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Biomedical subjects

J H Mathews

Publications and source records attributed to J H Mathews.

31 records · Page 2Linked to original sources

Identification of epitopes on the E glycoprotein of Saint Louis encephalitis virus using monoclonal antibodies.

Twenty-one hybridomas producing monoclonal antibodies specific for the E glycoprotein of St. Louis encephalitis (SLE) virus, strain MSI-7, have been isolated. Serologic reactivities were initially determined by cross-reactivity indirect immunofluorescence assays using 22 strains of SLE virus and 8 other related flaviviruses. Four groups demonstrating type-, subcomplex-, supercomplex-, and group-specific reactivity patterns were identified. Analysis of hemagglutination-inhibition (HI) and virus neutralization (N) subdivided the cross-reactivity groups into eight epitopes (E-1a,b,c,d, E-2, E-3, and E-4a,b). The antibodies could detect strain differences between SLE viruses isolated from various geographic areas. Analysis of the spatial arrangements of these epitopes using competitive binding assays with representative antibodies possessing similar binding avidities, indicated that the protein was a continuum of six overlapping domains.

Antibodies, Monoclonal↗

Interferon-mediated persistent infection of Saint Louis encephalitis virus in a reptilian cell line.

A persistent infection with Saint Louis encephalitis (SLE) virus in a poikilothermic cell line TH-1 (turtle heart cells) was studied. Infected TH-1 cells were subcultured weekly at 31 degrees C for 1 year and continued to produce low levels (10(2) to 10(3) p.f.u./ml) of virus without obvious cytopathic effects or marked cyclic events. Indirect fluorescent antibody and infectious centre assays indicated that less than 1% of the cells were producing detectable virus proteins or infectious virus. Defective-interfering particles, temperature-sensitive mutants and DNA provirus were not detected. Interferon (IFN) mediation of the persistent infection as considered since the persistently infected cells (PIC) and normal TH-1 cells were resistant to heterologous virus challenge after treatment with virus-free culture fluid from PIC. A direct relationship was found between the m.o.i. and the amount of IFN produced, plateauing at an m.o.i. of approx. 10. The reptilian IFN was physically and chemically similar to mammalian and avian IFN. Certain biological markers of the SLE virus changed during the persistent infection. It was less virulent for mice, showed distinct differences in cell culture host range and had increased thermal lability.

Animals↗

Determination of the protective epitopes on the glycoproteins of Venezuelan equine encephalomyelitis virus by passive transfer of monoclonal antibodies.

We have previously characterized seven unique antigenic epitopes on the two envelope glycoproteins of the Venezuelan equine encephalomyelitis (VEE) virus vaccine strain, TC-83, by using monoclonal antibodies. The in vitro function of virus neutralization was primarily associated with one epitope on the gp56 (gp56c). To determine which epitopes were important in protecting animals from VEE infection, purified monoclonal antibodies were inoculated i.v. into 3-wk-old Swiss mice. Twenty-four hours later these animals were challenged i.p. with 100 IPLD50 of virulent VEE virus (Trinidad donkey). High-avidity anti-gp56c, anti-gp50b, anti-gp50c, and anti-gp50d monoclonal antibodies protected animals from virus challenge. Rabbit antisera to the gp56 and the gp50 glycoproteins were also effective in protecting mice from challenge with virulent VEE virus. Less antibody was needed to protect animals if the antibody was directed against the critical neutralization site. Less avid antibodies to the gp56c and gp50b epitopes demonstrated little or no protection in vivo. Protection, therefore, appeared to be a function of the passive antibody's specificity, avidity, and ability to bind to virion antigenic determinants topologically proximal to the critical neutralization site.

Alphavirus↗

Serological reactions of fractionated hamster immunoglobulins with California group viruses.

Immunoglobulin M and immunoglobulin G (early and late) were separated by sucrose density gradient centrifugation from single inoculation hamster immune sera prepared against La Crosse, California encephalitis and snowshoe hare viruses. Fractionated antibodies were tested for differences in serological specificity by hemagglutination-inhibition, neutralization, and complement-fixation reactions. None of the immunoglobulins demonstrated a consistent pattern of superior specificity in serological reactions with closely related California group viruses. Results were most uniform in the neutralization test in that immunoglobulin M and early and late immunoglobulin G all showed similar cross-reactivities. By hemagglutination-inhibition and complement-fixation, a given immunoglobulin type from one serum would show good specificity while the same type from another serum would be quite cross-reactive. Immunoglobulin M neutralizing antibody fractions fixed complement as effectively as late immunoglobulin G neutralizing antibody fractions. Unlike results obtained by others with flavivirus immune sera, the immunoglobulin M fractions from California group immune sera were not more specific than immunoglobulin G fractions by neutralization, hemagglutination-inhibition, or complement-fixation tests. Single inoculation hamster antisera, prepared to California group viruses and collected late (28-30 days), were as specific in the neutralization test as antisera collected early (7-10 days).

Animals↗

Serum dilution neutralization test for California group virus identification and serology.

The serum dilution neutralization test was evaluated for serological diagnosis of California group arbovirus infections and identification of virus isolates. The technical advantages and the degree of subtype specificity of the serum dilution neutralization test over the hemagglutination inhibition test and the complement fixation test were demonstrated with paired specimens from human cases, single human survey sera, and sentinel rabbit sera. Twenty-one virus isolates from various geographical areas of the United States were also used to evaluate the efficacy of the serum dilution neutralization test for specific virus identification.

Adolescent↗

Effect of penicillin on the humoral and cellular immune response following group A streptococcal pharyngitis.

The effect of oral and parenteral penicillin on the development of cellular and humoral immune responses in chimpanzees infected with group A streptococcal M-types 1, 5 and 12 was investigated. The interrelationship between type-specific antibody response and enhancement of phagocytic competence of polymorphonuclear neutrophils was documented. Penicillin depressed or suppressed type-specific antibody response depending on the mode and dose of administration, probably because of its effect on the streptococci responsible for antibody stimulation. Penicillin was not demonstrated to have a direct effect on phagocytic ability in vitro. Therefore the primary effect of antibiotic therapy is the indirect relationship to suppression or inhibition of type-specific antibody response to M-protein which results in a diminution of phagocytic competence.

Administration, Oral↗

Opsonin system of the group B streptococcus.

The opsonization by polymorphonuclear leukocytes of group B streptococcal serotypes associated with neonatal sepsis and delayed meningitis was studied. A specific BIa opsonizing antibody (not related to the antipolysaccharide typing antibody) was present in only 10% of the population tested. Serotype BIa was not opsonized in the absence of this specific antibody. BIa antibody specificity was demonstrated by macroagglutination and absorption with BIa streptococci and extracts, but not by gel diffusion. The binding of complement by the BIa opsonin increased the mean phagocytic activity by 60%; complement was manifested via the classic and/or alternate C3-related pathway, but seldom by both concurrently. Serotypes BIb, BIc, BII, and BIII were naturally and nonspecifically opsonized in 95% of the human and baboon sera or plasma tested. Although similar levels of opsonization were present in hyperimmune rabbit sera, heat inactivation and homologous bacterial absorption did not reduce the level of phagocytic activity in the rabbit, human, or primate groups studied. These immunological studies confirmed previous findings that serotype BIa presents a serious hazard for neonatal sepsis, with a nearly 100% mortality. Exclusive isolation of BIII in delayed meningitis suggests that ingestion and subsequent killing by polymorphonuclear leukocytes of type III may differ from the other serotypes.

Absorption↗

The effect of medroxyprogesterone acetate on gonadotropin secretion in girls with precocious puberty.

Plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) as detected by radioimmunoassay have been found to be present in prepubertal children and show a gradual rise until the onset of puberty. Children with idiopathic true precocious puberty have plasma gonadotropin levels which are appropriate for their advanced degree of sexual development. A potent progestational agent, 6-methyl-17-hydroxyprogesterone acetate or medroxyprogesterone has been used in the treatment of precocious puberty and will suppress its physical manifestations. In this study the effect of medroxyprogesterone on gonadotropin levels was investigated in seven girls with true precocious puberty. Plasma LH values were found to be significant lower in patients receiving this agent than in a group of normal prepubertal girls. FSH values did not differ from the control group. One patient was evaluated prior to treatment and showed decreasing levels of LH after therapy was begun. These data suggest that medroxyprogesterone may act on the pituitary-hypothalamic axis to suppress the pubertal levels of LH.

Adult↗