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Biomedical subjects

M J Levin

Publications and source records attributed to M J Levin.

At least 73 records · Page 4Linked to original sources
PubMed1995

Cloning and sequence analysis of the TcP2 beta cDNA variants of Trypanosoma cruzi.

P2 beta acidic ribosomal protein is a relevant antigen in Chagas' disease. cDNA cloning demonstrated that Trypanosoma cruzi expresses at least six types of TcP2 beta transcripts that differed by point nucleotides substitutions. The distribution and type of mutations seemed to follow the typical structural organization of eukaryotic acidic ribosomal proteins. Most of the synonymous changes clustered in the amino-terminus, suggesting that conservation of this domain was crucial for an equivalent functional ability of each TcP2 beta variant to bind to the ribosome. Interestingly, most amino acid changes in the central-globular and hinge domains caused polymorphism in putative phosphorylatable sites.

Amino Acid Sequence↗
PubMed1995

Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.

Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.

Amino Acid Sequence↗
PubMed1995

Neonatal enterovirus infection: virology, serology, and effects of intravenous immune globulin.

A prospective study of the virology of and serological responses to enterovirus infection in 16 neonates (< or = 2 weeks of life) and their mothers was performed. At study entry, 11 neonates did not have detectable serum neutralizing antibody to their own viral isolates, despite the presence of neutralizing antibody in 9 of 11 mothers of these infants. Viremia and viruria were demonstrated in 8 and 7 neonates, respectively, with maximal detected titers of 6.3 x 10(3) 50% tissue culture infective dose per mL (TCID50) and 6.8 x 10(1) TCID50/mL, respectively. Viremia was associated with onset of illness in the first 5 days of life, low initial serum neutralization titer, and the presence of echovirus serotypes. Randomized administration of intravenous immune globulin (IVIG; 750 mg/kg) to nine neonates overall modestly increased serum neutralization titers but did not reduce the daily incidence of viremia and viruria compared with that of controls. However, receipt of IVIG containing a neutralization titer of > or = 1:800 to the patients' own viral isolates was associated with significantly higher serum neutralization titers and more rapid cessation of viremia and viruria. Future trials of IVIG for neonatal enterovirus disease should assess the efficacy and safety of higher or repeated doses of this agent and/or of IVIG selected for their high titers to frequently circulating and/or particularly virulent enterovirus serotypes.

Antibodies, Viral↗
PubMed1995

Use of cytomegalovirus immunoglobulin in multiply transfused premature neonates.

We undertook a randomized, placebo-controlled, double blind trial of cytomegalovirus (CMV) immunoglobulin (CMVIG) for prevention of CMV-associated disease in 183 multiply transfused, premature neonates. CMVIG (150 mg/kg) or placebo was given within 24 hours of the first transfusion and at Day 10. If an intravenous catheter was still in place an additional dose was given between Days 20 and 30. The globulin and placebo groups were well-matched with respect to birth weight, gestational age, Apgar score, birth to a CMV-seropositive mother, requirement for assisted ventilation and exposure to CMV-positive, unscreened blood products. Among infants followed for more than 10 days, 18 (10.5%) developed CMV infection; 9 had symptomatic CMV disease (5 placebo; 4 CMVIG). Among infants born to a CMV-seropositive mother, CMVIG use was associated with a CMV syndrome rate of 3.2% (95% confidence interval, 0.2 to 18.5%) compared to 12.5% (95% confidence interval, 4.5 to 27.6%) among placebo recipients (P = 0.163). Among placebo recipients infants born to CMV-seropositive mothers were more likely to have a virologically confirmed CMV syndrome than those born to a CMV-seronegative mother, despite receipt of blood not screened for CMV antibody (P = 0.012). Multivariate analysis demonstrated that two factors were independently associated with CMV acquisition: the volume of CMV-seropositive blood products transfused (P = 0.005); and birth to a CMV-seropositive mother (P = 0.006). Infusions of CMVIG were well-tolerated. This study reaffirms that perinatally acquired CMV disease is more common among infants born to CMV-seropositive mothers than CMV-seronegative mothers, even without use of CMV-screened blood products.

Antibodies, Viral↗
PubMed1995

Recurrent brainstem encephalitis associated with herpes simplex virus type 1 DNA in cerebrospinal fluid.

A 47-year-old man had recurrent signs and symptoms of brainstem encephalitis over a 4-year period. Although CSF viral cultures were repeatedly negative, herpes simplex virus type 1 (HSV-1) DNA was detected in CSF by polymerase chain reaction (PCR). HSV-1-specific antibodies were absent at the time of the first positive PCR test, but CSF seroconversion to high HSV-1-specific antibody titer subsequently occurred. CSF antibody to cytomegalovirus (CMV) and varicella-zoster virus (VZV) was not detectable, nor could CMV, VZV, or Epstein-Barr virus nucleic acid be detected by CSF by PCR. This is the first report of the use of CSF PCR for the rapid antemortem diagnosis of herpetic brainstem encephalitis.

Brain Stem↗
PubMed1995

Changing migration patterns in the Federated States of Micronesia.

"This article traces the changing role of migration in the Federated States of Micronesia during the twentieth century. We begin with a brief geographical, historical, and cultural overview of each state in the country, summarizing demographic change over the past 70 years and providing a foundation for understanding much of the area's past and present human mobility. Attention then turns to migration within the Federated States, focusing on data from censuses conducted in 1930, 1973, and 1980 and using supplemental information when possible. Emigration to destinations outside the country is examined briefly. Finally, we discuss potential causes and impacts of mobility in this emerging island nation."

Demography↗
PubMed1994

Herpes simplex virus infection as a cause of benign recurrent lymphocytic meningitis.

OBJECTIVE: To identify the role of herpes simplex virus (HSV) in causing benign recurrent lymphocytic meningitis. DESIGN: Prospective cohort study. SETTING: Tertiary referral center. PATIENTS: 20 consecutive patients with a provisional diagnosis of benign recurrent lymphocytic meningitis had cerebrospinal fluid specimens submitted between 1990 and 1993 to the diagnostic virology laboratory. Thirteen patients met our criteria for benign recurrent lymphocytic meningitis. MEASUREMENTS: Herpes simplex virus DNA was detected in cerebrospinal fluid specimens using the polymerase chain reaction, followed by hybridization with a HSV-specific DNA probe. Herpes simplex virus type 1 and type 2 DNA products were distinguished by digestion with restriction enzymes and analysis by gel electrophoresis. Anti-HSV antibodies in cerebrospinal fluid were detected by immunoblot. RESULTS: The patients had 3 to 9 attacks (mean, 4.6 attacks) of benign recurrent lymphocytic meningitis during periods ranging from 2 to 21 years (mean, 8.4 years). Three of 13 patients had known recurrent genital herpes. Cerebrospinal fluid analysis showed 48 to 1600 cells/microL, glucose levels of more than 2.22 mmol/L (40 mg/dL), and protein levels of 41 to 240 mg/dL (0.41 to 2.4 g/L). Herpes simplex virus DNA and anti-HSV antibodies were detected in cerebrospinal fluid samples in 11 of 13 patients (84.6%; 95% CI, 55% to 98%). Ten of these 11 patients had HSV type 2 DNA and HSV type 2 antibodies. One patient had HSV type 1 DNA and HSV type 1 antibodies in the cerebrospinal fluid. The remaining two patients had only anti-HSV type 2 antibodies. CONCLUSIONS: Herpes simplex virus, predominantly HSV type 2, was the major agent causing benign recurrent lymphocytic meningitis that met our specified diagnostic criteria.

Adult↗
PubMed1994

Clinical application of responder cell frequency estimates with four years of follow up.

Limiting dilution cultures have been used to estimate the frequency of T cells which respond to antigen stimulation in vitro, but nothing is known of the reproducibility of this assay when applied to human blood. We developed a simplified form of limiting dilution culture in which blood mononuclear cells were diluted in round bottom 96-well plates and cultured for 10 days. The assay was used to estimate the frequency of blood mononuclear cells proliferating in response to varicella-zoster virus antigen. 250 subjects aged 25-87 years were studied: 95 of these subjects had annual measurements repeated over a 4 year period. The coefficients of variation for intra-assay replicates was 5%, and for inter-assay comparisons was 17.6% and 26% for tests at a 1 or 3 month interval respectively. For subjects studied at 1 year intervals the coefficient of variation was 42% with the total variability equally distributed between the variation between subjects and the variation within subjects. These data provide the first quantitative data to validate limiting dilution cultures for the long term in vitro measurement of human T cell responses.

Adult↗
PubMed1994

A short interspersed repetitive element provides a new 3' acceptor site for trans-splicing in certain ribosomal P2 beta protein genes of Trypanosoma cruzi.

Four Trypanosoma cruzi genomic DNA fragments carrying different TcP2 beta genes have been isolated and sequenced. Three of them had a single TcP2 beta gene, while the 3.8-kb-long DNA segment encoding the TcP2 beta-H1.8 locus showed two TcP2 beta genes arranged in tandem. These genes were physically connected by a 428-bp-long DNA sequence that was also located immediately 5' to the first gene and immediately 3' to the second. Comparison of the 4 TcP2 beta gene loci, suggested that the insertion of this repeated element originated the duplication of its target sequence, a poly(dT) stretch. Approximately 1200 copies of this short sequence, named short interspersed repetitive element (SIRE), were found scattered in the genome. Analysis of the 5' non-coding regions of different TcP2 beta mRNAs, and RNA-PCR experiments suggested that the insertion of a SIRE upstream of a TcP2 beta-H1.8 gene introduced a new 3' spliced leader (SL) acceptor site in the TcP2 beta-H1.8 pre-mRNAs, encoded within the SIRE. Consequently, in the mature H1.8 mRNA the SL sequence is followed by 38 bases directly transcribed from the SIRE. Structural and functional features of this repeated element reveal similarity to the short interspersed repetitive DNA sequences detected in the genomes of several microorganisms.

Animals↗
PubMed1994

Safety and immunogenicity of a purified haemagglutinin antigen in very young high-risk children.

Forty-three high-risk preterm children received either one of three doses of purified hemagglutinin antigen (HA) (7.5 micrograms/0.25 ml, 22.5 micrograms/0.25 ml or 67.5 micrograms/0.25 ml) or standard split product vaccine (ST) (22.5 micrograms/ml dose) over the 1990-1991 influenza season. Components for all vaccines included A/Shanghai 16/89, A/Taiwan 1/86 and B/Yamagata 16.88. Sera for antibody was drawn before, 6 weeks and 4 months after the first vaccine dose. The study was randomized and blinded. All children received two 0.25 ml doses of vaccine 4 weeks apart. No significant local or systemic reactions occurred. Six weeks after the first dose, children receiving ST vaccine had significantly higher seroconversion rates to A/Shanghai (p = 0.03) and to A/Taiwan (p = 0.01) than did those receiving equivalent HA vaccine. However, seroconversion rates were significantly higher for those children receiving the highest HA dose. All four vaccine groups responded poorly to B/Yamagata. Geometric mean titres were low for all groups and declined over 4 months. These results suggest that the equivalent dose of HA vaccine offers no advantage over ST vaccine in the immunization of high-risk preterm children.

Antibodies, Viral↗
PubMed1994

Treatment and prevention options for respiratory syncytial virus infections.

Although the therapeutic antiviral agents ribavirin and amantadine ameliorate illness caused by influenza A and respiratory syncytial virus (RSV) in children, these agents are used infrequently because they are not cost-effective. Research currently is directed toward defining the high-risk groups for which these antiviral drugs should be used. Treatment of severe respiratory infection with specific immune globulin, either alone or in combination with antiviral drugs, is another therapeutic approach. Prevention of viral respiratory diseases is preferable because some lung damage occurs before the beginning of treatment, and damage resulting from the immune response may continue even after the virus is inhibited. As natural history and animal studies suggest, passive immunization can be achieved for neonates through active immunization of the mother during pregnancy. However, this approach is limited by the half-life of the transferred antibodies and the lack of antibody in premature infants. Standard immune globulin does not contain sufficient RSV neutralizing antibody titer to fully protect against severe RSV illness. Passive immunization with RSV immune globulin in infants and children has been shown to prevent or attenuate RSV in high-risk groups. Active immunization against some respiratory viruses has been achieved by administration of inactive virus (or their subunits), recombinant viral antigens, and live attenuated virus. Large trials are under way to determine the safety and immunogenicity of these vaccines for children in whom young age and serious underlying illness are significant barriers to primary immune response. The current research environment is suitable for the development of an immunization strategy to prevent many of the significant respiratory infections in children.

Child↗
PubMed1994

Immune response to secondary immunization with live or inactivated VZV vaccine in elderly adults.

Healthy varicella zoster virus (VZV) immune subjects > 55 years old, were immunized with 4,000 PFU of Oka strain VZV live vaccine or a similar amount of heat-inactivated vaccine. A subset of each group was also immunized with tetanus toxoid (TT) 3 months before receiving the VZV vaccine. The live and inactivated VZV vaccine groups had similar ages, sex distribution, and previous immunity to VZV. The live and inactivated VZV vaccines elicited similar increases in the frequency in blood of VZV-specific T cells, in vitro interferon-gamma production, and serum antibody levels both 3 and 12 months after immunization. Individuals with the highest responder cell frequency (RCF) at entry had the highest postimmunization RCF following either vaccine. There was no correlation at entry between the RCF to TT or RCF to VZV. There was a weak (P = 0.05) correlation in the incremental response to TT and VZV among individuals who responded to both vaccines. Entry variables that did not correlate with the response included percent of T cells or the CD45R0 (memory) T cell subset in blood, serum antibody levels, or amount of interferon-gamma production. The results indicate that the inactivated vaccine is safe for VZV-immune subjects and boosts their antibody and T-cell responses as effectively as the live vaccine for at least 1 year following immunization.

Aged↗
PubMed1994

Immune responses of elderly persons 4 years after receiving a live attenuated varicella vaccine.

Annually, for 4 years after a live attenuated varicella-zoster virus (VZV) vaccine was administered to 202 elderly (55 to > 87 years old) VZV-immune persons, the immune response of vaccinees was evaluated. Anti-VZV antibody levels were enhanced by vaccination for just 1 year. However, VZV-specific proliferating T cells in peripheral blood were increased in frequency from 1 in 68,000 to 1 in 40,000 at 1 year; VZV-responding T cells were still 1 in 51,000 4 years after vaccination. The calculated half-life of this enhanced immunity was 54 months. Age had little effect on response to the vaccine, but larger doses were associated with longer duration of enhanced immunity. Immunity in approximately 10%-15% of vaccinees, independent of dose, failed to increase with the vaccine. This might complicate the use of this vaccine for prevention or attenuation of herpes zoster in the elderly.

Age Factors↗
PubMed1994

Cytokine production in varicella zoster virus-stimulated limiting dilution lymphocyte cultures.

Human blood lymphocytes were stimulated with varicella zoster virus (VZV) antigen in limiting dilution cultures and the amounts of interferon-gamma (IFN-gamma) and IL-4 measured in the supernatants. The results indicate that up to 85% of proliferating cells of young adults produce IFN-gamma and up to 10% make IL-4. At limiting dilution, few if any wells were positive for both IFN-gamma and IL-4. The amount of IFN-gamma per well increased in the presence of antibody to IL-4, but anti-IFN-gamma not increase IL-4 production. The frequency of wells containing IFN-gamma was lower in subjects < 19 or > 55 years of age, and the amounts of IFN-gamma in positive wells was significantly lower in cultures of the older subjects' lymphocytes. The frequency of IL-4-making cells did not fall significantly with age. The data suggest that the age-related decline in the frequency of blood T cells which responds to VZV affects mainly the cells with a Th1-like cytokine phenotype.

Adolescent↗
PubMed1993

Prophylactic administration of respiratory syncytial virus immune globulin to high-risk infants and young children. The Respiratory Syncytial Virus Immune Globulin Study Group.

BACKGROUND: Infants with cardiac disease or prematurity are at risk for severe illness caused by respiratory syncytial virus. Immune globulin with a high titer of antibodies against respiratory syncytial virus may offer infants and young children at risk protection from this serious, common respiratory illness. METHODS: We studied 249 infants and young children (mean age, eight months) who had bronchopulmonary dysplasia due to prematurity (n = 102), congenital heart disease (n = 87), or prematurity alone (n = 60). Respiratory syncytial virus immune globulin was given monthly to some of these children in either a high dose (750 mg per kilogram of body weight; n = 81) or low dose (150 mg per kilogram; n = 79); 89 controls received no immune globulin. Group assignments were random. Assessments of respiratory illness and management were conducted without knowledge of the children's group assignments. RESULTS: There were 64 episodes of respiratory syncytial virus infection: 19 in the high-dose group, 16 in the low-dose group, and 29 in the control group. In the high-dose group there were fewer lower respiratory tract infections (7, vs. 20 in the control group; P = 0.01), fewer hospitalizations (6, vs. 18 in the control group; P = 0.02), fewer hospital days (43, vs. 128 in the control group; P = 0.02), fewer days in the intensive care unit (P = 0.05), and less use of ribavirin (P = 0.05). In the low-dose group there was a significant reduction only in the number of days in the intensive care unit (P = 0.03). Adverse events during the 580 infusions were generally mild and included fluid overload (in five children), oxygen desaturation (eight), and fever (six). Six children died: three in the high-dose group, three in the low-dose group, and none in the control group (P = 0.15), but no death was attributed to the use of immune globulin or to illness caused by respiratory syncytial virus. CONCLUSIONS: Administration of high doses of respiratory syncytial virus immune globulin is a safe and effective means of preventing lower respiratory tract infection in infants and young children at high risk for this disease.

Antibodies, Viral↗