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Biomedical subjects

M D Tolpin

Publications and source records attributed to M D Tolpin.

13 recordsLinked to original sources
PubMed1994

Human monoclonal anti-cytomegalovirus (CMV) antibody (MSL 109): enhancement of in vitro foscarnet- and ganciclovir-induced inhibition of CMV replication.

Human CMV causes a number of diseases that cause considerable morbidity and that can be life-threatening in immunocompromised patients, particularly those with AIDS. Ganciclovir (GCV) and Foscarnet (PFA) are currently the drugs of choice for management of CMV disease. Both are not without side effects and have a relatively narrow margin of safety. In this report the effects of a human IgG1 neutralizing monoclonal antibody MSL-109 (MSL, Sandoz Pharmaceuticals) on CMV replication was examined both alone or in combination with either GCV or PFA. Human embryonic lung fibroblasts were infected with CMV strain AD169 with a multiplicity of infection of 3 plaque forming units/cell for 1 h. Prior to infection the virus was incubated for 30 min at 37 degrees C with serial concentrations of the MSL Ab (0.1-3.0 micrograms/ml). Concentrations of GCV (0.3 to 30 microM) or PFA (50-400 microM) were added to CMV-infected cells that had been either previously incubated with MSL or not. Four days after infection CMV replication was measured by DNA/DNA probe hybridization using the Hybriwix system. MSL in combination with GCV had an additive effect that was observed at concentrations of GCV of 3-10 microM and MSL of 1-10 micrograms/ml. On the other hand, MSL (3-10 micrograms/ml) together with PFA (100-400 microM) produced a synergistic effect on CMV replication. The data suggest that MSL at doses achievable in humans, enhanced GCV- and PFA-induced antiviral effect in a dose-dependent manner and that the combination might be clinically useful in the treatment of CMV disease.

Antibodies, Monoclonal↗
PubMed1992

Genetic alterations in the gene encoding the major HBsAg: DNA and immunological analysis of recurrent HBsAg derived from monoclonal antibody-treated liver transplant patients.

A gene region encoding a segment of the major surface protein, HBsAg, of hepatitis B virus was analyzed from serum samples after orthotopic liver transplantation of three hepatitis B virus chronic carrier patients treated with a human anti-hepatitis B virus monoclonal antibody (SDZ OST 577). Each of these three patients became HBsAg negative after transplantation and therapy with the human anti-hepatitis B virus monoclonal antibody but returned to HBsAg positivity (first detected 143,251 and 252 days after the transplantation). Polymerase chain reaction DNA amplification was performed on DNA from serum samples showing low levels of recurrent HBsAg and reduced antigen reactivity with SDZ OST 577 antibody. Polymerase chain reaction DNA included a 230-bp highly conserved, major S gene region that was cloned into M13 bacteriophage; analysis of this DNA segment provided a consensus of DNA sequences for the serum samples exhibiting altered reactivity with the therapeutic monoclonal. Analysis of independent DNA clones from serum samples of patients exhibiting low but detectable recurrent serum levels of posttherapy HBsAg revealed the presence of S protein variant sequences when compared with polymerase chain reaction DNA derived from the original infected liver or pretherapy serum HBsAg. Genetic variation was predominant in a highly conserved peptide domain that has previously been implicated in antibody binding and neutralizing antibody epitopes. In independent patients infected with either adw or ayw hepatitis B virus subtypes, single nucleotide changes resulted in one to two amino acid differences for each variant allele (residues 124, 129, 131, 137, 140 and/or 145) when compared with pretherapy viral DNA. Administration of serum containing one of these variant viruses to a single hepatitis B-naive chimpanzee resulted in subclinical hepatitis and detectable levels of circulating anti-HBs and anti-HBc antibodies 49 and 70 days after virus administration, respectively. Hepatitis B virus DNA was recovered on liver biopsy between 6 and 8 wk after inoculation, although the animal remained persistently seronegative for HBsAg. DNA sequence analysis of both primate and patient liver hepatitis B virus confirmed the presence of the DNA encoding the S protein variant and associates this DNA with the predominant hepatotropic virus in liver infection.

Amino Acid Sequence↗
PubMed1984

HCMV envelope antigens induce both humoral and cellular immunity in guinea pigs.

Antibody and cellular immunity were measured in guinea pigs immunized with whole virion, with nucleocapsids of human cytomegalovirus or with solubilized antigens containing virus envelope proteins. All the three types of immunogens induced the production of humoral antibody as well as cytomegalovirus (CMV)-specific cellular immunity. In immunization experiments envelope antigen was as effective as immunization with whole virion.

Animals↗
PubMed1983

Enzymatic cleavage of a glycoprotein of respiratory syncytial virus.

The 75K glycoprotein of the A2 strain of respiratory syncytial virus was cleaved by digestion with trypsin or Staphylococcus aureus protease V8. The fragments resulting from trypsin digestion were 40K and 29K; those from the Staphylococcal protease were 49K and 37K.

Electrophoresis, Polyacrylamide Gel↗
PubMed1982

Evaluation of a phenotypic revertant of the A/Alaska/77-ts-1A2 reassortant virus in hamsters and in seronegative adult volunteers: further evidence that the temperature-sensitive phenotype is responsible for attenuation of ts-1A2 reassortant viruses.

In a previous study, a seronegative child to whom attenuated A/Alaska/77-ts-1A2 virus was administered (37 degrees C shutoff temperature for plaque formation) shed virus with an altered temperature-sensitive (ts) phenotype (40 degrees C shutoff temperature) (Murphy et al., Ann. N.Y. Acad. Sci. 354:172-182, 1980; Tolpin et al., Virology 112:505-517, 1981). This ts+ virus (FV1319) was evaluated for its level of replication in hamsters and for its virulence for humans. In hamsters, FV1319 ts+ virus replicated to the same level in the nasal turbinates as that of which the A/Alaska/77 wild-type virus replicated, but its replication in the lungs was reduced 40-fold. In contrast, the A/Alaska/77-ts-1A2 reassortant achieved a titer in hamster nasal turbinates that was significantly lower (P less than 0.005) than those achieved by the wild-type and the FV1319 viruses; the A/Alaska/77-ts-1A2 reassortant was not recoverable from the lungs. In seronegative adult volunteers, the pattern of replication of the FV1319 virus was similar to that of the A/Alaska/77 wild-type virus. The illness induced by the FV1319 ts+ virus was also similar to that caused by the wild-type virus. In contrast, the A/Alaska/77-ts-1A2 reassortant was satisfactorily attenuated in adult volunteers. These results suggest that attenuation of the A/Alaska/77-ts-1A2 reassortant virus in humans is a function of the ts phenotype: loss of this phenotype restored virulence. The ability of the A/Alaska/77-ts-1A2 reassortant to lose its ts phenotype and regain virulence during growth in a permissive host limits the usefulness of the ts-1A2 reassortants as vaccine viruses for humans.

Animals↗
PubMed1980

Inactivated mouse cytomegalovirus vaccine: preparation, immunogenicity, and protective effect.

Mouse cytomegalovirus (CMV) was rapidly and completely inactivated at 37 C by formalin diluted 1:4,000. Of 18 mice that received two doses of inactivated mouse CMV, 16 survived challenge with 250% lethal doses of mouse CMV; one of 11 mice receiving two doses of a control preparation survived the challenge (P < 0.005). After challenge with live virus, recognizable morbidity occurred in only four of 16 recipients of inactivated mouse CMV, but the virus was recovered from the salivary glands of 15 animals. Mice with reciprocal prechallenge titers of neutralizing antibody of < 4 demonstrated significantly higher morbidity and mortality than mice with higher antibody titers. Administration of inactivated mouse CMV did not depress responsiveness of spleen cells to phytohemagglutinin. Most mice immunized with inactivated virus developed only mild or subclinical infections after challenge with lethal doses of mouse CMV.

Animals↗
PubMed1979

Impaired cellular immunity to cytomegalovirus in congenitally infected children and their mothers.

Cell-mediated immunity to cytomegalovirus (CMV) was determined in congenitally infected children and their mothers by use of assays for CMV-specific lymphocyte blastogenesis and interferon production. Six viruric children responded poorly in both assays. Two older nonviruric children responded in the blastogenesis assay, and lymphocytes from one of them produced interferon. Mothers of older children usually responded in the blastogenesis assay, but only one of them produced interferon. Mothers whose infected infants were younger than nine months of age responded poorly in both assays, while control seropositive postpartum women generally responded normally. The cell-mediated immune defects detected in this study may play a role in the pathogenesis of congenital CMV infection.

Cytomegalovirus↗