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K Shigematsu

Publications and source records attributed to K Shigematsu.

105 records · Page 6Linked to original sources
PubMed1986

Increased number of angiotensin II receptors in the subfornical organ of spontaneously hypertensive rats.

Angiotensin II receptors were studied in the brain of spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto rats (WKY) by quantitative autoradiographic methods coupled to computerized microdensitometry and comparison with 125I-standards, after incubation of brain sections with 125I-Sar1-angiotensin II. Binding sites for angiotensin II were highly localized in the subfornical organ. The number of binding sites was higher in the subfornical organ of young (4-week-old) and adult (14-week-old) SHR when compared with WKY rats (young rats: 735 +/- 91 and 444 +/- 85 fmol/mg protein, SHR and WKY, respectively; adult rats: 1390 +/- 64 and 848 +/- 136 fmol/mg protein, SHR and WKY, respectively). Our results suggest that subfornical organ angiotensin II receptors are involved in genetic hypertension in the rat. An increased number of subfornical organ angiotensin II receptors substantiates the idea of an overactive central angiotensin II system in spontaneous hypertension.

Angiotensin II↗
PubMed1985

Functional morphology of the adrenocortical glomerular zone by incomplete ligation of bilateral ureters of rats. An experimental model for secondary aldosteronism.

We studied the adrenal cortex, particularly the glomerular zone of an experimental model for secondary aldosteronism produced in rats by incomplete ligation of both ureters. The experimental animals developed characteristic manifestations of the disease such as ascites and high serum potassium, PRA, and aldosterone content in the adrenal tissue. Microscopically, the width of the glomerular zone was markedly increased and this was related to hypertrophy of the cells of the glomerular zone. Lipid droplets in these cells were decreased. The enzymic activity of 3 beta-HSD showed a moderate increase in the transitional zone and a slight increase in the glomerular zone. Ultrastructurally, well-developed mitochondria and SER were seen in swollen cytoplasm and numerous microvillous projections were noted in the plasma membrane. These results suggest that the adrenal cortical cells in the glomerular zone are stimulated by high concentrations of serum potassium and renin-angiotensin.

Adrenal Cortex↗
PubMed1985

High-affinity substance P binding sites in rat sympathetic ganglia.

Substance P binding sites were characterized and quantitated in single rat sympathetic ganglia by incubation of tissue sections with 125I-Bolton-Hunter substance P, autoradiography, image analysis coupled with computer-assisted microdensitometry, and comparison with 125I standards. The prevertebral celiac-superior mesenteric sympathetic ganglia contained clusters of high-density, high-affinity substance P binding sites [maximum binding (Bmax) 7.12 +/- 0.20 pmol/mg protein; affinity constant (Ka) 2.08 +/- 0.02 X 10(9) M-1]. In the paravertebral superior cervical sympathetic ganglia, the number of high-affinity substance P binding sites was substantially lower (Bmax 1.38 +/- 0.04 pmol/mg protein; Ka 1.71 +/- 0.03 X 10(9) M-1). Future studies should address the issue of whether the substance P binding sites identified in prevertebral ganglia of the rat serve as receptors for the peptide presumed to be released by terminals of sensory neurons.

Animals↗
PubMed1984

Multiple pigmented adrenal cortical nodules associated with Cushing's syndrome. Histochemical, ultrastructural and quantitative studies.

Multiple pigmented adrenocortical nodules were found in a 25-year-old woman associated with Cushing's syndrome, whose laboratory data indicated that the adrenal cortex had been functioning autonomously and adrenocorticotrophic hormone (ACTH) from the pituitary gland as suppressed. The surgically removed left adrenal gland disclosed multiple black nodules measuring up to 3 mm in diameter and histologically consisting of large "compact cells" which contained numerous yellow-brown pigments, but adjacent cortical cells were not atrophied. This kind of adrenal lesion is generally regarded as nodular hyperplasia of the cortex. The present case revealed scanty lipid and markedly increased activity of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and glucose-6-phosphate-dehydrogenase (G6PD). Ultrastructural study showed abundant cytoplasm with a large number of mitochondria, well-developed smooth-surfaced endoplasmic reticulum (SER), less rough-surfaced endoplasmic reticulum (RER), lysosomes, and numerous granules in cells of the nodules. Mitochondria varied in size and shape up to occasional giant mitochondria. SER was vesicular or tubular forming a network of anastomosing tubules. Granules varied greatly in size from 400 millimicrons to 6 microns in diameter, with diverse electron densities, mostly exhibiting the structural features of lipofuscin. The ultrastructural features resembled those in black adenoma associated with Cushing's syndrome ever reported. Concentration of cortisol was increased in the tissue where numerous black nodules were contained.

3-Hydroxysteroid Dehydrogenases↗
PubMed1982

Isolated adrenocorticotropic hormone (ACTH) deficiency.

The case to be reported is that of a 72-year-old woman with isolated adrenocorticotropic hormone (ACTH) deficiency, who complained of anorexia and generalized malaise. The secretions of human growth hormone (HGH), prolactin (PRL), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) were all within normal limit. In spite of the extremely low level of cortisol, the plasma level of ACTH would not rise sufficiently, but a marked response of cortisol to ACTH stimulation was recognized. The postmortem examination revealed a decrease in basophilic or PAS-positive cells of the anterior pituitary gland which also showed a selective loss of ACTH-secreting cells over immunohistochemical study. Electron microscope could easily visualize somatotroph, mammotroph, thyrotroph, FSH- and LH-gonadtroph, but corticotroph was difficult to be discerned. Adrenocortical cells demonstrated atrophy and degeneration, for which the zona fasciculata and zona reticularis were narrowed. The zona glomerulosa was slightly enlarged in width.

Adrenal Glands↗
PubMed1980

Functional pathology of aldosterone-producing adenoma.

In addition to the morphological examination, the measurement of the content of corticosteroids was done in aldosterone-producing adenoma. Histologically, the adenoma consists of four types of cells. The major component of the adenoma was clear-type cells. In this type of cells, the activities of 3 beta-hydroxysteroid dehydrogenase and glucose-6-phosphate dehydrogenase showed weakly positive. The fine structure was characterized by numerous lipid vacuoles and poor organellae. On the contrary, intermediate- and compact-type cells revealed higher than moderate activities of these enzymes. Moreover, marked development of smooth endoplasmic reticulum and mitochondria was noted. Zona glomerulosa-type cells were observed only in a small part. The content of aldosterone and corticosterone in aldosterone-producing adenoma was significantly larger than those of the other type of adenoma. A tendency of positive correlation between the increase of compact-type cells and content of aldosterone was found. The cell origin of this aldosterone-producing adenoma and functional role of clear- and compact-type cells were also discussed.

3-Hydroxysteroid Dehydrogenases↗
PubMedDate not supplied

Quantitative distribution of angiotensin II binding sites in rat brain by autoradiography.

Angiotensin II binding sites were localized and quantified in individual brain nuclei from single rats by incubation of tissue sections with 1 nM 125I-[Sar1]-angiotensin II, [3H]-Ultrofilm autoradiography, computerized microdensitometry and comparison with 125I-standards. High angiotensin II binding was present in the circumventricular organs (organon vasculosum laminae terminalis, organon subfornicalis and area postrema), in selected hypothalamic nuclei (nuclei suprachiasmatis, periventricularis and paraventricularis) and in the nucleus tractus olfactorii lateralis, the nucleus preopticus medianus, the dorsal motor nucleus of the vagus and the nucleus tractus solitarii. High affinity (KA from 0.3 to 1.5 X 10(9) M-1) angiotensin II binding sites were demonstrated in the organon subfornicalis, the nucleus tractus solitarii and the area postrema after incubation of consecutive sections from single rat brains with 125I-[Sar1]-angiotensin II in concentrations from 100 pM to 5 nM. These results demonstrate and characterize brain binding sites for angiotensin II of variable high affinity binding both inside and outside the blood-brain barrier.

Angiotensin II↗
PubMedDate not supplied

Binding sites of atrial natriuretic peptide in tree shrew adrenal gland.

Adrenal gland binding sites for atrial natriuretic peptide-(99-126) (ANP) were quantitated in tree shrew (Tupaia belangeri) by incubation of adrenal sections with (3-[125I]-iodotyrosyl28) atrial natriuretic peptide-(99-126), followed by autoradiography with computerized microdensitometry. In the adrenal glands, there are three types of ANP binding sites. One is located in the zona glomerulosa (BMax 84 +/- 6 fmol/mg protein; Kd 122 +/- 9 pM); the second in the zona fasciculata and reticularis (BMax 29 +/- 2 fmol/mg protein; Kd 153 +/- 6 pM) and the third in the adrenal medulla (BMax 179 +/- 1 fmol/mg protein; Kd 70 +/- 2 pM). Besides the influence of ANP on the regulation of adrenocortical mineralcorticoid and glucocorticoid secretion our findings raise the possibility for a local site of action of atrial natriuretic peptide in the regulation of adrenomedullary catecholamines in the tree shrew, primates and man.

Adrenal Glands↗
PubMedDate not supplied

Binding of angiotensin and atrial natriuretic peptide in brain of hypertensive rats.

Atrial natriuretic peptides, produced in the mammalian cardiac atrium, are released into the general circulation and may be actively involved in the control of blood pressure and in fluid homeostasis as antagonists of the peripheral angiotensin system. Certain cardiovascular effects of atrial natriuretic peptides may be centrally mediated, as binding sites for atrial natriuretic factor (8-33) (ANF) have been localized to the subfornical organ. This circumventricular structure lacks a blood-brain barrier and is therefore accessible to circulating peptides. It contains large numbers of angiotensin II (AII) binding sites, and has been suggested as the main central site of action for circulating AII in the regulation of blood pressure and fluid metabolism. Here we have studied binding sites for rat atrial natriuretic peptide(6-33) (rANP) and AII in the brains of spontaneously (genetic) hypertensive rats (SHR) and their normotensive controls, Wistar Kyoto (WKY) rats, by quantitative autoradiography. Binding sites for both peptides were highly localized in the subfornical organ. The number of rANP binding sites was decreased in the subfornical organ of both young (4 weeks old) and adult (14 weeks old) SHR compared with age-matched normotensive controls. Conversely, the number of AII binding sites was higher in both young and adult SHR compared with WKY rats. Our results suggest a central role for rANP and AII in genetic hypertension; they may act as mutual antagonists in brain areas involved in control of blood pressure and fluid regulation.

Age Factors↗
PubMedDate not supplied

Inhibition of angiogenesis and tumorigenesis, and induction of dormancy by p53 in a p53-null thyroid carcinoma cell line in vivo.

Our recent in vitro findings for suppression of thrombospondin-1 (TSP1; an antiangiogenic factor) expression by wild-type (wt) p53 in a p53-null thyroid carcinoma cell line, FRO, prompted us to investigate the in vivo effect of exogenous wt-p53 and TSP1 expression on tumor growth and angiogenesis of FRO xenografts in nude mice. Overexpression of TSP1, which did not affect the in vitro cell growth, significantly inhibited the in vivo tumor growth and neovascularization but not tumorigenesis; all the mice inoculated with FRO cells expressing TSP1 developed tumors, which were smaller and less vascularized than those derived from FRO cells. In contrast, restoration of wt-p53 expression, which reduced the in vitro cell growth rate, inhibited tumorigenesis and induced a state of "dormancy". Thus, approximately 40% of mice inoculated with FRO cells expressing wt-p53 (FRO-p53) were tumor free and the remaining mice developed hypovascular tumors which remained small (< or = 5 mm in size) for up to 60 days. Of interest, the phenotype of FRO-p53 tumors reverted to a well vascularized, progressively expanding tumor by exogenous expression of vascular endothelial growth factor (a proangiogenic factor). Our data demonstrated wt-p53 inhibition of tumorigenesis and induction of dormancy by suppression of neovascularization in FRO cells. The results suggest that p53 gene therapy for thyroid carcinoma harboring p53 mutation may be more efficacious than we had expected from previous in vitro data.

Animals↗
PubMedDate not supplied

Effects of MPC-1304, a novel calcium antagonist, on stroke-prone spontaneously hypertensive rats.

The effects of MPC-1304, a newly developed 1,4-dihydropyridine derivative, on blood pressure and hypertensive complications in stroke-prone spontaneously hypertensive rats fed a high-salt diet (0.8% NaCl), were investigated. The antihypertensive effectiveness of nicardipine was used for the purpose of comparison. MPC-1304 and nicardipine were added to the diet, in doses of 0.01% (0.01% MPC-1304 diet), 0.03% (0.03% MPC-1304 diet) and 0.1% (0.1% nicardipine diet), respectively, throughout the experimental period (8 to 30 weeks of age). This chronic ingestion of MPC-1304 and nicardipine inhibited the development of hypertension and reduced the concentration of blood urea nitrogen, creatinine, triglyceride and total cholesterol in serum. Treatment with MPC-1304 inhibited the incidence of cerebral stroke, cardiac fibrosis, proliferative and fibrinoid arteriolitis and malignant nephrosclerosis. There was no significant difference in the antihypertensive effectiveness between 0.01% MPC-1304 and 0.1% nicardipine diets. Thus, MPC-1304 had antihypertensive effects in stroke-prone spontaneously hypertensive rats.

Administration, Oral↗