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Biomedical subjects

J C Marsh

Publications and source records attributed to J C Marsh.

At least 127 records · Page 7Linked to original sources
PubMed1982

Comparative effects of methotrexate, two nonclassic folic acid antagonists, and cytarabine on hematopoietic precursor cells.

The effects of three antifolates, methotrexate (MTX), triazinate (TZT), and a trimethoxyquinazoline derivative (TMQ), and of cytarabine (ara-C) on leukocyte-committed colony-forming cells from three species were compared using an assay allowing in vivo metabolism in an agar diffusion chamber. Dose-survival curves approximated plateaus, and the level of the plateau was variable among species. Canine marrow colony-forming cells were less sensitive to MTX (about 90% survival) than those from mice or man (25%-40% survival). Human marrow colony-forming cells were less sensitive (70% survival) to TZT than those from mice or dogs (25% survival). No interspecies differences were found for TMQ or ara-C. Mouse marrow in situ was less sensitive to iv MTX than mouse marrow in the chamber. No such difference was found for iv TMQ or ara-C. This comparison could not be made for ip TZT.

Animals↗
PubMed1982

Antitumor activity of the 3'-chloroethylnitrosourea analog of thymidine and the prevention by co-administered thymidine of lethality but not of anticancer activity.

The effect of the 3'-nitrosourea analog of thymidine (3'-[3-(2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine; 3'-CTNU) on the growth of the murine L1210 and P388 leukemias in mice was investigated. A single injection of 3'-CTNU (40 mg/kg) was minimally toxic to mice bearing the L1210 leukemia and produced 60-day survivors. The coadministration of thymidine did not prevent the initial loss of weight caused by 3'-CTNU but did prevent the lethality otherwise produced in non-tumor-bearing mice. A single dose of thymidine (2 g/kg) administered to L1210-bearing mice had no anticancer activity and when coadministered with 3'-CTNU had no detrimental effect on the potent antitumor effects of 3'-CTNU. Similar results were obtained against P388 leukemia. The hematopoietic toxicity produced by the administration of 3'-CTNU to non-tumor-bearing mice, as evidenced by changes in the white blood cells, neutrophil, and agar diffusion chamber precursor cell concentrations in the hematocrit and in bone marrow cellularity, could not be prevented by thymidine. Therefore, the lethality produced by 3'-CTNU is probably not related to hematopoietic toxicity since the coadministration of thymidine completely prevented any lethality.

Animals↗
PubMed1981

Chemical toxicity of the granulocyte.

The effect of chemicals, including pharmacologic agents, on blood granulocytes, may be considered in terms of the effects on the function of mature cells as well as on their number. In turn, the number of cells can be influenced by chemicals which affect production, destruction or distribution within the blood. Neutrophil functions which can be inhibited by chemical agents include chemotaxis, phagocytosis, degranulation, the metabolic burst related to membrane perturbation and intracellular killing. Some drugs can influence multiple neutrophil functions. Neutrophil production may be inhibited by toxic chemicals with a predictable effect, such as cancer chemotherapeutic drugs, where the effects are dose related, or the process may be influenced in an unpredictable (idiosyncratic) fashion, occurring only in a small proportion of patients exposed. Ineffective granulopoiesis with intramedullary death may be seen as a result of exposure to some drugs, as may increased neutrophil destruction, sometimes via an immunologic mechanism. Predictable neutrophil production inhibition by anticancer agents depends on dose, schedule, route of administration, metabolic integrity of organ systems such as liver and kidney, and the proliferative state of the marrow. For a given drug, factors which determine neutrophil toxicity include its mechanism of action, cytotoxic concentration, pharmacokinetics, metabolic and excretory pathway and target cells in the marrow. The use of assays for clonogenic hematopoietic precursor cells is allowing correlation with more traditional toxicologic methods and may be helpful in predicting specific hematologic toxicity in man, prior to actual clinical trials. The agar diffusion chamber assay for neutrophil-macrophage committed colony-forming cells is particularly useful since it allows in vivo exposure of the target cells to the agents being studied.

Animals↗
PubMed1980

Cyclophosphamide, cytosine arabinoside and methotrexate versus cytosine arabinoside and thioguanine for acute non-lymphocytic leukemia in adults.

One-hundred and fifty-one adults with acute non-lymphocytic leukemia (ANLL) were entered into an Eastern Cooperative Oncology Group protocol (EST-1473) comparing twice daily cytosine arabinoside and thioguanine (AT) with weekly cyclophosphamide, cytosine arabinoside, and methotrexate (CAM) for remission induction. Of 111 evaluable patients, 16 treated with CAM and 16 treated with AT entered complete remission (CR) on their initial therapy and 5 additional patients entered CR on crossover for a total of 37 or 33% of the evaluable patients. Of the 71 patients who survived three weeks or longer, the overall CR rate was 52%. Cytochemical studies were performed on 85% of the evaluable cases, Minor disagreements between morphologic subtypes of ANLL occurred in 50% of cases. There was no difference in response rates between the major subtypes of ANLL regardless of whether the investigator's diagnosis or the cytochemical reference laboratory diagnosis was used. The median survival of all evaluable patients was 4.9 weeks; those patients who responded with a CR had a median survival of 60 weeks, while those who did not have a median survival of less than 3 weeks. Age less than 60, ambulatory performance status, or fewer than 50% marrow blasts were also associated with a better response rate and longer survival. CAM had more severe mucositis and vomiting associated with it than did AT, but toxicities were otherwise comparble. Weekly CAM and AT appear to be equally effective regimens in the treatment of ANLL.

Adult↗
PubMed1980

Help seeking among addicted and nonaddicted women of low socioeconomic status.

Concern with the provision of health and welfare services to underserved or inappropriately served groups has led to numerous studies of patterns of service utilization. This article focuses on the help-seeking patterns of heroin-addicted and nonaddicted women of lower socioeconomic status. The results suggest addicts generally experience more problems than nonaddicts; those with few problems are less likely to use formal support systems; and black respondents, both addicts and nonaddicts, are less likely to use formal support systems. The evidence indicates that while addicts tend to use natural support systems less frequently than nonaddicts, addiction per se does not explain help seeking when race and number of problems are taken into account. The heavy reliance of both addicts and nonaddicts on informal helpers supports the value of professional efforts designed to facilitate or enhance these networks.

Adult↗
PubMed1980

Relationship of Bacillus Calmette-Guérin-induced suppressor cells to hematopoietic precursor cells.

Bacillus Calmette-Guérin (BCG) stimulated the proliferation of granulocyte-macrophage colony-forming cells (CFU) and activated suppressor cells that inhibit the immunization of T-lymphocytes in vitro. Increases in both CFU concentration and suppressor cell activity were moderate in the bone marrow and marked in the spleen of mice given BCG i.v. In the bone marrow, these increases were apparent 2 days after treatment with BCG, while in the spleen they did not occur until 7 days after BCG. A BCG strain that produced no increases in CFU concentration also produced no activation in suppressor cell activity. Fractionation of spleen cells through nylon wool and density gradients revealed that cell populations enriched in CFU were also enriched in suppressor cell activity. The paralelism in the response to CFU and suppressor cells to BCG indicates that there is a close relationship between these two cell populations.

Animals↗
PubMed1979

A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction.

In the past decade, we have studied four unrelated children with what we believe is a previously unreported disorder affecting the bone marrow and exocrine pancreas. During infancy these patients had the onset of severe, transfusion-dependent, macrocytic anemia plus a variable degree of neutropenia and thrombocytopenia. Their bone marrows had normal cellularity but were characterized by remarkable vacuolization of erythroid and myeloid precursors, hemosiderosis, and ringed sideroblasts. The vacuoles probably represented manifestations of cellular degeneration and death. In two patients, in vitro bone marrow cultures showed abnormal erythroid and myeloid progenitor cell growth and, in one child, abnormal vacuolated erythroid colonies. Family histories were unrevealing, parents were hematologically normal, and both sexes were involved. There was no evidence of specific nutritional deficiencies or exposure to agents associated with marrow vacuolization. A number of therapeutic interventions produced no effect. One child had clinical malabsorption. This child and one other had extensive pancreatic fibrosis at autopsy. The other two patients had findings indicating exocrine pancreatic dysfunction. Two children had splenic atrophy. This new syndrome, with associated bone marrow and exocrine pancreatic dysfunctions, differs in several respects from the syndrome of pancreatic liposis and neutropenia described by Shwachman et all and Bodian et al, and from other conditions with vacuolization of the marrow or sideroblastosis.

Anemia, Sideroblastic↗
PubMed1979

Comparison of the sensitivities of human, canine, and murine hematopoietic precursor cells to adriamycin and N-trifluoroacetyladriamycin-14-valerate.

The sensitivities of leukocyte-committed stem cells of human, dog, and mouse bone marrow to an 18-hr exposure to Adriamycin (ADR) and N-trifluoroacetyladriamycin-14-valerate (AD32) were compared using the agar diffusion chamber assay. The survival of in situ mouse marrow stem cells following the drugs was also measured. The in vivo doses required to produce 37% survival of hematopoietic precursor cells for human, dog, mouse, and in situ mouse marrow stem cells for ADR were 9.5, 3.5, 8, and 8 mg/kg, respectively, while those for AD32 were 22, 17, 37, and 40 mg/kg. Mouse bone marrow cellularity was reduced to 50% by drug doses producing 3 and 7% stem cell survival. AD32 given i.p. to mice was less effective than i.v. drug in producing marrow stem cell death, reduction of marrow cellularity, or acute lethality. Although more AD32 than ADR was required to kill marrow stem cells from each species and canine marrow stem cells were the most sensitive to either drug, human stem cells were relatively more sensitive to AD32 than were mouse stem cells. The reverse was true for ADR. Granulocytopenia may be an important limiting toxicity in the clinical use of AD32.

Animals↗
PubMed1978

Simultaneous assay by six methods of the effect on haemopoietic precursor cells of adriamycin, methyl CCNU, 60Co gamma-rays, vinblastine, and cytosine arabinoside.

The spleen colony assay, three agar colony assays and two repopulating assays have been employed to measure the effect of single doses of adriamycin, methyl CCNU, 60CO gamma-rays, vinblastine and repeated injection of cytosine arabinoside on early haemopoietic precursors. The results show that there is no consistent correlation between the effect of these agents on the six assays, and the differences in proliferation rate of the cells contributing to the various assays could not be demonstrated by the phase specific agents vinblastine and cytosine arabinoside. The relatively high survival of granulocyte repopulating ability after adriamycin and methyl CCNU indicates that the capacity for differentiation and maturation can be influenced by cytotoxic agents so that colony assays while estimating the number of progenitor cells surviving do not necessarily provide a reliable guide to the capacity of the cells for restoring haemopoiesis. Comparison of colony formation by normal bone marrow cells with the three agar colony assays showed that the agar diffusion chamber method gave three times as many colonies and a much smaller variation between experiments compared to the in vitro agar assay with endotoxin mouse serum as colony stimulating factor. The thin layer feeder cell method gave an intermediate number of colonies.

Animals↗
PubMed1978

A direct assay of granulocytic repopulating ability.

A direct method of assay of the 'granulocytic repopulating ability' (GRA) of bone marrow in normal or treated mice, which utilizes determinations of total bone marrow cellularity and peroxidase positive cells, is described. Ten days after transplantation of normal femoral marrow, the total number of marrow granulocytes in the recipients is proportional to the marrow dose in the range 0.01 to 0.03 of a femur. Above 0.01 femur the proportion of granulocytes is constant at about 60% so there is a high correlation between total cellularity and total granulocytes. Assay of erythroid repopulating ability can be performed in the same animals. Using the GRA assay, the results for the dose response curve for cyclophosphamide, and the relationship of GRA to erythroid repopulating ability (ERA) and spleen colony forming cells, are similar to those obtained using the endotoxin technique. The simplicity of the GRA technique enhances the feasibility of multiple simultaneous hematopoietic precursor cell assays.

Animals↗
PubMed1976

The effects of cancer chemotherapeutic agents on normal hematopoietic precursor cells: a review.

The effects of antineoplastic agents, singly or in combination, on normal hematopoietic precursor cells have been reviewed. Following a description of the assays used (e.g., spleen colony, in vitro colony, repopulating ability), the dose response and/or time response for each drug are presented by species and by assay as available. The schedule of drug administration, the time of the assay, and the proliferative state of the target population are the most important determinants. Alkylating agents, antitumor antibiotics, and 5-fluorouracil have exponential dose survival curves. "Phase-specific" agents such as antimetabolites, Vinca alkaloids, and ribonucleotide reductase inhibitors have plateaus in their dose survival curves, although the level of this plateau is different for different agents. Most drugs are more effective against rapidly proliferating cells although busulfan is less effective. Direct interspecies comparisons are possible with some of the clonogenic assays, which may allow prediction of the magnitude of human hematological toxicity for new agents or combinations.

Alkylating Agents↗
PubMed1976

Clinical effects and pharmacokinetics of different dosage schedules of adriamycin.

Adriamycin was administered to 60 adults and 21 children by 3 different dosage schedules: 22.5 mg/sq m (0.6 mg/kg) daily for 4 days, 15 mg/sq m (0.4 mg/kg) every 8 hr for a total of 6 doses, and 50 to 120 mg/sq m as a single dose every 3 to 4 weeks. Objective responses lasting more than 1 month occurred in 5 subjects with acute leukemias or lymphoma, 3 with transitional cell carcinomas, 2 with sarcomas, 2 with Ewing's sarcoma and 1 each with bronchogenic carcinoma, orchidoblastoma, and thymoma. Toxic reactions included nausea, vomiting, stomatitis, alopecia, and hematopoietic depression, but significant cardiac toxicity occurred in only 1 patient. Pharmacokinetic data, collected in 25 patients by fluorometric and chromatographic assay, suggested a biphasic plasma clearance of drug with initial and secondary half-lives of about 1.5 and 14 to 21 hr, respectively. When drug was given every 8 hr there was evidence of loss of an initial very rapid phase of distribution of adriamycin and its metabolites. Urinary excretion accounted for 3.4 to 38.1% of administered fluorescence over a 72-hr period; in the first 24 hr, between 48.2 and 100% of this urinary material was in the form of adriamycin; leter, this fraction declined. No adriamycin or its fluorescent metabolites could be extracted from the stools.

Blood Cells↗
PubMed1975

IgA associated lymphoplasmacytic tumor involving the conjunctiva, eyelid, and orbit.

A 65-year-old white man had an unusual disseminated lymphoid tumor that first appeared in the subconjunctival tissues of the right eye. The tumor later appeared in the skin, lymph nodes, and left upper eyelid and orbit. A monoclonal serum IgA spike was present although the urine did not contain Bence Jones proteins. The cells of the tumor appeared to be plasmacytoid lymphocytes. Prominent intranuclear inclusions, or Dutcher bodies, were present. Throughtout the 11-year history, the patient has been treated only with local excision and radiation.

Aged↗