摘要:

AbstractA newly described, drug‐carrier delivery system in which a lipophilic derivative is enzymatically converted to a hydrophilic compound was used to treat experimental herpes simplex virus (HSV) encephalitis. Because trifluorothymidine (TFT) does not cross the blood brain barrier, the lipophilic dihydropyridine derivative 3 ′hyphen;(N‐methyl‐ 1, 4‐dihydronicotinoyl)hyphen;5hyphen;'pivaloyltrifluorothymidine (DHTFT) was synthesized and characterized by HPLC. After intravenous administration of 20 mg/kg of DHTFT to rats, the quaternary, intermediate compound 3'‐N‐methyl‐1,4‐nicotinoyltrifluorothymidine was measured at levels of 7–8 m̈/g brain at 1 hour and 13.5 ± 0.8 m̈g/g brain at 4 hours. This compound had antiviral activity equivalent to that of TFT against HSV‐1 in a plaque reduction assay (ID 50 = 0.5–1.0 m̈g/ml), either directly or by conversion to TFT. Although survival was not prolonged in a rat model of HSV encephalitis, a statistically significant reduction in titer of HSV/g brain was achieved with daily intravenous treatment with DHTFT. TFT was not detected in brains of rats at 1 and 4 hours after intravenous DHTFT, but a low level was observed at 18 hours, 0.3 ± 0.05 pg/g brain. These data suggest that the lipophilic compound DHTFT or a lipophilic metabolite crossed the blood brain barrier and w

ISSN:0146-6615    

DOI:10.1002/jmv.1890200102

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractOnly recently have we begun to fully realize the diversity of virions within a single human isolate of the group B Coxsackieviruses. These intratypic (strain) differences may be one of the important factors influencing pathogenesis, e.g., myocarditis vs. pancreatitis. Yet, until the virion strains within a type can be well differentiated, a thorough analysis of the pathogenic potential of each is not possible. We compared two human isolates, JVB and Edwards, and 15 isolates derived from these two in search of determinants of strain specificity and to evaluate the diversity/stability of neutralization epitopes on the virions comprising each isolate. Polyclonal antisera failed to show strain specific determinants. However, monoclonal antibodies directed to individual neutralization epitopes defined strain specific differences. Plaque reduction neutralization tests with these monoclonal antibodies allowed the quantitation of the expression of epitopes on the virions in each isolate. These data helped to establish the limits of diversity and stability of the neutralization epitopes of Coxsackievirus B4 virions and describe the changes in epitopes among laboratory isolates.

ISSN:0146-6615    

DOI:10.1002/jmv.1890200103

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractWe studied 56 asymptomatic homosexual male volunteers in Pittsburgh for 11/2 yr for relationships between cytomegalovirus (CMV) and human T‐lymphotropic virus type III (HTLV‐III) infections. CMV was most frequently isolated from semen (8%) as compared with throat washings (5.9%) and urine (0%) on initial testing of CMV‐seropositive subjects. Other viruses commonly isolated from immunosuppressed patients (herpes simplex virus, adenovirus) were rarely detected in this cohort. Seropositivity to HTLV‐III was significantly associated with isolation of CMV from semen in our asymptomatic cohort (odds ratio = 9.5, p = .008). These results suggest that HTLV‐III infection is associated with selective, temporal activation of CMV in the genital tract of asymptomatic homos

ISSN:0146-6615    

DOI:10.1002/jmv.1890200104

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractSera collected from patients with acute hepatitis A virus (HAV) infection and convalescent sera were examined for cytolytic activity against HAV‐infected human‐embryo lung fibroblasts (HAV carrier fibroblasts).Using the51chromium release assay, no complement dependent antibody mediated cytolytic activity against HAV carrier cells could be detected. In control experiments with identical cell strains, anti‐herpes simplex virus (HSV) positive sera and complement caused specific lysis of HSV type 1 infected target cells.The data presented here do not support the hypothesis that in the possible immunopathogenesis of HAV infection, complement‐dependent cytolytic antibodies play an essenti

ISSN:0146-6615    

DOI:10.1002/jmv.1890200105

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe antibody to AN6520 antigen, which was isolated from the liver of a patient with non‐A, non‐B hepatitis (NANBH), has been detected frequently in convalescent sera from patients with NANBH by the passive hemagglutination (PHA) test. In a further study, we established hybridoma cells secreting antibodies against AN6520 antigen and obtained ascitic fluids with PHA titers ranging from 1: 105to 1: 107. In immunodiffusion with AN6520 antigen, all monoclonal antibodies were found to form an identical precipitin line. These lines were also identical to those formed by rabbit antiserum against AN6520 antigen and by convalescent sera from patients with NANBH. With one of the monoclonal antibodies, 1‐F12, solidphase radioimmunoassay (SP‐RIA) for detecting AN6520 antigen was developed as well as blocking RIA for anti‐AN6520 antibody detection. The antigen assay was 50 times more sensitive than the reverse passive hemagglutination (R‐PHA) test, with a sensitivity threshold of the 1 ng/ml of antigen solution; the antibody assay was 10 times more sensitive than PHA. The results with this blocking RIA were mostly in agreement with the data obtained by PHA. Furthermore, the antigen in human sera, which had never been detected by R‐PHA test, could be detec

ISSN:0146-6615    

DOI:10.1002/jmv.1890200106

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractDetection of AN6520 Ag/Ab in human sera had indicated a close association with non‐A, non‐B hepatitis (NANBH). In this study, we investigated the immunochemical nature of AN6520 Ag and measured the amounts in various human and chimpanzee organs in order to clarify the association with NANBH.AN6520 Ag was found to be composed of polypeptide(s) with an apparent molecular weight of 45,000 daltons (45 kD), which are noncovalently linked together. Human antibodies in convalescent sera from NANBH patients as well as monoclonal antibodies were found to recognize only the high‐order structure of the antigen, whereas rabbit antibody recognized both the high‐order structure and the reduced form of 45 kD polypeptide(s).AN6520 Ag could be detected in most of the livers tested including those without any liver damage and fetal livers; their amounts varied considerably from each other. The antigen could be detected also in organs other than liver, but in contrast to liver, the amounts were small and did not vary as much between individuals. From the data of immunoblotting using rabbit antibody, our observed variation of antigen content in liver was considered to be due to the difference in expression of 45 kD polypeptide(s).Although no specific relationship was found between the amount of the antigen in liver and NANBH, the antigen was found to increase several times in livers of chimpanzees after the inoculation of NANBH virus.These data suggest that AN6520 Ag is a normal cellular protein existing mainly in liver and that its quantity may vary under some conditions such a

ISSN:0146-6615    

DOI:10.1002/jmv.1890200107

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe purpose of this study was to determine whether Junín virus persistence in CNS of rats was capable of inducing late neurologic disease. Following intracerebral inoculation of newborn animals with XJ strain, three distinct stages could be discerned: an early phase of acute disease, up to 30 days pi, with 5% mortality; an intermediate one, extending to 280 days pi, without clinical signs but with evident viral persistence; and a final period of chronic illness, featuring clinical neurologic syndrome, severe perivascular inflammatory reaction, PAP‐labeled viral antigen in a few cerebral and cerebellar neurons, and virus recovery only by coculture. Late neurologic disease seems associated to the lack of effective clearance of brain virus, leading to viral persistence and long lasting immunologic stimulation. The importance of animal models for pathogenic studies on CNS persistent viral infections leading to late neurologic disease is stress

ISSN:0146-6615    

DOI:10.1002/jmv.1890200108

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractPleomorphic virus‐like particles have been observed by electron microscopy in the faeces of children and adults with diarrhoea. Some of these particles were approximately 100 nm in diameter and had a “fringe” of closely applied peplomers approximately 10 nm long; they closely resembled Berne virus of horses and Breda virus of calves, the two representatives of a newly proposed family called the Toroviridae. In one sample a toroidal nucleoprotein‐like structure was observed within the particles. For two samples a buoyant density of 1.14 g/ml was determined by centrifugation through a sucrose density gradient. One sample possessed a haemagglutination for rat erythrocytes. The serological relationship between these different viruses was observed by immune electron microscopy, haemagglutination inhibition, and serum neutralisation. The role of these viruslike particles as candidate pathogens of humans is di

ISSN:0146-6615    

DOI:10.1002/jmv.1890200109

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractWe have recorded the systemic and mammary/mucosal immune responses of women following natural infection with RS virus during the second and third trimesters of pregnancy. Anti‐RS virus IgG antibody levels in the sera of women collected in the first trimester of pregnancy showed a bimodal distribution with high and low antibody groups. Antibody levels increased after exposure to the winter RS virus epidemic in the second trimester of pregnancy, probably as a result of infection but only for women in the low antibody group. Despite the increases, antibody levels for these women remained well below those of the high antibody group. There was no rise in mean antibody levels after exposure in the third trimester, even among women with low antibody, suggesting a degree of immunosuppression in late pregnancy. There was no evidence that infection during pregnancy was associated with adverse consequences for the infant.Exposure to RS virus in the first two trimesters, but not the third, was associated with high colostral IgA antibody levels that were maintained in the milk throughout the first 7 weeks of lactation. There was a significant correlation between colostral and maternal nasal IgA antibody levels at delivery. Levels of blood or colostral lymphocyte transformation responses at delivery were unaffected by exposure to RS virus in pregnancy.These observations upon natural infection suggest that vaccination during pregnancy is likely to achieve only marginal effects upon serum antibody levels but boost maternal mammary/nucosal immunit

ISSN:0146-6615    

DOI:10.1002/jmv.1890200110

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY

摘要:

AbstractThe relative sensitivity of two enzyme detection procedures was investigated in a simultaneous “monoclonal” ELISA for herpes simplex virus (HSV). A cyclical enzyme amplified detection system with alkaline phosphatase. rather than horseradish peroxidase and a conventional chromogenic substrate, gave an increase in absolute sensitivity and a 20 to 30% increase in the detection of HSV in routine isolation‐positive genital specimens collected in transport medium. The HSV detection rate, with both procedures, was shown to vary with the site and clinical stage of lesion sampled; it was highest with penile vesicular lesions. Direct extraction of the swab specimen in a small volume of diluent further increased the sensitivity of antigen detection giving positive and negative predictive values of 100 and 96% respectively. The overall sensitivity of HSV detection was equivalent to that obtained by isolation in cell culture. The amplified ELISA offers an alternative, rapid, simple, non‐culture technique for routine HSV diagnosis that does not rely upon retention of virus vi

ISSN:0146-6615    

DOI:10.1002/jmv.1890200111

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1986

数据来源: WILEY