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Biomedical subjects

N Murayama

Publications and source records attributed to N Murayama.

At least 73 records · Page 4Linked to original sources
PubMed1995

Suppression of clofibrate-induction of peroxisomal and microsomal fatty acid-oxidizing enzymes by growth hormone and thyroid hormone in primary cultures of rat hepatocytes.

Using primary cultures of rat hepatocytes on a matri-gel, effects of peroxisome proliferator and omega-hydroxydodecanoic acid on cellular levels of acyl-CoA oxidase and CYP4A have been studied to determine the hormonal influence in serum-free media. Peroxisomal acyl-CoA oxidation, microsomal CYP4A content and laurate omega-hydroxylation were increased in rat hepatocytes by the addition of 100 microM clofibrate or Wy14,643 for two days. omega-Hydroxydodecanoic acid (100 microM) also increased peroxisomal acyl-CoA oxidation, but had no clear effect on microsomal CYP4A level and laurate omega-hydroxylation. CYP4A-mediated laurate omega-hydroxylation in hepatocytes was suppressed by the addition of pituitary growth hormone (0.05 mU/ml), but was not altered by the addition of triiodothyronine (30 nM). In contrast, clofibrate-mediated induction of acyl-CoA oxidase activity was decreased by the addition of either one of the hormones in hepatocytes. Suppression by those hormones was also observed with omega-hydroxydodecanoic acid-mediated induction of acyl-CoA oxidase activity. These results indicate the possibility that GH and T3 exert the suppressive effects on peroxisomal acyl-CoA oxidation through plural mechanisms with and without the alteration of CYP4A levels in livers.

Acyl-CoA Oxidase↗
PubMed1995

Dentatorubral-pallidoluysian atrophy (DRPLA): clinical, genetic, and neuroradiologic studies in a family.

The clinical, genetic, and neuroradiologic characteristics of dentatorubral-pallidoluysian atrophy (DRPLA) are delineated in six patients from three generations of a Japanese family. The clinical characteristics of the disease varied, the age at onset depending on patients with juvenile-onset were characterized by myoclonus, epilepsy, and mental retardation whereas cerebellar ataxia, choreoathetosis, and dementia were typical of adult- and senile-onset patients. All affected individuals showed one expanded allele with the repeat number of CAG at the DRPLA locus, ranging from 58 to 82, and a normal allele, ranging from 10 to 21. The most severely affected patient, a case of maternal transmission and with the largest allele, became bedridden in a vegetative state by age 12. On the CT and MRI, varying degrees of brain atrophy were present in all patients. T2-weighted MRI in patients with senile-onset showed symmetric high-signal lesions in the cerebral white matter, globus pallidus, thalamus, midbrain, and pons. However, MRI in younger patients revealed no such lesions and CT failed to demonstrate lesions in the globus pallidus and brain stem. Thus, intrafamilial heterogeneity of DRPLA was also evident on MRI. High-signal lesions involving both, subcortical white matter and thalamus may be characteristics of senile-onset patients and may correlate with their dementia.

Adult↗
PubMed1995

Analysis of triplet repeats in the huntingtin gene in Japanese families affected with Huntington's disease.

Huntington's disease (HD) is associated with the expansion of a CAG repeat in the huntingtin gene. Molecular analysis of the repeat in Japanese HD patients and normal controls was performed. The size of the CAG repeat ranged from 37 to 95 repeats in affected subjects and from seven to 29 in normal controls. A significant correlation was found between the age of onset and the CAG expansion. The length of the expanded repeat is unstable in meiotic transmission and large increases occur in paternal transmission. At the same time the CCG repeat polymorphism adjacent to the CAG repeat was analysed and haplotypes of HD chromosomes were identified. Strong linkage disequilibrium was found between the CAG repeat expansion and an allele of (CCG)10 in Japanese HD chromosomes. It is distinct from that described previously in western populations. Western HD chromosomes strongly associate with an allele of (CCG)7. Possible mechanisms underlying the disequilibrium in Japan are discussed.

Age of Onset↗
PubMed1995

Functional magnetic resonance imaging at 1.5 T during sensorimotor and cognitive task.

Functional activations of the human brain cortex were observed with a standard 1.5-tesla MR imaging system using a long time echo fast low-angle shot sequence. Neural activation increases regional cerebral blood flow resulting in increased capillaries and venous blood oxygenation. Processing requires adapted algorithms because the time course of intensity signal showed fluctuations of the baseline. The use of a 'follow-up' method to generate activation maps is proposed. Brain activation was detected in striate cortex during photic stimulation and in sensorimotor areas while subjects were moving their hands. In mental imagery tasks, we observed a primary and secondary visual cortex activation during memory recall of the flashing light. Motor ideation showed an activation of the rolandic areas.

Adult↗
PubMed1995

DNA analysis in hereditary dentatorubral-pallidoluysian atrophy: correlation between CAG repeat length and phenotypic variation and the molecular basis of anticipation.

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease with variable clinical phenotypes. Progressive ataxia, choreoathetosis, and dementia are the main clinical features of adult-onset cases, whereas the main feature in juvenile-onset DRPLA is progressive myoclonus epilepsy. Earlier onset is apparent in successive generations (anticipation). The molecular abnormality underlying DRPLA is an expanded, unstable CAG trinucleotide repeat on chromosome 12p. We analyzed 71 DNA samples obtained from 12 Japanese DRPLA pedigrees that included 38 affected individuals. Normal alleles had 7 to 23 repeats, DRPLA alleles 53 to 88 repeats. DRPLA alleles also were detected in five asymptomatic family members. Patients with juvenile onset had significantly larger repeats than did those with adult onset, and there was a significant negative correlation between CAG repeat length and age at onset. In 80% of the paternal transmissions, there was an increase of more than five repeats, whereas all the maternal transmissions showed either a decrease or an increase of fewer than five repeats. There was a significant correlation between father-child differences in repeat length and differences in age at onset. The analysis of CAG repeat length is a reliable diagnostic test for DRPLA and is of value for the presymptomatic detection of individuals at risk. The expansion of CAG repeats is important in phenotypic variation and anticipation. In addition, the sex of the transmitting parent has a significant effect on the molecular mechanism of anticipation.

Adolescent↗
PubMed1995

Effects of dicarboxylic acids on fatty acid-metabolizing enzymes in cultured rat hepatocytes.

A clear chain-length dependent effect was observed for peroxisomal fatty acid beta-oxidation and carnitine acetyltransferase and also for mitochondrial carnitine palmitoyltransferase in primary cultures of rat hepatocytes. The extent of modulation of peroxisomal beta-oxidation was higher with even-carbon numbered dicarboxylic acids than with odd-carbon numbered ones, although such a tendency was not detected in the mitochondrial reactions. These results indicate difference in the effect of fatty acid-derived dicarboxylates on peroxisomal and mitochondrial functions.

Animals↗
PubMed1995

Age- and sex-related alterations of microsomal drug- and testosterone-oxidizing cytochrome P450 in Sprague-Dawley strain-derived dwarf rats.

Effect of growth hormone (GH) on the age-related changes in hepatic cytochrome P450 (P450) was studied using GH-deficient dwarf and parental Sprague-Dawley rats. Microsomal testosterone (T) T2 alpha- and T2 beta-hydroxylations were lower in livers of mature male dwarf rats than the normals, whereas T16 beta-hydroxylation was rather higher in male dwarf rats. Although T2 alpha-, T2 beta-, T6 beta-, T16 alpha- and T16 beta-hydroxylations were barely detectable in senescence normal rats (24 months old), considerable levels of T6 beta-, T16 alpha- and T16 beta-hydroxylations were maintained in senescence dwarf rats (after 22 months old). These results are caused by the alteration of specific P450 forms including CYP2B1, CYP2B2, CYP2C11 and CYP3A2 in dwarf rats. Appearance of male-specific CYP2C11 and CYP3A2 and high levels of CYP2B1 and CYP2B2 in female dwarf rats indicate the role of pituitary GH on liver of normal rats. However, the additional role of a factor other than GH was suggested on the sex-related differences and age-associated alterations of specific P450 contents in dwarf rats. CYP2C11 appears in dwarf female rats with the same developmental profile as observed in normal male rats. This form appears apparently with the development of GH receptor in livers, suggesting the possibility that a factor independent from androgen and GH governs the ontogeny of this P450 in the liver. A female-specific protein, CYP2C12, in normal rat livers, also appeared in both sexes of senescence dwarf rats, suggesting the role of non-GH factor on the expression of this P450 in liver.

Age Factors↗
PubMed1995

[Effects of inhaled beclomethasone on height growth and bone metabolism in children with asthma].

To evaluate the influences of inhaled beclomethasone dipropionate (BDP), 7.3-30.9 (15.5 +/- 6.5) micrograms/kg/day, on bone metabolism and height growth, we performed a longitudinal study for 6 months in 34 children with asthma aged between 3 and 15 years. Bone mineral density estimated by digital image processing method (DIP) and serum level of osteocalcin did not show any significant change, but height growth was slightly suppressed in the patients who inhaled more than 15 micrograms/kg/day of BDP. We concluded that the decision to prescribe inhaled BDP should be made on the balance of the clinical effects and the improvement of quality of life against the possibility of side effects.

Administration, Inhalation↗
PubMed1995

[Subdural abscess following chronic subdural hematoma].

This is a report of subdural abscess following chronic subdural hematoma. An 86-year-old male was admitted to our hospital due to drowsiness and left hemiparesis. He had been suffering from a spike fever which originated during chronic cholecystitis and cholelithiasis and which had continued since 2 years prior to admission. On admission, CT scans revealed right chronic subdural hematoma, and the collection of a few old hematomas was suspected in the left subdural space. An emergency removal of the right hematoma was carried out by using right single burr hole. It was found that the old hematoma accompanied a yellow-white abscess in the subdural space. Escherichia coli were detected from a bacterial culture of the abscess. Postoperative enhanced MRI clearly showed the capsule of the right subdural abscess, and the left chronic subdural hematoma. Removal of the left hematoma was performed by using a left single burr hole. But the abscess did not exist in the left subdural space, and only old hematomas had collected there. The bacterial culture of the left old hematoma was negative. Escherichia coli might be implanted on the capsule of the right chronic subdural hematoma by bacteremia derived from chronic cholecystitis. It was considered that the formation of the subdural abscess might have developed through the deterioration of the immunological function under the influence of senility.

Aged↗
PubMed1994

Differential properties of brush-border membrane vesicles from early and late proximal tubules of rat kidney.

We describe the preparation and properties of BBM vesicles (BBMV) from the superficial and juxtamedullary rat renal cortex using Ca(2+)-precipitation method and/or by density gradient centrifugation. BBMV were characterized by the presence of BBM marker enzymes as distributed along microdissected proximal convoluted tubule and proximal straight tubules from superficial and juxtamedullary cortex. In tubules from both superficial and juxtamedullary cortex, the activities of gamma-glutamyltransferase and leucine aminopeptidase were 5-10 times higher in proximal straight tubules than in proximal convoluted tubule. The alkaline phosphatase was higher in proximal convoluted tubules than in straight tubules from superficial cortex, but it was lower in proximal convoluted than straight tubules from the juxtamedullary cortex. The Na+/Pi cotransport had higher Vmax and lower Km in BBMV from superficial cortex than from BBMV from juxtamedullary tissue. BBMV from superficial cortex separated on Percoll gradient showed a high activity of alkaline phosphatase and low activities of gamma-glutamyltransferase and leucine aminopeptidase. Conversely, BBM from juxtamedullary cortex separated into a major peak with very high activities of gamma-glutamyltransferase and leucine aminopeptidase, and lesser activity of alkaline phosphatase. These distinct BBMV fractions showed diverse Na+/Pi cotransport properties and BBM marker enzyme distributions. Thus, using the outlined methodology it is feasible to prepare BBMV derived predominantly from proximal convoluted tubules or from proximal straight tubules located in either superficial or deep cortical nephrons.

Animals↗
PubMed1994

Radioimmunoassay for DS-4574, an antiallergic agent: development, evaluation, and application to human plasma samples.

A sensitive radioimmunoassay (RIA) method for DS-4574, an antiallergic drug, in plasma has been developed. As the three major metabolites have a hydroxyl group on the cyclohexyl ring, the triazole ring in the terminal part of molecule was attached to ovalbumin with a spacer of beta-chloropropionic acid succinimido ester to prepare an immunogen. Anti-DS-4574 antisera was obtained in rabbits immunized with the immunogen emulsified in Freund's complete adjuvant. The detection limit of the present RIA method was 1 mg/mL of plasma, which was 100-fold more sensitive than the HPLC method developed previously. Cross-reactivities with three major metabolites were less than 3%. The precision of the assay based on triplicate samples showed intra- and inter-assay coefficients of variations of less than 5% and 4%, respectively. This RIA method was applied to plasma samples of six volunteers who had received a single oral 10 mg dose of DS-4574. Plasma concentrations increased rapidly and reached 60 ng/mL at 0.5 h after administration. The concentration decreased to near the detection limit at 4 h postdose. The present RIA method was shown to possess adequate sensitivity to evaluate pharmacokinetic properties of the drug for clinical study, which was not possible by the HPLC method.

Adult↗
PubMed1994

Changes in properties of neuronal responses in two cortical taste areas in rats of various ages.

Changes in the features of responses of cortical taste neurons were studied in granular insular (GI) and dysgranular insular (DI) areas of urethane-anesthetized SD rats of four age groups (4-10, 14-20, 25-35 and > 90 days). Stimuli included four basic taste stimuli, 0.1 M NH4Cl, and the water extract of a food pellet, applied to the entire oral cavity. At the age of 4-10 days, taste neurons showed no spontaneous discharge, and most responded to NH4Cl in a phasic fashion. In older age groups, however, there was a spontaneous discharge, and tonic taste responses were evident; some responded better to the four basic stimuli and to the food than to NH4Cl. With only a few days' difference in age, inhibitory responses were also noted in both areas. Average taste responses increased or decreased at different ages, depending on the type of taste stimulus and recording area. When taste responses were plotted against the four basic taste stimuli in the order of sucrose, NaCl, HCl and quinine along the abscissa, some neurons showed double-peaked response profiles. This suggests the convergence and mutual inhibition of afferents at single cortical neurons. The fraction of neurons with double-peaked response profiles increased at the age of 25-35 days in both areas. Neurons in rats aged 25-35 days were predominantly sensitive to either NH4Cl or NaCl, or to either food or sucrose. Neurons in rats of other ages, during the preweanling and the adult stages, tended to respond to both these stimuli. Our observations suggest that cortical taste neurons develop in the rat brain in accordance with the maturation of both the taste receptors and the neural networks.

Aging↗
PubMed1994

KP-10, a novel protein kinase C substrate in intact mouse epidermal cells, is phosphorylated by novel protein kinase C eta and/or zeta.

Recently this group found an endogenous substrate protein for Ca(2+)-independent novel protein kinase C (nPKC), i.e. KP-10 (pI 4.7/25,500 M(r)), in primary cultured mouse epidermal cells [Nishikawa, K. et al. (1992) Cell. Signal. 4, 757-776]. In the present study, the nPKC isozymes which phosphorylate KP-10 in these cells were determined. Western blot analysis revealed that PKC alpha, eta and zeta were present in epidermal cell 105,000 g supernatants and that the content of PKC zeta was much higher than those of PKC alpha and eta. Neither PKC beta, delta nor epsilon was detected in the 105,000 g supernatants. Phosphatidylserine and phorbol 12-myristate 13-acetate (PMA)-dependent KP-10 phosphorylating activity was immunoprecipitated by anti-PKC eta and zeta antibodies, but not by antiPKC alpha antibody. These results suggest that PKC eta and/or zeta phosphorylate KP-10 and play pivotal roles in intracellular signal pathways in intact epidermal cells.

Amino Acid Sequence↗
PubMed1994

Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p.

Dentatorubral and pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disorder characterized by combined systemic degeneration of the dentatofugal and pallidofugal pathways. We investigated a candidate gene and found that DRPLA patients had an expanded CAG trinucleotide repeat in a gene on the short arm of chromosome 12. The repeat size varied from 7-23 in normal individuals. In patients one allele was expanded to between 49-75 repeats or occasionally even more. Expansion was usually associated with paternal transmission and only occasionally with maternal transmission. Repeat size showed a close correlation with age of onset of symptoms and disease severity. We conclude that DRPLA is the seventh genetic disorder known to be associated with expansion of an unstable trinucleotide repeat.

Alleles↗
PubMed1994

Carbohydrate-related regulation of the ethanol-induced increase in serum gamma-glutamyl transpeptidase activity in adult men.

The dietary influence on ethanol-induced increase in serum gamma-glutamyl transpeptidase (gamma-GTP) activity was studied in 2165 healthy men 18-85 y of age living in Nagano Prefecture, Japan. As ethanol consumption increased, the intake of cereals, potatoes, vegetables, milk and dairy products, oils, fruit, confections, and sugar decreased, whereas the intake of meat increased. These associations suggest that ethanol consumption led to the decrease in the intake of carbohydrate and vegetable fat. Serum gamma-GTP activity was found to be positively related to ethanol consumption and negatively related to the intake of sugar, fruit, and confections. The activity was the highest in those whose percent energy intake from carbohydrates was the lowest. Stepwise-multiple-regression analysis identified the three variables ethanol, sugar, and fruit, as the factors associated with the value of gamma-GTP activity: ethanol on the one hand increased the activity, whereas sugar and fruit on the other hand decreased the activity. Moreover, a lowered sugar intake augmented the ethanol-induced increase in the enzyme activity. These results suggest that sugar intake plays a role in the ethanol-induced increase in serum gamma-GTP activity.

Adult↗