Search PubMed⌕ Search

Biomedical subjects

M Crawford

Publications and source records attributed to M Crawford.

At least 127 records · Page 7Linked to original sources
PubMed1989

1-Hydroxy-3-aminopyrrolid-2-one (HA-966) and kynurenate antagonize N-methyl-D-aspartate induced enhancement of [3H]dopamine release from rat striatal slices.

Excitatory amino acid receptors, including those of conventional N-methyl-D-aspartate (NMDA) type, are believed to be located on terminals of the nigrostriatal dopaminergic projection in the rat. Activation of these receptors enhances depolarization-induced dopamine release. Rat striatal slices were preloaded with [3H]dopamine (DA) and its subsequent release and possible modulation during excitatory amino acid receptor activation were investigated. Superfusion of slices with K+ (20 mM) produced a robust increase in [3H]DA release, which was markedly enhanced by the inclusion of N-methyl-D-aspartate (NMDA) or NMDLA in the buffer. No enhancement was observed following addition of glycine, suggesting that either the glycine binding site on the NMDA receptor complex was lacking, or that it was tonically fully activated. The latter appears to be the case since 1-hydroxy-3-aminopyrrolid-2-one (HA-966) (a purported antagonist at strychnine-insensitive glycine receptors) was able to antagonize the NMDA-induced enhancement of [3H]dopamine release. This action of HA-966 could subsequently be reversed by inclusion of glycine in the medium. While the action of NMDA was readily prevented by the inclusion of the competitive antagonist 2-amino-7-phosphonoheptanoate (AP7), this antagonism could not be reversed by either glycine or D-serine. Kynurenate behaved in an apparently identical manner to HA-966. Strikingly, the enhancement of dopamine release by kainate was unaffected by HA-966. These data indicate that NMDA receptor-mediated enhancement of [3H]DA release from striatal dopaminergic terminals can be modulated through strychnine-insensitive sites.

Animals↗
PubMed1989

Lymphoid neoplasia and the control of haemopoietic differentiation.

Our broad aims are to delineate oncogenic events in lymphoid neoplasia and to search for genes that control haemopoietic differentiation. To explore lymphoid neoplasia, we have constructed transgenic mice bearing different oncogenes coupled to the immunoglobulin heavy chain enhancer (E mu), to force expression within lymphocytes. The prototype E mu-myc mice are highly prone to lymphomagenesis, generating pre-B and B cell lymphomas. In their pre-neoplastic phase, E mu-myc expression perturbs B cell development, accelerating the accumulation of pre-B cells. Lymphomagenesis requires additional oncogenic events, such as ras activation, and can be reconstructed in vitro. Transgenic mice bearing the N-myc, N-ras, v-abl and bcr-v-abl oncogenes are also prone to tumours. A striking demonstration that oncogenes can perturb lineage commitment has emerged. Introduction of the v-raf gene into cloned E mu-myc transgenic B cells frequently led to a switch in haemopoietic lineage: the cells became macrophages. Two clues to this remarkable metamorphosis are that the macrophage lines produce a myeloid growth factor and most bear marked karyotypic alterations, perhaps indicating that the balance between a few critical lineage control genes has been disturbed. To explore the hypothesis that genes encoding the DNA-binding homeo box domain participate in haemopoiesis, cDNA libraries from haemopoietic sources were screened, and several distinct homeo box cDNAs were isolated. They revealed a complex pattern of expression among haemopoietic cell lines. These genes are attractive candidates for regulators of haemopoietic differentiation.

Animals↗
PubMed1989

Phase II study of combination 4'-epidoxorubicin and mitomycin C in recurrent epithelial ovarian cancer.

Thirty-three evaluable patients who had epithelial ovarian cancer that had not responded to treatment were entered into a phase II study of combination epirubicin and mitomycin C. Epirubicin (65 mg/m2) and mitomycin C (4 mg/m2) were administered separately, each as an i.v. bolus every 4 weeks. Ten patients (30%) had a complete or partial responses. The median duration of response was 20 weeks (range, 9-53). The regimen was well tolerated. Myelotoxicity occurred in four patients requiring hospitalization for septicaemia. Eleven patients had a blood transfusion. Alopecia was common, and nausea and vomiting, though frequent, usually mild. Cardiological toxicity was observed in one patient only. She developed congestive cardiac failure after an acute myocardial infarction. This regimen is active in advanced ovarian cancer that has not responded to prior treatment and warrants further study combination with other active drugs as a first-line regimen for ovarian cancer.

Adult↗
PubMed1989

A bcr-v-abl oncogene induces lymphomas in transgenic mice.

In chronic myeloid leukemia and some cases of acute lymphoblastic leukemia, a 9;22 chromosome translocation has fused most of the c-abl oncogene to a gene designated bcr. To explore in vivo the biological effects of the chimeric gene, we introduced a facsimile of the translocation product, a bcr-v-abl gene, into the mouse germ line under the control of the immunoglobulin heavy-chain enhancer or a retroviral long terminal repeat. Some transgenic mice bearing either construct developed clonal lymphoid tumors. T lymphomas predominated, but some pre-B lymphomas developed. The transgenes were expressed in the tumors but not detectably in the lymphoid tissues of nontumorous transgenic animals, implying that transcription is activated by a low-frequency somatic event. These results demonstrate that bcr-v-abl is tumorigenic in vivo and provide a new animal model for lymphomagenesis.

Animals↗
PubMed1989

Anti-class II antibody production prolongs renal allograft survival.

It is widely accepted that transfusions are beneficial to the outcome of renal allotransplantation. Whereas some investigators suggested that transfusions may induce both specific and nonspecific suppression of the cell-mediated immune response, others disagree. To lend clarity to this discrepancy, we collected 40 serum samples before and after blood transfusion therapy of first-time cadaveric renal allograft recipients and evaluated each for T cell and B cell cytotoxic antibodies using an Amos modified complement-dependent microlymphocytotoxicity assay. When greater than 10% of the panel cells reacted with a grade 4 or better, the panel was considered significant, and when a lymphocyte specificity was lysed by antibody-rich serum greater than 50% of the time, the antibody was considered specific. Control T and B cell PRA assays employed sera from 27 normal nontransfused volunteers of similar age and sex. Survival distributions of differences in the PRA before and after blood transfusions and posttransfusion PRA levels were compared using the Gehan generalized Wilcoxon test. Other factors which influence allograft survival such as HLA-A, -B and -DR matches, number of blood transfusions, immunosuppressive therapy, age, sex, parity, previous positive crossmatch, circulating cytotoxic antibodies matching the graft, prior dialysis, length of time on the waiting list, lapse of time between transfusion and transplantation and the underlying primary diagnosis were also considered using the Gehan generalized Wilcoxon test or the chi 2 approximation. Transfusion-related B cell cytotoxic antibodies, HLA-DR monospecific or multispecific antibodies and HLA-A, -B matching extended graft survival in a significant manner. Sex influenced the production of B and T cell transfusion-related cytotoxic antibodies with females producing greater quantities of antibodies than males. Parity and the production of monospecific or multispecific antibody were associated with an increase in transfusion-related B cell cytotoxic antibody. A difference in sex was not linked to the production of monospecific or multispecific HLA-DR antibodies. The majority of males failed to respond to multiple blood transfusions with the production of B cell cytotoxic antibodies although more than half were successfully grafted. All females and males who responded with the production of B cell cytotoxic antibodies monospecific or multispecific, with the exception of 1 female, demonstrated an allograft survival of greater than 1 year. In conclusion, differences between pre- and post-transfusion B cell PRAs and monospecific or multispecific HLA-DR antibodies identified in patient sera following transfusions were good predictors of renal allograft survival in both males and females.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Transfusion↗