tbuckley/cabot-search huggingface dataset:
Research on mechano growth factor: its potential for optimising physical training as well as misuse in doping
Authors: G Goldspink
Journal: British Journal of Sports Medicine (2005)

Mechano growth factor can produce rapid increases in muscle and strength, giving it considerable therapeutic and doping potential

The sequencing of the human genome showed that there are only about 40 000 genes. However, there are many more proteins. This is because some genes are spliced to produce different protein/peptides which usually have different biological functions. Combining physiological and molecular biology methods made it possible for our team to identify and characterise a local muscle growth/repair factor (MGF). This we found is derived from the insulin-like growth factor I (IGF-I) gene by alternative splicing, but, owing to a reading frame shift, MGF has a unique C-terminal peptide. After resistance exercise, the IGF-I gene is spliced towards MGF which “kick starts” hypertrophy and repair of local muscle damage by activating the muscle stem cells as well as anabolic processes. Interestingly, loss of muscle mass in old age and in certain diseases is associated with an impaired ability to express MGF. In these conditions it seems that the muscle stem (satellite) cell pool is not adequately replenished.

For some time it has been apparent that muscle mass and strength must be under the control of local growth factors because if one exercises a particular muscle, it is that muscle and not all the muscles of the body that undergo hypertrophy. A little over 10 years ago, our group set out to clone the factor(s) that are involved in autocrine regulation of muscle mass. For this purpose we needed to have an animal model in which we could make muscle grow rapidly. Previous work had shown that the tibialis anterior muscle in the mature rabbit, when held in the stretched position by plaster cast immobilisation combined with low voltage electrical stimulation, increased in mass by 35% in just over a week.1 It …
Selective tyrosine kinase inhibition by imatinib mesylate for the treatment of autoimmune arthritis
Authors: Ricardo T. Paniagua, Orr Sharpe, Peggy P. Ho, Steven M. Chan, Anna Chang, John P. Higgins, Beren H. Tomooka, Fiona M. Thomas, Jason J. Song, Stuart B. Goodman, David M. Lee, Mark C. Genovese, Paul J. Utz, Lawrence Steinman, William H. Robinson
Journal: Journal of Clinical Investigation (2006)

Tyrosine kinases play a central role in the activation of signal transduction pathways and cellular responses that mediate the pathogenesis of rheumatoid arthritis. Imatinib mesylate (imatinib) is a tyrosine kinase inhibitor developed to treat Bcr/Abl-expressing leukemias and subsequently found to treat c-Kit–expressing gastrointestinal stromal tumors. We demonstrate that imatinib potently prevents and treats murine collagen-induced arthritis (CIA). We further show that micromolar concentrations of imatinib abrogate multiple signal transduction pathways implicated in RA pathogenesis, including mast cell c-Kit signaling and TNF-α release, macrophage c-Fms activation and cytokine production, and fibroblast PDGFR signaling and proliferation. In our studies, imatinib attenuated PDGFR signaling in fibroblast-like synoviocytes (FLSs) and TNF-α production in synovial fluid mononuclear cells (SFMCs) derived from human RA patients. Imatinib-mediated inhibition of a spectrum of signal transduction pathways and the downstream pathogenic cellular responses may provide a powerful approach to treat RA and other inflammatory diseases.
An intensive Alpine climbing expedition and its influence on some anthropometric measurements.
Authors: S. J. Baker
Journal: British Journal of Sports Medicine (1980)

The effects of an intensive 4 week Alpine climbing expedition on percentage body fat, absolute body fat and lean body mass was investigated in 14 adult male students. Anthropometric measures were taken on two occasions during the training period prior to the expedition, twice during the expedition and finally eight weeks after the expedition had returned home. There was a 3% reduction in percentage body fat between the first testing occasion and the fourth taken towards the end of the expedition. Over the same interval there was a mean reduction of 2.6 kg in absolute body fat and a reduction in lean body mass of 2.47 kg. All three criterion mean values on the final testing session returned to or exceeded those taken on session one.
Immunosuppressive treatment of HBsAg-positive chronic liver disease: Significance of HBeAg
Authors: Ulrik Tage-Jensen, Jan Aldershvile, Poul Schlichting
Journal: Hepatology (1985)

In a randomized clinical trial in 148 patients of azathioprine vs. prednisone treatment of chronic aggressive hepatitis and/or nonalcoholic cirrhosis, 20 were HBsAg positive on entry. In this subgroup sequential serum samples were investigated for HBs and HBe markers by radioimmunoassay. At the time of evaluation, 13 patients were still alive; their median age was 53 years (25 to 72) and median follow-up time was 46 months (23 to 82). Of 16 patients with cirrhosis, 5 of 7 with persistence of HBeAg died, compared with 2 of 9 with anti-HBe. In three patients with anti-HBe, HBeAg reappeared several times with simultaneous rise in transaminase values. The overall survival was 65% after 5 years. The prognosis of HBsAg-positive chronic liver disease seemed to depend on the presence of cirrhosis and HBeAg rather than on improvement in biochemical activity during immunosuppressive treatment.
Relation between nocturnal symptoms and changes in lung function on lying down in asthmatic children.
Authors: A Greenough, L Everett, J Pool, J F Price
Journal: Thorax (1991)

Nocturnal symptoms are common in young asthmatic children. Such symptoms may be caused by increased impairment of lung function when they adopt the supine posture. Thirty one children aged 2.8-8.3 years were studied, of whom 20 had asthma (10 with frequent nocturnal symptoms) and 11 had no respiratory problems (control subjects). Peak expiratory flow (PEF) was measured with a Wright9s peak flow meter and functional residual capacity (FRC) by a helium gas dilution technique after 30 minutes of lying supine; the values were compared with FRC measured sitting and PEF standing. Peak flow fell significantly on adoption of the supine posture in the asthmatic children, but there was no difference in this fall between the asthmatic children with and without nocturnal symptoms. FRC also fell on adoption of the supine posture, but the decrease in FRC was significant only in the control children and the asthmatic children without nocturnal symptoms. The failure to find a greater fall in PEF or a greater change in FRC on adoption of the supine posture among asthmatic children with nocturnal symptoms suggests that mechanisms other than increased impairment of lung function are responsible for nocturnal asthma.
Cancer Risk in Women Exposed to Diethylstilbestrol In Utero
Authors: Elizabeth E. Hatch
Journal: JAMA (1998)

The association between in utero exposure to diethylstilbestrol (DES) and clear cell adenocarcinoma (CCA) of the vagina and cervix is well known, yet there has been no systematic study of DES-exposed daughters to determine whether they have an increased risk of other cancers. As many as 3 million women in the United States may have been exposed to DES in utero.To determine whether women exposed to DES in utero have a higher risk of cancer after an average of 16 years of follow-up.A cohort study with mailed questionnaires and medical record review of reported cancer outcomes.A cohort of 4536 DES-exposed daughters (of whom 81% responded) and 1544 unexposed daughters (of whom 79% responded) who were first identified in the mid-1970s.Cancer incidence in DES-exposed daughters compared with population-based rates and compared with cancer incidence in unexposed daughters.To date, DES-exposed daughters have not experienced an increased risk for all cancers (rate ratio, 0.96; 95% confidence interval [CI], 0.58-1.56) or for individual cancer sites, except for CCA. Three cases of vaginal CCA occurred among the exposed daughters, resulting in a standardized incidence ratio of 40.7 (95% CI, 13.1-126.2) in comparison with population-based incidence rates. The rate ratio for breast cancer was 1.18 (95% CI, 0.56-2.49); adjustment for known risk factors did not alter this result.Thus far, DES-exposed daughters show no increased cancer risk, except for CCA. Nevertheless, because exposed daughters included in our study were, on average, only 38 years old at last follow-up, continued surveillance is warranted to determine whether any increases in cancer risk occur during the menopausal years.
Insights Into Causal Pathways for Ischemic Heart Disease
Authors: Maxia Dong, Wayne H. Giles, Vincent J. Felitti, Shanta R. Dube, Janice E. Williams, Daniel P. Chapman, Robert F. Anda
Journal: Circulation (2004)

The purpose of this study was to assess the relation of adverse childhood experiences (ACEs), including abuse, neglect, and household dysfunction, to the risk of ischemic heart disease (IHD) and to examine the mediating impact on this relation of both traditional IHD risk factors and psychological factors that are associated with ACEs.Retrospective cohort survey data were collected from 17,337 adult health plan members from 1995 to 1997. Logistic regression adjusted for age, sex, race, and education was used to estimate the strength of the ACE-IHD relation and the mediating impact of IHD risk factors in this relation. Nine of 10 categories of ACEs significantly increased the risk of IHD by 1.3- to 1.7-fold versus persons with no ACEs. The adjusted odds ratios for IHD among persons with > or =7 ACEs was 3.6 (95% CI, 2.4 to 5.3). The ACE-IHD relation was mediated more strongly by individual psychological risk factors commonly associated with ACEs than by traditional IHD risk factors. We observed significant association between increased likelihood of reported IHD (adjusted ORs) and depressed affect (2.1, 1.9 to 2.4) and anger (2.5, 2.1 to 3.0) as well as traditional risk factors (smoking, physical inactivity, obesity, diabetes and hypertension), with ORs ranging from 1.2 to 2.7.We found a dose-response relation of ACEs to IHD and a relation between almost all individual ACEs and IHD. Psychological factors appear to be more important than traditional risk factors in mediating the relation of ACEs to the risk of IHD. These findings provide further insights into the potential pathways by which stressful childhood experiences may increase the risk of IHD in adulthood.
An unusual presentation of precursor T cell lymphoblastic leukemia/lymphoma with cholestatic jaundice: case report
Authors: Kevin J Patel, Sahibzada U Latif, Wanderley M de Calaca
Journal: Journal of Hematology & Oncology (2009)

Cholestatic jaundice as a presenting symptom of Precursor T-lymphoblastic leukemia (T-ALL)/lymphoma (T-LBL) has never been reported in literature. Similarly, precursor T-ALL/T-LBL is characteristically negative for synaptophysin. We report the first case of a patient with precursor T-ALL/T-LBL who presented with cholestatic jaundice and aberrant tumor expression of synaptophysin. 42 year old male presented with anorexia, nausea, jaundice, pale stools, dark urine and about 35 pound weight loss over the previous 3 weeks. The initial laboratory work was suggestive of cholestatic jaundice. Markedly elevated LDH (2025 U/L) and CA 19-9 (1778 u/ML) were also noticed. The CT scan of abdomen showed massive hepatomegaly with coarse echotexture with contracted gall bladder and normal sized common bile duct. Chest x-ray revealed a mediastinal mass with mediastinal widening. CT scan of the chest showed anterior mediastinal mass (16 cm × 10 cm). CT guided biopsy of the mass showed malignant lymphoma with diffuse proliferation of medium sized lymphoid cells. The neoplastic cells were positive for CD1a, CD3, CD4, CD5, CD8 and CD43 with aberrant expression of synaptophysin. PET CT scan again showed a large anterior mediastinal mass with diffuse liver involvement and abnormal activity in axial bones. CT guided liver biopsy and bone marrow biopsy revealed the same morphology and immunohistochemistry. Bone marrow aspirate showed 85% lymphoblasts. Thus, the diagnosis of precursor T-ALL/T-LBL was made and jaundice with elevated CA 19-9 were attributed to intrahepatic cholestasis. Our case illustrates an unusual presentation of hematological malignancies as cholestatic jaundice. It also indicates the non-specific nature of CA 19-9 for pancreaticobiliary malignancies. It is the first case report of neoplastic precursor T cell lymphoblasts with unusual expression of synaptophysin. Tissue biopsy with thorough immunohistochemistry is required to differentiate precursor T-ALL/T-LBL from thymoma and small cell carcinoma.
Catastrophic antiphospholipid syndrome during pregnancy and puerperium: maternal and fetal characteristics of 15 cases
Authors: J. A Gomez-Puerta, R. Cervera, G. Espinosa, R. A Asherson, M. Garcia-Carrasco, I. P da Costa, D. C O Andrade, E. F Borba, A. Makatsaria, S. Bucciarelli, M. Ramos-Casals, J. Font
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> The catastrophic variant of the antiphospholipid syndrome (APS) is a life-threatening form of presentation of this syndrome that can be triggered by several factors. <b>Aim:</b> To describe the characteristics of patients who developed catastrophic APS triggered during pregnancy and puerperium. <b>Methods:</b> A review of the first 255 cases collected in the website-based "CAPS Registry" was undertaken. Three new and unpublished cases of catastrophic APS developed during pregnancy and puerperium were added. <b>Results:</b> Fifteen cases were identified. The mean (range) age was 27 (17–38) years. Most patients had a previous unsuccessful obstetric history. In 7 of 14 (50%) cases with available medical history, the catastrophic APS appeared during pregnancy, in 6 (43%) during the puerperium and in 1 (7%) after curettage for a fetal death. The main clinical and serological characteristics were similar to those patients with catastrophic APS triggered by other factors, except for a history of a higher prevalence of previous abortions (p&lt;0.01). Several specific features were found, including the HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome in 8 (53%) patients, placental infarctions in 4 (27%) patients, and pelvic vein thrombosis and myometrium thrombotic microangiopathy in 1 (7%) patient each. Mortality rate was high for the mothers (46%), and for the babies (54%). <b>Conclusions:</b> It is important to consider the possibility of the development of catastrophic APS in those patients with signs of HELLP syndrome and multiorgan failure during pregnancy or puerperium, especially in those patients with previous history of abortions and/or thrombosis.
A large multi-pathogen waterborne community outbreak linked to faecal contamination of a groundwater system, France, 2000
Authors: A. Gallay, H. De Valk, M. Cournot, B. Ladeuil, C. Hemery, C. Castor, F. Bon, F. Mégraud, P. Le Cann, J.C. Desenclos
Journal: Clinical Microbiology and Infection (2006)
Children of Depressed Mothers 1 Year After Remission of Maternal Depression: Findings From the STAR*D-Child Study
Authors: Priya Wickramaratne, Marc J. Gameroff, Daniel J. Pilowsky, Carroll W. Hughes, Judy Garber, Erin Malloy, Cheryl King, Gabrielle Cerda, A. Bela Sood, Jonathan E. Alpert, Madhukar H. Trivedi, Maurizio Fava, A. John Rush, Stephen Wisniewski, Myrna M. Weissman
Journal: American Journal of Psychiatry (2011)

Maternal major depressive disorder is an established risk factor for child psychopathology. The authors previously reported that 1 year after initiation of treatment for maternal depression, children of mothers whose depression remitted had significantly improved functioning and psychiatric symptoms. This study extends these findings by examining changes in psychiatric symptoms, behavioral problems, and functioning among children of depressed mothers during the first year after the mothers' remission from depression.Children were assessed at baseline and at 3-month intervals with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version, the Child Behavior Checklist, and the Children's Global Assessment Scale for 1 year after their mothers' remission or for 2 years if the mothers did not remit. The authors compared children of early remitters (0-3 months; N=36), late remitters (3-12 months; N=28), and nonremitters (N=16).During the postremission year, children of early-remitting mothers showed significant improvement on all outcomes. Externalizing behavioral problems decreased in children of early- and late-remitting mothers but increased in children of nonremitting mothers. Psychiatric symptoms decreased significantly only in children of mothers who remitted, and functioning improved only in children of early-remitting mothers.Remission of mothers' depression, regardless of its timing, appears to be related to decreases in problem behaviors and symptoms in their children over the year after remission. The favorable effect of mothers' remission on children's functioning was observed only in children of early-remitting mothers.
Ornithine Decarboxylase Overexpression in Mouse 10T12 Fibroblasts: Cellular Transformation and Invasion
Authors: S. Kubota, H. Kiyosawa, Y. Nomura, T. Yamada, Y. Seyama
Journal: JNCI Journal of the National Cancer Institute (1997)

Ornithine decarboxylase (ODC) plays a pivotal role in the synthesis of polyamines, a group of chemical compounds that are essential for cell growth. Recent reports have shown that ODC overexpression may be involved in malignant transformation of immortalized NIH 3T3 cells. We have demonstrated that ODC-overproducing mouse breast cancer cells are more invasive in vitro than control cells. However, little information is available concerning the relationship between ODC overexpression, tumor invasion, and metastasis and the signal transduction pathways involved in ODC-induced transformation and invasion.Our purpose was twofold: 1) to determine whether ODC overexpression is directly involved in tumor cell invasion and 2) to determine whether ODC overexpression induces mitogen-activated protein (MAP) kinase activities that are associated with cell growth and transformation.We transfected C3H clone 8 mouse 10T1/2 fibroblasts with an expression vector that carries a complementary DNA encoding rat ODC. Neomycin-resistant cells that overproduced ODC (4-6.5 times the control levels) were isolated. The transformed phenotype of these cells was determined by assessing colony formation and anchorage-independent growth in soft agar. The invasiveness of the cells was studied by means of an invasion assay that used Matrigel-coated filters in Boyden chambers. The MAP kinase activity of the cells was assayed by an in-gel kinase assay, using myelin basic protein as the substrate.Overexpression of ODC induced not only cell transformation and anchorage-independent growth in soft agar but also invasiveness through a Matrigel-coated filter. The ODC-overproducing transfectants showed enhanced MAP kinase activity that paralleled the magnitude of cell invasiveness.ODC plays a pivotal role not only in cell transformation but also in cancer cell invasion. ODC overexpression enhanced MAP kinase activity.Our results demonstrate a connection between the polyamine/ODC and the MAP kinase signal transduction pathways and suggest that MAP kinase may play a pivotal role in ODC-induced cell transformation and invasion.
Dialysis Dosage in Acute Kidney Injury
Authors: Ravindra L. Mehta, Josée Bouchard
Journal: Journal of the American Society of Nephrology (2008)

In medicine, a key necessity is understanding how to dose therapy to achieve a desired response. For treatment of patients with chronic and acute kidney problems, dialysis techniques are routinely applied; however, establishing a dosage–response relationship for dialysis techniques is challenging
Transcranial Doppler Detection of Cerebral Fat Emboli and Relation to Paradoxical Embolism
Authors: Alejandro M. Forteza, Sebastian Koch, Iszet Campo-Bustillo, Jose Gutierrez, Diogo C. Haussen, Alejandro A. Rabinstein, Jose Romano, Gregory A. Zych, Robert Duncan
Journal: Circulation (2011)

The fat embolism syndrome is clinically characterized by dyspnea, skin petechiae, and neurological dysfunction. It is associated mainly with long bone fracture and bone marrow fat passage to the systemic circulation. An intracardiac right-to-left shunt (RLS) could allow larger fat particles to reach the systemic circulation. Transcranial Doppler can be a useful tool to detect both RLS and the fat particles reaching the brain.We prospectively studied patients with femur shaft fracture with RLS evaluation, daily transcranial Doppler with embolus detection studies, and neurological examinations to evaluate the relation of RLS and microembolic signals to the development of fat embolism syndrome. Forty-two patients were included; 14 had an RLS detected. Seven patients developed neurological symptoms; all of them had a positive RLS (P=<0.001). The patients with an RLS showed higher counts and higher intensities of microembolic signals (P=<0.05 and P=<0.01, respectively) compared with those who did not have an RLS identified. The presence of high microembolic signal counts and intensities in patients with RLS was strongly predictive of the occurrence of neurological symptoms (odds ratio, 204; 95% confidence interval, 11 to 3724; P<0.001) with a positive predictive value of 86% and negative predictive value of 97%.In patients with long bone fractures, the presence of an RLS is associated with larger and more frequent microembolic signals to the brain detected by transcranial Doppler study and can predict the development of neurological symptoms.
Randomised controlled trial of efficacy of teaching patients with bipolar disorder to identify early symptoms of relapse and obtain treatment
Authors: A. Perry, N. Tarrier, R. Morriss, E. McCarthy, K. Limb
Journal: BMJ (1999)

To determine the efficacy of teaching patients with bipolar disorder (manic-depressive psychosis) to identify early symptoms of relapse and seek prompt treatment from health services.Single blind randomised controlled trial with matching on four baseline variables using a minimisation algorithm.Mental health services in four NHS trusts (one teaching, three non-teaching).69 patients with bipolar disorder who had had a relapse in the previous 12 months.Seven to 12 individual treatment sessions from a research psychologist plus routine care or routine care alone.Time to first manic or depressive relapse, number of manic or depressive relapses, and social functioning examined by standardised interviews every six months for 18 months.25th centile time to first manic relapse in experimental group was 65 weeks compared with 17 weeks in the control group. Event curves of time to first manic relapse significantly differed between experimental and control groups (log rank 7.04, df=1, P=0.008), with significant reductions in the number of manic relapses over 18 months (median difference 30% (95% confidence interval 8% to 52%), P=0.013). The experimental treatment had no effect on time to first relapse or number of relapses with depression, but it significantly improved overall social functioning (mean difference 2.0 (0.7 to 3.2), P=0.003) and employment (mean difference 0.7 (0.1 to 1.3), P=0.030) by 18 months.Teaching patients to recognise early symptoms of manic relapse and seek early treatment is associated with important clinical improvements in time to first manic relapse, social functioning, and employment.