Atypical virus particles in HIV-1-associated persistent generalised lymphadenopathy.
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Deltaretrovirus↗
Biomedical subjects
S Gartner
Publications and source records attributed to S Gartner.
Risk of human immunodeficiency virus (HIV-1) infection among laboratory workers.
In a prospective cohort study of 265 laboratory and affiliated workers, one individual with no recognized risk factors for human immunodeficiency virus type 1 (HIV-1) infection was HIV-1 seropositive at the time of entry into the study. Molecular analyses of two HIV-1 isolates derived in two independent laboratories from a blood sample from this worker showed that the isolates were indistinguishable from a genotypic form of HIV-1 present in the H9/HTLV-IIIB cell line. Exposure to this strain of virus most probably occurred during work with concentrated virus or culture fluids from virus-producing cell lines under standard Biosafety Level 3 containment. Although no specific incident leading to this infection has been identified, undetected skin contact with virus culture supernatant might have occurred. This worker was the only one found to be positive among the subgroup of 99 workers who shared a work environment involving exposure to concentrated virus. The incidence rate of 0.48 per 100 person-years exposure indicates that prolonged laboratory exposure to concentrated virus is associated with some risk of HIV-1 infection, which is comparable to the risk for health care workers experiencing a needle stick exposure. While none of the ten workers with parenteral exposure to HIV-1 in this cohort became infected, a worker in another laboratory did seroconvert following an injury with a potentially contaminated needle. Strict Biosafety Level 3 containment and practices should be followed when working with concentrated HIV-1 preparations, and further refinement of the procedures may be necessary.
Acquired Immunodeficiency Syndrome↗
Role of mononuclear phagocytes and accessory cells in human immunodeficiency virus type I infection of the brain.
The cells responsible for persistence of viral infection in the brains of human immunodeficiency virus type I-positive individuals are most likely mononuclear phagocytes. The infection of other cell types within the brain is presumably the result of close interactions with HIV-I-producing cells of the mononuclear phagocytic lineage. During these interactions, both direct effects from HIV-I infection of brain cells as well as indirect mechanisms (namely the response of brain cells to the presence of virus-infected cells, particularly monocytes and macrophages) should be considered. In addition, the genomic variability of HIV-I could play a role in increasing the tropism of the virus for certain cell types.
Acquired Immunodeficiency Syndrome↗
Orbital T-cell lymphoma in human T-cell leukemia virus-I infection.
This is the first report of orbital involvement in systemic adult T-cell leukemia/lymphoma (ATLL). The etiologic agent of ATLL is the human T-cell leukemia virus-I (HTLV-I), the first retrovirus demonstrated to induce cancer in humans. The diagnosis of ATLL is based on characteristic clinicopathologic features in combination with serologic or virologic evidence of HTLV-I infection. Serum antibodies to HTLV-I were identified by immunofluorescent microscopy. Viral particles characteristic of HTLV-I were found in a culture of the patient's peripheral blood lymphocytes. The patient was a native of the Caribbean, one of the known endemic foci of HTLV-I infection. Adult T-cell leukemia/lymphoma should be considered in the differential diagnosis of orbital T-cell lymphomas.
Adult↗
Immunohistochemical, electron microscopic and in situ hybridization evidence for the involvement of lymphatics in the spread of HIV-1.
To investigate the role of the lymphatic vessels and the sinus systems of the lymph node in the spread of HIV-1, we evaluated 15 lymph nodes from patients with persistent generalized lymphadenopathy (PGL). Fifteen lymph nodes taken from patients with follicular hyperplasia not related to HIV-1 infection served as controls. Immunohistochemical and in situ hybridization techniques revealed infected cells within the sinuses and the efferent lymphatics of the PGL lymph nodes. In contrast, infected cells could not be detected within the walls of the high endothelial venules nor in the areas immediately adjacent. The parenchymal side of the marginal sinus was lined by a discontinuous endothelium. Macrophages and lymphocytes were located within the gaps of this endothelium. More importantly, when the enlarged follicle extended as far as the wall of the marginal sinus, the processes of follicular dendritic cells could be seen extending through the gaps into the lumen of the sinus. This suggests that these cells could transport antigens (including HIV-1) from the sinuses directly to the germinal centers. In addition, HIV-1 particles within cytoplasmic vacuoles were seen in infected macrophages located in the submarginal zone. Positive cells were also found in the extrafollicular lymphoid parenchyma, especially in the area between the marginal sinus and the follicles. The observed distribution of the virus-positive cells within the PGL lymph nodes strongly implicates the lymphatic vessels in the spread of HIV-1 infection.
Acquired Immunodeficiency Syndrome↗
Langerhans' cells are an actual site of HIV-1 replication.
Human epidermal Langerhans' cells (LC) are HLA-DR+/DQ+, CD1+, CD4+ dendritic antigen-presenting leukocytes. Based on the observation that in certain human immunodeficiency virus type 1 (HIV-1) infected individuals, LC are the only epidermal cells to react with monoclonal antibodies against HIV-1 isolate termed human T-lymphotropic virus IIIB/83 core proteins p17 and p24, we have proposed that LC can serve as a target for HIV-1. This contention was strengthened by the ultrastructural finding of HIV-1-like particles in the close proximity of LC and by the demonstration of signs of moderate to severe LC damage. Detailed electron microscopic analysis of skin and mucosal biopsies from an AIDS patient with p17/p24-positive LC now revealed not only mature HIV-1-like virions in the extracellular space surrounding LC and in intracytoplasmic LC vacuoles, but also developmental forms of HIV-1-like particles budding from LC surface membranes. Using peripheral blood derived monocytes/macrophages as targets for HIV-1 isolation, a virus isolate, designated human T-lymphotropic virus III WR-SK/86, was recovered from skin tissue from this patient by cocultivation and identified as unique by nucleic acid hybridization analysis. These findings now conclusively show that HIV-1 replicates in and is released from LC and support the concept that antigen-presenting cells (mononuclear phagocytes, LC) can serve as a reservoir for the acquired immunodeficiency syndrome virus.
AIDS-Related Complex↗
Isolation of HIV-1 from monocytes but not T lymphocytes.
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Acquired Immunodeficiency Syndrome↗
Drusen of the optic disk in retinitis pigmentosa.
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Eye Diseases↗
Virus isolation from and identification of HTLV-III/LAV-producing cells in brain tissue from a patient with AIDS.
Primary cultures from a brain biopsy specimen of a human T-cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) seropositive patient with progressive dementia contained small numbers of monocytoid cells and showed reverse transcriptase activity that persisted for as long as 100 days. Electron microscopy of these cells revealed the presence of HTLV-III/LAV virions. Subcultured cells removed from primary cultures by trypsinization were nonspecific esterase negative and did not express virus or show evidence of HTLV-III/LAV proviral sequences, while those remaining in the original flasks were nonspecific esterase positive and continued to produce virus. Virus from primary cultures was transmitted to peripheral blood-derived monocyte-macrophages and T cells. Virus production in T-cell cultures was transient while the monocyte-macrophages, like the primary cultures, produced virus for at least 120 days. Infection of several brain-derived cells with this and another HTLV-III/LAV isolate failed to demonstrate virus replication. These results indicate that the HTLV-III/LAV-infected cells recovered from the brain of this patient are cells of the mononuclear phagocyte series.
Acquired Immunodeficiency Syndrome↗
The role of mononuclear phagocytes in HTLV-III/LAV infection.
Cells with properties characteristic of mononuclear phagocytes were evaluated for infectivity with five different isolates of the AIDS virus, HTLV-III/LAV. Mononuclear phagocytes cultured from brain and lung tissues of AIDS patients harbored the virus. In vitro-infected macrophages from the peripheral blood, bone marrow, or cord blood of healthy donors produced large quantities of virus. Virus production persisted for at least 40 days and was not dependent on host cell proliferation. Giant multinucleated cells were frequently observed in the macrophage cultures and numerous virus particles, often located within vacuole-like structures, were present in infected cells. The different virus isolates were compared for their ability to infect macrophages and T cells. Isolates from lung- and brain-derived macrophages had a significantly higher ability to infect macrophages than T cells. In contrast, the prototype HTLV-III beta showed a 10,000-fold lower ability to infect macrophages than T cells and virus production was one-tenth that in macrophage cultures infected with other isolates, indicating that a particular variant of HTLV-III/LAV may have a preferential tropism for macrophages or T cells. These results suggest that mononuclear phagocytes may serve as primary targets for infection and agents for virus dissemination and that these virus-infected cells may play a role in the pathogenesis of the disease.
Acquired Immunodeficiency Syndrome↗
The relationship between retinal pigment epithelium and the choriocapillaris.
Absence of the choriocapillaris (CC) was observed histopathologically in human eyes with retinitis pigmentosa (RP). It was noted in areas where the overlying retinal pigment epithelium (RPE) was absent. Analysis of our material, as well as a review of the literature dealing with RP and related entities, as well as a number of other fundus disorders, suggested that the disappearance of the CC is secondary to REP degeneration. An experimental model using intravenous sodium iodate produced a similar sequence of events in the rabbit. We suggest that the RPE modulates structure and function of the CC. There is possibly a diffusable biochemical vascular modulation factor (VMF) which is required for normal CC fenestrae formation and maintenance, which is liberated by the normal RPE, and acts upon the vascular endothelium. Lack of VME causes the endothelium to lose its fenestrae and the vessel to occlude. This RPE-CC interaction is a further facet of the RPE which requires exploration in depth.
Aged↗
Pathology of retinitis pigmentosa.
Eyes from patients with retinitis pigmentosa were obtained at autopsy. They were processed in celloidin and examined by light microscopy. The earliest evidence of retinal degeneration occurred in the equatorial zone and then extended peripherally and centrally. In the eyes with the earliest involvement, a sequence could be demonstrated in the zone of transition from the less involved macula to the more degenerated retina at the equator. The probable order for the development of degenerative changes in our material appeared to be as follows: (1) migration of nuclei from the outer nuclear layer to the rod and cone layer and the outer plexiform layer; (2) degeneration and loss of photoreceptors and their nuclei in the outer nuclear layer; (3) loss of connecting fibers in the outer plexiform layer; (4) migration of the retinal pigment epithelium (RPE) into the retina, mainly around the blood vessels, but also as isolated balls and spots (this prominent feature, which characterizes the disease, is secondary and only follows the loss of the photoreceptors and their nuclei); (5) adhesion of the retinal to the retinal pigment epithelium or Bruch's membrane in spots or broad areas and; (6) possible transneuronal degeneration of some cells in the inner nuclear and ganglion cell layers. Gliosis of the disc was universal as was the presence of glial membranes from the disc extending over the posterior retina, especially prominent in the macular region. As the material was obtained from 16 to 35 years ago, we lack electrophysiologic and familial data and electron microscopy was not possible.
Adult↗
Long-term culture of normal and leukemic human bone marrow.
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Bone Marrow↗
Lange's folds: a meaningful ocular artifact.
Lange's fold is a postmortem artifact seen in enucleated eyes of infants and young humans. We also demonstrate its presence in young monkey eyes obtained at autopsy, but did not find it in the eyes of fetal monkeys removed by cesarean section and immediately preserved by freezing. The artifact is thought to occur in autopsy eyes due to the vitreous base and posterior lens zonules exerting traction upon the periphery of the retina. In the eyes of older humans the peripheral retina is firmly bound down to the subjacent retinal pigment epithelium following the loss of peripheral photoreceptors, and thus, Lange's fold cannot develop. Peripheral cystoid retinal degeneration was also noted in early infancy, became more prevalent with age, and was almost always noted by age 8 years.
Adolescent↗
Aging and degeneration of the human macula. 1. Outer nuclear layer and photoreceptors.
In a light microscopic study of the macula of 104 human eyes obtained at necropsy of patients aged 3 to 96 we found: (1) Displacement of nuclei from the outer nuclear layer into the outer plexiform layer occurred in small numbers early in life and markedly increased after age 30. (2) Displacement of nuclei from the outer nuclear layer to the layer of rods and cones was rare in early life but increased considerably after age 40. (3) Displacement of nuclei is probably secondary to shrinkage of their attached fibres and is associated with aging. (4) Displaced nuclei apparently undergo changes in size, shape, and chromatin content and may go on to necrosis. (5) Twenty-four of the 104 eyes studied had an obvious reduction in the numbers of nuclei in the outer nuclear layer and their photoreceptors in the macular zone. All were in eyes from patients over age 40. No concomitant defect was found in the subjacent pigment epithelium, Bruch's membrane, or the choriocapillaris. The loss of nuclei of the outer nuclear layer appears to be a primary retinal disorder associated with aging.
Adolescent↗
The induction of suppressor T cells by lipopolysaccharide in human peripheral blood lymphocyte cultures in the presence of fetal calf serum.
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Animals↗
Long-term culture of human bone marrow cells.
A method has been described for the long-term culture of human bone marrow cells in liquid medium. Hematopoiesis, as measured by the production of granulocytic-macrophage progenitor cells (CFUc), continued for at least 20 weeks and was dependent upon the presence of a marrow-derived adherent layer of cells. As in the case of murine marrow liquid cultures, the adherent layer consisted of mononuclear phagocytic cells, endothelial cells, and lipid-laden adipocytes, the latter being essential for long-term hematopoiesis. Optimal growth conditions included McCoy's medium supplemented with fetal bovine serum, horse serum, and hydrocortisone and incubation at 33 degrees C. Horse serum in conjunction with hydrocortisone appeared essential for the growth of adipocytes.
Adipose Tissue↗