Biomedical subjects

M Murayama

Publications and source records attributed to M Murayama.

At least 109 records · Page 6Linked to original sources

PubMed1996

Amphiphilic helix is essential for the activity of brain injury-derived neurotrophic peptide (BINP).

To study the structure-activity relationships of brain injury-derived neurotrophic peptide (BINP), 12 analogs were synthesized by replacing each amino acid residue with Gly. BINP showed CD spectra typical of an alpha-helical conformation in TFE solution which mimics the membrane environment. In the alpha-helical conformation, BINP showed an amphiphilic profile. Neurotrophic activities of BINP and its analogs were estimated from the effects on supporting septal cholinergic neurons and on rescuing hippocampal neurons from injury caused by glutamate. Both assays showed that the residues on the hydrophobic side of the amphiphilic helix were essential for the neurotrophic activity.

Amino Acid Sequence↗

PubMed1996

Localization of Alzheimer-associated presenilin 1 in transfected COS-7 cells.

Presenilin 1 (PS 1) is the recently identified gene, located on chromosome 14, of which missense mutations can cause early-onset familial Alzheimer's disease. To understand the normal biological function of presenilin 1, we examined the sub-cellular localization by using a monoclonal anti-presenilin 1 antibody. Immuno-electronmicroscopic and biochemical analysis indicated that presenilin 1 is localized on cellular membrane (plasma, endoplasmic reticulum, and perinuclear) in COS-7 cells overexpressing presenilin 1. Interestingly, the PS 1 immunoreactivity in the plasma membrane was concentrated in the regions with cell-cell contact. This observation suggests a possible role of PS 1 on the cell membrane as a cell adhesion molecule.

Alzheimer Disease↗

PubMed1996

Characteristics of patients with right bundle branch block and ST-segment elevation in right precordial leads. Idiopathic Ventricular Fibrillation Investigators.

To elucidate the clinical characteristics of patients with right bundle branch block and ST elevation in the right precordial leads, a prospective follow-up study was made in 63 registered patients, including 17 with a history of ventricular fibrillation (VF) and 14 with a history of syncope. The prevalence of coved type ST elevation was significantly higher in patients who had had cardiac events, and during the initial 15-month follow-up, 2 patients in the VF group died suddenly.

Adult↗

PubMed1996

No evidence of association between structural polymorphism at the dopamine D3 receptor locus and alcoholism in the Japanese.

Dopaminergic systems mediate reward mechanisms and are involved in reinforcing self-administration of dependence-forming substances, including alcohol. Studies have reported that polymorphisms of the dopamine D2 receptor, whose structure and function are similar to those of the dopamine D3 receptor, increase the susceptibility to alcoholism. These observations led to the examination of the possible association between a structural polymorphism of the D3 receptor gene and alcoholism. Genotyping results, employing a PCR-RFLP method, showed no difference in allele and genotype frequencies of the D3 BalI polymorphism (Ser9/Gly9) between Japanese alcoholics and controls. Moreover, these frequencies were not altered in alcoholics with inactive aldehyde dehydrogenase-2 (ALDH2), a well-defined negative risk factor for alcoholism. These results strongly suggest that the dopamine D3 receptor is not associated with alcoholism.

Adult↗

PubMed1996

Characterization of human presenilin 1 using N-terminal specific monoclonal antibodies: Evidence that Alzheimer mutations affect proteolytic processing.

The majority of cases of early-onset familial Alzheimer disease are caused by mutations in the recently identified presenilin 1 (PS1) gene, located on chromosome 14. PS1, a 467 amino acid protein, is predicted to be an integral membrane protein containing seven putative transmembrane domains and a large hydrophilic loop between the sixth and seventh membrane-spanning domain. We produced 7 monoclonal antibodies that react with 3 non-overlapping epitopes on the N-terminal hydrophilic tail of PS1. The monoclonal antibodies can detect the full-size PS1 at Mr 47000 and a more abundant Mr 28000 product in membrane extracts from human brain and human cell lines. PC12 cells transiently transfected with PS1 constructs containing two different Alzheimer mutations fail to generate the 28 kDa degradation product in contrast to PC12 cells transfected with wild-type PS1. Our results indicate that missense mutations in this form of familial Alzheimer disease may act via a mechanism of impaired proteolytic processing of PS1.

Alzheimer Disease↗

PubMed1996

Regulation of mitochondrial pyruvate dehydrogenase activity by tau protein kinase I/glycogen synthase kinase 3beta in brain.

According to the amyloid hypothesis for the pathogenesis of Alzheimer disease, beta-amyloid peptide (betaA) directly affects neurons, leading to neurodegeneration and tau phosphorylation. In rat hippocampal culture, betaA exposure activates tau protein kinase I/glycogen synthase kinase 3beta (TPKI/GSK-3beta), which phosphorylates tau protein into Alzheimer disease-like forms, resulting in neuronal death. To elucidate the mechanism of betaA-induced neuronal death, we searched for substrates of TPKI/GSK-3beta in a two-hybrid system and identified pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA in mitochondria. PDH was phosphorylated and inactivated by TPKI/GSK-3beta in vitro and also in betaA-treated hippocampal cultures, resulting in mitochondrial dysfunction, which would contribute to neuronal death. In cholinergic neurons, betaA impaired acetylcholine synthesis without affecting choline acetyltransferase activity, which suggests that PDH is inactivated by betaA-induced TPKI/GSK-3beta. Thus, TPKI/GSK-3beta regulates PDH and participates in energy metabolism and acetylcholine synthesis. These results suggest that TPKI/GSK-3beta plays a key role in the pathogenesis of Alzheimer disease.

Animals↗

PubMed1996

Molecular cloning and expression of the rat homologue of presenilin-1.

The rat homologue of the presenilin-1 (PS-1) gene, which is responsible for early-onset familial Alzheimer's disease linked to chromosome 14, was cloned and sequenced. The predicted amino acid sequence showed quite high homology among rat, mouse, and human PS-1. Especially, the amino acid sequences of the putative transmembrane domains were highly conserved among the three species. The expression ĺevel of the PS-1 gene increased during brain development and the number of transcripts of the PS-1 gene changed during brain development. We found one transcript of the PS-1 gene in embryonic day 12 (E12)-E15 rat brain and two transcripts in E18-adult rat brain. Therefore, PS-1 may play a role in neurogenesis.

Alzheimer Disease↗

PubMed1996

Assessment of posterior aortic wall motion using echocardiogram in patients with atrial fibrillation.

BACKGROUND AND HYPOTHESIS: Noninvasive evaluation of left ventricular (LV) diastolic function was performed on 12 patients with atrial fibrillation (AF) using posterior aortic wall echocardiogram and a parameter for determining the optimal heart rate in patients with chronic atrial fibrillation was considered. METHODS: Subjects were divided into two groups; one with no underlying cardiac disease (AF only group; n = 7) and the other with dilated cardiomyopathy (DCM group; n = 5). Left atrial emptying index (LAEI) obtained from the posterior aortic wall echocardiogram was used as the parameter of LV diastolic function, and R-R interval-LAEI relation and minimum R-R interval showing LAEI = 1.0 were investigated and compared between the two groups. RESULTS: There was a good correlation between R-R interval and LAEI until LAEI of 1.0 was obtained in all patients. Slope of the regression line was significantly steeper in the AF only group than in the DCM group, and minimum R-R interval showing LAEI = 1.0 was significantly shorter in the AF only group. CONCLUSION: Assessment of R-R interval-LAEI relation was useful for the noninvasive evaluation of LV diastolic function, and this parameter could be used for clinical application to determine the optimal heart rate in atrial fibrillation.

Aorta↗

PubMed1996

Polymorphisms of ethanol-oxidizing enzymes in alcoholics with inactive ALDH2.

Inactive aldehyde dehydrogenase-2 (ALDH2) is a well-known biological deterrent of heavy drinking among Asians, although some individuals who have inactive ALDH2 do become alcoholics. Unknown biological mechanisms facilitating the development of the disease may operate in such a way that these individuals overcome adverse reactions, or they may lower the intensity of the reactions. To examine our hypothesis that ethanol-oxidizing isoenzymes have lower catalytic properties in some persons, we investigated polymorphisms of ethanol-oxidizing enzymes that may alter their catalytic activities, viz., alcohol dehydrogenase-2 (ADH2) and -3 (ADH3), and cytochrome P450 2E1 (CYTP2E1), among 80 Japanese alcoholics with inactive ALDH2, 575 alcoholics with active ALDH2, and 461 controls. Although higher ADH2*1 and ADH3*2 allele frequencies were observed in alcoholics than in controls, there was no significant difference in ADH2 and ADH3 genotypes between alcoholics with inactive ALDH2 and alcoholics with active ALDH2. The genotype distributions of CYTP2E1 did not differ among the three groups, indicating no allelic association of the c1/c2 polymorphism of CYTP2E1 with alcoholism. These results suggest that genetic variations in ethanol-oxidizing activities are involved in the development of the disease, but that these variations are not specific in alcoholics with inactive ALDH2, a group at genetically low risk for alcoholism.

Adult↗

PubMed1996

Alcohol and aldehyde dehydrogenase genotypes and drinking behavior in Japanese.

The effects of the genotype of alcohol dehydrogenase-2 (ADH2) and mitochondrial aldehyde dehydrogenase (ALDH2) on drinking behavior were investigated in a population of 451 Japanese. Although the ALDH2*2 allele had a significant inhibitory effect on alcohol consumption, hence on drinking problems, the apparent association was not confirmed between ADH2 genotype and overall drinking patterns for either males or females. However, the frequency of the ADH2*2 allele was significantly lower in male Japanese classified as alcoholic on the basis of the Kurihama Alcoholism Screening Test than in nonalcoholic males. These results corroborate a previous study that revealed a significantly lower ADH2*2 allele frequency in hospitalized Japanese alcoholics than in the general population. Together, these studies suggest that the ALDH2*2 allele has an inhibitory effect on drinking behavior, irrespective of the level of alcohol consumption, whereas the effect of the ADH2 polymorphism only becomes apparent in individuals with higher alcohol consumption, such as alcoholics.

Adolescent↗

PubMed1996

Association between alcoholism and the dopamine D4 receptor gene.

A point mutation in the aldehyde dehydrogenase 2 gene (ALDH2(2) allele) is considered to be a genetic deterrent for alcoholism; however, 80 of 655 Japanese alcoholics had the mutant allele. Genotype factors that might increase susceptibility by overriding the deterrent showed a higher frequency of a five repeat allele of the dopamine D4 receptor 48 bp repeat polymorphism in alcoholics with ALDH2(2) than in 100 other alcoholics and 144 controls. Alcoholics with the five repeat allele also abused other drugs more often. These data suggest the involvement of the dopamine system in the development of alcoholism and other addictive behaviour.

Adult↗

PubMed1996

Sensory control mechanisms of the uropod equilibrium reflex during walking in the crayfish Procambarus clarkii

The temporal characteristics of statocyst and leg proprioceptive inputs to the uropod motor system were investigated in crayfish using behavioural and electromyographic analyses to elucidate their functional roles in the control of the uropod steering response under natural conditions. When the animal, which was suspended in the air without a footboard, was actively extending its abdomen, prolonged stimulation of the statocysts by body rolling elicited a maintained asymmetrical configuration of the bilateral uropods. Prolonged stimulation of the walking legs by footboard tilting with the animal body held in the upright position elicited a transient uropod response. When the treadmill was tilted while the animal was walking on it in the upright position, the uropods showed the same transient response. However, when the animal body was rolled, together with the treadmill, while the animal was walking on it, the uropods showed a transient response which was reversed in direction compared with that observed during body rolling without a footboard. This transient response was abolished by the removal of the statoliths. The results show that the statocysts and leg proprioceptors exert sustained and transient control effects, respectively, on the uropod motor system during walking. It is also suggested that the uropod response to body rolling during walking is controlled primarily by leg proprioceptor signals which result from statocyst-induced changes in the leg position.

Journal Article↗

PubMed1996

Angiographic and coronary risk factor analyses of Japanese patients with ischemic heart disease before age 40--a multicenter cooperative study.

Coronary angiographic and risk factor (RF) characteristics were analyzed in 133 Japanese patients with ischemic heart disease (IHD) who were less than 40 years old and who had undergone coronary angiography (CAG) during the past 10 years at six university hospitals in the Tokyo area. We compared the coronary angiographic characteristics of the subject group with those of 216 controls with coronary sclerosis detected by CAG who were more than 40 years old (older control group) and the RF characteristics with those of 133 sex- and age-matched volunteers (younger control group). Sixty seven percent of the subjects (89 cases) were diagnosed as having myocardial infarction (MI) and 33% (44 cases) had angina pectoris (AP). Coronary artery disorders in this group consisted of 103 (77%) cases of coronary sclerosis, 20 (15%) cases of coronary spasm and 10 (8%) cases of miscellaneous diseases, eg, possible vasculitis with connective tissue disease, congenital anomalies, etc. The incidences of significant (> or = 75%) sclerotic narrowing in 0 vessels (31%) and 1 vessel (49%) in the subject group were significantly (p < 0.01) higher than those in the older control group, while the incidence of multivessel disease was significantly (p < 0.05) less in the subject group than in the older control group. The incidences of the following coronary risk factors were significantly (p < 0.05) higher in the subjects than in the younger controls: smoking (83% vs 35%), hypercholesteremia (44% vs 10%), obesity (31% vs 9%), hypertension (29% vs 3%), familial IHD (28% vs 7%) and diabetes mellitus (19% vs 2%). Thus, zero- or single-vessel disease predominated in the younger subject group and the prevalence of coronary risk factors was significantly higher in the subject.

Adult↗

PubMed1996

Effects of cilazapril on exercise tolerance in the chronic phase of acute myocardial infarction.

The present study was conducted to investigate the effects of cilazapril on exercise tolerance and the hormone kinetics of catecholamines, the reninangiotensin-aldosterone system and alpha-atrial natriuretic peptide (ANP) in patients in the chronic phase of acute myocardial infarction (AMI). The subjects consisted of 19 cases of AMI. Cardiopulmonary exercise testing was performed 1 month after the onset of AMI, and patients were randomly assigned to either a group treated with 1 mg/day of cilazapril (9 cases) and or an untreated group (10 cases). After the completion of 2 months of exercise training at the anaerobic threshold (AT), blood samples were taken during a cardiopulmonary exercise test and various hormones were measured. In comparing the parameters of exercise tolerance before and after the completion of exercise training there were no significant differences between the 2 groups with respect to oxygen uptake, oxygen pulse, or exercise time at AT or at peak exercise. With regard to temporal changes in exercise tolerance, oxygen uptake, oxygen pulse and exercise time all tended to increase in both groups. With regard to hormone kinetics, the alpha-ANP concentration at peak exercise was significantly lower, and the noradrenaline secretions also tended to be lower, in the cilazapril-treated group, even though the peak exercise time was similar in both groups. These results may be support the hypothesis that cilazapril mitigates the left ventricular load during exercise therapy in patients in the chronic phase of AMI.

Aldosterone↗

PubMed1996

[A laser flow meter method for evaluating the peripheral blood flow in mice].

We have developed a method using a laser flow meter for investigating the effect of compounds on peripheral blood flow. The differences of blood flow in several portions and areas of the probe of a laser flow meter in the mouse and the effect of solvents for dissolving compounds on the blood flow were observed. The results indicated that the invisible area of blood vessels at the back or hind paw of the mouse was the most suitable placement position for the probe. In these placement positions, none of the tested solvents, 0.9% physiological saline solution, dimethylsulfoxide and 50% ethanol, had any significant effect on the peripheral blood flow. Next, using this method, we determined how the peripheral blood flow is affected by several drugs active on the circulatory system. By comparison between the present results from mice and previously reported data from other animals, it was shown that the effects of these cardiovascular agents on the peripheral blood flow in mouse skin showed similar tendencies to those in the previous reports using larger animals and sites other than the skin. However, a few of the drugs used in this experiment showed characteristic action on the peripheral blood flow in mice. Consequently, it was demonstrated that this method using the laser flow meter was useful as a simple first screening method to evaluate the effect of a compound on the peripheral blood flow.

Animals↗

PubMed1996

Contact hypersensitivity is suppressed after sensitisation by dinitrofluorobenzene of early stage iso-skin grafts.

Isologous free skin grafts were applied to the backs of BALB/c mice and contact hypersensitivity studied by epicutaneous application of DNFB (2,4-dinitro-1-fluorobenzene) to the grafted skin. In the first experiment, the grafted skin was sensitised and the elicitation reaction assessed by measuring the ear swelling after five days. Sensitisation was not successful until two weeks after grafting. In such non-responding animals, re-sensitisation with DNFB on the ungrafted skin area was also unsuccessful, indicating the establishment of immunological tolerance. This tolerance was considered antigen-specific, as re-sensitisation with oxazolone was successful. In the second experiment, spleen cell suspension, both untreated and treated in vitro with antiThy 1.2, antiLyt 1.2, and antiLyt 2.2 antibody, from non-DNFB-responding mice was transferred into normal mice. Subsequently these mice were sensitised with DNFB. Sensitisation was not successful in the untreated group or in those treated with antiLyt 1.2 antibody. On the other hand, the groups treated with antiThy 1.2 and antiLyt 2.2 antibody did become sensitised. These results indicate that the unsuccessful delayed hypersensitivity of the grafted skin was caused by suppressor T cells. In addition, the density of epidermal Langerhans cells was reduced in the early stages of skin grafting and morphological abnormalities were present. From these results, we conclude that contact sensitisation during the early stage of grafting skin not only produces suppression of ear swelling but also induces antigen-specific tolerance. These results also suggest that the suppression depends on the antigen-specific suppressor cells and that acquirement of tolerance is associated with a reduction in the number of epidermal Langerhans cells in the grafted skin and abnormalities in their structure.

Adjuvants, Immunologic↗

PubMed1996

[Relationship between ischemic ST depression and oxygen uptake kinetics during ramp exercise test in patients with effort angina].

The relationship between ischemic ST depression and oxygen uptake kinetics was examined during cardiopulmonary exercise test using the ramp protocol in 22 patients (17 males and 5 females, mean age 61.4 +/- 8.1 years) with ischemic ST change (horizontal or down sloping ST depression over 1 mm) during a previous multi-stage exercise test (Bruce method). Patients were classified into three groups according to coronary angiographic findings: absence of significant stenosis group (control, n = 7), single-vessel disease group (n = 7) and multivessel disease (MVD) group (n = 8). Peak exercise time, peak heart rate, peak systolic blood pressure, anaerobic threshold, peak oxygen uptake (peak Vo2), exercise time, heart rate, systolic blood pressure, and oxygen uptake at appearance of ischemic ST change were measured. The ratio of oxygen uptake increase at appearance of ischemic ST change was calculated. Peak Vo2 was lower in the MVD group than in the control group (20.9 +/- 6.2 vs 27.3 +/- 3.3 ml/min/kg, p < 0.05), and exercise time from the beginning of ramp exercise to the appearance of ischemic ST depression was shorter in the MVD group than in the control group (5.2 +/- 2.1 vs 8.2 +/- 1.9 ml/min/kg, p < 0.05). The ratio of oxygen uptake increase was smaller in the MVD group than in the control group (0.7 +/- 0.3 vs 1.2 +/- 0.2, p < 0.01). These results could be caused by impaired increase of cardiac output due to myocardial ischemia occurring during exercise. In the clinical setting, these phenomena could be used as a parameter for differentiating ischemic from non-ischemic ST depression or evaluating the sensitivity of ischemic heart disease.

Aged↗

PubMed1996

[Bradyarrhythmia].

Bradyarrhythmia has been well studied, and many results contributed to the progress of its treatments. When simple pacemaker like VVI was first invented, it seemed to have solved the problem, but the pacemaker did not improve the mortality rate until physiological pacing like DDD was invented. Permanent pacemaker implantation has now become standard means to solve the problem whether it was due to sinus node dysfunction or conduction disturbances. Recent trend of arrhythmia study has already been shifted to be focused on tachyarrhythmia, especially related to RF ablation. This new technique has revealed many informations related to mechanism of tachyarrhythmias, and also the basic functional structure of AV node and other cardiac conduction system. Such informations gave many knowledges about bradyarrhythmia. On the other hand, study on autonomic nervous system is not yet enough to unveil its role.

Autonomic Nervous System↗