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Biomedical subjects

A R Turner

Publications and source records attributed to A R Turner.

At least 55 records · Page 3Linked to original sources
PubMed1986

Effect of cis-platinum treatment on 67Ga-citrate localization and elimination in rabbits.

The treatment of rabbits with a typical dosage schedule of the chemotherapeutic drug cis-platinum resulted in an increased whole body retention of 67Ga-citrate due to decreased urinary and fecal excretion. The biodistribution of the tracer was also affected with most tissues showing greater accumulation. These changes are primarily related to drug-induced renal dysfunction, but other factors may also be involved.

Animals↗
PubMed1986

Effect of cis-platinum on the protein binding and pharmacokinetics of 67Ga-citrate.

Cis-platinum, a widely used chemotherapeutic drug, and K2PtCl4, a related complex, were found to inhibit the in vitro protein binding of 67Ga to human transferrin in isolated solution but not to whole serum. Cis-platinum treatment of rabbits resulted in enhanced protein binding and delayed blood clearance of subsequently injected 67Ga-citrate. These effects are related to the toxicity of the drug in vivo.

Animals↗
PubMed1986

Differentiation of K562 leukemia cells along erythroid, macrophage, and megakaryocyte lineages.

K562 is a human leukemic cell line used as model of hematopoietic differentiation. A variety of differentiation-inducing agents was used in this study, and the expression of surface membrane antigens associated with specific lineages of differentiation and changes in the cytochemistry of the induced cells were monitored. Sodium butyrate, hemin, retinoic acid, dimethyl sulfoxide (DMSO), phorbol myristate acetate (PMA), and interferon induced unique alterations in the binding of monoclonal antibodies specific for erythroid, granulocytic, monocytic, and megakaryocytic lineages. Hemoglobinization, Sudan Black B, glycogen content, nonspecific esterase, alkaline phosphatase, and 5'-nucleotidase staining were also altered. K562 cells were terminally differentiated with PMA to nitroblue tetrazolium-(NBT) positive macrophages. Expression of 3-fucosyl-N-acetyl lactosamine, previously thought to be myeloid specific but found on all early hematopoietic progenitors, was modulated during differentiation to nonmyeloid lineages. Lineage infidelity was noted during functional differentiation along all hematopoietic lineages. The presence of multiple lineage surface markers and cytoplasmic characteristics in leukemic cells is not indicative of lack of potential to differentiate. K562 cells cannot be compared to any normal stage of hematopoietic differentiation, but they do have the capacity to differentiate along erythroid, macrophage, and megakaryocytic lineages.

Antibodies, Monoclonal↗
PubMed1985

Vinblastine, bleomycin, and cisplatin in malignant germ cell tumors of the ovary.

Fourteen patients with malignant ovarian germ cell tumors were treated with vinblastine, bleomycin, and cisplatin. A complete clinical response was achieved in all 14 patients; however, 1 patient had small macroscopic disease present at second-look laparotomy. One patient died of bleomycin pulmonary toxicity. The remaining 13 patients are alive and free of disease from 20 months to 8 years and 8 months after initial diagnosis. Serum alpha-fetoprotein and beta-human chorionic gonadotropin levels were monitored in all patients and were found to be reliable indicators of response to treatment and disease status. The uninvolved ovary was preserved in seven patients without compromising the response to treatment, and one patient subsequently became pregnant. Vinblastine, bleomycin, and cisplatin chemotherapy appears to be a safe, effective combination and is recommended as the primary treatment of choice in the management of patients with malignant ovarian germ cell tumors.

Adolescent↗
PubMed1985

Induction of the expression of HLA class I antigens on K562 by interferons and sodium butyrate.

Using sodium butyrate and alpha, beta, and gamma interferons as inducing agents it has been possible to demonstrate the triggering of HLA class I antigen synthesis in the K562 cell line. This cell line, widely used to study hemopoietic differentiation, does not naturally express HLA antigens. This effect was confirmed by the detection of HLA class I antigens on the cell membrane with specific monoclonal antibodies, by immuneprecipitation, and by isolation of specific HLA ABC messenger RNA, in the induced cells. No synthesis of HLA class II antigens was observed. Because leukemic cells can be considered as a model representing certain stages of normal hemopoietic differentiation, the expression of HLA antigens on K562 cells induced to differentiate could be interpreted as an event related to the process of differentiation itself. The lack of expression of DR antigens may result from a genetic defect as observed for beta 2-microglobin in Daudi cells.

Antibodies, Monoclonal↗
PubMed1985

Suppression of hepatic hematopoiesis with radioactive gold (198Au).

A patient with idiopathic myelofibrosis of some 20 yr duration developed esophageal varices and ascites. No explanation for increased portal pressure other than hepatic hematopoiesis was found. Consequently, a trial of cobalt irradiation to the liver was undertaken with definite but transient decrease in ascites. Subsequently, two courses of radioactive colloidal gold were given, again with definite but transient beneficial effects on the degree of ascites. This latter benefit occurred without suppression of marrow function.

Aged↗
PubMed1984

Monoclonal antibody specific for granulocytic-lineage cells and reactive with human pluripotent and committed haematopoietic progenitor cells.

A murine monoclonal antibody (82H5, IgM class) has been developed that detects an antigenic determinant expressed by greater than 90% of normal granulocytes and 60-80% of light-density normal bone-marrow cells, including human pluripotential progenitors (colony-forming-unit-granulocyte, erythroid, macrophage, megakaryocyte; CFU-GEMM) and committed progenitors: granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and megakaryocytic (CFU-MK). This antibody did not react with erythrocytes, monocytes, platelets, lymphocytes from normal peripheral blood, lymphoblasts from patients with acute lymphoblastic leukaemia, or with lymphoid cells lines. The 82H5-defined antigenic determinant was expressed on greater than 90% of leukaemic cells of promyelocytic, myelomonocytic and monocytic morphology, and cell lines KG.1, ML.1, HL.60, K562 and U.937. Cortical thymocytes were unreactive with 82H5. Treatment of human bone-marrow cells with granulocytic-specific monoclonal antibody 82H5 plus complement significantly inhibited colony formation (48-74%; P less than 0.05) of CFU-GEMM, CFU-GM, BFU-E, CFU-MK, whereas treatment with control monoclonal anti-Ia antibody plus complement caused 79-89% inhibition. This antibody reacted strongly with 3-fuc-NAc lactosamine when tested with a panel of synthetic carbohydrate structures. We conclude that 82H5 may be a useful probe for phenotypic analysis of leukaemic cells and investigation of haematopoiesis.

Animals↗
PubMed1983

Translation of lymphocyte mRNA for mouse colony stimulating factor.

Poly A+ RNA has been purified from phorbol myristate acetate stimulated mouse EL4 cells. Translation, by microinjection into frog oocytes, gave biologically active interleukin 2 (IL2) and colony stimulating factor for granulocytes and macrophages (GM-CSF). These two mRNAs were separated by centrifugation through linear sucrose gradients. The sedimentation coefficients for IL2 and GM-CSF mRNAs were found to be 11.5S and 8S respectively. The clonal and cellular morphologies induced by the oocyte material corresponded to low concentrations of authentic GM-CSF.

Animals↗
PubMed1983

Stimulation of [3H]thymidine uptake in mouse marrow by granulocyte-macrophage colony stimulating factor from mouse lung conditioned medium.

Stimulation of [3H]thymidine uptake in mouse marrow cells by a haematopoietic factor, granulocyte-macrophage colony stimulating factor from mouse lung conditioned medium, was used to follow the activity of the factor in the medium, and during its partial purification from the medium. The assay was performed in microtitre plates and found to be much easier and faster than conventional colony counting. The marrow cells were incubated in flat-bottomed plates in the presence of the factor for 5 days before labelling with [3H]thymidine (2 muCi/well, 5 Ci/mmole) for 6 h. Stimulation of the [3H]thymidine uptake was compared with the development of granulocyte-macrophage colonies in semisolid methylcellulose culture. The activity followed by both assays showed identical behaviour when subjected to ammonium sulphate precipitation, Sephadex gel filtration, concanavalin-A-Sepharose chromatography and polyacrylamide gel electrophoresis.

Animals↗
PubMed1983

Identification of a hypoxic population of bone marrow cells.

A technique using collagenase has been devised to release and separate, with reproducibility, hematopoietic cells (HC) from various microenvironments of mouse femurs. HC were assayed by an in vitro gel culture technique used traditionally to score granulocyte-macrophage precursor cells (CFU-C). CFU-C which resided in the medullary cavity and endosteal regions were sensitive to ionizing radiation and resistant to misonidazole (MISO) cytotoxicity. CFU-C which resided within the compact bone were resistant to ionizing radiation and sensitive to the cytotoxic action of MISO. These results suggest that HC which reside in the bone are hypoxic and retain clonogenic potential. When animals were exposed to various treatments with MISO followed by myelotoxic doses of cyclophosphamide (CTX) or total body irradiation (TBI), the LD50 of both agents was significantly reduced. This result suggests that a hypoxic component of HC could be important in the regenerative process within the marrow after such myelotoxic trauma.

Animals↗
PubMed1983

Abnormal biodistribution of radiogallium in persons treated with phenytoin.

After incidentally observing a patient in whom abnormal uptake of gallium-67 citrate appeared to be explained by treatment with phenytoin, we have conducted a prospective study. Of sixteen persons with a seizure disorder treated with phenytoin, five (31%) had abnormal uptake of radiogallium either in the mediastinum, pulmonary hilum or both. Of nineteen historical control patients only one had such abnormal uptake. Phenytoin may thus cause the false-positive uptake of radiogallium in lymph nodes; this finding may also prove to have nosological importance in identifying patients at particular risk of the side-effects of this drug.

Drug Interactions↗
PubMed1982

Monoclonal antibodies against human granulocytes and myeloid differentiation antigens.

Monoclonal antibodies (MCA) were obtained by immunizing BALB/c mice with 99% pure granulocytes from normal donors or with a whole leukocyte suspension obtained from a chronic myelogenous leukemia (CML) patient, and then fusing the mouse spleen cells with a 315-43 myeloma cell clone. Four MCA were selected and studied using ELISA, immunofluorescence, cytotoxicity assays, and FACS analysis. Antibodies 80H.1, 80H.3, and 80H.5 (from normals) and 81H.1 (from CML) detected antigens expressed on neutrophils. Antibodies 80H.1 and 80H.3 (IgG) also reacted with monocytes but not with other blood cell subsets. Antibodies 80H.5 and 81H.1 (IgM) were cytotoxic and reacted strongly with most of the cells of the neutrophil maturation sequence, i.e., myeloblasts, promyelocytes, myelocytes, and mature granulocytes. Antibodies 80H.5 and 81H.1 also inhibited CFU-GM growth stimulated by leukocyte feeder layers or placental conditioned media, but did not inhibit BFU-E and CFU-E. Antigens recognized by 80H.3, 80H.5, and 81H.1 were expressed both on a proportion of cells from HL.60, KG.1, ML.1, and K562 myeloid cell lines, and on a proportion of blast cells isolated from patients with acute myelogenous leukemia. They were not found on lymphoid cell lines or lymphoid leukemia cells. These MCA recognize either late differentiation antigens expressed on mature neutrophils and monocytes (80H.1 and 80H.3) or early differentiation antigens (80H.5 and 81H.1) specific to the granulocytic lineage. They may be useful for a better definition of those antigens specific to hematopoietic stem cells and their relationship with normal or neoplastic hematopoiesis.

Animals↗
PubMed1982

Gynecomastia after cytotoxic therapy for metastatic testicular cancer.

Four men with metastatic nonseminomatous testicular cancer, who had received combination chemotherapy, experienced transient gynecomastia. Serum hormone levels were measured during and after the resolution of the gynecomastia. These levels indicated toxic effects on Leydig's cells and germinal epithelium concurrent with raised serum estradiol levels in the absence of tumor. The gynecomastia may have been caused by Leydig's cell dysfunction or refeeding after substantial weight loss. This benign form of gynecomastia must be recognized to avoid unnecessary investigation and treatment.

Adult↗
PubMed1982

Comparison of colony stimulating activities secreted into mouse lung conditioned medium in the presence and absence of lithium chloride.

Inclusion of lithium chloride during the process of secretion of granulocyte-macrophage colony stimulating activity (CSA) into mouse lung conditioned medium resulted in an increased production of CSA. CSA produced in the presence of lithium chloride was compared to the CSA produced in its absence by means of ammonium sulfate precipitation, Sephadex G-1CO (S) chromatography, concanavalin A-Sepharose chromatography and polyacrylamide gel electrophoresis. It was found that the two activities behaved identically, indicating that lithium-induced increase in CSA does not involve a qualitative change in the molecule of the colony stimulating factor, but reflects an increased production (or release) of a CSF molecule that is similar to the one produced in its absence.

Animals↗