Induction of class II molecules by cytomegalovirus in rat heart endothelial cells is inhibited by ganciclovir

Abstract Cytomegalovirus (CMV) has been demonstrated to induce class II antigen expression in endothelial cells. To study whether ganciclovir (DHPG) has an effect on CMV-induced class II expression, cultured rat heart endothelial cells were infected with rat CMV (RCMV) and treated with different DHPG concentrations. Class II antigens in endothelial cells were detected by a monoclonal antibody and immunoperoxidase technique. Control cells did not express class II antigen, but during RCMV infection 92% of cells were class II-positive. DHPG treatment (1, 10, 100 and 1000 μg/ml) decreased RCMV-induced class II expression from 73% to 59%, 6% and 0%, respectively. As DHPG inhibits CMV DNA polymerase, our present results suggest that DHPG affects RCMV-induced class II expression via the inhibition of RCMV DNA replication.     

Functional polymorphism of p53 and CCR5 genes in the long-lived of the Siberian region

The P53 protein is a key regulator of modified-cell apoptosis. The functional oligonucleotide polymorphism of the p53 gene causes the substitution of arginine (Arg) for praline (Pro) in the codon 72. A reduced apoptotic activity of p53 and, as a consequence, development of oncology pathology is associated with the above polymorphism. CCR5 is a compound transmembrane receptor-protein, which apart from chemokines, binds with some molecules and is a coreceptor for HIV-1. 32 bp deletion within the CCR5 encoding region results in the loss of the protein's receptor function. It has been demonstrated that the transmission of the "external" (in respect to cell) stimulus, via the CCR5 system, induces expression of the p53 gene and initiates apoptosis. Allele variants and p53 and CCR5 genotypes (separately and in combinations) were investigated, within the present case study, for 131 long-livers from Novosibirsk and Tyumen Regions. A trend was detected towards accumulation of the p53 Pro alleles in association with the CCR5del32 allele in the study group, which, as the authors believe, can enhance the genome resistance to variable factors that cut the life span.     

Results of surgical intervention depending on duration of preoperative treatment of pulmonary tuberculosis patients

The case histories of 428 patients operated on for tuberculosis were analyzed. Three groups were identified. They were as follows: 1) 121 patients untreated with bactericidal drugs before surgery; 2) 247 patients treated less than 6 months before it; 3) 160 patients treated more than 6 months before surgery. Various complications due to resection of the lung were observed in 30 (7%) patients undergone surgery. They were 6.6, 6.8, and 7.5% in Groups 1, 2, and 3, respectively. A clinical effect was achieved in 99.8% of cases. The late outcomes of surgical intervention were studied within 1 to 10 years in 354 patients, including 102, 119, and 133 patients in Groups 1, 2, and 3, respectively. Progressive and recurrent tuberculosis was revealed in 7 (6.8%), 11 (9.2%), and 18 (13.5%), respectively. Thus, immediate and late outcomes of surgical treatment were not worse in patients with tuberculomas untreated with bactericidal drugs before surgery than in those who receive long-term therapy that substantially reduces the duration of therapy, which is a most important task of modern phthisiology. So patients should be operated on when they are found to have pulmonary tuberculomas without signs of a progressive tuberculous process.     

Mechanisms of coxsackievirus-induced damage to human pancreatic beta-cells

Enteroviruses may be involved in the pathogenesis of insulin-dependent diabetes mellitus, either through direct beta-cell infection or as triggers of autoimmunity. In the present study we investigated the patterns of infection in adult human islet cell preparations (consisting of 56+/-14% beta-cells) by several coxsackieviruses. The cells were infected with prototype strains of coxsackievirus B (CBV) 3, 4, and 5 as well as coxsackievirus A9 (CAV-9). The previously characterized diabetogenic strain of coxsackievirus B4 (CBV-4-E2) was used as a reference. All viruses replicated well in beta-cells, but only CBVs caused cell death. One week after infection, the insulin response of the beta-cells to glucose or glucose plus theophylline was most severely impaired by CBV-3 and CBV-5 infections. CBV-4 also caused significant functional impairment, whereas CAV-9-infected cells responded like uninfected controls. After 2 days of infection, about 40% of CBV-5-infected cells had undergone morphological changes characteristic of pyknosis, i.e. highly distorted nuclei with condensed but intact chromatin. Both mitochondria and plasma membrane were intact in these cells. DNA fragmentation was found in 5.9+/-1.1% of CBV-5-infected beta-cell nuclei (2.1+/-0.3% in controls; P<0.01). CAV-9 infection did not induce DNA fragmentation. One week after infection the majority of infected cells showed characteristics of secondary necrosis. Medium nitrite and inducible nitric oxide synthase messenger ribonucleic acid levels were not significantly up-regulated by CBV infection. These results suggest that several enteroviruses may infect human beta-cells. The infection may result in functional impairment or death of the beta-cell or may have no apparent immediate adverse effects, as shown here for CAV-9. Coxsackie B viruses cause functional impairment and beta-cell death characterized by nuclear pyknosis. Apoptosis appears to play a minor role during a productive CBV infection in beta-cells.