties may be altered in pathological states, we have adapted this method to study some of the
Exercises for improving bone strength
Authors: C H Turner, A G Robling
Journal: British Journal of Sports Medicine (2005)

The effectiveness of exercise on bone strength depends on its type, timing, and duration

Regular exercise has effects on bone density, size, and shape, resulting in substantial improvements in mechanical strength. The positive association between exercise and bone mass has prompted many physicians and public health officials to recommend that people engage in daily exercise, with the goal of reducing the incidence of osteoporotic fracture and the morbidity/mortality that ensues. However, there is no clear consensus on exactly how one should exercise in order to reap the greatest returns in terms of bone health. What exercises are best? How often should one exercise? Is it sometimes better not to exercise?

Proper exercise can add new bone and/or reduce bone loss to ultimately affect bone mass, but bone mass (or areal bone mineral density) is merely a surrogate measure for bone strength. The real issue at hand is whether or not a person will fracture their hip, spine, or wrist. Bone mineral content and bone mineral density are related to bone strength, but sometimes inferring strength from bone mineral measurements can be misleading. With exercise, small gains in bone mineral can result in large improvements in bone strength,1 because new bone formation is often localised to …
Relation of inflammatory process with COPD phenotype
Authors: Sibel Atis Nayci, Eylem Sercan Özgür, Cengiz Özge, Ahmet Ilvan
Journal: European Respiratory Journal (2012)

Aim: Chronic obstructive lung disease (COPD) does not have a uniform clinical and morphological nature. The aim of the study was to characterize the inflammatory process in two distinct forms of COPD (chronic bronchitis or emphysema).

Methods: 33 COPD patients were investigated. They were divided into two groups: emphysema (n=15) and chronic bronchitis patients (n=18). The distinguishing criteria were the presence of emphysema in HRCT and hyperinflation in pulmonary function test.

The concentration of inflammatory mediators in BAL (IL-8, TNFα, myeloperoxidase (MPO), and neutrophil elastase (NE)) and blood (IL-8, TNFα, CRP and fibrinogen) were measured.

Results: The severity of obstruction (FEV1%) was similar in the two groups (p=0.57). The median BAL concentration of inflammatory mediators (IL-8, TNFα, MPO, NE) did not differ between two groups (p values were 0.82, 0.10, 0.69, and 0.49, respectively). Also serum concentrations of IL-8, TNFα, CRP and fibrinogen were similar between chronic bronchitis and emphysema patients (p values were 0.92, 0.50, 0.32, and 0.53, respectively).

Conclusions: We have shown no differences between the two COPD phenothypes in respect of systemic and bronchial inflammatory profile. This result may indicate a possible similar character of inflammation in chronic bronchitis and emphysema phenotypes.
Patient preferences for autonomy in decision making in asthma management
Authors: R J Adams
Journal: Thorax (2001)

<h3>BACKGROUND</h3> Lower patient preferences for autonomy in management decision making during asthma exacerbations have been associated with an increased risk for future hospital admissions. We sought to examine patient preferences for asthma self-management autonomy, and the clinical and psychosocial factors associated with autonomy preferences. <h3>METHODS</h3> A cross sectional observational study was performed with data collected between June 1995 and December 1997 of 212 adult patients with moderate to severe asthma managed, at least in part, at two teaching hospitals. Subjects completed a survey of autonomy preferences, quality of life, clinical morbidity and health service use, asthma knowledge, self-efficacy, coping styles, and psychosocial measures. <h3>RESULTS</h3> Patients preferred clinicians to assume the major role in most decision making about their management. However, patients wished to remain in control in choosing when to seek care and wanted to share decisions regarding initiating changes in medications during a moderate exacerbation. Multiple regression analysis showed that concerns about adverse effects of medications, education level, an active coping style, perceptions of the propensity of physicians to involve them in treatment decision making, and concerns about costs causing delays in seeking medical care were associated with preferences for autonomy in decision making. Autonomy preferences were not related to measures of concurrent clinical asthma control or health related quality of life. <h3>CONCLUSIONS</h3> In a group of patients with moderate to severe asthma, a high proportion of whom were from socioeconomically disadvantaged backgrounds, education level, perceived physician behaviour, cost barriers to care, and psychosocial factors (but not clinical asthma control or management) were related to patient preferences for autonomy in management decision making during asthma exacerbations. This has implications for asthma action plans and design of self-management programmes.
The Importance of Menaquinones in Human Nutrition
Authors: J. W. Suttie
Journal: Annual Review of Nutrition (1995)

Bacterially produced menaquinones, 2-methyl-1,4-naphthoquinones with an unsaturated polyisoprenoid chain at the 3-position, are biologically active forms of vitamin K that are present in high concentrations in the human lower bowel. Menaquinones are found in human liver and circulate in human plasma at much higher concentrations than previously thought. Numerous case reports of antibiotic-induced, vitamin K-responsive hypothrombinemias have been taken as evidence that menaquinones contribute importantly to satisfying the human vitamin K requirement. However, more recent production of symptoms of vitamin K insufficiency in normal human subjects by dietary restriction of vitamin K argues against their nutritional significance. Current data support the view that menaquinones may partially satisfy the human requirement but that their contribution is much less than previously thought.
EFFECTS OF CREATINE AND GLUTAMINE SUPPLEMENTS IN COMPARISON WITH PROPER NUTRITION ON WRESTLERS
Authors: Masoud Abbasalipour, A Hashemi
Journal: British Journal of Sports Medicine (2013)

Aim In this study, we investigated the effects of glutamine and creatine supplements and proper nutrition on hand grip strength and agility of athletes. Materials and Methods The samples for this study included 28 elite wrestlers of Mazandaran province, Iran aged 18 to 25 years old. They were randomly divided into four groups. Proper nutrition with carbohydrate solution made of 5% honey instead of water, creatine supplement group (0.3 g/Kg/ for 15 days), glutamine group (0.3 g/kg for 15 days), control group. After a usual warm-up exercises for 15 minutes, for the agility test, 9x4 agility test was performed and following a 10-min rest period, subjects used hand grip for the grip strength test; after 15 days of glutamine and creatine supplements and proper nutrition consumptions, the physical performance tests were conducted in the same condition. Statistical analyses were performed using SPSS software. Results Statistical analysis of the grip strength and agility in post test showed significant difference between the proper nutrition, in comparison with the control group (p&lt;0.05). Therefore, it seems that through proper nutrition (which provides all necessary substances for an elite athlete) there is no need for these supplementation agents and the proper nutrition can be used as an alternative for these supplements. Conclusion The group which received the proper nutrition showed more increase in speed and power performance compared to the creatine and glutamine groups. It seems that if elite athletes consume proper nutrition and especially get benefit from honey, there is no further need to use supplements. Finally, from the findings of the present study it can be concluded that the proper nutrition can be used as a competent alternative for the common supplements such a creatine and glutamine.
The chemotherapeutic agent DMXAA potently and specifically activates the TBK1–IRF-3 signaling axis
Authors: Zachary J. Roberts, Nadege Goutagny, Pin-Yu Perera, Hiroki Kato, Himanshu Kumar, Taro Kawai, Shizuo Akira, Ram Savan, David van Echo, Katherine A. Fitzgerald, Howard A. Young, Lai-Ming Ching, Stefanie N. Vogel
Journal: The Journal of Experimental Medicine (2007)

Vascular disrupting agents (VDAs) represent a novel approach to the treatment of cancer, resulting in the collapse of tumor vasculature and tumor death. 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is a VDA currently in advanced phase II clinical trials, yet its precise mechanism of action is unknown despite extensive preclinical and clinical investigations. Our data demonstrate that DMXAA is a novel and specific activator of the TANK-binding kinase 1 (TBK1)–interferon (IFN) regulatory factor 3 (IRF-3) signaling pathway. DMXAA treatment of primary mouse macrophages resulted in robust IRF-3 activation and ∼750-fold increase in IFN-β mRNA, and in contrast to the potent Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS), signaling was independent of mitogen-activated protein kinase (MAPK) activation and elicited minimal nuclear factor κB–dependent gene expression. DMXAA-induced signaling was critically dependent on the IRF-3 kinase, TBK1, and IRF-3 but was myeloid differentiation factor 88–, Toll–interleukin 1 receptor domain–containing adaptor inducing IFN-β–, IFN promoter-stimulator 1–, and inhibitor of κB kinase–independent, thus excluding all known TLRs and cytosolic helicase receptors. DMXAA pretreatment of mouse macrophages induced a state of tolerance to LPS and vice versa. In contrast to LPS stimulation, DMXAA-induced IRF-3 dimerization and IFN-β expression were inhibited by salicylic acid. These findings detail a novel pathway for TBK1-mediated IRF-3 activation and provide new insights into the mechanism of this new class of chemotherapeutic drugs.
Mutations in the hereditary haemochromatosis gene HFE in professional endurance athletes
Authors: J L Chicharro, J Hoyos, F Gómez-Gallego, J G Villa, F Bandrés, P Celaya, F Jiménez, J M Alonso, A Córdova, A Lucia
Journal: British Journal of Sports Medicine (2004)

Hereditary haemochromatosis, a disease that affects iron metabolism, progresses with a greater or lesser tendency to induce iron overload, possibly leading to severe organ dysfunction. Most elite endurance athletes take iron supplements during their active sporting life, which could aggravate this condition.To determine the prevalence and discuss potential clinical implications of mutations of HFE (the gene responsible for hereditary haemochromatosis) in endurance athletes.Basal concentrations of iron, ferritin, and transferrin and transferrin saturation were determined in the period before competition in 65 highly trained athletes. Possible mutations in the HFE gene were evaluated in each subject by extracting genomic DNA from peripheral blood. The restriction enzymes SnaBI and BclI were used to detect the mutations 845G-->A (C282Y) and 187C-->G (H63D).Our findings indicate a high prevalence of HFE gene mutations in this population (49.2%) compared with sedentary controls (33.5%). No association was detected in the athletes between mutations and blood iron markers.The findings support the need to assess regularly iron stores in elite endurance athletes.
Use of magnetic perfusion-weighted imaging to determine epidermal growth factor receptor variant III expression in glioblastoma
Authors: Elana S. Tykocinski, Ryan A. Grant, Gurpreet S. Kapoor, Jaroslaw Krejza, Leif-Erik Bohman, Timothy A. Gocke, Sanjeev Chawla, Casey H. Halpern, Joanna Lopinto, Elias R. Melhem, Donald M. O'Rourke
Journal: Neuro-Oncology (2012)

Identification of the epidermal growth factor receptor variant III (EGFRvIII) mutation in glioblastoma has become increasingly relevant in the optimization of therapy. Traditionally, determination of tumor EGFRvIII-expression has relied on tissue-based diagnostics. Here, we assess the accuracy of magnetic resonance perfusion-weighted imaging (MR-PWI) in discriminating the EGFRvIII-expressing glioblastoma subtype. We analyzed RNA from 132 primary human glioblastoma tissue samples by reverse-transcription polymerase chain reaction (RT-PCR) for the EGFRvIII and EGFR wild-type mutations and by quantitative RT-PCR for expression of vascular endothelial growth factor (VEGF). Concurrently, 3 independent observers reviewed preoperative 1.5-Tesla (T)/SE or 3.0-Tesla (T)/GE MR perfusion images to determine the maximum relative tumor blood volume (rTBV) of each of these tumors. EGFRvIII-expressing glioblastomas showed significantly higher rTBV, compared with those tumors lacking EGFRvIII expression. This association was observed in both the 1.5T/SE (P = .000) and 3.0T/GE (P = .001) cohorts. By logistic regression analysis, combining the 2 MR system cohorts, rTBV was a very strong predictor of EGFRvIII mutation (odds ratio [rTBV] = 2.70; P = .000; McFadden's ρ2 = 0.23). Furthermore, by receiver-operating characteristic curve analysis, rTBV discriminated EGFRvIII with very high accuracy (Az = 0.81). In addition, we found that VEGF upregulation was associated, although without reaching statistical significance, with EGFRvIII expression (P = .16) and with increased rTBV (F-ratio = 2.71; P = .102). These trends suggest that VEGF-mediated angiogenesis may be a potential mediator of angiogenesis to increase perfusion in EGFRvIII-expressing glioblastomas, but there are likely several other contributing factors. This study demonstrates the potential to use rTBV, a MR-PWI–derived parameter, as a noninvasive surrogate of the EGFRvIII mutation.
Colchicine for Periodic Peritonitis
Authors: Hobart A. Reimann
Journal: JAMA (1975)

After 25 years of unsuccessful therapeutic trials, colchicine suppressed episodes of periodic peritonitis (recurrent polyserositis, familial Mediterranean fever) in most reported cases after 1972 and in 12 of 14 patients in this study. Dosage of 0.65 mg daily was continuous, but intermittent therapy timed in accordance with predicted episodes is under trial. Suppression of episodes by the drug serves as the only diagnostic test available.
MPs call for risk assessment review of safety of UK blood supply
Authors: A. O'Dowd
Journal: BMJ (2014)

The government should order a full review of the UK blood supply to gauge whether it contains a significant risk of the degenerative brain disease variant Creutzfeldt-Jakob Disease (vCJD) being passed on, MPs have said.

The recommendation came from the House of Commons Science and Technology Committee in a new report that follows the committee’s recent inquiry into the issue. The report criticises the government for its “casual attitude” to transmission of the disease and for not remaining vigilant.1

The disease, sometimes called the human form of bovine spongiform encephalopathy (BSE) or “mad cow disease,” emerged after widespread exposure to BSE prions in the late 1980s and early 1990s through contaminated …