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Biomedical subjects

T Ohnuma

Publications and source records attributed to T Ohnuma.

At least 127 records · Page 7Linked to original sources
PubMed1983

Effects of harringtonine in combination with acivicin, adriamycin, L-asparaginase, cytosine arabinoside, dexamethasone, fluorouracil or methotrexate on human acute myelogenous leukemia cell line KG-1.

Harringtonine (HT) is a new antitumor agent reported to be active in patients with leukemia and lymphoma. The interaction of HT with various antitumor agents was studied in vitro using a human acute myelogenous leukemia cell line KG-1. For the analysis of the drug - drug interaction at the cellular level, Steel proposed the concept of an envelope of additivity. Using this concept, the effect of a two drug combination can be classified as supraadditive (enhancement of the effect), non-interactive (additive), subadditive, and protective (antagonistic). Combination of HT and cytosine arabinoside or HT and dexamethasone produced only additive effects. Combination of HT and methotrexate was subadditive. For HT plus adriamycin or HT plus 5-fluorouracil, data points indicated both subadditive and protective interaction. HT plus acivicin or HT plus L-asparaginase combinations were found to be protective of each other. None of the seven agents produced supraadditive interaction. These results may provide the basis for selecting sequential rather than concurrent combinations which include HT for the treatment of leukemia in man.

Alkaloids↗
PubMed1983

67Ga-transferrin and 67Ga-lactoferrin binding to tumor cells: specific versus nonspecific glycoprotein-cell interaction.

In order to evaluate the mechanisms which facilitate the transfer of 67Ga from transferrin in plasma to intracellular binding sites, lactoferrin, a glycoprotein with high affinity for 67Ga, was used as a probe to study the effect of protein binding on gallium uptake by tumor cells. The in vivo effect of transferrin and lactoferrin on the biodistribution of 67Ga was studied in nude mice bearing human malignant mesothelioma. Tumor uptake of 67Ga was reduced 30% by transferrin and 57% by lactoferrin compared with 67Ga-citrate alone. Liver uptake of 67Ga, however, was significantly increased by binding to lactoferrin. The in vitro binding of 67Ga to tumor cells (Burkitt's lymphoma) was apparently promoted by the addition of transferrin or lactoferrin to the incubation medium, but this glycoprotein enhancement of gallium uptake by the cells was dependent on the albumin level, decreasing in absolute uptake as the albumin concentration was increased, suggesting nonspecific binding of glycoproteins to cells. Because of the significant amount of nonspecific binding of 67Ga-labeled glycoprotein complexes in cell culture experiments, in vitro experiments should be used with caution in developing a hypothesis on the mechanisms of cellular uptake of radiogallium. In vivo experiments suggest different mechanisms for cellular uptake of 67Ga in neoplastic tissue and in liver.

Adult↗
PubMed1983

Cardiac beat-to-beat variation as an indicator of neuropathy and the frequency of its abnormality in diabetes mellitus.

The cardiac beat-to-beat variation and the maximum constriction velocity and acceleration of the pupillary light reflex have been considered indices of parasympathetic neuropathy. The abnormality of these indices was evaluated in 191 non-diabetics and 151 diabetics. The cardiac beat-to-beat variation decreased gradually with age in non-diabetics as well as diabetics. It was small in diabetics compared to non-diabetics in corresponding age group between 10 and 59 years. In diabetics it was still smaller in the presence of peripheral neuropathy than in its absence. The overall prevalence of this abnormality was 30.1% in diabetics but only 3.0% in non-diabetics. In diabetics it rose to 40.0, 42.6 and 52.2% in the presence of motor, sensory and motor plus sensory nerve neuropathy, respectively. In 63 diabetics examined for both cardiac beat-to-beat variation and pupillary light reflex, no statistical difference was observed between the frequency of these abnormalities. These observations indicate an extremely high prevalence of abnormality in autonomic nerve function in diabetics especially in the presence of abnormality in autonomic nerve function in diabetics especially in the presence of other types of neuropathy, so that diabetics with peripheral neuropathy should be carefully examined for autonomic neuropathy and vice versa. Besides, the measurement of the cardiac beat-to-beat variation is similar in sensitivity in the detection of neuropathy to the measurement of pupillary light reflex.

Adolescent↗
PubMed1983

[Drug sensitivity of human acute myelocytic leukemia cells (HL-60) and normal human myelocytes (CFU-C) in a co-culture].

The chemotherapeutic susceptibility of normal human granulocyte-macrophage progenitor cells (CFU-C) and established human acute myelogenous leukemia (AML) cells (HL-60) in co-culture were determined. Nucleated marrow cells (2 X 10(5)) and HL-60 cells (5 X 10(3)) were mixed in 0.33% agar containing McCoy's 5a medium, 10% fetal calf serum, 0.1 ml of human placenta-conditioned medium and various concentrations of vincristine, cytosine arabinoside or daunorubicin to a total of 1.1 ml. They were incubated in 5% humidified CO2 at 37 degrees C for 8 to 10 days. CFU-C and HL-60 colonies were differentiated morphologically. In the absence of chemotherapeutic agents, the CFU-C colony formation was inhibited with the increasing number of HL-60 cells. CFU-C is equivalent or less sensitive than the leukemic cells in separate culture, but in co-culture it becomes more susceptible to vincristine and daunorubicin. These data indicate AML cells exert inhibitory effects on normal marrow CFU-C. In such state, normal hematopoietic cells become more susceptible to certain chemotherapeutic agents.

Adult↗
PubMed1983

Doxorubicin-induced skin ulcer in the piglet.

Skin ulceration produced by inadvertently extravasated doxorubicin is characterized by a prolonged course accompanied by severe morbidity, and it has proven to be notoriously difficult to treat. In attempts to identify possible antidotes, 11 different pharmacologic agents were tested using piglets, because their skin is anatomically similar to that of man. Among the agents studied, topical application of DMSO daily for 7 days tended to decrease the maximal diameter and accelerate healing of skin ulcers produced by intradermal doxorubicin. alpha-Tocopherol appeared to worsen the ulceration. None of the 11 agents studied prevented the development of ulcerations completely.

Animals↗
PubMed1983

Dialyzability of methyl-GAG.

Methyl-GAG at low doses was administered to an anephric male patient with metastatic hypernephroma, who required hemodialysis. No toxicity was observed. Measurement of serum levels of methyl-GAG showed that the drug is dialyzable. Thus, when methyl-GAG is considered for patients who are anephric and are being dialyzed, full doses are allowable. In addition, dialysis should be effective in rapidly eliminating the drug in patients who develop toxic effects.

Adenocarcinoma↗
PubMed1983

Mitoxantrone in patients with acute leukemia in relapse.

Twenty-six patients with acute leukemia in relapse were treated with mitoxantrone (dihydroxyanthracenedione dihydrochloride). The drug was given as a rapid i.v. infusion for 5 days, and doses were escalated from 8 mg/sq m daily for 5 days to 20 mg/sq m daily for 5 days. Five of 12 patients with acute lymphoblastic leukemia were induced into complete remission; one patient was induced into complete remission twice. The marrow response lasted from 3 to 50+ weeks. Among 12 patients with acute myelogenous leukemia, there was one complete and one partial remission, with response duration lasting 8 and 2 weeks. One patient with chronic myelogenous leukemia in blastic crisis also had a partial remission lasting 17 weeks. Remissions occurred at doses ranging from 8 to 14 mg/sq m daily for 5 days. All responders had been treated previously with anthracyclines. Drug-induced side effects included dose-limiting oral mucositis, sporadic nausea and vomiting, and transient elevations of the hepatic enzymes. Approximately one-third of the patients had septic complications during the myelosuppressive phase following treatment. We believe that mitoxantrone has definite utility in the treatment of acute leukemia in relapse.

Acute Disease↗
PubMed1983

Effects of physiological oxygen concentration on human tumor colony growth in soft agar.

Cloning efficiencies of 67 fresh human tumor specimens, consisting of 29 ovarian, 10 lung, and 7 each of colon, breast, mesenchymal, and miscellaneous tumors, from 58 patients were studied using the technique of Hamburger and Salmon to evaluate the effect of incubation in a 5% rather than 20% oxygen environment. Under the low-oxygen tension, carcinomas exhibited an average of 170% increase in cloning efficiency (p less than 0.01). The number of carcinomas forming at least 30 colonies/dish increased from 22 to 27. Mesenchymal tumors, however, exhibited a 20% decrease in cloning efficiency (not significant). A mixture of 5% oxygen, 5% carbon dioxide, and 90% nitrogen gives a higher cloning efficiency than 20% oxygen, 5% carbon dioxide, and 75% nitrogen for certain human carcinomas in semisolid agar.

Agar↗
PubMed1982

Portable infusion pumps in ambulatory cancer chemotherapy.

Fifty-seven adult patients receiving chemotherapy were treated with a total of 133 infusions using portable user-worn infusion pumps, the Autosyringe AS*2F Cormed ML6-4, and two earlier versions of the latter, the Sigmamotor ML6-2 and ML6-3. Ninety-eight infusions were given on an ambulatory basis. Fourteen infusions were given through peripheral venous catheters, 115 through central venous catheters, and four intra-arterially. Of 127 evaluable infusions, 65 were completed within 5% and 87 within 10% of the planned rate; results are similar for both inpatient and outpatient infusions. The Cormed ML6-4 pump was equal to the Autosyringe AS*2F in reliability but superior to the latter in patient preference. There were no instances of dangerously rapid administration of the drug. The only serious catheter complications were a pneumothorax after insertion of a subclavian catheter in one patient and cellulitis in a leukopenic patient with a Broviac catheter. All but three patients preferred outpatient therapy to hospitalization. Outpatient therapy costs about $300 per day less than in-hospital treatment.

Adult↗
PubMed1982

Vindesine: a phase II study in childhood malignancies-a report for cancer and leukemia group B.

Vindesine, a semisynthetic derivative of vinblastine sulfate, was tested for antitumor activity and clinical toxicity in 36 children. The drug was administered to the initial 13 patients entered into the study a 2 mg/m2/day for five days by IV bolus. Because of severe neurotoxicity and life-threatening gastrointestinal toxicity, the regimen in 23 patients was modified to 4mg/m2 IV infusion over four hours, weekly. This latter regimen was well tolerated, with acceptable gastrointestinal, hematological, and neurotoxicity. One child with acute lymphocytic leukemia resistant to vincristine had a transient M1 remission bone marrow. Improvement or stable disease was noted in one patient each with Ewing's sarcoma, neuroblastoma, and Hodgkin's disease.

Adolescent↗
PubMed1982

Establishment of methotrexate-resistant human acute lymphoblastic leukemia cells in culture and effects of folate antagonists.

A human acute lymphoblastic T-cell line, MOLT-3, was fed with Roswell Park Memorial Institute Medium 1640-10% fetal bovine serum-antibiotics, containing increasing concentrations of methotrexate (MTX). After 10 months of feeding, the cells became resistant to 10(-7) M MTX; resistance was not reversed when the cells were placed in the original MTX-free medium. At 10(-7) M MTX, the concentration which produced complete inhibition of the parent MOLT-3 cell growth, the resistant cells were not inhibited at all. On a 50% inhibitory concentration basis, the resistant cells were approximately 30-fold more resistant to MTX. The parent MOLT-3 and the resistant line had the same doubling time of approximately 36 hr. There were no differences in light microscopic morphology. MOLT-3 produced loose colonies on 0.5% agar enriched with fetal bovine serum, whereas the colonies of the resistant line were tightly packed. The development of resistance was accompanied by a 4- to 5-fold decrease in [3H]MTX transport (MOLT-3/MTXt). Kinetic analysis of MTX uptake showed that the resistant subline did not have an altered Km for MTX (6.6 microM) but had a decreased Vmax of about 20% of the parent cell line. These data suggest that either the number of folate transport sites or the turnover rate of these sites has been reduced in the MTX-resistant cell line. Dihydrofolate reductase was only minimally elevated in the resistant cell line. The MTX-resistant cell line was cross-resistant to dichloromethotrexate. The sensitivity of the resistant line to the substituted 2,4-diaminoquinazoline and pyrimidine compounds, 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino) methyl] quinazoline (JB-11) and 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine, increased more than 3-fold. While leucovorin equally reversed the MTX effects on the parent and resistant cells, leucovorin reversal of 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino) methyl] quinazoline and 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine effects was limited only to the parent cell line. 2,4-diamino-5-methyl-6-[(3',4',5'-trimethoxyanilino) methyl] quinazoline or 2,4-diamino-5-(3',4'-dichlorophenyl)-6-methylpyrimidine plus leucovorin might prove to be unique in treating patients with acute lymphoblastic leukemia when the leukemic cells develop transport resistance to MTX.

Animals↗