[Expression of atrial natriuretic polypeptide in ventricles of heart with hypertrophic cardiomyopathy: an immunohistochemical study of endomyocardial specimens].

To investigate the ventricular expression of atrial natriuretic polypeptide (ANP) in human hypertrophic heart, we conducted an immunohistochemical study using endomyocardial biopsy specimens obtained from the right side of the interventricular septum (RVB), left ventricular free wall (LVB), or both of 39 patients with hypertrophic cardiomyopathy (HCM), and 9 control subjects without hypertrophy. No HCM patients had apparent congestive heart failure. ANP was not present in control subjects' RVB or LVB specimens, but was found in HCM patients', showing its characteristic distribution patterns (RVB > LVB, p < 0.

Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats.

To investigate the effect of pulmonary alveolar hypoxia on the synthesis and release of endothelin (ET)-1, ET-1-like immunoreactivity (-LI) levels of the lung and plasma were measured in conscious unrestrained rats under hypoxic conditions. Sixty-min exposure to alveolar hypoxia (10% O2 or 5% O2) increased the ET-1-LI level in the lung. The plasma ET-1-LI level in hypoxic rats also increased significantly.

Expression and distribution of atrial natriuretic peptide in human hypertrophic ventricle of hypertensive hearts and hearts with hypertrophic cardiomyopathy.

To investigate the ventricular expression of atrial natriuretic peptide (ANP) in human hypertrophic hearts, we conducted an immunohistochemical study of 130 endomyocardial biopsy specimens obtained from the right side of the ventricular septum (RVB), left ventricular free wall (LVB), or both from a total of 80 patients: 44 patients with hypertrophic cardiomyopathy (HCM), 14 with apical hypertrophic cardiomyopathy (APH), 13 with hypertensive hearts (HHD), and nine without hypertrophy (controls). No patients had apparent congestive heart failure. ANP was not seen in ventricular myocytes in controls but was identified in biopsy specimens of hypertrophic hearts, and its distribution was characteristic in each hypertrophic group: 15 RVB (37%) and two LVB (7%) of the HCM group, one RVB (7%) and two LVB (18%) of the APH group, and zero RVB (0%) and five LVB (46%) of the HHD group.

Endothelin in patients with chronic renal failure.

To investigate the pathophysiological significance of endothelin-1 (ET-1) in renal failure, we measured plasma and urine concentrations of ET-1-like immunoreactivity (LI) by radioimmunoassay (RIA). The plasma ET-1-LI level was significantly increased in hemodialyzed and nonhemodialyzed patients with chronic renal failure (CRF). The increase in the plasma ET-1-LI level in CRF was much larger than that in other diseases in which the plasma ET-1-LI level was reported to be increased.

Isolation and characterization of porcine endothelin-like peptide.

Two endogenous molecules possessing an endothelin-like sequence with an apparent molecular weight of 7 kDa were isolated from serum-free culture medium of porcine aortic endothelial cells, using a specific radioimmunoassay. N-terminal sequences of two molecules were identical to each other and were Ser-Leu-Lys-Asp-Leu-Phe-Pro-Ala-Lys-Ala-Ala-Asp-Arg-Arg-Asp-Arg-X-Gln-X- Ala-X- Gln-Lys-Asp, which corresponds to the sequence [94-117] of preproendothelin-1. This finding indicates that these two molecules may be closely related peptides such as the oxidized form or disulfide analogues and also suggests that the endogenous peptide possessing an endothelin-like sequence is generated by proteolytic cleavage at paired basic amino acids Arg92-Arg93.

Pathophysiological role of augmented atrial natriuretic polypeptide gene expression in DOCA-salt hypertension. Effects of atrial natriuretic polypeptide monoclonal antibody.

To elucidate the pathophysiological significance of endogenous atrial natriuretic polypeptide (ANP) in hypertension, we investigated the biosynthesis and secretion of ANP in deoxycorticosterone acetate (DOCA)-salt hypertensive rats and also examined the effect of passive immunization with monoclonal antibody raised against alpha-rat ANP on the development of hypertension in DOCA-salt rats. The plasma ANP level in DOCA-salt rats was significantly elevated in comparison to control rats. While the atrial ANP concentration in DOCA-salt rats was not significantly altered, the atrial level of ANPmRNA in DOCA-salt rats was two-fold higher than that in control rats.

Determination of manganese concentrations in the spinal cords from amyotrophic lateral sclerosis patients by inductively coupled plasma emission spectroscopy.

Continuing analytical studies on environmental factors in the foci of amyotrophic lateral sclerosis (ALS) in the Kii Peninsula of Japan and Guam, and metal analysis using neutron activation analysis in central nervous system (CNS) tissues from ALS cases indicate that chronic exposure to metals such as aluminum and manganese, together with a deficiency of minerals such as calcium and magnesium, may play a causative role in the neurodegeneration seen in ALS. An accurate and simple method for detecting minerals and trace metals in small, fresh samples of CNS tissue is necessary in order to follow the pathogenetic behavior of these elements. In this paper, we describe a method for measuring manganese (Mn) content in CNS tissue samples taken from mouse brain using inductively coupled plasma (ICP) spectroscopy and present results of the determination of Mn contents in spinal cord samples from ALS cases using the same method.

Preparation of monoclonal antibodies against brain natriuretic peptide and their application to radioimmunoassay and passive immunization.

Two monoclonal antibodies (mAbs) directed toward brain natriuretic peptide (BNP), KY-BNP-I and KY-BNP-II, have been produced. Both mAbs against BNP possessed high affinities for BNP, with association constants (Ka) of 4.0 X 10(9) M-1 (KY-BNP-I) and 2.

Expression and distribution of atrial natriuretic polypeptide in the ventricles of children with myocarditis and/or myocardial infarction secondary to Kawasaki disease: immunohistochemical study.

We studied the expression and distribution of atrial natriuretic polypeptide in the ventricles of 27 autopsied children with Kawasaki disease. Fourteen of the children had died in the acute stage of the disease. Three without any coronary artery aneurysms died due to myocarditis, while 11 with coronary artery aneurysms also had myocarditis but died of coronary heart disease.

Pro-thyrotropin-releasing hormone concentrations in the brain of ataxic mice.

Concentrations of pro-thyrotropin-releasing hormone (pro-TRH) were studied in the brain of the Weaver ataxic mouse, the Purkinje cell degenerative mouse (pcd-ataxic mouse), the Staggerer ataxic mouse and the C3H mouse. The brain tissue was dissected into 7 parts, e.g.

Identification and distribution of atrial natriuretic polypeptide in ventricular myocardium of humans with myocardial infarction.

The expression of atrial natriuretic polypeptide (ANP) in the ventricles of human hearts with myocardial infarction (MI) was studied immunohistochemically. Immunoreactive myocytes were identified in the ventricular tissues of all of 16 hearts with old MI (both with and without heart failure) and in all five hearts with subacute MI, but not in any of the eight hearts without MI nor in the five with acute MI. In the nonfailing hearts with MI, ANP positive myocytes surrounded the areas of infarction, and were also seen in the subendocardium of the infarcted segment.

Rat brain natriuretic peptide. Isolation from rat heart and tissue distribution.

We have isolated a cardiac natriuretic peptide of 5,000 d from atrial tissues from 500 rats and determined its amino acid sequence. The 5,000 d atrial natriuretic factor was elucidated to be a 45 amino acid peptide with the sequence of S-Q-D-S-A-F-R-I-Q-E-R-L-R-N-S-K-M- A-H-S-S-S-C-F-G-Q-K-I-D-R-I-G-A-V-S-R-L-G-C-D-G-L-R-L-F by sequencing the native peptide and its lysyl endopeptidase digests. The sequence of this peptide was identical to the amino acid sequence (51-95) of the rat brain natriuretic peptide precursor deduced from the complementary DNA (cDNA) sequence.

Application of monoclonal antibodies for endothelin to hypertensive research.

We developed six kinds of monoclonal antibodies against endothelin (ET)-1 recognizing different epitopes with high affinities (5 x 10(10) M-1 to 5 x 10(11) M-1). Using these monoclonal antibodies, we developed radioimmunoassays for ET-1 with different specificities. Cross-reactivities with ET-2 ranged from 80% to 100%, and those with ET-3 ranged from 3% to 60%.

Rat brain natriuretic peptide--tissue distribution and molecular form.

Using an antiserum against the ring structure of rat brain natriuretic peptide (rat BNP), we have established a specific radioimmunoassay (RIA) for rat BNP and elucidated its tissue distribution and molecular form. Rat BNP-like immunoreactivity (-LI) was detected in the highest amount in cardiac extracts (574.0 +/- 138.

Magnesium concentration in brains from multiple sclerosis patients.

Magnesium (Mg) concentrations were studied in the brains of 4 patients with definite multiple sclerosis (MS) and 5 controls. The magnesium contents were determined by inductively coupled plasma emission spectrometry in autopsy samples taken from 26 sites of central nervous system tissues, and visceral organs such as liver, spleen, kidney, heart and lung. The average Mg content in the CNS tissues, as well as visceral organs except for spleen, of MS patients showed a significantly lower value than that seen in control cases.

Axonal degeneration of ascending sensory neurons in gracile axonal dystrophy mutant mouse.

The distribution of axonal spheroids was examined in the central nervous system of gracile axonal dystrophy (GAD) mutant mice. Only few spheroids are observed in the gracile nucleus of the medulla in normal mice throughout the period examined, while they are first noted in GAD mice as early as 40 days after birth. The incidence of spheroids shifts from the gracile nucleus to the gracile fasciculus of the spinal cord with the progress of disease, suggesting that the degenerating axonal terminals of the dorsal ganglion cells back from the distal presynaptic parts in the gracile nucleus, along the tract of the gracile fasciculus, toward the cell bodies in the dorsal root ganglion.

Appearance of atrial natriuretic peptide in the ventricles in patients with myocardial infarction.

To study whether atrial natriuretic peptide (ANP) is present in the ventricles in patients with myocardial infarction, we have examined ventricular tissues from five patients with myocardial infarction and five control subjects without cardiovascular diseases by the indirect immunoperoxidase method using monoclonal antibody to alpha-human ANP. Immunoreactivity for ANP was observed in the subendocardial cardiac cells of infarcted as well as noninfarcted segments of the left ventricles in all patients with myocardial infarction. In a case of biventricular infarcts, the subendocardial cardiac cells of the right ventricle were also stained.

Isolation and sequence determination of human brain natriuretic peptide in human atrium.

We isolated human brain natriuretic peptide (human BNP) from the human atrium. Sequence analysis has revealed that it is a 32-amino-acid peptide with the sequence S-P-K-M-V-Q-G-S-G-C-F-G-R-K-M-D-R-I-S-S-S-S-G-L-G-C-K-V-L-R-R-H, which is identical to the C-terminal sequence (77-108) of the human BNP precursor deduced from the cDNA sequence. The sequence of human BNP (77-108) is preceded by Pro75-Arg76 in the human BNP precursor, which is the same processing signal as Pro97-Arg98 of the precursor of atrial natriuretic peptide (ANP).

Atrial natriuretic peptide in the ventricles of patients with dilated cardiomyopathy and human foetuses.

Immunohistochemical examination of atrial natriuretic peptide (ANP) was performed on endomyocardial biopsy specimens from 8 patients with dilated cardiomyopathy (DCM), 10 human foetal hearts obtained from legal abortions, and 8 adult hearts from autopsy control subjects without cardiovascular diseases. The indirect immunoperoxidase method, using specific monoclonal antibody to alpha-human ANP was employed. Immunoreactivity was observed at the light microscope level in the working ventricular cardiocytes of all patients with DCM as dark-brown, granular deposits.

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.

Detection and characterization of endothelin-1-like immunoreactivity in rat plasma.

Using two radioimmunoassays (RIAs) for endothelin-1 (ET-1) with and without a substantial cross-reactivity with ET-3, we have measured the plasma ET-1-like immunoreactivity (-LI) level in rat plasma. ET-1-LI was detected in plasma from male Wistar rats. ET-1-LI in rat plasma consisted of three components with molecular weights of 6K, 4K and 2.