tbuckley/cabot-search huggingface dataset:
Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice
Authors: E Ikebe, A Kawaguchi, K Tezuka, S Taguchi, S Hirose, T Matsumoto, T Mitsui, K Senba, A Nishizono, M Hori, H Hasegawa, Y Yamada, T Ueno, Y Tanaka, H Sawa, W Hall, Y Minami, K T Jeang, M Ogata, K Morishita, H Hasegawa, J Fujisawa, H Iha
Journal: Blood Cancer Journal (2013)

In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression.
Effects of intracellular sodium and hydrogen ion on the sodium activated potassium channel in isolated patches from guinea pig ventricular myocytes
Authors: M. W Veldkamp, J. Vereecke, E. Carmeliet
Journal: Cardiovascular Research (1994)

The Na+ activated K+ channel (IK(Na)) may be activated during ischaemia when the intracellular Na+ concentration is raised. As ischaemia is also associated with intracellular acidification, the influence of intracellular pH on this K+ channel was investigated.The effects of intracellular Na+ and H+ on the IK(Na) channel were investigated in isolated patches from guinea pig ventricular myocytes by the patch clamp technique.Increase of intracellular Na+ increased the open probability of the channel. Intracellular acidification had no effect on the single channel conductance, but significantly decreased the open probability of the channel in the pH range 7.5-6.5. The effect of intracellular pH on open probability was about the same in a wide range of intracellular Na+ concentrations. The lower open probability induced by acidification seemed to be caused by prolonged closed times.Because the effects of increased intracellular Na+ and decreased pH on open probability are opposite, it is suggested that the IK(Na) channel might be important under conditions of raised intracellular Na+ with relatively unchanged intracellular pH. Consequently, it is hypothesised that this channel may be involved in adaptation of action potential duration at high heart rate and in action potential shortening in the border zone of regional ischaemic areas.
Insulin resistance and hepatitis C: an evolving story
Authors: M. Eslam, M. A. Khattab, S. A. Harrison
Journal: Gut (2011)

Insulin resistance and diabetes are inextricably linked to chronic hepatitis C. Our understanding of this relationship continues to improve. This review focuses on the molecular mechanisms relating insulin resistance to hepatitis C with a subsequent overview of the consequences of hepatitis C-associated insulin resistance and diabetes, as well as perspectives for future management.
An Address on the Relation of Puerperal Fever to the Infective Diseases and Pyaemia
Authors: T. S. Wells
Journal: BMJ (1875)

IN opening a discussion this evening on-the relation of puerperal fever to the infective diseases wvlich are among the most numerous class of cases treated by the plhysician anid general practitioner, anld to tlle varied forms of trauimatic fever which, tinder the head of py-cemia, faIl more frequently unider the care of the operating surgeon than of the obstetrician, I wrish particularly to impress upon all wito lhoniour me by
Infliximab in spondyloarthropathy associated with Crohn's disease: an open study on the efficacy of inducing and maintaining remission of musculoskeletal and gut manifestations
Authors: S Generini
Journal: Annals of the Rheumatic Diseases (2004)

To evaluate the efficacy and tolerability of anti-tumour necrosis factor alpha (TNFalpha) monoclonal antibody (infliximab) in the treatment of spondyloarthropathy (SpA) associated with active and inactive Crohn's disease (CD).Twenty four patients with SpA associated with active or inactive CD (16 active, 8 quiescent) were treated with anti-TNFalpha monoclonal antibody (infliximab) with repeated infusions for a period of 12-18 months. The treatment aimed at ameliorating the general musculoskeletal and spinal pain, controlling peripheral arthritis and enthesitis, decreasing the BASDAI score, modifying acute phase reactants, and reducing CD activity.Infliximab improved both gastrointestinal (p<0.01) and overall articular symptoms (BASDAI, p<0.01; general musculoskeletal and spinal pain, p<0.01; peripheral arthritis, p<0.01) in patients with active CD. Additionally, infliximab effectively controlled not only axial involvement and peripheral arthritis but also enthesitis (p<0.01) and prevented inflammatory bowel disease reactivation in patients with inactive CD and low inflammatory markers. Amelioration of gut and musculoskeletal involvement persisted for up to 12 months.Infliximab may act on the inflammation of entheses and of periarticular structures, which usually does not cause a change in the haematological markers that are the main indicators of pain and joint ankylosis in SpA. Infliximab induces and maintains remission of CD while at the same time treating active and severe SpA, suggesting that it should be the preferred drug for the treatment of active and severe SpA associated with active or quiescent CD.
Novel presentation of coeliac disease after following the Atkins' low carbohydrate diet
Authors: D A van Heel, J Dart, S Nichols, D P Jewell, R J Playford
Journal: Gut (2005)

Low carbohydrate diets are currently being promoted as an effective treatment for weight reduction.1 The most popular, the Atkins’ diet, is a worldwide bestseller with over 10 million book copies sold (the earliest being Dr Atkins’ New Diet Revolution 2). Two randomised clinical trials in obese patients have shown effective weight loss at six months on the Atkins’ diet compared with a low fat calorie reduced diet although the difference was not significant or sustained at 12 months.3,4 The Atkins’ diet recommends unlimited protein and fat intake, with carbohydrate intake initially restricted to 20 g/day (5–10% of daily calorie intake), mainly as salad greens and other non-starchy vegetables. In the longer term maintenance phase, the diet remains low in cereal grains (wheat, rye, and barley), which are toxic in coeliac disease. …
Tumor Necrosis Factor-α Downregulates Endothelial Nitric Oxide Synthase mRNA Stability via Translation Elongation Factor 1-α 1
Authors: Guijun Yan, Bei You, Shao-Ping Chen, James K. Liao, Jianxin Sun
Journal: Circulation Research (2008)

Endothelium-derived nitric oxide (NO) is an important regulator of vascular function. NO is produced by endothelial NO synthase (eNOS), whose expression is downregulated by tumor necrosis factor (TNF)-alpha at the posttranscriptional level. To elucidate the molecular basis of TNF-alpha-mediated eNOS mRNA instability, eNOS 3' untranslated region (3'-UTR) binding proteins were purified by RNA affinity chromatography from cytosolic fractions of TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs). The formation of 3'-UTR ribonucleoprotein complexes, with molecular weight of 52 and 57 kDa, was increased by TNF-alpha. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis of the 52-kDa protein identified 3 peptides that comprise the peptide sequence of translation elongation factor 1-alpha 1 (eEF1A1). In HUVECs, TNF-alpha rapidly increased eEF1A1 expression, which is maximal after 1 hour and persists for up to 48 hours. RNA gel mobility-shift and UV cross-linking assays indicated that recombinant glutathione S-transferase-eEF1A1 fusion protein specifically binds to a UC-rich sequence in the 3'-UTR of eNOS mRNA. In addition, the domain III of eEF1A1 mediates the binding of eNOS 3'-UTR in eEF1A1. Overexpression of eEF1A1 markedly attenuated the expression of eNOS and luciferase gene fused with eNOS 3'-UTR in both COS-7 cells and bovine aortic endothelial cells (BAECs). Furthermore, adenovirus-mediated overexpression of eEF1A1 increased eNOS mRNA instability, whereas knockdown of eEF1A1 substantially attenuated TNF-alpha-induced destabilization of eNOS mRNA and downregulation of eNOS expression in HUVECs. These results indicate that eEF1A1 is a novel eNOS 3'-UTR binding protein that plays a critical role in mediating TNF-alpha-induced decrease in eNOS mRNA stability.
Resistance to β-lactams among blood isolates of Salmonella spp. in European hospitals: results from the SENTRY Antimicrobial Surveillance Program 1997-98
Authors: L.S. Tzouvelekis, V. Lukova, P.T. Tassios, A.C. Fluit, R.N. Jones, N.J. Legakis
Journal: Clinical Microbiology and Infection (2003)
The utility of brain natriuretic peptide in patients with stable chronic lung diseases
Authors: Yoko Kida, Hiromi Tomioka, Reina Sekiya, Syuuji Yamashita, Toshihiko Kaneda, Chihiro Nishio, Masahiro Kaneko, Hiroshi Fujii, Kyosuke Ishihara
Journal: European Respiratory Journal (2012)

Background: Cor pulmonare and pulmonary hypertension with chronic lung diseases are related to low exercise capacity and poor prognosis. Plasma brain natriuretic peptide (BNP) is a useful biomarker for monitoring of heart failure.

Objective: The aim of our study is to investigate the utility of BNP in stable chronic lung diseases (COPD, intestinal pneumonia, post-tuberculous lung disorder and others).

Methods: 111 patients with chronic lung diseases(male/female=73/38, mean74.8±8.0yrs; excluding Af rhythm, LVEF≤40% and renal dysfunction) who were admitted to a three-weeks comprehensive inpatient pulmonary rehabilitation program, were assessed by pulmonary function tests, 6-minute walking test, and health-related quality of life as evaluated by SF-36. Plasma BNP was measured and echocardiography was also performed.

Results: It made no difference among types of lung disease for BNP (56.4±57.2pg/ml, mean38.5), RVPs (44.4±12.2mmHg, mean44.0) and LVEF (62.3±6.5%, mean62.0). LVEF was not correlated with BNP. Compared BNP normal group (<18.4pg/ml) with high group (≥18.4pg/ml), there was a difference for Borg scale at rest (0.84±0.77‚ 2.02±0.57 p=0.0047*) and 6MWD (262.2±73.3m, 188.5±93.0m p=0.0044*). BNP was significantly correlated with 6MWD (r=-0.2270, p=0.0457*). RVPs was also correlated with 6MWD and SpO2 both at rest and on effort. But no significant correlation was shown between BNP and RVPs (r=0.1541, p=0.1540). Also, BNP was not correlated with QOL score (SF-36) and pulmonary function.

Conclusions: Plasma BNP was correlated with exercise capacity in stable chronic lung diseases. BNP may be a useful biomarker for administrating cor pulmonare and pulmonary hypertension with chronic lung diseases.
The third component of complement protects against Escherichia coli endotoxin-induced shock and multiple organ failure.
Authors: Z M Quezado, W D Hoffman, J A Winkelstein, I Yatsiv, C A Koev, L C Cork, R J Elin, P Q Eichacker, C Natanson
Journal: The Journal of Experimental Medicine (1994)

We investigated whether the third component of complement (C3) is involved in the pathophysiology of endotoxic shock, and if it is involved, whether it plays a protective role or whether it mediates shock and multiple organ failure. In a prospective, controlled investigation, six Brittany spaniels that were homozygous for a genetically determined deficiency of C3 (C3 deficient, < 0.003% of normal serum C3 levels) and six heterozygous littermates (controls, approximately 50% of mean normal serum C3 level) were given 2 mg/kg of reconstituted Escherichia coli 026:B6 acetone powder as a source of endotoxin, intravenously. All animals were given similar fluid and prophylactic antibiotic therapy, and had serial hemodynamic variables obtained. After E. coli endotoxin infusion, C3-deficient animals had higher peak levels of endotoxin and less of a rise in temperature than controls (P < 0.05). During the first 4 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean central venous pressure and mean pulmonary artery pressure than controls (P < 0.02). During the first 48 h after E. coli endotoxin infusion, C3-deficient animals had significantly greater decreases in mean arterial pH, left ventricular ejection fraction, and mean pulmonary capillary wedge pressure, and greater increases in mean arterial lactate, arterial-alveolar O2 gradient, and transaminases (aspartate aminotransferase and alanine aminotransferase) than controls, (all P < 0.05). After E. coli endotoxin infusion, C3-deficient animals compared to controls had significantly less of a decrease in mean C5 levels (P < 0.01), but similar (P = NS) increases in circulating tumor necrosis factor levels, bronchoalveolar lavage neutrophils, and protein, and similar (P = NS) decreases in blood leukocytes and platelets. Two of six C3-deficient animals and two of six controls died. In summary, after intravenous infusion of E. coli endotoxin, canines with C3 deficiency have decreased endotoxin clearance and worse E. coli endotoxin-induced shock and organ damage. Thus, the third component of the complement system plays a beneficial role in the host defense against E. coli endotoxic shock.
A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study
Authors: L Heimans, K V C Wevers-de Boer, K Visser, R J Goekoop, M van Oosterhout, J B Harbers, C Bijkerk, I Speyer, M P D M de Buck, P B J de Sonnaville, B A M Grillet, T W J Huizinga, C F Allaart
Journal: Annals of the Rheumatic Diseases (2013)

To assess which treatment strategy is most effective in inducing remission in early (rheumatoid) arthritis.610 patients with early rheumatoid arthritis (RA 2010 criteria) or undifferentiated arthritis (UA) started treatment with methotrexate (MTX) and a tapered high dose of prednisone. Patients in early remission (Disease Activity Score <1.6 after 4 months) tapered prednisone to zero and those with persistent remission after 8 months, tapered and stopped MTX. Patients not in early remission were randomised to receive either MTX plus hydroxychloroquine plus sulfasalazine plus low-dose prednisone (arm 1) or to MTX plus adalimumab (ADA) (arm 2). If remission was present after 8 months both arms tapered to MTX monotherapy; if not, arm 1 changed to MTX plus ADA and arm 2 increased the dose of ADA. Remission rates and functional and radiological outcomes were compared between arms and between patients with RA and those with UA.375/610 (61%) patients achieved early remission. After 1 year 68% of those were in remission and 32% in drug-free remission. Of the randomised patients, 25% in arm 1 and 41% in arm 2 achieved remission at year 1 (p<0.01). Outcomes were comparable between patients with RA and those with UA.Initial MTX and prednisone resulted in early remission in 61% of patients with early (rheumatoid) arthritis. Of those, 68% were in remission and 32% were in drug-free remission after 1 year. In patients not in early remission, earlier introduction of ADA resulted in more remission at year 1 than first treating with disease-modifying antirheumatic drug combination therapy plus prednisone.
Identification of the Major Allergens of the Venom from the South American Social Wasp Agelaia Pallipes
Authors: C.E.S. Galvao, L.K. Iwai, L.D. Santos, M.A. Mendes, M.S. Palma, F.F.M. Castro, E. Cunha Neto, J. Kalil
Journal: Journal of Allergy and Clinical Immunology (2006)
Obstructive sleep apnoea and its therapy influence high-density lipoprotein cholesterol serum levels
Authors: J. Börgel, B. M. Sanner, A. Bittlinsky, F. Keskin, N. K. Bartels, N. Buechner, A. Huesing, L. C. Rump, A. Mügge
Journal: European Respiratory Journal (2005)

Recent studies suggest an association of obstructive sleep apnoea (OSA) with cardiovascular risk factors, such as dyslipidaemia. The present study analyses the effects of OSA and its therapy on serum lipid concentrations in 470 OSA patients in a single centre study. Multivariate regression showed a significant association between the apnoea–hypopnoea index and high-density lipoprotein cholesterol (HDL-C) serum levels (n = 366), independent of age, sex, body mass index, diabetes and lipid lowering medication. There were no independent associations with total cholesterol, triglyceride and low-density lipoprotein cholesterol serum levels. During follow-up (6 months) with effective bilevel or continuous positive airway pressure therapy in 127 patients (lipoproteins: n = 86) without change in their lipid lowering therapy, the mean HDL-C serum level increased significantly by 5.8% from 46.9±15.8 to 49.6±15.3 mg·dL −1 (mean± SD ). An independent relationship was found between the change of apnoea–hypopnoea index and the change of high-density lipoprotein cholesterol or triglycerides, respectively. All patients with abnormal serum lipid/lipoprotein levels improved significantly under bilevel or continuous positive airway pressure therapy. This study demonstrates an influence of obstructive sleep apnoea and its therapy on high-density lipoprotein cholesterol levels.
Type 2 segmental Cowden disease vs. Proteus syndrome
Authors: R. Happle
Journal: British Journal of Dermatology (2007)

Conflicts of interest: none declared. Sir, Loffeld et al.1 recently reported an unusual case of systematized epidermal naevus showing loss of heterozygosity (LOH) for a PTEN mutation. Because this 3‐year‐old boy had various additional anomalies including hydrocephalus, lipomas, cutis marmorata‐like lesions of the legs and asymmetrical growth of limbs with unilateral macrodactyly, the authors categorized the case as an example of Proteus syndrome (PS). I should like to propose another name for this disorder. For the following reasons, the designation ‘type 2 segmental Cowden disease (CD)’ seems more appropriate. The patient's mother had the same PTEN germline mutation as her son and clinical features of CD. Moreover, the authors found LOH for the PTEN mutation in DNA extracted from the epidermal naevus, which is why this disorder can undoubtedly be categorized as a type 2 segmental manifestation of CD. In autosomal dominant skin disorders, we can distinguish today two different types of mosaic manifestation.2 A type 1 segmental involvement reflects heterozygosity for the underlying mutation and shows a degree of severity corresponding to that encountered in the nonsegmental phenotype. By contrast, a type 2 segmental manifestation results from LOH in a heterozygous embryo. The degree of segmental involvement is far more pronounced and these lesions are superimposed on the ordinary, nonsegmental phenotype. This conception of dichotomous types of severity has recently been proven in Hailey–Hailey disease.3 The interesting case presented by Loffeld et al. can be taken as additional molecular confirmation of the concept in a family with CD.
Left Ventricular Remodeling and Renal Function in Never-Treated Essential Hypertension
Authors: Pierre Fesler, Guilhem du Cailar, Jean Ribstein, Albert Mimran
Journal: Journal of the American Society of Nephrology (2003)

In the general population, renal function linearly declines with age; hypertension may accelerate this decline. Because concentric left ventricular (LV) hypertrophy is a strong marker of the severity of hypertension, the influence of LV geometry on the age-associated decline in renal function was assessed in 195 normotensive subjects and 645 patients with never-treated essential hypertension with an average duration of 30 mo. According to LV mass and relative wall thickness, hypertensive patients were divided into normal LV (NL, 48%), concentric remodeling (CR, 19%), and concentric (CH, 22%) and eccentric (EH, 11%) hypertrophy. GFR and effective renal plasma flow (ERPF) were estimated by isotopic clearance technique. GFR and ERPF were inversely correlated with age in normotensive and hypertensive subjects, and no marked influence of the BP level or the presence of LV hypertrophy was detected. However, the slope of the regression line of GFR versus age was accentuated (P < 0.01) in patients with CH or CR (slope values of -0.95 +/- 0.11, -0.86 +/- 0.14 ml/min per yr, respectively) when compared with patients with EH or NL (slope values of -0.58 +/- 0.16 and -0.58 +/- 0.08 ml/min per yr, respectively). No such results were obtained when creatinine clearance was considered. Urinary albumin excretion was higher in patients with concentric or eccentric LV hypertrophy than in patients with concentric LV remodeling or normal LV. These results demonstrate that in never-treated essential hypertension, the age-associated decline in GFR is markedly influenced by the concentric pattern of LV response to hypertension rather than the level of BP and/or the presence of LV hypertrophy.
Polyenephosphatidylcholine prevents alcoholic liver disease in PPARα-null mice through attenuation of increases in oxidative stress
Authors: Wataru Okiyama, Naoki Tanaka, Tamie Nakajima, Eiji Tanaka, Kendo Kiyosawa, Frank J. Gonzalez, Toshifumi Aoyama
Journal: Journal of Hepatology (2009)
Cyclooxygenase-1 gene polymorphisms in patients with different asthma phenotypes and atopy
Authors: J. Shi
Journal: European Respiratory Journal (2005)

Cyclooxygenase-1 (COX-1) regulates the biosynthesis of prostaglandins, which are important mediators in asthma. The possible association of COX-1 gene polymorphisms with asthma has not been investigated. The allele frequencies of 20 COX-1 polymorphisms were determined in a random Australian Caucasian population using MassARRAY technology. Informative and potentially functional promoter (c.8592C&gt;T, c.1676C&gt;T) and coding region (c.22C&gt;T, c.50C&gt;T) polymorphisms were investigated in carefully phenotyped patients with mild (n = 316), moderate (n = 241), severe (n = 86) or aspirin-intolerant asthma (AIA) (n = 58), and in nonasthmatic subjects (n = 477). There were no allelic, genotypic or haplotypic associations between these four polymorphisms and asthma or asthma severity. Over-representation of the c.50TT genotype among AIA patients (3.4%) compared with aspirin-tolerant patients (0.8%), and a global haplotype association with AIA did not reach statistical significance. The c.22TT genotype was less frequent among atopic (0.1%) rather than nonatopic individuals (1.2%; odds ratio = 9.05, 95% confidence interval 1.01–81.29). In conclusion, the present investigation of cyclooxygenase-1 polymorphisms in asthma indicates that they do not appear to play a substantial role in genetic pre-disposition for asthma or asthma severity. However, the c.22TT genotype confers a small protective effect against atopy. Potential associations with aspirin-intolerant asthma were identified and warrant further investigation in a larger population of aspirin-intolerant asthma patients.