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Biomedical subjects

M Mukoyama

Publications and source records attributed to M Mukoyama.

At least 163 records · Page 9Linked to original sources

Simultaneous measurement of atrial natriuretic polypeptide (ANP) messenger RNA and ANP in rat heart--evidence for a preferentially increased synthesis and secretion of ANP in left atrium of spontaneously hypertensive rats (SHR).

Tissue levels of atrial natriuretic polypeptide (ANP) messenger RNA (ANPmRNA) and ANP in the rat heart were measured simultaneously. In Wistar rats, ANPmRNA of the same size (approximately 0.95 kbp) was detected in all four chambers of the rat heart. The ANPmRNA level was the highest in the right atrium, and the left atrial level was slightly lower than the right atrial level. Ventricular levels were more than two orders of magnitude lower than atrial levels. Tissue ANP concentrations of four chambers were roughly parallel to ANPmRNA levels. In spontaneously hypertensive rats (SHR) with the elevated plasma ANP level, the ANPmRNA level in the left atrium was substantially increased. The left/right ratio of atrial ANPmRNA level in SHR (150%) was higher than that in control Wistar Kyoto rats (WKY) (90%). In contrast, the left/right ratio of atrial ANP concentration was decreased in SHR (44%) compared with that in WKY (84%). The ratio of ANP to ANPmRNA levels in the left atrium of SHR was about three times smaller than that in the right atrium of SHR, and those in bilateral atria of WKY. These results indicate that the biosynthesis and secretion of ANP from the left atrium is preferentially increased in SHR. Thus, simultaneous determination of ANPmRNA and ANP levels is a refined strategy of investigation for the biosynthesis, storage and secretion of ANP.

Animals↗

Lack of change in indoleamine metabolism in spinal cord of patients with amyotrophic lateral sclerosis.

Indoleamine metabolism was determined by high-performance liquid chromatography with electrochemical detection in the cervical spinal cord of patients with amyotrophic lateral sclerosis (ALS) and controls with non-neurological diseases. The concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were the highest in the ventral horn compared with other regions of the spinal cord both in ALS and controls. There was no significant change in the concentration of 5-HT in any region of the spinal cord between ALS and controls. In addition, the concentration of 5-HIAA in ALS was lower than that in controls, however, no statistical significance was observed.

Adult↗

Atrial natriuretic polypeptide in spinal cord and autonomic ganglia.

Using a radioimmunoassay for alpha-rat atrial natriuretic polypeptide (alpha-rANP), tissue levels of alpha-rANP-like immunoreactivity (-LI) in the rat spinal cord and autonomic ganglia were investigated. The alpha-rANP-LI level was higher in the more caudal parts of the spinal cord and the highest in the sacral spinal cord. alpha-rANP-LI was also detected in the superior cervical and coeliac ganglia. Gel permeation chromatographic analysis showed that the major peak of alpha-rANP-LI in the spinal cord was a low molecular weight form co-eluted with synthetic alpha-rANP. Reverse-phase high performance liquid chromatographic analysis revealed that alpha-rANP-LI with a low molecular weight in the spinal cord consisted of several components, two major components of which co-migrated with synthetic alpha-rANP (4-28) and alpha-rANP (5-28), whereas little immunoreactivity was eluted at the position of alpha-rANP. These findings suggest the involvement of ANP in the function of the spinal cord and autonomic nervous system.

Animals↗

Conversion of beta-human atrial natriuretic polypeptide into alpha-human atrial natriuretic polypeptide in human plasma in vitro.

Using synthetic beta-human atrial natriuretic polypeptide (beta-hANP), an antiparallel dimer of alpha-hANP, and radioimmunoassay (RIA) for alpha-ANP which also detects beta-hANP, we investigated the disappearance profile and the change in the molecular form of exogenously added beta-hANP in human plasma in vitro, compared with those of alpha-hANP. The ANP-like immunoreactivity (ANP-LI) level in beta-hANP-added human plasma exhibited slower disappearance than that in alpha-hANP-added plasma during the incubation at 37 degrees C. High performance-gel permeation chromatography and reverse phase-high performance liquid chromatography coupled with RIA revealed that beta-hANP (6K) was converted into a smaller peptide with an approximate molecular weight of 3K corresponding to alpha-hANP during the incubation. Amino acid analysis and amino-terminal sequencing confirmed that the converted peptide from beta-hANP in human plasma is authentic alpha-hANP. The demonstrated conversion of beta-hANP into alpha-hANP in human plasma could be relevant to the in vivo natriuretic and diuretic actions with slower onset and longer duration of this unique peptide.

Amino Acids↗

Life spans of Duchenne muscular dystrophy patients in the hospital care program in Japan.

Analysis of 176 autopsy cases of Duchenne muscular dystrophy (DMD) demonstrated that (1) hospitalized patients showed longer life spans than their non-hospitalized affected maternal uncles, (2) patients hospitalized recently lived longer than those hospitalized in the past, and (3) pulmonary infection has become a less frequent cause of death in recent years, whereas dystrophic changes of the cardiac and respiratory muscles are more closely related with recent fatal cases. These results indicate the changing life span expectancy of patients with DMD and the changes in cause of death over the last decade, probably owing to the benefits of a hospital care program.

Adolescent↗

Secretory form of atrial natriuretic polypeptide as cardiac hormone in humans and rats.

To elucidate the secretory form of atrial natriuretic polypeptide from the atrium, the molecular form of atrial natriuretic polypeptide in the perfusate from the isolated beating rat heart and in plasma taken at the coronary sinus of 10 patients during cardiac catheterization has been investigated using high performance gel permeation chromatography and reverse phase high performance liquid chromatography coupled with radioimmunoassay for atrial natriuretic polypeptide. Atrial natriuretic polypeptide in the perfusate from the rat heart showed a single peak eluting at the position of a low molecular weight form of atrial natriuretic polypeptide, without any detectable amounts of atrial natriuretic polypeptide with high molecular weights. The major component of atrial natriuretic polypeptide in the rat heart perfusate co-migrated with rat alpha-atrial natriuretic polypeptide in reverse phase high performance liquid chromatography. In 9 out of 10 patients atrial natriuretic polypeptide in plasma taken at the coronary sinus revealed a single peak of atrial natriuretic polypeptide emerging at the position of human alpha-atrial natriuretic polypeptide in gel filtration. Only one plasma sample had a small quantity of high molecular weight forms with the predominant low molecular weight form of atrial natriuretic polypeptide. The major component of atrial natriuretic polypeptide in the plasma extract from the coronary sinus was identified with human alpha-atrial natriuretic polypeptide. These results indicate that alpha-ANP, a 28-amino acid polypeptide, is secreted as a cardiac hormone into the coronary blood stream from the atrium.

Animals↗

Modulatory role of vasopressin in secretion of atrial natriuretic polypeptide in conscious rats.

To investigate whether vasopressin is involved in the secretory mechanism of atrial natriuretic polypeptide (ANP), effects of arginine-vasopressin (AVP) administered iv on plasma ANP levels were studied in conscious, unrestrained rats. The administration of 100 ng and 1 microgram of AVP caused a dose-dependent increase of the plasma ANP level, which was blocked by a V1-receptor antagonist of AVP, and was attenuated by 5 ml blood volume reduction before the stimulation. The injection of less than 10 ng of AVP induced no significant effects on ANP secretion. However, the administration of 5 ng of AVP significantly enhanced ANP secretion induced by intravascular volume expansion with 3 ml saline infusion. These results suggest the possible physiological significance of AVP as a modulator rather than a direct stimulator of ANP secretion from the heart.

Animals↗

Central actions of atrial natriuretic polypeptides in spontaneously hypertensive and normotensive rats.

The effects of intracerebroventricular (i.c.v.) administration of ANP on blood pressure and intakes of water and salt were examined, using conscious, unrestrained normotensive Wistar rats and spontaneously hypertensive rats (SHR). In normotensive rats, i.c.v. administration of alpha-rat ANP (alpha-rANP), alpha-human ANP (alpha-hANP), alpha-rANP (4-28) and alpha-rANP (5-28) at the dose of 1.5 nmol significantly attenuated water intake induced by i.c.v. injection of 0.1 nmol of angiotensin II (AII). Centrally administered alpha-hANP (5 micrograms) also attenuated AII-induced pressor response. Centrally injected alpha-hANP (1 microgram) produced a greater reduction of water intake after 24-hour water deprivation in SHR compared to control Wistar Kyoto rats (WKY). Central infusion of alpha-hANP for 1 week also reduced the salt appetite of SHR, as shown by two bottle preference test with 0.3 M NaCl solution and tap water, while it had no effect on drinking behavior of WKY. These results suggest the central antagonistic relationship of the ANP and renin-angiotensin systems and the possible involvement of brain ANP in the pathophysiology of genetically hypertensive rats.

Angiotensin II↗

[Fundamental study on ataxic mice (wriggle mouse Sagami)].

Wriggle mouse Sagami (WMS), a newly discovered BALB/C mouse strain, is characterized by its locomotor instability, abnormal gait pattern and neck wriggling. Although the growth of WMS mice is delayed, compared with normal BALB/C mice, the brain size corresponds to the relatively smaller body weight. In gross or histological examinations no local atrophy appears in the cerebrum, cerebellum, brain stem or spinal cord. The c-GMP level in the WMS cerebellum is decreased, but the c-AMP level is normal. The ataxic gait is not improved significantly by the administration of thyrotropin releasing hormone (TRH). These results indicate that the mechanism inducing ataxia and abnormal gait pattern in WMS may be different from those in other genetically-determined ataxic mice, e. g., Rolling mouse Nagaya (RMN), PCD, Staggerer and Reeler.

Animals↗

Atrial natriuretic polypeptide in brain--implication of central cardiovascular control.

Biologically active peptides isolated in the peripheral organs often distribute in the central nervous system and vice versa. Accumulating evidence supports the concept that the effects of centrally active peptides are often, although not always, complementary to their peripheral actions. Atrial natriuretic polypeptide (ANP) is one of these biologically active peptides. Evidence presented here indicates that ANP is involved in the cardiovascular control as a neuropeptide in the central nervous system as well as a circulating hormone in the periphery.

Animals↗

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes with acanthocytosis: a clinicopathological study of a unique case.

A case of a unique combination of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like syndrome (MELAS) with acanthocytosis is reported. Neuropathological examination revealed pellagra-like change in Betz cells, brain-stem neurons and anterior horn cells as well as findings compatible with mitochondrial encephalomyopathies. Abnormal function of nicotinic acid-related enzymes could be the cause of the complicated clinicopathologic findings in this case. This is the first report of MELAS with acanthocytosis.

Acanthocytes↗

Concentrations of thyrotropin-releasing hormone in the brain of patients with amyotrophic lateral sclerosis.

Concentrations of thyrotropin-releasing hormone (TRH) were measured by a specific radioimmunoassay in the brain of 11 patients with amyotrophic lateral sclerosis (ALS) and 6 controls (myocardial infarction, gastric cancer, multiple myeloma, cerebrovascular disease, amyloid neuropathy). TRH was found in all parts of the dissected brain tissues (pedunculus cerebri, corpus callosum, capsula interna, motor area) in patients with ALS and controls. The TRH concentrations in the brain of patients with ALS were significantly lower in the pedunculus cerebri, compared with controls, and tended to decrease in the motor area and corpus callosum, but not significantly. Changes in TRH concentrations did not always correlate with pathohistological changes. These findings suggest that TRH is widely distributed in the human brain and decreases in some part of the ALS brain.

Amyotrophic Lateral Sclerosis↗

Atrial natriuretic polypeptide in the brain: implication of central cardiovascular control.

Biologically active peptides isolated from peripheral organs often occur in the central nervous system, and vice versa. There is evidence that the effects of centrally active peptides are often, although not always, complementary to their peripheral actions. Atrial natriuretic polypeptide (ANP) is one of these biologically active peptides. Evidence presented here indicates that ANP is involved in the cardiovascular control as a neuropeptide in the central nervous system as well as a circulating hormone in the periphery.

Animals↗

Concentrations of immunoreactive thyrotropin-releasing hormone in the brain of patients with olivoponto-cerebellar atrophy.

The concentrations of immunoreactive thyrotropin-releasing hormone (ir-TRH) in the brain of patients with olivoponto-cerebellar atrophy (OPCA) were studied. Three patients with OPCA and 8 non-central nervous system degenerative diseases were subjects in this study. Ir-TRH concentration in the brain was measured by radioimmunoassay. Ir-TRH was present in all parts of the dissected brain tissues (hypothalamus, frontal lobe, cerebellar cortex, olivary n., dentate n. and caudate n.) of patients with OPCA and non-central nervous system degenerative diseases. Ir-TRH concentration in the brain of case 1 and 2 was lower in the cerebellar cortex and olivary n., in contrast, ir-TRH concentration in case 3 was higher in the dentate n. The regions and the severity of pathological changes were different in each case of OPCA and changes in ir-TRH concentration in the brain did not always correlate with the severity of pathological changes. These findings suggest that changes in ir-TRH concentration in the brain of patients with OPCA may differ in each case, and may play some pathophysiological role in OPCA.

Adult↗

Neoplastic angioendotheliosis of the central nervous system.

A case of neoplastic angioendotheliosis demonstrating unusual manifestations is reported. A 56-year-old male showed recurrent attacks of neurological symptoms including paraplegia, brain-stem symptoms, tonic seizures, aphasia, apraxia and cortical blindness over 2 years. The EEG disclosed transient, periodic, lateralized, epileptiform discharges. Brain CT scan revealed low-density areas mainly in the white matter. Other laboratory examinations were negative except for CSF protein fractions. Post-mortem examination disclosed remarkable intravascular proliferation of atypical cells in the CNS with prominent proliferation of blood vessels and softening. Other organs were not affected, which suggested that the atypical cells had a high affinity to CNS blood vessels.

Brain↗