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Biomedical subjects

Y Homma

Publications and source records attributed to Y Homma.

At least 271 records · Page 15Linked to original sources
PubMed1987

Inhibition of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat urinary bladder carcinogenesis by alpha-difluoromethylornithine.

The effect of oral administration of alpha-difluoromethylornithine (DFMO), an irreversible ornithine decarboxylase inhibitor, on N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN)-induced rat urinary bladder carcinogenesis was investigated. Four-wk-old male Fischer 344 rats, 30-38 per group, were divided into 3 groups; each group was divided into 3 subgroups. In Group A, 6-wk treatment with 0.05% BHBN in drinking water was followed by either 0.5% (A1), 0.2% (A2), or 0% (A3) DFMO in drinking water for 34 wk. In Group B, coadministration in drinking water of 0.01% BHBN and either 0.5% (B1), 0.2% (B2), or 0% (B3) DFMO was continued for 30 wk. Group C consisted of animals receiving 0.5%, 0.2%, or 0% DFMO in drinking water for 34 wk without prior or cocarcinogen treatment. Bladder tumorigenesis was clearly inhibited by DFMO; tumor incidence was 14 of 37 (38%) in A1, 16 of 38 (42%) in A2, and 31 of 35 (89%) in A3, and 7 of 35 (20%) in B1, 14 of 35 (40%) in B2, and 28 of 35 (80%) in B3 (P less than 0.01, DFMO groups as compared to the respective control A3 or B3). The average tumor volume was strikingly reduced in Group A rats given DFMO (3.0 mm3 in A1, 5.0 in A2, and 38.6 in A3). Significant suppression of tumor multiplicity (number of tumors/tumor-bearing bladder) was observed in DFMO-treated subgroups in Group B (1.1 in B1, 1.3 in B2, and 1.8 in B3). In both Groups A and B, however, DFMO failed to suppress hyperplastic changes (simple hyperplasia) or preneoplastic lesions (nodulopapillary hyperplasia). Systematic examination of all pertinent organs excluding the brain showed no adverse effects attributable to DFMO treatment except for decrease in body weight (less than 7%), which was consistently observed in the groups receiving 0.5% DFMO, and reduction in the combined weight of the prostate and seminal vesicles (less than 20%), which was noted in Group B in which exposure to DFMO was started at a younger age. These results indicate that oral administration of DFMO is quite effective in suppressing (or retarding) BHBN-induced carcinogenesis with minimal untoward effects and confirm the similar inhibitory effects demonstrated earlier with the heterotopically transplanted rat urinary bladder system.

Administration, Oral↗
PubMed1987

The effect of CS-514 on serum lipids and apolipoproteins in hypercholesterolemic subjects.

CS-514 is a metabolic product of compactin and has a potent cholesterol-lowering effect in vitro and in animal studies by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The efficacy and adverse effects of the agent were studied in 41 hypercholesterolemic subjects by administering daily doses of 5, 20, or 40 mg for four weeks under double-blind conditions. Mean total serum cholesterol level was reduced by 11.1% in the 5-mg group, 18.8% in the 20-mg group, and 25.3% in the 40-mg group. Marked reduction of total serum cholesterol level was also observed in heterozygous familial hypercholesterolemics. Mean low-density lipoprotein cholesterol level and apolipoprotein B concentration decreased by 38.5% and 28.8%, respectively, in the 40-mg group, while high-density lipoprotein cholesterol level increased by 11.8%. No serious clinical and laboratory abnormalities were observed. Plasma cortisol and testosterone levels were not significantly affected. These results suggest that CS-514 will be a useful agent in the treatment of nonfamilial and heterozygous familial hypercholesterolemia.

Adult↗
PubMed1987

Induction of high-grade, high-stage carcinomas in the rat urinary bladder.

The hypothesis that biologic aggressiveness of bladder cancer is determined by carcinogen dose was tested using heterotopically transplanted rat urinary bladders (HTBs). Young male Fischer rats, which were recipients of normal bladders, were divided into three groups; the first group received 0.5 mg of N-methyl-N-nitrosourea (MNU) into HTBs for six doses, a second, 0.05 mg for six doses and the third, 1 mg for three doses. Separately, a group of animals received bladders from rats treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) in drinking water for 4 weeks; the transplanted bladders then were treated with 0.5 mg of MNU for six doses. Treatment with the larger dose of MNU resulted in a significant increase in tumor incidence and frequency of invasive carcinomas. The combination carcinogen treatment induced more invasive carcinomas than the single treatment. The data suggest that deeply invasive carcinomas may develop in two ways: the first is by emergence of a more anaplastic cell population within a pre-existing noninvasive carcinoma and the second is by the de novo development of an invasive carcinoma directly from a severely dysplastic urothelium, which is acceptable as carcinoma in situ. Squamous differentiation was characteristic of deeply invasive carcinomas. The dose of carcinogen(s) is a determinant of aggressiveness of bladder carcinomas.

Animals↗
PubMed1987

Comparison of selectivity of LDL removal by double filtration and dextran-sulfate cellulose column plasmapheresis, and changes of subfractionated plasma lipoproteins after plasmapheresis in heterozygous familial hypercholesterolemia.

The possibility of selective removal of low density lipoprotein (LDL) by double filtration (DF) and dextran-sulfate cellulose (DSC) column plasmapheresis in hypercholesterolemia and the acute recovery process of the subfractionated plasma lipoproteins after plasmapheresis in heterozygous familial hypercholesterolemia were investigated. Sixty-six percent of the LDL cholesterol and 42% of the HDL cholesterol were removed by 2.5 L DF plasmapheresis with the second filters having average pore diameters of 30 nm and 40 nm. Fifty-nine percent of the LDL cholesterol was removed by 2.5 L DSC column plasmapheresis, while HDL cholesterol did not change. Therefore, DSC column plasmapheresis could remove LDL much more specifically than DF plasmapheresis. VLDL increased rapidly and reached the preplasmapheresis level within four days after plasmapheresis. IDL returned to the preplasmapheresis level in 2 weeks. The LDL1 level was approximately 80% of the preplasmapheresis level on the 14th day. LDL2 reached the peak at the seventh day. HDL2 and HDL3 moved in the same manner and reached the peak on the seventh day after DF plasmapheresis.

Adult↗
PubMed1987

The effect of temperature of fluorescence for liquid scintillators and their solvents.

The pulse-height distributions for 241Am and 131mXe in PPO solutions of the aromatic hydrocarbons, i.e. benzene, o-xylene, m-xylene, ethylbenzene and cumene are found to shift toward higher pulse-heights with decreasing temperature. Under u.v. excitation, the fluorescence intensity of these pure aromatic hydrocarbons increases markedly and the fluorescence maximum is found to shift to longer wavelengths with decreasing temperature. In conjunction with observations of the pulse-height shift in liquid scintillators and the fluorescence emission from the pure solvents, the pulse-height shifts observed are interpreted in terms of excimer formation in the aromatic hydrocarbons.

Americium↗
PubMed1987

[An autopsy case of myoclonus epilepsy associated with ragged-red fibers (Fukuhara disease)].

In 1980, Fukuhara et al. have reported two patients with "myoclonus epilepsy associated with ragged-red fibers" (MERRF), which is at present accepted as a distinctive clinical entity among the mitochondrial encephalomyopathies. We describe here postmortem findings of the case whose clinical findings were reported in detail by Fukuhara et al. (1980) as Case 1. The neuropathological findings were summarized as follows: 1) degeneration of dentate nucleus, red nucleus, globus pallidus, subthalamic nucleus and pontine tegmentum, 2) degeneration of the Clarke's column, spinocerebellar tract, posterior column and corticospinal tract, as well as of the posterior spinal nerve root and sural nerve, and 3) degeneration of substantia nigra, locus ceruleus, cerebellar cortex and inferior olivary nucleus. The lesions were degenerative in nature, and their distribution was different from those of dentato-rubropallidoluysian atrophy, Joseph's disease or Friedreich's ataxia. It was concluded that MERRF is a single disease entity also from pathological point of view.

Adult↗
PubMed1987

Rat urinary bladder denuded of urothelium. An in vivo model for the epithelial-stromal interactions in carcinogenesis.

To investigate epithelial-stromal interactions in bladder carcinogenesis, the authors developed an experimental model using a heterotopically transplanted rat urinary bladder (HTB). A rat urinary bladder which was completely denuded of epithelial cells ex vivo with hypotonic shock and a nonionic detergent was transplanted into a syngeneic recipient. No reepithelialization occurred during the 8-week posttransplant period. The basal lamina remained intact throughout this period and showed linear immunofluorescence with antibodies against laminin, Type IV collagen, and heparan sulfate-proteoglycan. When 1 X 10(5) to 5 X 10(5) dispersed normal urothelial cells were delivered into the HTB through an attached reservoir 4 days after transplantation, complete resurfacing by inoculated cells occurred within a few days. A transient hyperplasia was followed by a normal 2-3-cell-thick urothelial organization in 4 weeks. Cultured bladder carcinoma cells also resurfaced the denuded bladder basal lamina; the progressive growth of this neoplastic epithelium resulted in carcinoma in situ as well as foci of invasive carcinoma within 4 weeks following inoculation. This in vivo system has an advantage over other in vivo and in vitro models in that complete removal of epithelial cells can be achieved easily and completely; the course after reepithelialization can be modified by subsequent treatment, progression of neoplastic development can be closely observed by a change in the color of the aspirate, its cytology, and biochemical analysis of secretions; and an adequate amount of tissue can be available for subsequent examinations. The model is potentially useful not only for studying epithelial-stromal interactions during carcinogenesis, but also for examining the mechanisms of tumor invasion and metastasis.

Animals↗
PubMed1987

The dependence of maximal expiratory flow on vital capacity: a theoretical analysis.

The decrease of maximal expiratory flow rates (Vmax) at the 50 or 25 per cent level of vital capacity (V50, V25) in idiopathic pulmonary fibrosis (IPF) has been reported by several investigators, and most of them simply concluded that small airway obstruction was associated with IPF. However, Jayamanne et al. (1978) stressed that the reduced airflow in this disease was due to the reduction of lung volume than to abnormally elevated resistance to airflow in small airways. Theoretical analysis on the influence of lung volume on Vmax using a mathematical model supported the opinion of Jayamanne et al.

Forced Expiratory Flow Rates↗
PubMed1987

[An autopsy case of progressive supranuclear palsy showing "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy (Imai)"].

Eleven cases of "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy" were first reported by Imai in 1980. Three cases were added by Hayashi and Hayashi (1983). However there have been so far no autopsy cases, remaining the nosological position of this syndrome uncertain. The authors have had an opportunity of observing the third case in the report by Hayashi and Hayashi for 8 years and autopsy was done as well. Case report The patient was a female farmer. On account of postural-reflex troubles, the pulsion phenomenon and feet freezing, which had progressed since the age of 54, she easily tumbled over. Eight years after the beginning of those symptoms, vertical oculomotor palsy, pseudobulbar palsy and dementia were added; she was diagnosed as a progressive supranuclear palsy. Before this diagnosis, her illness was being regarded as "pure akinesia without rigidity and tremor and with no effect by L-dopa therapy". Neck dystonia was not observed even in the terminal stage. She died at the age of 65. The total clinical course was about 11 years. Pathological observation The brain weighed 1,170 g before fixation. Marked atrophy of the subthalamic nucleus, globus pallidus and pontine tegmentum was observed. The substantia nigra was shown to be severely depigmented. Microscopically, loss of neurons and gliosis were seen in the subthalamic nucleus, globus pallidus, substantia nigra, hypothalamus, superior colliculus, central grey matter, brain stem reticular formation, cerebellar dentate nucleus, etc. The characteristic finding was the appearance of neurofibrillary tangles in these regions.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1986

Activation of phosphatidic acid metabolism of human erythrocyte membranes by perfringolysin O.

The effect of perfringolysin O on the lipid metabolism of human erythrocyte membranes was investigated. Erythrocytes were prelabeled with [3H]arachidonic acid and [32P]inorganic phosphate. In the presence of calcium ion(5.5 mM), the effect of perfringolysin O on lipid metabolism was very similar to that of an calcium-ionophore A23187. In the absence of calcium ion, the accumulation of phosphatidic acid and its following decreasing trend were observed during the reaction with the toxin. Such changes were not caused by filipin. These results suggest that perfringolysin O causes the activation of a diglyceride-phosphatidic acid cycle, which might be involved in the calcium transport.

Bacterial Toxins↗
PubMed1986

The effect of CS-514, an inhibitor of HMG-CoA reductase, on serum lipids in healthy volunteers.

CS-514 is a competitive inhibitor of HMG-CoA reductase. The effect of this agent on serum lipids and lipoproteins was studied in 10 healthy normocholesterolemic male volunteers by giving 20 mg of CS-514 or placebo twice a day for 7 days under double-blind conditions. The mean total serum cholesterol level decreased by 18.6% in the CS-514 group, whereas it increased by 7.4% in the placebo group and the difference between the two groups was statistically significant (P less than 0.01). LDL cholesterol and LDL apo B values were reduced by 22.6% and 23.2%, respectively. Serum triglyceride level did not change significantly. No clinical or laboratory abnormalities were observed.

Administration, Oral↗
PubMed1986

Comparison of selectivity of LDL removal by double filtration and dextran-sulfate cellulose column plasmapheresis.

The possibility of selective removal of VLDL, IDL and LDL by double filtration (DF) and dextran-sulfate cellulose (DSC) column plasmapheresis was investigated in hypercholesterolemia. Two and a half liters of plasma were treated. Sixty six percent of TC and 68% of LDL-C were removed by DF plasmapheresis. The removal rate of HDL-C was 50% which was significantly lower than that of LDL-C. The removal rate of apoprotein A-I and A-II was also significantly lower than that of apoprotein B. Sixty percent of LDL-C and 61% of apoprotein B were removed by DSC column plasmapheresis while the decrease of HDL-C, apoprotein A-I and A-II was minimal. Therefore, DSC column plasmapheresis could remove atherogenic lipoproteins more selectively than DF plasmapheresis.

Adult↗