PubMed Health⌕ Search

Biomedical subjects

R Kennett

Publications and source records attributed to R Kennett.

11 recordsLinked to original sources
PubMed1989

The effects of gamma interferon on the natural killer and tumor cells of children with neuroblastoma. A preliminary report.

Human neuroblastoma cells lack HLA-A,-B,-C molecules which can be induced in vitro by gamma interferon (gamma IFN). To test the hypothesis that the same induction would occur in vivo leading to tumor regression, a Phase I study was initiated. Seven patients with neuroblastoma were entered on a Phase I study of recombinant gamma IFN in children. Three received 0.05 mg/m2 intravenously (IV) three times a week, three received 0.1 mg/m2 for 4 weeks, and one patient withdrew from study before receiving adequate treatment for evaluation. No significant clinical response was seen. The side effects were fever and chills, and no serious toxicity occurred. Natural killer (NK) and lymphocyte activated killer (LAK) precursor activity of peripheral blood mononuclear cells was determined before and during treatment, and expression of HLA-A,B,C molecules was looked for on the tumor cells in the bone marrow of five patients. The NK activity initially low, reached control levels in six patients, but the increase was transient. The LAK precursor activity remained normal. Expression of HLA-A,B,C, initially absent, was induced on the neuroblastoma cells in four of six patients.

Antigens, Neoplasm↗
PubMed1989

Expression of HLA-DR mRNA in T cells following activation is early and can precede DNA synthesis.

The stimulation of T cells is accompanied by the appearance of a number of activation antigens not found on resting T cells. We have studied the expression of one group of such antigens, the HLA class II antigens (DR, DQ and DP), following stimulation with PHA and PMA. Immunofluorescence studies using monoclonal antibodies indicated that cell surface class II determinants were detectable as little as 30 minutes following stimulation, and that their levels remained constant for about 24 hours, after which they began to increase. Studies on the molecule level demonstrated an increase in the steady state levels of mRNA for DR beta by 15 minutes. Immunoblot analysis of resting T cell lysates using a monoclonal antibody reactive with DR detected a polypeptide of approximately 28 KDa, which agrees with the known molecular mass of the light chain of class II molecules on SDS-PAGE, suggesting that the rapid surface expression might have been due to the presence of pre-formed class II polypeptides. These results demonstrate 1) that T cells defined as resting by conventional criteria contain class II polypeptides and 2) that increases in steady state levels of class II mRNA is a very early event which precedes the initiation of DNA synthesis.

DNA Replication↗
PubMed1977

Assignment of the structural genes for the alpha subunit of hexosaminidase A, mannosephosphate isomerase, and pyruvate kinase to the region q22-qter of human chromosome 15.

Concordant segregation of the expression of the alpha subunit of human hexosaminidase A, human mannosephosphate isomerase, and pyruvate kinase was observed in somatic cell hybrids between either thymidine kinase-deficient mouse cells or thymidine kinase-deficient Chinese hamster cells and human white blood cells carrying a translocation of the distal half (q 22-qter) of the long arm of chromosome 15 to chromosome 17. A positive correlation was established between the expression of these human phenotypes and the presence of the distal half of the long arm of human chromosome 15.

Carbohydrate Epimerases↗
PubMed1976

Permanent lymphoid lines from genetically marked lymphocytes: success with lymphocytes recovered from frozen storage.

Permanent human lymphoid cell lines were established successfully from peripheral blood lymphocytes which had been separated for HL-A typing and stored in liquid nitrogen for two years. Frozen lymphocytes were chosen from two siblings who were homozygous at the LA and FOUR HL-A loci. Thawed lymphocytes were transformed with EB virus produced by the marmoset lymphoid line B95-8. No chromosome abnormalities were seen on karyotypes prepared on cells from the established human lymphoid lines using G and Q banding techniques. HL-A typing showed the expected HL-A antigens plus a considerable number of additional reactions. Separation of lymphocytes and freezing them for possible future use requires a relatively small investment. This method of preserving cells can be applied to patients with interesting genetic disorders or other biochemical markers to provide cells which can be transformed and propagated years later.

Blood Preservation↗
PubMed1975

Human intraspecific somatic cell hybrids: a genetic and karyotypic analysis of crosses between lymphocytes and D98/AH-2.

A number of human intraspecific hybrids were produced by fusing the 8-azaguanine-resistant cell line D98/AH-2 with PHA-stimulated lymphocytes from a normal human male, followed by selection in HAT medium. The parent cells differed in zymogram patterns for 4 enzyme systems. Hypoxanthine-guanine phophoribosyltransferase was missing in D98/AH-2 and was determined in the hybrids by the normal gene derived from the lymphocyte donor's X chromosome. The HL-A antigens of the lymphocyte donor as well as the W28 specificity from HeLa were easily recognized by a cytotoxicity assay on the hybrid cells, while D98/AH-2 itself was not killed in the normal way by any HL-4 typing sera. The initial hybrid karyotype in all lines was relatively stable, but slow loss of chromosomes occurred following extended growth in culture. The importance of the culture conditions for the rate of chromosome loss was demonstrated. The behavior of several chromosomes was followed in the hybrids and their derivatives. There was relatively nonspecific loss of small numbers of chromosomes, showing that loss of chromosomes from both the D98/AH-2 and the normal lymphocyte parent can occur. Cell lines resistant to 6-thioguanine were selected from the sensitive hybrids. Most had lost the lymphocyte donor's X chromosome, thereby losing the only active allele for HGPRT present in the initial hybrids. However, one line, DMR41, apparently retained the X chromosome and may have a mutated allele for HGPRT. Two lines that are the products of spontaneous segregation are also described. DM4CS and DM17A.

Acid Phosphatase↗
PubMed1971

Extrinsic Cotton effects in hapten--carrier and hapten--antibody interactions.

Two homogeneous univalent hapten-protein conjugates, prepared by the covalent attachment of a single 2,4-dinitrophenyl (DNP-) or 2,4,6-trinitrophenyl (TNP-) side chain to the cysteine-SH in the active site of the enzyme papain, have been found to exhibit large Cotton effects in the wavelength region of the absorption bands of the DNP or TNP groups. This indicates that the DNP or TNP groups are noncovalently bound to some asymmetric region(s) of the papain molecule. These homogeneous papain conjugates are antigens that can elicit anti-DNP or anti-TNP antibody production in mice or rabbits. It is suggested that the noncovalent binding of a hapten to the surface of its carrier protein may profoundly affect the characteristics of the anti-hapten antibodies that are elicited. It has also been observed that the specific binding of these papain conjugates, and of the simple haptens DNP-lysine or TNP-lysine, to anti-hapten antibodies produces characteristic extrinsic Cotton effects.

Antibody Formation↗