tbuckley/cabot-search huggingface dataset:
Physiological profile in relation to playing position of elite college Gaelic footballers
Authors: M C McIntyre, M Hall
Journal: British Journal of Sports Medicine (2005)

To examine the physiological profile, and its relation to playing position, of elite college Gaelic footballers.The subjects were 28 elite Gaelic footballers (12 backs, 12 forwards, and four midfielders; mean (SD) age 21 (1.67) years), who won a major intervarsity tournament (Sigerson Cup) three times in succession.There was general similarity among the members of the team, probably the result of a typical, common training programme. The team means for stature (1.81 (0.05) m), body mass index (81.6 (6.5)) and percentage body fat (14.5 (3.1)%), power output by Wingate test (absolute power 912 (152) W or 10.72 (1.6) W/kg) and sit and reach test (22.3 (5.5) cm) displayed no significant differences when analysed according to playing position. However, midfielders did have significantly larger body mass than backs (p<0.05) and greater maximal oxygen consumption (p<0.01) and greater vertical jumping ability than backs and forwards (vertical jump power output, p<0.01; vertical jump, p<0.01). Midfielders also had greater absolute handgrip strength (p<0.01).The differences exhibited by midfielders despite identical training suggests that they stem from physiological adaptation to competition rather than training.
Long-Term Survival in Patients Presenting With Type B Acute Aortic Dissection
Authors: Thomas T. Tsai, Rossella Fattori, Santi Trimarchi, Eric Isselbacher, Truls Myrmel, Arturo Evangelista, Stuart Hutchison, Udo Sechtem, Jeanna V. Cooper, Dean E. Smith, Linda Pape, James Froehlich, Arun Raghupathy, James L. Januzzi, Kim A. Eagle, Christoph A. Nienaber
Journal: Circulation (2006)

Follow-up survival studies in patients with acute type B aortic dissection have been restricted to a small number of patients in single centers. We used data from a contemporary registry of acute type B aortic dissection to better understand factors associated with adverse long-term survival.We examined 242 consecutive patients discharged alive with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. Three-year survival for patients treated medically, surgically, or with endovascular therapy was 77.6+/-6.6%, 82.8+/-18.9%, and 76.2+/-25.2%, respectively (median follow-up 2.3 years, log-rank P=0.61). Independent predictors of follow-up mortality included female gender (hazard ratio [HR],1.99; 95% confidence interval [CI], 1.07 to 3.71; P=0.03), a history of prior aortic aneurysm (HR, 2.17; 95% CI, 1.03 to 4.59; P=0.04), a history of atherosclerosis (HR, 2.48; 95% CI, 1.32 to 4.66; P<0.01), in-hospital renal failure (HR, 2.55; 95% CI, 1.15 to 5.63; P=0.02), pleural effusion on chest radiograph (HR, 2.56; 95% CI, 1.18 to 5.58; P=0.02), and in-hospital hypotension/shock (HR, 12.5; 95% CI, 3.24 to 48.21; P<0.01).Contemporary follow-up mortality in patients who survive to hospital discharge with acute type B aortic dissection is high, approaching 1 in every 4 patients at 3 years. Current treatment and follow-up surveillance require further study to better understand and optimize care for patients with this complex disease.
Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas
Authors: M. Brada, L. Viviers, C. Abson, F. Hines, J. Britton, S. Ashley, S. Sardell, D. Traish, A. Gonsalves, P. Wilkins, C. Westbury
Journal: Annals of Oncology (2003)
Effect of dietary potassium chloride in borderline hypertensive rats.
Authors: G F DiBona, S Y Jones
Journal: Journal of the American Society of Nephrology (1992)

The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat. With increased dietary sodium chloride intake, the borderline hypertensive rat develops hypertension and exaggerated cardiovascular and renal responses to acute environmental stress, similar to those observed in the hypertensive spontaneously hypertensive rat parent. In other models of sodium chloride-sensitive hypertension with different genetic background (Dahl rat), dietary potassium chloride supplementation protects against the development of hypertension, increased sympathetic nervous system activity, and exaggerated responses to acute environmental stress. This investigation sought to determine whether the dietary sodium chloride-induced development of both the hypertension and the exaggerated responses to acute environmental stress could be reversed or prevented by increased dietary potassium chloride intake. Dietary potassium chloride intake was increased with a 1% potassium chloride drinking solution either after 12 wk of 8% sodium chloride intake (reversal) or concomitant with the onset of 12 wk of 8% sodium chloride intake (prevention). An increase in dietary potassium chloride intake did not reverse or prevent the development of either the hypertension or the exaggerated cardiovascular and renal responses to acute environmental stress in borderline hypertensive rats fed 8% sodium chloride. It is concluded that the difference in genetic background between borderline hypertensive rats and other models of sodium chloride-sensitive hypertension is an important determinant of the protective effect of dietary potassium chloride supplementation.
Bronchial responsiveness, oscillations of peak flow rate and symptoms in patients with mitral stenosis
Authors: G Rolla, C Bucca, L Brussino, M Bugiani, S Bergerone, D Malara, M Morea
Journal: European Respiratory Journal (1992)

To better characterize airway hyperresponsiveness reported in cardiac patients questionnaire-recorded symptoms, bronchial responsiveness to methacholine (Mch) and to ultrasonically nebulized distilled water (UNDW), diurnal oscillations of peak expiratory flow (PEF) rate were evaluated in 32 patients with moderate mitral stenosis. Twenty patients were responsive to Mch (defined as provocative dose producing a 20% fall in forced expiratory volume in one second (PD20 FEV1) less than 3.2 mg) (geometric mean PD20 FEV1 851 +/- 154 micrograms SE). Only two patients showed a fall in FEV1 greater than 20% after UNDW challenge. Patients responsive to Mch challenge had lower FEV1 as percentage of vital capacity (FEV1/VC) (80 +/- 4.8 vs 83 +/- 3.8%, p less than 0.05), higher coefficient of variation of PEF (CV-PEF) (7.1 +/- 2.8 vs 5 +/- 2.4, p less than 0.05) and higher prevalence of wheeze (70 vs 25%, p less than 0.05) in comparison with patients non-responsive to Mch challenge. CV-PEF was significantly related to FEV1 (r = 0.347, p less than 0.05) and maximal expiratory flow at 50% expired volume (MEF50) (r = 0.405, p less than 0.05). The probability of responding to Mch bronchial challenge increased proportionally with the increase in CV-PEF and the decrease in FEV1, FEV1/VC and MEF50. Airway hyperresponsiveness of patients with mitral stenosis seems to be more similar to that reported in bronchitic than in asthmatic patients.
A Murine Model of HUS
Authors: Tiffany R. Keepers, Mitchell A. Psotka, Lisa K. Gross, Tom G. Obrig
Journal: Journal of the American Society of Nephrology (2006)

Hemolytic uremic syndrome (HUS), which is caused by Shiga toxin–producing <i>Escherichia coli</i> infection, is the leading cause of acute renal failure in children. At present, there is no complete small animal model of this disease. This study investigated a mouse model using intraperitoneal co-injection of purified Shiga toxin 2 (Stx2) plus LPS. Through microarray, biochemical, and histologic analysis, it was found to be a valid model of the human disease. Biochemical and microarray analysis of mouse kidneys revealed the Stx2 plus LPS challenge to be distinct from the effects of either agent alone. Microarrays identified differentially expressed genes that were demonstrated previously to play a role in this disease. Blood and serum analysis of these mice showed neutrophilia, thrombocytopenia, red cell hemolysis, and increased serum creatinine and blood urea nitrogen. In addition, histologic analysis and electron microscopy of mouse kidneys demonstrated glomerular fibrin deposition, red cell congestion, microthrombi formation, and glomerular ultrastructural changes. It was established that this C57BL/6 mouse is a complete model of HUS that includes the thrombocytopenia, hemolytic anemia, and renal failure that define the human disease. In addition, a time course of HUS disease progression that will be useful for identification of therapeutic targets and development of new treatments for HUS is described.
Sonographic and Electrodiagnostic Evaluations in Patients With Aromatase Inhibitor–Related Arthralgia
Authors: Omer Dizdar, Levent Özçakar, Fevziye Ünsal Malas, Hakan Harputluoglu, Nilufer Bulut, Sercan Aksoy, Yavuz Ozisik, Kadri Altundag
Journal: Journal of Clinical Oncology (2009)

To investigate the prevalence of arthralgia in breast cancer patients taking aromatase inhibitors (AIs) and perform a detailed rheumatologic assessment including autoimmune serology, musculoskeletal sonography, and electromyography (EMG) in these patients.Postmenopausal patients with stage I to III breast cancer who were taking adjuvant AIs were enrolled (n = 92). Patients who were not receiving hormone treatment were included as a control group (n = 28). Musculoskeletal sonography and EMG were applied to the patients and the controls along with markers of autoimmunity.Thirty patients (32.6%) reported to have AI-related new-onset or worsening arthralgia. The most commonly affected joints were knee (70%), wrist (70%), and small joints of the hand (63%). Patients taking AIs had increased tendon thicknesses compared with those who never received AIs (P < .001). Patients with AI-related arthralgia had higher rates of effusion in hand joints/tendons than those without arthralgia (P = .033). More patients with AI-related arthralgia had EMG findings consistent with carpal tunnel syndrome (CTS) than those without arthralgia (P = .024). No significant difference was observed in erythrocyte sedimentation rates, C-reactive protein, antinuclear antibody, antidouble stranded DNA antibody, rheumatoid factor, or anticyclic citrullinated peptide levels between patients and controls or between those with and without arthralgia.Patients with AI-related arthralgia often show tenosynovial changes suggesting tenosynovitis, exerting local problems but lacking a systemic inflammatory component. Our finding of increased CTS frequency also supports this hypothesis.
Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial
Authors: Stéphane Palfi, Jean Marc Gurruchaga, G Scott Ralph, Helene Lepetit, Sonia Lavisse, Philip C Buttery, Colin Watts, James Miskin, Michelle Kelleher, Sarah Deeley, Hirokazu Iwamuro, Jean Pascal Lefaucheur, Claire Thiriez, Gilles Fenelon, Cherry Lucas, Pierre Brugières, Inanna Gabriel, Kou Abhay, Xavier Drouot, Naoki Tani, Aurelie Kas, Bijan Ghaleh, Philippe Le Corvoisier, Patrice Dolphin, David P Breen, Sarah Mason, Natalie Valle Guzman, Nicholas D Mazarakis, Pippa A Radcliffe, Richard Harrop, Susan M Kingsman, Olivier Rascol, Stuart Naylor, Roger A Barker, Philippe Hantraye, Philippe Remy, Pierre Cesaro, Kyriacos A Mitrophanous
Journal: The Lancet (2014)
Effect of insulin and acute diabetes on plasma FFA and ketone bodies in the fasting rat
Authors: Frederick A. Bieberdorf, Sidney S. Chernick, Robert O. Scow
Journal: Journal of Clinical Investigation (1970)

The metabolism of FFA and ketone bodies was studied in fasted rats by infusing at a constant rate tracer amounts of FFA-(3)H, beta-hydroxybutyrate-(14)C or acetoacetate-(14)C for periods up to 2 hr. Blood that was removed for analyses was replaced by continuous transfusion. The rates of turnover of FFA, beta-hydroxybutyrate, and acetoacetate in rats fasted for 2 days were, respectively, 3.2, 5.6, and 2.5 mumoles/100 g body weight per min. Infusion of mannoheptulose with anti-insulin serum increased plasma glucose, FFA, and ketone body concentrations and decreased the specific activity of plasma FFA. Injection of insulin (20 mU i.v.) decreased almost simultaneously plasma glucose, FFA, and ketone body concentrations and increased the specific activity of FFA, but it did not affect the plasma concentration of FFA-(3)H. The findings indicate that insulin deprivation increased and insulin injection decreased the release of FFA from body tissues in fasting rats. The plasma FFA concentration in fasting rats was increased by infusing chylomicrons and heparin, but this had very little effect on either plasma ketone body or glucose concentrations. Insulin injection (20 mU i.v.) lowered the plasma ketone body concentration in these animals. Studies using beta-hydroxybutyrate-(14)C showed that insulin (50 mU i.v.) decreased ketogenesis in the presence of a sustained high plasma FFA concentration and had no effect on uptake of circulating ketone bodies. The results indicate that plasma FFA concentration is not the sole determinant of plasma ketone body concentration and that insulin can suppress ketone body production through some means other than lowering plasma FFA concentration.
Allergic contact dermatitis and vulvar dermatoses
Authors: P. MARREN, F. WOJNAROWSKA, S. POWELL
Journal: British Journal of Dermatology (1992)

Vulval itch and discomfort are often intractable symptoms and the response to standard therapy can be unsatisfactory. There is some evidence that vulvar sensitivity to irritants is higher than that of forearm skin, but the incidence of relevant allergic contact sensitivity amongst this patient population is unknown. The patch-test data over a 5-year period of 135 patients with persistent vulval symptoms were reviewed and 63 patients had positive results. Of these, 39 had positive results considered to be relevant to their clinical condition. Medicaments and their constituents were responsible for most of these reactions and more than half the patients had multiple allergies.
Cellular protein breakdown and systemic inflammation are unaffected by pulmonary rehabilitation in COPD
Authors: C. E Bolton, R. Broekhuizen, A. A Ionescu, L. S Nixon, E. F M Wouters, D. J Shale, A. M W J Schols
Journal: Thorax (2006)

<b>Background:</b> Pulmonary rehabilitation can improve the functional capacity, but has a variable effect on the low fat-free mass (FFM) in patients with chronic obstructive pulmonary disease. <b>Hypothesis:</b> Pulmonary rehabilitation would not affect catabolic drives such as systemic inflammation and also protein breakdown. <b>Methods:</b> Patients (n = 40) were studied at the start of an 8-week in-patient pulmonary rehabilitation programme, at the end of the programme and 4 weeks later. FFM and functional capacity (quadriceps strength, handgrip strength and peak workload) were assessed. Pseudouridine (PSU) urinary excretion (cellular protein breakdown) and inflammatory status were determined. Healthy participants had a single baseline assessment (n = 18). <b>Results:</b> PSU, (IL)-6 and soluble tumour necrosis factor (sTNF)α R75 were increased in patients compared with healthy participants, whereas FFM and functional capacity were reduced (all p&lt;0.01). PSU was inversely related to both FFM and skeletal muscle function. FFM and functional parameters increased with rehabilitation, but PSU and inflammatory status were unaffected. The gain in FFM was lost 4 weeks after the completion of rehabilitation (p&lt;0.01). <b>Conclusion:</b> The anabolic effect of pulmonary rehabilitation improved FFM, but it did not reverse the increased protein breakdown or systemic inflammation. Thus, on cessation of pulmonary rehabilitation the FFM gains were lost owing to a loss of anabolic drive.
Integrating Murine and Clinical Trials with Cabozantinib to Understand Roles of MET and VEGFR2 as Targets for Growth Inhibition of Prostate Cancer
Authors: Andreas Varkaris, Paul G. Corn, Nila U. Parikh, Eleni Efstathiou, Jian H. Song, Yu-Chen Lee, Ana Aparicio, Anh G. Hoang, Sanchaika Gaur, Lynnelle Thorpe, Sankar N. Maity, Menashe Bar Eli, Bogdan A. Czerniak, Yiping Shao, Mian Alauddin, Sue-Hwa Lin, Christopher J. Logothetis, Gary E. Gallick
Journal: Clinical Cancer Research (2015)

We performed parallel investigations in cabozantinib-treated patients in a phase II trial and simultaneously in patient-derived xenograft (PDX) models to better understand the roles of MET and VEGFR2 as targets for prostate cancer therapy.In the clinical trial, radiographic imaging and serum markers were examined, as well as molecular markers in tumors from bone biopsies. In mice harboring PDX intrafemurally or subcutaneously, cabozantinib effects on tumor growth, MET, PDX in which MET was silenced, VEGFR2, bone turnover, angiogenesis, and resistance were examined.In responsive patients and PDX, islets of viable pMET-positive tumor cells persisted, which rapidly regrew after drug withdrawal. Knockdown of MET in PDX did not affect tumor growth in mice nor did it affect cabozantinib-induced growth inhibition but did lead to induction of FGFR1. Inhibition of VEGFR2 and MET in endothelial cells reduced the vasculature, leading to necrosis. However, each islet of viable cells surrounded a VEGFR2-negative vessel. Reduction of bone turnover was observed in both cohorts.Our studies demonstrate that MET in tumor cells is not a persistent therapeutic target for metastatic castrate-resistant prostate cancer (CRPC), but inhibition of VEGFR2 and MET in endothelial cells and direct effects on osteoblasts are responsible for cabozantinib-induced tumor inhibition. However, vascular heterogeneity represents one source of primary therapy resistance, whereas induction of FGFR1 in tumor cells suggests a potential mechanism of acquired resistance. Thus, integrated cross-species investigations demonstrate the power of combining preclinical models with clinical trials to understand mechanisms of activity and resistance of investigational agents.
The human urinary proteome contains more than 1500 proteins, including a large proportion of membrane proteins.
Authors: Jun Adachi, Chanchal Kumar, Yanling Zhang, Jesper V Olsen, Matthias Mann
Journal: Genome biology (2006)

Abstract Background Urine is a desirable material for the diagnosis and classification of diseases because of the convenience of its collection in large amounts; however, all of the urinary proteome catalogs currently being generated have limitations in their depth and confidence of identification. Our laboratory has developed methods for the in-depth characterization of body fluids; these involve a linear ion trap-Fourier transform (LTQ-FT) and a linear ion trap-orbitrap (LTQ-Orbitrap) mass spectrometer. Here we applied these methods to the analysis of the human urinary proteome. Results We employed one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis and reverse phase high-performance liquid chromatography for protein separation and fractionation. Fractionated proteins were digested in-gel or in-solution, and digests were analyzed with the LTQ-FT and LTQ-Orbitrap at parts per million accuracy and with two consecutive stages of mass spectrometric fragmentation. We identified 1543 proteins in urine obtained from ten healthy donors, while essentially eliminating false-positive identifications. Surprisingly, nearly half of the annotated proteins were membrane proteins according to Gene Ontology (GO) analysis. Furthermore, extracellular, lysosomal, and plasma membrane proteins were enriched in the urine compared with all GO entries. Plasma membrane proteins are probably present in urine by secretion in exosomes. Conclusion Our analysis provides a high-confidence set of proteins present in human urinary proteome and provides a useful reference for comparing datasets obtained using different methodologies. The urinary proteome is unexpectedly complex and may prove useful in biomarker discovery in the future.
Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease.
Authors: B Zhang, H J Edenberg, D W Crabb, R A Harris
Journal: Journal of Clinical Investigation (1989)

Maple syrup urine disease (MSUD) results from a deficiency of branched chain alpha-ketoacid dehydrogenase (BCKDH). We have studied the etiology of MSUD by determining the enzyme activity, protein, and mRNA levels of BCKDH in fibroblasts from a classic MSUD patient and his parents. By enzymatic amplification of the patient's mRNA followed by cloning and DNA sequencing, we have identified a T to A transversion that alters a tyrosine to an asparagine at residue 394 of the E1 alpha subunit. Amplification of both mRNA and genomic DNA, in combination with allele-specific oligonucleotide hybridization, demonstrated that the father was heterozygous for this mutant allele. The mother was homozygous for the allele encoding the normal Tyr394, but expressed only about half of the normal level of mRNA and protein. The patient was genetically heterozygous for this altered allele, although only the abnormal allele was expressed as mRNA. We conclude that the patient was a compound heterozygote, inheriting an allele encoding an abnormal E1 alpha from the father, and an allele from the mother containing a cis-acting defect in regulation which abolished the expression of one of the E1 alpha alleles. Our results revealed for the first time that a case of MSUD was caused by structural and regulatory mutations involving the E1 alpha subunit.
Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome
Authors: Takeshi Ouchi, Akiharu Kubo, Mariko Yokouchi, Takeya Adachi, Tetsuro Kobayashi, Daniela Y. Kitashima, Hideki Fujii, Björn E. Clausen, Shigeo Koyasu, Masayuki Amagai, Keisuke Nagao
Journal: The Journal of Experimental Medicine (2011)

Epidermal Langerhans cells (LCs) extend dendrites through tight junctions (TJs) to survey the skin surface, but their immunological contribution in vivo remains elusive. We show that LCs were essential for inducing IgG1 responses to patch-immunized ovalbumin in mice that lacked skin dendritic cell subsets. The significance of LC-induced humoral responses was demonstrated in a mouse model of staphylococcal scalded skin syndrome (SSSS), a severe blistering disease in which the desmosomal protein Dsg1 (desmoglein1) is cleaved by Staphylococcus aureus–derived exfoliative toxin (ET). Importantly, ET did not penetrate TJs, and patch immunization did not alter epidermal integrity. Nevertheless, neutralizing anti-ET IgG1 was induced after patch immunization and abolished upon LC depletion, indicating that antigen capture through TJs by LCs induced humoral immunity. Strikingly, the ET-patched mice were protected from developing SSSS after intraperitoneal ET challenge, whereas LC-depleted mice were susceptible to SSSS, demonstrating a vital role for LC-induced IgG1 in systemic defense against circulating toxin in vivo. Therefore, LCs elicit humoral immunity to antigens that have not yet violated the epidermal barrier, providing preemptive immunity against potentially pathogenic skin microbes. Targeting this immunological process confers protection with minimal invasiveness and should have a marked impact on future strategies for development of percutaneous vaccines.