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Biomedical subjects

M Arima

Publications and source records attributed to M Arima.

At least 181 records · Page 10Linked to original sources

Reduction of acid sphingomyelinase activity in human fibroblasts induced by AY-9944 and other cationic amphiphilic drugs.

AY-9944 (trans-1,4-bis(2-chlorobenzylaminoethyl)cyclohexane dihydrochloride), a cationic amphiphilic drug, caused a rapid, irreversible and dose-dependent reduction of acid sphingomyelinase activity in normal human fibroblasts without changing the activities of other lysosomal hydrolases tested. Examinations of activities against synthetic substrates and of the pH-dependency of sphingomyelinase in the drug-treated cells also suggested that the reduction of activity was specific to acid sphingomyelinase. Such a specific reduction was also found with 12 other cationic amphiphilic drugs, most of which have been shown to be inducers of experimental phospholipidosis in animals and/or cultured cells. These results strongly suggest that acid sphingomyelinase is involved in the process of drug-induced lipidosis. The reduction of acid sphingomyelinase seemed not to be due to direct inhibition by these drugs, a specific loss of the enzyme into the culture medium, the presence of inhibitor in the drug-treated cells, or impaired synthesis of the enzyme. There was no indication that changes in the catalytic properties of the enzyme, or changes in the requirement of detergents for its activity occurred in the cell. These results suggest that AY-9944 and other cationic amphiphilic drugs may cause the reduction of acid sphingomyelinase activity by inducing an increased rate of degradation of the enzyme or by causing an irreversible inactivation via some undetected factor.

Cations↗

Variable radiosensitivity in fibroblasts from patients with tuberous sclerosis.

It has been reported that some of the cultured cell strains derived from patients with tuberous sclerosis (TS) showed hypersensitivity to gamma-rays or a radiomimetic chemical. Thirteen fibroblast cell strains from 11 patients with TS were examined for their sensitivity to x-rays as determined from their colony-forming ability. All strains derived from normal-appearing skin of patients, either sporadic or familial cases, showed sensitivity within the normal control range. Five cell strains originating from tumorous skin of 3 patients did not show hypersensitivity. It was concluded that the sensitivity to x-rays of cultured cells of TS is essentially normal. However, the mean D0 or D10 values of the strains from tumorous skin tended to be lower compared to those for normal skin of patients. In addition, we could confirm the hypersensitivity to x-rays in the cell strains of TS which had been shown to be hypersensitive to gamma-rays. These results appear to indicate that at least some of the cells of TS are liable to change to exhibit a hypersensitive trait in unknown acquired conditions.

Cell Line↗

The effect of caffeine ingestion on pharmacokinetics of caffeine and its metabolites after a single administration in pregnant rats.

The pharmacokinetics of caffeine and its metabolites were studied in pregnant rats in order to clarify the effects of maternal caffeine ingestion on the caffeine disposition. On gestational day 18 the single intravenous or oral 10 mg/kg dose of caffeine was administered to pregnant rats who had received drinking water containing 0.04% caffeine or water ad lib during the premating and/or pregnant periods. Concentrations of caffeine and its dimethylxanthines were simultaneously determined by high-performance liquid chromatography. The caffeine plasma concentration-time curves were analyzed by assumption of a one-compartment model. The apparent volume of distribution of caffeine in rats given caffeine only during pregnancy was decreased. The elimination rate constant (kel) of caffeine in most of the rats taking caffeine during pregnancy was increased. The rats which had received caffeine throughout the premating and pregnant periods had a relatively high total body plasma clearance (CL) of caffeine. The kel and the CL widely varied in the rats taking caffeine during pregnancy. The individual values of kel or CL in pregnant rats were significantly correlated with the molar concentration ratios of the metabolites to caffeine in plasma at 8 h after administration of caffeine. It is concluded that the caffeine disposition is influenced by the different modes of maternal caffeine ingestion during the premating and/or pregnant periods.

Administration, Oral↗

[Clinical statistics on outpatients, inpatients and operations in 1983].

Statistical studies on 1,990 outpatients, 574 inpatients and 606 operative procedures at our department in 1983 revealed the following. The most frequent diseases among the outpatients were urogenital infections followed by anomalies, tumors and stones. The major diseases among the inpatients were hypospadias, vesicoureteral reflux, congenital urethral stenosis, benign prostatic hypertrophy and bladder tumor. A total of 606 operations were performed on 559 patients, and the five major operations were hypospadias repair (80), TUR-P (54), optic internal urethrotomy (51), ureterocystoneostomy (40) and orchidopexy (34).

Adolescent↗

[Cerebral palsy--investigation of its causal factors and genetical background].

In the last 30 years the prevalence rate of cerebral palsy (CP) has remarkably decreased in Japan. The decrease is arbitrarily attributed to the reduced frequency of such risk factors for CP, as low birthweight, severe asphyxia, and kernicterus in the neonatal period. However, there is no statistical data providing the evidence that CP patients complicating these risk factors have actually decreased so far. In order to make clear the bases of the decrease in prevalence of CP, we examined the changing patterns in the suggested cause of CP, experienced in the last 30 years. The investigation included the maternal condition of pregnancy and delivery, in relation to the neonatal risk factors, and genetic background of the family. In CP, low birthweight babies of 2500 gm or less were common (36.9%) and the mean birthweight (2689 gm) was obviously smaller than that of general population. In spite of the constant decline of the incidence of low birthweight babies in the general population in the last 30 years, the ratio of low birthweight to total births in CP group had not changed in this study period. It was concluded that the low birthweight following premature birth is still an important predisposing factor of CP. Asphyxia was frequently seen in the CP population. The rate of asphyxia was significantly higher in the group with a normal birthweight more than 2501 gm (58.4%), or gestational weeks longer than 36 weeks (57.7%), comparing with that of low birthweight (41.1%), or premature (40.7%) group.(ABSTRACT TRUNCATED AT 250 WORDS)

Asphyxia Neonatorum↗

Caffeine and its dimethylxanthines and fetal cerebral development in rat.

The relationship between the distribution and pharmacokinetic behavior of caffeine and its dimethylxanthines in pregnant rats and fetuses and fetal cerebral development was compared in four groups with different modes of oral caffeine ingestion by the mothers. During the premating period and pregnancy, female Wistar rats were divided into 0.04% caffeine (C) and water (W) groups, respectively. When the groups are expressed as W or C before mating-W or C during pregnancy, the fetal body weight was low in the three caffeine-treated groups (W-C, C-W and C-C) and the fetal cerebral weight was the lowest in the W-C group. The mean concentration of caffeine or metabolites in maternal plasma, maternal liver, placenta and fetal cerebrum on gestational day (g d) 21 was increased in the W-C group compared to in the C-C group. The concentration of caffeine in fetal cerebrum was increased but that of metabolites was not, compared to the concentration of caffeine or metabolites in the placenta. Radioactivity in fetal cerebrum after intraperitoneal injection of 14C-caffeine was higher in the W-C group than in the other three groups. After intravenous injection of caffeine the apparent volume of distribution of caffeine in maternal plasma was markedly decreased in the W-C group, and the plasma molar concentration ratio of theophylline to caffeine was significantly increased in both the W-C and C-C groups. The adverse effect of maternal caffeine ingestion on the fetal cerebrum may be associated with the decreased apparent volume of distribution of caffeine in maternal plasma and the high caffeine content of fetal cerebrum.

Abnormalities, Drug-Induced↗

The immunosuppressive mode of action of mizoribine.

Mizoribine (MIZ) suppressed the mitogen response and mixed lymphocyte reaction (MLR) significantly at doses of 100 micrograms/ml and 10 micrograms/ml in a dose-response analysis. The 50% inhibition dose (ID50) was between 10 micrograms/ml and 1.0 microgram/ml, both in the mitogen response and MLR. In a kinetic study of the MLR, the degree of suppression with MIZ at a given dosage was essentially the same as the degree of suppression observed in the dose-response analysis when MIZ was added to MLR cultures from day 0 to day 4. In addition, MLR was more susceptible to the suppressive activity of MIZ at 100 micrograms/ml when MIZ was added near the peak of lymphocyte proliferation. This experiment also showed that MLR suppression induced by MIZ at 10 micrograms/ml was reversible and MLR activity had completely recovered 6-8 hr after its removal. MIZ had no inhibitory action on MLR-derived cytotoxic cells or the effector phase of cell mediated lymphocytotoxicity. These results clearly demonstrate that MIZ suppresses lymphoproliferation, but has no effect on the recognition phase or effector phase of cytotoxic lymphocytes.

Dose-Response Relationship, Immunologic↗

Localization of type V collagen and type IV collagen in human cornea, lung, and skin. Immunohistochemical evidence by anti-collagen antibodies characterized by immunoelectroblotting.

Tissue distribution of Type V collagen in comparison with Type IV collagen was investigated by indirect immunofluorescence microscopy. Affinity-purified rat antibodies to Type IV and Type V collagens obtained from human placenta reacted specifically only with the corresponding type of collagen in both native and denatured conformations. In indirect immunofluorescent stainings of human skin, lung, and cornea tissues, Type IV and Type V collagens showed distinct distributions. Type IV collagen was distributed exclusively in basement membrane. However, Type V collagen had two characteristic features; a diffuse distribution in interstitium and the locations on or adjacent to basement membrane. On the basis of these findings and of biochemical characterization of the collagens, it is postulated that Type V collagen is an intermediate collagen, possibly having a function of binding or connecting of interstitial collagen fibrils with membranous collagen networks.

Adult↗

[Indication and result of renal autotransplantation for renovascular hypertension].

Twenty patients with renovascular disease in 22 kidneys were treated surgically by the method of renal autotransplantation at our department during the 13 years from 1970 to 1982. Etiological disorders included 11 cases of fibromuscular dysplasia, 3 cases of atherosclerosis, 3 cases of aortitis syndrome, two cases of renal artery aneurysm and one case of renal artery thrombosis. Age distribution ranged from 13 to 64 years old (average 28.9 years), and male to female ratio was 1 to 3. Ex vivo surgery was carried out in 11 of these 20 cases. Angioplasty in 9 cases, endarterectomy and partial nephrectomy in one case each were performed extracorporeally. Reconstruction of the urinary tract was needed for 14 kidneys in 13 patients, 12 kidneys were treated by UCN, and PU anastomosis was performed in 2 kidneys in 2 patients. Outcome of renal autotransplantation was "cured" in 17 cases and "improved" in 3 cases during follow-up period from 8 months to 13 years. Revision was successful for the postoperative complication such as urine leakage, bladder tamponade, perirenal fluid collection and ileus.

Adolescent↗