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Biomedical subjects

H R Gelderblom

Publications and source records attributed to H R Gelderblom.

At least 73 records · Page 4Linked to original sources
PubMed1990

Molluscum contagiosum associated with AIDS: a case report with ultrastructural study.

The clinical features of perioral molluscum contagiosum in a patient with the acquired immunodeficiency syndrome are described. Light microscopy and thin section electron microscopy revealed epidermal cells in different stages of degeneration showing two types of cytoplasmic inclusions. The basement membrane exhibited discontinuities and multiple laminations which may be a response to viral-induced cytotoxic effects.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Negative staining EM for the detection of Epstein-Barr virus in oral hairy leukoplakia.

The performance of two different EM techniques applied for the detection of Epstein-Barr Virus (EBV) in oral hairy leukoplakia (HL) was assessed, i.e. the conventional two-step method of negative staining (CNS) and negative staining after Airfuge enrichment (ANS). Scrape specimens from the lateral borders of tongue of 66 HIV-positive patients with or without HL, of 3 patients with infectious mononucleosis and of 10 HIV-negative patients were evaluated. While CNS resulted in virus detection only in 25% of clinically diagnosed HL cases, EBV was detected by ANS in 85% of clinically suspected cases of HL. Scrape specimens of individuals negative for HIV were negative in EM while 2 of 3 mononucleosis patients were positive without clinical evidence for HL. Due to this high sensitivity the method of negative staining after Airfuge enrichment appears to be useful in the diagnosis of HL. The finding of EBV in clinically normal oral mucosa in HIV-seropositive individuals is interesting and indicates that EBV expression may precede the clinical appearance of HL.

Adult↗
PubMed1990

Infection of the human monocytic cell line Mono Mac6 with human immunodeficiency virus types 1 and 2 results in long-term production of virus variants with increased cytopathogenicity for CD4+ T cells.

The recently established human monocytic cell line Mono Mac6 expressing distinct characteristics of mature monocytes/macrophages was tested for its susceptibility to infection with human immunodeficiency virus. Inoculation of the cells with the T-cell-tropic human immunodeficiency virus strains human T-lymphotropic virus type IIIB and lymphadenopathy-associated virus type 2 led to a noncytopathic productive infection becoming apparent only after a latency period of up to 56 days. The infectibility of the Mono Mac6 cells was dependent on low levels of CD4 expression, as demonstrated by blocking experiments with various CD4-specific antibodies. Increasing with time after infection (greater than 200 days), the cultured Mono Mac6 cells released virus variants which showed shortened latency periods when passaged onto uninfected Mono Mac6 cells. Also, cytopathogenicity for several CD4+ T cells of the Mono Mac6-derived virus was drastically increased; thus, the infection of the H9 cell line with low doses of virus (less than 0.1 50% tissue culture infective dose per cell) led to giant syncytium formation within 1 day and subsequent death of all fused cells. We propose Mono Mac6 cells as a new model for the study of human immunodeficiency virus infecting the monocyte/macrophage lineage, particularly with regard to virus-host cell interaction and the influence of cell differentiation and activation on latency and development of virulence. The human immunodeficiency virus-infected Mono Mac6 cell may also serve as a valuable tool for in vitro testing of antiviral therapies.

CD4 Antigens↗
PubMed1990

HIV: early virus-cell interactions.

Two entry mechanisms of HIV occur in both lymphocytes and macrophages incubated with purified virus suspensions: (a) direct fusion of the viral envelope with the cell membrane and (b) receptor-mediated endocytosis via clathrin-coated pits and vesicles. Both mechanisms are shown in detail in a time-interval series of electron micrographs. The two lipid bilayers of the viral envelope and of the cellular membrane usually fuse seamlessly within 1-3 min at 37 degrees C, but occasionally membrane ruptures occur, leading to rapid cytopathic effects, i.e., vacuolization and cytolysis only a few minutes later. In the course of virus-cell fusion, gp 120 is integrated into the cell membrane; subsequent syncytia formation was observed after 1 h of incubation. The core disintegrates and releases the viral ribonucleoprotein through the opening at the fusion site into the cytoplasm.

Adsorption↗
PubMed1989

Morphogenesis and morphology of HIV. Structure-function relations.

Fine structure and antigenic make-up analysis of HIV were combined in a 2D model, from which functional aspects can be deduced. On the envelope 72 probably trimeric surface knobs (gp120) are connected to the virion via the transmembrane protein gp41. Gp120 is shed during ageing of the virion, but host cell antigens stay firmly anchored to the envelope. Underneath the envelope, p17 forms the matrix protein layer, while the capsid of the double cone shaped core is built up of p24. The relation between biochemical findings and morphogenesis and maturation of HIV as well as aspects of pathogenesis and vaccination are discussed.

Forecasting↗
PubMed1989

Compartment-specific immunolocalization of conserved epitopes of the glycoprotein gB of herpes simplex virus type 1 and bovine herpes virus type 2 in infected cells.

Monoclonal antibodies directed against a surface glycoprotein of the bovine herpes virus type 2 (BHV-2, bovine herpes mammillitis virus) recognize also determinants of the major glycoprotein gB of the human herpes simplex virus type 1 (HSV-1). Cross-reacting antigens of the virions and in infected cells were localized with immunocytochemical methods, immunofluorescence as well as pre-embedding and cryoultramicrotomy immune electron microscopy. All antibodies stain to different degrees cell free BHV-2 and HSV-1 virions. In the cell two predominant staining patterns could be observed indicating that expression of epitopes is dependent upon the cell compartment: (i) staining of cytoplasmic membranes and enveloped particles within membrane systems and (ii) staining of intranuclear antigens. Antibodies tagging intranuclear antigens react with moderately dense material or with the periphery of nucleocapsids. This unexpected result is interpreted in terms of two hypotheses: (1) presence of common epitopes on two entirely different herpesvirus proteins conserved in HSV-1 and BHV-2 and (2) transport of gB or its precursor into the nucleus.

Animals↗
PubMed1989

Quaternary structure of the immunostimulating complex (iscom).

Proteins of either HIV-1, hepatitis B, or rabies virus were incorporated with the adjuvant substance Quil A and cholesterol into the immunostimulating complex: iscom. Formation and symmetry of this regular complex were analyzed by electron microscopy. Micellar structures with a diameter of about 12 nm, occasionally with a 7-nm stain-filled center, were formed in a 0.03% water suspension of Quil A. Cavities or holes appeared in the smooth structures of cholesterol upon the addition of Quil A, and after mixing Quil A and cholesterol 1:1 fragile and flattened structures of matrix were produced with a diameter of about 40 nm. By freeze-drying the matrix was preserved as a cage-like, isometric particle. Stable iscom particles composed of Quil A, cholesterol, and selected viral proteins had an approximate diameter of 32 nm. The particles had an uniform, cage-like structure, exhibiting icosahedral symmetry, irrespective of the viral proteins incorporated. Tilting experiments and rotational image analysis indicated that the iscoms were composed of 20 morphological subunits assembled in a pentagonal dodecahedron with a hole on each of the 12 pentagonal faces. The symmetrical shape of the iscom might explain both its remarkable stability and its capacity to efficiently present antigens to the immune system.

Adjuvants, Immunologic↗
PubMed1989

Oral hairy leukoplakia: observations in 95 cases and review of the literature.

Oral hairy leukoplakia (HL) was observed in 25.4% of 373 HIV-seropositive patients (n = 95). 87 were men of an average age of 37.1 yr, 8 were women (30.3 yr). 71.6% of the patients were male homosexuals. At initial diagnosis of HL the majority of cases was classified as CDC IVc1 (45.3%) and CDC II (22.1%). Average CD4/CD8 ratio (n = 19) was 0.24 with a range of 0.04-1.0. Thirty biopsies of HL revealed some of the histologic features thought to be characteristic. In only 20 of 30 biopsies EB-virus-specific-capsid antigen was detected. The problems of clinical and histological diagnosis of HL are discussed. Further strict criteria are necessary in order to define HL more distinctly.

Adult↗
PubMed1988

The organization of the envelope projections on the surface of HIV.

The organization of envelope projections (knobs) of four different isolates of the human immunodeficiency virus types 1 and 2 (HIV-1 and -2) was studied using surface replica and thin section electron microscopy (EM) in combination with rotational image enhancement. All HIV strains show an identical organization of knobs on the virus envelope. The surface of an "ideal", well-preserved HIV particle is studded with 72 knobs arranged in a T = 7 laevo symmetry. The role of the p 17 protein, which is coating the inner leaflet of the viral envelope, is discussed as a matrix protein functioning as a scaffold for the envelope and its projections during morphogenesis as well as with mature virions.

HIV↗
PubMed1988

Monoclonal antibodies directed against human immunodeficiency virus (HIV) gag proteins with specificity for conserved epitopes in HIV-1, HIV-2 and simian immunodeficiency virus.

Monoclonal antibodies (MAbs) were raised against gag proteins of human immunodeficiency virus type 1 (HIV-1), strain HTLV-IIIB. One of 29 antibodies was specific for p17 of HIV-1. Twenty of 28 MAbs reactive with the major core protein p24 of HIV-1 showed cross-reactivity with HIV-2, and five of these also detected the corresponding antigens of simian immunodeficiency virus (SIVmac). The MAbs were reactive in several tests, i.e. ELISA, immunostaining of Western blots, immunofluorescence, alkaline phosphatase-anti-alkaline phosphatase immunocytochemistry and immunoelectron microscopy. The submembrane protein p17 was clearly localized within the virion.

Animals↗
PubMed1987

Isolation frequency and growth properties of HIV-variants: multiple simultaneous variants in a patient demonstrated by molecular cloning.

The biological properties and efficiency of isolation of different HIV (LAV/HTLV III, ARV, and AAV) subtypes were evaluated by recovering and growing HIV on fresh peripheral human lymphocytes. Cultures for virus isolation were performed from more than 180 German AIDS, ARC, LAS, and virus-exposed asymptomatic patients. The virus isolation rate depended on the state of health of the patients being close to 80% in AIDS patients, 30-40% in ARC/LAS patients, and lower in asymptomatic HIV seropositive patients. The cytopathic effects of the HIV isolates obtained on lymphocyte-cell cultures ranged from no effect to marked syncytia formation and cytopathogenicity. Marked differences were also observed in the replication rate of the various isolates. These properties were stable in all in vitro passages of the viruses performed so far and allowed to tentatively define four subtypes of HIV. In the majority of AIDS cases with neurological symptoms well-growing strains were obtained from peripheral blood, while all but two isolates from the cerebrospinal fluid of the same patients grew remarkably slowly and to only low titres on lymphocytes, suggesting that selection of variants for growth at specific sites of the body occurs. For one of the most cytopathogenic strains the influence of several variables of culture conditions (cell type, corticosteroids, IL-2, and polybrene) on virus replication was studied. Apart from polybrene, all parameters strongly influenced replication.

AIDS-Related Complex↗
PubMed1987

Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins.

Ultrathin section and surface replica electron microscopy were applied in combination with immunoelectron microscopy to elucidate the fine structure of HIV. The shell of the tubular core shows p24 antigenicity, while p17 is located at the inner leaflet of the lipid membrane. The virus particle is studded with 70-80 protrusions. These knobs have a diameter of 15 nm, a height of 9 nm, and are probably arranged in a T = 7 I symmetry. The major envelope protein gp120 is spontaneously shed from the viral surface. A possible role of released gp120 in pathogenesis is discussed.

Cell Line↗
PubMed1987

Detection of HIV envelope specific antibodies by immunoelectron microscopy and correlation with antibody titer and virus neutralizing activity.

Human antisera positive for HIV were evaluated on HTLV-IIIB producing cells by two different immunoelectron microscopic (IEM) techniques. In preembedding immunoferritin IEM a heavy label was observed with early budding HIV. Under the same conditions cell released 'mature' particles were almost negative, which could be explained by the direct observation that most of the surface glycoprotein knobs are lost spontaneously during virus maturation. Using freshly infected cultures after agarose embedding, immunogold labelling of ultrathin cryosections allowed us to detect and differentiate internal core as well as virus envelope antigens. A good qualitative correlation between neutralization titers and IEM labelling intensity was observed. This type of immunocryoultramicrotomy appears to be useful for the detection of antigens in and on the virion. It might turn out valuable for the characterization of the env gp120 epitopes of HIV.

AIDS-Related Complex↗
PubMed1987

Ultrastructural findings in oral Kaposi's sarcoma (AIDS).

Ten biopsies of oral Kaposi's sarcoma were examined histologically and ultrastructurally. Histologically, early and late tumor stages could be differentiated. On the ultrastructural level, endothelial-like and spindle-shaped tumor cells were revealed. Tumor cells associated with vessel-like spaces showed partly interrupted basal membranes, Weibel-Palade bodies, desmosomes and tight-junctions, while spindle-shaped cells lacked these ultrastructural features of endothelial cells. Within the cytoplasm of endothelial-like cells, aggregates of tubular structures were observed. Histological and ultrastructural findings in oral Kaposi sarcoma are comparable to those of such other organs as skin and intestines. The ultrastructural findings indicate an endothelial origin, at least of endothelial-like tumor cells.

Acquired Immunodeficiency Syndrome↗