tbuckley/cabot-search huggingface dataset:
MRE11 Expression Is Predictive of Cause-Specific Survival following Radical Radiotherapy for Muscle-Invasive Bladder Cancer
Authors: Ananya Choudhury, Louisa D. Nelson, Mark T.W. Teo, Sameer Chilka, Selina Bhattarai, Colin F. Johnston, Faye Elliott, Johanna Lowery, Claire F. Taylor, Michael Churchman, Johanne Bentley, Margaret A. Knowles, Patricia Harnden, Robert G. Bristow, D. Timothy Bishop, Anne E. Kiltie
Journal: Cancer Research (2010)

Abstract Radical radiotherapy and surgery achieve similar cure rates in muscle-invasive bladder cancer, but the choice of which treatment would be most beneficial cannot currently be predicted for individual patients. The primary aim of this study was to assess whether expression of any of a panel of DNA damage signaling proteins in tumor samples taken before irradiation could be used as a predictive marker of radiotherapy response, or rather was prognostic. Protein expression of MRE11, RAD50, NBS1, ATM, and H2AX was studied by immunohistochemistry in pretreatment tumor specimens from two cohorts of bladder cancer patients (validation cohort prospectively acquired) treated with radical radiotherapy and one cohort of cystectomy patients. In the radiotherapy test cohort (n = 86), low tumor MRE11 expression was associated with worse cancer-specific survival compared with high expression [43.1% versus 68.7% 3-year cause-specific survival (CSS), P = 0.012] by Kaplan-Meier analysis. This was confirmed in the radiotherapy validation cohort (n = 93; 43.0% versus 71.2%, P = 0.020). However, in the cystectomy cohort (n = 88), MRE11 expression was not associated with cancer-specific survival, commensurate with MRE11 being a predictive marker. High MRE11 expression in the combined radiotherapy cohort had a significantly better cancer-specific survival compared with the high-expression cystectomy cohort (69.9% versus 53.8% 3-year CSS, P = 0.021). In this validated immunohistochemistry study, MRE11 protein expression was shown and confirmed as a predictive factor associated with survival following bladder cancer radiotherapy, justifying its inclusion in subsequent trial designs. MRE11 expression may ultimately allow patient selection for radiotherapy or cystectomy, thus improving overall cure rates. Cancer Res; 70(18); 7017–26. ©2010 AACR.
Baicalein protects rat cardiomyocytes from hypoxia/reoxygenation damage via a prooxidant mechanism
Authors: A WOO, C CHENG, M WAYE
Journal: Cardiovascular Research (2004)

Baicalin and its aglycone baicalein are the major flavonoid components of the root of Scutellaria baicalensis. Recent studies have shown that they can attenuate oxidative stress in various in vitro models as they possess potent antioxidant activities. This study investigated alternative protective mechanisms of baicalein in a cardiomyocyte model.Neonatal rat cardiomyocytes pretreated with the test compound were subjected to hypoxia/reoxygenation. The extent of cellular damage was accessed by the amount of released lactate dehydrogenasePretreatment with baicalein up to 10 microM reduced lactate dehydrogenase release significantly (P<0.001), while pretreatment with baicalin up to 100 microM was ineffective. The cardioprotective effect of baicalein is not due to its antioxidant effect, because an adverse effect rather than a protective effect was observed when baicalein was present during hypoxia. Cotreatment with N-acetylcysteine attenuated the protective effect of baicalein and concomitantly increased intracellular reactive oxygen species level and the cytotoxic effect of baicalein, but N-acetylcysteine alone did not have such effects. In addition, cotreatment with catalase, but not superoxide dismutase or mannitol, reversed the cardioprotective effect of baicalein, suggesting the involvement of hydrogen peroxide in the cardioprotective mechanism. The NAD(P)H:quinone oxidoreductase inhibitors dicoumarol and chrysin also abolished the cardioprotective effect of baicalein. While pretreatment with baicalein did not increase antioxidant enzyme activities, it alleviated calcium accumulation in cardiomyocytes undergoing simulated ischemia.These results highlight the important role of hydrogen peroxide produced during the auto-oxidation of baicalein in the cardioprotective effect of baicalein.
Tendency towards erosive regression on magnetic resonance imaging at 12 months in rheumatoid arthritis patients treated with rituximab
Authors: U M. Dohn, M Ostergaard, P Bird, A Boonen, J S Johansen, J M Moller, M S Hansen
Journal: Annals of the Rheumatic Diseases (2009)

Magnetic resonance imaging (MRI) may provide a more complete and accurate assessment of the effect of new therapies on joint destruction and joint inflammation in rheumatoid arthritis (RA) patients than conventional methods. The primary aim of this pilot study was, by means of MRI and radiography, to evaluate changes in joint inflammation and/or destruction in rituximab-treated RA patients.

We included 10 adult RA patients, who, as part of routine clinical practice, were commencing their first treatment course with rituximab. Rituximab was the first biological treatment for six patients (four had a history with cancer and one had a benign neuroendocrine tumour), the remaining patients were previously treated with one to three tumour necrosis factor-alpha antagonists. Rituximab (1000 mg) was administered intravenously at days 0 and 14, preceded by 100 mg methylprednisolone intravenously. High-resolution MRI (voxel size 0.4 × 0.4 × 0.4 mm) of the dominant wrist and second to fifth metacarpophalangeal joints, and radiographs of hands, wrists and forefeet were acquired at baseline, 6 and 12 months. T1-weighted three-dimensional fast-field echo, contrast-enhanced fat-suppressed and short tau inversion …
Pubertal Timing, Bone Acquisition, and Risk of Fracture Throughout Life
Authors: Jean-Philippe Bonjour, Thierry Chevalley
Journal: Endocrine Reviews (2014)

Pubertal maturation plays a fundamental role in bone acquisition. In retrospective epidemiological surveys in pre- and postmenopausal women, relatively later menarcheal age was associated with low bone mineral mass and increased risk of osteoporotic fracture. This association was usually ascribed to shorter time exposure to estrogen from the onset of pubertal maturation to peak bone mass attainment. Recent prospective studies in healthy children and adolescents do not corroborate the limited estrogen exposure hypothesis. In prepubertal girls who will experience later menarche, a reduced bone mineral density was observed before the onset of pubertal maturation, with no further accumulated deficit until peak bone mass attainment. In young adulthood, later menarche is associated with impaired microstructural bone components and reduced mechanical resistance. This intrinsic bone deficit can explain the fact that later menarche increases fracture risk during childhood and adolescence. In healthy individuals, both pubertal timing and bone development share several similar characteristics including wide physiological variability and strong effect of heritable factors but moderate influence of environmental determinants such as nutrition and physical activity. Several conditions modify pubertal timing and bone acquisition, a certain number of them acting in concert on both traits. Taken together, these facts should prompt the search for common genetic regulators of pubertal timing and bone acquisition. It should also open epigenetic investigation avenues to pinpoint which environmental exposure in fetal and infancy life, such as vitamin D, calcium, and/or protein supplies, influences both pubertal timing and bone acquisition.
Experimental Viral Hepatitis in the Dog: Production of Persistent Disease in Partially Immune Animals*
Authors: D. J. Gocke, R. Presig, T. Q. Morris, D. G. McKay, S. E. Bradley
Journal: Journal of Clinical Investigation (1967)

Experimental infection with canine hepatitis virus has been studied in a series of 49 dogs. The pattern of response to infection was distinctly modified by the immune status of the animal. All of 19 fully susceptible dogs had an acute, fulminating fatal hepatitis when infected with a standard dose of virus, and all of 19 dogs with high levels of immunity to the virus survived without apparent illness. However, 11 dogs were spontaneously encountered with partial immunity to the infectious agent, and these animals developed different, prolonged forms of hepatitis following infection. In four animals death occurred in 8-21 days following what may be called a subacute course. The remaining seven dogs survived up to 8 months with evidence of chronic hepatic damage. The subacute and chronic forms of hepatitis were reproduced experimentally in seven of eight fully susceptible dogs which were passively immunized against the canine hepatitis virus by administration of hyperimmune serum. Although the virus could be found in sites of hepatic damage in the early stages of the subacute and chronic diseases, it could not be demonstrated in the later stages which were characterized by persistent hepatic damage and a marked chronic inflammatory reaction. Dogs with chronic hepatitis eventually developed extensive hepatic fibrosis. The pathologic, physiologic, virologic, and immunologic features of these experimental forms of viral hepatitis are described.
Evidence-based topical treatments for tinea cruris and tinea corporis: a summary of a Cochrane systematic review
Authors: E.J. van Zuuren, Z. Fedorowicz, M. El-Gohary
Journal: British Journal of Dermatology (2014)

Tinea cruris and tinea corporis are common fungal infections. Most can be treated with a variety of topical antifungals. This review aimed to assess the evidence for the effectiveness and safety of topical treatments for tinea cruris and tinea corporis. Searches included the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, Medline, Embase, LILACS and ongoing trials registries (August 2013). One hundred and twenty-nine randomized controlled trials (RCTs) with 18 086 participants evaluated a range of interventions - mostly azoles. Pooling of data for several outcomes was only possible for two individual treatments. In five studies, terbinafine showed a statistically significant higher clinical cure rate compared with placebo [risk ratio (RR) 4·51, 95% confidence interval (CI) 3·10-6·56]. Data for mycological cure could not be pooled owing to substantial heterogeneity. Across three studies, mycological cure rates favoured naftifine (1%) compared with placebo (RR 2·38, 95% CI 1·80-3·14) but the quality of the evidence was low. Combinations of azoles with corticosteroids were slightly more effective than azoles for clinical cure, but there was no statistically significant difference with regard to mycological cure. Sixty-five studies were assessed as 'unclear' and 64 as being at 'high risk' of bias; many were over 20 years old, and most were poorly designed and inadequately reported. Although most active interventions showed sufficient therapeutic effect, this review highlights the need for further, high-quality, adequately powered RCTs to evaluate the effects of these interventions, which can ultimately provide reliable evidence to inform clinical decision making.
Cardiac capillary cells release biologically active nitric oxide at an early stage of in vitro development
Authors: Dominique Thuringer, Catherine Rucker-Martin, Christian Frelin
Journal: Cardiovascular Research (2000)

Objective: Coronary microvascular endothelial cells (EC) may regulate the myocardial contractile function by releasing cardioactive agents such as nitric oxide (NO). However, understanding of these regulatory mechanisms is complicated by the fact that EC exhibit marked phenotypic changes, such as the loss of endothelial NO synthase (eNOS), when they are placed into culture. Recently, it has been shown that eNOS gene expression is regulated by specific cell–cell interactions with mural cells depending on vascular beds. Since EC and pericytes (PL) are closely associated in capillaries, we have enzymatically isolated these cells from rat hearts to develop a primary culture of capillary cells favoring the re-establishment of cell interactions in vitro. Methods: Expression of transcripts for both eNOS and the inducible isoform (iNOS), was evaluated by using reverse transcription, polymerase chain reaction and Southern blot analysis. Expression of NOS proteins was detected with specific rhodamine-labeled antibodies. Production of NO was assessed (i) from nitrite measurements in culture supernatants by the Griess reaction, and (ii) from its antiproliferative action on cardiac fibroblasts (FIB) in non-contacted cocultures (reporter-cell bioassay) compared to that of sodium nitroprusside in homotypic FIB cultures. Fura-2 fluorescence was used to measure agonist-induced changes in cytosolic free calcium levels. Results: In our heterotypic cultures, EC firstly proliferated to form spots of monolayers (i.e. first phase) before to be covered by PL on the following days (i.e. second phase). The data from RT-PCR analysis demonstrate the presence of mRNAs of both eNOS and iNOS at all developmental stages of the culture. However, eNOS protein was only detected and restricted to EC. During the first phase of cell growth (5–8 days), cells released nitrite and a labile factor, clearly identified as NO, that inhibited the FIB proliferation in reporter-cell bioassay. These effects, not observed during the second phase of cell growth (15–20 days), were prevented by hemoglobin (50 μM) and by Nω-nitro-l-arginine methyl ester (l-NAME; 100 μM). At the two periods of culture, EC increased rapidly their cytosolic Ca2+ concentration in response to bradykinin (10 nM). However, this calcium response was associated with an increase in nitrite production only in older cultures. Conclusions: Our data indicate that heterotypic cultures of native capillary cells preserve the eNOS expression by EC. This enzyme is basally active at an early stage of in vitro development, and then becomes activatable by a Ca2+-mobilizing agonist. NO released by growing EC downregulates the proliferation of cardiac FIB, an effect which could be important in the cardiovascular plasticity.
Effective ways of restoring muscular imbalances of the rotator cuff muscle group: a comparative study of various training methods
Authors: P C Malliou, K Giannakopoulos, A G Beneka, A Gioftsidou, G Godolias
Journal: British Journal of Sports Medicine (2004)

Many studies have compared different training methods for improving muscular performance, but more investigations need to be directed to the restoration of muscular imbalances.To determine the most effective training for altering strength ratios in the shoulder rotator cuff.Forty eight physical education students were randomly assigned to four groups (12 per group): (a) experimental group who carried out multijoint dynamic resistance training for shoulder internal and external rotation movement (pull ups or lat pull downs, overhead press, reverse pull ups, push ups) (MJDR group); (b) experimental group who exercised the same muscle group using dumbbells weighing 2 kg (isolated group); (c) experimental group who followed an isokinetic strengthening programme for the rotator cuff muscle group (isokinetic group); (d) control group who had no strength training. Testing was performed in the supine position with the glenohumeral joint in 90 degrees of abduction in the coronal plane, with a range of motion of 0-90 degrees of external rotation and 0-65 degrees of internal rotation at angular velocities of 60, 120, and 180 degrees /s. The test procedure was performed before and after the exercise period of six weeks.One way analysis of variance found no differences between the groups for the initial tests. Analysis of variance with repeated measures showed that the strength ratios in all the experimental groups had altered after the exercise period, with the isokinetic group showing the most significant improvement.Isokinetic strengthening is the most effective method of altering strength ratios of the rotator cuff muscle.
Authors’ Reply
Authors: R E Ferner, S E McDowell
Journal: Journal of the Royal Society of Medicine (2006)

Mr O'Doherty glosses over our most obvious finding: more and more doctors are being prosecuted for gross negligence manslaughter. The Crown Prosecution Service (CPS) cannot confirm or refute this, because they do not keep relevant statistics. We hope this will change.

Mr O'Doherty criticizes us for using the published evidence to classify the aetiology of acts that have led to manslaughter charges. We recognized the difficulties with this approach in our article. We maintain that a doctor who makes a slip of the sort that is inevitable in human actions should not be judged criminally negligent, whatever dire consequences there are for the patient. This is consistent with the legal test that the CPS must of course apply, that the error was so bad that no reasonable doctor of the same level of experience, in the same situation, would have made that error.

The Code of the CPS requires that, for a case to be brought, the jury should be more likely than not to convict.1 The outcome of any individual case is binary: ‘convicted’ or ‘acquitted.’ Laws of statistics apply even to lawyers. If the probability of conviction were exactly 0.5, then there would be just a 5% chance of the observed 14 convictions in 39 cases brought since the CPS and their colleagues in Northern Ireland were set up.2 The CPS can take no comfort from the fact that nearly a quarter of recent cases were abandoned before trial or dismissed by the judge.

We impute no emotional motives to the CPS in our article. We do contrast society's desire for retributive justice with the desire to reduce deaths from errors. This is crucial. Society has to choose whether to exact retribution, or to minimize harm. All those involved need to realize that the two goals are inconsistent.
Staphylococcus caprae bone and joint infections: a re-emerging infection?
Authors: P. Seng, M. Barbe, P.O. Pinelli, F. Gouriet, M. Drancourt, A. Minebois, N. Cellier, C. Lechiche, G. Asencio, J.P. Lavigne, A. Sotto, A. Stein
Journal: Clinical Microbiology and Infection (2014)
Impact of Soluble Epoxide Hydrolase and Epoxyeicosanoids on Human Health
Authors: Christophe Morisseau, Bruce D. Hammock
Journal: The Annual Review of Pharmacology and Toxicology (2012)

The presence of epoxyeicosatrienoic acids (EETs) in tissues and their metabolism by soluble epoxide hydrolase (sEH) to 1,2-diols were first reported 30 years ago. However, appreciation of their importance in cell biology and physiology has greatly accelerated over the past decade with the discovery of metabolically stable inhibitors of sEH, the commercial availability of EETs, and the development of analytical methods for the quantification of EETs and their diols. Numerous roles of EETs in regulatory biology now are clear, and the value of sEH inhibition in various animal models of disease has been demonstrated. Here, we review these results and discuss how the pharmacological stabilization of EETs and other natural epoxy-fatty acids could lead to possible disease therapies.
Complement Factor H Mutation in Familial Thrombotic Thrombocytopenic Purpura with ADAMTS13 Deficiency and Renal Involvement
Authors: Marina Noris, Sara Bucchioni, Miriam Galbusera, Roberta Donadelli, Elena Bresin, Federica Castelletti, Jessica Caprioli, Simona Brioschi, Friedrich Scheiflinger, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2005)

Thrombotic thrombocytopenic purpura is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease ADAMTS13, which favors platelet adhesion and aggregation in the microcirculation. The disease manifests mainly with central nervous system symptoms, but cases of renal insufficiency have been reported. Presented are findings of the genetic basis of phenotype heterogeneity in thrombotic thrombocytopenic purpura in two sisters within one family. The patients had ADAMTS13 deficiency as a result of two heterozygous mutations (causing V88M and G1239V changes). In addition, a heterozygous mutation (causing an S890I change) in factor H of complement was found in the patient who developed chronic renal failure but not in her sister, who presented with exclusive neurologic symptoms.
Effect of Inhalation of Hot Humidified Air on Experimental Rhinovirus Infection
Authors: J. Owen Hendley
Journal: JAMA (1994)

Nasal inhalation of steam has been proposed as treatment of viral colds on the assumption that increased intranasal temperature will inhibit replication of rhinovirus (RV). The effect of steam inhalation on RV shedding by infected volunteers was examined in this study.Randomized controlled trial. Volunteers experimentally infected with RV were treated with machine-generated humidified air, which was either hot (active) or at room temperature (placebo). Viral shedding was assessed over the 4 days following treatment.Local hotel.Twenty volunteers from the university community who were susceptible to the challenge virus.Two 30-minute intranasal treatments, the first at 24 hours after inoculation and the second at 48 hours. The temperature of active vapor was 42 degrees C to 44 degrees C and of placebo vapor was 22 degrees C.Viral titers in nasal washings on each of 5 days following inoculation.Mean viral titers prior to the first treatment were 10(1.7) tissue culture infectious doses per milliliter in the active group and 10(1.5) in the placebo group. Mean titers for the next 4 days were 10(1.7), and 10(1.7), 10(1.2), and 10(0.9)/mL in the active group and 10(1.8), 10(1.9), 10(1.6), and 10(0.7)/mL in the placebo group (no significant difference). The proportion of volunteers who shed virus on each day was also similar in the two groups.Two nasal inhalation treatments with steam had no effect on viral shedding in volunteers with experimental RV colds.
Energy Transfer Is the Single Most Important Factor for the Difference in Vascular Response between Isolated Ultrafiltration and Hemodialysis
Authors: FRANK M. VAN DER SANDE, ULRICH GLADZIWA, JEROEN P. KOOMAN, GEORGE BO[Combining Diaeresis]CKER, KAREL M. L. LEUNISSEN
Journal: Journal of the American Society of Nephrology (2000)

Differences in vascular reactivity between isolated ultrafiltration (i-UF) and hemodialysis (UF + HD) have been attributed to various factors, including differences in core temperature (CT) and energy transfer (ET). However, the relative importance of these thermal factors is not known. The aim of this study was to elucidate to what extent differences in ET are responsible for the divergent vascular response between i-UF and UF + HD. During four different dialysis treatments in 15 patients, four measurements were performed that consisted of 1 h of i-UF, UF + HD at a dialysate temperature (T(d)) of 37.5 degrees C (UF + HD(37.5)), UF + HD at T(d) 35.5 degrees C (UF + HD(35.5)), and UF + HD with a similar ET as during i-UF(UF + HD(ET-set)). The UF rate in all sessions was 1 L/h. CT ( degrees C) decreased significantly during i-UF and UF + HD(ET-set) (P < 0.05), increased significantly during UF + HD(37.5) (P < 0.05), and remained unchanged during UF + HD(35. 5) (NS). Forearm vascular reactivity increased significantly during i-UF, UF + HD(ET-set), and UF + HD(35.5) (P < 0.05), but not during UF + HD(37.5) (NS). Venous tone increased significantly during i-UF, UF + HD(35.5), and UF + HD(ET-set) (P < 0.05), and decreased significantly during UF + HD(37.5) (P < 0.05). When i-UF and UF + HD are matched for ET, all differences in vascular response disappear, showing that differences in ET are the single most important factor for the observed difference in vascular response between i-UF and UF + HD. In contrast to UF + HD(37.5), vascular reactivity was improved when the increase in CT was prevented during UF + HD(35.5) and appeared to increase more when CT was lowered. Preventing the increase in CT during UF + HD appears to be mandatory for optimization of hemodynamic stability during dialysis.