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Biomedical subjects

A Ravid

Publications and source records attributed to A Ravid.

61 records · Page 4Linked to original sources

Peanut agglutinin, a new mitogen that binds to galactosyl sites exposed after neuraminidase treatment.

Peanut agglutinin, purified by affinity chromatography, agglutinates lymphocytes from mouse, rat, guinea pig, and man only after their treatment with neuraminidase. However, it stimulates only neuraminidase-treated rat and human cells. A similar number cell surface receptors for peanut agglutinin was found on neuraminidase-treated rat and mouse lymphocytes although the latter cells were not stimulated by the lectin. Galactose specifically inhibited the agglutination and stimulation of lymphocytes by peanut agglutinin. Sequential treatment of lymphocytes with neuraminidase and beta-galactosidase markedly reduced the response of the cells to stimulation by peanut agglutinin, soybean agglutinin, and galactose oxidase. It is suggested that the same galactosyl residue may be the target for the initial step in triggering lymphocytes by the above mentioned mitogens.

Agglutination Tests↗

1,25-Dihydroxyvitamin D3 acts directly on human lymphocytes and interferes with the cellular response to interleukin-2.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) inhibits mitogen-induced lymphocyte proliferation in peripheral blood mononuclear cell preparations. Receptors for 1,25(OH)2D3 are present in monocytes and are acquired by lymphocytes upon activation. It is not clear whether the hormone inhibits lymphocyte mitogenesis by a direct action on the lymphocyte or only indirectly by affecting the regulatory monocytes. We addressed this question by using highly purified human lymphocyte preparations which contain less than 0.1% monocytes. 1,25(OH)2D3 inhibited the stimulation of purified lymphocytes by phytohemagglutinin and in the presence of fixed accessory cells, which cannot respond to 1,25(OH)2D3. The inhibitory effect attained 35% similar to that obtained in the presence of monocytes. 1,25(OH)2D3 inhibited interleukin 2 (IL-2)-driven stimulation of purified T cells in three different systems: cells treated with a submitogenic concentration of phytohemagglutinin, IL-2-dependent cells which bear receptors for IL-2 and naive cells in the absence of other mitogens. We conclude: (1) the human T lymphocyte is a direct target for 1,25(OH)2D3; (2) 1,25(OH)2D3 inhibits the response of activated, IL-2-receptor-bearing human T cells to interleukin-2.

Calcitriol↗

Separation of normozoospermic human spermatozoa into subpopulations by selective agglutination with peanut agglutinin.

Incubation of human spermatozoa of normozoospermic origin with the galactose specific lectin peanut agglutinin (PNA) resulted in agglutination of the majority of sperm. This finding enabled separation of sperm into two subpopulations. The major one, accounting for 87.0 +/- 12.7 (SD)% consisted of agglutinating sperm (PNA+), while the minor subpopulation (PNA-) did not bind the lectin. The correlation between the percentages of PNA- sperm and acrosome-damaged sperm, as detected by light microscopy prior to separation, was analysed and an overlapping has been found. Light and electron microscopy examination revealed that the PNA- cells were either acrosomeless or possessed severely damaged acrosomes while the PNA+ sperm were mostly free of such pathologies. Following treatment of sperm with fluorescin-conjugated PNA the single cells lacked any labeling while the agglutinates exhibited fluorescence. However, the binding of the lectin to sperm was non-uniform and differences in fluorescence intensity at various parts of the head have been observed. The sialic acid content in PNA+ sperm was found to be significantly higher (7.5 +/- 2.2 micrograms/10(8) sperm) as compared to PNA- sperm (2.1 +/- 0.6 micrograms/10(8) sperm). It was suggested that sialic acid content could be a biochemical indicator of acrosomal integrity. Separation of sperm by selective PNA agglutination might be valuable for elimination of sperm affected by acrosomal pathologies from the ejaculate.

Galactose↗

A high proportion of double-headed and double-tailed sperm in semen of a human male. A case report.

We present the case of a patient whose semen contained 30% of sperm with double heads and double tails at various stages of attachment due to abnormal meiosis. The genital system, sperm density, endocrinological profile and karyotype were normal. It is postulated that abundance of the above-noted type of sperm pathology in the human semen might not necessarily be associated with oligozoospermia or fertility impairment.

Adult↗

Separation of sub-populations of sperm with higher fertility potential from normal and pathological semen by peanut agglutinin.

Incubation of human sperm from semen with counts below 20 x 10(6)/ml with peanut agglutinin (PNA) resulted in agglutination of about 70% of sperm. An inverse correlation was found between non-agglutinating (PNA) sperm and sperm density (r = 0.48, p less than 0.01) and a direct correlation with acrosome-damaged sperm (r = 0.83, p less than 0.001). Binding of 125I-PNA to sperm revealed high, and possibly also low affinity binding sites on sperm from both normozoospermic and oligozoospermic origins. Quantitative transmission electron microscopy analysis revealed that agglutinated, PNA+, sperm had lower frequency of acrosomeless spermatozoa than PNA(-)-sperm (44% versus 77%) and higher fertility score (+0.18 +/- 0.1 and -1.5 +/- 0.87 respectively, p less than 0.01). Removal of PNA- sperm from oligozoospermic semen may increase the fertility score of the remaining sperm.

Cell Separation↗

Failure of thalidomide to inhibit tumor growth and angiogenesis in vivo.

Thalidomide was recently suggested to be angiogenesis-inhibitor following the demonstration of its activity in a rabbit cornea micropocket model. The purpose of the present study was to test its efficacy in solid tumors in mice. B16-F10 melanoma and CT-26 colon carcinoma cells were injected subcutaneously, intravenously and intraperitoneally, and mice received daily gavage of 0.3-1.0 mg thalidomide starting either two or 10 days following tumor cell injection. The tumors were measured and compared with controls. There was no growth retardation in CT-26 bearing mice nor in mice with pulmonary or peritoneal metastases of B16-F10 melanoma. In 3/7 groups of mice with SC B16-F10 tumors, growth retardation was demonstrated, however the difference was not statistically significant. All tumors eventually reached maximal size, similar to controls. Morphological evaluation of the blood vessels oriented towards the tumor revealed that in both thalidomide and control groups, all mice had developed an intact network of new blood vessels. In our model for the oral administration of thalidomide inhibition of tumor growth and angiogenesis did not occur. We hypothesize that the lack of sustained antiangiogenic response was either due to immune modulation or to tumor heterogeneity and adaptation.

Animals↗