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Biomedical subjects

M Murayama

Publications and source records attributed to M Murayama.

At least 55 records · Page 3Linked to original sources

[Effect of angiotensin converting enzyme inhibitor lisinopril on sympathetic heart rate response during exercise in the early phase of acute myocardial infarction].

OBJECTIVES: Sympathetic heart rate response decreases in patients with left ventricular dysfunction. Angiotensin converting enzyme (ACE) inhibitors effectively prevent heart failure after myocardial infarction. However, the effect of ACE inhibitors on heart rate response is not well known. The present study investigated the effect of ACE inhibitors on sympathetic heart rate response in the early phase of acute myocardial infarction. METHODS: Sixty-five patients with acute myocardial infarction receiving no beta-blocking agents participated in the study. The subjects consisted of 25 patients (mean age 60.2 +/- 10.7 years) treated with ACE inhibitor lisinopril from the initial stage and 40 control subjects (mean age 57.7 +/- 7.6 years). Cardiopulmonary exercise testing with a treadmill was performed using the ramp protocol in the first month and the third month after the onset of the disease. Heart rate (HR) was measured in the resting state (rest) and immediately after peak exercise (peak). At the same time, blood samples were obtained to investigate the changes in the plasma level of norepinephrine (NE). The degree of sympathetic heart rate response was evaluated as follows: (peak HR - rest HR)/¿(peak NE - rest NE)/rest NE¿ x 100. RESULTS: There were no significant differences between the 2 groups in the first month in anaerobic threshold, peak oxygen uptake and plasma brain natriuretic peptide concentration. Though the change of heart rate was not significant, the change in the plasma level of norepinephrine was significantly lower in the lisinopril group (9.3 +/- 4.4 vs 5.7 +/- 2.8, p < 0.01). In the first month, the heart rate response in the control group was markedly lower than that in the lisinopril group (8.7 +/- 3.5 vs 15.2 +/- 8.5 beats/min/%, p < 0.01). In the third month, the significant difference between the 2 groups disappeared (10.7 +/- 7.9 vs 14.0 +/- 9.7 beats/min/%, NS) due to the increase of the value in the control subjects. CONCLUSIONS: From these results, we conclude that ACE inhibitors are effective to improve sympathetic heart rate response during exercise in the early phase of myocardial infarction.

Anaerobic Threshold↗

Enhancement of amyloid beta 42 secretion by 28 different presenilin 1 mutations of familial Alzheimer's disease.

Families bearing mutations in the presenilin 1 (PS1) gene develop early onset familial Alzheimer's disease (FAD). Further, some PS1 mutants enhance secretion of the longer form of amyloid beta protein (Abeta42). We constructed cDNAs encoding human PS1 harboring 28 FAD-linked mutations, and examined the effects of the expressed PS1 mutants on Abeta42 secretion in beta amyloid precursor producing COS-1 cells. All the mutants significantly enhanced the ratio of Abeta42 to total Abeta compared with wild-type PS1. However, the increase in Abeta42 ratio in cells with each PS1 mutation did not correlate with the reported age of onset of FAD caused by that mutation. These results suggest that increased Abeta42 secretion is important for the development of Alzheimer's disease (AD), but may not be the only factor contributing to the onset of AD.

Age of Onset↗

Increased serum levels and sinusoidal expression of thrombomodulin in acute liver damage.

Thrombomodulin (TM) is a surface glycoprotein of endothelial cells involved in both anticoagulation and antifibrinolysis. In this study, we assessed the clinical significance of TM in acute liver damage by using a rat model induced by intraperitoneal injection of D-galactosamine (Gal-N). Serum TM levels were measured with enzyme immunoassay utilizing rabbit anti-rat TM antibody. Simultaneously, immunohistochemical examination was performed using the same antibody. Serum TM levels increased significantly after the injection of Gal-N compared with preinjection levels, peaking from 48 to 72 hours after injection and normalizing by 168 hours. Changes in parenchymal damage were synchronized with changes of TM, and changes of TM levels mirrored changes of liver weight. In immunohistochemical examination, TM immunoreactivity was observed only on the endothelial surfaces of both the artery and portal vein within Glisson's sheath in controls. After injection of Gal-N, TM immunoreactivity was gradually intensified, especially around the necrotic area and the central veins. These findings disappeared with improvement of parenchymal damage. Both the increase of serum TM levels and intensified TM immunoreactivity in the liver were synchronized with acute liver parenchymal damage induced by Gal-N. These findings on TM are related to endothelial damage with parenchymal necrosis and liver regeneration interacting with both homeostasis of microcirculation and healing of parenchymal damage.

Acute Disease↗

Impaired proteolytic processing of presenilin-1 in chromosome 14-linked familial Alzheimer's disease patient lymphocytes.

Many cases of early-onset familial Alzheimer's disease (FAD) are caused by mutations in the presenilin 1 (PS1) and PS2 genes. PS1 protein is generated as a 47 kDa protein and is endoproteolytically cleaved into N-terminal 28 kDa and C-terminal 19 kDa fragments in vivo. To examine whether mutated PS1 protein is abnormally metabolized, we performed immunoblot analysis of lymphoblasts from familial Alzheimer's disease patients and controls. More full-length PS1 was apparently detected in samples from PS1 mutants than those from PS2 mutant and controls. This result suggests that impaired proteolysis of PS1 may be associated with the pathogenesis of FAD. Moreover, our simple test using lymphocytes from FAD patients might be useful from a diagnostic point of view.

Alzheimer Disease↗

Natural course of combined limb and palatal tremor caused by cerebellar-brain stem infarction.

After infarction of the left superior cerebellar peduncle and dentate nucleus, a patient developed tremor of the left upper limb beginning on the twelfth day followed by palatal tremor appearing 10 months after infarction. Surface electromyogram revealed a difference in the frequency of the tremor in the upper limb and soft palate. When the palatal tremor appeared, brain magnetic resonance T2-weighted images revealed high signal intensity of the contralateral, right inferior olivary nucleus. Subsequently, when the amplitude of palatal tremor became less severe, the high olivary signal intensity subsided whereas the hypertrophy of the nucleus remained. This patient provides useful information on the pathogenesis of skeletal and palatal tremor with brain stem or cerebellar lesions based on the differences in the onset and frequency of tremors and morphologic changes in the inferior olive.

Arm↗

Effect of angiotensin-converting enzyme gene polymorphism on left ventricular remodeling after anteroseptal infarction.

BACKGROUND AND HYPOTHESIS: Genetic influence on cardiac remodeling is uncertain. The purpose of this study is to determine the effects of polymorphism of the angiotensin-converting enzyme (ACE) gene on cardiac remodeling after myocardial infarction. METHODS: The subjects were 43 patients with old anteroseptal myocardial infarction. Based on the polymorphism of the ACE gene, they were classified into a deletion group of 25 patients (D/D genotype in 4 and D/I genotype in 21) and an insertion group of 18 patients (all I/I genotype). Echocardiograms were used to determine left ventricular end-diastolic and end-systolic diameters, interventricular septal and posterior wall thicknesses, left ventricular mass, left atrial diameter, and left ventricular ejection fraction. Blood concentrations of atrial and brain natriuretic peptide were also measured. RESULTS: Left ventricular end-systolic and end-diastolic dimensions, left ventricular mass, and levels of both atrial and brain natriuretic peptide were significantly higher in the deletion group. In contrast, septal thickness, posterior wall thickness, and ejection fraction showed no differences between the two groups. CONCLUSIONS: In patients with old anteroseptal infarction, ACE gene polymorphism of the D/D and D/I genotypes has a stronger influence on left ventricular remodeling than polymorphism of the I/I genotype.

Aged↗

Twenty-nine missense mutations linked with familial Alzheimer's disease alter the processing of presenilin 1.

1. Full-length form of human presenilin 1 (PS1) is processed and an N-terminal fragment (28 KD) and C-terminal fragment (19 KD) are generated. To elucidate the possible role of presenilin mutations in Alzheimer's disease (AD), the authors analyze the effects of AD-linked mutations on PS1 processing in cultured cells. 2. Complementary DNAs encoding genes for human PS1 harboring twenty-nine missense mutations linked with familial Alzheimer's disease (FAD) were introduced into PC12 cells. Human PS1 exogenously expressed in the cells was detected by immunoblotting using a monoclonal antibody that recognized the N-terminal region of human PS1. The amounts of full-length form (48 KD) and N-terminal fragment (28 KD) of PS1 was quantified by densitometrical analysis. 3. The ratio of the N-terminal fragment to total PS1 was reduced by twenty-nine mutations. The specific effects on PS1 processing varied according to mutation. 4. These results suggest that AD-linked missense mutations of PS1 are involved in neurodegeneration via inhibition of PS1 processing.

Alzheimer Disease↗

Use of mobile low-bandwith telemedical techniques for extreme telemedicine applications.

BACKGROUND: Telemedicine is traditionally associated with the use of very expensive and bulky telecommunications equipment along with substantial bandwidth requirements (128 kilobytes per second [kbps] or greater). Telementoring is an educational technique that involves real-time guidance of a less experienced physician through a procedure in which he or she has limited experience. This technique has been especially dependent on the aforementioned requirements. Traditionally, telemedicine and telementoring have been restricted to technically sophisticated sites. The telemedicine applications through the existing telecommunication infrastructure has not been possible for underdeveloped parts of the world. STUDY DESIGN: Telemedicine and telementoring were applied using low-bandwidth mobile telemedicine applications to support a mobile surgery program in rural Ecuador run by the Cinterandes Foundation and headed by Edgar Rodas, MD. A mobile operating room traveled to a remote region of Ecuador. Using a laptop computer equipped with telemedicine software, a videoconferencing system, and a digital camera, surgical patients were evaluated and operative decisions were made over low-bandwidth telephone lines. Similarly, surgeons in the mobile unit in Ecuador were telementored by an experienced surgeon located thousands of miles away at Yale University School of Medicine. RESULTS: Five preoperative evaluations were conducted from Sucua to Cuenca, Ecuador, with excellent clinical correlation. Additionally, a laparoscopic cholecystectomy was successfully telementored from the department of surgery at Yale University School of Medicine to the mobile surgery unit in Ecuador. The telementored surgery was performed using a telephone line with a baud rate of 12 kbps. CONCLUSIONS: Mobile, low-bandwidth telemedicine applications used in the proper technical and clinical algorithms can be very effective in supporting remote health care delivery efforts. Advantages of such applications include increased cost-effectiveness by limiting travel, expanding services to patients, and increased patient quality assurance.

Ecuador↗

Chemical species of organotin compounds in sediment at a marina.

A bottom sediment collected in a marina was analyzed for organotin species, and >20 organotin compounds including biodegraded ones were confirmed by comparison with the synthesized standards using gas chromatography (GC)/mass spectrometry and a GC/atomic emission detection system. Their structures were also determined in comparison with those in a technical grade of tri-n-butyltin chloride (TBTC). Eleven organotin compounds were found in the technical TBTC. Among them, unexpected organotin compounds, such as di-n-butyl(2-ethylhexyl)tin chloride and di-n-butyloctyltin chloride, were identified, although the levels were low. These compounds were also found in the sediment sample. The relationship between organotin compounds in the technical TBTC and those in marine products was also discussed.

Chromatography, Gas↗

Some sulfur-containing metabolites of tri-n-butyltin chloride in male rats.

In an attempt to elucidate metabolic destination of TBTO, sulfur-containing metabolites were investigated in the urine. Tri-n-butyltin chloride (TBTC), tri-n-butyltin oxide (TBTO), and their in vitro metabolites in rat liver microsomal enzyme systems, di-n-butyl(3-hydroxybutyl)tin chloride (T3OH), di-n-butyl(3-oxobutyl)tin chloride (T3CO), dibutyltin dichloride (DBTC), and monobutyltin trichloride (MBTC), were intraperitoneally administered to rats. In particular, administration of T3OH and T3CO gave higher amounts of mercapturic acid derivatives, such as N-acetyl-S-(3-oxobutyl)-L-cysteine (3CO-MA) and N-acetyl-S-(3-hydroxybutyl)-L-cysteine (3OH-MA), than TBTC or TBTO. On the other hand, DBTC and MBTC did not yield measurable amounts of 3CO-MA and/or 3OH-MA. The appearance of organotin metabolites in urine indicates that T3OH, T3CO, and hypothesized secondary metabolites, such as n-butyl(3-hydroxybutyl)(3-oxobutyl)tin chloride, n-butyl(3-hydroxybutyl)(4-hydroxybutyl)tin chloride, etc., are subject to the action of glutathione S-transferase to give mercapturic acid derivatives. These sulfur-containing metabolites (3CO-MA and 3OH-MA) were also found in control rat urine.

Animals↗

Dual roles of proteasome in the metabolism of presenilin 1.

Presenilin 1 (PS1) has been identified as a causative gene for most early-onset familial Alzheimer's disease. Biochemical studies revealed that PS1 exists predominantly as two processed fragments in cells and brain tissues. We prepared stably transfected cells expressing the wild-type and familial Alzheimer's disease-associated mutants of PS1 and investigated the enzyme that participates in the metabolism of PS1. After treatment of the cells with proteasome inhibitors, the full-length PS1 was significantly accumulated. The levels of N- and C-terminal fragments were also increased. The accumulation of PS1 with a deletion of exon 10, which is unable to be processed, on treatment of the transfected cells with lactacystin indicated that proteasome can degrade full-length PS1. A synthetic peptide that includes the processing region of PS1 was cleaved by 20S proteasome at the putative processing sites after Met288 and Glu299. Metabolic labeling experiments showed that the appearance of the N-terminal fragment was attenuated by the inhibitor. Finally, 28-kDa N- and 20-kDa C-terminal fragments were generated by purified PS1 in vitro. These data indicated that the proteasome pathway is involved in PS1 processing. These results demonstrate that the proteasome pathway plays dual roles in processing and degradation of PS1.

Acetylcysteine↗

Response to granulocyte colony-stimulating factor in an autoimmune neutropenic adult.

Clinical value of granulocyte colony-stimulating factor (G-CSF) for autoimmune neutropenia (AIN) has not been well established. We experienced an adult case of AIN which showed an excellent response to G-CSF. A 75-year-old female was admitted with high-grade fever. Her neutrophil count was remarkably low (neutrophil 0.09 x 10(9)/l). Antigranulocyte autoantibody was demonstrated in her serum by an immunofluorescence method and she was diagnosed as AIN. Administration of G-CSF (filgrastim 5 microgram/kg) gave a rapid increase of neutrophils (from 0.11 x 10(9)/l to 2.10 x 10(9)/l on the second day), which has enabled us to preserve the use of G-CSF for emergency, that is, for overt serious infection.

Aged↗

Magnesium dynamics and sympathetic nervous system activity in patients with chronic heart failure.

This study was undertaken in patients with heart failure to investigate the relation between plasma norepinephrine (NE) concentration and Mg dynamics. The study subjects comprised 16 patients with chronic heart failure (mean age 64.9+/-10.0 years). Cardiopulmonary exercise testing was performed on all patients, and anaerobic threshold (AT), peak oxygen uptake (peak VO2) and peak exercise time were measured. Resting and peak values of plasma NE concentration and serum and erythrocyte magnesium concentration were also measured. The results were as follows: the serum Mg concentration was increased significantly immediately after exercise (p<0.01), and the erythrocyte Mg concentration showed a tendency to decrease (p<0.1). The resting plasma NE level was inversely correlated with AT (p<0.05, r=-0.57), peak VO2 (p<0.05, r=-0.55) and peak exercise time (p<0.01, r=-0.62). When the plasma NE concentration at rest was analyzed in 2 groups of patients, ie, those with higher than average and those with lower than average concentrations, the resting erythrocyte Mg concentration was significantly lower in the high-NE group (2.2+/-0.3 mg/dl) than in the low-NE group (2.7+/-0.5 mg/dl) (p<0.05). The data indicate that patients with chronic heart failure associated with high NE levels at rest who showed low exercise tolerance have intracellular hypomagnesemia, which may be caused by Mg migration from intracellular to extracellular spaces.

Adult↗

Exercise-induced changes in plasma atrial natriuretic peptide and brain natriuretic peptide concentrations in healthy subjects with chronic sleep deprivation.

Recent observations have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) correlate with cardiac function or prognosis in heart failure patients. However, relatively little is known about changes in their plasma concentration during commonly occurring physiological states such as fatigue. Therefore, this study was designed to examine the physiological changes of plasma ANP and BNP concentrations using a chronic sleep-deprivation model. Bicycle ergometer cardiopulmonary exercise tests were performed in 10 healthy volunteers (mean age: 22.7 years). Blood samples for measuring ANP and BNP were drawn during the resting state and immediately after each exercise test. Cardiac output (CO) was measured during the exercise test by the impedance method. The study conditions were designed as follows: (A) a day following a period of normal sleep (control state) and (B) a day preceded by 1 month during which sleep lasted <60% of normal (chronic sleep-deprived state). Results were as follows. (1) Peak oxygen uptake and peak CO decreased during the sleep-deprived state compared with the control state. (2) There was no difference between peak heart rates measured during exercise under the 2 conditions. (3) Plasma ANP concentration during exercise increased significantly during the control state, whereas only a tendency toward increase was observed during the sleep-deprived state. (4) Plasma BNP concentration during exercise tended to increase in the control state compared with the resting state, whereas there was no difference in plasma BNP between after exercise and resting state in the sleep-deprived state. These results indicate that changes of ANP or BNP induced by exercise tended to be decreased by chronic sleep deprivation.

Adult↗

Effects of exercise training on the recovery of the autonomic nervous system and exercise capacity after acute myocardial infarction.

This study investigated the effects of aerobic exercise training on the early phase of the recovery process following acute myocardial infarction (AMI) in terms of the autonomic nervous system, cardiac function and exercise capacity. Twenty-eight patients in the first week after the onset of AMI were assigned randomly to either a training group or a control group. The training group performed aerobic exercise for 2 weeks. Cardiopulmonary exercise testing was performed 3 times during the 3 months after the onset. Heart rate variability, plasma norepinephrine (NE) levels, and cardiac index (CI) during exercise were measured. In the training group, plasma NE level and deltaCI (peak CI-rest CI) were significantly improved from 1 to 3 weeks after the onset, and the high frequency of heart rate variability and peak oxygen uptake were significantly increased up to 3 months after the onset. In the control group, the plasma NE level and the deltaCI during the 1-3 weeks post-AMI, the high frequency of heart rate variability and the peak oxygen uptake showed a tendency to improve up to 3 months after the onset. These results indicate that sympathetic nervous activity improves soon after the onset of AMI, in conjunction with improvement in cardiac function, and that this improvement is not affected by exercise training. In contrast, the recovery of parasympathetic nervous activity requires a longer period, along with the recovery of exercise capacity, which is facilitated by even short-term aerobic exercise training.

Aged↗

Development of a new analytical method for the electrocardiogram using short-time first Fourier transforms.

To detect the minute electric potential inside the QRS complex, a new frequency domain method was designed using short-time First Fourier Transforms (SFFT) and high-frequency sampling (oversampling). SFFT improved the frequency resolution by oversampling that was applied to this analysis. The electric potential data of 15,000 points received weighted, running average processing and was subtracted from the original waveform to reduce the low-frequency component. The data in a segment of 160 ms, including QRS, was processed by frequency analysis with the SFFT computation routine. The ECG of healthy individuals was analyzed by this method and its usefulness evaluated. The processing waves of the X-axis, Y-axis, and Z-axis of a representative normal subject were formed into 3 groups of peak electric potential. SFFT enabled the detection of the structure inside the QRS complex without signal averaging, and is considered capable of evaluating the process of excitement inside the QRS complex in the various heart diseases.

Adult↗