tbuckley/cabot-search huggingface dataset:
Peripheral vascular structure and function in hypertrophic cardiomyopathy
Authors: Nicola Jayne Rowley, Daniel J Green, Keith George, Dick H J Thijssen, David Oxborough, Sanjay Sharma, John D Somauroo, Julia Jones, Nabeel Sheikh, Greg Whyte
Journal: British Journal of Sports Medicine (2012)

Background Hypertrophic cardiomyopathy (HCM) is characterised by idiopathic cardiac enlargement and represents the most frequent cause of sudden cardiac death in athletes under the age of 35 years. Differentiation between physiological (ie, exercise-related) and pathological (ie, HCM-related) cardiac remodelling is challenging. In line with cardiac remodelling, vascular structure and function are altered following training, but little is known about peripheral vascular adaptations in HCM. We hypothesised that, while HCM patients and athletes would exhibit similar cardiac characteristics, differences would be apparent in their brachial and carotid arteries. Methods In age-matched groups of HCM patients (n=18, 39±15 years), highly competitive athletes (n=18, 38±12 years) and recreational controls (n=10, 37±14 years), we used high-resolution ultrasound to assess the diameter and wall thickness of the carotid and brachial arteries, with flow-mediated dilator function (FMD) of the brachial arteries also assessed. Results A significant difference between athletes and HCM was evident in arterial wall thickness (carotid 519±60 vs 586±102 µm, p&lt;0.05; brachial 345±80 vs 456±76 µm, p&lt;0.05) and the brachial artery peak blood flow response following forearm ischaemia, an index of resistance artery remodelling (998±515 vs 725±248 ml/min, p&lt;0.05). Similar differences were noted between athletes and controls, while controls and HCM did not differ. Brachial FMD% was not different between groups. Conclusions Athletes and HCM subjects, who can be difficult to differentiate on the basis of cardiac measures, exhibit differences in indices of arterial structure. While this may be a disease-related effect, we cannot discount a generic impact of physical activity on arterial structure, as the athlete's arteries were also different to untrained control subjects. Future studies should assess artery function and structure in athletic HCM subjects.
Reduced level of serine16 phosphorylated phospholamban in the failing rat myocardium: a major contributor to reduced SERCA2 activity
Authors: Jørn B Sande, Ivar Sjaastad, Ingvild B Hoen, Janny Bøkenes, Theis Tønnessen, Even Holt, Per K Lunde, Geir Christensen
Journal: Cardiovascular Research (2002)

Objective: Heart failure is associated with alterations in contractile parameters and accompanied by abnormalities in intracellular calcium homeostasis. Sarcoplasmic reticulum Ca2+ ATPase (SERCA2) and phospholamban (PLB) are important in intracellular calcium cycling. The aim of the present study was to examine mechanisms causing reductions in SERCA2 activity in the failing heart. Methods: Myocardial infarction (MI) was induced in male Wistar rats, and animals with congestive heart failure were examined 6 weeks after the primary operation. Results: Serine16 monomeric and pentameric phosphorylated PLB were significantly downregulated (50 and 55%, respectively), whereas threonine17 phosphorylated PLB was unchanged in failing compared to sham hearts. Protein phosphatases 1 and 2A were significantly upregulated (26 and 42%, respectively) and phosphatase 2C significantly downregulated (29%), whereas the level of protein kinase A regulatory subunit II remained unchanged during heart failure. Increasing PLB phosphorylation by forskolin in isolated cardiomyocytes after inhibition of the Na+–Ca2+ exchanger activity had significantly greater effect on SERCA2 activity in failing than in sham cells (49 and 20% faster transient decline, respectively). Decreasing PLB phosphorylation by the protein kinase A inhibitor H89 had significantly less effect on SERCA2 activity in failing compared to sham cardiomyocytes (20 and 75% slower transient decline, respectively). Conclusion: The observed changes in SERCA2 activity after increasing and decreasing serine16 PLB phosphorylation in cardiomyocytes from sham and failing hearts, suggest that the observed reduction in serine16 PLB phosphorylation is one major factor determining the reduced SERCA2 activity in heart failure after MI.
Effects of Different Expiratory Maneuvers on Inspiratory Muscle Force Output
Authors: SPYROS ZAKYNTHINOS, THEODOROS VASSILAKOPOULOS, ANTONIOS MAVROMMATIS, CHARIS ROUSSOS, GEORGE E. TZELEPIS
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

We assessed the effects of two different expiratory maneuvers (fast [F] or slow [S]) on the ability of normal subjects (n = 12, age 35 ± 6 yr) to generate maximal inspiratory pressures and maximal inspiratory flows near residual volume (RV). With the F maneuver, the subject exhaled rapidly to RV and immediately performed a maximal inspiratory effort, whereas with the S maneuver the subject exhaled slowly to RV, paused for 4 to 6 s at RV, and then inspired forcefully. Maximal static inspiratory pressure against an occluded airway (Pi max), and maximal dynamic inspiratory pressure (Pi dyn) and maximal inspiratory flow (V˙ i max) with no added resistance, as well as the electromyographic activity of the parasternal muscles, were measured during each maneuver. Both maneuvers were initiated from TLC and were performed randomly. In comparison with the S maneuver, the F maneuver yielded values of higher (mean ± SE) Pi max (148 ± 5 cm H2O versus 135 ± 7 cm H2O, p < 0.05), Pi dyn (33 ± 2 cm H2O versus 28 ± 2 cm H2O, p < 0.05), and V˙ i max (12.3 ± 0.4 L/s versus 11.4 ± 0.6 L/s, p < 0.05). In addition, the rate of rise of Pi max, the rate of rise of Pi dyn, and the integrated peak electromyographic activity of the parasternal muscles were significantly greater with the F than with the S maneuver, suggesting greater inspiratory muscle (IM) activation. The enhanced IM activation may be related to a specific inspiratory–expiratory muscle interaction similar to the agonist–antagonist interactions described for a pair of skeletal muscles.
Cadence selection affects metabolic responses during cycling and subsequent running time to fatigue
Authors: F Vercruyssen, R Suriano, D Bishop, C Hausswirth, J Brisswalter
Journal: British Journal of Sports Medicine (2005)

To investigate the effect of cadence selection during the final minutes of cycling on metabolic responses, stride pattern, and subsequent running time to fatigue.Eight triathletes performed, in a laboratory setting, two incremental tests (running and cycling) to determine peak oxygen uptake (VO2PEAK) and the lactate threshold (LT), and three cycle-run combinations. During the cycle-run sessions, subjects completed a 30 minute cycling bout (90% of LT) at (a) the freely chosen cadence (FCC, 94 (5) rpm), (b) the FCC during the first 20 minutes and FCC-20% during the last 10 minutes (FCC-20%, 74 (3) rpm), or (c) the FCC during the first 20 minutes and FCC+20% during the last 10 minutes (FCC+20%, 109 (5) rpm). After each cycling bout, running time to fatigue (Tmax) was determined at 85% of maximal velocity.A significant increase in Tmax was found after FCC-20% (894 (199) seconds) compared with FCC and FCC+20% (651 (212) and 624 (214) seconds respectively). VO2, ventilation, heart rate, and blood lactate concentrations were significantly reduced after 30 minutes of cycling at FCC-20% compared with FCC+20%. A significant increase in VO2 was reported between the 3rd and 10th minute of all Tmax sessions, without any significant differences between sessions. Stride pattern and metabolic variables were not significantly different between Tmax sessions.The increase in Tmax after FCC-20% may be associated with the lower metabolic load during the final minutes of cycling compared with the other sessions. However, the lack of significant differences in metabolic responses and stride pattern between the run sessions suggests that other mechanisms, such as changes in muscular activity, probably contribute to the effects of cadence variation on Tmax
Seasonal Variation in Chronic Heart Failure Hospitalizations and Mortality in France
Authors: Fabrice Boulay, Frédéric Berthier, Olivier Sisteron, Yves Gendreike, Pierre Gibelin
Journal: Circulation (1999)

Circannual variation in blood pressure and in the incidence of acute myocardial infarction is well known but has not been investigated in chronic heart failure. This report describes and compares the seasonal variation of chronic heart failure hospitalizations and mortality in the French population.All deaths that occurred among French adults over the period 1992 to 1996 (n=138 602) and all discharges by adults in French public hospitals for chronic heart failure over the period 1995 to 1997 (n=324 013) were examined retrospectively. First, chronic heart failure deaths in France occurred with a striking annual periodicity and peaked in winter (December through January), both in the overall population and in subgroups defined by age (>44 years old) and sex. The distribution of cumulative monthly deaths differed by nearly 35%, ranging from a peak of 20% above average in January to 15% below average in August (Roger's test: P<0.001). Second, hospitalizations for chronic heart failure in French public hospitals followed a similar seasonal pattern (P<0.001), with a winter-spring predominance (+7% to +10% from December through April). Third, for persons >/=85 years old, excess hospitalizations occurred earlier in the year, with marked synchronized peaks in January for both mortality and hospitalizations (P<0.001).Clear seasonal variations in adult chronic heart failure hospitalizations and deaths were identified. The considerable economic impact on health care services warrants further epidemiological investigations and a more comprehensive approach to disease management.
Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4+ T cell subset that inhibits this autoimmune potential.
Authors: D Fowell, D Mason
Journal: The Journal of Experimental Medicine (1993)

Diabetes was induced in a normal nonautoimmune rat strain by rendering the animals relatively T cell deficient using a protocol of adult thymectomy and sublethal gamma irradiation. All male rats and 70% of females developed an acute syndrome with severe loss of weight and hyperglycemia. Diabetes in these lymphopoenic rats was associated with extensive insulitis involving CD4+ and CD8+ T cells and macrophages. The CD8+ T cells were essential for the development of diabetes but not insulitis. The autoimmune diabetes and insulitis were completely prevented by the injection of a particular CD4+ T cell subset, isolated from healthy syngeneic donors, of the phenotype CD45RClow T cell receptor alpha/beta+ RT6+ Thy-1- OX-40-. Cells of this protective phenotype, which make up about 5% of thoracic duct lymphocytes, were found to provide help for secondary antibody responses and produce interleukin 2 (IL-2) and IL-4, but no interferon gamma, on in vitro activation. These data provide evidence for the presence of autoreactive T cells in the normal immune system of the rat and reveal that in the intact animal these cells are prevented from expressing their autoreactive potential by other T cells.
High levels of fusidic acid-resistant<i>Staphylococcus aureus</i>in dermatology patients
Authors: M. Shah, M. Mohanraj
Journal: British Journal of Dermatology (2003)

Antibiotic resistance is a significant problem both in hospitals and the community. Topical antibiotics are widely used for dermatological problems and this may be leading to the emergence of resistant bacteria.To assess the level of fusidic acid-resistant Staphylococcus aureus inpatients with dermatological problems.All microbiology samples over a 4-month period were tested for antibiotic sensitivities. Patients with cultures positive for S. aureus were studied.The study shows 50% of S. aureus isolates from dermatology patients were resistant to fusidic acid. This figure rose to 78% inpatients with atopic eczema. Of patients with fusidic acid-resistant S. aureus isolates, 96% had used a fusidic acid-containing preparation within the previous 6 months. The level of fusidic acid resistance in S. aureus samples cultured from nondermatology patients was only 9.6%, a level significantly below that for dermatology patients (P < 0.001).High levels of fusidic acid-resistant S. aureus are found in dermatology patients. Inappropriate use of topical antibiotics in dermatology patients leading to fusidic acid resistance may threaten the efficacy of systemic fusidic acid for the treatment of serious S. aureus infections. Education of health professionals and restriction of the use of fusidic acid is needed.
Alpha-Smooth Muscle Actin (ACTA2) Is Required for Metastatic Potential of Human Lung Adenocarcinoma
Authors: Hye Won Lee, Young Mi Park, Se Jeong Lee, Hyun Jung Cho, Duk-Hwan Kim, Jung-Il Lee, Myung-Soo Kang, Ho Jun Seol, Young Mog Shim, Do-Hyun Nam, Hyeon Ho Kim, Kyeung Min Joo
Journal: Clinical Cancer Research (2013)

Metastatic relapse of primary lung cancer leads to therapeutic resistance and unfavorable clinical prognosis; therefore, identification of key molecules associated with metastatic conversion has significant clinical implications. We previously identified a link between early brain metastasis of lung adenocarcinoma and amplification of the α-smooth muscle actin (ACTA2) gene. The aim of present study was to investigate the prognostic and functional significance of ACTA2 expression in cancer cells for the metastatic potential of lung adenocarcinomas.ACTA2 expression was analyzed in tumor cells from 263 patients with primary lung adenocarcinomas by immunohistochemistry, and was correlated with clinicopathologic parameters. The expression of ACTA2 in human lung adenocarcinoma cells was modulated with short hairpin RNAs (shRNA) and siRNAs specifically targeting ACTA2.The patients with lung adenocarcinomas with high ACTA2 expression in tumor cells showed significantly enhanced distant metastasis and unfavorable prognosis. ACTA2 downregulation remarkably impaired in vitro migration, invasion, clonogenicity, and transendothelial penetration of lung adenocarcinoma cells without affecting proliferation. Consistent with the in vitro results, depletion of ACTA2 in human lung adenocarcinoma PC14PE6 cells significantly reduced their metastatic potential without altering their tumorigenic potential. Expression of c-MET and FAK in lung adenocarcinoma cells was also reduced by ACTA2-targeting siRNAs and shRNAs, and was accompanied by a loss of mesenchymal characteristics.These findings indicate that ACTA2 regulates c-MET and FAK expression in lung adenocarcinoma cells, which positively and selectively influence metastatic potential. Therefore, ACTA2 could be a promising prognostic biomarker and/or therapeutic target for metastatic lung adenocarcinoma.
Effects of hydration and water deprivation on blood viscosity during a soccer game in sickle cell trait carriers
Authors: Mor Diaw, Abdoulaye samb, Saliou Diop, Niama Diop Sall, Abdoulaye Ba, Fallou Cissé, Philippe Connes
Journal: British Journal of Sports Medicine (2012)

The present study compared the changes in blood viscosity, hydration status, body temperature and heart rate between a group of sickle cell trait (SCT) carriers and a control (Cont) group before and after a soccer game performed in two conditions: one with water offered ad libitum (hydration condition; Hyd) and the other one without water (dehydration condition; Dehyd). Blood viscosity and haematocrit per blood viscosity ratio (HVR; an index of red blood cell oxygen transport effectiveness) were measured before and at the end of each game. Resting blood viscosity was greater in the SCT carriers than in the Cont group. The increase of blood viscosity over baseline at the end of the game in the Cont group was similar in the two conditions. In contrast, the change in blood viscosity occurring in SCT carriers during soccer games was dependant on the experimental condition: (1) in Dehyd condition, blood viscosity rose over baseline; (2) in Hyd condition, blood viscosity decreased below resting level reaching Cont values. The Cont group had higher HVR than SCT carriers at rest. HVR remained unchanged in the Cont group at the end of the games, whatever the experimental condition. Although HVR of SCT carriers decreased below baseline at the end of the game performed in Dehyd condition, it increased over resting level in Hyd condition reaching the values of the Cont group. Our study demonstrated that ad libitum hydration in exercising SCT carriers normalises the blood hyperviscosity.
Akt-Dependent Cytokine Production in Mast Cells
Authors: Jiro Kitaura, Koichi Asai, Mari Maeda-Yamamoto, Yuko Kawakami, Ushio Kikkawa, Toshiaki Kawakami
Journal: The Journal of Experimental Medicine (2000)

Cross-linking of FcεRI induces the activation of three protein tyrosine kinases, Lyn, Syk, and Bruton's tyrosine kinase (Btk), leading to the secretion of a panel of proinflammatory mediators from mast cells. This study showed phosphorylation at Ser-473 and enzymatic activation of Akt/protein kinase B, the crucial survival kinase, upon FcεRI stimulation in mouse mast cells. Phosphorylation of Akt is regulated positively by Btk and Syk and negatively by Lyn. Akt in turn can regulate positively the transcriptional activity of interleukin (IL)-2 and tumor necrosis factor (TNF)-α promoters. Transcription from the nuclear factor κB (NF-κB), nuclear factor of activated T cells (NF-AT), and activator protein 1 (AP-1) sites within these promoters is under the control of Akt activity. Accordingly, the signaling pathway involving IκB-α, a cytoplasmic protein that binds NF-κB and inhibits its nuclear translocation, appears to be regulated by Akt in mast cells. Catalytic activity of glycogen synthase kinase (GSK)-3β, a serine/threonine kinase that phosphorylates NF-AT and promotes its nuclear export, seems to be inhibited by Akt. Importantly, Akt regulates the production and secretion of IL-2 and TNF-α in FcεRI-stimulated mast cells. Altogether, these results revealed a novel function of Akt in transcriptional activation of cytokine genes via NF-κB, NF-AT, and AP-1 that contributes to the production of cytokines.
The renal urodilatin system: clinical implications
Authors: W Forssmann
Journal: Cardiovascular Research (2001)

A renal natriuretic peptide and the 'renal urodilatin system' were identified after the observation that immunoassayable ANP in urine may not be identical to the circulating cardiac hormone ANP, which is a peptide of 28 amino acids. Urodilatin (INN: Ularitide) is a natriuretic peptide isolated from human urine and belongs to the family of A-type natriuretic peptides. Urodilatin is differentially processed to a peptide of 32 amino acids from the same precursor as ANP. It is synthesized in kidney tubular cells and secreted luminally. After secretion from epithelial cells of the distal and/or connecting tubules, Urodilatin interacts downstream at distal segments of the nephron with luminally located receptors whereby it regulates Na+ and water reabsorption. Thus, the physiological function of the renal Urodilatin system can be described as a paracrine intrarenal regulator for Na+ and water homeostasis, considering Urodilatin as a real diuretic-natriuretic regulatory peptide. However, the regulation upon which the Urodilatin secretion depends is still not clear. Since Urodilatin has been discovered, a great number of pharmacological and clinical investigations have been carried out using Urodilatin as a drug for several indications. So far, clinical phase I and II studies for acute renal failure, congestive heart failure, and bronchial asthma have been performed.
Twin survival in therapeutic abortion.
Authors: C P Douglas
Journal: BMJ (1970)

biopsy specimens, examined with the electron microscope, have indeed revealed the presence of viral formations of 800-1600 A, resembling myxovirus-coronavirus structures (Fig.).It may help to recall that coronaviruses were only recently recognized as an independent viral unit distinct from myxoviruses in the light of serological findings.4Our own observations, and the contribu- tions of Drs.Spencer and Andersen, suggest that the myxovirus-coronavirus organisms that we have detected may be involved in the genesis of hepatitis, with azathioprine acting as an activator and revealer of viruses already present in the liver.Further evidence in favour of a relationship between myxovirus- coronavirus organisms and hepatitis is pro- vided by Dr. A. J. Zuckerman and others (31 January, p. 262), who found a coronavirus in the serum of a chronic hepatitis patient, and by Holmes et al.,5 who found one in the serum of two acute hepatitis patients reacting positively for Australia antigen.-
Kleine-Levin syndrome: a unique cause of fatigue in an athlete * Commentary
Authors: C M J Conklin, J E Taunton
Journal: British Journal of Sports Medicine (2005)

Kleine-Levin syndrome (KLS) is a rare disorder characterised, most notably, by periodic episodes of hypersomnolence and hyperphagia. Associated features of the disorder include a lack of concentration, mood changes, and anxiety. Laboratory tests may show slight changes in the electroencephalogram. However, clinical presentation and laboratory tests are normal during asymptomatic intervals. KLS most often presents in adolescent males, with complete recovery by the 3rd to 4th decade of life. Possible precipitating factors include excessive workload, febrile illness, and respiratory infections. Presented is a classical case of KLS in an adolescent male athlete. The patient's history, complete laboratory results, and symptoms are discussed. Possible treatments for this disorder are also mentioned, along with diagnostic criteria.
Adjuvant effects of non-toxic immunomodulator ginsan in cyclophosphamide-treated mice
Authors: Ji-Young Shim, Jie-Young Song, Ji-Yeon Ahn, Sarah Park, Youngsoo Han, Yeon-Sook Yun
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C69 

Ginsan is a polysaccharide extracted from Panax ginseng that is known to have multiple immunomodulatory effects. This study evaluated the chemo-adjuvant effect of ginsan on mice in combination with cyclophosphamide (CP). CP is one of the most common drugs used in cancer chemotherapy. With the high increase of herbal medicine consumptions, anti-cancer drug and herbal medicine interactions can frequently arise when drugs are co-administered and give an impact on the pharmacokinetics of any coadministered drugs. Mice injected with ginsan (10-200mg/kg, i.p ) exhibited no changes of serum enzymatic activities of AST, ALT, and ALP, as well as even protected mice from CCl4-induced hepatotoxicity. When ginsan (100 mg/kg) was injected with a sublethal dose (250 mg/kg) of a CP treatment, the mice survived up 53% compared with only 10 % in the CP alone treated group on day 30. The treatment of ginsan accelerated the recovery of the bone marrow cells and blood neutrophils by approximately 1.3- and 1.75-fold faster than CP treated control mice at 5 days after CP administration, respectively. The treatment with ginsan also increased the mRNA expression levels of TNF-α, IL-1β, IL-6, SCF, and GM-CSF with respect to that of the CP alone treated group. Similarly, the number of the self-renewal potential of hematopoietic progenitor cells, CFU-s, was significantly higher in the mice treated with ginsan. These results show that the treatment with ginsan demonstrated a significant immunomodulating effect in combination with CP and no toxicity on liver, which indicates its wide applications in reducing the adverse effects of chemotherapy and improving general conditions of patients.