Evolution of type C viral genes: preservation of ancestral murine type C viral sequences in pig cellular DNA.

Domestic pigs (Sus scrofa) and other members of the family Suidae have multiple copies of type C viral gene sequences in the cellular DNA of all their tissues. Partially homologous viral gene sequences are also found in cellular DNA of rodents, particularly Muridae. The results lead to the conclusion that type C viral genes were introduced into the Suidae lineage as a result of trans-species infection by an ancestral xenotropic murine virus. The rate of evolution of the virogene sequences in the pig appears to be much slower than that of genes that have remained in the rodent lineage; this may be a consequence of transfer from a shorter-lived animal (the rodent) to a longer-lived one (the pig). We estimate the time of gene transmission as 5-10 million years ago and conclude that the present-day porcine type C virogenes most closely approximate the viral genes as they were several million years ago in the rodent lineage.     

Immunologic approaches to acute leukemia in the elderly

The outcome of older patients with acute leukemia remains poor with few long-term survivors, indicating the need for treatment approaches that target pro-apoptotic pathways not influenced by chemotherapy resistance. For a long time, natural killer (NK) cells have held promise for cancer immunotherapy because, unlike T lymphocytes, they can kill tumor cells without the need for tumor-specific antigen recognition. In the treatment of acute leukemia, NK cell-based therapies have focused on in vivo expansion and activation with cytokines with only modest success. However, recent understanding of the importance of NK receptors for the recognition and lysis of leukemia cells suggests novel therapeutic strategies. The balance of inhibitory and activating signals through surface receptors, recognizing major histocompatibility complex (MHC) class I and class I-like molecules on target cells, determines whether NK cells activate killing. In this review, we discuss the biologic rationale for therapeutic strategies harnessing NK cells and focus on novel directions for their future use in elderly patients with acute leukemia.     

Significance of hepatic expression of hepatitis C viral antigens in chronic hepatitis C

To determine the significance of hepatic expression of hepatitis C viral (HCV) antigens, HCV core and NS4 antigens were detected by immunohistochemistry in 46 patients with chronic HCV infection. Serum HCV RNA was quantitated by branched DNA assay in 41 and HCV genotype determined in 30 patients. HCV core and NS4 antigens were detected exclusively in the cytoplasm of hepatocytes in 83% and 61% of patients, respectively. There was no correlation between the expression of HCV antigens and clinical, biochemical, histological parameters and HCV genotype. Hepatic expression of HCV antigens was positively associated with serum HCV-RNA levels (P<0.02). At the end of interferon- (IFN) therapy, expression of HCV antigens remained either unchanged or decreased in 11/12 patients studied (undetectable in all four patients who had complete and sustained response). We conclude that hepatic expression of HCV core and NS4 antigens parallels serum HCV-RNA levels and IFN therapy reduces hepatic expression of these viral antigens.     

GB virus type C infection polarizes T-cell cytokine gene expression toward a Th1 cytokine profile via NS5A protein expression

Human immunodeficiency virus (HIV) disease progression is associated with a helper T cell 1 (Th1) to helper T cell 2 (Th2) cytokine profile switch. Persistent GB virus type C (GBV-C) infection is associated with survival and a serum Th1 cytokine profile in HIV-infected individuals. We found that GBV-C infection increased gene expression of Th1 cytokines and decreased Th2 cytokine expression in peripheral blood mononuclear cells. Furthermore, expression of GBV-C NS5A protein in a CD4(+) cell line resulted in upregulation of Th1 cytokines (tumor necrosis factor α) and downregulation of Th2 cytokines (interleukin 4, interleukin 5, interleukin 10, interleukin 13). GBV-C-induced modulation in T-cell cytokines may contribute to the beneficial effect of GBV-C in HIV-infected individuals.     

Immunologic detection of endothelial cells in human whole blood

In this report we show that human endothelial cells (EC) can be detected in circulating blood by means of the EC-specific monoclonal antibody (MoAb) designated as CLB-HEC 19 and expressed quantitatively as number of cells per milliliter of whole blood. We first developed a method that was able to recover cultured human EC added to whole blood by Percoll density gradient centrifugation. The final recovery of the EC was 91.6% (SE = 0.65%). The EC were identified in the gradient subfractions by indirect immunofluorescence with the MoAb CLB-HEC 19. This method was then applied to the separation and characterization of EC or EC remnants from the whole arterial and venous blood taken from two groups of patients subjected to heart catheterization. Firstly, a preliminary blood screening of random samples was performed in a group of eight patients (group I) using a scoring evaluation for the presence of EC and the results were expressed as positivity index. Secondly, the complete blood screening of a group of ten patients (group II) was performed for the detection of immunofluorescent cells and the results were expressed as number of EC per milliliter of whole blood. Our results show in both group I and II a significant presence of EC in the blood after catheterization compared with their basal values. The minimal detectable concentration of EC was 0.06 cells/mL (SE = 0.057) of whole blood. We consider this technique as a suitable clinical test for the detection of EC injury in cardiovascular pathology.     

Immunologic complications of the hepatitis C virus

An increasingly wide variety of extrahepatic manifestations have been reported in patients with chronic hepatitis C virus (HCV) infection. Many are immunologic in nature and may be precipitated by interferon-based therapy. Among these associations, mixed cryoglobulinemia is the most prevalent and best characterized. Additional HCV-related immunologic complications include autoantibody production, rheumatologic disorders, immune-mediated cytopenias, and lymphoproliferative disorders; the certainty of association varies for many of these conditions. The mechanisms through which HCV induces these complications are incompletely understood. In this review, we discuss the immunologic complications of HCV infection, focusing on their epidemiology, pathogenesis, and treatment.     

Immunologic approaches to blockade of the renin-angiotensin system: a review

Several immunologic approaches to blockade of the renin-angiotensin system (RAS) have been reported, involving most of the proteins and peptides of the biochemical cascade: renin, substrate, angiotensins, and converting enzyme. None as yet has involved blockade of angiotensin II receptors. Earlier and more recent studies used passive transfer of heterologous antibodies or active immunization against RAS proteins and peptides. Passive transfers have been performed with both polyclonal antibodies and now with specific monoclonal immunoglobulins. The latter are better defined in affinity, quantity, and capacity to bind and thus inhibit the biologic activity of the antigen. Active immunization produced long-term blockade of part or all of the biologic activity of the system. The immunopathologic consequences of the use of antibodies raised against a self-antigen could be of interest in defining the predominant site of storage and secretion of the relevant protein and hence the respective roles of different tissues in the production of specific proteins in, for example, the vascular pulmonary bed for converting enzyme and renal arterial tree for renin. In all cases immunologic methods offer in vivo experimental models of short- or long-term RAS blockade that could be compared with pharmacologic methods, such as converting-enzyme inhibition, angiotensin II antagonists, and renin inhibitors.     

丙型肝炎病毒在肝外组织复制状态和抗原表达

目的 探讨丙型肝炎肝外组织丙型肝炎病毒（ｈｅｐａｔｉｔｉｓ Ｃ ｖｉｒｕｓ,ＨＣＶ）感染和复制状态及其意义。方法 分别采用免疫组织化学和逆转录多聚酶链反应（ｒｅｖｅｒｓｅ ｔｒａｎｓｃｒｉｐｔａｓｅ ｐｏｌｙｍｅｒａｓｅ ｃｈａｉｎ ｒｅａｃｔｉｏｎ,ＲＴＰＣＲ）方法检测９例丙型肝炎肾,心,胰腺和肠等肝外组织ＨＣＶ多种抗原和正链,负链ＨＣＶ ＲＮＡ。结果 ９例中６例（６６．７％）在肝外组织检出ＨＣ     

Effect of glycyrrhizin on viral replication and quasispecies in patients with type C chronic hepatitis

The effects of glycyrrihizin on liver-function, amounts of HCV RNA and viral complexity in patients with chronic hepatitis C were examined. The subjects were 27 type C chronic hepatitis patients who did not respond to previous interferon therapy. They were given 60 ml of Stronger Neo-Minophagen C, a preparation of glycyrrhizin combined with glycine and cysteine, three times a week for 16 weeks. The treatment was effective in 20 patients (74.1%), whose serum levels of aminotransferase fell to one half of that before treatment, but was not effective in seven patients (25.9%). No significant differences were noted at the beginning of the therapy in the backgrounds (age, sex, serum levels of aminotransferase, etc.( of the effective and non-effective groups. Also, no significant differences in HCV RNA quantity and viral complexity of HCV RNA were observed between the two groups. The results suggest that glycyrrhizin improves serum ALT levels without changing the amounts of HCV RNA and viral complexity, suggesting that the effect might depend on host factors such as the immune response.