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Biomedical subjects

M J Levin

Publications and source records attributed to M J Levin.

At least 145 records · Page 8Linked to original sources
PubMed1986

Reduced cellular immunity to varicella zoster virus during treatment for acute lymphoblastic leukemia of childhood: in vitro studies of possible mechanisms.

To determine the effect of antileukemic therapy on preexisting immunity to varicella zoster virus, we studied 20 children with acute lymphoblastic leukemia maintained in complete continuous remission for greater than 1 year. Cellular immunity was tested by lymphocyte proliferation in response to varicella antigen. Antiviral antibody was measured using the fluorescent antibody to membrane antigen technique. Reduced lymphocyte proliferation was found in 9 of 16 seropositive patients when compared to an age-related control group. On the other hand, antibody titers in patients receiving chemotherapy remained positive and were essentially unchanged from pretreatment values. Shingles occurred in two of nine children with diminished and none of seven patients with normal cellular immunity, suggesting that proliferative responses to varicella antigen may have predicative value in identifying patients at risk for viral reactivation. Additional studies were done to determine if defective antigen presentation or reduced lymphocyte responder-cell frequency could account for the subnormal proliferative responses. Intact presentation of varicella antigens by patient mononuclear cells to parental, virus-specific T-cell blasts suggested that antigen processing was not defective. However, varicella-specific responder-cell frequencies measured by limiting dilution analysis were found to be depressed in most patients, including some with normal proliferative responses. Our findings indicate that therapy for acute lymphoblastic leukemia in children can be associated with depressed cell-mediated immunity to varicella zoster virus even though patients remain seropositive. Further studies suggest that while monocyte-mediated antigen presentation remains intact, virus-specific lymphocyte numbers decline and probably contribute to decreased cellular immunity to varicella zoster virus in children being treated for leukemia.

Adult↗
PubMed1986

Noma in children with severe combined immunodeficiency.

Three Native American children with severe combined immunodeficiency developed noma, a necrotizing gingivostomatitis not previously reported in this country. The similarity between the clinical findings and those observed in monkeys with simian AIDS prompted us to evaluate our patients and their families for human retroviral infection. Antibodies to HTLV-I or HTLV-III/LAV proteins were not identified in patients nor in their family members. Standard bacterial and viral cultures similarly failed to identify a suspect pathogen.

Antibodies, Viral↗
PubMed1986

A placebo-controlled trial of topical 8% arildone cream early in recurrent genital herpes.

Arildone is an aryl diketone which is inhibitory in vitro against herpes simplex virus type 2 at a concentration of 2 micrograms/ml or less. One hundred forty-five patients with recurrent genital herpes were enrolled in a multicenter, randomized, placebo-controlled, double-blind trial to evaluate the efficacy and safety of an 8% arildone cream. Patients initiated therapy a mean of 9.9 h and a maximum of 24 h after the reported onset of lesions and applied medication 6 times daily for 7 days. The duration of viral shedding was shorter among women (P less than 0.05) and the duration of local itching was shorter among men (P less than 0.05) in patients that received arildone than in those that received placebo, but there were no significant differences between treatment groups in duration of pain, time to crusting or healing of lesions, or percentage of patients developing new lesions. Mild local irritation after application of ointment was common and occurred equally in both treatment groups. Despite early application, topical arildone cream was ineffective in the therapy of acute recurrences of genital herpes.

Administration, Topical↗
PubMed1985

Transient transcriptional inhibition of the transferrin gene by cyclic AMP.

Transferrin mRNA content and gene transcription rate were measured in the liver of rats submitted to iron overload or depletion, castration, treatment with sexual steroid hormones, glucagon and cyclic AMP. The influence of puberty in males and females and of pregnancy was also analysed. Glucagon and cyclic AMP reduced mRNA level by about 50% at the 12th hour of treatment and transferrin gene transcription by as much as 95% at the 30th minute of drug infusion, with a secondary increase of the transcription rate for a protracted treatment. None of the other hormones tested had any detectable effect on transferrin gene expression, the same being true for iron overload or depletion.

Animals↗
PubMed1985

Topical acyclovir treatment of herpes zoster in immunocompromised patients.

Topical acyclovir favorably influences the healing of localized herpes zoster in immunocompromised patients. This therapy, or placebo, was applied to forty-three patients in a random access, double-blind trial, four times daily for 10 days, beginning within 72 hours after the onset of skin lesions. The mean time to pustulation is decreased from 12.4 to 6.7 days and the mean time to crusting is decreased from 16.0 to 11.4 days (p = 0.038 and 0.086, respectively) by topical treatment. The mean time to 50% healing is decreased from 24.5 to 15.2 days and the mean time to 100% healing is decreased from 34.9 to 25.8 days (p = 0.023 and 0.033, respectively). Favorable effects in treated patients are not associated with a more rapid decline in lesion virus titer, but do accrue without any toxicity.

Acyclovir↗
PubMed1985

Transferrin gene expression visualized in oligodendrocytes of the rat brain by using in situ hybridization and immunohistochemistry.

The presence and production of transferrin in the adult rat brain have been investigated using both immunohistochemistry and in situ hybridization in tissue sections. Indirect immunofluorescence with four distinct antisera against rat and human transferrin and one monoclonal antibody against human transferrin demonstrated labeling of the cytoplasm of oligodendrocytes (a category of glial cells) in most parts of the brain, especially in the white matter. In situ hybridization using rat transferrin 32P-labeled cDNA as a probe revealed the presence of transferrin mRNA in glial cells whose appearance, distribution, and organization exactly matched those of the cells decorated with the transferrin antibodies. These results provide evidence that the transferrin gene is expressed in the central nervous system and that transferrin is synthesized by and stored within oligodendrocytes in the adult rat brain. These data suggest that this molecule could have a specific function in nervous system activity.

Animals↗
PubMed1985

Use of an enzyme-linked immunosorbent assay performed directly on fixed infected cell monolayers for evaluating drugs against varicella-zoster virus.

An in situ enzyme-linked immunosorbent assay (ELISA), performed directly on fixed varicella-zoster virus-infected monolayers, was used to quantitate viral antigen, and by color reduction it was used to evaluate the activity of drugs against varicella-zoster virus. Color production in the ELISA (optical density) was directly related to the dose of input virus. Antigen representing 5 to 10 plaques could be detected 3 days after infection. The ELISA was specific and reproducible, as shown by absorption and repeat experiments, respectively. A color-reduction test by ELISA was compared with the conventional plaque-reduction assay for its ability to measure the antiviral activity of acyclovir, bromovinyldeoxyuridine, trifluorothymidine, and vidarabine against four strains of varicella-zoster virus. In all cases but one the 50% inhibitory doses were lower when measured by ELISA than by the plaque-reduction assay. This in situ ELISA color reduction method had the following advantages over the conventional plaque-reduction assay: the endpoint was an objective measurement; there was less well-to-well variation; the assay was sensitive to changes in plaque size as well as plaque number; it was less labor intensive.

Acyclovir↗
PubMed1985

Factors affecting the detection of enteroviruses in cerebrospinal fluid with coxsackievirus B3 and poliovirus 1 cDNA probes.

Enteroviruses are common pathogens of meningitis and encephalitis, and infections are often difficult to distinguish clinically from bacterial and herpetic infections of the central nervous system. An array of enteroviruses added to cerebrospinal fluid in reconstruction experiments were detected by a dot hybridization assay. Optimal handling and processing conditions for infected cerebrospinal fluid were established, and the effect on the hybridization reaction of humoral and cellular components of the inflammatory response was determined. Six hybridization probes, derived from poliovirus 1 and coxsackievirus B3, were then tested, singly and in combinations, to optimize the sensitivity and spectrum of the assay. Implications for enteroviral taxonomy based on these experiments are discussed.

DNA↗
PubMed1985

Rapid detection of respiratory syncytial virus in nasopharyngeal secretions by enzyme-linked immunosorbent assay.

A new enzyme-linked immunosorbent assay (ELISA) respiratory syncytial virus antigen detection kit (Ortho Diagnostics, Inc., Raritan, N.J.) was compared with virus culture and with the indirect fluorescent antibody test (FAT) by using fresh nasal washings from children with suspected respiratory syncytial virus infection. Both uncentrifuged nasal washings and pellets from centrifuged split specimens were examined by ELISA. The ELISA was considered positive when the optical density was greater than the mean background optical density plus 0.15. Specimens positive by ELISA but negative by culture and FAT were reexamined in an ELISA blocking assay. Of 337 uncentrifuged specimens, 124 (37%) were positive by culture, 107 (32%) were positive by FAT, and 166 (49%) were positive by ELISA. Blocking assays showed that 21 of 30 (70%) of the seemingly false-positive ELISA tests were, in fact, true-positives and that the cultures and FATs were falsely negative. A patient specimen was considered positive when it was positive by virus culture, FAT, or blocking assay. The sensitivity, specificity, and positive predictive value of the ELISA test were 88, 94, and 95%, respectively. Centrifugation of nasal washings raised the sensitivity from 88 to 92% but reduced the specificity from 94 to 81%. We conclude that the Ortho ELISA test of uncentrifuged nasal washings is more sensitive than virus culture or indirect FAT and is highly specific.

Antigens, Viral↗
PubMed1985

Characterization of the human newborn response to herpesvirus antigen.

An investigation was made into the human newborn cellular response to herpes simplex virus type 1 (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV) to understand more about the nature of the neonate's susceptibility to overwhelming infection by these viruses. Newborn mononuclear cells sustained the proliferation in culture of maternal (i.e., haplotype-matched) T cell blasts with specificity for HSV, CMV, or VZV (p less than 0.05). This is evidence for intact antigen-processing capability by newborn monocytes. The response of the maternal T cell blasts appeared to be HLA-haplotype-restricted as suggested by experiments in which maternal T cell blasts were limited in number. Our culture conditions elicited responses predominantly from the T4+ lymphocyte subset. A low frequency of herpesvirus-specific T4+ lymphocytes in newborn blood might contribute to deficient viral immunity, so we evaluated the virus-specific T cell responding frequency in human newborns in limiting dilution cultures. We were unable to find a herpesvirus-specific responder cell frequency greater than 1:1,400,000 in nonimmune newborns. Three of seven adults who had no serum antibody to CMV had a CMV responder cell frequency (RCF) of 1:100,000 to 1:200,000. The RCF to HSV in immune children, ages 18 mo to 12 yr, and adults, ages 13 to 80 yr, ranged from 1:14,000 to 1:18,000. We conclude that newborn monocyte processing of herpesvirus antigen is intact, that T cell RCF is low in neonates, and that immunity to HSV after infection outside the newborn period results in comparable RCF between adults and children.

Adult↗
PubMed1985

Lysis of varicella zoster virus infected cells by lymphocytes from normal humans and immunosuppressed pediatric leukaemic patients.

Varicella zoster virus (VZV) is an important cause of morbidity and mortality in immunosuppressed children but little is known of the cellular mechanisms of VZV immunity. We therefore developed a clinically applicable system to study responses to VZV infected cells. Fresh blood mononuclear cells (MNC) from VZV immune donors killed VZV infected fibroblasts in an 18 h 51Cr release assay. The specificity for virus was confirmed by cold target inhibition. An enhancing role for HLA matching was demonstrated using targets mismatched for HLA, and blocking by antibodies to HLA framework and T cell subsets. Cytotoxicity was not blocked with anti-Ia or anti-VZV antibodies. Killing of VZV infected target cells was reduced in seven out of nine VZV antibody positive patients in remission who were receiving maintenance treatment for acute lymphocytic leukaemia. Three of these patients had normal lymphocyte proliferative responses to VZV. Of the two patients with normal cytotoxic responses to VZV, one had reduced proliferation. It therefore appears that presence of VZV antibody, T cell proliferative responses, and cytotoxicity are independently variable. Cytotoxicity may be more susceptible to immunosuppression than either antibody or T cell proliferation.

Antibodies, Viral↗
PubMed1984

Transplacental passage of influenza A/Bangkok (H3N2) mimicking amniotic fluid infection syndrome.

Influenza virus infection complicating pregnancy remains a matter of concern because of the frequency of these infections and possible associated increased maternal and perinatal risks. Influenza A/Bangkok (H3N2) infection occurred in a gravid woman in association with fever, chills, and uterine tenderness and contractions together with maternal and fetal tachycardia. Initial evaluations led to consideration of amniotic fluid infection syndrome with planned termination of the pregnancy. Examination of amniotic fluid obtained by amniocentesis showed neither microorganisms nor neutrophils, and close monitoring and supportive measures were continued. Amniotic fluid and maternal nasopharyngeal washing both yielded influenza A/Bangkok (H3N2). Mother and fetus were closely monitored until term. Cord blood samples demonstrated hemagglutination inhibition and complement fixation antibody titers of 1:32 and greater than 1:512, respectively. Cord blood IgM and IgA hemagglutination inhibition antibody concentrations were 6,400 and 3,200 micrograms/ml, respectively, consistent with transplacental infection. This is the first confirmation of transplacental influenza infection. This generally self-limited viral infection may mimic the amniotic fluid infection syndrome and put mother and fetus at risk for potentially harmful untimely delivery.

Adult↗
PubMed1984

Expression of the transferrin gene during development of non-hepatic tissues: high level of transferrin mRNA in fetal muscle and adult brain.

Using a cloned rat transferrin cDNA probe, we looked for transferrin mRNA in the various rat tissues during development. In all the cases the mRNA detected seemed to be the same and to be product of a single gene. The transferrin gene is early expressed at a high level during liver differentiation. In the muscle and other non-hepatic and non-nervous tissues, the gene expression is maximal just before birth (19-20th day of gestational age), then markedly decreases during the postnatal development, the mRNA level being very low in the adult tissues. In brain, by contrast, transferrin mRNA level is very low before birth, then gradually increases during the postnatal development and reaches a plateau in the adult. Maximal mRNA concentration in fetal muscle (2 days before birth) and adult brain is about 1:7 to 1:10 of that obtained in adult liver. These results are analyzed in the light of the evidence that transferrin is not only an iron-binding protein, but also a factor involved in cell proliferation and differentiation, and particularly in nerve control of muscle differentiation.

Aging↗
PubMed1984

Factors influencing quantitative isolation of varicella-zoster virus.

Optimal conditions are described for the recovery of cell culture-derived varicella-zoster virus (VZV). Of the cells tested, human embryonic lung fibroblasts were the most sensitive. Storage and handling procedures were examined to determine the stability of VZV in viral transport medium. When the initial VZV titer was high (2 X 10(4) PFU/ml) 40% of the VZV survived room temperature for 24 h and 75% of the VZV remained viable for this long at 4 degrees C. Recovery was 5- to 10-fold less at lower initial VZV titers (less than 2 X 10(3) PFU/ml). Other factors which influenced VZV recovery included freezing at -20 degrees C, the use of cotton or calcium alginate swabs, and filtration to remove bacterial contaminants. The tissue culture methods described were used in a reconstruction experiment to demonstrate that VZV could be recovered from a laboratory coat or human skin (0.1 to 0.3% of input VZV) or from a stethoscope (19% of input VZV) as late as 30 min after inoculation. During a clinical trial using optimal VZV recovery procedures, 76% of the patients with herpes zoster yielded VZV when first cultured, and 60% remained culture positive for an additional 48 h.

Alginates↗
PubMed1984

Use of bone marrow fibroblasts to prepare targets for an HLA restricted-cytotoxicity assay system.

Methods are described for obtaining and growing fibroblasts from bone marrow for use as virus-infected targets. Fibroblasts obtained at the time of routine marrow examination were maintained through 12 to 18 passages as confluent monolayers. Bone marrow fibroblasts could be infected with varicella-zoster virus, and these infected cells were suitable targets for a 51Cr-release cytotoxicity assay. Since these virus-infected cells retain their HLA-A and -B antigens, they are readily available to study the immune cells which mediate virus-specific cytotoxicity.

Adolescent↗
PubMed1984

Use of subgenomic poliovirus DNA hybridization probes to detect the major subgroups of enteroviruses.

Three nucleic acid hybridization probes were derived from DNA clones of the poliovirus type 1 genome. Used in dot hybridization experiments, the probes successfully detected members of each of the major enteroviral subgroups. The hybridization patterns obtained with the three probes suggested that a highly conserved nucleotide sequence existed among the enteroviruses tested, mapping between bases 220 and 1809 in the poliovirus genome. Two new antiviral agents capable of inhibiting enterovirus replication in tissue culture were used to demonstrate the specificity of the probes for viral RNA.

Animals↗