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Biomedical subjects

M Ikeda

Publications and source records attributed to M Ikeda.

At least 721 records · Page 40Linked to original sources
PubMed1997

Vitamin B12 enhances GABA content but reduces glutamate content in the rat suprachiasmatic nucleus.

The present study attempted to elucidate effects of vitamin B12 (VB12) on the rat suprachiasmatic nucleus (SCN), which is the locus of the circadian clock in mammals, by evaluating the contents of its major neurotransmitters, gamma-aminobutyric acid (GABA) and glutamate (Glu). First, contents of these amino acids were analyzed from tissue samples prepared at three different circadian times (CTs) in free-running rats under constant dim illumination. The content of GABA was highest in the middle of the resting phase (CT 6), intermediate early in the active phase (CT 14), and lowest late in the active phase (CT 20), whereas Glu content indicated inverse circadian variations. Subsequently, effects of intracerebroventricularly infused VB12 were assayed at CT 20. Compared with the saline-infused control, the infusion of VB12 (30 nmol/30 microliters) at CT 12-15 significantly increased GABA content but decreased Glu content. The quantitative balance of these amino acids after VB12 infusion was similar to that at CT 6 in noninfused rats. These results suggest that infusion of VB12 to active rats shifts the ratio of SCN neurotransmitters toward that observed in resting rats.

Animals↗
PubMed1997

Sympathetic outflow to the skeletal muscle in humans increases during prolonged light exercise.

To investigate the effects of exercise duration on muscle sympathetic nerve activity (MSNA), heart rate, blood pressure (BP), tympanic temperature, blood lactate concentration, and thigh electromyogram were measured in eight volunteers during 30 min of cycling in the sitting position at an intensity of 40% of maximal oxygen uptake. MSNA burst frequency increased 18 min after exercise was begun (25 +/- 4 bursts/min at baseline and 36 +/- 5 bursts/min at 21 min of exercise), reaching 41 +/- 5 bursts/min at the end of exercise. Heart rate and systolic BP increased during exercise. Twenty minutes after commencement of exercise, however, both systolic and diastolic BP values tended to drop compared with the initial period of exercise. Tympanic temperature increased in a time-dependent manner, and the increment was significant 12 min after exercise was begun. Blood lactate concentration and integrated electromyogram showed no significant changes during exercise. The increased MSNA during prolonged light-intensity exercise may be a secondary effect of the drop in BP as a result of blood redistribution caused by thermoregulation rather than by metaboreflex.

Adult↗
PubMed1997

Regulation of MHC class I expression by inflammatory cytokines in rat mesangial cells.

We investigated the regulation of major histocompatibility complex (MHC) class I expression by inflammatory cytokines and nitric oxide (NO) in rat mesangial cells by enzyme-linked immunosorbent assay and flow cytometry. MHC class I molecule expression on mesangial cells was significantly stimulated by interferon gamma, tumor necrosis factor alpha and interleukin 1beta, but not by interleukin 6, in a dose-dependent manner. Addition of SIN-1, an NO donor, did not affect the expression of cytokine-induced MHC class I expression. These results suggest that under inflammatory conditions mesangial cells may act as antigen-presenting cells in response to stimulation by cytokines and may be involved in the pathogenesis of immune-mediated glomerular disease.

Animals↗
PubMed1997

Cholesterol-mediated changes of neutral cholesterol esterase activity in macrophages. Mechanism for mobilization of cholesteryl esters in lipid droplets by HDL.

Cholesteryl esters (CE) in lipid droplets undergo a continual cycle of hydrolysis and reesterification by neutral cholesterol esterase (N-CEase) and acyl CoA:cholesterol acyltransferase (ACAT), respectively. The mechanism by which HDL mobilizes CE from lipid droplets in J774 A.1 cells was investigated, focusing on N-CEase activity. We asked whether HDL enhances the activity and, if so, what signals induce the change of the activity. An incubation of cells with HDL enhanced the decline of cholesteryl-[l-14C]-oleate in foam cells and increased N-CEase activity in the supernatant of cell homogenate in a concentration-dependent manner, whereas incubation with LDL decreased the activity. In addition, N-CEase activity was fivefold higher when cells were cultured in 10% lipoprotein-deficient serum (LPDS) medium (2 micrograms cholesterol/mL) than when cultured in 10% fetal calf serum medium (31 micrograms cholesterol/mL), suggesting that changes in N-CEase activity are mediated by cholesterol. An addition of cholesterol (0 to 30 micrograms/mL) in LPDS medium markedly inhibited N-CEase activity with a concomitant increase in cellular cholesterol concentration. This inhibitory effect of cholesterol was also observed in mouse peritoneal macrophages. In vitro addition of cholesterol did not affect N-CEase activity. Treatment of cells with HMG-CoA reductase inhibitors enhanced N-CEase activity, whereas ACAT inhibitor decreased the activity. Northern blot analysis of N-CEase mRNA showed that the expression was not altered by the presence of cholesterol in LPDS medium. These results suggest that cholesterol downregulates N-CEase activity, probably through cholesterol-dependent appearance of some factors.

Animals↗
PubMed1997

Natriuretic peptide family as a novel antimigration factor of vascular smooth muscle cells.

Vascular smooth muscle cell (SMC) migration is proposed to be an important process in the initiation and/or progression of atherosclerosis. The present study examined the effects of the natriuretic peptide family (atrial, brain, and C-type natriuretic peptides; ANP, BNP, and CNP) on the migration of cultured rat SMCs, using Boyden's chamber methods. Fetal calf serum (FCS) and platelet-derived growth factor (PDGF)-BB potently stimulated SMC migration. Rat ANP(1-28), rat BNP-45, and rat CNP-22 clearly inhibited SMC migration stimulated with FCS or PDGF-BB in a concentration-dependent manner. CNP-22 had the most potent inhibitory effect compared with other natriuretic peptides. When PDGF-BB-induced migration was separated into chemotactic and chemokinetic activities, the chemotactic component was strongly inhibited by these natriuretic peptides. Such inhibition by these natriuretic peptides was paralleled by an increase in the cellular level of cyclic GMP. The addition of a cyclic GMP analogue, 8-bromo cyclic GMP, and an activator of the cytosolic guanylate cyclase, sodium nitroprusside, significantly inhibited FCS- and PDGF-BB-stimulated migration in a concentration-dependent manner. These results suggest that natriuretic peptides, especially CNP-22, inhibit FCS- or PDGF-BB-stimulated SMC migration at least in part through a cyclic GMP-dependent process. Thus, the natriuretic peptide family may play a role as an antimigration factor of SMCs under certain circumstances.

Animals↗
PubMed1997

Premorbid brain size as a determinant of reserve capacity against intellectual decline in Alzheimer's disease.

OBJECTIVE: Both the magnitude of brain atrophy and premorbid brain size determine the volume of the brain affected by Alzheimer's disease. To examine the possibility that premorbid brain volume is a determinant of cognitive reserve in patients with Alzheimer's disease, the relation between diffuse brain atrophy and cognitive decline and the impact of premorbid brain size on cognitive decline were studied in patients with Alzheimer's disease. METHOD: By measuring whole brain volume and intracranial volume in 60 patients with probable Alzheimer's disease, mild to moderate in severity, with the use of high-resolution magnetic resonance imaging and image processing, the authors studied the impact of premorbid brain volume and magnitude of diffuse brain atrophy on cognitive functions. On the basis of the normative brain-calvarium relationship derived from data an 28 healthy adults and the total intracranial volume measure of each patient, the magnitude of brain atrophy and premorbid brain volume were estimated. RESULTS: After control for the effects of age, sex, and education as confounding factors, it was found that the Alzheimer's disease patients' intelligence was correlated both positively with premorbid brain volume and negatively with magnitude of brain atrophy, while impairments in language and memory were correlated with magnitude of brain atrophy but not with premorbid brain volume. CONCLUSIONS: These findings partially support the hypothesis that premorbid brain volume is a determinant of reserves against intellectual decline in Alzheimer's disease.

Adult↗
PubMed1997

Deletion of the thyroid hormone beta1 receptor increases basal and triiodothyronine-induced growth hormone messenger ribonucleic acid in GH3 cells.

The conserved diversity, restricted distribution, and differential regulation of the thyroid hormone receptor (TR) isoforms raise the possibility of isoform-specific functions. We have addressed the roles of individual TRs in GH gene expression in GH3 cells by using an isoform-specific antisense RNA to delete TRbeta1. An antisense RNA vector, directed against the isoform-specific coding sequence of the parent TRbeta1 complementary DNA, was constructed. Stable transfected GH3-derived cell lines expressing this construct were established. Appropriate control cell lines were established in parallel. Depletion of TRbeta1 in cells expressing the antisense construct was confirmed at both the messenger RNA and protein levels. Total TR expression was maintained in these cells by a reciprocal increase in TRbeta2 levels. This perturbation of the TR population was associated with a 10.5-fold increase in basal and a 5.0-fold increase in T3-stimulated GH gene expression, but no increase in total T3 binding of nuclear extracts. In transient cotransfection experiments, there were no differences between control cells and those expressing the antisense construct in either basal or T3-stimulated expression of reporters containing a variety of thyroid hormone response elements. Depletion of TRbeta1 in GH3 cells results in a reciprocal increase in TRbeta2. These changes are associated with increased basal and T3-stimulated GH gene expression, which are not due to a nonspecific enhancement of basal or hormone-stimulated transcription. We demonstrate that TRbeta1 is not required for T3 induction of the GH gene in GH3 cells and that TRbeta1 and TRbeta2 are not equivalent in their effects on basal repression of the GH promoter. The data illustrate the potential for isoform- and promoter-specific dissociation of the repression and activation properties of the TRs.

Animals↗
PubMed1997

Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue.

The Na+/I- symporter (NIS) is important in hormone synthesis in the thyroid gland. NIS activity, as reflected by I- uptake, was increased by TSH (1 mU/mL) or forskolin (10 mumol/L) in primary cultured human thyroid cells. Northern blot analysis revealed that incubation of these cells with TSH or forskolin for 24 h increased the abundance of NIS messenger ribonucleic acid (mRNA) 2.3- and 2.5-fold, respectively. Immunoblot analysis revealed 2.7- and 2.4-fold increases, respectively, in the amount of NIS protein after 48 h, suggesting that elevated levels of intracellular cAMP induced the expression of NIS in human thyrocytes. We then studied the levels of NIS mRNA and protein in Graves' thyroid tissue and found that the amount of NIS mRNA in thyroid tissue from individuals with Graves' disease (n = 5) was 3.8 times that in normal thyroid tissue (n = 5). The abundance of NIS mRNA was significantly correlated with that of thyroid peroxidase or thyroglobulin mRNAs, but not with that of TSH receptor mRNA, in the Graves' and normal thyroid tissue specimens. The amount of NIS protein was also increased 3.1-fold in Graves' thyroid tissue compared with that in normal thyroid tissue. The increased expression of NIS may thus contribute to the development of Graves' disease.

Blotting, Northern↗
PubMed1997

A presenilin-1 mutation in a Japanese family with Alzheimer's disease and distinctive abnormalities on cranial MRI.

Some patients with familial Alzheimer's disease (FAD) have mutations in the presenilin-1 (PS-1) gene on chromosome 14. We report a Japanese family with AD and an Ala285Val substitution in exon 8 of the PS-1 gene. FAD in this family was characterized by relatively late onset (mean age, 50 years) and absence of myoclonus, seizures, or paratonia. Levels of tau were markedly elevated in CSF whereas CSF levels of amyloid beta protein were normal. MRI of the cranium showed marked linear signal abnormalities within white matter in the parieto-occipital lobes, consistent with cortical amyloid angiopathy of the type encountered in patients with the PS-1 gene mutation.

Alzheimer Disease↗
PubMed1997

Inhibitory effect of heparin on collagen fiber formation in hepatic cells in culture.

When M cells derived from rat liver and then transformed by treatment with 4-dimethylaminoazobenzene were cultured in vitro, the culture became covered with a collagen fiber network. When the M cells were cultured in the presence of more than 10 micrograms/ml heparin, no collagen fiber formation was observed. The inhibitory effect was evident at 5 micrograms/ml but was not significant at 1 microgram/ml. High performance liquid chromatography (HPLC) showed that about 50% decrease in hydroxyproline content occurred in the presence of 10 micrograms/ml heparin. The inhibition by heparin reached a plateau at 10 micrograms/ml. Other glycosaminoglycans such as heparan sulfate, keratan sulfate, chondroitin sulfate B and chondroitin sulfate C did not show a significant effect on hydroxyproline content. Modified heparins slightly decreased hydroxyproline content, but the collagen fibers were still observed. These results indicate that the native structure of heparin is important to attain the complete inhibition of collagen fiber formation; the basic structure, (-GlcUA or IdUA beta 1-4 GlcNSO3-)n, is important. HPLC, Northern blot analysis and Western blot analysis for rat type I collagen revealed that collagen synthesis is independent of heparin, but that collagen fiber formation is prevented by heparin.

Animals↗
PubMed1997

Cytoprotective effects of 4,6-bis(1H-pyrazol-1-yl)pyrimidine and related compounds on HCI.ethanol-induced gastric lesions in rats.

Bis(1H-pyrazol-1-yl)- and bis(1H-imidazol-1-yl)pyrimidines were synthesized and evaluated for cytoprotective effects. Among them, 4,6-bis(1H-pyrazol-1-yl)pyrimidine (3) showed a potent inhibitory effect on the HCl.ethanol-, ethanol-, and water immersion stress-induced gastric lesions in rats, and a very low acute toxicity. One of the major factors responsible for the cytoprotective effects of 3 is the increase in the bicarbonate secretion. This compound appears to be a promising cytoprotective drug for the treatment of gastric mucosal ulcers.

Animals↗
PubMed1997

Hyperproduction of L-threonine by an Escherichia coli mutant with impaired L-threonine uptake.

An efficient production strain for L-threonine fermentation was derived from Escherichia coli by multiple rounds of mutation programs that aimed at deregulation of the L-threonine biosynthetic pathway and blocking of L-threonine degradation pathways. When the optimum amount of DL-methionine was added, this strain KY10935, an L-methionine auxotroph, gave 100 g/liter L-threonine after 77 h cultivation. In this strain, key enzymes in the L-threonine biosynthetic pathway were highly derepressed, but some were inhibited by lower concentrations of L-threonine than the accumulated level. Such incomplete deregulation of the pathway was accounted for by the intracellular concentration of L-threonine being lower than the extracellular level. In an assessment of L-threonine transport in terms of phenotypic growth responses to the amino acid, L-threonine-auxotrophic mutants with a lesion in the L-threonine operon were derived from strain KY10935 by selection for auxotrophy for dipeptide L-alanyl-L-threonine or glycyl-L-threonine, the transport systems of which were different from those of L-threonine. All three independent mutants isolated needed an extraordinarily high concentration (10 mg/ml) of L-threonine, but grew in the presence of a low concentration (10 micrograms/ml) of either dipeptide, indicating that strain KY10935 had impaired L-threonine uptake. These results suggested that the strain had an unusual mechanism of L-threonine hyperproduction: the inability to take up L-threonine that had accumulated extracellularly decreased the steady-state level of intracellular L-threonine, freeing the remaining regulatory steps of feedback inhibition.

Amino Acids↗
PubMed1997

Effects of angiotensin AT1 receptor antagonist on volume overload-induced cardiac gene expression in rats.

The present study was undertaken to examine the effects of volume overload on cardiac gene expression and the possible role of angiotensin AT1 receptor in such expression. Cardiac volume overload was prepared by abdominal aortocaval shunt in rats. Rats with aortocaval shunt were treated with 1) vehicle, 2) an angiotensin AT1 receptor antagonist, CS-866 (10 mg/kg/d), or 3) an angiotensin-converting enzyme inhibitor, temocapril (10 mg/kg/d), for 7 days. Cardiac tissue mRNA was measured by Northern blot analysis with specific probes. Aortocaval shunt not only caused cardiac hypertrophy but also upregulated the gene expression of atrial natriuretic polypeptide, collagen III, and downregulated Ca(2+)-ATPase expression in the left ventricle. These changes were prevented by treatment with CS-866, while temocapril failed to normalize left ventricular Ca(2+)-ATPase expression. Unlike the left ventricle, the significant downregulation of alpha-myosin heavy chain and transforming growth factor-beta 3 by aortocaval shunt was observed in the right ventricle, and CS-866 normalized this decreased expression of transforming growth factor-beta 3. The left and right atria showed increased expression of collagen type I as well as of collagen type III and atrial natriuretic polypeptide, and these increases were more effectively prevented by CS-866 than by temocapril. Thus, the effects of cardiac volume overload on cardiac performance-related gene expression differ between the ventricles and atria. Our results suggest that AT1 receptor partially contributed to volume overload-induced changes in cardiac gene expression and that AT1 receptor antagonists and angiotensin-converting enzyme inhibitors have different effects in this model of cardiac hypertrophy.

Actins↗
PubMed1997

Nutritional evaluation of women in urban and rural areas in Korea as studied by total food duplicate method.

Nutrient intake was studied by the total food duplicate method in 141 adult working women (at the ages of 21 to 56 years) in four regions (Seoul, Pusan, Chunan and Haman) in Korea. Clinical, hematological and anthropometrical examinations were conducted in parallel. The nutrient intakes were estimated in reference to the weight of each food item and the national standard food composition tables for Korean population, and evaluated in comparison with the nationally recommended dietary allowances (RDA). The intakes were essentially sufficient when evaluated on a group basis. Plant-based foods were major sources of both protein (67%) and lipid (72%). Dinner was the most substantial sources of all nutrients. Further evaluation on an individual basis taking 80-120% RDA as acceptable showed that young people (at the ages of 20-29 years) and those in Seoul had highest prevalence of insufficient intake of nutrients, especially energy, protein and iron. Consumption of rice, the traditional staple food, was the lowest in Seoul and in the youngest groups as compared with others. The prevalence of overweight cases was also the lowest in the Seoul participants. The two observations when combined apparently suggest the difficulties in public nutrition.

Adult↗
PubMed1997

Nutritional evaluation of Chinese working women in the city of Tainan, Taiwan.

Nutritional survey was conducted in 1994 in Tainan City, southern Taiwan. Total food duplicate samples were collected from 52 women volunteers. Clinical examinations, anthropometry, hematology and serum biochemistry were also conducted. The intakes of nutrients were estimated from the weights of food items in reference to the standard food composition tables for Taiwanese. On average, the participants took 1,973 kcal energy, 69 g protein, 73 g lipid and 269 g carbohydrate per day. Animal-based foods accounted for 49% and 36% of protein and lipid sources, respectively, but fish and shellfish contributed only 11% for protein and essentially nil for lipid. Lunch was the most substantial meal of the day. When classified by age (i.e., 22-29, 30-39 and 40-66 year-old groups), no age-related difference was detected among the three groups in all nutrients except for crude fiber. Comparison with recommended dietary allowance (RDA) for Taiwanese, the insufficiency ratios were more than 50% for minerals (i.e., Fe and Ca) and vitamins (except for vitamin C). Excess in the lipid energy ratio (> 30%) was observed in 60% of the study population. In agreement with this high lipid intake, 17% of the participants had BMI of > 25, and triglyceride levels were elevated (> 150 mg/100 ml) in 27%. There were no anemic case despite the low Fe intake (14 mg/day).

Adult↗
PubMed1997

Nutritional evaluation of women in urban areas in continental China.

In 1993-1995, a nutritional survey was conducted in China, in which 50 women each in three cities of Beijing, Shanghai and Nanning (thus 150 in total) volunteered to offer 24-hr total food duplicates and peripheral blood samples. People daily took 1,776 kcal (7,431 kJ) energy, 57 g protein, 75 g lipid, 218 g carbohydrate, 439 mg calcium, 24 mg iron, 3,398 mg sodium and 1,521 mg potassium. When compared with the recommended dietary allowance for Chinese, intakes of energy, iron and possibly vitamin C were sufficient in a majority of the participants, but not so in cases of calcium, and several vitamins. The lipid energy ratio was 38% on an average and was higher than 30% in a majority (73%) of the people. BMI, but not the lipid energy ratio, correlated with the serum triglyceride level. In accordance with high iron intake, the prevalence of anemia was low. Inter-city differences were evident in nutrient sources. Thus, Beijing people took more amounts of protein and lipid from meats (including eggs and milk), whereas plant-based foods were important sources of lipid in Shanghai and that of protein in Nanning. Furthermore, consumption of rice was significantly lower in Beijing than in Shanghai and Nanning, whereas wheat consumption was higher in Beijing than in Shanghai and Nanning.

Adult↗
PubMed1997

Pioglitazone (AD-4833) ameliorates insulin resistance in patients with NIDDM. AD-4833 Glucose Clamp Study Group, Japan.

We evaluated the effect of pioglitazone, a thiazolidinedione compound, on insulin-stimulated glucose disposal (Rd) and its efficacy on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM). Twenty NIDDM subjects (mean age 58.2+/-9.4 year, body mass index (BMI) 23.9+/-3.4 kg/ m2 (mean+/-S.D.], three with diet alone, 17 with sulfonylureas [SU]) participated in this trial from five diabetes clinics. Euglycemic (5.3 mmol/liter) hyperinsulinemic (insulin infusion rate 9 micromoles x kg[-1] x min[-1]) clamp studies were performed before and after oral administration of pioglitazone (30 mg/day) for 87+/-10 days. The Rd significantly improved from 5.5+/-2.5 to 8.3+/-3.1 mg x kg(-1) x min(-1). Fasting plasma glucose (FPG) level significantly decreased from 11.0+/-2.0 mmol/liter to 8.9+/-1.1 mmol/liter with a significant improvement in the hemoglobin A1c level from 9.2+/-1.8% to 8.3+/-1.5%. Fasting serum insulin and C peptide levels decreased from 83+/-36 pmol/liter and 0.62+/-0.21 nmol/liter to 66+/-29 pmol/liter and 0.58+/-0.25 nmol/liter, respectively. Fasting serum triglyceride and free fatty acids levels significantly decreased with concomitant increase of fasting serum HDL-cholesterol levels from 1.2+/-0.2 to 1.5+/-0.3 mmol/liter. The change in Rd between before and after pioglitazone administration correlated with baseline values of FPG (rho=0.633), serum insulin (rho=0.653), BMI (rho=0.456), Rd (rho 0.558) and 1,5-AG (rho=-0.522). These data indicate that pioglitazone enhances the insulin action in NIDDM patients on diet alone or SU, and thereby improves both plasma glucose level and lipid profiles.

Administration, Oral↗