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Biomedical subjects

M N Oxman

Publications and source records attributed to M N Oxman.

At least 37 records · Page 2Linked to original sources

Immobilization of viral antigens on filter paper for a [125I]staphylococcal protein A immunoassay: a rapid and sensitive technique for detection of herpes simplex virus antigens and antiviral antibodies.

A new technique is described for the rapid detection and quantitation of herpes simplex virus (HSV) antigens and antiviral antibodies. It involves immobilization of HSV antigens on filter paper discs and subsequent analysis by 125I-labeled staphylococcal protein A (SPA) radioimmunoassay. A specially designed 96-well filtration device is employed which serves both as an incubation chamber and as a filtration manifold. It is rapid, simple, sensitive and specific, and requires only small volumes of antiserum and few target cells. The results may be readily and objectively quantitated. This technique permits the simultaneous assay of a large number of specimens in less than 1 h. Its sensitivity is considerably greater than that of other currently used immunologic techniques, and it is amenable to automation. These characteristics suggest that this [125I]SPA immunofiltration technique may be applicable to the rapid diagnosis of viral infections.

Antibodies, Viral↗

Extrapulmonary manifestations of adenovirus type 7 pneumonia simulating Reye syndrome and the possible role of an adenovirus toxin.

Three children developed extensive extrapulmonary disease in the course of fatal adenovirus type 7 pneumonia. Several clinical features, including the unexpected onset of coma, suggested the development of Reye syndrome, but biochemical and histopathologic findings were inconsistent with this diagnosis. Virologic and pathologic studies did not reveal evidence of extrapulmonary adenovirus infection, despite clinical involvement of the liver, skeletal muscle, and central nervous system. The detection in premortem sera from all three patients of adenovirus penton antigen, known to be cytotoxic in vitro, suggests a possible mechanism for the production of extrapulmonary pathology in the absence of extrapulmonary virus infection.

Adenoviridae Infections↗

Proliferative and interferon responses by peripheral blood mononuclear cells after bone marrow transplantation in humans.

The capacity of peripheral blood mononuclear cells from bone marrow transplant recipients to proliferate and produce interferon in response to mitogens and specific antigens was tested. Proliferation in response to phytohemagglutinin or pokeweed mitogen occurred in cells from more than 90% of the recipients, and interferon was present in 60 to 70% of the supernatants from these cultures, even when tested as soon as 8 weeks after transplantation. Proliferation in response to bacterial antigens was infrequent, and interferon release was not detected. In the early post-transplantation period (less than 13 weeks), cells from only two of four cytomegalovirus (CMV) antibody-positive patients proliferated normally in response to CMV antigen and interferon release was detected only once. In the late post-transplantation period (more than 13 weeks), in only two of five instances did cells proliferating in response to CMV antigen release interferon. The response to CMV antigen of mononuclear cells from many transplant recipients differs from that of cells from normal controls.

Antigens, Viral↗

Persistent and fatal central-nervous-system ECHOvirus infections in patients with agammaglobulinemia.

We observed persistent ECHOvirus infection of the central nervous system, as defined by continued presence of isolatable virus in cerebrospinal fluid, in five patients with agammaglobulinemia. The immunologic deficit in each was characterized by absence of surface-immunoglobulin-bearing B lymphocytes and of lymph-node cortical follicles, but normal T-cell function. ECHOviruses 30, 19, 9 and 33 were recovered from cerebrospinal fluid for periods varying from two months to three years. The patients had few signs of acute central-nervous-system infection. Three of the five patients had a dermatomyositis-like syndrome, with peripheral lymphocytes that reacted with anti-human leukemia-specific primate and rabbit serums in a cytotoxicity assay. These data suggest that intact B-cell function is essential for eradication of ECHOvirus infection of the central nervous system.

Adult↗

Antibody to varicella-zoster virus-induced membrane antigen: immunofluorescence assay using monodisperse glutaraldehyde-fixed target cells.

A sensitive and reproducible technique was developed for the detection of antibody to varicella-zoster virus-induced membrane antigen (VZMA) by immunofluorescence. Controlled trypsinization and glutaraldehyde fixation were employed to prepare a monodisperse suspension of noninfectious VZMA-positive target cells that can be stored indefinitely at -72 degrees C. A microtiter immunofluorescence assay utilizing these target cells was shown to provide a sensitive and specific means for the detection and quantitation of antibody to varicella-zoster virus. The properties of the target cell preparation and the characteristics of the assay make practical the rapid assessment of immunity to the varicella-zoster virus.

Antibodies, Viral↗

New human adenovirus (candidate adenovirus type 35) causing fatal disseminated infection in a renal transplant recipient.

An antigenically distinct adenovirus is described which was isolated in March 1973 from the lungs and kidney of a 61-year-old woman who died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. Complement fixation, hemagglutination inhibition, and serum neutralization tests on sequential serum specimens from the patient confirmed that the adenovirus infection occurred in coincidence with her clinical illness and failed to document concomitant infection by any other common respiratory agent. Pathological and virological findings indicated that the pneumonia was only one manifestation of a disseminated adenovirus infection, the source of which may have been a latent infection pre-existing in the donor kidney. The adenovirus, purified by terminal dilution and plaque procedures, has antigenic, morphological, biological, biophysical, host susceptibility, and hemagglutinating properties characteristic of adenovirus group 1A. Buoyant densities in CsCl are 1.340 g/ml for the virion, 1,300 g/ml for the group complement-fixing (hexon) antigen, and 1.290 g/ml for the major soluble complete hemagglutinin (dodecon). The virus was serologically distinct from adenoviruses 1 to 34 in reciprocal serum neutralization tests with antisera to these viruses. We propose this virus as candidate adenovirus type 35 (holden).

Adenoviridae Infections↗

Molecular mechanisms of the antiviral action of interferon: effects of interferon on the transcription of viral messenger RNA.

Evidence from a number of virus-cell systems, discussed above and in other papers in this section, shows that the resistance to virus infection induced by interferon is characterized by inhibition of both primary transcription and translation. This may be because interferon induces two (or more) distinct "antiviral proteins" which inhibit, respectively, the transcription and the translation of virus genetic information. Although both may be present in interferon treated cells, the one which is manifest in any given experimental system may depend on whether transcription or translation is the primary event in the replication of the particular virus, and upon the accessibility of the viral nucleic acid. Alternatively, inhibition of transcription and translation may be mediated by a single antiviral protein which is able to distinguish viral from cellular nucleotide sequences in both DNA and RNA. The interferon-induced ribosome-associated inhibitors of viral mRNA translation (see related papers in this section) are prime candidates for such an antiviral protein.

DNA Viruses↗

Photodynamic inactivation in recurrent infections with herpes simplex virus.

Photodynamic inactivation with neutral red (a heterotricyclic dye) and light was evaluated in a placebo-controlled study of 170 episodes of recurrent infection with herpes simplex virus in 96 patients. The technique inactivated herpes simplex virus in vitro. However, no beneficial effect, either on the rate of resolution of herpetic lesions or on the interval to subsequent recurrences, was observed in treated patients. These negative results should not deter further investigation of photodynamic inactivation as a potential treatment for herpes simplex virus infections, but the clinical application of this form of therapy should be limited to properly controlled studies until its efficacy is proven.

Clinical Trials as Topic↗

Evaluation of the safety of amantadine-HC1 and the role of respiratory viral infections in children with cystic fibrosis.

Amantadine-HC1, an antiviral drug clinically effective against most strains of influenza A virus, was evaluated in a double-blind trial in 153 children with cystic fibrosis during the initial appearance of influenza A/England/42 virus in the New England area. Infection with this variant strain of influenza virus did not reach epidemic proportions during the study, so that the effectiveness of amantadine in this study population could not be fully assessed. However, the potential symptomatic and biochemical toxicity of amantadine was carefully monitored in a pediatric population. Serologic screening by complement fixation tests indicated that respiratory viruses may be important pathogens in exacerbations of respiratory disease in patients with cystic fibrosis.

Adolescent↗

Mechanism of interferon action: further evidence for transcription as the primary site of action in simian virus 40 infection.

Interferon inhibits the replication of simian virus 40 (SV40) in monkey cells and reduces markedly the formation of both early virus protein (i.e. SV40 T antigen) and early SV40 RNA. This suggests that in SV40 infection interferon acts primarily by inhibiting transcription. To test this conclusion further, we examined alternative mechanisms which might explain these results and made the following observations. (1) The quantity of input SV40 DNA in the nucleus 24 h post infection (p.i.) was the same in interferon-treated and control cells. Thus interferon does not appear to diminish the quantity of SV40 DNA template available for transcription. (2) Chemical inhibitors of protein synthesis did not mimic the selective inhibition of early SV40 RNA formation induced by interferon, indicating that the transcription of early SV40 RNA is not dependent upon the prior synthesis of any virus-induced protein. Thus a block in translation cannot readily explain the reduced formation of early SV40 RNA in interferon-treated cells. (3) Fractionation of SV40 infected cells after a one-hour labelling period showed that interferon produced a comparable reduction in the quantity of early SV40 RNA in the nucleus and the cytoplasm. Thus the observed inhibition of early SV40 RNA is not due solely (if at all) to enhanced cytoplasmic degradation. These results indicate that the primary effect of interferon in SV40 infected monkey cells is either to inhibit the transcription of early virus RNA or to enhance its turnover in the nucleus.

Cell Line↗

Failure of neutral-red photodynamic inactivation in recurrent herpes simplex virus infections.

Because photodynamic inactivation of herpes simplex virus infections may not be free of hazard, the efficacy of photodynamic inactivation with neutral red and light was evaluated in a placebo-controlled study of 170 episodes of recurrent herpes simplex virus infection in 96 patients. The preparation of neutral red that was used was shown to photoinactivate herpes simplex virus in vitro, but had no significant effect on the rate of resolution of herpetic lesions (P greater than 0.10) or on the frequency of subsequent recurrences (P greater than 0.10), except for orolabial lesions, in which an adverse effect on the rate of subsequent recurrences was observed (P less than 0.05). In the absence of demonstrated efficacy, the routine use of neutral red and light in patients with recurrent herpes simplex virus infections should be discontinued. Furthermore, other photoactive dyes should not be used until their efficacy has been demonstrated by suitably controlled clinical trials.

Administration, Topical↗

Fatal disseminated adenovirus infection in a renal transplant recipient.

A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.

Adenoviridae↗

Herpes simplex virus microneutralization: a simplification of the test.

The herpes simplex virus (HSV) microneutralization test has been simplified; its use has been demonstrated for the identification of HSV isolates as type 1 (HSV-1) or type 2 (HSV-2) and for the measurement of antibodies to HSV-1 and HSV-2. In this test, the relation between the neutralization titer and virus input is linear, and thus test results can be expressed as corrected neutralization titers, rather than as the more complex neutralizing potency values previously proposed. By means of this test, 45 of 46 clinical isolates of HSV were unequivocally identified as either HSV-1 or HSV-2. Evaluation of neutralizing antibody to HSV infection was more difficult because some neutralizing antibody to the heterotypic HSV is produced after primary infection with HSV-1 or HSV-2, because patients previously infected with one HSV type may show a variety of serological responses to subsequent heterotypic infection, and because human sera obtained early after primary HSV infection may not yet exhibit a type-specific response.

Antibodies, Viral↗

Hospital management of patients and personnel exposed to communicable diseases.

Patients and personnel who are exposed to certain communicable diseases in a hospital setting often require therapeutic or epidemic control measures which may differ from measures employed following community exposure. This paper offers guidelines for reducing the hospital spread of communicable diseases by preventive measures (admission screening procedures, immunizations for personnel), and post-exposure management of patients and personnel. It is intended as a companion to the "Hospital Isolation and Precaution Guidelines" for patients with clinically manifest infections which appeared previously.

Child↗

Control of simian virus 40 gene expression in adenovirus-simian virus 40 hybrid viruses. Synthesis of hybrid adenovirus 2-simian virus 40 RNA molecules in cells infected with a nondefective adenovirus 2-simian virus 40 hybrid virus.

The effect of interferon on simian virus 40 (SV40) and adenovirus 2 (Ad2) T antigen synthesis has been examined in cells infected with SV40, with Ad2, and with a nondefective Ad2-SV40 hybrid virus, Ad2(+)ND(4). The induction of SV40 T antigen by SV40 was highly sensitive to interferon, whereas the induction of Ad2 T-antigen by Ad2 was resistant. This difference in interferon sensitivity was also noted in cells simultaneously infected with both viruses. However, the induction of SV40 T antigen by Ad2(+)ND(4), which contains covalently linked SV40 and Ad2 DNAs, was as resistant to interferon as the induction of Ad2 T antigen. This change in the interferon sensitivity of SV40 T antigen synthesis suggests that the expression of at least this portion of the SV40 genetic information in Ad2(+)ND(4) is under Ad2 genetic control. When RNA extracted from Ad2(+)ND(4)-infected cells was examined by means of sequential hybridization with Ad2 DNA, elution, and rehybridization with SV40 DNA, 27% of the SV40-specific RNA was found to be linked to Ad2 RNA. No such linkage was detected in control mixtures of Ad2 and SV40 RNAs. The presence of Ad2 and SV40 nucleotide sequences in the same RNA molecule implies that, in Ad2(+)ND(4) infection, transcription is initiated in the DNA of one virus (Ad2 or SV40) and continues without interruption across the point of junction into the DNA of the other virus. Furthermore, the interferon resistance of Ad2(+)ND(4)-induced SV40 T antigen synthesis suggests that transcription of the genetic information for SV40 T antigen is initiated in a region of Ad2 DNA.

Adenoviridae↗