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Biomedical subjects

S Misawa

Publications and source records attributed to S Misawa.

At least 289 records · Page 16Linked to original sources

Inversion of chromosome 3 in a case of chronic myelogenous leukemia with abnormal thrombopoiesis.

A patient with chronic myelogenous leukemia (CML) associated with a remarkable increase of micromegakaryocytes in bone marrow was revealed to have an abnormality of a long arm of chromosome #3, i.e., inv(3)(q21q26), in addition to a complex Ph translocation: t(9;22;15)(q34;q11;q22). Although several cases of acute leukemia with inv(3)(q21q26) and abnormal megakaryocytes have been reported, this is the first case in which the association of inv(3)(q21q26) with a megakaryocytic abnormality was observed in a patient with CML. Our findings suggest that this structural rearrangement may be more specifically associated with abnormal thrombopoiesis than are other structural anomalies of 3q.

Blood Platelets↗

Prefixation treatment with ethidium bromide for high resolution banding analysis of chromosomes from cultured human bone marrow cells.

Prefixation treatment of cultured human bone marrow cells with a DNA intercalating agent, ethidium bromide (EBr), induced a dose- and time-related elongation of chromosomes. When compared with EBr-free cultures, a 2.9-fold increase in the yield of early mitotic cells with more than 400 bands per haploid set of chromosomes was achieved by simply adding 10 micrograms/ml of EBr during the last 2 hours of culture. The proportion of early mitotic cells was equal to that obtained in methotrexate synchronized cultures. Fluorescence banding methods using base composition specific agents actinomycin D/DAPI for AT base pairs and chromomycin A3/distamycin A for GC suggested that EBr does not have base specificity, because EBr did not alter the banding patterns of chromosomes obtained with these staining procedures.

Aged↗

Detection of clonal karyotypic abnormalities in most patients with acute nonlymphocytic leukemia examined using short-term culture techniques.

Cytogenetic studies using short-term culture methods, both with and without methotrexate synchronization, were performed on 53 consecutive patients with acute nonlymphocytic leukemia. Among 50 patients with adequate specimens, 42 (84%) showed a clonal karyotypic abnormality. Numerical changes were observed in 22 cases. Chromosome #8 was most frequently gained (eight cases), whereas chromosome #7 was most frequently lost (five cases). Structural rearrangements were detected in 35 cases. A 5q- was seen in three cases, 6q- in two, 7q- in four, standard or variant t(8;21) in four, 11p- in two, t(11q23;-) in two, t(15;17) in four, inv(16) in two, and inv(20) in two. In five patients small abnormal clones were observed, which represented less than 10% of the total cells analyzed. In five other patients the sole abnormality detected was a tiny structural rearrangement. There was no significant difference in remission rate or in survival among groups of patients without clonal abnormality, with a mixture of normal and abnormal karyotypes or with only abnormal cells. Patients who showed complex karyotypes (four or more chromosomal alterations) had a very poor prognosis. In contrast, patients with t(8;21) tended to have a favorable survival outlook. A normal karyotype was associated with an intermediate prognosis.

Acute Disease↗

Trimethadione tolerance test for evaluation of functional reserve of the liver in patients with liver cirrhosis and esophageal varices.

Dimethadione (DMO)/trimethadione (TMO) ratios in serum after oral administration of TMO were investigated in 15 normal subjects and in 20 patients with cirrhosis and esophageal varices. Severe impairment of liver function was associated with a decrease in total cholesterol, total protein and plasma albumin, or an increase in total bilirubin, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, serum gamma-glutamyl transpeptidase and indocyanine green retention rate (ICG R15). Serum concentration ratios of DMO to TMO at 2 or 4 h after oral administration of TMO in patients were significantly decreased by 67 or 66%, respectively, compared to normal subjects. DMO/TMO ratios at 2 or 4 h following oral administration of TMO were well correlated with the liver function parameters (plasma albumin r = 0.758 at 2 h, r = 0.776 at 4 h; total protein r = 0.613 at 2 h, r = 0.619 at 4 h; ICG R15 r = -0.683 at 2 h, r = -0.746 at 4 h, in patients only; cholinesterase r = 0.873 at 2 h, r = 0.908 at 4 h) as well as with pharmacokinetic parameters (total body clearance r = 0.794 at 2 h, r = 0.786 at 4 h) in both the normal subjects and the patients. It suggests that the DMO/TMO ratio obtained in a single blood sample collected after oral administration of TMO might provide a useful measure for function hepatic reserve.

Adult↗

Hepatic trimethadione-oxidizing capacity remains normal in patients with extrahepatic cholelithiasis.

In the present study, using trimethadione (TMO) as an indicator substrate, we estimated pre- and post-operative differences in hepatic drug-oxidizing capacity in patients with extrahepatic cholelithiasis. Only total and direct bilirubin values were significantly higher in preoperative patients than in the controls. After operative procedures, those parameters did not show significant differences from corresponding control values. The serum dimethadione (DMO)/TMO ratios estimated 4 h after administration of 4 mg/kg of TMO. Neither pre- nor post-operative serum DMO/TMO ratios were significantly different from those in the controls. These results suggest that the hepatic drug-oxidizing capacity in patients with extrahepatic cholelithiasis remains unchanged even though the bilirubin level deviated from normal.

Bilirubin↗

Influence of short-term water deprivation on kinetics of trimethadione and its metabolite in rats.

The effects of acute (24-, 48- or 72-hr) water deprivation on the disposition kinetics of trimethadione (TMO) and its only metabolite, dimethadione (DMO), and on the microsomal hepatic drug-oxidizing enzyme activities were investigated in male rats. The DMO/TMO ratios in the serum at 2 hr after intravenous administration of 100 mg/kg TMO were significantly decreased in 48- and 72-hr water-deprived rats, but in 24-hr water-deprived rats, the DMO/TMO ratios were not changed as compared to controls and food restrictions. In the 48- and 72-hr water-deprived rats, contents of cytochrome p-450 and activities of aminopyrine N-demethylase were significantly decreased. On the other hand, activities of aniline hydroxylase in these rats were significantly increased as compared to controls and food restrictions. These results suggest that the effects of water deprivation on drug metabolism not only depend on the time of water deprivation but also vary with the indicator substrate.

Aminopyrine N-Demethylase↗

Chromosome aberrations in leukocytes of filaria-infected indigenous inhabitants in the Philippines.

In the course of genetic population surveys of a tribal group of the Philippine Negritos living on Mindanao island, microfilariae (Wuchereria bancrofti) were incidentally found on the microscopic slides for a cytogenetic investigation. Structural chromosome aberrations in the cultured leukocytes from 19 filaria-infected and 22 uninfected subjects were studied. The frequencies of chromosome type aberrations such as dicentrics and chromosome breaks in the infected subjects were significantly higher than those in the uninfected subjects (P less than 0.05). The frequencies of chromatid type aberrations, however, were not significantly different between the filaria-infected subjects and the uninfected subjects.

Black People↗

Association of the translocation (15;17) with malignant proliferation of promyelocytes in acute leukemia and chronic myelogenous leukemia at blastic crisis.

Cytogenetic studies were performed on nine patients with acute promyelocytic leukemia. Every patient had an identical translocation (15;17) or, in one case, a variant three-way rearrangement between chromosomes 7, 15, and 17. Another patient with chronic myelogenous leukemia was examined at the time of blastic crisis when the patient's bone marrow was infiltrated by hypergranular promyelocytes and blasts. Bone marrow cells contained a t(15;17) as well as a Ph1 chromosome. Only the latter abnormality was observed in the chronic phase of the disease. The translocation (15;17) was detected in all ten patients when bone marrow or peripheral blood cells were cultured for 24 hours prior to making chromosome preparations. However, the t(15;17) was not seen in three of these same cases when bone marrow cells were processed directly. These findings indicate that the t(15;17) is closely associated with acute proliferation of leukemic promyelocytes and that detection of this karyotypic defect may be influenced by the particular cytogenetic processing method used in different laboratories. An analysis of the banding pattern in the variant translocation provided additional evidence favoring chromosomal breakpoints at or very near the junction between bands 17q12 and 17q21 and at 15q22.

Bone Marrow↗

A case of acute lymphoblastic leukemia with severe hypodiploidy.

A case of acute lymphoblastic leukemia with a severe hypodiploid chromosome constitution is reported. The modal chromosome number was 36, and the karyotype of these cells was 36,X, -X, -2, -3, -5, -7, -9, -12, -13, -15, -16, -17, -20, +21, +mar,del(1) (p13.1p22.3),inv(3)(q13.3q29). In addition to a haploid set, extra copies of chromosomes #6, #10, #14, #18, and #21 were found, as in most cases with severe hypodiploid karyotypes. A second, near-triploid cell line was also observed. An examination of chromosomal heteromorphisms suggested that the severe hypodiploid clone originated either from a near-triploid cell or from a common precursor cell.

Chromosome Aberrations↗

A variant 15;17 translocation in a patient with acute promyelocytic leukemia.

We report a 36-year-old male with typical features of acute promyelocytic leukemia (APL) in whom a new variant 15;17 translocation, t(8p+;17q-), was found. Using G- and Q- banding techniques, the chromosome breaks were found to be near the junction of 8p12 and 8p21 and band 17q12, respectively. The breakpoint on 17q in our case was similar to that in previously described cases with a standard translocation (15;17). Consequently, this chromosome break or rearrangement at band 17q12, rather than the recipient site of translocation of the deleted material, appears to be of crucial importance in the genesis of APL.

Adult↗

Effects of cimetidine and diethylaminoethyl 2,2-diphenylvalerate HCL (SKF 525-A) on trimethadione metabolism in the rat.

The effects of cimetidine and diethylaminoethyl 2,2-diphenylvalerate (SKF 525-A) on trimethadione (TMO) metabolism were examined in the rat. The pretreatment of rats with cimetidine (100 mg/kg, i.p.) or SKF 525-A (40 mg/kg, i.p.) resulted in a prolongation of half-life (T1/2), an increase in the area under the curve (AUC) and a decrease in the total body clearance (CL) of TMO. However, the apparent volume of distribution (Vd) of TMO was not changed. The activities of hepatic cytochrome P-450-dependent drug-oxidizing enzymes such as aminopyrine and TMO N-demethylase, and aniline hydroxylase activities were decreased by pretreatment of rats with cimetidine or SKF 525-A. Cytochrome P-450 contents were not changed. The inhibition of aminopyrine and TMO N-demethylase activities in the rat pretreated with cimetidine or SKF 525-A was noncompetitive. These results suggest that cimetidine and SKF 525-A inhibited TMO metabolism in a similar manner to the rat pretreated with their doses.

Animals↗