The temporal expression of amyloid precursor protein mRNA in vitro in dissociated hippocampal neuron cultures.

The subunit protein of the neurofibrillary tangle, the core protein of the neuritic plaque, and the amyloid of the cerebrovasculature in Alzheimer disease and normal aging is a unique 42-amino acid protein (amyloid beta-protein), suggesting a common origin for these pathological entities. However, the expression of the amyloid precursor protein mRNA (APP mRNA) from which the amyloid beta-protein is derived varies between specific neuronal populations. To determine the conditions under which neuronal synthesis of amyloid beta-protein might contribute to the formation of these structures, we have studied the temporal pattern of APP mRNA expression in developing fetal rabbit hippocampal neurons in vitro. Using in situ hybridization with a biotinylated riboprobe transcribed from a cDNA which includes the region encoding the amyloid beta-protein, we have observed a developmentally specific pattern of APP mRNA hybridization during neuronal maturation in vitro.

Long-term follow-up of 60 patients with chronic hepatitis B. I. Seroconversion in the hepatitis B e-system, frequency of delta infection and histological outcome.

Sixty patients with liver biopsy documented chronic hepatitis B attending Roslagstull Hospital for Infectious Diseases, Stockholm, Sweden, were followed during a mean period of 53 months (range 7-133 months) in order to evaluate the frequency of delta infection and HBeAg seroconversion as well as the histological outcome as assessed by liver biopsy. Spontaneous HBeAg clearance and development of anti-HBe occurred among 17 of 36 initially HBeAg positive patients (47%), corresponding to an annual seroconversion rate of 11%. Biochemical improvement was noted in 7/17 patients (41%) after seroconversion as against in 2/19 patients (10.5%) with HBeAg persistence. Superinfection with the delta agent was seen to be associated with severe liver injury among drug addicts and immigrants with chronic hepatitis B. In the absence of a delta infection, progressive liver disease seemed to be associated with persistence of HBeAg. Although none of the homosexual men studied were delta superinfected, 71% developed chronic active hepatitis (CAH) with or without cirrhosis (CI).

Definition of three serotypes of Hantaviruses by a double sandwich ELISA with biotin-avidin amplification system.

A total of seven different isolates of Hantaviruses from five mammalian species and six geographical areas were examined by a double sandwich ELISA with biotin-avidin amplification system. Three serotypes were recognized by comparing antigen titres to homologous and heterologous antibody and blocking antibody titres to homologous and heterologous antigens. Serotype 1 included four strains: Hantaan virus isolated from Apodemus agrarius in South Korea, Hupei-I isolated from acute-phase serum from a patient with epidemic haemorrhagic fever (EHF) in China, SR-11 isolated from a laboratory rat associated with an EHF outbreak in Sapporo, Japan, and Tchoupitoulas isolated from a wharf rat (Rattus norvegicus) trapped in New Orleans, La., U.S.A. Serotype 2 included two strains of nephropathia epidemica virus, Hällnäs-I and Puumala, isolated from Clethrionomys glareolus trapped in nephropathia epidemica foci in Sweden and Finland, respectively. Serotype 3 included one strain, Prospect Hill-I, isolated from Microtus pennsylvanicus, trapped in Frederick, Md., U.S.A.

Isolation and propagation of nephropathia epidemica virus in bank voles.

Three strains of nephropathia epidemica (NE) virus were isolated from lung tissues of bank voles (Clethrionomys glareolus) and a grey-sided vole (C. rufocanus) trapped in Västerbotten county, Sweden. Two of these isolates were serially passaged in seronegative laboratory-bred bank voles. Experimentally infected animals developed a subclinical infection characterized by virus persistence, particularly in lung tissue. Attempts to infect other species of colonized rodents with NE virus and to isolate NE virus from acute phase patient blood were unsuccessful. The serial propagation of NE virus in colonized bank voles provides opportunities to study experimental infection in its reservoir rodent host.

Delta infection among patients with chronic hepatitis B in the Stockholm region.

The prevalence, epidemiology and consequences of delta infection were analysed in 60 patients attending the Roslagstull Hospital for Infectious Diseases, Stockholm, Sweden, between 1972 and 1982. All of the patients had biopsy-documented chronic hepatitis B. Using radioimmunoassay techniques, sera from all patients were tested for antibodies to hepatitis A virus, for hepatitis B surface antigen and the corresponding antibody, for antibodies to hepatitis B core antigen, for hepatitis B e antigen and the corresponding antibody and for antibodies to delta antigen. All 60 patients underwent a liver biopsy which was repeated in 28 patients. 32% of the patients (19/60) were found to be anti-delta positive. The majority of the anti-delta positive patients were either immigrants from non-European countries or addicts (both 9/19 or 47%). Infections with delta agent were found to have already occurred in the Stockholm region in the early 1970s. During the study period, four of the patients developed clinical and laboratory signs of acute hepatitis in association with a delta infection. Among the anti-delta positive patients, 63% (12/19) were classified as having chronic active hepatitis, with or without cirrhosis, as against 39% (16/41) of the anti-delta negative patients. Histological progression to cirrhosis was observed in two of the four anti-delta positive patients with initial chronic active or chronic persistent hepatitis.

Indirect immunofluorescence tests in Korean hemorrhagic fever and epidemic (endemic) nephropathia: treatment at low pH for removal of 'nonspecific' fluorescence in tissues from immunocompetent hosts.

A 'nonspecific' fluorescence probably caused by immunocomplexes appears in the lung tissue of immunocompetent hosts infected with Korean hemorrhagic fever (KHF) or epidemic nephropathy (EN) viruses. Indirect immunofluorescence tests with such KHF- or EN-infected tissue as antigen are unsatisfactory for the detection of low-titer antibody or the reading of titer endpoints. Treatment of acetone-fixed lung sections at pH 3.0 followed by washing with 0.01 M phosphate-buffered saline and distilled water apparently dissolves the immunocomplexes, resulting in an effective removal of the 'nonspecific' fluorescence while the viral antigens are not significantly impaired. Lung sections of KHF-infected Apodemus agrarius coreae and EN-infected Clethrionomys glareolus, acetone-fixed and treated at pH 3.0, were used for the antigenic differentiation of the EN and KHF viruses.

Epstein-Barr virus-associated and other antiviral antibodies during intense BCG administration to patients with Burkitt's lymphoma in remission.

Patients with Burkitt's lymphoma in chemotherapy-induced remission received through dermal scarifications one or two doses per week of approximately 3 X 10(8) living BCG organisms (Pasteur Institute vaccine). This treatment was always followed by usually rapid increases by 1--4 log2 steps in the antibody titers to Epstein-Barr virus (EBV)-associated cell membrane antigens. Titer increases of less than 2.5 log2 steps within the first month after the start of BCG treatment correlated with a significantly elevated frequency of extradural relapse as compared to that seen in patients with larger titer rises. During this time, antibodies to EBV-associated viral capsid antigens and early antigens of D and R specificity, as well as antibodies against herpes simplex, varicella, cytomegalovirus, measles, and respiratory syncytial virus antigens, did not show any consistent or impressive changes.