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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 973 records · Page 54Linked to original sources
PubMed1991

[Chemotherapy in cancers of the gallbladder and bile ducts].

Chemotherapy for cancers of the biliary tract remains underdeveloped, mainly because of their low incidence. There have been no well-designed chemotherapeutic trials based on a sufficient number of cases in this field. The summarized results from the literature and our experience indicate no standard regimen for chemotherapy of the biliary tract cancers. To improve chemotherapy for these cancers, the development of new active anticancer agents is essential. And, for clinical trials of chemotherapy for this relatively rare cancer, a cooperative group study is considered to be necessary to obtain meaningful results within a reasonable period.

Adenocarcinoma↗
PubMed1990

Combined histochemical and biochemical analysis of sex hormone dependence of ferric nitrilotriacetate-induced renal lipid peroxidation in ddY mice.

Ferric nitrilotriacetate (Fe-NTA) induces renal proximal tubular necrosis, a consequence of lipid peroxidation, that finally leads to a high incidence of renal adenocarcinoma in rats and mice. Male animals are much more susceptible than female animals to both effects. Moreover, the distribution of the susceptible proximal tubules is different between male and female animals. The present study investigated the effects of castration and sex hormones on Fe-NTA-induced renal lipid peroxidation. Male and female ddY mice were either left untreated, castrated, and/or treated with testosterone or estriol. Histochemical (reactivity to cold Schiff's reagent) and biochemical (thiobarbituric acid-reactive substance) evaluations were performed 1 h after the i.p. injection of Fe-NTA (5 mg iron/kg). Testosterone treatment and/or oophorectomy increased the Schiff positivity of the renal cortical proximal tubules and the amount of thiobarbituric acid-reactive substance (testosterone-treated female greater than intact female, P less than 0.005; castrated female greater than intact female, P less than 0.1; castrated and testosterone-treated female greater than intact female, P less than 0.005). In contrast, estriol treatment and/or orchiectomy decreased the Schiff positivity of the renal cortical proximal tubules and the amount of thiobarbituric acid-reactive substance (estriol-treated male less than intact male, P less than 0.01; castrated male less than intact male, P less than 0.01; castrated and estriol-treated male less than intact male, P less than 0.005). Estradiol treatment produced similar results to estriol treatment (estradiol-treated male less than intact male, P less than 0.005). Castration and/or administration of the opposite sex hormone reversed the sex difference in the distribution of proximal tubules susceptible to lipid peroxidation. However, the i.v. injection to male mice, 5 min prior to the Fe-NTA treatment, of conjugated estrogen that is promptly excreted via the urine produced no significant effect. Thus, altered metabolic pathways rather than the direct scavenging activity of estrogens seem to be involved in the sex hormone-dependent difference of lipid peroxidation. Genetically determined sex hormone status appears to have influenced the incidence of Fe-NTA-induced renal adenocarcinoma in intact animals.

Acetates↗
PubMed1990

[MR imaging of intracerebral hematomas: sequential changes of signal intensities on a 0.2T permanent magnetic system].

We performed 67 examinations in 27 patients with intracerebral hemorrhage on a 0.2T permanent magnet system. MR appearance of the hematomas on T-1 weighted and T-2 weighted images (T1WIs, T2WIs) was carefully evaluated according to the chronological course of the lesions after the ictus. The signal intensity of each hematoma was classified into four stages in terms of the degradation process of hemoglobin. Four hematomas examined within 24 hours after the ictus (ultra-acute stage) appeared slightly hypointense or isointense relative to the normal brain tissue on T1WIs and markedly hyperintense on T2WIs. Three of those lesions became partially or totally hypointense on T2WIs at the acute stage (one to three days after the ictus), though all appeared in general isointense on T1WIs. The hematomas at the subacute stage (four days to two weeks after the ictus) were hyperintense on both T1WIs and T2WIs. At the chronic stage (more than two weeks after the ictus) the signal pattern of hematomas became variable: hyperintense on both T1WIs and T2WIs early at this stage; hypointense on T1WIs but mostly hyperintense on T2WIs latter. The results indicate the clinical feasibility of a low tesla system for MR evaluation of intracerebral hematomas.

Adult↗
PubMed1990

[A long survived case of malignant pheochromocytoma treated with alpha-methyl-p-tyrosine and midaglizol (DG-5128)].

Survival period of malignant pheochromocytoma treated only conservatively is reported to be less than one year by T. Sato. A patient of malignant pheochromocytoma with liver metastasis has been treated with alpha-methyl-p-tyrosine (alpha MPT), tyrosine hydroxylase inhibitor, in the last 5 years. Catecholamine levels markedly decreased and he has a long survival time. He lives over 17 years from the detection of malignant pheochromocytoma. alpha MPT was considered to have a role to protect a patient from cardiomyopathy induced by hyper-catecholaminemia and to have the action of inhibiting the growth of this tumor. The growth of this tumor was very slow. Since this case had insulin independent diabetes mellitus, insulin therapy was applied, however, blood glucose level was not controlled well. Then we tried midaglizol (DG-5128), alpha 2-adrenoceptor antagonist, to control diabetes mellitus and a sufficient control was obtained. C-peptide level in urine was increased concomitant with decrease of blood glucose. This fact suggested that insulin secretion was improved. It is well known that catecholamine, especially noradrenaline has an inhibiting action on insulin secretion from beta cell. This action was appeared through alpha 2-adrenergic receptor. DG-5128 has an action as alpha 2-adrenoceptor antagonist. We think an inhibiting action on insulin secretion of catecholamine was diminished through its action as adrenoceptor antagonist. Kawazu et al. reported that catecholamine levels, heart rate and blood pressure did not change by DG-5128 administration in healthy subjects. In this patient, no change was appeared either. No major complication was observed during this treatment.

Adrenal Gland Neoplasms↗
PubMed1990

Induction of DNA damage by dimethylarsine, a metabolite of inorganic arsenics, is for the major part likely due to its peroxyl radical.

To reveal the mechanisms of previously reported lung-specific DNA strand scissions in murine after oral administration of dimethylarsinic acid (DMAA), a main metabolite of inorganic arsenics in mammals, the ultimate substance causing DNA lesion was investigated using dimethylarsine which was a further metabolite of DMAA. The alkaline elution assay using 3H-labeled DNA showed that a major portion of the strand breaks was not suppressed by SOD and catalase, suggesting an ultimate substance other than active oxygen participated in the DNA damage. By ESR analysis, a radical estimated to be (CH3)2AsOO. was detected as a reaction product of dimethylarsine and molecular oxygen. This peroxyl radical, rather than active oxygen, was assumed to play a major role in DNA damage.

Arsenic Poisoning↗
PubMed1990

Characteristics of asparagine-linked sugar chains of sphingolipid activator protein 1 purified from normal human liver and GM1 gangliosidosis (type 1) liver.

Asparagine-linked sugar chains of sphingolipid activator protein 1 (SAP-1) purified from normal human liver and GM1 gangliosidosis (type 1) liver were comparatively investigated. Oligosaccharides released from the two SAP-1 samples by hydrazinolysis were fractionated by paper electrophoresis and by Aleuria aurantia lectin-Sepharose and Bio-Gel P-4 (under 400 mesh) column chromatography. Structures of oligosaccharides in each fraction were estimated from data on their effective molecular sizes, behavior on immobilized lectin columns with different carbohydrate-binding specificities, results of sequential digestion by exoglycosidases with different aglycon specificities, and methylation analysis. Sugar chains of SAP-1 purified from normal human liver and from GM1 gangliosidosis (type 1) liver were different from each other, although both of them were derived from complex-type sugar chains. The sugar chains of the former were the following eight degradation products from complex-type sugar chains by exoglycosidases in lysosomes: Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6(Man alpha 1----3)Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man alpha 1----6Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, Man beta 1----4GlcNAc beta 1----4GlcNAcOT, Man beta 1----4GlcNAc beta 1----4(Fuc alpha 1----6)GlcNAcOT, GlcNAc beta 1----4GlcNAcOT, and GlcNAcOT. In contrast to these, the sugar chains of the latter were sialylated and nonsialylated mono- to tetraantennary complex-type sugar chains that were not fully degraded due to a metabolic defect in acid beta-galactosidase activity.

Asparagine↗
PubMed1990

[In vivo insulin sensitivity in adrenodemedullated rats].

Insulin sensitivity and responsiveness were determined in adrenal demedullated rats (ADMX) with euglycemic insulin clamp technique. Adrenal medulla was extirpated bilaterally a week before the study. Catheters were placed at right atrium via right jugular vein for sampling blood and at inferior vena cava via femoral vein for the infusion of insulin and glucose solution. Insulin was infused at rates of 4.4, 8.8, 14.7, 29.3, 88.0, 293.0 mU/kg/min. Blood was collected every five min. during the clamp and glucose infusion rate was modulated to control the blood glucose concentrations at fasting levels. Glucose metabolism was calculated from the amount of glucose infused from 60th to 120th min. during the euglycemic clamp. The results obtained were as follows: 1. Glucose metabolisms of ADMX in each infusion rate of insulin, 4.4, 8.8, 14.7, 29.3, 88.0, 293.0 mU/kg/min were 5.2 +/- 0.5, 12.5 +/- 0.5, 17.6 +/- 1.2, 19.8 +/- 2.3, 29.0 +/- 1.5, and 25.2 +/- 1.9 mg/kg/min, respectively. 2. Glucose metabolisms of control group in each dose were 6.6 +/- 0.4, 9.0 +/- 0.9, 18.5 +/- 1.2, 23.4 +/- 2.4, 24.6 +/- 1.1, and 27.0 +/- 1.3 mg/kg/min, respectively. 3. Significant difference (p less than 0.01) in glucose metabolism between ADMX and control was observed at the insulin infusion rate of 8.8 mU/kg/min which might be equivalent to physiological hyperinsulinemia. 4. There were not any differences in insulin responsiveness between both groups. These results suggest that epinephrine regulates insulin sensitivity under physiological hyperinsulinemic condition via defects of insulin receptors.

Adrenal Medulla↗
PubMed1990

An experimental study of nerve regeneration through chemically treated allografts.

We carried out experiments in rabbits to determine whether treating nerve transplants with gradually increasing concentrations of ethanol, ether and ficin would inhibit the graft-host immune reaction to the allograft. After treatment with ethanol, the basal laminar scaffold of the Schwann cell remained intact and there was satisfactory axonal regeneration. The results after additional treatment with ether or ficin did not achieve such good results. Preservation of the basal lamina is considered to be the essential factor in allowing neural regeneration in these circumstances.

Animals↗
PubMed1990

A case of chronic GM1 gangliosidosis presenting as dystonia: clinical and biochemical studies.

Clinical and biochemical studies are reported on a 32-year-old man with GM1 gangliosidosis who presented with a slowly progressive dystonia that began when he was aged 7 years and eventually became almost totally incapacitating at the age of 35. There was only mild intellectual deterioration, but myoclonus, seizures and macular cherry-red spots were never observed. Proton-density and T2-weighted MRI scans showed symmetrical hyperintense lesions of both putamina. No increase of GM1 ganglioside was found in plasma or cerebrospinal fluid, and the metabolism of GM1 ganglioside in cultured skin fibroblasts from the patient was also almost normal, although the residual activity of GM1 ganglioside beta-galactosidase activity was only 10% of normal. These findings suggest that impaired GM1 ganglioside metabolism is not present systemically as it is in the infantile and juvenile types of the disorder, but is mainly confined to the central nervous system in chronic GM1 gangliosidosis.

Adult↗
PubMed1990

Study of pathogenesis in twitcher mouse, an enzymatically authentic model of Krabbe's disease.

The twitcher mouse was investigated by examining in vivo synthesis of galactosylceramide (Galcer) and galactosylsphingosine (Galsph) in a sciatic nerve culture, and in vitro enzymic activities for synthesis of Galcer and Galsph in the spinal cord from normal and affected mice. For the in vivo study, the sciatic nerve was incubated for 24 h in medium containing [3H]galactose, or [3H]-sphingosine-labeled Galcer or Galsph. With [3H]galactose, reduced synthesis of Galcer was found as early as 1 week of age and synthesis decreased to about 15% of normal value at 4 weeks. Increased Galsph was detected after 7 days of feeding with galactose. In a study of [3H]sphingosine-labeled Galcer and Galsph feeding, Galcer did not induce Galsph synthesis in either normal or affected mice, and synthesis of Galcer from Galsph was found only in normal mice, suggesting that Galcer was synthesized from sphingosine after hydrolysis of Galsph. In vitro, the activities of UDP-galactose: ceramide galactosyltransferase and UDP-galactose: sphingosine galactosyltransferase were reduced to less than 50% of control after 2 weeks of age in affected mice. We conclude that (1) decreased Galcer was due to impaired synthesis of Galcer, (2) Galsph was synthesized from galactose and not from deacylation of Galcer, and (3) Galsph accumulation was due not to increased synthesis but to decreased hydrolysis.

Age Factors↗
PubMed1990

Importance of attitude evaluation in diabetes patient education.

Attitudes were evaluated according to the 'Personal Responsibility Attitude Assessment System' (PRAS), which allows grading of patients' attitudes into five levels of perception of responsibility toward their disease. In 59 diabetics evaluated in this study, no sex difference was observed in attitude level, but more of those aged less than 40 years showed lower attitude levels (levels 1-4) than those aged 40 years or over (P less than 0.01). Of those aged 40 or over, more patients with a high attitude level (level 5) had had diabetes for 10 years or longer than those with low attitude levels (levels 1-4) (P less than 0.05). Among those not treated with insulin, patients with a low attitude level showed higher hemoglobin A1 (HbA1) levels (P less than 0.01) and more frequently had retinopathy (P less than 0.05) than patients with high attitude levels. As for women, low attitude level patients consumed less fruit, meat or fish, and vegetables (P less than 0.05) but more fat and sweetening agents (P less than 0.05) than high attitude level patients. These results suggest an association between the attitude level of diabetic patients evaluated by PRAS and the degree of their self-care. Evaluation of patients' attitudes is important in predicting the response to educational intervention in diabetes.

Adult↗
PubMed1990

Decreased concentration of 1,25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with X-linked hypophosphatemic rickets: effect of phosphate supplementation.

Abnormal renal tubular phosphate transport is considered to be the primary defect in X-linked hypophosphatemic rickets (XLH). However, the resistance to vitamin D treatment in XLH cannot be explained by hypophosphatemia alone. Since most of the actions of vitamin D are mediated by its receptors (VDR), abnormalities of VDR have been postulated in XLH. In order to investigate this possibility, we measured the concentration of VDR in PHA-activated peripheral mononuclear cells from 10 XLH patients. Patients without phosphate supplementation showed significantly lower concentration (21.7 +/- 5.1 fmol/mg protein, mean +/- SEM) compared to the normal controls (60.7 +/- 4.0). On the contrary, there was no significant difference between the phosphate-supplemented patients (58.3 +/- 2.7) and controls. There was a significant positive correlation between VDR concentration and serum phosphate (P less than 0.05). In two patients, VDR was increased after daily phosphate supplementation was started. These results indicate that a decreased concentration of VDR secondary to persistent hypophosphatemia is one of the causes of vitamin D resistance in XLH.

Adolescent↗
PubMed1990

The effect of thyroid hormone on the activities of lactase in the culture of fetal rat intestine.

The effects of thyroid hormone on lactase activities were studied in vitro organ culture of fetal rat intestine. Triiodothyronine inhibited lactase activities regardless the presence of dexamethasone. Also triiodothyronine decreased lactase activities when added after dexamethasone increased lactase activities. Our results suggest that thyroid hormone may have a role in the maturational changes of lactase activities during weaning.

Animals↗
PubMed1990

Tumor accumulation mechanism of 99mTc-DL-homocysteine, a model compound for the development of tumor-imaging radiopharmaceuticals.

To elucidate the tumor accumulation mechanism of 99mTc-DL-homocysteine (99mTc-Hcy), the role of mercaptalbumin, a carrier protein of 99mTc-Hcy in blood, was studied. 99mTc-Hcy bound to serum mercaptalbumin was carried to tumor tissue, efficiently adsorbed onto the cell surface, released from albumin, and taken up by the cells. An enlarged capillary permeability observed in tumor tissue played an important role in the transport process.

Animals↗
PubMed1990

Changes in cerebral white matter in a case of congenital muscular dystrophy (non-Fukuyama type).

A 3-year-old Japanese boy with congenital muscular dystrophy (CMD) and normal intelligence is presented. He had not learned to crawl, shuffled on his bottom, and could not walk. At 7 months, his CT-scan had showed periventricular low density and mild ventricular dilatation, and spike or sharp wave discharges were seen on EEG. At three years of age, his CT-scan revealed wide-spread hypodensity in the cerebral white matter, EEG showed multifocal discharges, and MRI showed abnormal high density area in the cerebrum on spin echo image. These findings suggest the existence of an intermediate form of CMD between the Fukuyama type of CMD and the classical occidental type of CMD. The combination of repeated CT and MRI scans seems necessary for the evaluation of CNS abnormalities in CMD.

Biopsy↗
PubMed1990

Changes of DNA methylation level during pre- and postnatal periods in mice.

DNA methylation in an adult mammalian body shows tissue-specificity. But when and how the specificity is established in the process of development has not yet been elucidated. Here we have investigated age-dependent changes in the amount of 5-methyldeoxycytidine (5mdC) that DNA of various mouse tissues contains during the late-fetal and postnatal periods, using high-performance liquid chromatography. The tissue-specificity in the 5mdC level was observed in the late-fetal stage, and the level continued to change during the subsequent periods. The most pronounced alterations were observed in brain and liver, where similar biphasic changes were seen, but at different ages. At maturation, the 5mdC levels were high in thymus, spleen and brain, intermediate in lung, and low in liver and sperm. The data demonstrate the importance of the peri- and postnatal periods in establishment of tissue-specificity in 5mdC content.

Aging↗