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Biomedical subjects

S Zolla-Pazner

Publications and source records attributed to S Zolla-Pazner.

At least 127 records · Page 7Linked to original sources
PubMed1989

Human immunodeficiency virus-infected T cells and monocytes are killed by monoclonal human anti-gp41 antibodies coupled to ricin A chain.

Two human monoclonal antibodies specific for the envelope glycoprotein (gp), gp41, of the human immunodeficiency virus were conjugated to deglycosylated ricin A chain. These immunotoxins killed human immunodeficiency virus-infected H9 (T cell) and U937 (monocyte) cell lines but were nontoxic to the uninfected cell lines or to class II-positive Daudi cells. Specific killing of infected H9 cells could be completely blocked by recombinant gp160 and partially blocked by unconjugated anti-gp41 antibody but was not blocked by recombinant gp120 or human IgG demonstrating specificity for gp41. The specific toxicity of the immunotoxins for infected U937 cells was markedly potentiated by chloroquine.

Antibodies, Monoclonal↗
PubMed1989

AIDS: a syndrome of immune dysregulation, dysfunction, and deficiency.

Acquired immune deficiency syndrome (AIDS) is a disease caused by the human immunodeficiency virus (HIV) in which cellular immune functions are severely impaired. Acute infection and subsequent destruction of helper T cells, although occurring readily in cell cultures, do not appear to be the only mechanisms mediating helper T cell loss. Other mechanisms that may account for the loss of helper T cells include: T cell syncytia formation, decreased T cell production, and autoimmune-related destruction of helper T cells. Immune abnormalities seen early in the course of HIV infection include immune hyperactivation and autoimmune phenomena suggestive of immune dysregulation rather than immune deficiency. Many changes in immune function are, in fact, seen in HIV-seropositive patients who possess a normal number of helper T cells. Mechanisms (other than the loss of helper T cells) that may contribute to the immune abnormalities seen in these patients include noninfectious effects of HIV and HIV proteins, effects of HIV on non-T cells, autoimmune-related manifestations of HIV infection, and HIV-induced activation of normal immunosuppressive circuits.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Oligomeric structure of gp41, the transmembrane protein of human immunodeficiency virus type 1.

We characterized the structural forms of the human immunodeficiency virus env-encoded proteins with a panel of monoclonal and polyclonal antibodies. Western blot (immunoblot) assays with antibodies specific for gp41 invariably recognized a major component of 160 kilodaltons and a less intense component of 120 kilodaltons in viral lysates. We demonstrated that these species are noncovalently associated tetramers and trimers of gp41 which represent the native form of this protein in virions. These complexes were stable when boiled in the presence of low concentrations of sodium dodecyl sulfate but were dissociated to gp41 monomers at high sodium dodecyl sulfate concentrations. Moreover, two human monoclonal antibodies preferentially recognized the oligomeric complexes over monomeric gp41 in Western blots, indicating the presence of epitopes recognized by the human immune system on the gp41 multimers which are not efficiently expressed by the dissociated monomers. The demonstration of the existence of multimeric env complexes and the enhanced and altered antigenicity of such multimers may be relevant to the design of subunit and recombinant human immunodeficiency virus env vaccines.

Antibodies, Monoclonal↗
PubMed1988

Association of human immunodeficiency virus infection and autoimmune phenomena.

Patients infected with human immunodeficiency virus have a variety of presentations including fevers, lymphadenopathy, rash, renal dysfunction, and neurologic and hematologic disorders. Many of these features are also seen in patients with systemic lupus erythematosus (SLE). Herein are described five patients ultimately diagnosed as having acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC) in whom the differential diagnosis included SLE because of multi-system disease and autoimmune phenomena, especially positive antinuclear antibodies. Serum samples from 151 consecutive patients with AIDS or ARC were examined and 19 with low titer-positive antinuclear antibodies were found (17 at 1:20 and two at 1:160). These observations suggest that SLE and human immunodeficiency virus infection may share clinical and serologic features.

AIDS-Related Complex↗
PubMed1988

B-cell activation in HIV infection: relationship of spontaneous immunoglobulin secretion to various immunological parameters.

Peripheral blood mononuclear cells from HIV-infected individuals spontaneously secrete elevated levels of IgG, IgM and IgD. This increased level of synthesis and secretion is similar in HIV-infected subjects with no or few symptoms, in ARC patients and in AIDS patients. Thus, abnormal B-cell activation is characteristic of patients with mild as well as severe manifestations of HIV infection. The level of spontaneous cellular secretion of IgG, IgM and IgD correlates with serum levels of these isotypes. Levels of spontaneous cellular secretion of IgG and IgM correlate negatively with the percentage but not with the absolute number of T4-positive cells and correlate positively with the percentage but not with the absolute number of T8-positive cells. The data suggest that the proportional distribution of these T-cell subsets is a critical factor in the B-cell dysregulation leading to overproduction of IgG and IgM. On the other hand, spontaneous IgD secretion correlates with neither the percent nor the absolute number of T4 or T8 cells suggesting that the increase of IgD-secretion by B cells is independent of the T-cell defects. The data imply that more than one mechanism underlies the B-cell activation in HIV-infected individuals.

AIDS-Related Complex↗
PubMed1987

Control of B cell proliferation: arrest of B cells in late G1 underlies immunosuppression induced by plasma cell tumors.

Immunosuppression in mice bearing plasma cell tumors (PC-mice) provides a model system for the study of negative B cell regulation. Our previous studies demonstrated that B cell proliferation is suppressed in these mice by a cascade of interactions involving macrophages and soluble factors. The present report pinpoints the G1 phase of the cell cycle as the stage of B cell proliferation inhibited in PC-mice. Modulation of surface immunoglobulin (sIg) with anti-mu, an early membrane activation event, occurred normally on B cells from the spleens of PC-mice. However, examination of the size profile and the expression of sIgD and sIgM on B cells from the spleens of PC-mice showed an accumulation of large-sized, low intensity sIgD+ cells, suggesting a block in B cell activation in the late G1 phase of the cell cycle. This was confirmed by experiments in vitro that demonstrated that although LPS-stimulated B cells from the spleens of PC-mice enlarged to a size characteristic of G1 phase, most did not additionally enlarge into S phase even after 3 days of culture, nor did they incorporate significant amounts of [3H]thymidine. Additional confirmation of a block in late G1 was obtained by using analysis of [3H]thymidine incorporation, cell size, and cell cycle after normal cells were cultured in supernatants from cloned PC lines containing the factor(s) that initiates the cascade of events leading to suppression of B cell proliferation. The relevance of these findings to PC-induced immunosuppression and to the regulation of normal B cell proliferation during the G1 phase of the cell cycle is discussed.

Animals↗
PubMed1987

Potential use of serotherapy in the prevention and treatment of infection with the human immunodeficiency virus.

While prevention of infection with the human immunodeficiency virus (HIV) using prophylactic immunization and treatment with anti-viral drugs would appear to be the methods of choice for the prevention and treatment of this infection, neither safe and effective vaccines nor anti-viral agents have yet been developed. A third approach should thus be considered which could be employed both for prophylaxis and treatment of this disease. This approach utilizes specific, anti-HIV antibodies, passively administered, to prevent and/or slow the infectious process. The disadvantages of using xenogeneic antibodies and the advantages of using human antibodies are discussed. The need for large quantities of human antibodies to HIV necessitates the production of cell lines producing these antibodies. The various techniques of producing these lines are summarized. Finally, preliminary data supporting the feasibility of producing human cell lines producing antibody to HIV are presented.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Nonrandom development of immunologic abnormalities after infection with human immunodeficiency virus: implications for immunologic classification of the disease.

Blood specimens from 165 intravenous drug users who were seropositive for the human immunodeficiency virus (HIV), from 158 seropositive homosexual men with lymphadenopathy, and from 77 patients with acquired immunodeficiency syndrome (AIDS) were assessed immunologically. Immunologic parameters were analyzed by the Guttman scalogram technique to determine if immunologic abnormalities occurred in a nonrandom pattern. The following four patterns emerged: (i) seropositivity for HIV with no immunologic abnormalities; (ii) seropositivity for HIV with a depressed T4/T8 cell ratio; (iii) seropositivity with a depressed T4/T8 cell ratio and T4-cell depletion; and (iv) seropositivity with a depressed T4/T8 cell ratio, T4-cell depletion, and lymphopenia. Ninety-two to 100% of subjects in each of the three groups of patients were found "to scale" because the abnormalities occurred in the cumulative, ordered fashion described. This nonrandom occurrence of abnormalities indicates an ordered progression of immunologic abnormalities in individuals infected with HIV, a finding useful in the staging of both symptomatic and asymptomatic HIV-seropositive subjects.

AIDS-Related Complex↗
PubMed1987

Detection of HTLV-III antibody in cerebrospinal fluid from patients with AIDS and pre-AIDS with the use of a commercial test system.

Sixty-one paired sera and cerebrospinal fluid (CSF) specimens were tested for the presence of human T-cell lymphotropic virus/lymphadenopathy-associated virus (HTLV-III) antibodies. Of 16 sera negative for HTLV-III antibodies by enzyme-linked immunosorbent assay (ELISA), the corresponding CSF results were also negative. Forty-two of 45 (93%) CSF specimens tested (in which the corresponding sera were HTLV-III antibody positive) were positive by ELISA. Western blot analysis (WB) of 24 paired specimens, as well as retrospectively acquired case histories, confirmed the results obtained by ELISA.

AIDS-Related Complex↗
PubMed1987

Serum IgD elevation is an early marker of B cell activation during infection with the human immunodeficiency viruses.

Serum IgD levels in individuals infected with the human immunodeficiency viruses (HIV) were studied as a means of monitoring the character and timing of B cell activation in individuals with this infection. Significantly increased levels of IgD were characteristic of homosexual men who were HIV seropositive but asymptomatic or mildly symptomatic. The hyper IgD globulinaemia became progressively more pronounced in patients with increasingly severe infection and reached its most marked level in patients with AIDS-related complex (ARC). In ARC patients, IgD levels were increased 8.8-fold above normal which was disproportionately greater than the 2.4-fold increase in IgG, the 1.8-fold increase in IgA and the 1.6-fold increase in IgM. IgD levels declined in AIDS patients (although remained elevated compared to controls). The data suggest that an unusual type of B cell activation is responsible for the unique pattern of hypergammaglobulinaemia seen in this disease and that the B cell activation occurs early in the pathogenesis of HIV infection, often before development of symptoms, and continues throughout the course of infection.

AIDS-Related Complex↗
PubMed1986

Immunosuppression and infection in multiple myeloma.

Patients with multiple myeloma are at increased risk of severe bacterial infection. A variety of immune deficits has been described in such patients, including a decreased primary antibody response and defects in complement and granulocyte function. The depressed humoral response appears to result primarily from the activity of suppressor monocytes. Pneumovax (Merck Sharp & Dohme, West Point, Penn) should be administered to patients with myeloma, although its effectiveness in this population has not been proven. The role of other potential modalities of treatment and prophylaxis, such as IV gamma globulin, requires further study.

Bacterial Infections↗
PubMed1985

The acquired immunodeficiency syndrome: an ultrastructural study.

Blood and a variety of tissues from 97 patients with the acquired immunodeficiency syndrome (AIDS) and 25 with the AIDS prodrome were studied ultrastructurally. Tubuloreticular structures (TRS) were found in 85 per cent of the patients with AIDS and in 92 per cent of those with the prodrome. Test tube and ring-shaped forms (TRF), found in 41 per cent of the patients with AIDS and in 8 per cent of those with the prodrome, increased with disease progression. Among the patients with AIDS, as the number of sites examined per case increased, the incidence of TRS and TRF tended to approach 100 per cent, suggesting that they are present in all patients with AIDS. Other changes seen frequently were immunologic capping of blood lymphocytes, intramitochondrial iron in blood reticulocytes and marrow normoblasts, megakaryocytic immaturity and platelet phagocytosis, collections of membranous rings in hepatocytic cytoplasm, suggestive of non-A, non-B hepatitis, and proliferations and engorgement of hepatic Ito cells with lipid. The data suggest that TRS and TRF can be used as diagnostic and prognostic markers.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Control of B cell proliferation: inhibition of responses to B cell mitogens induced by plasma cell tumors.

A multitude of factors has been described that positively and negatively regulate B cell proliferation. A model system for the study of negative control of B cell function is provided by mice bearing plasmacytomas (PC-mice). In PC-mice, the primary immune response, as measured by development of antibody-forming cells (AFC), is severely suppressed. The present report specifically identifies a block in B cell proliferation as the apparent cause of this reduction in AFC production. Thus, the proliferative response of B cells from the spleens of PC-mice (PC-spleens) was significantly impaired when stimulated with four different B cell mitogens (lipopolysaccharide, Salmonella typhimurium mitogen, anti-mu conjugated to Sepharose, and 8-mercaptoguanosine). Nevertheless, the mitogen-responsiveness of these B cells was recovered when they were segregated by various methods from macrophages. These data suggest that the proliferative ability of the B cells in PC-spleens is inherently normal. In concordance with this conclusion, it was shown that suppressor cells from PC-spleens can block the proliferation of normal B cells derived from nontumor-bearing mice. This inhibition does not require direct cell contact and is mediated via soluble factors. The relevance of these results to previous studies of PC-induced immunosuppression and to the control of normal B cell proliferation is discussed.

Animals↗
PubMed1984

Quantitation of beta 2-microglobulin and other immune characteristics in a prospective study of men at risk for acquired immune deficiency syndrome.

Serum samples from 24 patients with acquired immune deficiency syndrome (AIDS) and from 15 patients with an early or milder form of this disease ("suspected AIDS") were found to contain elevated levels of beta 2-microglobulin (beta 2M). Therefore, prospective studies of 40 asymptomatic homosexual men from New York City were undertaken to determine whether quantitation of beta 2M and other immunologic variables was useful in recognizing those in populations at high risk for this disease who have a high probability for experiencing symptoms consistent with AIDS. After 20 to 26 months of follow-up, two of those persons now have AIDS and four have suspected AIDS. All six of these persons had elevated serum beta 2M levels and other immunologic abnormalities when they entered this study. Of those tested, only one other man had an increased level of beta 2M; neither he nor any of the remaining 33 persons in this group developed AIDS.

Acquired Immunodeficiency Syndrome↗