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Biomedical subjects

K Sakamoto

Publications and source records attributed to K Sakamoto.

At least 649 records · Page 36Linked to original sources

The effect of diltiazem on hepatic drug oxidation assessed by antipyrine and trimethadione.

The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500-mg antipyrine and 250-mg trimethadione was studied in six healthy male subjects. Diltiazem decreased the total body clearance from 34.0 +/- 8.0 to 28.6 +/- 6.1 mL/min (P less than .01), and prolonged the elimination half-life from 12.6 +/- 3.0 to 14.3 +/- 2.5 hours (P less than .01) of antipyrine without any changes in volume of distribution. The cumulative renal excretion (% dose) of antipyrine was significantly increased from 2.23 +/- 0.73 to 2.78 +/- 0.83% (P less than .05). Clearances of production for three major antipyrine metabolites, norantipyrine (4.31 +/- 1.64 to 3.50 +/- 1.28 mL/min, P less than .01), 3-hydroxymethylantipyrine (4.67 +/- 1.63 to 3.82 +/- 1.34 mL/min, P less than .01) and 4-hydroxyantipyrine (10.47 +/- 3.41 to 8.16 +/- 2.82 mL/min, P less than .01) were reduced significantly by diltiazem. On the other hand, diltiazem did not produce any significant changes in pharmacokinetic parameters of trimethadione and plasma concentration ratio, oxidative major metabolite of trimethadione to trimethadione itself. These results suggest that other drugs metabolizing the same hepatic oxidative pathways as antipyrine, may be influenced by diltiazem.

Adult↗

Explant organ culture: a review.

Organ explant culture models offer several significant advantages for studies of patho-physiologic mechanisms like cell injury, secretion, differentiation and structure development. Organs or small explants/slices can be removed in vivo and maintained in vitro for extended periods of time if careful attention is paid to the media composition, substrate selection, and atmosphere. In the case of human tissues obtained from autopsy or surgery, additional attention must be paid to the postmortem interval, temperature, hydration, and cause of death. Explant organ culture has been effectively utilized to establish outgrowth cell cultures and characterize the histiotypic relationships between the various cell types within an organ or tissue.

Animals↗

Isolation of a population of transiently transfected quiescent and senescent cells by magnetic affinity cell sorting.

Rous sarcoma virus (RSV) and cytomegalovirus (CMV) promoters were tested for activity in proliferating and nonproliferating (quiescent or senescent) human embryo fibroblasts. These promoters were cloned upstream of the coding sequence for the Tac subunit of the interleukin 2 receptor, and activity was calculated from the fraction of Tac antigen positive cells detected in a coupled transient transfection/magnetic affinity cell sorting assay. Differences in promoter activities are substantial in quiescent cells: the efficiency of the RSV promoter is no greater than background whereas the CMV promoter is equally active in serum concentrations ranging from 0.5 to 20%. While both promoters are functional in growing cells (WI-38 and HeLa), the CMV promoter exhibits twofold greater activity. Surprisingly, in senescent cells both promoters exhibit the same degree of activity.

Avian Sarcoma Viruses↗

The late waves of brainstem auditory evoked potentials in children with cerebrovascular diseases.

We examined brainstem auditory evoked potentials (BAEPs) in 28 children with cerebrovascular diseases and 38 normal control subjects and investigated the neuroanatomic correlations of the late waves (VI and VII) of the BAEPs. The patients included 19 patients with moyamoya disease and 9 with other cerebrovascular accidents. Wave VI was more consistently seen (only missing in 2 cases, 5%-2 ears, 3%) than wave VII (missing in 26 cases, 68%-40 ears, 53%) in the control group. Absent, depressed or prolonged wave VI correlated well with cerebral lesions involving internal capsule and basal ganglia, while wave VII had a less significant correlation with any cerebral lesions in children with cerebrovascular diseases.

Adolescent↗

Clinical and neuropathological findings in severe athetoid cerebral palsy: a comparative study of globo-Luysian and thalamo-putaminal groups.

We divided cases of severe athetoid cerebral palsy originating perinatally into two groups neuropathologically, the "globo-Luysian group" (GL) and the "thalamo-putaminal group" (TP). The major abnormal sites in GL were the pallidum and subthalamic nucleus, and in TP the thalamus and putamen. The lesions in TP were more widespread and frequently accompanied by fibrillary gliosis in the central gray matter of the midbrain, and subthalamic nuclei were dominantly devastated. Concerning the etiology, GL and TP were related to perinatal severe jaundice and neonatal asphyxia, respectively. The patients in TP showed lower mental ability and suffered from more intractable convulsions than those in GL. In GL, rigidospasticity was frequently demonstrated with fluctuation of athetoid movements, while in TP various abnormalities of muscle tone were observed, with rather restricted athetosis.

Adolescent↗

Inhibitory effect of aclarubicin on endothelium-dependent relaxation of rat aorta.

The effects of aclarubicin on endothelium-dependent and -independent vasorelaxations were investigated in aortic strips from rats. Aclarubicin (5.9-23.6 microM) inhibited endothelium-dependent relaxation and the increment of the cyclic GMP level in aortic strips in response to acetylcholine but not the endothelium-independent relaxation and the increase of cyclic GMP level in response to sodium nitroprusside. Aclarubicin also inhibited endothelium-dependent relaxations in response to ATP and calcium ionophore A23187. These results suggest that aclarubicin can inhibit endothelium-dependent relaxation by acting somewhere distal to receptor stimulation in vascular endothelial cells.

Acetylcholine↗

Cerebral infarction: early detection by means of contrast-enhanced cerebral arteries at MR imaging.

The authors describe a new magnetic resonance (MR) imaging sign of acute cerebral ischemia/infarction. Abnormally contrast material-enhanced curvilinear structures were demonstrated in eight patients in the evolving area of cerebral ischemia/infarction within 26 hours after the ictus on contrast-enhanced, high-field-strength (1.5-T), T1-weighted spin-echo images. The abnormal enhancement is considered to represent cortical arterial vessels of markedly slowed circulation in areas of underlying brain injury, which will eventually progress to frank brain infarction. This was demonstrated at computed tomographic (CT) and follow-up MR examinations. Characteristically, the degree of the contrast enhancement of vessels appeared most intense in the proximal portions, and the intensity of enhancement gradually diminished in the more distal portions of these vessels as they pass over the convexities and finally disappear.

Acute Disease↗

Long-term explant culture of human colon and a 3-step transformation model for rat colonic epithelium.

Our previous studies have suggested that colonic epithelium from rodents pretreated in vivo with suboptimal doses of carcinogen could be more easily maintained in explant culture. Transformation of colonic epithelium from these explants may be induced by subsequent exposure to additional genotropic agents. Therefore, we describe the development of a 3-step transformation model which uses (1) in vivo pretreatment with a suboptimal dose of 1,2-dimethylhydrazine (DMH) followed by (2) in vitro organ culture and exposure to xenotropic murine sarcoma virus (X-MSV), and finally (3) xenograft maintenance in nude mice to allow sufficient time for transformation. Male Wistar rats were injected intramuscularly with 20 mg DMH/kg 10 times per week followed by the removal and explant culture of the colon, which was then treated in vitro with X-MSV, and transplanted into nude mice after 1 week of culture. All the nude mice (n = 6) transplanted with rat colon explants contained viable xenograft explant epithelium and 1 of the 6 showed transformation. Our results demonstrate that the epithelium from animals pretreated with suboptimal doses of carcinogens can be easily transformed. We also demonstrate that human colonic epithelium is viable for an extended period of time in this model. Based on these results, we hypothesize that such a 3-step transformation model is applicable for carcinogenesis studies of various organs from different species, including human if one uses dysplastic or 'pre-neoplastic initiated' tissues obtained at surgery (e.g., ulcerative colitis; Barret's esophagus, etc.).

Animals↗

Development of a radioimmunoassay for human group-II phospholipase A2 and demonstration of postoperative elevation.

A radioimmunoassay (RIA) for the determination of human group-II phospholipase A2 (M-PLA2) has been developed. M-PLA2 was purified from human spleen. Monoclonal antibody (IgG) was prepared by fusion of splenic cells from immunized mice with M-PLA2 and the mouse myeloma cell line NS-1. The RIA was carried out by a single antibody method. The assay is sensitive (0.78 micrograms/l), reproducible and specific. In healthy individuals, the serum M-PLA2 concentration ranges from 1.4 to 4.2 micrograms/l, the average being 2.2 +/- 0.1 micrograms/l (mean +/- SE). Using the RIA, we found increased serum M-PLA2 in patients with various infections and malignant tumors. We also showed the postoperative transient elevation of serum M-PLA2 in cases without any infectious complications. The elevation was independent of the surgical procedure or site. The maximum serum M-PLA2 level was seen on the 2nd to 4th postoperative day. In these patients, the serum M-PLA2 and C-reactive protein levels were significantly correlated. The present study indicated that serum M-PLA2 is an acute phase reactant.

Acute-Phase Proteins↗

Effects of physical exercise and cold stimulation on serum testosterone level in men.

The concentrations of testosterone (TS) and other related hormones in serum were examined before and after physical exercise with a bicycle ergometer (90 Watts, 20 min.) and a cold water stimulation in 32 19-year-old males. While exercising, the serum TS level significantly increased by 20.8% (p less than 0.05), the luteinizing hormone (LH) level by 3.6% (p less than 0.05) and noradrenaline (NA) level by 140.0% (p less than 0.01). During cold water stimulation, TS decreased by 10.0%, LH increased by 22.1% and NA decreased by 23.8%. Based on changes in hormone levels within the individual during the loads. there was a significant positive correlation coefficient (r) between TS and LH, and between TS and NA, with r (TS-LH) = 0.399 (p less than 0.05) and r (TS-NA) = 0.481 (p less than 0.05) for physical exercise, while r (TS-LH) = 0.403 (p less than 0.05) and r (TS-NA) = 0.431 (p less than 0.05) for cold water stimulation, respectively. These results suggest that physical exercise increases TS level in serum by increasing LH and NA levels, but these tendencies were not found with cold water stimulation.

Adult↗

A case of non-Hodgkin's lymphoma associated with hypercalcemia.

A patient with a diffuse, small cleaved cell, non-Hodgkin's lymphoma associated with marked hypecalcemia was described. Antibody to the adult T-cell leukemia-lymphoma virus was absent. Although bone marrow was infiltrated by lymphoma cells, destructive or lytic bone lesions could not be detected. The serum level of immunoreactive parathyroid hormone C-terminal (PTH-C) was normal. The serum level of 1, 25-dihydroxyvitamin D was lower than normal. This case suggests that other humoral substances produced by lymphoma cells may be responsible for hypercalcemia.

Humans↗

[Erythrocyte membrane abnormality of essential hypertension with special reference to membrane fluidity and Na(+)-K+ ATPase activity].

UNLABELLED: To clarify the pathogenesis of essential hypertension (EHT), the biophysical property (fluidity) and Na(+)-K+ ATPase activity of the erythrocyte membrane were pursued. Seventeen patients with EHT, 14 normotensives (NT) with familial history of hypertension and 25 healthy controls (CONTROL) without familial history of hypertension were subjected in this study. Electron spin resonance (ESR) method using 5- or 16-stearic acid label (SAL) was used to measure the membrane fluidity of erythrocytes. Since little changes in the Na(+)-K+ ATPase activity may be expected, the bioluminescence method was adopted to measure the enzyme activity. By evaluation of several measuring conditions for the enzyme activity, the method was revealed to be highly sensitive and reproducible, as has been reported by Lechi. A significant decrease was found in the erythrocyte membrane fluidity of EHT patients using 16-SAL with the parameter of peak height ratio (ho/h-1), when compared with that of CONTROL (EHT: 5.31 +/- 0.13; CONTROL: 5.20 +/- 0.11, p less than 0.05). The decrease of erythrocyte membrane fluidity, values of peak height ratio using 16-SAL, correlated significantly with the systolic blood pressure (r = 0.36 p less than 0.05) and diastolic pressure (r = 0.34 p less than 0.05). The values of peak height ratio of NT (5.26 +/- 0.17) were found in between those of EHT and CONTROL. The levels of erythrocyte membrane Na(+)-K+ ATPase activity in EHT showed higher than those of CONTROL, but the difference was not significant. They did not correlate with the membrane fluidity and the blood pressure. The artificial modifications of membrane cholesterol contents of erythrocytes made the same directional changes in both the membrane fluidity and the enzyme activity. The results showed that the abnormality of biophysical property existed in the deeper portion of the erythrocyte membrane and indicated the possibility of hereditary perpetuation of EHT. As to changes in Na(+)-K+ ATPase activity, no definite contributory relation to EHT has been identified.

Adult↗

[Morphological changes in the pleura caused by intracavitary administration of bleomycin].

We administered bleomycin to the intrapleural cavity of hamsters and observed acute and chronic histological changes of visceral pleura using light and electron microscopies. At 7 days after bleomycin challenge, we could find out the pleural thickening with infiltration of inflammatory cells, and then formation of pleural fibrosis at 28 days. However, in our study there was no abnormal findings of the lung parenchyma in morphology and intraalveolar cells, and lung distensibility. The dose (10-20 units/kg body weight) used in the study did not cause the abnormal changes in the parenchyma, although pleural thickening occurred. We suggest that intracavitary bleomycin administration is safely used for the treatment of malignant pleural effusion.

Animals↗

Relation between functions and conformational characteristics of modified nucleosides found in tRNAs.

Conformational characteristics of N4-acetyl-2'-O-methylcytidine (ac4Cm), 5-methyl-2'-O-methylcytidine (m5Cm) and N2-dimethyl-2'-O-methylguanosine (m2(2)Gm) found in tRNAs from extremely thermophilic archaebacteria were analyzed by proton NMR spectroscopy. The 2'-O-methylation of ac4C, m5C and m2(2)G was found to stabilize the C3'-endo form and therefore cause "conformational rigidity". In particular, the ac4Cm was found to be extremely rigid due to additive effects of the N4-acetylation and 2'-O-methylation. Therefore, tRNAs from the extremely thermophilic archaebacteria use the base modifications in combination with the 2'-O-methylation, resulting in stabilization of the A-type conformation at specific positions in the tRNAs even at very high temperatures. In contrast, mesophile tRNAs use for a given site only one of these ribose and base modifications each of which is effective enough by itself at ordinary temperatures. These findings are consistent with our previous findings that roles of a variety of post-transcriptional modifications are to regulate the conformational rigidity/flexibility which is essential for the tRNA functions.

Archaea↗

[Sulfuric acid submicron aerosols induce morphological changes in the central airways in the guinea pig].

We examined the airway injury of the guinea pig exposed to sulfuric acid submicron aerosols (1 mg/m3). The animals were exposed to filtered air (sham control) or to submicrometer-sized sulfuric acid aerosols for 4 hr/day, 6 days/week, with sacrifices after 4 hours, 3 days, 1, 2, and 4 weeks of acid exposure. Light and electron microscopic examinations revealed that epithelial injury such as disappearance of cilia in the central airways was observed and the severity of the injury increased with exposure duration. This experimental study shows that submicrometer particles of sulfuric acid induces significant alterations in the central airways and may be involved in the incidence of asthma attack.

Aerosols↗

Elevation of serum group II phospholipase A2 in patients with cancers of digestive organs.

We demonstrated the elevation of serum Group II phospholipase A2 (PLA2) in 56.5% of patients with cancers of digestive organs. The elevation of serum Group II PLA2 was more frequently seen in patients with advanced or metastasized cancer than in those with early cancer (66.7 vs. 35.0%). There was no correlation between serum Group II PLA2 and carcinoembryonic antigen (CEA) in these patients. A combined assay of Group II PLA2 and CEA increased the sensitivity of detection of all, early and advanced cancers from 37.1, 15.0 and 47.6% with CEA alone to 71.0, 45.0 and 83.3%, respectively.

Carcinoembryonic Antigen↗

[Long-term prognosis of Crohn's disease].

Two hundred and three patients with Crohn's disease seen at our clinics and affiliated centers from April 1973 to August 1988 were followed for 4.4 +/- 3.2 years (mean +/- SD), in order to evaluate the prognosis of Crohn's disease in Japan. These 203 patients (142 males and 61 females) fulfilled the following criteria; 1) they have been followed at the outpatients clinic for more than six months or 2) they have been admitted to us for more than a month. Of these, 83 (40.9%) had ileitis, 60 (29.6%) ileocolitis, 25 (12.3%) colitis, 15 (7.5%) miscellaneous types and the remaining 20 (9.9%) had undergone bowel resection. Cumulative survival rate and cumulative probability of surgery were calculated by life table method. Cumulative survival rate in these patients was compared with expected survival rate of sex and age matched general population. Cumulative survival rates five and ten years after diagnosis were 98.9% and 98.9%, respectively. There were no significant differences in the survival rates between two groups. Cumulative probability of surgery five and ten years after onset of symptoms were 16.2% and 39.1%, respectively. Cumulative probability of surgery five and ten years after diagnosis were 25.9% and 46.9%, respectively. From these results, the prognosis of Japanese patients with Crohn's disease appears to superior to that in European and American literatures.

Adult↗