tbuckley/cabot-search huggingface dataset:
Reversible Membranous Nephropathy Associated With the Use of Nonsteroidal Anti-inflammatory Drugs
Authors: M. Gene Radford
Journal: JAMA (1996)

To investigate the frequency of membranous nephropathy associated with nonsteroidal anti-inflammatory drug (NSAID) use and identify associated clinical characteristics.Retrospective chart review.A large group practice that staffs 2 large teaching hospitals.All patients diagnosed as having stage I or early stage II membranous nephropathy by renal biopsy between January 1975 and May 1995.Nephrotic syndrome was said to be associated with NSAID use if patients developed nephrotic syndrome while taking an NSAID and if other causes of membranous nephropathy were excluded and a rapid remission of the nephrotic syndrome followed withdrawal of the drug.Of 125 patients identified with early membranous nephropathy, 29 were taking NSAIDs at the time symptoms of nephrotic syndrome developed. Thirteen of these patients met the criteria for NSAID-associated membranous nephropathy. None of these patients had any evidence of renal insufficiency or significant proteinuria after follow-up periods ranging from 5 months to 13 years. In addition to diclofenac and fenoprofen, which have previously been implicated, ibuprofen, nabumetone, naproxen, and tolmetin were found to be associated.Nephrotic syndrome due to membranous nephropathy should be recognized as an idiosyncratic drug reaction to many NSAIDS. Because withdrawal of the drug may result in prompt and complete recovery of normal renal function, a history of NSAID intake should be sought in patients with membranous nephropathy.
Borrelia burgdorferi activates a T helper type 1-like T cell subset in Lyme arthritis.
Authors: H Yssel, M C Shanafelt, C Soderberg, P V Schneider, J Anzola, G Peltz
Journal: The Journal of Experimental Medicine (1991)

18 cloned T cell lines reactive with Borrelia burgdorferi proteins, all CD3+4+8-TCR-alpha/beta+ and restricted by HLA class II proteins, were isolated from four patients with chronic Lyme arthritis. Analysis of these T cell clones indicated that the T cell response to the Lyme disease spirochete is not oligoclonally restricted; yet all produced the same pattern of lymphokines, resembling that of murine type 1 T helper cells, after antigen-specific or nonspecific stimulation. Therefore, a subset of human CD4+ T cells, with a distinct profile of lymphokine secretion, is selectively activated by the pathogen inciting this chronic inflammatory disease.
Evolutionary history and functional implications of protein domains and their combinations in eukaryotes
Authors: Masumi Itoh, Jose C Nacher, Kei-ichi Kuma, Susumu Goto, Minoru Kanehisa
Journal: Genome biology (2007)

Abstract Background In higher multicellular eukaryotes, complex protein domain combinations contribute to various cellular functions such as regulation of intercellular or intracellular signaling and interactions. To elucidate the characteristics and evolutionary mechanisms that underlie such domain combinations, it is essential to examine the different types of domains and their combinations among different groups of eukaryotes. Results We observed a large number of group-specific domain combinations in animals, especially in vertebrates. Examples include animal-specific combinations in tyrosine phosphorylation systems and vertebrate-specific combinations in complement and coagulation cascades. These systems apparently underwent extensive evolution in the ancestors of these groups. In extant animals, especially in vertebrates, animal-specific domains have greater connectivity than do other domains on average, and contribute to the varying number of combinations in each animal subgroup. In other groups, the connectivities of older domains were greater on average. To observe the global behavior of domain combinations during evolution, we traced the changes in domain combinations among animals and fungi in a network analysis. Our results indicate that there is a correlation between the differences in domain combinations among different phylogenetic groups and different global behaviors. Conclusion Rapid emergence of animal-specific domains was observed in animals, contributing to specific domain combinations and functional diversification, but no such trends were observed in other clades of eukaryotes. We therefore suggest that the strategy for achieving complex multicellular systems in animals differs from that of other eukaryotes.
Chemotherapy-Induced Amenorrhea in Patients With Breast Cancer With a <i>BRCA1</i> or <i>BRCA2</i> Mutation
Authors: Adriana Valentini, Amy Finch, Jan Lubiński, Tomasz Byrski, Parviz Ghadirian, Charmaine Kim-Sing, Henry T. Lynch, Peter J. Ainsworth, Susan L. Neuhausen, Ellen Greenblatt, Christian Singer, Ping Sun, Steven A. Narod
Journal: Journal of Clinical Oncology (2013)

Purpose To determine the likelihood of long-term amenorrhea after treatment with chemotherapy in women with breast cancer who carry a BRCA1 or BRCA2 mutation. Patients and Methods We conducted a multicenter survey of 1,954 young women with a BRCA1 or BRCA2 mutation who were treated for breast cancer. We included premenopausal women who were diagnosed with invasive breast cancer between 26 and 47 years of age. We determined the age of onset of amenorrhea after breast cancer for women who were and were not treated with chemotherapy, alone or with tamoxifen. We considered chemotherapy-induced amenorrhea to have occurred when the patient experienced ≥ 2 years of amenorrhea, commencing within 2 years of initiating chemotherapy, with no resumption of menses. Results Of the 1,426 women who received chemotherapy, 35% experienced long-term amenorrhea. Of the 528 women who did not receive chemotherapy, 5.3% developed long-term amenorrhea. The probabilities of chemotherapy-induced amenorrhea were 7.2% for women diagnosed before age 30 years, 33% for women age 31 to 44 years, and 79% for women diagnosed after age 45 years (P trend &lt; .001). The probability of induced amenorrhea was higher for women who received tamoxifen than for those who did not (52% v 29%; P &lt; .001). Conclusion Age at treatment and use of tamoxifen are important predictors of chemotherapy-induced amenorrhea in women who carry a BRCA1 or BRCA2 mutation. The risk of induced long-term amenorrhea does not seem to be greater among mutation carriers than among women who do not carry a mutation.
Defective Tbx2-dependent patterning of the atrioventricular canal myocardium causes accessory pathway formation in mice
Authors: Wim T.J. Aanhaanen, Bastiaan J.D. Boukens, Aleksander Sizarov, Vincent Wakker, Corrie de Gier-de Vries, Antoni C. van Ginneken, Antoon F.M. Moorman, Ruben Coronel, Vincent M. Christoffels
Journal: Journal of Clinical Investigation (2011)

Ventricular preexcitation, a feature of Wolff-Parkinson-White syndrome, is caused by accessory myocardial pathways that bypass the annulus fibrosus. This condition increases the risk of atrioventricular tachycardia and, in the presence of atrial fibrillation, sudden death. The developmental mechanisms underlying accessory pathway formation are poorly understood but are thought to primarily involve malformation of the annulus fibrosus. Before birth, slowly conducting atrioventricular myocardium causes a functional atrioventricular activation delay in the absence of the annulus fibrosus. This myocardium remains present after birth, suggesting that the disturbed development of the atrioventricular canal myocardium may mediate the formation of rapidly conducting accessory pathways. Here we show that myocardium-specific inactivation of T-box 2 (Tbx2), a transcription factor essential for atrioventricular canal patterning, leads to the formation of fast-conducting accessory pathways, malformation of the annulus fibrosus, and ventricular preexcitation in mice. The accessory pathways ectopically express proteins required for fast conduction (connexin-40 [Cx40], Cx43, and sodium channel, voltage-gated, type V, α [Scn5a]). Additional inactivation of Cx30.2, a subunit for gap junctions with low conductance expressed in the atrioventricular canal and unaffected by the loss of Tbx2, did not affect the functionality of the accessory pathways. Our results suggest that malformation of the annulus fibrosus and preexcitation arise from the disturbed development of the atrioventricular myocardium.
Eosinophil activities modulate the immune/inflammatory character of allergic respiratory responses in mice
Authors: E. A. Jacobsen, W. E. LeSuer, L. Willetts, K. R. Zellner, K. Mazzolini, N. Antonios, B. Beck, C. Protheroe, S. I. Ochkur, D. Colbert, P. Lacy, R. Moqbel, J. Appleton, N. A. Lee, J. J. Lee
Journal: Allergy (2013)

Background The importance and specific role(s) of eosinophils in modulating the immune/inflammatory phenotype of allergic pulmonary disease remain to be defined. Established animal models assessing the role(s) of eosinophils as contributors and/or causative agents of disease have relied on congenitally deficient mice where the developmental consequences of eosinophil depletion are unknown. Methods We developed a novel conditional eosinophil-deficient strain of mice (iPHIL) through a gene knock-in strategy inserting the human diphtheria toxin (DT) receptor (DTR) into the endogenous eosinophil peroxidase genomic locus. Results Expression of DTR rendered resistant mouse eosinophil progenitors sensitive to DT without affecting any other cell types. The presence of eosinophils was shown to be unnecessary during the sensitization phase of either ovalbumin (OVA) or house dust mite (HDM) acute asthma models. However, eosinophil ablation during airway challenge led to a predominantly neutrophilic phenotype (>15% neutrophils) accompanied by allergen-induced histopathologies and airway hyper-responsiveness in response to methacholine indistinguishable from eosinophilic wild-type mice. Moreover, the iPHIL neutrophilic airway phenotype was shown to be a steroid-resistant allergic respiratory variant that was reversible upon the restoration of peripheral eosinophils. Conclusions Eosinophil contributions to allergic immune/inflammatory responses appear to be limited to the airway challenge and not to the sensitization phase of allergen provocation models. The reversible steroid-resistant character of the iPHIL neutrophilic airway variant suggests underappreciated mechanisms by which eosinophils shape the character of allergic respiratory responses.
Proinsulin Concentration Is an Independent Predictor of All-Cause and Cardiovascular Mortality
Authors: Marjan Alssema, Jacqueline M. Dekker, Giel Nijpels, Coen D.A. Stehouwer, Lex M. Bouter, Robert J. Heine
Journal: Diabetes Care (2005)

OBJECTIVE—High proinsulin concentration may be a better predictor for cardiovascular disease (CVD) mortality than insulin concentration. Previous observations may have been confounded by glucose tolerance status or lack of precision because of high intraindividual variability. We investigated the longitudinal relation of means of duplicate measurements of insulin and proinsulin with all-cause and CVD mortality in a population-based cohort taking glucose tolerance status into account. RESEARCH DESIGN AND METHODS—Fasting and post–75-g glucose-load (2-h) glucose, insulin, and proinsulin values were determined in duplicate on separate days in 277 participants with normal glucose metabolism, 208 participants with impaired glucose metabolism, and 119 newly detected patients with type 2 diabetes of the Hoorn Study. Insulin resistance and β-cell function were estimated by homeostasis model assessment (HOMA-IR and HOMA-B, respectively), and the fasting proinsulin-to-insulin ratio was calculated. Subjects were followed with respect to mortality until January 2003. RESULTS—Fasting proinsulin levels were significantly associated with all-cause and CVD mortality. The hazard ratios (HRs) per increase in interquartile range adjusted for age and sex were 1.21 (95% CI 1.04–1.42) for all-cause mortality and 1.33 (1.06–1.66) for CVD mortality. Adjustment for glucose tolerance status and HOMA-IR did not substantially change the associations. CONCLUSIONS—Fasting proinsulin was associated with all-cause and CVD mortality, independent of glucose tolerance status and insulin resistance and largely independent of other CVD risk factors. Proinsulin might play a role in the relationship between insulin resistance and CVD.
Courses for Coaches?
Authors: Kenneth Jones
Journal: British Journal of Sports Medicine (1975)

51participation in other sports (in this case soccer and cricket are quoted), but, if one takes into account the number of boys who play soccer and cricket, and the number of hours they participate in these activities, then the percentage of concussions/deaths per 'man'-hour of participation falls into insignificance -though I readily concede that one death is one death too many.Again, many other sports offer the chance for young boys to participate at various levels (e.g.local, regional and national), most sports provide an opportunity for competition abroad, and all sports bring together "people of all sorts in the very best kind of comradeship" (Blonstein, 1974).In conclusion, it is my belief that amateur boxing has little more to offer to the 'average' schoolboy than any other sport.
Leukocyte Engagement of Platelet Glycoprotein Ibα via the Integrin Mac-1 Is Critical for the Biological Response to Vascular Injury
Authors: Yunmei Wang, Masashi Sakuma, Zhiping Chen, Valentin Ustinov, Can Shi, Kevin Croce, Alexandre C. Zago, Jose Lopez, Patrick Andre, Edward Plow, Daniel I. Simon
Journal: Circulation (2005)

Leukocyte-platelet interactions are critical in the initiation and progression of atherosclerosis as well as restenosis. Although the leukocyte integrin Mac-1 (alphaMbeta2, CD11b/CD18) has been implicated in the firm adhesion and transmigration of leukocytes at sites of platelet deposition, the precise alphaMbeta2 counterligand responsible for mediating adhesion-strengthening interactions between neutrophils and platelets in vivo has not previously been identified.Our previous studies have established the P201-K217 sequence in the alphaMI domain as the binding site for platelet glycoprotein (GP) Ibalpha. Here we report that antibody targeting of alphaM(P201-K217) reduced alphaMbeta2-dependent adhesion to GP Ibalpha but not other alphaMbeta2 ligands, including fibrinogen, intercellular adhesion molecule-1, and junctional adhesion molecule-3. Anti-alphaM(P201-K217) inhibited the firm adhesion of both human and murine leukocytes to adherent platelets under laminar flow conditions. In a mouse femoral artery wire injury model, antibody targeting of alphaM(P201-K217) reduced leukocyte accumulation after injury that was accompanied by inhibition of cellular proliferation and neointimal thickening.This study demonstrates that GP Ibalpha is a physiologically relevant ligand for alphaMbeta2 and that integrin engagement of GP Ibalpha is critical to leukocyte function and the biological response to vascular injury. These observations establish a molecular target for selectively disrupting leukocyte-platelet complexes that promote inflammation in thrombosis and restenosis.
What Are Preschool Children Eating? A Review of Dietary Assessment
Authors: Mary K Serdula, Maria P Alexander, Kelley S Scanlon, Barbara A Bowman
Journal: Annual Review of Nutrition (2001)

Accurate assessment of dietary intake among preschool-aged children is important for clinical care and research, for nutrition monitoring and evaluating nutrition interventions, and for epidemiologic research. We identified 25 studies published between January 1976 and August 2000 that evaluated the validity of food recalls (n = 12), food frequency questionnaires (n = 9), food records (n = 2), or other methods (n = 2). We identified four studies that evaluated the reproducibility of food frequency questionnaires. Validity studies varied in validation standard and study design, making comparisons between studies difficult. In general, food frequency questionnaires overestimated total energy intake and were better at ranking, than quantifying, nutrient intake. Compared with the validation standard, food recalls both overestimated and underestimated energy intake. When choosing a method to estimate diet, both purpose of the assessment and practicality of the method must be considered, in addition to the validity and reproducibility reported in the scientific literature.
Bilateral Oophorectomy and the Risk of Incident Diabetes in Postmenopausal Women
Authors: Duke Appiah, Stephen J. Winters, Carlton A. Hornung
Journal: Diabetes Care (2013)

Ovarian hormones regulate glucose uptake and insulin sensitivity. Despite the high frequency of surgical menopause, its relationship with diabetes has not been extensively investigated. We assessed the association between hysterectomy with or without bilateral oophorectomy (BSO) status, menopausal age, and reproductive life span with incident diabetes.Data were from a cohort of 2,597 postmenopausal women enrolled in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study without diabetes mellitus at baseline. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% CIs.After a median follow-up time of 9.2 years, the incidence of diabetes (in cases per 1,000 person-years) was 7.4 for women with no hysterectomy or BSO, 8.2 for hysterectomy alone, and 8.5 for hysterectomy with BSO. Hysterectomy status was associated positively with diabetes (HR 1.66, 95% CI 1.23-2.23). However, the elevated risk was restricted to women with both hysterectomy and BSO after adjustment for relevant confounders (HR 1.57, 95% CI 1.03-2.41). An earlier age at menopause and a shorter reproductive life span also exhibited a linear relationship with the development of diabetes irrespective of type of menopause (P for trend = 0.001).Women with hysterectomy concomitant with BSO may represent a unique population with elevated risk for diabetes and other chronic diseases. Therefore, the decision to remove the ovaries at the time of hysterectomy for benign conditions during the premenopausal years should be balanced with the risk of diabetes and its potential complications. Furthermore, the mechanism linking BSO to diabetes mellitus needs to be clarified.
HEREDITY OF THE Rh BLOOD TYPES
Authors: Alexander S. Wiener, Eve B. Sonn, Ruth B. Belkin
Journal: The Journal of Experimental Medicine (1944)

Data are presented concerning the Rh blood types in 97 families with 275 children and in 135 mother-child combinations. The results obtained are in complete agreement with the theory of six allelic genes. When the theory is tested by applying the chi square and gene frequency methods to data on the distribution of the Rh types in the population, the agreement is also satisfactory. The practical implications of the findings are discussed.
Is Atherosclerosis in Diabetes and Impaired Fasting Glucose Driven by Elevated LDL Cholesterol or by Decreased HDL Cholesterol?
Authors: Heinz Drexel, Stefan Aczel, Thomas Marte, Werner Benzer, Peter Langer, Willi Moll, Christoph H. Saely
Journal: Diabetes Care (2005)

OBJECTIVE—To evaluate the atherogenicity of lipids in coronary patients with normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes. RESEARCH DESIGN AND METHODS—Serum lipid values, the presence of angiographic coronary artery disease (CAD) at baseline, and the incidence of vascular events over 2.3 years were recorded in 750 consecutive patients undergoing coronary angiography. RESULTS—Triglycerides significantly (P &amp;lt; 0.001) increased and HDL cholesterol (P &amp;lt; 0.001) as well as LDL particle diameter (P &amp;lt; 0.001) significantly decreased from subjects with NFG &amp;lt;5.6 mmol/l (n = 272) over patients with IFG ≥5.6 mmol/l (n = 314) to patients with type 2 diabetes (n = 164). Factor analysis revealed two factors in the lipid profiles of our patients: triglycerides, HDL cholesterol, apolipoprotein A1, and LDL particle diameter loaded high on an HDL-related factor, and total cholesterol, LDL cholesterol, and apolipoprotein B loaded high on an LDL-related factor. In patients with type 2 diabetes, the HDL-related factor (odds ratio 0.648 [95% CI 0.464–0.904]; P = 0.011), but not the LDL-related factor (0.921 [0.677–1.251]; P = 0.597), was associated with significant coronary stenoses ≥50%. Consistently, in the prospective study, the HDL-related factor (0.708 [0.506–0.990]; P = 0.044), but not the LDL-related factor (1.362 [0.985–1.883]; P = 0.061), proved significantly predictive for vascular events in patients with type 2 diabetes. CONCLUSIONS—The low HDL cholesterol/high triglyceride pattern is associated with the degree of hyperglycemia. In coronary patients with type 2 diabetes, this pattern correlates with the prevalence of CAD and significantly predicts the incidence of vascular events.
Bracing superior to neuromuscular training for the prevention of self-reported recurrent ankle sprains: a three-arm randomised controlled trial
Authors: Kasper W Janssen, Willem van Mechelen, Evert A L M Verhagen
Journal: British Journal of Sports Medicine (2014)

Background Ankle sprain is the most common sports-related injury with a high rate of recurrence and associated costs. Recent studies have emphasised the effectiveness of both neuromuscular training and bracing for the secondary prevention of ankle sprains. Aim To evaluate the effectiveness of combined bracing and neuromuscular training, or bracing alone, against the use of neuromuscular training on recurrences of ankle sprain after usual care. Methods 384 athletes, aged 18–70, who had sustained a lateral ankle sprain, were included (training group n=120; brace group n=126; combi group n=138). The training group received an 8-week home-based neuromuscular training programme, the brace group received a semirigid ankle brace to be worn during all sports activities for 12 months, and the combi group received both the training programme, as well as the ankle brace, to be worn during all sports activities for 8 weeks. The main outcome measure was self-reported recurrence of the ankle sprain. Results During the 1-year follow-up, 69 participants (20%) reported a recurrent ankle sprain: 29 (27%) in the training group, 17 (15%) in the brace group and 23 (19%) in the combi group. The relative risk for a recurrent ankle sprain in the brace group versus the training group was 0.53 (95% CI 0.29 to 0.97). No significant differences were found for time losses or costs due to ankle sprains between the intervention groups. Conclusions Bracing was superior to neuromuscular training in reducing the incidence but not the severity of self-reported recurrent ankle sprains after usual care.