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Biomedical subjects

T Miyahara

Publications and source records attributed to T Miyahara.

At least 127 records · Page 7Linked to original sources
PubMed1994

Determination of the target volume of HeLa cells treated with platinum-195 m radiolabeled cis-diammine(1, 1-cyclobutane-dicarboxylato)-platinum(II); comparison with cis- and trans-diamminedichloroplatinums(II).

HeLa S-3 cells were treated with 195mPt-radiolabeled cis-diammine(1, 1-cyclobutane-dicarboxylato)platinum(II) (carboplatin) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with carboplatin at 37 degrees C for 1, 2 and 3 h were 553.4, 194.3 and 68.7 microM, respectively. By using identically treated cells, the numbers of Pt-atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells. In this way the D0 values (D0, dose that would give an average of one lethal event per member of the population), expressed as the drug concentration, were substituted for the number of Pt atoms combined with each fraction. The target volumes, the efficiency of Pt atom to kill cells expressed as the reciprocals of the D0 values, were then calculated with each fraction. The results suggested that DNA was the primary target for cell killing by carboplatin. The target volumes for DNA were 0.891 x 10(4), 2.01 x 10(4) and 3.96 x 10(4) nucleotides for 1, 2 and 3 h treated cells, respectively. The cell killing effects of carboplatin were lower than those of cis-diamminedichloroplatinum(II) (CDDP) by factors of 6.0, 2.8 and 2.6 for 1, 2 and 3 h treatments at 37 degrees C, respectively, in terms of the target volume, while those in terms of the mean lethal dose (D0) were 59.5, 29.0 and 21.5, respectively.

Antineoplastic Agents↗
PubMed1994

Binding characteristics of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-2-platin um(II) to DNA, RNA and protein molecules in HeLa cells and its lethal effect: comparison with cis- and trans-diamminedichloroplatinums(II).

HeLa S-3 cells were treated with 195mPt-radiolabeled (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)-2-platinum(II) (DWA2114R) under various conditions, and the relationship between the lethal effect of the agent and the number of platinum (Pt) atoms binding to DNA, RNA and proteins was examined. The values of mean lethal concentration for the cells treated with DWA2114 at 37 degrees C for 1, 2 and 3 h were 137.3, 75.10 and 51.17 microM, respectively. Cells were treated identically and the numbers of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells. In this way, the D0 values (D0, dose that would give an average of one lethal event per member of the population), expressed as the drug concentration, were substituted for the number of Pt atoms combined with each fraction. The target volumes, the efficacy of Pt atom to kill cells expressed as the reciprocals of the D0 values, were then calculated for each fraction. Our findings suggested that DNA was the primary target molecule for cell killing by DWA2114R. The target volumes for DNA were 3.36 x 10(4), 4.00 x 10(4) and 4.10 x 10(4) nucleotides for 1-, 2- and 3-h treated cells, respectively. The cell-killing effects of DWA2114R were lower than those of cis-diamminedichloroplatinum(II) (CDDP) by factors of 1.54, 1.42 and 2.51 for 1-, 2- and 3-h treatments at 37 degrees C, respectively, in terms of the target volume, while those in terms of the mean lethal dose (D0) were 14.8, 11.2 and 16.0, respectively. The efficacy of DWA2114R in killing the cells was 2.6 times greater than that of CDDP in the 3-h treatment at 0 degrees C.

Carboplatin↗
PubMed1994

Hemodynamic parameters during dynamic exercise in patients with silent myocardial ischemia in the presence or absence of hypertrophy.

Hemodynamic parameters during supine leg exercise-induced myocardial ischemia were investigated in ten patients without left ventricular hypertrophy (group I), and in ten patients with left ventricular hypertrophy (group II). Both groups of patients had previously been diagnosed as having totally asymptomatic silent myocardial ischemia. Both groups were comparable in age, sex, left ventricular ejection fraction at rest, and extent of coronary artery disease. All of the patients exercised to the same extent without angina or its usual equivalent. Left ventricular filling pressure increased from 4 +/- 2 mmHg at rest to 11 +/- 3 mmHg at peak exercise in group I, and from 7 +/- 4 mmHg at rest to 19 +/- 7 mmHg at peak exercise in group II. Left ventricular filling pressure at peak exercise was significantly greater in group II than in group I (p < 0.01). Totally asymptomatic silent myocardial ischemia can be seen with either normal or mildly abnormal left ventricular filling dynamics during exercise. In addition patients with coexistent left ventricular hypertrophy can have severely abnormal left ventricular filling dynamics during exercise without ischemic cardiac pains. Therefore, severe ischemia and/or stretching of the ventricular wall may be necessary, but not sufficient, for the occurrence of chest pain.

Adult↗
PubMed1994

Electrocardiographic diagnosis of left ventricular hypertrophy improved by considering both QRS voltage and ST-T criteria.

We evaluated the usefulness of a combination of QRS voltage and the pattern of ST-T abnormality in the electrocardiographic diagnosis of left ventricular hypertrophy (LVH) in 100 middle-aged men: 32 normals, 59 with hypertension (HT), and 9 with hypertrophic cardiomyopathy (HCM) with evidence of LVH (RV5 or RV6 > or = 2.6 mV, SV1 + RV5 or SV1 + RV6 > or = 3.5 mV). They The subjects were classified into three groups based on ST-T pattern: normal (group N), early strain (group ES), and strain (group S). Echocardiographic evidence of LVH was present in 52.0% (52/100) of the subjects: 72.8% (43/59) of the patients with HT, all 9 patients with HCM, and none of the 32 normals. Echocardiographic evidence of LVH was present in 31.3% (20/64) of group N, 73.3% (11/15) of group ES, and all 21 subjects of group S. In patients with HT, the incidence of echocardiographic LVH was higher in group S (100%) than in both group ES (78.6%) and group N (60.6%). QRS voltage (RV5, RV6, RV5 + SV1, and RV6 + SV1) was significantly correlated with interventricular spetal thickness (IVST), IVST+LVPWT/2, and LV mass, as determined by echocardiography, in patients with LVH (IVST or left ventricular posterior wall thickness (LVPWT) of > or = 12 mm) (r = 0.55 to r = 0.75, p < 0.05), but not in patients without LVH (IVST and LVPWT < 12 mm). There were significant correlations between QRS voltage indices (RV5, RV6, RV5 + SV1, and RV6 + SV1) and IVST, IVST+LVPWT/2, and LV mass in group S (r = 0.68 to r = 0.86, p < 0.05), but not in group N. Values for IVST and LV mass were significantly greater in group S than in groups ES or N. The combination of QRS criteria and ST-T findings reflected the echocardiographic assessment of LVH, especially in patients with HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Differences in metabolism between 26,26,26,27,27,27-hexafluoro-1 alpha, 25-dihydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3 in cultured neonatal mouse calvaria.

We investigated the metabolism of 26,26,26,27,27,27-hexafluoro-1 alpha,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3, ST-630) and 1 alpha,25-dihydroxyvitamin (1,25(OH)2D3) in cultured neonatal mouse calvaria to elucidate why ST-630 is more potent than 1,25(OH)2D3 in stimulating bone resorption in organ culture. The metabolites were extracted with ethyl acetate or chloroform/methanol (1:1) from cultured calvaria or medium incubated with [3H]-ST-630 or [3H]-1,25(OH)2D3 for various periods, and separated by high performance liquid chromatography. [3H]-ST-630 in cultured calvaria was converted to [3H]-26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3(26,27-F6-1,23,25(OH)3D3,ST-232), which stimulated bone resorption equipotently as 1,25(OH)2D3. The amount of [3H]-ST-232 produced in the bone increased with passage of the culture period. In contrast, the amount of [3H]-ST-630 in the bones decreased in the 2 day cultures. In the medium, [3H]-ST-630 was hardly detectable for 2 days. This suggests that ST-630 is metabolized to ST-232 which is retained in the bones. On the other hand, some [3H]-1,25(OH)2D3 was metabolized to inactive forms detectable in the medium. Therefore, the high potency of ST-630 in stimulating bone resorption in organ culture may be associated with a difference between ST-630 and 1,25(OH)2D3 in the mode of metabolism in the cultured bones.

Animals↗
PubMed1994

[A clinical study on fluconazole against pulmonary mycosis associated with respiratory diseases].

In 34 hospitals in Kyushu area, the clinical effects and safety of fluconazole (FLCZ) against pulmonary mycosis were studied. To a total of 108 patients with respiratory diseases was FLCZ administered. The results were as follows. 1. Sixty-six cases were evaluable for the clinical efficacy of FLCZ. In 8 cases of pulmonary cryptococcosis, the clinical efficacy rate was 100% (8/8). In 58 cases of pulmonary aspergillosis, it was 43.1% (25/38). Overall, the clinical efficacy rate was 50% (33/66). 2. Fungi were eliminated in 3 of 6 cases in which Cryptococcus was detected, and were eliminated in 8 and reduced in 4 of 30 cases in which Aspergillus spp. including A. fumigatus were detected. 3. Side effects were observed in 5 of 87 cases (5.7%), none of them was serious, however. Abnormal results of laboratory tests that might be related to the FLCZ administration were observed in 5 cases (5.7%). 4. From these results, fluconazole appears to be a potent antifungal agent for treatment of pulmonary mycosis.

Adult↗
PubMed1993

Calcium regulating activity of 24a-homo-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3.

Two fluoro analogs of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24a-homo-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24aF2-homo-1,25(OH)2D3], and 26,27-dimethyl-24,24-difluoro-1 alpha,25-dihydroxyvitamin D3 [24F2-1,25(OH)2(Me)2D3] were examined for calcium (Ca)-regulating activity. The objective of the present study was to determine whether or not fluoro substitution at 24-position would alter activities of the original compounds, that is, 26,27-dimethyl 1 alpha,25-dihydroxyvitamin. D3[1,25(OH)2(Me)2D3] and 24-homo-1 alpha,25-dihydroxyvitamin D3 [24homo-1,25(OH)2D3], respectively. The relative activities of 24aF2-homo-1,25(OH)2D3, 24F2-1,25(OH)2(Me)2D3, and 1,25(OH)2D3 in competing with 1,25(OH)2D3 for binding to chick intestinal cytosol receptor were 0.28:0.5:1.0. The relative potencies of the same series of compounds in competition for the vitamin D-deficient rat serum binding sites were 0.04:0.15:1. Bone-resorbing activities of two fluoro analogs in cultures of neonatal mouse parietal bones were more potent than that of 1,25(OH)2D3. Similar results were recognized in stimulating activities of osteoclast-like cell formation. Responses of two fluoro analogs to intestinal Ca absorption were similar to that of 1,25(OH)2D3. The potencies of 1,25(OH)2D3 and its fluoro analogs in bone Ca mobilization were the highest with 1,25(OH)2D3, followed by 24F2-1,25(OH)2(Me)2D3 and 24aF2-homo-1,25(OH)2D3, in that order. From these results and the data of Paulson et al., fluoro substitution in 24-position of 1,25(OH)2D3 apparently does not alter their activities,hence, the fluoro substitution at 24-position of 1,25(OH)2D3 and the elongation of side chain of 1,25(OH)2D3 may not intensify Ca-regulating activity.

Animals↗
PubMed1993

Effect of antianginal agents on the relationship between rate-pressure product and myocardial oxygen uptake.

To evaluate the effects of antianginal agents on the correlation between rate-pressure product and myocardial oxygen uptake, multistage supine leg exercise tests were performed by 21 patients with stable effort-induced angina pectoris before and after administration of antianginal drugs (a calcium channel blocker of the dihydropyridine class [10 mg of nisoldipine orally] in 11 patients and a beta-blocker [0.2 mg/kg of propranolol intravenously] in 10 patients). The rate-pressure product was closely correlated with myocardial oxygen uptake before and after administration of each drug. However, the slope of the regression line of rate-pressure product (X) and myocardial oxygen uptake (Y) became significantly steeper after the calcium channel blocker administration, and the Y-intercept was significantly increased by administration of the beta-blocker. Myocardial oxygen uptake was increased after administration of the calcium channel blocker and the beta-blocker compared with control values at corresponding rate-pressure product. These observations should be considered when the rate-pressure product is used to predict myocardial oxygen uptake in patients with angina pectoris who are receiving antianginal drugs.

Adult↗
PubMed1993

Potentiating effects of organomercuries on clastogen-induced chromosome aberrations in cultured Chinese hamster cells.

Mercury compounds are among the most serious environmental pollutants. In this communication, the potentiating effects of organic and inorganic mercuries on clastogen-induced chromosome aberrations were studied in Chinese hamster CHO K1 cells. Post-treatment with monoalkylated mercuries--methyl mercuric chloride (MeHgCl) and ethyl mercuric chloride (EtHgCl)--increased the number of breakage- and exchange-type aberrations induced by 4-nitroquinoline 1-oxide (4NQO) and methyl methanesulfonate. With the DNA crosslinking agents mitomycin C (MMC) and cisplatin, MeHgCl enhanced both types of aberrations while EtHgCl enhanced breakage-type aberrations only. Since these monoalkylated mercuries did not show clastogenic effects by themselves under the present experimental conditions, the increases in chromosome aberrations were not additive. Dialkylated mercuries (dimethyl mercury and diethyl mercury) and inorganic mercuries (HgCl and HgCl2) did not show any potentiating effects. When MMC- or 4NQO-treated cells were post-treated with MeHgCl during the G1 phase, both breakage- and exchange-type aberrations were enhanced. Treatment with EtHgCl during the G1 phase also enhanced both types of aberrations induced by 4NQO. With MMC, however, G1 treatment with EtHgCl did not show any potentiating effect. MeHgCl and EtHgCl treatments during the G2 phase enhanced breakage-type aberrations only. Based on these results, the following possible mechanisms for potentiation of clastogenicity by monoalkylated mercuries were suggested; (1) they interfere with repair of base lesions induced by 4NQO and MMS during the pre-replicational stage, thereby increasing unrepaired DNA lesions which convert into DNA double-strand breaks in S phase, (2) MeHgCl (but not EtHgCl) also inhibits repair of crosslinking lesions during the pre-replicational stage, and (3) their G2 effects enhance breakage-type aberrations only.

4-Nitroquinoline-1-oxide↗
PubMed1993

Inorganic cadmium increases the frequency of chemically induced chromosome aberrations in cultured mammalian cells.

The co-clastogenic effect of cadmium ion (Cd2+) was studied in Chinese hamster CHO K1 cells and excision repair-deficient human XP20SSV cells. Cd2+ at < or = 28.0 microM did not show any clastogenic effects under the experimental conditions used. Cd2+ post-treatment at < or = 3.50 microM, however, increased the number of both breakage- and exchange-type chromatid aberrations induced by mitomycin C (MMC) and 4-nitroquinoline 1-oxide (4NQO) in CHO K1 cells. Enhancement of chromosome aberrations induced by MMC was observed when CHO K1 cells were treated with Cd2+ during the G1 phase. Cd2+ was also co-clastogenic with MMC in XP20SSV cells. Its co-clastogenic effect, however, was not observed in 4NQO-treated XP20SSV cells. These results suggest that Cd2+ inhibits DNA pre-replicational repair, perhaps DNA excision repair, thereby causing co-clastogenic effects.

4-Nitroquinoline-1-oxide↗
PubMed1993

Determination of the target volume of HeLa cells treated with platinum-195m radiolabeled trans-diaminedichloroplatinum(II): a comparison with cis-diaminedichloroplatinum(II).

HeLa S-3 cells were treated with 195mPt-radiolabeled trans-diaminedichloroplatinum(II) (TDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with TDDP at 37 degrees C for 1, 2 and 3 h were 163.7, 65.8 and 24.9 microM, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules was determined after the cells were fractionated using the method of Schneider. In this way, the D0 values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes, expressed as the reciprocals of the D0 values, were calculated for each fraction. The results suggested that DNA and high molecular weight RNAs (except t-RNA), under some limited condition, could be the target molecules for cell killing by TDDP. The target volumes for DNA were 1.31 x 10(3), 3.01 x 10(3) and 6.26 x 10(3) nucleotides for 1, 2 and 3 h treated cells, respectively. Cell killing effects of TDDP were lower than CDDP by a factor of 39.5, 19.0 and 16.5 for 1, 2 and 3 h treatments at 37 degrees C, respectively, when viewed from the stand point of the target volume, while those from the mean lethal dose (D0) were 17.6, 9.8 and 6.7, respectively.

Cell Survival↗
PubMed1993

Hemodynamic mechanisms of the antianginal action of a novel vasodilator FK409 in dynamic exercise-induced angina.

FK409 is a novel vasodilator with a unique chemical structure. We wished to elucidate the mechanisms of antianginal action of FK409 in dynamic exercise-induced angina. Twelve patients with stable effort angina pectoris were studied before and after a single 40-mg oral dose of FK409. Chest pain was induced in all of 12 patients during the control multistage bicycle ergometer exercise. After FK409 administration, the same workload did not induce chest pain in 6 patients. The ST segment at peak exercise showed less severe depression from 0.15 +/- 0.02 to 0.05 +/- 0.01 mV (p < 0.001). Left ventricular (LV) filling estimated by the Doppler method was reduced, and pulmonary artery wedge pressure decreased significantly (p < 0.001) throughout exercise testing after FK409. Myocardial oxygen uptake and coronary sinus flow throughout exercise testing decreased significantly (p < 0.05) after FK409 administration. The results of the present study demonstrate that decrease in myocardial oxygen demand may be caused by pre- and afterload reduction and that it could be a major mechanism of the antianginal action of FK409. However, other mechanisms such as redistribution of coronary blood flow to the subendocardium, direct dilatation of the stenotic parts of the epicardial arteries, and an increase in collateral blood flow should be considered additional possible mechanisms of the antianginal action of FK409.

Aged↗
PubMed1993

Hyperthermic enhancement of cytotoxicity and increased uptake of cis-diamminedichloroplatinum(II) in cultured human esophageal cancer cells.

Thermal enhancement of cytotoxicity of cis-diamminedichloroplatinum(II) (CDDP) has been well recognized and applied clinically to chemotherapy of various malignancies, but its fundamental mechanism remains to be elucidated. In order to obtain a clue to this mechanism, we analyzed the effect of hyperthermia on the uptake and subsequent distribution of [195mPt]CDDP in two lines of esophageal cancer cells (KYSE-150 and KYSE-170) established from clinical patients. First, we observed a significant increase in [195mPt]CDDP uptake by both types of cells at increasingly higher temperatures. The incorporated CDDP was distributed between the nucleus and the cytosol at a ratio of approximately 3:1, and the ratio remained the same at various temperatures. The CDDP was found in all four molecular fractions, i.e., DNA, RNA, protein, and TCA-soluble, with a slight preference for DNA at higher temperatures. Enhancement of cytotoxicity required simultaneous, and not sequential, treatments with CDDP and hyperthermia; hyperthermia after CDDP treatment increased the efflux of CDDP from the cells, and rather reduced the cytotoxicity of CDDP. These results suggest that thermal enhancement of the cytotoxicity of CDDP is caused mainly by acceleration of the drug entry into the cell, probably due to increased permeability, and a consequent increase in the amount of CDDP binding to DNA. This mechanism gives support for clinical trial of simultaneous treatment with CDDP and hyperthermia.

Carcinoma, Squamous Cell↗
PubMed1993

Abnormal postexercise systolic blood pressure response is a good indicator of impaired left ventricular filling during supine cycle ergometer exercise in patients with coronary artery disease.

To determine whether the postexercise systolic blood pressure (SBP) response is a useful marker of left ventricular filling abnormalities, supine leg exercise testing was conducted in 14 control subjects and 70 patients with coronary artery disease (CAD). An abnormal postexercise SBP response (the ratio of SBP after 3 min of recovery to the peak exercise SBP) was defined as 0.85 or more, which represented the cutoff point with the highest sensitivity and specificity for prediction of pulmonary artery wedge pressure (PAWP) of at least 20 mmHg at peak exercise in CAD patients. There was a significant difference between the SBP ratios of the two groups (Control, 0.72 +/- 0.05; CAD, 0.86 +/- 0.13; p < 0.01). There was no significant difference between the PAWP of the two groups at rest, but the PAWP at peak exercise was significantly higher in the CAD group (20.2 +/- 8.9 mmHg) than in the control group (11.5 +/- 4.0 mmHg)(p < 0.01). PAWP at peak exercise was > or = 20 mmHg in 35 (50%) of the 70 CAD subjects. The SBP ratio was significantly correlated with PAWP at peak exercise (r = 0.67, p < 0.01) in the CAD group, but not in the control group. An SBP ratio of > or = 0.85 showed a sensitivity of 80% and a specificity of 80% for predicting a peak exercise PAWP of > or = 20 mmHg in CAD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗