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Biomedical subjects

A A Gottlieb

Publications and source records attributed to A A Gottlieb.

At least 19 recordsLinked to original sources
PubMed1996

Rationale and clinical results of using leucocyte-derived immunosupportive therapies in HIV disease.

Leucocyte dialysates contain a number of substances which exert important effects on human cell-mediated immunity. In this report, we describe several properties of a designated subfraction, IMREGR-1, which is obtained by a second dialysis against a membrane having a 3500 m.w. cutoff. These include the ability to augment and accelerate reactions of delayed hypersensitivity against antigens to which the test subject has been previously sensitized, and the ability to enhance the expression in vitro on CD4 lymphocytes of the p55 subunit of the receptor for Interleukin-2. We also report our observation that in a patient with advanced HIV disease whose lymphocytes had lost there ability to properly express the IL-2 receptor, treatment with IMREGR-1 over a period of months restored the expression of the IL-2 receptor on the patient's CD4+ lymphocytes towards normal.

Adjuvants, Immunologic↗
PubMed1995

A novel methodology for quantitating the enhancement of cutaneous delayed-type hypersensitivity by IMREG-1: a measure of the immunopotentiation of cell-mediated immunity.

IMREG-1, a low-molecular-weight immunomodulator derived from normal human leukocyte dialysates, has been shown to enhance cutaneous delayed-type hypersensitivity (DTH) responses to recall antigens. Both IMREG-1 and the biologically active peptides (Tyr-Gly[YG] and Tyr-Gly-Gly[YGG]) identified therein are able to accelerate and enhance DTH in a concentration-dependent manner. In this study, we describe a novel methodology for analyzing and quantitating this response and demonstrate its use with data comparing drug to placebo. Subjects demonstrating prior sensitivity to a recall antigen (tetanus toxoid) received intradermal injections of tetanus toxoid alone (control) and either dilutions of IMREG-1 plus antigen, or placebo plus antigen, on the volar surface of the forearm. The response, as measured by area of erythema, was calculated and plotted as a function of time. The area under the resulting curve (AUC) was then determined by use of the trapezoidal rule, whereby the area of a trapezoid formed between each sequential pair of time points was calculated. The AUC computed for each site receiving a dilution of IMREG-1 or placebo (test) was compared with the AUC computed at the site that received antigen alone (control) by means of a test to control (T/C) ratio. The respective T/C ratios for designated dilutions of IMREG-1 or placebo provided a basis of comparison between responses to IMREG-1 and to placebo, while also controlling for individual sensitivity in response to antigen. We demonstrate in this study that the enhanced response to IMREG-1 plus antigen is statistically different from that seen with placebo plus antigen. This response, as a function to time, predominantly appears in the 12- to 24-hr period after injection, illustrating the ability of the immunomodulator to accelerate, enhance, and sustain a DTH response. We further conclude that the effect of IMREG-1 in this context is one of immunopotentiation of cell-mediated immunity.

Adjuvants, Immunologic↗
PubMed1995

HIV retrotransposon activity and the immunopathogenesis of AIDS.

This article presents the new hypothesis that HIV retrotransposon insertional mutagenesis induces genomic effects that bring about immune dysfunction through disruption, deletion or rearrangement of the genome of the host. This activity may be augmented by the action of most, if not all, the cofactors of HIV-induced disease.

Acquired Immunodeficiency Syndrome↗
PubMed1995

An AIDS training program for rural mental health providers.

A total of 194 mental health care providers in Arkansas, primarily from rural areas and small communities, participated in a four-hour training program designed to improve their knowledge about the psychosocial and neuropsychiatric aspects of HIV and AIDS. Participants' responses to questionnaires completed before and after training indicated that the program was successful in achieving its goal. However, only a minimal number of providers reported completing drug, alcohol, and sexual histories and AIDS risk assessments for any of their patients before the training occurred. The authors emphasize the importance of AIDS training for rural providers.

AIDS Dementia Complex↗
PubMed1992

Is AIDS education related to condom acquisition?

The acquisition and subsequent use of condoms are two important behaviors that sexually active adolescents must adopt to reduce the transmission of human immunodeficiency virus (HIV). The aims of this study were: first, to evaluate whether combining prescriptions for free condoms with anticipatory guidance would increase the number of adolescents actually using the prescription-redemption plan; and second, to see if education about acquired immunodeficiency syndrome (AIDS) might make adolescents more willing to obtain an HIV blood test. Adolescents were randomly assigned to one of three groups, but only those who were sexually active were included in the data analyses. Each participant was given a prescription to be redeemed for free condoms at the hospital pharmacy, and each was privately offered a confidential, free HIV blood test. Education about AIDS did not increase the likelihood that adolescents would take the blood test, since only seven subjects did so. Our logistic regression model showed the most significant variables influencing a teenager to obtain condoms were gender, socioeconomic status, lifetime number of partners, and experimental condition. Anticipatory guidance concerning HIV promoted the use of the prescription-redemption plan especially among more sexually active males who come from middle-class families.

AIDS Serodiagnosis↗
PubMed1991

Modulation of concanavalin A-induced, antigen-nonspecific regulatory cell activity by leu-enkephalin and related peptides.

We have developed a system in which human peripheral blood mononuclear cells (PBMC) stimulated with concanavalin A (Con A) can be examined for regulatory cell activity upon coculture with responder cells undergoing mitogenic proliferation. Low concentrations of Con A resulted in the induction of helper function, while higher concentrations of Con A induced suppressor activity in the PBMC population. However, for each individual donor a particular concentration of Con A can be found at which point no regulatory cell activity is observed. This "balance point" provides a set of conditions under which the ability of an immunomodulator to up-regulate or down-regulate the system can be studied. The ability of leu-enkephalin to positively or negatively regulate an immune response was examined under these circumstances. The addition of leu-enkephalin to cultures stimulated by Con A at this balance point enhanced both suppressor cell (Ts) and helper cell (Th) activity in a concentration-dependent manner. The induction of Ts activity displayed a bimodal response at concentrations between 10(-12) to 10(-13) M and 10(-9) to 10(-10) M, while the induction of Th activity was consistently observed at 10(-11) M. Similar effects were seen with either of the peptides Tyr-Gly and Tyr-Gly-Gly, corresponding to the first two and three amino acids of the N-terminal ends of the enkephalins. Th activity was consistently enhanced at 10(-13) M Tyr-Gly-Gly and 10(-14) M Tyr-Gly. This suggests that leu-enkephalin may either positively or negatively regulate immune responses and that the intact leu-enkephalin molecule is not required for these effects.

Concanavalin A↗
PubMed1991

Clinical and immunologic observations in patients with AIDS-related complex treated with IMREG-1.

An immunomodulator, IMREG-1, derived from human leukocyte dialysates exerts a variety of effects on the cell-mediated immune system, including acceleration and amplification of delayed hypersensitivity to recall antigens, modulation of gamma-interferon production in response to antigen, and enhanced expression of the p55 portion of the receptor for interleukin-2 on CD4+ cells. On the basis of initial studies of IMREG-1 in patients with AIDS-Related Complex (ARC), a multicenter randomized, double-blind, placebo controlled trial of this agent was carried out. The results indicate that patients who received IMREG-1 had a lower risk of progression to frank AIDS than those who received placebo. A decline in the rate of reduction of numbers of CD4+ cells, as well as fewer symptoms were also observed in patients who received IMREG-1 as compared with placebo.

AIDS-Related Complex↗
PubMed1990

Adolescent wellness. Facilitating compliance in social morbidities.

The establishment of a well adolescent schedule needs to be developed similar to the scheduled clinical visits in pediatric care. However, providing adolescent wellness visits without appropriate financial reimbursement for time expended and without increased provider training may make "well" adolescent visits an unrealistic expectation. However, two major trends will significantly impact on the future of adolescent health care. These include a sharp increase in numbers of adolescents beginning in 1990 and the poverty within the adolescent population. These data suggest that obstacles, whether personal, financial, or educational, need to be addressed quickly in order to resolve these problems because of increasing numbers of adolescents and related morbidities through the year 2000. The increasing trend of juvenile poverty in this population has been significantly associated with a number of the new morbidities such as substance abuse, STD, pregnancy, and the latest morbidity, AIDS. Without a wellness schedule, it is likely that adolescents will continue to represent an underserved population; as a consequence, mortalities and morbidities will increase through the year 2000. The issue of adherence to prescribed medical regimens in the adolescent population is an interesting, complex, and especially challenging one when faced with the social morbidities. Although preliminary work in this area has progressed in the last 15 years, greater attention must be paid to the needs of adolescents in order to determine effective strategies that can minimize the effects of the current morbidities. It is important for the primary care physician not to become overwhelmed with the scope of problems that adolescents have or become discouraged because anticipatory guidance seems ineffective. Repeated dosages of anticipatory guidance should not be viewed as limitations or failures but rather as necessary and standard care. One should consider such interventions as similar to immunizations, in which certain vaccines result in life-long immunity. One would not eliminate the tetanus vaccine because the patient must receive periodic boosters. Similarly, as health care professionals, we should not consider interventions designed to preclude behavior or mental health problems as failures if periodic and developmentally appropriate relevant "boosters" are necessary. Anticipatory guidance is an extremely effective tool that every primary care physician has at his or her disposal to assist in the diagnosis of problematic behavior in adolescents and to preclude problems. Future research needs to focus on documenting strategies that can be utilized by physicians on a daily basis without excessive time or financial constraints.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Development of immunomodulators for treatment of HIV infection.

Although considerable attention has been devoted to development of antiviral drugs for therapy of HIV infection, relatively little priority has been directed to correction of the progressive immunologic defect that develops in these patients. We described the development of the therapeutic effect of an immunosupportive biological agent (IMREG-1) derived from human leukocytes. Specifically, IMREG-1 reduced the risk of progression from advanced AIDS-related complex (ARC) based on a randomized double-blinded control trial over a six month period of the laboratory and clinical parameters predictive of a high risk of progression from ARC to AIDS. The comparative value of CD4+ cell numbers, anergy to recall antigens and symptomatology in assessing risk of progression were also examined.

AIDS-Related Complex↗
PubMed1988

Documentation of an AIDS virus infection in the United States in 1968.

The acquired immunodeficiency syndrome was first recognized as a clinical entity in the United States in the early 1980s; however, the issue of when human immunodeficiency virus, the causative agent of the acquired immunodeficiency syndrome, was introduced into at-risk populations in the United States is unresolved. Previously, we reported the case study of a 15-year-old black male who was admitted to St Louis City Hospital in 1968 for extensive lymphedema of the genitalia and lower extremities. Chlamydial organisms were widely disseminated and isolated from numerous body fluids and organs. Over a 16-month clinical course his condition progressively deteriorated, and at autopsy there was widespread Kaposi's sarcoma of the aggressive, disseminated type. Recently performed Western blot and antigen capture assays on serum and autopsy tissue specimens frozen since 1969 have disclosed that this sexually active teenager was infected with a virus closely related or identical to human immunodeficiency virus type 1. The clinical and immunologic findings together suggest that an immunosuppressive retrovirus existed in the United States before the late 1970s.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Cell surface effects of human immunodeficiency virus.

Cell killing by human immunodeficiency virus (HIV) is thought to contribute to many of the defects of the acquired immunodeficiency syndrome (AIDS). Two types of cytopathology are observed in HIV-infected cultured cells: cell-cell fusion and killing of single cells. Both killing processes appear to involve cell surface effects of HIV. A model is proposed for the HIV-mediated cell surface processes which could result in cell-cell fusion and single cell killing. The purpose of this model is to define the potential roles of individual viral envelope and cell surface molecules in cell killing processes and to identify alternative routes to the establishment of persistently-infected cells. Elucidation of HIV-induced cell surface effects may provide the basis for a rational approach to the design of antiviral agents which are selective for HIV-infected cells.

Biological Transport, Active↗
PubMed1986

Cell killing by ultraviolet-inactivated human immunodeficiency virus.

Extensive cell killing and cytopathology were observed within 24 hr after exposure of a clonal cell line of human T-4 lymphocytes (RH9) to culture supernatants containing human immunodeficiency virus (HIV). Ultraviolet-irradiated HIV-containing culture fluids were also capable of killing RH9 cells and of inducing specific cytopathic effects which were indistinguishable from those induced by unirradiated virus-containing preparations. The uv-irradiated HIV was incapable of forming proviral DNA using the endogenous virion genomic RNA as a template. The RH9 cells persistently infected with HIV did not release soluble cytotoxic factors to account for the cell killing observed when culture supernatants were added to uninfected RH9 cells. The fraction involved in cell killing had the hydrodynamic properties of a retrovirus. These results suggest that a virion component is responsible for cell killing by HIV.

Cell Line↗
PubMed1986

Inhibition of interleukin 2 production and expression of the interleukin 2 receptor by plasma from acquired immune deficiency syndrome patients.

Plasmas from acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) patients were screened for their ability to inhibit mitogen-induced proliferation of normal human lymphocytes. Plasmas from 67% of the individuals examined contained significant suppressive activity. Additional studies on the mechanism of action of the plasma inhibitor demonstrated that it functions as a nonlymphotoxic inhibitor of interleukin 2 production by stimulated human lymphocytes, and that this activity is accompanied by suppression of expression of the cell surface receptor for interleukin 2. A more detailed understanding of the action of this activity may aid in the design of therapy to minimize the contribution of this agent to the immune anergy observed in these patients.

Acquired Immunodeficiency Syndrome↗