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M S Ascher

Publications and source records attributed to M S Ascher.

At least 19 recordsLinked to original sources
PubMed1992

A comparison of HIV-1, HBV, and HTLV-I/II seroprevalence rates of injured patients admitted through California emergency departments.

STUDY OBJECTIVE: To determine the seroprevalence rates of hepatitis B virus (HBV) and human T-lymphotropic virus (HTLV-I/II) and to compare these rates with the HIV-1 seroprevalence rate in a sample of injured patients admitted through ten California emergency departments. DESIGN: Prospective blinded testing for serologic markers for HBV, HTLV-I/II, and HIV-1 on routinely collected blood samples. SETTING: Ten California hospitals were chosen to reflect geographic and demographic diversity. TYPE OF PARTICIPANTS: All injured adult patients who were admitted to a participating hospital through the ED during consecutive three-month periods from June through November 1989. MEASUREMENTS: Serum samples were tested for HIV-1 antibody, HTLV-I/II antibody, and hepatitis B surface antigen (HBsAg) using standard methods. Mann-Whitney U tests, chi 2 tests for independence, sign tests, chi 2 tests for goodness of fit, and logistic regression were used as appropriate. RESULTS: Seroprevalence rates were as follows: HBV, 2.6% (57 of 2,209); HTLV-I/II, 2.0% (46 of 2,262); and HIV-1, 1.4% (31 of 2,264). CONCLUSION: The seroprevalence rate of HBV was slightly higher than that of HIV-1 in this sample of injured patients. Mortality estimates suggest, however, that HBV and HIV-1 pose roughly similar risks to emergency personnel, although the risk of HBV infection can be markedly reduced by vaccination. The data from this and other studies suggest that the ED incidence of HTLV-I/II in United States is low. The relative health risks to emergency personnel from HTLV-I/II appear to be minimal at this time.

California↗
PubMed1992

The natural history and pathogenesis of HIV infection.

Infection with human immunodeficiency virus (HIV) results in progressive deterioration of the cell-mediated immune system characterized by T-helper-cell dysfunction and loss in the face of signs of generalized immune-system activation. The final stage of HIV disease, AIDS, has a myriad of opportunistic infections and malignancies as its hallmarks. The causal relationship between HIV and this complex disease pattern is clear but the mechanisms by which it occurs are not well understood. There are a number of new developments in our understanding of the natural history of HIV infection from a laboratory standpoint. Our review of this information raises further questions as to the validity of the conventional "cytopathic" model and all its direct descendants. In response to these conflicts, we have developed and present an alternative hypothesis in which AIDS pathogenesis, in all its manifestations, is seen as the outcome of one central process, excess immune activation generated by the interaction of virus with the CD4 receptor. The implications of this hypothesis on therapy of HIV infections are discussed.

HIV Infections↗
PubMed1992

Distribution of HIV type 1 infection in childbearing women in California.

The incidence of acquired immunodeficiency syndrome (AIDS) is increasing among California heterosexuals and children. To assess human immunodeficiency virus (HIV)-1 infection in childbearing women, we conducted a blinded serosurvey of newborns. Dried blood specimens taken from 99% of California births during the third quarter of 1988 (n = 135,808) and linked only to maternal demographic categories were tested for HIV-1 antibody by enzyme immunoassay and confirmed by Western blot. Period prevalence of HIV-1 infection was 7.4 per 10,000 childbearing women. Prevalence was highest for Black women and was also elevated for Hispanic and San Francisco Bay Area women. Findings suggest that California Hispanic women will make up an increasing proportion of new AIDS cases.

Adult↗
PubMed1992

Seroprevalence of HIV-type 1 in a northern California health plan population: an unlinked survey.

We conducted an unlinked seroprevalence survey for human immunodeficiency virus-type 1 (HIV-1) of 9821 persons who had a routine personal health appraisal examination in 1989 while members of the Kaiser Permanente Medical Care Program in northern California. An outside laboratory performed enzyme immunoassay (EIA) analyses, and the California Viral and Rickettsial Diseases Laboratory confirmed EIA-reactive samples by immunofluorescent assay and Western blot assay. Only 20 specimens (0.2%) were confirmed as positive, and 18 were from men. These data suggest that, at the time of this survey, HIV-1 infection was not widespread in the northern California population represented by this health plan membership.

Adolescent↗
PubMed1992

Prevalence of human T cell lymphotropic virus types 1 and 2 (HTLV-1/2) in selected Tijuana subpopulations.

To assess the prevalence of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) infections among potentially high-risk populations in the city of Tijuana, Mexico, the prevalence of specific antibodies was determined and information on risk behaviors was obtained between June and October 1988. The study involved 631 presumably healthy individuals, randomly selected from a study population recruited sequentially from prisoners, prostitutes, and injecting drug users (IDUs), and randomly from homosexual and bisexual men. The presence of HTLV-1/2 antibodies was determined by enzyme immunoassay and an immunofluorescence method, and positive reactions were confirmed by a radioimmunoprecipitation assay and Western blot. The prevalence of HTLV-1/2 was 2% (2 of 105) among prostitutes, 7% (29 of 410) among prisoners, 1% (1 of 105) among homosexual/bisexual men, and 21% (22 of 106) among IDUs. To properly identify the specific HTLV type, a subsequent sample of 41 imprisoned IDUs were voluntarily and anonymously recruited in June 1990 and asked to donate 20 ml of whole blood. Twenty-two percent (9 of 41) were serologically positive for HTLV-1/2, and polymerase chain reaction analysis performed on peripheral blood mononuclear cells identified HTLV-2 as the specific virus prevalent in this group. Two individuals were positive for human immunodeficiency virus type 1 (HIV-1). One of these individuals was coinfected with HTLV-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1992

The relationship between AIDS and immunologic tolerance.

A hypothesis is presented in which the immunodeficiency and cell loss leading to acquired immune deficiency syndrome and the clonal deletion associated with immunologic tolerance occur through a common mechanism. In a previous publication we proposed that the interaction of human immunodeficiency virus (HIV) with CD4 delivers activation signals that disrupt immune system regulation. In this article, we compare the biology of HIV infection with recent discoveries concerning the "two-signal" molecular mechanism for thymic selection. We propose that two-signal activation is normally followed by clonal expansion and the programmed death of most or all daughter cells through mechanisms that are proportional to the strength and duration of the activation signals. In the thymus, self-reactive cells are trapped in the continuous presence of both antigen signals (signal 1) and costimulatory signals (signal 2), leading to clonal deletion. In mature lymphocytes, we propose that HIV infection contributes a chronic high-affinity signal 2, which shifts the equilibrium of antigen-activated T-cell populations further toward programmed death. This leads to incremental memory cell deficits and gradual clonal deletion at a rate dependent on the frequency of antigen exposure and the ability of an HIV quasispecies to induce signal 2.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The HIV-1 seroprevalence rate of injured patients admitted through California emergency departments. California HIV-1 Emergency Department Seroprevalence Study Group.

STUDY OBJECTIVES: To measure the HIV seroprevalence of injured emergency department patients in a number of California hospitals and to examine the relationship between ED seroprevalence and local AIDS incidence. DESIGN: Prospective blinded testing for HIV-1 antibody was performed on routinely collected blood samples. SETTING: Ten California hospitals; group 1 included three hospitals from counties of high AIDS incidence (more than 40 cases per 100,000 population), group 2 included three hospitals from counties of intermediate AIDS incidence (20 to 40 cases per 100,000 population); and group 3 included four hospitals from counties of low AIDS incidence (less than 20 cases per 100,000 population). TYPE OF PARTICIPANTS: Eligible patients were all adult trauma victims admitted to a participating hospital through the ED during a consecutive three-month period occurring between June and November 1989. MEASUREMENTS: HIV-1 antibody testing was done using enzyme immunoassay confirmed by immunofluorescence assay. Equivocal results were confirmed by Western blot. Mann-Whitney U test, chi 2 test, and multiple logistic regression were used where appropriate. RESULTS: There were 2,264 patients with adequate blood samples for serologic testing. The seroprevalence rates for hospitals in groups 1, 2, and 3 were significantly different (chi 2 = 8.44, P = .02): Group 1, 2.5% (19 of 756: 95% confidence interval [CI], 1.5% to 3.9%); group 2, 0.9% (10 of 1,078; CI, 0.5% to 1.7%); and group 3, 0.5% (two of 430; CI, 0.06% to 1.7%). CONCLUSION: This study suggests that local AIDS incidence rates do not necessarily predict the seroprevalence rates of injured patients who are admitted through local EDs.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Immune response to HIV p24 core protein during the early phases of human immunodeficiency virus infection.

The immune response to the p24 core antigen of human immunodeficiency virus type 1 (HIV-1) was studied in serial samples collected prospectively from 52 homosexual males in two separate cohorts from Amsterdam and San Francisco. p24 antibody levels were quantified with an antigen sandwich immunoassay using p24 recombinant antigen as capture and probe. Titers and slopes of dilution curves reflecting antibody affinity were analyzed. Only 45 of 52 men developed a measurable primary immune response to p24. In 17 (33%) patients there was a low response with maximum antibody titer below 66, shallow (low affinity) dilution curve, and 10 of the 17 became HIV antigen positive over a 2 year period. In 24 (46%) of the 52 patients titers ranged from 100-4000, steeper dilution curves were noted, and none became HIV antigen positive. Four (8%) men developed a strong immune response with high titers (greater than 12,000) and high affinity type dilution curve. Over time, after the peak immune response, antibody titer declined in some individuals related in part to the formation of immune complexes between HIV-1 p24 antigen and antibody which were dissociable. In vitro, the addition of increasing amounts of purified p24 antigen corresponded to decreasing antibody titer and a shallower dilution curve suggesting a preferential consumption of high affinity antibodies for complex formation. The magnitude of immune response to HIV-1 p24 antigen varies widely in infected homosexual men. Both the intrinsic ability to mount an immune response and immune complex formation contribute to the measurable antibody level.

Bisexuality↗
PubMed1991

The initial immune response to HIV and immune system activation determine the outcome of HIV disease.

A study was conducted to assess the relative contribution of the HIV-1-specific immune response and -nonspecific immune activation to HIV disease progression. The titer of antibody to the p24 core protein and the concentration of serum neopterin were measured in 238 HIV-1-seropositive subjects in a prospective cohort study of homosexual men. Antibody titers were extremely variable among cohort participants but relatively stable over time, suggesting inherent differences in the initial immune response capacity. Neopterin concentrations were also variable at cohort entry but generally increased over time. These two markers, measured at cohort entry, had powerful and independent predictive value for the development of AIDS up to 54 months before diagnosis. Subjects with low antibody titers and high levels of neopterin, had the highest incidence of AIDS (60% over 54 months). Patients with low antibody or high neopterin alone had an intermediate risk (34% incidence) and less than 10% of those with high antibody and low neopterin developed AIDS. We propose that the initial immune response to HIV and virus-mediated immune system activation are independent and innately variable components of an individual's response to HIV infection that interact to determine the clinical outcome.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A multicenter proficiency trial of gene amplification (PCR) for the detection of HIV-1.

The sensitivity and specificity of the polymerase chain reaction (PCR) for the detection of HIV-1 proviral DNA was determined in five laboratories with extensive experience in PCR testing. Five panels consisting of 105 HIV-1-seronegative specimens from regularly repeating blood donors with no risk factors for HIV infection and 99 HIV-1-seropositive and culture-positive specimens from a cohort of homosexual/bisexual men were sent under code to each laboratory. Amplification procedures and testing algorithms by which specimens were judged positive, negative, or indeterminate varied between laboratories. The average sensitivity for the five laboratories was 99.0%, with two laboratories achieving 100%. The average specificity was 94.7%, varying between 90.5 and 100%. The overall false-positive rate was 1.8%, the false-negative rate was 0.8%, and the indeterminate rate was 1.9%. Of 1,005 determinations made by the five laboratories, 32 (3.2%) were misclassifications. Most of the classification errors occurred in specimens from uninfected individuals and were distributed among the laboratories in such a way as to indicate laboratory error rather than the inherent reactivity of some samples. This emphasizes the need for standardization of PCR testing and caution in interpreting positive PCR reactions in HIV-1-seronegative persons.

DNA, Viral↗
PubMed1990

Immunofluorescence for serodiagnosis of retrovirus infection.

Indirect immunofluorescence antibody testing is a mainstay of retrovirus serodiagnosis in the public health community, affording quick, inexpensive, and clear results with significant advantages over Western blot testing. Limitations regarding training of personnel and availability of reagents will probably continue and limit indirect immunofluorescence antibody testing to the present users.

Bibliographies as Topic↗
PubMed1990

AIDS as immune system activation. II. The panergic imnesia hypothesis.

A hypothesis is presented in which HIV infection leads to immunodeficiency through indirect subversion of critical T cell regulatory mechanisms. Acting at the T cell receptor complex (TCR), viral components (gp120) mimic the natural ligands of CD4, molecules of the major histocompatibility complex (MHC), and deliver physiologically active, inappropriate signals resulting in generalized, uncontrolled lymphocyte activation, or "panergy." Clinical manifestations of panergy include autoimmune phenomena, lymphadenopathy, hyperglobulinemia, and symptoms mediated by lymphokines. Immunologic unresponsiveness occurs early in HIV infection prior to T cell depletion because activated cells do not respond to further stimulation. Ultimately, activation disrupts T cell homeostasis by interference with the generation of memory cells ("imnesia") and leads to net T cell loss, clonal deletion, and the development of AIDS. The clinical and immunologic features of HIV disease and AIDS are reviewed from this perspective. This hypothesis is consistent with the paucity of infected T cells, the clinical findings of both AIDS-related complex (ARC) and frank AIDS, the prolonged "incubation period," and a role for antigen-specific cofactors. Based on this view of HIV pathophysiology, therapeutic modalities should avoid immune stimulation and seek to block aberrant gp120 signals at CD4 and eliminate HIV-infected cells.

Acquired Immunodeficiency Syndrome↗