HIV-1tat induced apoptosis of T-cells is not mediated by TGF-β

Recent reports have demonstrated that the HIV-1 transactivator protein,tat, induces apoptosis in T-lymphocyte cell lines, as well as in peripheral blood mononuclear cells, and stimulates a cascade of events resulting in up-regulation of the potent immunosuppressive cytokine, transforming growth factor-β (TGF-β). In this study we evaluated the ability of TGF-β to mediatetat induced apoptosis in T-lymphocyte cell lines. T-cells treated exogenously with either TGF-β1 or a combination of tat and pan-specific TGF-β neutralizing antibodies showed little change in the amount of apoptosis. When treated with pan-specific TGF-β neutralizing antibodies, Jurkat cells that stably expresstat protein (Jurkat-tat) showed only a modest decrease in apoptosis, while CEM-TART cells (CEM T-cells expressing both HIV-1tat andrev) demonstrated little change in the amount of apoptosis. In conclusion, we have demonstrated that TGF-β does not play a significant role in mediatingtat induced T-cell apoptosis.     

Human alphavbeta3 integrin potency and specificity of TA138 and its DOTA conjugated form (89)Y-TA138

The present study was undertaken to define the alphavbeta3-binding potency and specificity of TA138, a nonpeptide integrin antagonist, and its conjugated form, 89Y-TA138. Various integrin-specific binding and functional assays as well as cell-adhesion assays were used to determine the potency and integrin specificity for TA138 and 89Y-TA138. Both TA138 and 89Y-TA138 inhibited alphavbeta3-mediated [125I]echistatin binding to 293-beta3-transfected cells, with IC50 values of 0.046 and 0.059 microM, respectively, and IC50 values of 0.012 and 0.018 microM, respectively, in inhibiting an alphavbeta3 integrin-mediated 293-beta3-transfected cell adhesion to fibrinogen. TA138 inhibited human umbilical vein endothelial cell adhesion to fibrinogen, with an IC50 value of 0.052 +/- 0.006 microM. Both TA138 and 89Y-TA138 demonstrated a relatively high degree of specificity for human alphavbeta3 integrin as compared with other human integrins, including alphavbeta5, alphaIIbbeta3, and alpha5beta1 (IC50 > 10 microM). Both 89Y-TA138 and TA138 demonstrated comparable alphavbeta3 affinity and specificity as compared with other closely related human integrins such as alphavbeta5, alphaIIbbeta3, or alpha5beta1.     

Periodontal diseases and the risk of coronary heart and cerebrovascular diseases: a meta-analysis

BACKGROUND: This meta-analysis was conducted to examine the relationship between periodontal diseases and coronary heart diseases (CHD) and cerebrovascular diseases (CVD) in observational studies. METHODS: This study was based on seven cohort studies and four studies of other designs that met prestated inclusion criteria. Information on study design, year of publication, study location, sample size, study population, participant characteristics, measurement of risk factors, exposure and outcome measures, matching, controlling for confounders, and risk estimates was abstracted independently by two investigators using a standard protocol. RESULTS: Subjects with periodontitis had an overall adjusted risk of CHD that was 1.15 times (95% confidence interval [CI]: 1.06 to 1.25; P = 0.001) the risk for healthy subjects. There was no heterogeneity among the studies in the overall relative risk estimate (P = 0.472). As compared to healthy subjects, those with periodontitis had an overall adjusted relative risk of CVD of 1.13 (95% CI: 1.01 to 1.27; P = 0.032). CONCLUSIONS: Findings indicated that periodontal infection increases the risk of CHD and CVD. However, this meta-analysis provided no evidence for the existence of strong associations between periodontitis and CHD and CVD. Larger and better-controlled studies involving socially homogeneous populations and measuring specific periodontal pathogens are required to identify a definite association between periodontal disease and the risk of coronary heart disease and cerebrovascular disease.     

Alpha-interferon with ribavirin in the treatment of hemodialysis patients with hepatitis C

INTRODUCTION: Hepatitis C Viral (HCV) infection is the leading cause of chronic liver disease in end-stage renal disease patients (ESRD). The impact of HCV on patient and graft survival posttransplantation is controversial. The most successful approach is to eliminate the virus while the patient is on dialysis prior to transplantation. The main aim of this pilot study was to assess the efficacy of combined alpha-interferon (alpha-IFN) and ribavirin treatment of HCV hemodialysis (HDx) patients, by comparing the sustained virological response to that obtained by local historical data on treatment with alpha-IFN alone. A secondary aim was to establish the optimal therapeutic dose of ribavirin in this regimen. METHODS: Twenty HCV-HDx patients who were histologically (liver biopsy) and virologically (HCV-PCR)-positive were selected randomly. They received combination therapy with 3 million units (MU) of alpha-IFN and 200 mg of ribavirin three times a week. Initially nine patients were treated for 24 weeks. Later, another 11 patients were randomly selected to give the combination for 48 weeks. RESULTS: Six of the nine patients who were treated for 24 weeks (66%) became HCV-PCR-negative by the end of the treatment period. They continued to have a sustain virologic response at 6 months after the cessation of therapy. Six of the 11 patients (55%) who were treated for 48 weeks became HCV-PCR-negative at the end, and at 6 months after cessation of treatment. Of the first six responders, 4 (66%) maintained a sustained virologic response at 1 year postcessation of therapy. Nine of the 11 patients had genotype 4 and 1. No side effects were reported for a ribavirin dose of 200 mg three times a week. CONCLUSION: This pilot study suggests that combination treatment for 24 weeks and 48 weeks with 3 MU alpha-IFN and 200 mg ribavirin three times a week, elicited a sustained virologic response in HDx patients with HCV infection better than IFN alone with minimal side effects. A prospective, double-blind, controlled study using pegylated INF plus ribavirin is currently underway.     

Two cases of adreno-hepatic fusion in cynomolgus monkeys (Macaca fascicularis)

In this report we describe 2 cases of adreno-hepatic fusion (AHF) in Cynomolgus monkeys (Macaca fascicularis) used in short-term toxicity studies. AHF is defined as the union of hepatic tissue with the adrenal gland with close intermingling of the respective parenchymal cells. In this condition, a continuous intervening connective tissue septum is lacking. AHF is believed to be a congenital anomaly caused by a defect or delay in the formation of the organ capsules from the intermediate primitive mesenchymal stroma. To our knowledge, this is the first time this anomaly is described in the monkey.     

Rupture of excluded popliteal artery aneurysm: implications for type II endoleaks--a case report

The fate of popliteal artery aneurysms after ligation and bypass is believed to be relatively innocuous. The patient presented in this report, however, experienced spontaneous rupture of a popliteal aneurysm 11 years after ligation and bypass. Magnetic resonance angiography was used to establish the diagnosis of rupture, which was subsequently confirmed at surgery. Intraoperative arteriography demonstrated persistent collateral arterial perfusion of the excluded popliteal aneurysm sac. The collateral arterial flow originated from the superior and inferior lateral genicular arteries. The persistent arterial perfusion resulted in growth of the aneurysm from 4.2 to 7.0 cm over the 11-year period. The ruptured aneurysm was successfully treated by direct arterial exposure and suture ligation of the collateral vessels performed from within the aneurysm sac. The development of popliteal aneurysm expansion and rupture as a result of collateral arterial perfusion suggests that persistent collateral perfusion of abdominal aortic aneurysms after endovascular repair (type II endoleak) may lead to aneurysm rupture. Therefore, close observation and intervention for aneurysm expansion to prevent rupture of the excluded aneurysm are warranted.