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Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 271 records · Page 15Linked to original sources
PubMed1984

Detection of cytogenetic regions influencing RNA polymerase activity in Drosophila melanogaster by segmental aneuploid mapping.

In a search for loci with RNA polymerase related function, we have screened the Drosophila melanogaster genome for regions effective in eliciting a dosage response for total RNA polymerase activity using segmental aneuploids generated by the use of Y-autosome translocations. From this screen we have identified a total of six cytogenetically defined regions which elicit significant dosage response: a single X-chromosome region, 9C-11A, within which resides a known RNA polymerase locus and five noncontiguous regions on chromosome 3 with no previously identified RNA polymerase related function.

Age Factors↗
PubMed1984

Phase I clinical investigation of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887), a new purine antimetabolite.

9-beta-D-Arabinofuranosyl-2-fluoroadenine 5'-monophosphate (NSC 312887) is a new purine antimetabolite that has been evaluated in a Phase I clinical trial. The schedule of administration consisted of a single i.v. infusion over a period of 30 min once each day for 5 consecutive days, repeated at 4-week intervals. Thirteen patients received 30 courses of the drug in a dose range of 18 to 40 mg/sq m/day. Granulocytopenia and thrombocytopenia were dose limiting. Repeated courses produced similar degrees of granulocytopenia, but in 7 of 7 patients receiving 2 or more courses, the degree of thrombocytopenia was less severe during the first than during subsequent courses. Myelosuppression in humans was more severe than predicted from the mouse model. Lymphopenia was profound at all dose levels, but reversed within 3 weeks. Somnolence occurred during infusion in 8 of 13 patients, but quickly cleared after the infusion was completed. The infused drug was rapidly dephosphorylated in plasma and then cleared so there was no cumulation of drug in plasma when it was rapidly infused once each day in these doses. Phase II studies of 9-beta-D-arabinofuranosyl-2-fluoroadenine 5'-monophosphate are planned at a starting dose of 18 mg/ sq m/day for patients with prior chemotherapy or radiotherapy and 25 mg/sq m/day for those without prior therapy, as a single dose on each of 5 consecutive days repeated at 21- to 28-day intervals.

Adenocarcinoma↗
PubMed1983

Biosynthetic relationship between the major matrix proteins of adrenal chromaffin granules.

The matrix of the chromaffin granule contains a family of acidic proteins, collectively known as the chromogranins. It has been suggested that this family results from protease action on the major component, chromogranin A. Evidence for this has now been obtained from in vitro translation of adrenal medullary messenger RNA and immunoprecipitation of translation products using an antiserum directed against chromogranin A, but which also recognises other chromogranins.

Animals↗
PubMed1983

Synthesis of rat-liver lactate dehydrogenase and characterization of its mRNA.

Rat liver lactate dehydrogenase (LDH) has been synthesized in hepatocytes and in a cell-free translation system. The subunit synthesized in both systems displayed the same electrophoretic mobility upon sodium dodecyl sulfate/polyacrylamide slab gel electrophoresis. Sequence analysis of the subunits translated in vitro and synthesized in vivo indicated N-acetyl-alanyl-alanine for both N termini. Thus, the newly synthesized subunit does not exhibit an amino-terminal extension. The mRNA for the lactate dehydrogenase subunit was exclusively found in free polysomes. A size of 2120 +/- 240 nucleotides was estimated for the mRNA. Only about 50% of these nucleotides are needed to code for the polypeptide chain of the enzyme.

Amino Acid Sequence↗
PubMed1983

Subcutaneous culture chamber for continuous infusion of monoclonal antibodies.

Monoclonal antibodies allow the precise definition of molecular components present on tumour cell surfaces. Some human monoclonal antibodies prepared by fusing intratumoral lymphocytes from patients undergoing craniotomy for malignant glioma with cells from a specially derived human lymphoid line (LICR-LON-HMy2) bind to glioma surface components. To study the feasibility of continuous administration of human monoclonal antibodies directed against glioma we designed a chamber which enables hybridoma cells to be cultured in the subcutaneous tissue. This chamber allows antibodies to diffuse out, and nutrients and oxygen necessary for continued cell viability to diffuse in. Cells are unable to traverse the membrane pores of the device, so there is no risk that malignant cells put in the chamber can metastasise. The chamber has now been inserted in one patient with recurrent glioma, in whom the kinetics of internally labelled antibody release has been monitored.

Antibodies, Monoclonal↗
PubMed1983

Antimelanoma hybridoma antibodies against partially purified melanoma antigen.

We have immunised BALB/c mice with a melanoma antigen obtained after papain solubilisation of the membranes of a metastatic melanoma tumour and fused the immune spleen cells to the mouse myeloma line P3-NS1/1-Ag4.1. The produced hybridoma antibodies (Mel-PV antibodies) recognised the initial melanoma antigen in haemagglutination, but did not react with any of the HLA phenotypes tested by cytotoxicity on a panel of B lymphocytes with known HLA-A and B phenotypes. We rosetted red blood cells coated with protein A with dispersed cells from fresh melanoma tumours, and a high degree of specificity for human malignant melanocytes was observed. Purified Mel-PV antibodies were also tested by indirect immunofluorescence and found to be oriented towards cytoplasmic components of malignant melanoma cells. These results indicate that the use of melanoma antigens for preparing monoclonal antibodies maintained a satisfactory degree of specificity and may be an adequate starting point for defining common and specific antigenic determinants on human melanoma.

Animals↗
PubMed1983

Human hybridomas from patients with malignant disease.

Lymphocytes from 180 patients with a variety of malignant diseases were collected and fused with a human myeloma-derived line, LON-LICR-HMy2/CAM1. A total of 162 hybridomas was obtained. Only B lymphocyte markers were found on the surface of the fusion products. Flow cytometric analysis revealed a stably increased DNA content in the hybridoma cells. Some hybridoma supernatants were found to contain new Ig chains. Anti-tumour binding activity was found in 12 supernatants.

Antibodies, Monoclonal↗
PubMed1983

Localisation of malignant glioma by a radiolabelled human monoclonal antibody.

Human monoclonal antibodies were produced by fusing intratumoral lymphocytes from patients with malignant gliomas with a human myeloma line. One antibody was selected for further study after screening for binding activity to glioma cell lines. The patient from whom it was derived developed recurrent glioma. 1 mg of antibody was purified, radiolabelled with 131I, and administered intravenously. The distribution of antibody was determined in the blood, CSF and tumour cyst fluid and compared with that of a control human monoclonal immunoglobulin. Antibody localisation in the tumour was observed and confirmed by external scintiscanning.

Adult↗
PubMed1983

Detection of lymphocytes in malignant gliomas by monoclonal antibodies.

Lymphocytes are not present in normal brain but are known to infiltrate malignant gliomas. The reasons for this infiltration and the signals involved are not understood. The lymphocyte content of 15 malignant gliomas removed at time of surgery was studied, using monoclonal antibodies to T and B cell surface antigens and immunofluorescence. An average of 41% of infiltrating cells possessed surface Ig, with 21% bearing the common T cell marker. There was no evidence of oligoclonal restriction of light chain types.

Adolescent↗