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Biomedical subjects

M Ascher

Publications and source records attributed to M Ascher.

13 recordsLinked to original sources

Dissociation of immunologic and virologic responses to highly active antiretroviral therapy.

OBJECTIVE: Immunologic markers, levels of HIV DNA, and infectious HIV were compared in partial responders (PR) to HAART who had high plasma HIV RNA levels but stable or increasing levels of CD4+ peripheral blood mononuclear cells (PBMC), and patients with complete failure (CF) who had very low or decreasing levels of CD4+ PBMC and high plasma HIV RNA levels. DESIGN AND METHODS: CD4 and CD8 levels were monitored by flow cytometry. Beta2-microglobulin (beta2M) and neopterin levels were measured by quantitative enzyme immunoassays. Plasma and PBMC from 11 PR and 13 CF were analyzed for infectious HIV levels in limiting dilution cultures. Polymerase chain reaction (PCR) assays were used to quantify cellular HIV DNA and plasma HIV RNA. RESULTS: In comparison with CF, PR had little or no CD4+ cell loss, a substantial increase in CD8+ cells, significantly fewer positive plasma HIV cultures (p = .03), lower frequencies of infectious HIV in total PBMC (p = .005) and in CD4+ PBMC (p < .001), and lower frequencies of HIV DNA in CD4+ PBMC (p = .007). CONCLUSIONS: Lower levels of infectious HIV and a lower frequency of CD4+ PBMC that contain "productive" HIV DNA in PR as compared with CF may contribute to the stable or increasing CD4+ PBMC levels of the PR. However, HAART may also have effects on lymphocyte homeostasis independent of its antiviral activity.

Anti-HIV Agents↗

Occupational exposure leading to hantavirus pulmonary syndrome in a utility company employee.

Hantavirus pulmonary syndrome is a newly recognized rodent-borne zoonosis. We report a case of hantavirus pulmonary syndrome in an employee of a California utility company who was probably occupationally exposed to Sin Nombre virus. Environmental assessment and genetic comparison of the patient's hantavirus isolates to hantavirus isolates from rodents trapped at possible sites of exposure suggested that the patient contracted his infection at the work site. The study revealed a close correspondence between the patient's viral genotype and that from a rodent trapped at the work site. This report alerts the public health and medical community to the fact that employees of utility companies and similar industries may be an important risk group in areas where hantavirus is endemic and emphasizes the need to incorporate strategies for preventing exposure to hantavirus and other emerging infections into occupational safety protocols.

Animals↗

Isla Vista virus: a genetically novel hantavirus of the California vole Microtus californicus.

Prospect Hill virus (PH) was isolated from a meadow vole (Microtus pennsylvanicus) in 1982, and much of its genome has been sequenced. Hantaviruses of other New World microtine rodents have not been genetically characterized. We show that another Microtus species (the California vole M. californicus) from the United States is host to a genetically distinct PH-like hantavirus, Isla Vista virus (ILV). The nucleocapsid protein of ILV differs from that of PH by 11.1% and a portion of the G2 glycoprotein differs from that of PH by 19.6%. ILV antibodies were identified in five of 33 specimens of M. californicus collected in 1975 and 1994-1995. Enzymatic amplification studies showed that 1975 and 1994-1995 ILV genomes were highly similar. Secondary infection of Peromyscus californicus was identified in Santa Barbara County, California. A long-standing enzootic of a genetically distinct hantavirus lineage is present in California voles.

Animals↗

Dominant glycoprotein epitope of four corners hantavirus is conserved across a wide geographical area.

A newly identified hantavirus, tentatively called Four Corners virus (FCV), was found to be the aetiological agent of a 1993 outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States. Immunodominant epitopes of 43 and 31 amino acids were identified in the nucleocapsid protein and G1 glycoprotein, respectively. The G1 genes of different hantaviruses are highly divergent, suggesting that geographically diverse FCVs might fail to cross-react owing to antigenic drift. We now show that the immunodominant epitope of G1 is conserved among 18 FCVs from a broad geographical area, despite extensive nucleotide sequence heterogeneity. Antibodies from all 45 HPS patients, separated by more than 3000 km were shown to be reactive with the dominant G1 epitope. Evidence for limited cross-reactivity between the G1 antigen of a novel hantavirus of the cotton rat and that of FCV is presented.

Amino Acid Sequence↗

Comparison of six commercial human T-cell lymphotropic virus type I (HTLV-I) enzyme immunoassay kits for detection of antibody to HTLV-I and -II.

Three licensed and three research human T-cell lymphotropic virus type I (HTLV-I) enzyme immunoassay (EIA) kits were evaluated with a panel of 213 serum or plasma samples which were previously tested by the indirect immunofluorescence method for HTLV-I and -II antibodies. The three research kits were found to be more sensitive and specific than the three licensed kits.

Evaluation Studies as Topic↗

HIV antibody seroprevalence among prisoners entering the California correctional system.

A cross-sectional blind study was conducted in the spring of 1988 to estimate the extent of human immunodeficiency virus (HIV) infection among inmates entering the California correctional system. Of the 6,834 inmates receiving entrance physical examinations during the study period, 6,179 (90.4%) had serum tested for the presence of HIV antibodies after routine blood work was completed and personal identifiers were removed. Seroprevalence was 2.5% (95% confidence interval, 2.1% to 3.0%) among the 5,372 men tested and 3.1% (95% confidence interval, 2.1% to 4.5%) among the 807 women tested. Seroprevalence was more than twice as high among men arrested in the San Francisco Bay Area as in those arrested elsewhere in the state. The regional differences in HIV seroprevalence observed among entering inmates mirror infection rates reported among intravenous drug users from the same regions.

California↗

Complement activation in type 1 human diabetes.

Complement activation was quantitated in serum and plasma of diabetic and normal subjects by sensitive competitive equilibrium radioimmunoassays (RIA) for C3a, C4a, C5a, Factor B, and a newly described C5 neoantigen (termed C5 activation antigen, and abbreviated C5-AA) in a stable 54-kDa fragment of C5. Plasma C3a levels were significantly elevated in 8 of 16 patients with newly diagnosed Type 1 diabetes (P less than 0.0005) with the mean C3a concentration for these patients being more than 10-times greater than the mean value of normal controls. C4a levels were also elevated in 2 of these patients (P less than 0.02), but C5a levels, although higher than normal, were not significantly increased. In contrast, the levels of C5-AA in the serum of all patients (11/11) with chronic Type 1 diabetes were significantly higher than in control Type 2 patients (noninsulin-dependent diabetes) (P less than 0.0005) and 4 of 7 patients with new onset insulin-dependent diabetes mellitus also had significantly higher levels of C5-AA than the Type 2 patients (P less than 0.01). The levels of Factor B in the serum of 5 of 9 patients with new onset diabetes were significantly higher than normal (P less than 0.0025). Five recent onset Type 1 diabetes patients were evaluated longitudinally for C3a, C4a, and C5a: in 3 the levels of C3a were elevated during new onset disease decreasing into the normal range during remission; in 2 of these patients C4a was also significantly elevated and the levels decreased during remission; and in 3 patients the levels of C5a were not significantly elevated but they decreased during remission. Purified human complement proteins and complement hemolytic assays were used to measure complement activation in serum during incubation with rat pancreatic islet cells. With diluted normal human serum, less than 20% of C3 or Factor B were consumed during 30 min at 37 degrees C, while with new onset Type 1 diabetic patient sera up to 90% of C3 and Factor B were consumed in 5/6 sera and 4/6 sera, respectively. These findings suggest (a) that complement activation fragments C3a, C4a, and C5a are generated in vivo in new onset Type 1 diabetes; (b) that both the classical and the alternative complement pathways may be activated; and (c) that this may result in a measurable activation of C5 generating biologically and immunologically active C5a and other C5 activation fragments.(ABSTRACT TRUNCATED AT 400 WORDS)

Complement Activation↗

Comparison of porcine and semisynthetic human insulins using euglycemic clamp-derived glucose-insulin dose-response curves in insulin-dependent diabetes.

In order to compare the biologic effectiveness of porcine and semisynthetic human insulins, a euglycemic clamp method was used in eight insulin-dependent diabetic subjects. Each subject was tested for each insulin on separate days. In order to derive glucose-insulin dose-response curves for both insulins, sequential but constant infusion rates of 0.2, 0.5, 1.0, and 2.0 mU/kg/min were performed. Plasma glucose levels attained during the euglycemic clamp were 96 +/- 3 mg/dL. At each insulin infusion rate, the steady-state glucose infusion rate required to maintain euglycemia was measured. At each increment of insulin infused, steady-state glucose infusion rates for porcine insulin were 1.12 +/- 0.22, 1.90 +/- 0.59, 4.28 +/- 0.61, and 9.37 +/- 0.66 mg/kg/min compared with 1.27 +/- 0.42, 2.38 +/- 0.20, 4.25 +/- 0.43, and 8.87 +/- 0.67 mg/kg/min for semisynthetic human insulin. By ANOVA, no significant difference was noted between the two insulins. Because insulin infusion rates may not result in predictable circulating free insulin levels in subjects who have circulating insulin antibodies, free insulin levels were determined. When steady-state glucose infusion rates were compared with free insulin levels achieved at the four insulin infusion rates, dose-response curves for both porcine and semisynthetic human insulins were virtually identical. These data suggest that semisynthetic human insulin has equivalent biologic effects on overall glucose metabolism compared with porcine insulin in insulin-dependent diabetes.

Adult↗

Conjoint treatment of a mother and her 16-month-old toddler.

This paper offers a partial account of the ongoing treatment of a 16-month-old toddler who presented with a history of a psychogenic rash; a feeding disorder; bowel retention; an intolerance to physical separation from mother, even in the house; and a marked insomnia, all dating from the time she was 8 months old. I came to understand the infant's constellation of symptoms, interpersonally, as part of a three-generational intercommunication that included toddler, mother, and mother's mother and, intrapsychically, as a failure in the separation-individuation process. A nodal point in the treatment and in symptom relief occurred when the toddler became aware, in her 17th month, of the anatomical difference. This clinical example is presented to support the idea (Roiphe & Galenson 1981) that such early genital awareness may act as a spur to ego development and may further ego organization, allowing the child an opportunity to master partially what had been phase-specifically traumatic during the symbiotic phase.

Child Behavior Disorders↗