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Biomedical subjects

S Misawa

Publications and source records attributed to S Misawa.

At least 307 records · Page 17Linked to original sources

Chromosomal alterations in acute leukemia patients studied with improved culture methods.

Cytogenetic studies, using improved short-term culture techniques, were performed on 64 patients with acute leukemia to determine the incidence and kinds of clonal karyotypic changes detectable with this newer methodology. An adequate number of analyzable mitoses was obtained from 59 patients. Clonal chromosomal alterations were found in 88% (52 of 59) of patients, as compared to approximately 50% in previous studies of acute leukemia in which conventional techniques were used. From our series, abnormal karyotypes were detected in 37 of 44 (84%) cases with primary acute nonlymphocytic leukemia, all 5 with secondary acute nonlymphocytic leukemia, and all 10 with acute lymphoblastic leukemia. Among the entire group of patients, several recurrent abnormalities were observed, e.g., -7 in eight cases, +8 in seven cases, t(15;17) in four cases, and t(8;21) or a variant of this translocation in four cases. In five patients, the only abnormality was a rather subtle structural rearrangement (e.g., tiny deletion). Five other patients had clonal changes which were found in less than 10% of the mitoses examined in each case. Our results indicate that most patients with acute leukemia, both acute nonlymphocytic leukemia and acute lymphoblastic leukemia, have clonal chromosome abnormalities associated with their disease.

Acute Disease↗

Double minute chromosomes in acute myeloblastic leukemia.

Two patients with acute myeloblastic leukemia (AML) with double minute chromosomes (dmins) are described. One patient had dmins in approximately one-third of bone marrow cells examined at diagnosis; no other karyotypic changes were observed. The dmins disappeared when the patient achieved a complete remission. The second patient developed acute leukemia as a second cancer, having previously received radiotherapy and chemotherapy for a breast carcinoma. At the time of diagnosis of AML, the patient exhibited dmins in 12% of bone marrow cells; other complex karyotypic changes were observed. Data on the clinical and cytogenetic features of these cases are compared with those of other reported cases of acute leukemia with dmins. The possible biologic and clinical significance of dmins in acute leukemia is discussed.

Acute Disease↗

Effects of cimetidine and ranitidine on trimethadione metabolism in the rat.

Pretreatment of rats with cimetidine (100 mg/kg, i.p.) resulted in a prolongation of TMO half-life, an increase in the area under the curve (AUC) and a decrease of clearance (Cl), whereas in the rats pretreated with ranitidine (120 mg/kg, i.p.), these parameters were not changed. The apparent volume of distribution (Vd) values were not changed by either of the drugs as compared to controls. Activities of hepatic cytochrome P-450-dependent metabolizing enzymes such as aminopyrine- and TMO N-demethylase and aniline hydroxylase activity were decreased by pretreatment of rats with cimetidine, whereas in the rats pretreated with ranitidine, these enzyme activities were not changed. Cytochrome P-450 contents were not changed by either of the drugs as compared to controls. The inhibition manner of aminopyrine- and TMO N-demethylase activities in the rats pretreated with cimetidine was noncompetitive. These results indicate, together with the previous findings, that cimetidine treatment inhibited TMO metabolism, but ranitidine did not.

Aminopyrine N-Demethylase↗

Sister chromatid exchanges induced by cancer chemotherapeutic agents in vitro and in vivo: consideration of the hazard of drugs as possible mutagens and carcinogens causing second malignancies.

Sister chromatid exchanges (SCEs) induced by chemotherapeutic agents currently used for treating various malignancies were studied in vitro and in vivo. Whether the agents are potentially mutagenic/carcinogenic is discussed on the basis of recent clinicopathological observations on secondary malignancy. In the in vitro studies, the induction of SCEs by various anticancer agents, including three anticancer antibiotics, six alkylating agents, and three antimetabolites, was examined and compared with induction by two known carcinogens, 4-nitroquinoline 1-oxide and N-ethyl-N'-nitronitrosoguanidine. In the in vivo studies, SCE frequencies were examined in the lymphocytes from 74 blood samples drawn from 40 patients with cancer or leukemia at various times after the agents had been administered alone or in combination. The SCE frequencies induced by the anticancer antibiotics were variable because the drugs had different modes of action: generally, the drugs have strong cytotoxicity that must affect the viability of cells. On the other hand, alkylating agents induced significantly high levels of SCE frequencies in vitro; the modes of SCE inducibility were similar to those of the two carcinogens. The fact that cells were viable up to relatively high molar concentrations of the agents and that high SCE levels persisted for a long period suggests that the lesions induced by alkylating agents are long-lived and may therefore be more frequently involved in mutagenesis. This finding may be compatible with the clinical observation that the vast majority of patients with second malignancy are found in the group treated with alkylating agents. Antimetabolites generally showed only a weak SCE induction or none in vivo and in vitro.

Alkylating Agents↗

Cardio-respiratory effects of paraquat with and without emetics on Wistar rats.

We investigated the effects of paraquat products both containing and devoid of emetics on the cardio-respiratory functions of Wister rats. Anesthetized rats were administered intravenously 0.46 ml/kg Gramoxone, a commercial product containing 24% paraquat and an emetic. Paraquat equivalence equalled 110 mg/kg body weight. ECG and respiratory curves were recorded with a polygraph. Fifteen seconds after injection, A-V block and bradycardia occurred and the heart stopped beating soon after. Though the heart was severely affected, the respiratory curve differed very little from pre-injection values. Administration of pure, 24% paraquat solution (110 mg/kg body weight) inhibited respiration and almost no change was recorded by the ECG. Administration of Paragreen A, a commercial product containing 24% paraquat with no emetic, produced slight change in the ECG but respiration soon became strained and stopped. In accordance with this data, we propose that the emetic contained in Gramoxone is primarily responsible for the cardiovascular failure.

Animals↗

Eosinophilic differentiation of the human promyelocytic leukemia cell line, HL-60.

HL-60 promyelocytic leukemia cells differentiated to eosinophils and eosinophilic precursors when cultured under mildly alkaline conditions (pH 7.6-7.8) for 7 d without refeeding. New cytoplasmic granules appeared blue in the least mature cells and red in the most mature cells when stained with Wright-Giemsa. The granules also stained with Luxol-fast-blue, a characteristic of eosinophil granules. Furthermore, most cells contained the eosinophil major basic protein (MBP); the Charcot-Leyden Crystal (CLC) protein (lysophospholipase), eosinophil peroxidase, acid phosphatase, and arylsulfatase were also detected in a portion of these cells. The eosinophil major basic protein was found in a high proportion of undifferentiated cells, and thus may be constituitively produced. By examining finely banded chromosomes, translocation break points were demonstrated at q22 on one chromosome 16 and at q23 on the other homologue; abnormalities in this region of the long arm of 16 are a characteristic finding in the recently described syndrome of acute myelomonocytic leukemia (AMMoL) with abnormal bone marrow eosinophils. In common with the bone marrow eosinophils in these patients, the HL-60 eosinophil granules contained chloroacetate esterase and periodic-acid Schiff (PAS) reactive material; crystalloid inclusions were rare. Therefore, the HL-60 cell line appears to be an in vitro model for eosinophilopoiesis and may be specially suited for the study of the abnormal eosinophils seen in certain malignant conditions.

Blood Proteins↗

Promyelocytic blast crisis in chronic granulocytic leukemia with 15;17 translocation.

A patient with Philadelphia chromosome Ph1-positive chronic granulocytic leukemia (CGL) developed an acute transformation associated with a hemorrhagic diathesis and bone marrow infiltration by hypergranular promyelocytes and blasts. Cytogenetic analysis of bone marrow metaphase cells at transformation showed a t(15;17) superimposed upon the Ph1-positive cell line. These findings suggest a critical relationship between the t(15;17) and arrest of myeloid leukemic cell differentiation at the promyelocyte stage.

Adult↗

Centromere spreading in acute nonlymphocytic leukemia.

Centromere spreading (CS) was observed in bone marrow chromosomes from a patient with acute myeloblastic leukemia (AML), prior to therapy. The abnormality was found in a direct specimen, in a 24-hr culture, and in a culture treated with the methotrexate synchronization technique. A small hypodiploid clone, 45,XY,-19, was also observed. This case provides further evidence that CS can occur in acute nonlymphocytic leukemia (ANLL). The possible relationship between CS and hypodiploidy in this and other reported cases of ANLL is discussed.

Aged↗

Abnormalities of chromosome 16 in association with acute myelomonocytic leukemia and dysplastic bone marrow eosinophils.

Six patients with M4 acute myelomonocytic leukemia ( AMMoL ) were identified who had abnormalities of chromosome 16 in bone marrow cells. Five had a pericentric inversion, inv(16)( p13q22 ), and a sixth patient had a translocation, t(16;16)(p13.1;q22). Each of these six patients had bone marrow eosinophils that were abnormal in morphology on light and/or electron microscopy and by cytochemical stains. The eosinophils constituted 1%-24% of nucleated marrow cells. Of 61 acute nonlymphocytic leukemia (ANLL) patients, all those with AMMoL and abnormal bone marrow eosinophils had an inv(16) or a t(16;16). One other patient in this group had a rearrangement of chromosome 16 (with a break in the short arm at band p13); however, the ANLL type was M1 and no abnormal eosinophils were present. Four patients with ANLL types other than M4 had an increase in marrow eosinophils; three in whom the eosinophils appeared normal and one with ANLL-M2 and bizarre eosinophils morphologically distinct from those seen in AMMoL . Chromosome pair 16 was normal in the latter four patients. AMMoL with dysplastic bone marrow eosinophils appears to represent a unique clinicopathologic entity associated with several related abnormalities affecting 16q . The morphologic features of both blasts and eosinophils may be more important than the absolute number of eosinophils in the marrow in identifying this group of patients. This may have prognostic importance as five of six patients achieved complete remission with standard antileukemic therapy and are still alive.

Adult↗

Acquired chromosome rearrangements, including fine interstitial deletions, in a patient with Down syndrome and monoblastic leukemia.

A female child with Down syndrome who developed acute monoblastic leukemia is reported. Anemia associated with milk leukopenia was first recognized when the patient was 14 months old. Acute monoblastic leukemia was diagnosed 1 year later; cytogenetic studies were performed on circulating leukemic cells at this time. Analysis of elongated, finely banded chromosomes revealed three structural rearrangements, including two rather subtle interstitial deletions, in addition to trisomy 21 which was representative of the patient's constitutional karyotype. The karyotype of the leukemic cells was 47,XX,+21,t(3;18)(p23;q11.2), del(7)(q31.1q31.3), del(9)(p22p24 or p21p23). The patient received no cytostatic chemotherapy and died 4 months after the diagnosis of acute leukemia was made.

Child, Preschool↗

Effects of allyl alcohol and bromobenzene on trimethadione metabolism in the rat.

The relationship between the serum concentration ratio of 5,5-dimethyl-2,4-oxazolidinedione (DMO) to trimethadione (TMO) and the cytochrome P-450-dependent drug-oxidizing enzyme activity in rats pretreated with different dose levels of bromobenzene (BZ) and allyl alcohol (AA) was investigated. Pretreatment of rats with increasing dose levels of BZ and AA resulted in a prolongation of TMO half-life, an increase in the area under the curve (AUC), a decrease in clearance (Cl) and a decrease in the apparent volume of distribution (Vd). At each dose of BZ and AA used, there was a good correlation between DMO/TMO ratios in serum and activities of hepatic cytochrome P-450-dependent drug-oxidizing enzymes, such as cytochrome P-450 content, aminopyrine N-demethylase, TMO N-demethylase and aniline hydroxylase activities. However, the correlation between the serum DMO/TMO ratio and the alcohol dehydrogenase activity in AA treated rats was poor, whereas the activity of this enzyme was not changed in BZ treated rats. These results, together with the previous findings, indicate that determination of the serum levels of TMO and DMO may a useful index of drug-oxidizing capacity of rats with hepatic necrosis specified regions.

1-Propanol↗

Ph1-positive acute lymphoblastic leukemia with a 14q+ chromosome abnormality.

A 13-yr-old Japanese female with acute lymphoblastic leukemia (ALL) that was associated with a Philadelphia chromosome (Ph1) as well as a 14q+ chromosome abnormality is reported. The cell surface phenotype of leukemic cells was determined to be non-T, non-B ALL on the basis of positive Ia-like antigen, terminal deoxynucleotidyl transferase activity, and lack of receptors for sheep erythrocytes, surface immunoglobulin, or intracytoplasmic mu-chain immunoglobulin. The combination of both a Ph1 and a 14q+ has not been reported previously in patients with ALL.

Adolescent↗