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Biomedical subjects

A Nagae

Publications and source records attributed to A Nagae.

12 recordsLinked to original sources

Effect of dietary NaCl on tyrosine hydroxylase in the superior cervical ganglia of Dahl rats.

To investigate the involvement of peripheral catecholamines in the development of Dahl-Iwai salt-sensitive (DIS/Eis) hypertension, we performed immunohistochemical staining of tyrosine hydroxylase (TH) in the superior cervical ganglia (SCG) of DIS/Eis rats and Dahl-Iwai salt-resistant (DIR/Eis) rats, and in situ hybridization histochemistry for demonstration of TH mRNA localization in the SCG of these rats. DIS/Eis and DIR/Eis rats were fed on a high (8%) salt diet or on a low (0.3%) salt diet for 4 weeks. Nerve cells in the SCG of DIS/Eis high salt rats exhibited more intense TH-immunoreactivity (P < 0.01) and hybridization signals (P < 0.01) than those of the other experimental groups. These findings suggest that activation of peripheral sympathetic nerves may account for hypertension in DIS/Eis rats on a high salt diet.

Animals↗

A case of central diabetes insipidus with spontaneous remission after 8 years of the disease.

A 55-year-old male smoker developed polyuria and polydipsia in November 1983. A water deprivation study revealed a defect in the urine concentrating function, which was corrected by vasopressin. Plasma antidiuretic hormone (ADH) was not increased by smoking. His condition was well controlled by deamino-D-arginine vasopressin. However, since February 1992 he has become completely free from the need for medication to control his urine volume. Re-evaluation studies with water deprivation and smoking revealed dramatic improvements in the urine concentrating function and ADH response. A patient with idiopathic diabetes insipidus with spontaneous remission after 8 years is reported.

Diabetes Insipidus↗

High concentration of carboxypeptidase M in lungs: presence of the enzyme in alveolar type I cells.

The presence of high concentrations of membrane-bound carboxypeptidase M in human, baboon, dog, and rat lung was established by employing a variety of techniques. The activity of the enzyme in the membrane-enriched fractions of human, baboon, dog, and rat lung, measured with fluorescent dansyl substrate (DNS-Ala-Arg), was 198, 261, 484, and 153 nmol/h/mg protein, respectively. This activity in the lung was much higher than that found in the heart, liver, or kidney. The enzyme, optimally active around neutral pH, was completely inhibited by 10 microM 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and was activated by 1 mM CoCl2 to 170%. Antibody to human carboxypeptidase M immunoprecipitated the solubilized carboxypeptidase from human (98%), baboon (81%), and dog (88%) lung membrane fractions. Carboxypeptidase M is attached to lung membranes by a phosphatidylinositol glycan anchor; thus, it is released with bacterial phospholipase C. Membrane fractions from cultured human pulmonary arterial endothelial cells also contained high carboxypeptidase M activity (254 nmol/h/mg protein). A Northern blot of poly(A)+ RNA from various human tissues showed the presence of a high level of carboxypeptidase M mRNA in human lung and placenta. Finally, immunohistochemistry, employing purified antibody to the enzyme, revealed in fluorescent light microscopy that carboxypeptidase M is present in alveolar type I pneumocytes and in macrophages in apparently lower concentration. In contrast, type II alveolar epithelial cells gave negative results. Because carboxypeptidase M cleaves a variety of active peptides (e.g., bradykinin, anaphylatoxins), it may protect the alveolar surface from the effects of these peptides. In addition, carboxypeptidase M could be a marker enzyme for type I cells.

3-Mercaptopropionic Acid↗

Carboxypeptidase M in brain and peripheral nerves.

Carboxypeptidase M (CPM), a plasma membrane-bound enzyme, cleaves C-terminal basic amino acids with a neutral pH optimum. We studied its distribution in human, baboon, and dog brain and in dog peripheral nerves. Areas were dissected, homogenized, centrifuged, and assayed for activity with dansyl-Ala-Arg. The corpus callosum and the pyramidal and optic tract were especially rich in CPM, whereas basal ganglia and cortex had low activity. The identity of the basic carboxypeptidase activity with CPM was shown by similarities in subcellular localization, membrane attachment, substrate hydrolysis, inhibition by a specific basic carboxypeptidase inhibitor, and cross-reaction with anti-human CPM antiserum. This antiserum immunoprecipitated an average of 85% of the activity in human and baboon brain and approximately 66% in dog brain. CPM co-purified with myelin extracted from the brain. Consistent with results obtained in placenta and cultured kidney cells, CPM in the brain appears to be membrane-bound via a phosphatidylinositol glycan anchor. In the peripheral nerves, the specific activity in dog sciatic nerve and in vagus was high (98 and 149 nmol/h/mg of protein, respectively). In immunohistochemical studies, glia in the brain, which appear to be oligodendrocytes or astrocytes, and the outer aspects of myelin sheaths and Schwann cells in sciatic and vagus nerves were stained. We conclude that in some areas of the CNS and the PNS, CPM is closely associated with myelin and myelin-forming cells. Northern blot analysis revealed the presence of mRNA coding for CPM in the brain, showing that the enzyme is indeed synthesized there.

3-Mercaptopropionic Acid↗

[Molecular forms of plasma atrial natriuretic peptide (ANP) after three kinds of ANP releasing stimulation].

This study analyzed by high performance gel permeation chromatography (HPGC) molecular forms of atrial natriuretic peptide (ANP) in plasma from anesthetized dogs stimulated by balloon inflation at the main pulmonary artery (Group A, n = 4), right atrial pacing (Group B, n = 4) and low-molecular dextran injection to right atrium (Group C, n = 4). Mean pulmonary arterial (PA) pressure, mean right atrial (RA) pressure, mean arterial pressure, heart rate and ECG were monitored by polygraph system Mean PA pressure in Group A, heart rate in Group B and mean RA pressure in Group C increased significantly by the stimulation (p less than 0.01, p less than 0.001 and p less than 0.05 respectively). Other parameters were not changed significantly in the three groups. There were significant increases in ANP concentration after the three stimulations (Group A: 52.4 +/- 5.4 (SD) pg/ml----86.4 +/- 12.2 (SD) pg/ml, Group B: 43.8 +/- 6.7 (SD) pg/ml----72.0 +/- 14.1 (SD) pg/ml, Group C: 42.7 +/- 8.8 (SD) pg/ml----69.3 +/- 10.0 (SD) pg/ml; each p less than 0.01). Gel filtration profiles showed that the increased form of plasma ANP in the three groups was alpha-ANP. These results suggest that alpha-ANP may be a main molecular form in plasma from dogs stimulated by the stretch of pulmonary arterial wall and right atrial wall, and atrial pacing.

Animals↗

Statine-containing dipeptide and tripeptide inhibitors of human renin.

Dipeptide and tripeptide derivatives containing a statine residue were synthesized as inhibitors of human renin. ES-305, bis[(1-naphthyl)methyl]acetyl(BNMA)-histidyl-statine 2(S)-methylbutylamide was found to be a highly potent inhibitor of human renin with a Ki value of 1.7 X 10(-9) M. Dipeptide derivatives with the BNMA group at the N-terminal (BNMA-Val-Sta-isoleucinol [ES-313], BNMA-Leu-Sta-isoleucinol [ES-316], and BNMA-Nle-Sta-isoleucinol [ES-317]) had potencies against human renin that were similar to the potency of ES-305. All these dipeptide derivatives competitively inhibited human renin. The inhibitors were also potent against monkey renin but were less effective against renins from pig, goat, dog, rabbit, and rat. ES-305 had little effect on cathepsin D and pepsin at the concentration of 10(-5) M. The other derivatives showed detectable inhibition of cathepsin D (IC50, 10(-6) - 10(-7) M) and pepsin (10(-5) - 10(-6) M). All the compounds had little or no effect on trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at the concentration of 10(-5) M. Our results indicate that ES-305 is a highly potent and specific inhibitor of human renin. This compound is superior to other, previously described statine-containing renin inhibitors with respect to molecular size and enzyme specificity.

Amino Acids↗

Pulmonary arterial pressure and plasma concentration of atrial natriuretic factor (ANF) in patients with heart disease.

To study the factors controlling the release of atrial natriuretic factor (ANF), we analyzed the peripheral plasma ANF concentration in 34 patients with heart disease who underwent cardiac catheterization. A significant positive correlation between plasma ANF concentration and pulmonary arterial pressure (systolic, r = 0.87; diastolic, r = 0.75; mean, r = 0.85; each p less than 0.001) was found in all the patients examined. There were significant positive correlations between plasma ANF concentration and systolic right ventricular pressure (r = 0.86, p less than 0.001), pulmonary capillary wedge pressure (r = 0.50, p less than 0.01) and mean right atrial pressure (r = 0.39, p less than 0.05). A weak but significant negative correlation was found between plasma ANF concentration and stroke volume index (r = -0.43, p less than 0.05). The correlation coefficient between plasma ANF concentration and mean pulmonary arterial pressure was significantly stronger than those between plasma ANF concentration and pulmonary capillary wedge pressure, and between plasma ANF concentration and mean right atrial pressure (p less than 0.05 and p less than 0.01, respectively). In 10 patients with mitral valvular disease, significant correlations with plasma ANF concentration were also found for pulmonary arterial pressure (systolic, r = 0.80; diastolic, r = 0.82; mean, r = 0.82; each p less than 0.01). These findings suggest that pulmonary arterial pressure may play an important role in the mechanism of release of ANF from atrial cardiocytes.

Adult↗

Asymptomatic hereditary xanthinuria: a case report.

A 22-year-old man with hereditary xanthinuria is reported. A biochemical study of the patient showed elevated serum levels of xanthine and hypoxanthine with concomitant increases in urinary excretion of xanthine and hypoxanthine. The xanthine oxidase activity in the duodenal mucosa of the patient was about 1.5% of normal value. Urinary excretion of xanthine and hypoxanthine of his parents and his eldest brother were significantly higher than the corresponding normal values, but the values were much less than those of the patient. The results suggested that the patient was homozygote, and his parents and his eldest brother were heterozygotes.

Adult↗

Primary aldosteronism with cortisol overproduction from bilateral multiple adrenal adenomas.

A 55-year-old woman with bilateral multiple adenomas showed hypertension, muscle weakness, hypokalemia, moon-like face and truncal obesity. Increased serum and urinary levels of aldosterone were observed. Serum cortisol level did not show a normal circadian rhythm. Microscopic examination of the resected tumors showed two types of adenoma cells; one (golden yellow tumor) was a large clear cell with foamy cytoplasm which possibly secreted aldosterone and the other (dark brown tumor) was an acidophilic cell with lipofuscin which might have produced cortisol. This is a very rare case of primary aldosteronism with Cushing's syndrome due to multiple bilateral adrenal adenomas.

Adenoma↗