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Biomedical subjects

M Mukoyama

Publications and source records attributed to M Mukoyama.

At least 127 records · Page 7Linked to original sources
PubMed1989

Ventricular expression of atrial natriuretic polypeptide and its relations with hemodynamics and histology in dilated human hearts. Immunohistochemical study of the endomyocardial biopsy specimens.

To investigate the mechanism of expression of atrial natriuretic polypeptide (ANP) in human ventricles, we conducted an immunohistochemical study of ANP in biventricular endomyocardial biopsy specimens obtained from a total of 49 patients with cardiac dilatation due to dilated cardiomyopathy (21 patients), postmyocarditis (18 patients), or volume overload (five patients) and subjects with no dilatation as controls (five patients). Four-micron thick sections were stained by an indirect immunoperoxidase method using monoclonal antibody to alpha-human ANP as the primary antibody. The frequency of ANP-present myocytes was calculated in each specimen and compared with clinical, echocardiographic, hemodynamic, angiographic, and histologic parameters. ANP-present myocytes were noted in all of the 21 patients with dilated cardiomyopathy, in 11 of the 18 patients with postmyocarditis, in four of the five patients with volume overload, and in zero of the five controls. The mean percentage of ANP-present myocytes was significantly greater in the left-side specimens (35 +/- 37%) than in the right-side ones (2 +/- 4%). The percentage of ANP-present myocytes in the left-side specimens significantly correlated with peak systolic or end-diastolic wall stress (r = 0.67 and 0.58), left ventricular end-systolic or end-diastolic volume index (r = 0.75 and 0.69), or left ventricular end-diastolic pressure (r = 0.42) and inversely correlated with ejection fraction (r = -0.73), systolic left ventricular wall thickness (r = -0.58), or cardiac index (r = -0.30). Expression of ANP was rarely seen in the cases with normal wall stresses, normal ejection fraction, normal volume, or normal myocyte size. However, it was seen frequently even in hearts with normal levels of left ventricular end-diastolic pressure and cardiac index (compensated hearts). The percent of ANP-present myocytes in both sides significantly correlated with size of myocytes (r = 0.48 at right and r = 0.57 at left side) or degree of fibrosis (r = 0.45 at right and r = 0.48 at left side). These results suggest that ANP expression is augmented in the dilated ventricles regardless of the causes of dilatation and that the augmentation is a compensatory mechanism as prevention against decompensation responding to reduced contractility, excess of wall stresses, or both, concomitantly occurring with cardiac dilatation and myocardial hypertrophy.

Adult↗
PubMed1989

Chronic blockade of endogenous atrial natriuretic polypeptide (ANP) by monoclonal antibody against ANP accelerates the development of hypertension in spontaneously hypertensive and deoxycorticosterone acetate-salt-hypertensive rats.

To explain the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in the development of hypertension, we examined the effect of chronic, repetitive administrations of MAb raised against alpha-rat ANP in two rat models of hypertension, spontaneously hypertensive rats of the stroke prone substrain (SHR-SP), and deoxycorticosterone acetate (DOCA)-salt rats. Weekly intravenous administrations of MAb with high affinity for alpha-rat ANP, named KY-ANP-II (MAb[KY-ANP-II]), started at the age of 6 wk, significantly augmented the rise in blood pressure of SHR-SP, compared with control SHR-SP treated with another MAb with quite low affinity for alpha-rat ANP, named KY-ANP-I (MAb[KY-ANP-I]), throughout the observation period. The administrations of MAb[KY-ANP-II] had no significant effect on blood pressure of age-matched normotensive Wistar Kyoto rats, compared with those receiving MAb[KY-ANP-I]. Weekly administrations of MAb[KY-ANP-II] also significantly aggravated hypertension in DOCA-salt rats. Blood pressure of DOCA-salt rats treated with MAb[KY-ANP-II] was significantly higher than that of DOCA-salt rats treated with MAb[KY-ANP-I] throughout 8 wk of DOCA and 1% saline administration. The administration of MAb[KY-ANP-II] also significantly attenuated exaggerated diuresis and natriuresis in DOCA-salt rats compared with those treated with MAb[KY-ANP-I]. Elevated plasma cGMP levels of both SHR-SP and DOCA-salt rats were significantly reduced by the administration of MAb[KY-ANP-II]. These results suggest the compensatory role of augmented secretion of ANP in these hypertensive rats and support the concept that augmented secretion of ANP could represent an antihypertensive deterrent mechanism.

Animals↗
PubMed1989

Effects of naloxone on vasopressin secretion in conscious rats: evidence for inhibitory role of endogenous opioid peptides in vasopressin secretion.

The effects of naloxone, an opioid antagonist, on arginine vasopressin (AVP) secretion were examined in conscious unrestrained rats under both basal and stimulated conditions. Intravenous injection of naloxone in a dose of 0.1 mg/kg did not significantly affect the basal plasma AVP level. However, 0.5 or 2.5 mg/kg naloxone significantly raised the basal AVP level in euhydrated rats. Naloxone (0.5 mg/kg) significantly enhanced AVP secretion after 72-h water deprivation. However, the enhancement was more prominent in euhydrated rats than in dehydrated rats. Pretreatment with naloxone (0.5 mg/kg) also significantly prolonged AVP secretion induced by intracerebroventricular injection of angiotensin-II (100 ng). Moreover, naloxone (0.5 mg/kg) significantly increased AVP secretion induced by intracerebroventricular injection of carbachol (10 ng). Naloxone (0.5 mg/kg) altered neither basal blood pressure nor the angiotensin-II-induced pressor response, but augmented the carbachol-induced pressor response. This suggests that facilitation of AVP secretion by naloxone is not due to a reflex mechanism resulting from decreased blood pressure. These results indicate that endogenous opioid peptides exert a tonic inhibitory control on AVP secretion in rats.

Angiotensin II↗
PubMed1989

Immunohistochemical localization and semi-quantification of atrial natriuretic polypeptide (ANP) in formalin-fixed-paraffin-embedded normal human hearts--comparative study with radioimmunoassay.

The presence of atrial natriuretic polypeptide (ANP) was immunohistochemically demonstrated in the formalin-fixed and paraffin-embedded tissues of 25 autopsied normal human hearts using monoclonal antibody. The ANP amounts were immunohistochemically semiquantified and compared with amounts measured by radioimmunoassay (RIA). The 25 autopsied hearts were divided into 5 groups according to the interval of formalin fixation or the length of time between death and fixation. Formalin-fixation intervals were one week in group 1A and 1B; 1 year in group 2; 4 to 5 years in group 3 and 10 to 12 years in group 4. The hearts of group 1A, 2, 3 and 4 were fixed within 5 hours after death. Those of group 1B were fixed 14 to 18 hours at 4 degrees C. After fixation, the left and right atrial appendages (LAA and RAA), the left and right atrial free walls (LA and RA), the left and right ventricular free walls (LV and RV) and the ventricular septum (VS) were transmurally dissected from each heart. They were embedded in paraffin, cut into 4 microns sections and immunohistochemically stained by the avidin-biotin-peroxidase complex (ABC) method using monoclonal antibody against alpha-human ANP. Under a light microscope, they were evaluated semiquantitatively according to the incidence of ANP-positive cells and the intensity of immunostaining. For every heart in group 1A, the tissue concentrations of ANP in the different parts were also measured separately by RIA before fixation. ANP-positive myocytes were noted in the atria of all hearts of all groups, but no in any ventricular myocytes. Both their incidence and grade in the atria were similar among groups 1A, 1B and 2. However, they were less in group 3, and least in group 4 among all groups. For all groups, they decreased in the following order: LAA greater than RAA not equal to LA greater than RA; the inner 1/3 greater than the middle 1/3 greater than the outer 1/3 of the atrial walls. The order in LAA, RAA, LA and RA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of dietary vitamin E supplement on gracile axonal dystrophy (gad) mice.

We have studied the effects of dietary vitamin E supplement on the clinical signs and pathological changes in GAD (gracile axonal dystrophy) mice. The control diet contained 2 mg of dl-alpha-tocopheryl acetate (2 I.U.) and vitamin E-supplemented diet contained 58.5 mg of dl-alpha-tocopheryl nicotinate (50 I.U.), per 100 mg of feed. The diet was given to normal (gad/+) and GAD (gad/gad) mice from 21 to 130 days of age. During the feeding, there was no improvement in clinical signs in the GAD mice fed the vitamin E-supplemented diet. The gracile nucleus of the medulla oblongata and the gracile fascicules of the spinal cord were investigated for pathology at 130 days of age, and alpha-tocopherol was also assayed in the serum, liver, brain and spinal cord at that time. There were no pathological differences in the gracile nucleus and fascicules between the GAD mice fed the control and vitamin E-supplemented diet. The alpha-tocopherol levels in the serum and target organs in the control GAD mice were not significantly different from those in control normal mice, showing that GAD mice could absorb and transport alpha-tocopherol. In the supplemented GAD mice, no significant increases in alpha-tocopherol levels were observed in the liver, brain or spinal cord. Particularly, the percentage increase of alpha-tocopherol level in the liver of GAD mice was very low in comparison with that in normal mice, even though the liver can store vitamin E. Thus it may be that the capacity to store vitamin E is lowered in GAD mice. Further studies are needed to investigate in detail the vitamin E metabolism in the mutant mice.

Animals↗
PubMed1989

[Diabetic ophthalmoplegia--a clinico-pathological study of the first case in Japan].

Many reports of diabetic ophthalmoplegia have been published from the clinical points of view. However, there have been only three autopsied cases in which the ocular nerves were investigated histopathologically. A 72-year-old housewife was diagnosed to have glycosuria at the age of 67, but no medical treatment was done. She admitted to the hospital, because of acute onset of right eyelid drooping and diplopia for previous four days. She showed complete eyelid ptosis, moderate dilatation of right pupil, loss of light reaction, and extraocular muscle palsy except abduction on the right. Blood pressure was normal. A glucose tolerance test was diabetic and HbA1c was moderately increased. Her diabetes was fairly well-controlled with a diet therapy and injection of lente insulin. Two and a half months after admission, the course of illness became regressive. Seven months later, external ophthalmoplegia was disappeared and only slight anisocoria was seen. She readmitted to the hospital one year and eleven months later, because of anorexia and emaciation. She died of adenocarcinoma of the stomach without chemotherapy. The duration from onset of ocular symptoms to death was two years and one month. At postmortem examination, stomach cancer infiltrated extensively to the abdominal and pelvic viscera, but no metastasis to the nervous system or intraorbital tissues was found. There were mild to moderate atherosclerotic changes in the small-and middle-sized arteries of the kidneys, pancreas and adrenal glands corresponding to her age. Moderate atherosclerosis was found in all of the major arteries including Willis ring, siphon of the right internal carotid artery and Vertebro-basilar one.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

[A case of chronic renal hemodialysis and intracranial hypertension--a study on CSF dynamics].

There are many reports on the disequilibrium syndrome due to dialysis in patients with chronic renal failure. However, they do not mention the findings of CT cisternography and MRI. We intend to investigate the mechanism of CSF dynamics in a patient with disequilibrium syndrome by means of these radiological examinations. A 31 year-old woman who had suffered from renal failure for 18 years was found to have prominent increase of serum creatinine (18.1 mg/dl) and BUN (127 mg/dl) 3 years ago. At that time, digital marking of the skull was already present by X-ray examination without other destruction in bone survey of the whole body. She was hemodialysed by the hollow fiber kidney three times weekly (dialysis time 4.5 hours, dialysate osmotic pressure 270 mOsm/kg H2O). Three months ago, she began to complain of severe headache, nausea and vomiting 2 hours after the beginning of dialysis, so that she was referred to Kosei Hospital. On admission, she showed exophthalmus, concentric narrowing of the visual field, optic atrophy and hyperreflexia in jaw and four extremities. After admission, she received hemodialysis therapy thrice weekly (dialysis time 5 hours, dialysate osmotic pressure 290 mOsm/kg H2O). At the same time, 200 ml of glycerol (contents of glycerin 10, fructose 5, NaCl 0.9%) was administered intravenously during dialysis, which ameliorated the symptoms of intracranial hypertension. Laboratory studies revealed marked decrease of serum creatinine, BUN and uric acid levels and osmotic pressure, and increase of blood pH at the time of postdialysis compared with predialysis. Manometric CSF pressure increased up to 310 mmH2O at the day without dialysis before the glycerol administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Enzyme immunoassay for alpha-human atrial natriuretic polypeptide--direct measurement of plasma level.

A sandwich enzyme immunoassay for alpha-human atrial natriuretic polypeptide (alpha-hANP) was developed. Polystyrene balls were coated with monoclonal IgG1 specific for the N-terminal half of the ring structure of alpha-hANP, and rabbit Fab' specific for the C-terminal (17-28) of alpha-hANP was conjugated to horseradish peroxidase. The polystyrene ball was incubated with alpha-hANP standards or plasma and subsequently with the conjugate. Bound peroxidase activity was measured by fluorimetry. No addition of hANP-free plasma for the standard curve was required when less than 50 microliters of plasma sample was used. The detection limit of alpha-hANP was 30 fg (10 amol). Using 50 microliters of plasma, we could detect 0.6 ng (0.2 pmol)/l without extraction. The basal plasma alpha-hANP level of healthy men in a supine position after an overnight fast was 24.5 +/- 13.2 (SD) ng/l and tended to decrease (15.3 +/- 8.5 (SD) ng/l) after intravenous administration of furosemide (40 mg) and subsequent one hour walking. There was a highly significant correlation between the plasma alpha-hANP concentrations measured by this enzyme immunoassay and by radioimmunoassay (r = 0.92). This enzyme immunoassay for alpha-hANP allows measurement of plasma alpha-hANP without extraction even in the volume-contracted state.

Adult↗
PubMed1988

A monoclonal antibody against N-terminus of alpha-atrial natriuretic polypeptide (alpha-ANP): a useful tool for preferential detection of naturally circulating ANP.

A monoclonal antibody directed against the N-terminus of alpha-atrial natriuretic polypeptide (alpha-ANP), named KY-ANP-II, was produced by fusion of a non-producing mouse myeloma cell line, X63-Ag8.653, with spleen cells from a BALB/c mouse immunized with synthetic alpha-human ANP (alpha-hANP) conjugated to bovine thyroglobulin. The obtained antibody showed a high affinity for alpha-hANP with a Ka of 6.6 X 10(10) M-1. With this monoclonal antibody, a specific radioimmunoassay for alpha-hANP was established. The minimal detectable level of alpha-hANP in this radioimmunoassay was 0.8 fmol (2.5 pg)/tube, and IC50 was 8 fmol (25 pg)/tube. The radioimmunoassay recognized alpha-rat ANP on an equimolar basis, whereas there was no detectable cross-reactivity with alpha-ANP [4-28] or alpha-ANP [5-28]. Thus, the monoclonal antibody can detect a hormonal form of ANP, alpha-ANP, but not neuropeptide forms of ANP, alpha-ANP [4-28] and alpha-ANP [5-28]. These results indicate that KY-ANP-II becomes a useful tool for preferential detection of a circulating form of ANP and for investigation of the physiological and pathophysiological significance of ANP as a hormone.

Animals↗
PubMed1988

Augmented synthesis of beta-human atrial natriuretic polypeptide in human failing hearts.

To elucidate the synthesis of atrial natriuretic polypeptide (ANP) in the failing heart, eighteen human right auricles obtained at cardiovascular surgery were studied. The concentration of alpha-human ANP-like immunoreactivity (alpha-hANP-LI) in human right auricles ranged from 13.8 to 593.5 micrograms/g, and the tissue alpha-hANP-LI concentration in severe congestive heart failure (CHF) (New York Heart Association (NYHA) functional class III or IV) was much higher than those in mild CHF of NYHA class I and class II. The alpha-hANP-LI in the human auricle consisted of 3 major components of ANP, gamma-human ANP (gamma-hANP), beta-human ANP (beta-hANP) and alpha-human ANP (alpha-hANP). The predominant component of alpha-hANP-LI was gamma-hANP in the mild CHF, whereas beta-hANP and/or alpha-hANP were prevailing in the severe CHF and, especially, beta-hANP was markedly increased in human failing hearts.

Adult↗
PubMed1988

Immunohistochemical localization of atrial natriuretic polypeptide (ANP) in human atrial and ventricular myocardiocytes.

To date, there have been few immunohistochemical investigations of atrial natriuretic polypeptide (ANP) in human cardiac tissue, especially the ventricles. In this study, myocardial tissue was obtained from two sources: the bilateral atria and ventricles at autopsy; and biopsy tissues from the right auricle and left ventricle of a patient with myocardial infarction undergoing surgery. These tissues were examined by the avidin-biotin immunoperoxidase technique using three kinds of primary ANP-antibodies. ANP-immunoreactivity was observed in the perinuclear region of myocytes of all tissues examined. The intensity of the reaction was stronger in atrial tissue, weaker in ventricular tissue. In the later tissue, the positive-staining myocytes were not part of the pulse-conducting system. Although the tissues we studied were not obtained from normal hearts, our data demonstrates that ANP-reactivity can be detected in ventricular myocytes outside the pulse-conducting system.

Atrial Natriuretic Factor↗
PubMed1988

Exaggerated secretion of atrial natriuretic polypeptide during dynamic exercise in patients with essential hypertension.

The plasma concentration of atrial natriuretic polypeptide (ANP) was measured in nine patients with essential hypertension during two grades of exercise tests performed in the supine position on a bicycle ergometer. The plasma ANP concentration significantly increased from 97.0 +/- 19.2 pg/ml to 107.6 +/- 23.7 pg/ml (p less than 0.05) during low-grade exercise (50% of the maximal heart rate) and from 96.2 +/- 16.5 pg to 192.8 +/- 30.7 pg/ml (p less than 0.01) during high-grade exercise (75% of the maximal heart rate). During high-grade exercise plasma epinephrine and norepinephrine concentrations showed significant increases. The plasma ANP concentration was significantly correlated with systolic blood pressure (r = 0.51; p less than 0.05). Patients with essential hypertension showed greater absolute increases in the plasma ANP concentration and systolic blood pressure during exercise compared to normotensive subjects. These results suggest that exercise stimulates secretion of ANP in response to its intensity in patients with essential hypertension and that a greater rise in atrial pressure, resulting from a greater elevation of systolic blood pressure, may be involved in the exaggerated secretion of ANP in patients with essential hypertension.

Atrial Natriuretic Factor↗
PubMed1988

Potent depressor action of leumorphin, a kappa-opioid agonist, in conscious rats.

To investigate the role of leumorphin, a kappa-opioid agonist derived from proenkephalin B (neoendorphin/dynorphin precursor) in the central cardiovascular control, the effects of intracerebroventricular (ICV) administration of leumorphin on basal blood pressure and angiotensin II (AII)-stimulated pressor response were examined in conscious unrestrained rats. The ICV injection of 0.06 and 0.6 nmol of leumorphin caused a significant decrease in basal blood pressure (delta mean arterial pressure (MAP): -6.5 +/- 2.7 and -7.2 +/- 1.7 mm Hg, respectively). The ICV injection of AII (0.1 nmol) elicited a pressor response (delta MAP: 21.4 +/- 1.1 mm Hg). This pressor response was significantly reduced by the simultaneous administration of leumorphin, and furthermore, the blood pressure was lowered below the basal level. These depressor actions of leumorphin were partially antagonized by the preadministration of naloxone, an opiate antagonist. These results together with our previous works on the potent inhibitory actions of leumorphin on drinking and vasopressin secretion suggest the possible involvement of leumorphin in the central regulation of blood pressure and body fluid homeostasis.

Animals↗
PubMed1988

Expression of atrial natriuretic factor gene in hearts from neonates of spontaneously hypertensive rats and stroke-prone spontaneously hypertensive rats.

In order to further elucidate the expression of the atrial natriuretic factor (ANF) gene in spontaneously hypertensive rats (SHR) and the substrain, stroke-prone SHR (SHRSP), ANF messenger (m)RNA levels in the atrium and in the ventricle were measured in neonates of SHR and SHRSP and were compared with those in control Wistar-Kyoto rats (WKY). The levels of ANF mRNA in ventricles of the three strains reached approximately 7% of those in atria; however, no significant difference was observed in atrial and ventricular ANF mRNA levels among the three strains. These results demonstrate that the expression of the ANF gene in hearts from neonates of WKY, SHR and SHRSP is similar among the three strains.

Animals↗
PubMed1988

Peptides derived from atrial natriuretic polypeptide precursor in human and monkey brains.

Using radio-immunoassays for the C-terminal sequence of alpha-atrial natriuretic polypeptide [atrial natriuretic factor (ANF)-(99-126)], alpha-ANP (17-28) [ANF-(115-126)], which corresponds to gamma-human ANP [115-126; gamma-hANP-(115-126)] and for the N-terminal sequence of gamma-hANP [human ANF-(1-126)], gamma-hANP-(1-25) [human ANF-(1-25)], we detected the parallel distribution of alpha-hANP-like immunoreactivity and gamma-hANP-(1-25)-like immunoreactivity in the human and monkey brains, with the highest concentrations in the midbrain and the pons. High performance gel permeation chromatography coupled with the two radio-immunoassays and also with another radio-immunoassay using a monoclonal antibody against the N-terminal sequence of alpha-ANP revealed that gamma-ANP is synthesized in the brain and cleaved into N-terminally deleted form(s) of alpha-ANP and 10-K N-terminal fragment(s) of gamma-ANP, which coexist within the neuron. These results suggest that the post-translational processing of gamma-ANP in the brain is different from that in the heart.

Animals↗