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Biomedical subjects

H Noguchi

Publications and source records attributed to H Noguchi.

At least 307 records · Page 17Linked to original sources
PubMed1989

Radiosensitivity test for cancer of the uterine cervix.

In selecting the method of treating uterine cervical cancer, radiosensitivity is one of the most important factors. To know this factor before treatment, we are trying to estimate radiosensitivity with changes of primary tumors before and after the irradiation. Tumors must be irradiated uniformly with small doses, and based on these considerations, we are attempting external test irradiation for estimation of radiosensitivity. Radiosensitivity was determined histopathologically by comparing the results of histological specimens taken before and seven days after test irradiation. Radiosensitivity is closely related to prognosis: of 183 cases with good sensitivity, 146 cases (79.8%) were surviving at five years after radiotherapy. On the other hand, the five-year survival rate of cases with poor sensitivity was only 37.2%. Comparing radiation with operation in operable cases of stage I and II, the five-year survival rate in cases with good sensitivity was about the same (90%). On the contrary, in cases with poor sensitivity, there was a substantial difference: that is, 66.0% of operated cases had a five-year survival compared with 39.7% of radiated cases.

Female↗
PubMed1988

Rapid methylation of genomic DNA in proliferating T-cells from bovine thymocytes.

Two subpopulations of bovine calf thymus cells were separated by buoyant density centrifugation. The low-density cells (L-cells) showed high response to T-cell mitogens, while the high density cells (H-cells) did not. The DNA-metabolizing enzyme activities were elevated 10-fold in L-cells in comparison with those in H-cells. L-cells contained a DNA-replicating complex, DNA replitase, while H-cells did not. These observations suggested that L-cells were proliferating, mature T-cells and H-cells were dying intrathymic cells. A DNA methyltransferase was associated with DNA replitase in L-cells. In order to determine whether replitase-associated DNA methyltransferase functions at replicating regions, the methylation pattern of genomic DNA of L-cells was compared with that of H-cells. No significant difference was found in the extent of CpG dinucleotide methylation, and in the location of mC in the satellite I DNA sequence as identified by Southern hybridization and direct sequencing. Thus the majority of methylation patterns of genomic DNA did not change during T-cell development in the thymus. The results indicated that the methylation patterns were rapidly maintained in proliferating T-cells. Although methods employed in the present study might not be sensitive enough to detect transient hemimethylation, it is suggested that the rapid methylation might be catalyzed, albeit not completely, by a DNA methyltransferase associated with the DNA replitase complex.

Animals↗
PubMed1988

Multiple-dose pharmacokinetics of nilvadipine in healthy volunteers.

Nilvadipine, a new antihypertensive and antianginal drug, was studied in six healthy male volunteers to evaluate its steady-state pharmacokinetics after oral dosing. The subjects were given a single dose of 4 mg, followed by 4 mg every 12 hours for six days after a washout period of more than 3 days. The pharmacokinetics of nilvadipine were well described by a linear model of triexponential equation with zero-order absorption. The steady state was reached by the fourth day of multiple dosing, with a twofold accumulation of trough plasma concentration and no accumulation of peak concentration. The mean plasma concentration at steady state was 1.0 ng/mL. The optical enantiomers of nilvadipine were also determined in the plasma. The plasma concentration of (+)-nilvadipine was about two and a half times higher than that of (-)-nilvadipine, and this ratio was unaffected by multiple dosing.

Administration, Oral↗
PubMed1988

A case of Vibrio vulnificus infection.

Vibrio vulnificus, a recently described strain of the halophilic Vibrio species, was isolated from the blood of a 73-year-old man, who developed rapidly progressive wound infection and fatal septicemia. Twenty-one patients with Vibrio vulnificus infection have been reported in the Japanese literature. Vibrio vulnificus most frequently causes primary septicemia and necrotising cellulitis after the eating of raw fish or shellfish or after exposure to seawater. The infection is characterized by its occurring during the warm months of the year, in patients with underlying diseases, especially liver diseases, and the mortality rate is surprisingly high. Clinicians should therefore consider the possibility of Vibrio vulnificus infection in the differential diagnosis of severe wound infections. Early surgical intervention and intensive antibiotic therapy are recommended for preventing the progress of the septicemia.

Aged↗
PubMed1988

Uterine body invasion of carcinoma of the uterine cervix as seen from surgical specimens.

To estimate the actual states of uterine body invasion of carcinoma of the uterine cervix, 301 radically hysterectomized specimens were reviewed histologically. Incidence of uterine body invasion was 21.6% in all cases (65 cases out of 301), 7.8% in stage Ib, 25.5% in stage IIa, and 38.2% in stage IIb. Most of the positive invasion cases had spread to other surrounding tissues. Vaginal wall was invaded in 58.5% of all positive cases, parametrial infiltration was recognized in 87.7%, and pelvic lymph node metastasis was seen in 52.3%. On the contrary, in negative cases these were 33.9, 19.1, and 15.7%, respectively. There was a higher incidence of the L type of Imai's CPL classification among positive cases of uterine body invasion than among negative cases (81.5% vs 38.1%). When cervical cancer spread into the uterine body, peritoneal carcinomatosis and distant metastasis increased. Thus the outcome of patients with positive invasion was, naturally, poor. Patients with negative invasion had a 5-year survival rate of 92.4%, compared to 53.8% in patients with positive uterine body invasion. These results suggest that uterine body invasion of carcinoma of the uterine cervix is an important prognostic factor and treatment should be modified in such cases.

Adenocarcinoma↗
PubMed1988

Sensitive sandwich enzyme immunoassay of human growth hormone (hGH) in serum and urine using monoclonal antibody-coated polystyrene balls.

A sensitive sandwich enzyme immunoassay for human growth hormone (hGH) using monoclonal antibody is described. A monoclonal anti-hGH IgG-coated polystyrene ball was incubated with hGH and subsequently with affinity-purified rabbit anti-hGH Fab'-horseradish peroxidase conjugate. Peroxidase activity bound to the polystyrene ball was assayed by fluorimetry using 3-(4-hydroxyphenyl) propionic acid as a substrate. The detection limits of hGH in serum and urine were 1.5 ng/l using 20 microliters of serum and 0.2 ng/l using 0.15 ml of urine, respectively. The specificity and assay precision were satisfactory. hGH levels in serum and urine determined by the present sandwich enzyme immunoassay using monoclonal anti-hGH IgG-coated polystyrene balls were well correlated to those determined by the previous sandwich enzyme immunoassay using rabbit anti-hGH IgG-coated polystyrene balls. Levels of hGH in urine collected as first morning voids from healthy subjects aged 19-28 yr were 6.4 +/- 3.2 (SD) ng/g creatinine. However, the present assay gave lower hGH levels than the previous assay. This was at least partly explained by the fact that hGH in urine was less efficiently bound to monoclonal anti-hGH IgG-polystyrene balls than standard hGH, while the binding of hGH in urine and standard hGH to rabbit anti-hGH IgG-coated polystyrene balls was equally efficient. In addition, gel filtration showed that 22K hGH, a major component, in urine was less efficiently bound to monoclonal anti-hGH IgG-coated polystyrene balls than standard 22K hGH. The nature of hGH in serum and urine remains to be investigated.

Adult↗
PubMed1988

Oxidation of nilvadipine, a new dihydropyridine calcium antagonist, to the corresponding pyridine by rat liver microsomes.

1. The oxidation of nilvadipine, a 1,4-dihydropyridine derivative, by rat liver microsomes and sex-related differences in this activity were investigated. 2. The kinetic data (Km and Vmax) for the formation of the corresponding pyridine analogue by liver microsomes from adult male rat (7 weeks old) were similar to those for the disappearance of nilvadipine, indicating that the aromatization of nilvadipine is the primary metabolic step. 3. The formation of the pyridine analogue required the presence of NADPH-generating system and was significantly inhibited by cytochrome c, metyrapone, and 7,8-benzoflavone, indicating the participation of cytochrome P-450. Phenobarbital pretreatment of rats caused an increase in the metabolism of nilvadipine. 4. Nilvadipine oxidase activity in adult male rat was about 10 times higher than that in adult female rat. In contrast, marked sex-related differences were not seen in immature rat (21 days old), and the activity was approximately twice as high as that in adult female rat. No activity was detected in the postmitochondrial fractions of lung, kidney, brain, heart, pancreas or small intestine of adult male rat.

Age Factors↗
PubMed1988

Disposition of 6-chloro-2-pyridylmethyl nitrate, a new anti-anginal compound, in rats and dogs.

1. The absorption, distribution, metabolism and excretion of 6-chloro-2- pyridylmethyl nitrate, a new anti-anginal compound, were investigated in rats and dogs after intravenous and peroral administration of the 14C-labelled or unlabelled drug. 2. The half-lives of plasma levels for the alpha and beta phase and systemic availability were 6 min, 42 min and 26-50% respectively in rats, and 8 min, 66 min and 5% respectively in dogs. 3. Radioactivity was rapidly distributed in the tissues of rats, and recovered mainly in the 0-24 h urine (95% of dose within 24 h) with no excretion in the expired air. 4. Several metabolites were detected on t.l.c. of rat and dog urine, and four were identified as N-(chloro-2-pyridylcarbonyl)-glycine (M1, 56%), N-acetyl-S-(6- chloro-2-pyridylmethyl)-L-cysteine (M2, 29%), 6-chloro-2-pyridinecarboxylic acid (M3, 5%) and 6-chloro-2-pyridylmethyl. beta-D-glucuronate (M4, 7%). No unchanged drug was excreted.

Angina Pectoris↗
PubMed1988

Pharmacokinetics of nilvadipine, a new dihydropyridine calcium antagonist, in mice, rats, rabbits and dogs.

1. The pharmacokinetics of nilvadipine in male and female rats, and in male mice, rabbits and dogs were studied after i.v. and oral dosing. 2. After i.v. dosing (0.1 mg/kg), the plasma concentrations of nilvadipine declined two- or three-exponential with terminal half-lives of 0.73 h in mice, 1.2 h in male and female rats, 3.7 h in rabbits and 5.0 h in dogs. Sex difference in pharmacokinetics after i.v. dosing in rats was not found. The systemic plasma clearance was in the order of mice greater than rats greater than rabbits greater than dogs, and nearly equalled the hepatic blood flow in each species. The volume of distribution at steady-state was high (greater than 4 L/kg) in all species. 3. After oral dosing, plasma concentrations of nilvadipine peaked within 1 h in all species except for middle and higher doses (4 and 16 mg/kg) in dogs. The area under the plasma concentration-time curves in male rats (3.2-100 mg/kg) and dogs (1-16 mg/kg) increased in proportion to the dose. Bioavailability was low in male rats (3-4%) and rabbits (2%), but in other species was 29-44%. The oral clearance in male rats was about 8 times higher than in female rats. 4. The free fraction of nilvadipine in plasma was 1.94% in mice, 1.89% in rabbits and 0.85% in dogs, with no dependence on plasma concentration over a range of 10-100 ng/ml.

Animals↗
PubMed1988

[Treatment with degradable starch microspheres (DSM) in malignant hepatic tumors-clinical experience of implantable drug delivery system (Port-A-Cath)].

Chemoembolization with degradable starch microspheres (DSM) was performed in twelve cases of hepatocellular carcinoma, one case of cholangioma, and one case of metastatic liver cancer. The following results were obtained. (1) Tumor regression of over 50% was observed in eight of fourteen cases. Tumor regression of over 25% was obtained in ten of fourteen cases. (2) Half of the cases had fever, pain and leukocytopenia, but they were slight and transient. (3) Implantable drug delivery system (Port-A-Cath) was applied for intra-arterial chemoembolization in four cases. The longest implantation period was 662 days and 33 infusions were made. These results suggest that chemoembolization with DSM can be effectively used in the treatment of malignant hepatic tumors.

Adenoma, Bile Duct↗
PubMed1988

[Assessment of therapeutic effects by transcatheter arterial embolization (TAE) in hepatic malignant tumors with degradable starch microspheres (DSM)].

Transcatheter arterial embolization (TAE) with degradable starch microspheres (DSM) was carried out for fourteen cases with hepatic malignancies including twelve cases with hepatocellular carcinoma (HCC), one case with cholangiocarcinoma and one with metastatic liver cancer. DSM combined with anticancer agents were administered through a catheter introduced by Seldinger's method, in ten cases and through subcutaneously implanted drug delivery system (Port-A-Cath) in four cases. The dose of DSM was 900 mg/body and adriamycin 30-40 mg/m2 through the catheter or 12-14 mg/m2 through Port-A-Cath was used for HCC and cholangiocarcinoma. A same dose of DSM and mitomycin C 15 mg/m2 was administered for metastatic liver cancer through the catheter immediately after angiography. Results were as follows: 1) Partial response (PR) was obtained in six cases (50%) with HCC, and there were two other cases with minor response (MR). PR in cholangiocarcinoma and CR in metastatic liver cancer were obtained. 2) There were no adverse effects in four cases with Port-A-Cath. 3) The concentration of adriamycin in the peripheral venous blood was lower than that of one shot therapy, and decreased rapidly within an hour. These results suggested that good therapeutic effects can be obtained by TAE with DSM combined with anticancer agents for hepatic malignancies.

Adenoma, Bile Duct↗
PubMed1988

Stereoselective oxidation and plasma protein binding of nilvadipine, a new dihydropyridine calcium antagonist, in man.

The stereoselectivity in the plasma protein binding and oxidative metabolism of nilvadipine, a new dihydropyridine calcium antagonist, in man was studied. The free fraction values (fp) for the plasma protein binding of (+)- and (-)-nilvadipine determined by equilibrium dialysis were 1.00 and 0.90%, respectively; the fp of the (+)-nilvadipine was a little higher than that of the (-)-enantiomer. Marked differences between enantiomers were not observed in the blood to plasma ratio. On the other hand, Vmax/Km value, which is equivalent to the intrinsic clearance of the drug, for the oxidation of (+)-nilvadipine to the corresponding pyridine analogue by human liver microsomes was 0.43-0.54 times less than that for the oxidation of the (-)-enantiomer.

Blood Proteins↗