Semliki forest virus: cause of a fatal case of human encephalitis.

A fatal case of human encephalitis has been observed for which our results indicate that Semliki Forest virus (SFV) was the etiologic agent. This is surprising in view of the fact that this virus, which has been widely studied, was believed to be one of the arboviruses nonpathogenic for man. Described are the clinical course, the virological examinations performed, and the histopathological findings in the central nervous system.

Complications of mumps infection, islet-cell antibodies, and HLA.

To investigate whether the development of islet-cell antibodies (ICA) in the course of mumps infection is associated with a "diabetes-like" immunogenetic condition, 45 children with mumps complications as well as 56 children with insulin-dependent diabetes mellitus (IDDM) were typed for HLA ABC and DR antigens. ICA were detected in 14 out of 35 mumps patients. In the IDDM group, significant deviations from antigen frequencies of normal controls were observed for HLA Bw39, DR2, DR3, and DR4. In contrast, in ICA positive mumps patients, the frequency of these antigens was normal, but Aw24 was significantly increased. Thus, no immunogenetic similarities of both groups of patients could be detected.

Effect of spleen exposure to ultrasound on cellular and antibody-mediated immune reactions in man.

Spleen exposure to ultrasound has been reported to influence antibody response to sheep red blood cell injection in mice (decreased hemagglutination and hemolytic titers and IgM, IgG2a and IgG2b levels and elevated IgG1 levels). In a controlled clinical trial, we investigated the possible immunosuppressive side-effect of splenic exposure (2.0 mW/m2, 3.5 MHz, 5 minutes) to ultrasound on the immune response to Rubella vaccination in 41 anti-Rubella antibody-negative volunteers. The measured parameters (blood cell count, IgA, IgM, IgG including subclasses IgG1-IgG4, isoagglutinins, anti-Rubella hemagglutinin and hemolysin titers, complement C3, skin tests to mumps and tuberculin, T, B and O lymphocytes, esterase-positive and negative T-cell subsets) suggest changes dependent on the time of vaccination, but provide no evidence of an immunosuppressive effect of ultrasound in man.

Clinical and immunological aspects of hepatitis B virus infection in children receiving multidrug cancer chemotherapy.

For two reasons hepatitis B virus infection is an important problem in patients with cancer. First, multidrug cancer chemotherapy may reactivate or worsen a previously benign chronic HBV infection. Second, patients undergoing cancer chemotherapy are at an increased risk of acquiring and spreading HBV which may result in an endemic infection. HBV reactivation may precipitate into a severe acute disease including fulminant hepatitis. In contrast, the acquisition of HBV during cancer chemotherapy commonly takes a mild clinical course but frequently leads to persistently high viremia. This state of immunotolerance to viral antigens allows viral replication without any sign of liver cell destruction. Withdrawal of chemotherapy does not cause significant changes if infection occurred during cytotoxic chemotherapy. Infection with HBV during cancer chemotherapy, therefore, may be considered as a model of an induced antigen-specific immunotolerance. In agreement with this hypothesis, vaccination against HBV during cancer chemotherapy does not prevent spread of HBV in oncology wards as it does not produce significant anti-HBs titers. Furthermore, vaccination even suppresses the immune response to later booster doses after chemotherapy has been withdrawn.

A monoclonal antibody that recognizes a formalin-resistant epitope on the p 24 core protein of HIV-1.

A murine monoclonal antibody (called H-11) that binds to the p 24 core protein of HIV-1 was characterized by radioimmuno-precipitation, immunofluorescence, western blot assays, immunocytochemistry and immunohistochemistry. This antibody was found to be especially suited for demonstrating the presence of HIV-1 in formalin-fixed, paraffin-embedded tissues.

[Pre- and perinatal infections with sexually transmissible microorganisms]. / Prä- und perinatale Infektionen mit sexuell übertragbaren Erregern.

The sexually transmissible pathogenic microorganisms, which are also capable of initiating pre- or perinatal infections, include Neisseria gonorrhoeae, Treponema pallidum, Chlamydia trachomatis serovars D through K, group B streptococci, urogenital mycoplasmas, herpes simplex viruses types I and II, cytomegalovirus, hepatitis B virus, human immunodeficiency viruses, human papillomaviruses, Candida spp. and Trichomonas vaginalis. With special emphasis on paediatric and neonatological aspects, brief discussions of the following topics are presented: the epidemiology of these agents, the diseases they can induce in pregnancy, the mode of infection of and the diseases in the fetus and neonate, the preventive measures, the diagnosis and therapy.

A case of Coxsackie A9 virus infection with orchitis.

A thirteen-year-old boy with bilateral orchitis was diagnosed as being infected by Coxsackie A9 virus by isolation of the virus from a throat swab and a fecal specimen. Serologic investigations revealed the development of transitory specific neutralizing IgM antibodies against the isotate and of persistent antibodies belonging to the other immunoglobulin classes. An etiology of the orchitis by any of the infectious agents usually found with this condition could be excluded.

No adverse prognostic influence of hepatitis B virus infection in acute childhood lymphoblastic leukemia.

In the years 1980-1985 72 children with acute lymphoblastic leukemia were diagnosed and treated by intensive combination chemotherapy (BFM protocols 79, 81, 83). Of these children 33 acquired a Hepatitis B-virus-carrier state with 1983 as the peak year of incidence. Both groups of patients, the infected and the uninfected ones, were comparable as to prognostic factors. All except 8 patients are off chemotherapy after a total duration of treatment of 1 1/2 or 2 years. Probability for event-free survival (life table analysis, maximum observation time 82 months, minimum 12 months) is equal (0.77 vs. 0.75) in both groups. With 3 exceptions, all HBV-infected patients still carry the HBs-antigen in the serum; 22 of the 30 living patients in the infected group developed anti-HBc.

[Cytomegaly infection in infancy in a family with demonstrated HIV antibodies]. / Frühkindliche Cytomegalie-Infektionen in einer Familie mit HIV-Antikörpernachweis.

Cytomegalovirus (CMV) was isolated from the urine of babies from two consecutive pregnancies of a mother. The first baby had died of pneumonia at the age of six months, two years before the second confinement (twins of different sexes). The male twin was examined at the age of eight months on account of generalized lymphomas, pulmonary infiltrates and thrombopenia. He excreted CMV in the urine, and HIV antibodies were found in the serum. All members of the family (also the baby who died in 1983, from whom serum samples had been stored at -20 degrees C) finally proved to be carriers of antibodies against HIV. The parents and the female twin did not show any clinical symptoms indicating a HIV infection; however, CMV was also isolated from a urine sample from the mother.

Metabolism of myoinositol in avian and mammalian cells infected with naked and enveloped DNA and RNA viruses.

The uptake of 3H-inositol into the pool of free inositol and its incorporation into the lipid phosphatidylinositol have been studied in various avian and mammalian cells infected by different viruses. In all the virus-cell systems investigated, virus infection results in a drastically reduced amount of free 3H-inositol about 3 to 5 h post-infection, demonstrable in the infected cells as compared to the mock-infected controls. In contrast, the incorporation of 3H-inositol into lipid can be enhanced, reduced, or not influenced at all, depending on the virus-cell system under observation.

Generation of human anti-rubella monoclonal antibodies from human hybridomas constructed with antigen-specific Epstein-Barr virus transformed cell lines.

Human monoclonal antibodies (humab) directed against viral antigens were developed by combining immortalization of human primary B lymphocytes by Epstein-Barr virus (EBV) infection with consecutive fusion of selected immortalized lymphoblasts with an established, human lymphoblastoid cell line. Using EBV infection a high rate of immortalized B lymphoblastoid cells was obtained which unfortunately could not be cloned because at least 10 cells per microtiter well had to be seeded to get cells growing. However, fusion of these immortalized lymphoblastoid cells which had been selected for antiviral humab production with an established cell line resulted in hybridomas which could easily be cloned. Among the antiviral humab producing hybridomas thus generated, were three which produced anti-rubella humab. Rubella virus consists of three structural proteins, the core protein C and the two envelope proteins E1 and E2. By the western blot technique we were able to show that two humab reacted with the core protein and the third humab with the envelope protein E1. From the hybridomas grown in stationary cultures, highly purified humab preparations were obtained by subjecting the concentrated culture supernatant to immuno-affinity chromatography.

Neurogenic spread of Semliki Forest virus in mice.

We present evidence that in SFV-infected mice the virus invades the brain via nervous tracts, and that in the early stage of infection of the brain itself dissemination is restricted to neurons. After intranasal (i.n.) application, migration along the neuronal route appeared to be the principle mechanism of spread irrespective of the virulence of the strain used. After subcutaneous (s.c.) infection, neuronal spread could also be demonstrated, however the pattern and time course of brain invasion were different. The LD50 of strain Hd depended significantly on the route of virus application: compared with the i.n. route, its value increased after s.c. infection. This increase was correlated with high plasma interferon induction and natural killer cell activation. In contrast, these activities were virtually absent during the early course after i.n. infection.

Mumps, mumps vaccination, islet cell antibodies and the first manifestation of diabetes mellitus type I.

To connect mumps and diabetes mellitus in children is an old problem in medical literature. The typical occurrence of ICA at the onset of diabetes in children, as well as the incidence of ICA approximately 3 weeks after mumps infection support the hypothesis of a direct relationship between virus infection and diabetes. But the mumps infection alone is not the key factor. Mumps vaccination may not provide protection against diabetes mellitus, it may even provoke it. (Genetic determination, expressed by the HLA-phenotype in all the patients reported, does not allow a differentiation.)

Hepatitis C virus transmission by a blood donation negative in nucleic acid amplification tests for viral RNA.

Hepatitis C virus (HCV) was transmitted by transfusion of a platelet concentrate made from an anti-HCV and HCV-PCR-negative blood donation. Even a negative nucleic acid amplification test cannot completely prevent transmission of HCV.

Virus infection islet cell antibodies and islet cell function in type I diabetes mellitus.

The detection of islet cell antibodies has led to an increasing interest in autoimmune mechanisms in Type I diabetes mellitus. Other phenomena, such as insulitis in juvenile diabetics and in experimental animals, cellular immune reactions and concommitant antibodies against other endocrine organs, antinuclear antibodies and circulating immune complexes have supported such speculations. HLA-association and viral-infections could be predisposing and inducing factors. However, with one exception, the occurrence of ICA in a group of mumps infected children did not result in the development of diabetes mellitus over 3-4 years, nor could it be correlated with HLA-pattern. The islet cell antibodies block glucose stimulated insulin secretion in vitro without complement, while Type I diabetic sera with complement are beta cell cytotoxic irrespective of their ICA concentration. It is still not clear whether these mechanisms play any role in vivo. Therapeutic intervention before the clinical manifestation of the disease is as yet not possible due to the lack of markers indicating a subclinical autoimmune process.

The value of quantitative measurement of HBeAg and HBsAg before interferon-alpha treatment of chronic hepatitis B in children.

Serum concentrations of HBsAg, HBeAg and hepatitis B virus DNA were measured quantitatively before interferon treatment in 23 children (17 boys, 6 girls) suffering from chronic hepatitis B, and correlated to the outcome of the treatment. Five children remained HBsAg- and HBeAg-positive throughout the treatment and 6 months after the end of the treatment (non-responders), 12 children eliminated HBeAg but not HBsAg (partial responders) and six eliminated HBeAg and HBsAg (complete responders). The five non-responders had significantly higher initial HBsAg and HBeAg concentrations and significantly lower alanine aminotransferase levels than the partial or complete responders. The six complete responders had significantly lower HBsAg concentrations than the partial or non-responders, and seemed to be younger. No significant difference in HBV DNA levels was found in the three response groups. These data suggest that quantitative assays of HBsAg and HBeAg are particularly useful in selecting patients with chronic hepatitis B for interferon therapy.

Islet cell antibodies and the development of diabetes mellitus in relation to mumps infection and mumps vaccination.

Islet cell antibodies were investigated in 127 non-diabetic children after mumps infection and in four out of seven children who developed diabetes mellitus shortly after active mumps vaccination. Twenty-one of the children who had mumps and all four vaccinated children who were tested had islet cell cytoplasmic antibodies. In contrast, islet cell surface antibodies were detected in 43 out of 68 patients with mumps infection and in 32 out of 44 patients with other viral diseases. All but one mumps-infected child and all the other viral infected patients investigated did not develop diabetes mellitus. The mumps-infected ICA positive children did not show those HLA-frequencies associated with Type 1 diabetes.