Miracle-dz/UniFAR-FTUs huggingface dataset:
Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein increases env incorporation into particles and fusogenicity and infectivity

Growth of macaque simian immunodeficiency virus (SIVmac) in certain cloned human T-cell lines, such as HUT.78, selects for isolates containing a premature stop codon within the cytoplasmic domain of the transmembrane envelope glycoprotein. In contrast, propagation of virus in macaques or in their cultured T cells favors replication of virus containing the full-length envelope glycoprotein. To elucidate the causes of this phenomenon, we used a human immunodeficiency virus pseudotyping system to assess the effects on infectivity of the cytoplasmic domains of envelope glycoproteins obtained from SIVmac1A11 and SIVmac239. These envelopes contain truncated and full-length cytoplasmic domains, respectively. By analyzing human immunodeficiency virus particles containing selectable genes pseudotyped with each glycoprotein or with chimeric derivatives, we found that truncation of the cytoplasmic domain resulted in a significant advantage in viral entry into HUT.78 T cells and CD4+ U87.MG glial cells. Truncation of the cytoplasmic domain significantly enhanced both envelope density on particles and envelope-mediated cell-to-cell fusion. It is likely that one or both of these effects contribute to the observed differences in infectivity and to the selection of virions with short cytoplasmic tails in human T cells.
Serum paraoxonase activity before and after treatment of thyrotoxicosis

objective Antioxidant effects of paraoxonase, a high density lipoprotein (HDL)‐associated enzyme that inhibits low density lipoprotein cholesterol (LDL‐C) oxidation in human serum, have been reported. Patients with thyroid dysfunction are more susceptible to oxidative stress, and may show enhanced LDL‐C oxidation. The purpose of this study was to evaluate serum paraoxonase activity in patients with hyperthyroidism before and after treatment with methimazole (MMI).
Gender difference in NASH susceptibility: Roles of hepatocyte Ikkβ and Sult1e1

Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep) in male but not female mice. Gene profiling identifies sulfotransferase family 1E (Sult1e1), which encodes a sulfotransferase E1 responsible for inactivation of estrogen, as a gene upregulated in NASH in both genders and most conspicuously in male IkbkbΔhep mice having worst NASH and lowest plasma estradiol levels. LXRα is enriched to LXRE on Sult1e1 promoter in male WT and IkbkbΔhep mice with NASH, and a Sult1e1 promoter activity is increased by LXRα and its ligand and augmented by expression of a S32A mutant of IκBα. These results demonstrate striking gender differences in regulation by IKKβ of high cholesterol saturated fat diet-induced metabolic changes including NASH and suggest hepatocyte IKKβ is protective in male due at least in part to its ability to repress LXR-induced Sult1e1. Our findings also raise a caution for systemic IKK inhibition for the treatment of NASH as it may exacerbate the disease in male patients.
Oestrogen receptors alpha and beta differ in normal human breast and breast carcinomas

The identification of a second oestrogen receptor, oestrogen receptor (ER) β, has led to a need to assess the relative importance of the classical ERα and ERβ in human breast and breast carcinomas. ERα and ERβ mRNA was assessed in 61 carcinomas, 8 benign breast lesions, and 30 samples of normal breast using reverse transcriptase (RT)‐nested polymerase chain reaction (PCR). Immunohistochemical analysis of ERα and ERβ was performed in 62 carcinomas, the 38 non‐malignant breast tissues, and 32 normal breast samples with menstrual cycle data. ERα mRNA was detected in 92% of breast cancers, with ERβ mRNA (wild‐type and/or variant form) in 85%; 72% had ERα protein, 62% progesterone receptor (PgR), and 32% ERβ. ERα protein had a strong correlation with grade; ERβ did not, although it was present in three of four grade I carcinomas and in special types. There was no correlation between the presence of ERα and ERβ protein. In non‐malignant breast, similar expression of ERα and β was observed, apart from expression of ERβ in stromal cells and myoepithelium, the latter being confirmed by RT‐PCR and western blotting. There were differences in ERα in relation to the menstrual cycle but not PgR or ERβ. The findings indicate a need to understand the role and regulation of ERβ in normal breast and the reason for its down‐regulation in mammary carcinogenesis. Copyright © 2002 John Wiley & Sons, Ltd.
The cytosolic chaperone &agr;-crystallin B rescues folding and compartmentalization of misfolded multispan transmembrane proteins

Summary The &agr;-crystallin B chain (CRYAB or HspB5) is a cytosolic chaperone belonging to the small heat shock protein family, which is known to help in the folding of cytosolic proteins. Here we show that CRYAB binds the mutant form of at least two multispan transmembrane proteins (TMPs), exerting an anti-aggregation activity. It rescues the folding of mutant Frizzled4, which is responsible for a rare autosomal dominant form of familial exudative vitreoretinopathy (Fz4-FEVR), and the mutant ATP7B Cu transporter (ATP7B-H1069Q) associated with a common form of Wilson's disease. In the case of Fz4-FEVR, CRYAB prevents the formation of inter-chain disulfide bridges between the lumenal ectodomains of the aggregated mutant chains, which enables correct folding and promotes appropriate compartmentalization on the plasma membrane. ATP7B-H1069Q, with help from CRYAB, folds into the proper conformation, moves to the Golgi complex, and responds to copper overload in the same manner as wild-type ATP7B. These findings strongly suggest that CRYAB plays a pivotal role, previously undetected, in the folding of multispan TMPs and, from the cytosol, is able to orchestrate folding events that take place in the lumen of the ER. Our results contribute to the explanation of the complex scenario behind multispan TMP folding; additionally, they serve to expose interesting avenues for novel therapeutic approaches.
The role of CD40 in CD40L- and antibody-mediated platelet activation

Summary Our initial finding that CD40– and CD40 ligand (CD40L)-deficient mice displayed prolonged tail bleeding and platelet function analyzer (PFA-100) closure times prompted us to further investigate the role of the CD40-CD40L dyad in primary hemostasis and platelet function. Recombinant human soluble CD40L (rhs CD40L), chemical cross-linking of which suggested a trimeric structure of the protein in solution, activated platelets in a CD40-dependent manner as evidenced by increased CD62P expression. CD40 monoclonal antibody (mAb) M3, which completely blocked rhs CD40L-induced platelet activation, also prolonged PFA-100 closure times of normal human blood. In contrast, CD40 mAb G28–5 showed less potential in blocking rhs CD40L-induced CD62P expression and did not affect PFA-100 closure times. However, when added to the platelets after rhs CD40L, G28–5 significantly enhanced the platelet response by causing clustering of, and signaling through, FcγRII. Similarly, higher order multimeric immune complexes formed at a 1/3 molar ratio of M90, a CD40L mAb, to rhs CD40L induced strong FcγRII-mediated platelet activation when translocated to the platelet surface in a CD40-dependent manner, including the induction of morphological shape changes, fibrinogen binding, platelet aggregation, dense granule release, microparticle generation and monocyte-platelet-conjugate formation. The results suggest that CD40 may play a role in primary hemostasis and platelet biology by two independent mechanisms: First, by functioning as a primary signaling receptor for CD40L and, second, by serving as a docking molecule for CD40L immune complexes. The latter would also provide a potential mechanistic explanation for the unexpected high incidence of CD40L mAb-associated thrombotic events in recent human and animal studies. Parts of this work have been presented on the 46th Annual Meeting of the American Society of Hematology (San Diego, 2004).
Impact of chronic renal insufficiency on clinical outcomes in patients undergoing saphenous vein graft intervention with drug‐eluting stents: A multicenter Southern Californian Registry

Objectives: To evaluate the clinical outcomes in patients with chronic renal insufficiency (CRI) who undergo saphenous vein graft (SVG) intervention with drug‐eluting stents (DES). Background: Patients with CRI have higher rates of major adverse cardiac events (MACE) after percutaneous revascularization. SVG intervention is associated with increased rates of MACE compared with percutaneous revascularization of native arteries. However, the impact of CRI on SVG intervention with DES has not been well delineated. Methods: Consecutive patients who underwent SVG intervention with DES at five medical centers from April 2003 to December 2007 were included in this analysis. Results: A total of 172 patients, 39 patients with CRI and a serum creatinine ≥1.5 mg dL−1, and 133 patients without CRI, underwent SVG intervention with DES. Patients with CRI were more often older, diabetic, and had a longer mean total stent length. At 1 year, patients with CRI had a higher MACE rate (35.9% vs. 15.8%, hazard ratio [HR] 2.48, 95% confidence interval [CI] 1.26–4.88, log rank P = 0.009), mainly driven by higher mortality (20.5% vs. 9.8%, HR 3.41, 95% CI 1.10–10.58, log rank P = 0.024). There was a trend toward higher rates of target vessel revascularization in the CRI group (21.8% vs. 10.3%, HR 2.42, 95% CI 0.94–6.24, log rank P = 0.059). Stent thrombosis rates were not different between patients with and without CRI (2.6% vs. 2.3%, P = 0.8). Multivariable analysis revealed that CRI was the only significant predictor of 1‐year MACE (HR 2.2, 95% CI 1.1–4.3; P = 0.03). Conclusions: Patients with CRI who underwent SVG intervention with DES had higher risks of MACE and death compared with patients with preserved renal function. Further treatment strategies are needed in this high‐risk group who undergo SVG intervention with DES. © 2010 Wiley‐Liss, Inc.
Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men.

OBJECTIVES We investigated whether a session of prior exercise could ameliorate postprandial endothelial dysfunction. BACKGROUND Endothelial function is impaired after fat ingestion, and this may be related to rises in triglyceride concentrations. Exercise reduces postprandial triglyceride concentrations. METHODS Ten lean (waist <90 cm) and 10 centrally obese (waist >100 cm) middle-aged men each underwent two oral fat tolerance tests (blood taken fasting and for 8 h after a high-fat meal containing 80 g fat and 70 g carbohydrate). On the afternoon before one test, subjects performed a 90-min treadmill walk (exercise); no exercise was performed before the control test. Endothelium-dependent and -independent microvascular function was assessed using laser Doppler imaging in the fasted state and at two hourly intervals during the 8-h postprandial period. RESULTS Exercise reduced both fasting and postprandial triglyceride concentrations by 25% in both the lean and centrally obese groups (p < 0.0005). For all subjects taken together, exercise improved fasting endothelium-dependent function by 25% (p < 0.05), and, although there was a significant postprandial decrease in both endothelium-dependent and -independent function in both the control and exercise trials (p < 0.01), postprandial endothelium-dependent and -independent function were 15% and 20% higher, respectively, in the exercise trial than the control trial (both p < 0.05). CONCLUSIONS A session of prior exercise improves fasting and postprandial vascular function in middle-aged men. This may be one mechanism by which exercise influences cardiovascular risk.
[Effects of exogenous basic fibroblast growth factor on in-sheathed tendon healing and adhesion formation].

OBJECTIVE To explore the effects of exogenous basic fibroblast growth factor (bFGF) on in-sheathed tendon healing and adhesion formation. METHODS Ninety Leghorn chickens were randomly divided into 3 groups (groups A, B and C), 30 animals for each group, and the right third digitorum longus tendon of the chicken was transected to make defect models. In group A, the tendon was sutured in situ after transection. In group B, the tendon was sutured after 0.6 microl fibrin sealant (FS) was applied at repair site. In group C, the tendon was sutured after 0.6 microl FS mixed with 500 ng bFGF was applied at repair site. At 1, 2, 4 and 8 weeks after operation, the tendons of 6 chickens in each group were harvested for morphological and histological evaluation. Six specimens of each group was obtained for biomechanical test at 8 weeks. RESULTS The gross observation showed that the differences of grading of tendon adhesion were not significant between groups A, B, and C 8 weeks after operation (P > 0.05). Histological evaluation showed that there were no significant differences in fibroblast counting and the content of collagen fibers between groups A and B (P > 0.05). The angiogenesis, fibroblast proliferation and collagen production in the sheath, epitendon and parenchyma at repair site in group C occurred earlier and were more than those in groups A and B, showing significant differences (P < 0.05). The biomechanical tests showed that the gliding excursion of the tendon in group A, B and C were 3.44 +/- 0.43, 3.51 +/- 0.56 and 2.84 +/- 0.42 mm respectively; the work of flexion were 14.87 +/- 1.72, 14.08 +/- 1.85 and 20.62 +/- 3.52 Nmm respectively; the ultimate tensile strength of the tendon was 10.34 +/- 1.45, 11.26 +/- 1.83 and 15.02 +/- 2.20 N respectively; showing no significant differences between groups A and B (P > 0.05), but showing significant differences between group C and groups A, B (P < 0.05). CONCLUSION The exogenous bFGF at tendon repair site can facilitate in-sheathed tendon healing, but also increase the tendon adhesion formation.
Long-term results of endovascular therapy for proximal subclavian arterial obstructive lesions.

BACKGROUND Endovascular therapy is a treatment option for localized occlusion of the subclavian artery. In this report the long-term experience with 59 patients is presented. METHODS Between June 1998 and September 2008, we used endovascular therapy to treat 61 subclavian arterial obstructive lesions in 59 patients (46 males and 13 females, 34 - 82 years of age with a mean age (61.9 + or - 11.0) years). Twenty patients (34%) had clinical symptoms due to vertebrobasilar insufficiency, 26 (44%) had disabling arm ischemia, and 13 (22%) had both symptoms. We performed all procedures under local anesthesia. The approaches were from the femoral artery (n = 47), brachial artery (n = 1, involving bilateral subclavian disease) or both (n = 11). Sixty stents were implanted. All patients were followed-up at 1, 3, 6, and 12 months post-procedure, and annually thereafter. RESULTS We achieved technical success in 58 (95.1%) arteries, all of which were stented. There were three technical failures; two were due to the inability to cross over an occlusion, necessitating the switch to an axillo-axillary bypass, and the third was due to shock after digital subtraction angiography and prior to stenting. Arterial stenosis pre- and post-stenting was (83.6 + or - 10.8)% and (2.5 + or - 12.5)% (P < 0.01). Clinical success was achieved in 55 of the 59 patients (93.4%). Of the four clinical failures, three were technical and the remaining patient had a stent thrombosis. Systolic blood pressure difference between the two brachial arteries was (44.7 + or - 18.5) vs. (2.2 + or - 3.9) mmHg (P < 0.01). Primary patency was 98% at 12 months, 93% at 24 months, and 82% at 5 years. Five patients were lost to follow-up by 12 months post-stenting. Significant recurrent obstruction developed in five patients with resumption of clinical symptoms. The overall survival rate was 98.2% at 12 months, 89.5% at 24 months, and 84.5% at 5 years. CONCLUSIONS Endovascular therapy for proximal subclavian arterial obstructive lesions is effective and successful. This minimally invasive treatment may be the first choice of treatment for proximal subclavical arterial obstructive lesions.
A quantitative study of fixation stability in amblyopia.

PURPOSE To determine whether fixation instability contributes to reduced visual acuity in amblyopia, we compared fixation instability, quantified by the Nidek MP-1 microperimeter, in amblyopic and nonamblyopic children. METHODS Participants were 89 children (5-17 years old) with strabismus (n = 31), anisometropia (n = 29), or both conditions (n = 29). Fixation instability was measured using the Nidek MP-1 microperimeter, which calculated horizontal and vertical eye position at 25 Hz as the child attempted steady fixation for 30 seconds. Fixation instability was quantified as the 95% bivariate contour ellipse area (95% BCEA), the best-fit ellipse within which 95% of fixation occurred during the 30-second test. BCEA was normalized by log transformation. RESULTS Children with amblyopia had significantly larger BCEAs for amblyopic eyes (mean = 0.56 log deg(2)) than fellow eyes (mean = 0.2 log deg(2), P < 0.01) and right eyes of normal controls (mean = 0.12 log deg(2), P ≤ 0.01). Fixation instability was significantly greater along the horizontal axis of the ellipse for amblyopic (mean = 3.53°) than fellow (mean = 1.98°, P = 0.008), and control (mean = 1.62°, P < 0.001) eyes. CONCLUSIONS Fixation instability in amblyopic eyes of children with strabismus and/or anisometropia, and the associated poor stereoacuity probably is the consequence of decorrelated binocular experience early in life. Longer duration of decorrelated visual experience is associated with increased fixation instability, poorer stereoacuity, and more severe amblyopia. Treatments that minimize the duration of decorrelated visual experience may improve stereoacuity and decrease fixation instability.
Protective effects of tranexamic acid on clopidogrel before coronary artery bypass grafting: a multicenter randomized trial.

IMPORTANCE Excessive bleeding and transfusion increase morbidity and mortality in patients receiving coronary artery bypass grafting (CABG), especially in those exposed to antiplatelet agents. OBJECTIVE To evaluate the influence and interaction of clopidogrel bisulfate and tranexamic acid on bleeding and transfusion outcomes. DESIGN A multicenter randomized and blinded trial. SETTING Seven medical centers across China. PARTICIPANTS Patients eligible for randomization were 1173 men and women aged 18 to 85 years undergoing primary and isolated on-pump CABG; 570 adults were randomized and 552 were analyzed. Patients were recruited and stratified into 3 levels according to preoperative clopidogrel exposure (clopidogrel ingestion ≤7 days, clopidogrel discontinuation >7 days, and nonexposure). INTERVENTION Patients were randomized to receive tranexamic acid (10-mg/kg-1 bolus and 10-mg/kg-1/h-1 maintenance dose) or placebo. MAIN OUTCOME MEASURE The primary outcomes included blood loss, major bleeding, and red blood cell (RBC) transfusion volume and exposure. RESULTS As compared with controls, clopidogrel increased blood loss (mean difference [MD], 270 mL; 95% CI, 135 to 404 mL), major bleeding (risk difference [RD], 18.5; 95% CI, 7.85 to 29.2), volume of RBCs transfused (MD, 2.97 U; 95% CI, 1.51 to 4.43 U), and RBC transfusion exposure (RD, 17.9; 95% CI, 8.51 to 27.2). As compared with placebo, tranexamic acid reduced blood loss (MD, -278 mL; 95% CI, -380 mL to -176 mL), major bleeding (RD, -19.5; 95% CI, -27.7 to -11.4), volume of RBCs transfused (MD, -2.58 U; 95% CI -3.61 U to -1.55 U), and RBC transfusion exposure (RD, -18.9; 95% CI, -26.4 to -11.4). Subgroup analysis demonstrated a significantly enhanced effect of tranexamic acid especially in patients with impaired platelet function. CONCLUSIONS AND RELEVANCE Preoperative clopidogrel exposure increased bleeding and transfusion requirements in patients receiving on-pump CABG. Tranexamic acid reduced this risk and provided extra protection selectively in the patients with persistent clopidogrel exposure within 7 days before surgery. TRIAL REGISTRATIONL clinicaltrials.gov Identifier: NCT01060163.
Détermination de la réponse d'un site aux séismes à l'aide du bruit de fond : évaluation expérimentale

De nombreuses etudes d'effet de site permettent de comparer les techniques disponibles aujourd'hui. Le principal objectif de ce travail est d'evaluer une nouvelle methode experimentale, basee sur le rapport spectral des composantes horizontales sur la composante verticale d'un enregistrement de bruit de fond. Le premier pas favorable de l'evaluation concerne la stabilite de ces rapports h/v bruit de fond pour chaque site. Puis, les resultats sont compares, d'une part aux fonctions de transfert obtenues par enregistrement des seismes, d'autre part, aux modelisations numeriques des effets de site. Pour les sols meubles sur lesquels les seismes devraient etre amplifies selon les autres approches, les frequences de resonance des terrains sont mises en valeur avec precision. La methode ii/v est etendue avec succes aux enregistrements de seismes. Par contre, les fonctions de transfert par rapport au substratum etablies a partir du bruit de fond, sont moins convaincantes. Finalement, l'evaluation experimentale met en valeur l'efficacite de la methode h/v bruit de fond, au moins pour les forts contrastes d'impedance. Cette technique rapide, economique et precise en frequence, parait bien adaptee aux etudes de microzonage