Angiogenic properties of Kaposi's sarcoma-derived cells after long-term culture in vitro

Cells derived from lung biopsies and pleural effusions from AIDS patients with Kaposi's sarcoma (KS) of the lungs were established in long-term culture with the aid of conditioned medium from HTLV-II-transformed T cells (HTLV-II CM). These AIDS-KS cells were similar to the so-called spindle cells in KS lesions and had some of their features. They produced factors that supported their own growth (autocrine) and the growth of other cells (paracrine), including umbilical vein endothelium and fibroblasts. That the AIDS-KS cells also expressed potent angiogenic activity was demonstrated by the chorioallantoic membrane assay and by subcutaneous inoculation of AIDS-KS cells into nude mice, which resulted in the development of angiogenic lesions composed of mouse cells and showing histological features similar to those of human KS lesions. These data suggest that AIDS-associated KS and possibly other types of KS may be initiated by signals that induce the growth of particular cells (spindle cells of lymphatic or vascular origin) and the expression of autocrine and paracrine activities.     

The use of animals in research

A law professor, who was a member of the National Academy of Sciences/National Research Council committee which authored The Use of Laboratory Animals in Biomedical and Behavioral Research, argues that political attacks by animal rights organizations constitute the most important practical aspect of this issue because they lead to restrictions that severely inhibit the ability of researchers to afford the use of animals. Researchers and "patient groups" must be mobilized to struggle against these organizations in order to prevent a disaster from overtaking biomedical research in the United States.     

Antibodies to the core protein of lymphadenopathy-associated virus (LAV) in patients with AIDS

Lymphadenopathy-associated virus ( LAV ), a human T- lymphotrophic retrovirus isolated from a homosexual man with lymphadenopathy, has been causally associated with acquired immunodeficiency syndrome (AIDS). A sensitive and specific radioimmunoprecipitation test was developed for the detection of antibodies to the major core protein of LAV , p25 (molecular weight 25,000). Antibody to LAV p25 was found in the serum of 51 of 125 AIDS patients, 81 of 113 patients with lymphadenopathy syndrome, 0 of 70 workers at the Centers for Disease Control (some of whom had handled specimens from AIDS patients), and 0 of 189 random blood donors. Of a group of 100 homosexual men from San Francisco whose serum was obtained in 1978, only one had antibody to LAV p25; in contrast, of a group of 50 homosexual men in the same community whose serum was obtained in 1984, 12 had antibodies to LAV p25.     

Polypeptide-binding membrane receptors: analysis and classification

Polypeptide receptors on mammalian plasma membranes can be categorized on the basis of function. The binding of ligand by class I receptors results in changes in cell metabolism or behavior. Hormone-receptor interactions typify this group. The binding of ligand by class II receptors in ligand internalization. Although changes in cellular activity may result from metabolism of the internalized ligand, the interaction between ligand and class II receptor does not itself lead to alterations in cell behavior. Class II receptors include those for low-density lipoproteins and for alpha-macroglobulin-protease complexes. Although receptors within each category are chemically disparate, they show striking similarities in behavior. Analysis of the behavioral patterns of receptors in each category reveals insights into receptor physiology and allows for a prospective analysis of receptor characteristics.     

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.     

Limulus lateral eye: properties of receptor units in the unexcised eye

Single receptor units in the compound eye of the horseshoe crab were illuminated, and their impulse discharges were recorded without removing the eye from the animal. The receptors were spontaneously active in darkness and responded without saturation over a light intensity range of 10(10) to 1. When the eye was excised, the receptors did not discharge in darkness and had an intensity range of 10(5) to 1, as is usually found. Experiments show that these and other differences result from cutting off the blood supply to the eye when it is excised. In addition, the range and shape of the intensity characteristic suggest that more than one receptor mechanism encodes light intensity in this eye.     

Clonal depletion in neonatal tolerance

Specific unresponsiveness can be induced in neonatal and adult BALB/c mice by antibody against antigen-specific receptor (antireceptor antibody). When heterologous antireceptor antibody is used in the indirect fluorescence technique, the number of fluorescent cells in these animals is significantly lower than in normal animals. Fluorescent cells appear after a relatively brief incubation of cells from adult-suppressed animals, whereas no fluorescent cells are detected when cells from neonatally treated animals are incubated briefly. Evidently, treating neonatal mice with antireceptor antibody specifically depletes the antigen-responsive clone. In contrast, antireceptor antibody causes reversible blockade of responsive cells in adult-suppressed animals.