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Biomedical subjects

N Hanna

Publications and source records attributed to N Hanna.

At least 127 records · Page 7Linked to original sources

Expression of metastatic potential of tumor cells in young nude mice is correlated with low levels of natural killer cell-mediated cytotoxicity.

Of 6- and 3-week-old nude mice given intravenous injections of murine tumor cells with well-defined metastatic properties, only the 3-week-old mice developed lung tumor colonies in significant numbers. The quantitative differences in metastatic potential among tumor cell lines injected into syngeneic recipients were also maintained following intravenous injection into young nude mice. Successful metastasis in 3-week-old nude mice is correlated with the low levels of natural killer cell activity detected in these young recipients. Boosting of the natural killer cell activity of 3-week-old nude mice by the administration of bacterial adjuvants and interferon inducers significantly inhibited metastasis formation. The differences in metastasis development could not be attributed to differences in the initial arrest of tumor cells in the pulmonary vascular bed, but rather to a better survival of the arrested cells in the lungs of 3-weeks-old nude mice as compared with 6-week-old counterparts. We concluded that low levels of NK cell activity are associated with increased incidence of experimental metastasis.

Animals↗

Role of natural killer cells in the destruction of circulating tumor emboli.

A close correlation was demonstrated between levels of host natural cytotoxic (NC) and/or natural killer (NK) cell activity and capacity to eliminate blood-borne tumor cells. The outcome of experimental metastasis of several tumors with defined biologic behavior was studied in syngeneic mice exhibiting low NK cell activity [3-wk-old normal mice and cyclophosphamide (Cy)-treated adult mice] and high NK cell activity (normal adult mice). An iv injection of metastatic tumor cells into 3-week-old or Cy-treated mice markedly enhanced experimental pulmonary metastasis. The increased incidence of metastasis in mice exhibiting low activity of NK cells was not due to enhanced tumor cell arrest in the lung but rather to increased tumor cell survival. Boosting the NK activity of 3-week-old, but not Cy-treated, mice with interferon inducers inhibited metastasis formation. The adoptive transfer of spleen cells from syngeneic mice or allogeneic nude mice that have high NK activity shortly before (but not after) iv tumor challenge abrogated the Cy-induced enhancement of metastasis. The reactive lymphoid cells were non-T, nonadherent to nylon wool, sensitive to Cy treatment, and endowed with a natural ability to kill tumor cells during a short (12-24 hr) period. The conclusions were that NC-NK cells are important in host defense against circulating tumor cells and therefore can prevent the development of tumor cells into metastases.

Adjuvants, Immunologic↗

Normal immunosuppressive protein inhibition of human and murine lymphoblastoid cell line proliferation.

Normal immunosuppressive protein, prepared from human plasma by DEAE-cellulose chromatography, inhibits DNA synthesis in human cell lines of lymphocytes of both T and B origin. It also inhibits [3H]thymidine incorporation in mouse cell lines. Normal immunosuppressive protein was able to inhibit the proliferation of these cells, although they were already transformed and had a high rate of DNA synthesis. On the other hand, it does not inhibit myeloid cells or fibroblasts.

Alpha-Globulins↗

Normal immunosuppressive protein purification and quantitative estimation experiments.

An improved method for the preparation and purification of normal immunosuppressive protein (NIP) is described. The purified material has a molecular weight between 10,000 and 25,000. Its biological and serological activity is approximately 10--20 times higher than that of the crude fraction. An antibody to normal immunosuppressive protein prepared in rabbits made the quantitative estimation of NIP by a haemaggluination inhibition test possible. Similarly, a very sensitive assay for the quantitative determination of NIP by its inhibitory effect on the proliferation of EL-4 tumor cells is also described. Eluates prepared from polyacrylamide gels were active in inhibiting EL-4 tumor cell proliferation and neutralized the anti-NIP activity in the haemagglutination inhibition test.

Animals↗

Normal immunosuppressive protein: in vitro inhibition of DNA synthesis in T and B lymphocytes and lymphoid cell lines.

The biologic activity of normal immunosuppressive protein (NIP) isolated from human plasma was studied. NIP was found to inhibit the proliferation of both T and B lympohcytes in vitro. It suppressed the DNA synthesis of normal mouse lymphocytes responding to the mitogens phytohemagglutinin and lipopolysaccharide, as well as the [3H]Thymidine and [3H]leucine uptake by T and B lymphoid cell lines of human and murine origin. The lymphoid specificity of NIP was demonstrated by showing that DNA and protein synthesis of normal and transformed fibroblasts and other nonlympohid cell lines was not affected by NIP treatment. Furthermore, by using lymphoid cell lines we were able to show that 1) NIP inhibits the process of ongoing DNA and protein synthesis; 2) the duration of the cells' exposure to NIP is crucial for obtaining optimal effect; and 3) the inhibitory effect of NIP is totally reversible.

Animals↗

Separation of rat pituitary thyrotrophic cells.

A method for the enrichment of live thyrotrophic pituitary cells is described. Pituitary glands of young male rats were removed into Earle's solution and dispersed in a 0.1% trypsin solution containing 0.5% bovine serum albumin, pH 7.2. Nylon fibres (25 microgram) were used for the separation of the thyrotrophic cells, by stringing them across a plastic frame which fitted a plastic Petri dish containing the cell suspension. The fibres were washed with light petroleum (b.p. 60--80 degree C) and carbon tetrachloride, hydrolysed with 3 M-HCL for 30 min at room temperature and washed with distilled water and phosphate-buffered saline (pH 7.2). The fibres were treated with thyrotrophin releasing hormone (TRH) alone or in the presence of soluble carbodiimide solution. After incubation for 1 h at room temperature, the fibres were transferred to a new Earle's medium and cells were released from the fibres by plucking them with a needle. The separated thyrotrophic cells were identified by radioimmunoassay and by electron microscopy. Using the above-mentioned methods, enrichment of thyrotrophic cells was obtained. Thus, the amounts of TSH, prolactin, LH and GH released, during 2 h of incubation, by 1.5 x 10(6) unseparated cells were 6.8 +/- 0.65, 4.1 +/- 0.47, 4.8 +/- 0.52 and 5.2 +/- 0.68 microgram respectively, while the same number of purified thyrotrophic cells released 76.1 +/- 0.42, 1.2 +/- 0.3, 0.6 +/- 0.35 and 1.6 +/- 0.22 microgram of the same hormones (means +/- S.E.M.).

Animals↗

Normal immunosuppressive protein: inhibitory effect on immune response against tumour cells.

Normal immunosuppressive protein isolated from human plasma was found to inhibit the generation of primary cytotoxic effector lymphocytes against allogeneic tumour cells in vitro. Total inhibition was observed when NIP was present during the early stages of the sensitization process. In contrast, the generation of secondary cytotoxic lymphocytes in vitro was only slightly inhibited even though large amounts of NIP were used. The inhibition of target cell lysis by sensitized lymphocytes required long preincubation of a relatively small number of effector cells with large amounts of NIP and was most significant when tested at low effector: target cell ratios. Under the same conditions NIP showed no inhibitory effect on the cytotoxic activity of immune macrophages. The present in vitro experiments suggest that NIP exerts its effect through inhibition of DNA synthesis and cellular proliferation and to a limited extent only, by inducing specific suppressor cells.

Alpha-Globulins↗

Study of a new anomaly of the vermilion border of the lip.

A new anomaly of the vermilion border of the lip is described in which part of the vermilion border is replaced by normal skin. Thirty-six cases are reported of this new anomaly, seven of which sought medical advice for this condition.

Adolescent↗

Comparison of the effect of various methods of dissociation on the protein composition of rat liver ribosomal subunits.

Rat liver ribosomes were dissociated into subunits using EDTA, sodium pyrophosphate, high concentrations of KC1, as well as by incubation with puromycin in presence of 0.5 M KC1. The subunits obtained were analyzed using the density gradient centrifugation technique and their ribosomal proteins were separated by means of two-dimensional polyacrylamide gel electrophoresis. The ribosomal protein patterns of the two subunits isolated using each of the dissociating method were compared to the protein patterns of monosomes prepared by puromycin treatment alone. Our results revealed that the use of chelating agents to dissociate the ribosomes resulted in the loss of some ribosomal proteins from the small subunit. On the other hand, the use of KC1 in high concentrations to dissociate the ribosomes did not appear to cause any major loss of proteins from the ribosomes except for some acidic proteins.

Animals↗