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Biomedical subjects

K Naruse

Publications and source records attributed to K Naruse.

At least 109 records · Page 6Linked to original sources

Angiotensin II stimulates both aldosterone secretion and DNA synthesis via type 1 but not type 2 receptors in bovine adrenocortical cells.

Angiotensin II (Ang II) type 2 receptor (AT2) has been shown to counteract the type 1 receptor (AT1)-mediated biological actions of Ang II in the cardiovascular system. The biological significance of AT2 receptor in the adrenals however remains unknown. In the present study, we investigated the roles of AT1 and AT2 receptor subtypes in the regulation of aldosterone secretion and DNA synthesis in bovine adrenocortical zona glomerulosa cells in vitro. Ang II (1 mumol/l)-stimulated aldosterone secretion was completely suppressed by AT1 antagonist CV-11974 but not affected by AT2 receptor antagonist PD-123319. Effects on DNA synthesis were investigated by determining the incorporation of BrdU into the nuclei of the cultured zona glomerulosa cells. Ang II (1 mumol/l)-stimulated DNA synthesis of the cells was also completely suppressed by CV-11974 but not by PD-123319. These results suggest that AT1 receptor but not AT2 receptor is the predominant receptor subtype which mediates the Ang II-stimulated aldosterone secretion and cell growth in bovine adrenocortical cells.

Adrenal Cortex↗

Mesangial cell activation in the collagenofibrotic glomerulonephropathy. Case report and review of the literature.

Collagenofibrotic glomerulonephropathy is a new disease entity of unknown pathogenesis, which is characterized by the deposition of type III collagen within the mesangial matrix. We have investigated a case in which many mesangial cells in the type III collagen-deposited glomeruli were alpha-smooth muscle actin (ASMA) positive and showed an increase of subplasmalemmal filaments, indicating the activation and myofibroblastic transformation. It is suggested that the activated mesangial cells may synthesize the type III collagen deposited in the subendothelial space and mesangial matrix.

Actins↗

Deferential roles of angiotensin receptor subtypes in adrenocortical function in mice.

The functional significance of angiotensin II (Ang II) receptor subtypes in adrenals remains unknown. Ang II receptor type 1a (AT1a) expression was localized by in situ hybridization to the zona glomerulosa and zona fasciculata, while AT1b was localized to the zona glomerulosa. Plasma aldosterone and corticosterone levels were measured after injection with Ang II or the type 2 receptor (AT2) agonist CGP-42112 in wild-type and AT1a deficient mice. Aldosterone and corticosterone levels were lower in AT1a deficient mice. Ang II increased plasma aldosterone levels in AT1a deficient mice, but to a lesser extent in mice pretreated with nonselective AT1a/AT1b antagonist, CV-11974. CGP-42112 did not affect aldosterone levels. Ang II increased corticosterone levels in wild-type mice but not in AT1a deficient mice. Results suggest Ang II stimulates aldosterone secretion via AT1a and AT1b in the zona glomerulosa and corticosterone secretion via AT1a in the zona fasciculata, and provide first evidence for differential roles of AT1a and AT1b in the adrenals.

Adrenal Cortex↗

Efficacy of a bioreactor filled with porcine hepatocytes immobilized on nonwoven fabric for ex vivo direct hemoperfusion treatment of liver failure in pigs.

We developed a new bioreactor for a bioartificial liver filled with porcine hepatocytes immobilized on polyester nonwoven fabric (NWF) and in our previous study showed that this NWF bioreactor has promising in vitro efficiency. In the present study, we investigated the efficacy of the NWF bioreactor in a direct hemoperfusion experiment conducted to treat pigs with liver failure. Porcine hepatocytes were isolated from the whole liver of a Sangen strain pig. They were immobilized in a 200 ml column containing NWF via perfusion in a closed circuit for 24 h to prepare a NWF bioreactor. The following day an operative liver failure model was produced by creating a portocaval shunt and ligating the entire hepatoduodenal ligament in the porta hepatis. Perfusion treatment was initiated 4 h after operative induction of liver failure and continued for about 1 h. The pigs which underwent perfusion treatment showed significant improvements in survival and blood data, including ammonia, total bile acid, glucose, and prothrombin time, attributed to significant improvements in the post- as compared to the prebioreactor levels in the perfused blood of the treated pigs. These beneficial effects of the NWF bioreactor were based on its excellent composition which allows the accommodation of adequate numbers of hepatocytes and direct contact between hepatocytes and perfused blood.

Ammonia↗

An inhibitor of aldose reductase and sorbitol accumulation from Anthocepharus chinensis.

A flavonoid glycoside was isolated from Anthocepharus chinensis. Its structure was elucidated by spectral data and determined to be myricetin 3-O-(4"-acetyl)-alpha-fucoside. This flavonoid glycoside and its aglycone showed potent inhibition against rat and porcine lens aldose reductase. The flavonoid aglycone also inhibited sorbitol accumulation in human red blood cells.

Aldehyde Reductase↗

Gene expression and roles of angiotensin II type 1 and type 2 receptors in human adrenals.

Although stimulation of aldosterone secretion is one of the functions of angiotensin II, the gene expression and biological significance of the angiotensin II receptor subtypes, AT1 and AT2, in the human adrenal have not been characterized. We therefore investigated the transcription levels of the receptor subtype genes and their roles in regulation of steroid secretion by human adrenals. The expression of AT1 and AT2 receptor mRNA was assessed by reverse transcription-polymerase chain reaction followed by Southern blot analysis in normal adrenocortical tissues (n = 6) and a series of adrenal tumour tissues: aldosterone-producing adrenocortical adenoma (n=6), Cushing's syndrome (n = 6) and pheochromocytoma (n = 6). The role of the two receptor subtypes in steroid secretion in vitro was examined by incubating the tissue with angiotensin II(1 microM) with or without the selective AT1 antagonist CV-11974 (1 microM). Both AT1 and AT2 receptor mRNA transcripts were demonstrated in all of the human adrenal tissues tested. Angiotensin II-induced aldosterone secretion was suppressed 50% upon the addition of CV-11974. The selective AT2 agonist CGP-42112 increased aldosterone secretion by 55% over the control, which was not suppressed by CV-11974. Angiotensin II and CGP-42112 did not affect cortisol secretion. These results suggest that both AT2 and AT1 receptors may be involved in the regulation of aldosterone secretion and tumorigenesis of the human adrenals.

Adenoma↗

Peroxide production and apoptosis in cultured cells carrying mtDNA mutation causing encephalomyopathy.

When cybrids with a point mutation, which locates in the tRNALeu(UUR) gene of mtDNA and causes a mitochondrial encephalomyopathy (MELAS syndrome), were exposed to a high concentration of oxygen (95%), the peroxide production markedly increased by 6 h of oxygen exposure, whereas the peroxide production was similar among the cybrids under a normal concentration of oxygen. The peroxide production by oxygen exposure was enhanced particularly in cybrids with high proportions of the mutant mtDNA and low respiratory capacities. The appearance of apoptotic cells by oxygen exposure was high in cybrids with the impaired respiratory function due to the mutation. An antioxidant NAC successfully suppressed both the peroxide production and apoptosis. These results imply that the peroxide production plays an important role in inducing apoptosis in cells carrying the mtDNA mutation causing encephalomyopathy.

Acetylcysteine↗

The role of myofibroblasts at the tumor border of invasive colorectal adenocarcinomas.

BACKGROUND: In order to elucidate the significance of myofibroblasts in invasive growth of colorectal adenocarcinomas, we examined the number of myofibroblasts at the tumor border of colorectal adenocarcinomas. METHOD: A total of 91 invasive colorectal adenocarcinomas were examined immunohistochemically using anti-alpha-smooth muscle actin (ASMA) and high-molecular-weight caldesmon (h-CD) antibodies; 25 carcinomas confined to the submucosa (sm carcinomas), 40 carcinomas confined to the muscularis propria (mp carcinomas) and 26 carcinomas invading the subserosa or adventitia (ss carcinomas). We considered ASMA-positive and h-CD-negative stromal cells as myofibroblasts. RESULTS: Twenty-seven (67%) of the 40 mp carcinomas and 25 (96%) of the 26 ss carcinomas had a small number of myofibroblasts at the tumor border facing the muscularis propria. CONCLUSIONS: Although direct evidence is lacking, there is a possibility that the further immediately vertical and radial invasion of carcinoma cells into the subserosa or adventitia is associated with a smaller number of myofibroblasts at the tumor border facing the muscularis propria in mp carcinomas, resulting in a low incidence of mp and a high incidence of ss carcinomas in the colorectum.

Adenocarcinoma↗

Well differentiated adult-type fibrosarcoma arising from the occipital subcutaneous tissue in a 17-year-old man: case report with immunohistochemical study.

We report a case of a 17-year-old man with a spindle cell tumor in the occipital subcutaneous tissue. The enucleated tumor, measuring 2.5 x 2.0 x 1.0 cm, had a broad-bean shape and well circumscribed border and was localized to the subcutis without dermal involvement. Microscopically, the tumor was composed of uniform spindle cells showing interlacing bundle formation and a herringbone pattern. The neoplastic cells were separated by collagen fibers in parallel fashion, the amount of which varied with different areas in the tumor. Mitotic figures were eight mitoses per 50 high-power fields in number. The neoplastic cells were positive for vimentin, Factor-XIIIa, alpha-smooth muscle actin and CD34, but negative for desmin, calponin, high molecular weight caldesmon, smooth muscle myosin heavy chain, collagen type IV, laminin and S-100 protein. These immunohistochemical results indicated that the neoplastic cells showed differentiation toward fibroblasts/myofibroblasts/dendritic interstitial cells. Although more than 50% of the neoplastic cells were positive for CD34, the present tumor should be diagnosed as well differentiated fibrosarcoma, adult type, rather than extrapleural solitary fibrous tumor and fibrosarcomatous areas of dermatofibrosarcoma protuberans, on the basis of routine microscopic findings mentioned above.

Adolescent↗

Gene expression of endothelin-1 and endothelial-type nitric oxide synthase in cardiovascular tissues of stroke-prone spontaneously hypertensive rats/Izm: effects of the angiotensin-converting enzyme inhibitor aracepril.

We studied target organ-protective effects of aracepril, an angiotensin-converting enzyme inhibitor, and the expression of endothelin-1 (ET-1) and nitric oxide synthase (NOS) mRNA. Aracepril (30 mg/kg) was administered orally to Izumo strain of stroke-prone spontaneously hypertensive rats (SHR-SP/Izm) for 8 weeks from 4 weeks of age and for 4 weeks from 8 weeks of age. The expression of ET-1 and endothelial NOS (eNOS) mRNA in the heart, aorta, kidneys, and brain cortex, and the expression of neuronal NOS (bNOS) mRNA in brain cortex, were analyzed by RT-PCR/Southern blotting or RNase protection analysis. Administration of aracepril markedly lowered blood pressure and decreased left ventricular weight in SHR-SP/Izm. Expression of ET-1 mRNA in the heart, kidneys, and brain was significantly enhanced in SHR/SP/Izm compared with that in WKY/Izm. Aracepril significantly decreased the expression of ET-1 mRNA, whereas there was no significant change of that in the aorta. Although expression of eNOS mRNA in the heart, aorta, and kidneys did not show any significant difference between the two strains of rats, administration of aracepril for 8 weeks significantly decreased the expression of eNOS and bNOS mRNA in brain tissue. These results suggested that aracepril may protect major target organs by modifying the expression of ET-1 and NOS mRNA, in addition to its hypotensive effect.

Angiotensin-Converting Enzyme Inhibitors↗

Characteristics of protrusive and lateral excursions of the mandible in children with the primary dentition.

This study characterizes the mandibular protrusive and lateral excursions of children with primary dentition. With use of a Selspot system, the protrusive and lateral excursions of nine children with the primary dentition and nine adults with the permanent dentition were measured and compared. This system was able to analyse the simultaneous movements of multiple points on the mandible of a subject in three dimensions. Furthermore, the system proved appropriate for use in young children because of the small burden imposed on them during the measurements. Using this subject-friendly system, the directions of the mandibular excursion for five reference points on the mandibular dental arch at each measurement distance (i.e. at 0.5 mm intervals) for three projected angles (frontal, sagittal and horizontal) were calculated. From the results it was found that the excursions of the primary dentition can move more horizontally and more forward with small descent compared with the permanent dentition. The underlying reason for these findings may be physiological growth, maturation, and adaptation of the occlusal function.

Adult↗

So-called neoplastic myoepithelial cells in chondroid syringomas/mixed tumors of the skin: their subtypes and immunohistochemical analysis.

An immunohistochemical study of nine cases of chondroid syringomas/mixed tumors of the skin was performed to elucidate the nature of the so-called neoplastic myoepithelial cells (NMEC) in tumor tissues. These nine tumors contained NMEC of considerable variability in number from one tumor to another. These NMEC were classified into three types: (i) hyaline cells (plasmacytoid cells); (ii) spindle NMEC; and (iii) polyhedral cells. They showed different immunostaining patterns, as the following describes. Cytokeratin 14 was positive in most of the spindle NMEC and a large number of the polyhedral cells, and in a small number of the hyaline cells. Concerning low molecular weight cytokeratins, most of the hyaline cells showed immunoreactivity, whereas they were negative in many of the spindle NMEC and were expressed only in a small number of the polyhedral cells. alpha-Smooth muscle actin and muscle-specific actin were positive in the spindle NMEC but negative in any of the hyaline cells and polyhedral cells. These findings strongly indicate that the hyaline cells and the spindle NMEC are of the simple epithelial and myoepithelial types, respectively. The findings also suggest that the polyhedral cells show differentiation toward basal cells of the sweat gland dermal ducts or myoepithelial cells.

Adenoma, Pleomorphic↗

Periodic discharge of adrenocorticotropin and vasopressin associated with focal glomerulosclerosis.

We report the first case of the syndrome of periodic adrenocorticotropin (ACTH) and vasopressin (ADH) discharge associated with focal glomerulosclerosis. Approximately 30 cases of this syndrome have so far been reported in Japan, but no cases associated with renal dysfunction have yet been reported. The patient, a 10-year-old Japanese boy, was referred to our hospital because of recurrent attacks of vomiting. He was diagnosed as having this syndrome from clinical and laboratory findings. While various drugs were tried to manage his vomiting attacks, only valproic acid appeared to be effective in reducing the frequency of the attacks. Chronic nephritis was manifested when the patient was 12 years old, which required treatment with continuous ambulatory peritoneal dialysis. Valproic acid was proved to be effective in reducing the number of attacks over 4 months.

Adrenocorticotropic Hormone↗

Molecular genetics of the complement C3 convertases in lower vertebrates.

Evolution of the two gene families of the complement system involved in the formation of the C3 convertases, B/C2 and C3/C4/C5, was studied at the cDNA level in lower vertebrates. Cyclostomes, the most primitive extant vertebrates, seem to possess only one member each of these families, indicating that gene duplication between B and C2 or among C3, C4 and C5 occurred in the lineage of jawed vertebrates. Typical C3 and C4 cDNAs were identified in both amphibian (Xenopus) and teleost (medaka fish), locating the C3/C4 gene duplication before the divergence of ray-finned fish and lobe-finned fish. On the other hand, typical B cDNA was identified in Xenopus, whereas teleost counterparts from three species all showed intermediate character between B and C2, suggesting the possibility that the B/C2 gene duplication occurred in the tetrapod lineage. Genetic linkage between these two family genes within the MHC was observed in Xenopus but not in medaka fish.

Animals↗

Soluble thrombomodulin and antibodies to bovine glomerular endothelial cells in patients with Henoch-Schönlein purpura.

AIM: To evaluate the clinical significance of soluble thrombomodulin and antiendothelial cell antibodies (AECA) in children with Henoch-Schönlein purpura. METHODS: Binding of serum AECA to bovine glomerular endothelial cells was evaluated by enzyme linked immunosorbent assay, cytotoxicity against glomerular endothelial cells by spectrophotometric assay, and soluble thrombomodulin concentrations by sandwich enzyme immunoassay. RESULTS: IgA AECA were detected in seven of 15 patients with Henoch-Schönlein purpura and nephritis, but were not detected in patients without nephritis or in controls. Patients with Henoch-Schönlein nephritis had raised titres of IgA AECA and serum thrombomodulin; severe proteinuria and renal histological changes were associated with raised titres of IgA AECA and raised serum thrombomodulin. No subjects had complement dependent cytotoxicity against glomerular endothelial cells. CONCLUSIONS: High titres of IgA AECA and raised serum thrombomodulin may be clinically useful markers of renal involvement in patients with Henoch-Schönlein purpura.

Adolescent↗

Involvement of SA channels in orienting response of cultured endothelial cells to cyclic stretch.

The present work was designed to elucidate the involvement of Ca(2+)-permeable stretch-activated (SA) channels in the orienting response of endothelial cells to uniaxial cyclic stretch. Endothelial cells from human umbilical vein were cultured on an elastic silicone membrane and subjected to uniaxial cyclic stretch (120% in length, 1 Hz). The cells started to change their morphology 15 min after the onset of stretch, and > 90% of the cells oriented perpendicularly to the stretch axis after 2 h. Associated with the orienting response, cell elongation proceeded with a slower rate. Both of the orientating and elongating responses were largely inhibited by the removal of external Ca2+ or by Gd3+, a potent blocker for the SA channel, but not by nifedipine. Intracellular Ca2+ concentration ([Ca2+]i) transiently increased in response to uniaxial stretch, and the basal [Ca2+]i gradually increased during cyclic stretch. This Ca2+ response was inhibited by the removal of extracellular Ca2+ or by the addition of Gd3+. These results suggest that stretch-dependent Ca2+ influx through SA channels is essential in the stretch-dependent cell orientation and elongation.

Cell Polarity↗

Bystander tumoricidal effect and gap junctional communication in lung cancer cell lines.

Tumor cells expressing the herpes simplex virus-thymidine kinase (HSV-tk) gene become sensitive to ganciclovir (GCV), and the phenomenon by which tumor cells surrounding the HSV-tk expressing cells also become sensitive to GCV is known as the "bystander effect." The purpose of this study was to investigate the bystander effect in human lung-cancer cell lines, and the role of gap-junctional intercellular communication as the mechanism responsible for it. Gap-junctional intercellular communication was measured both with a dye-transfer assay involving single-cell microinjection of Lucifer Yellow and with a PKH26/calcein-AM double-dye-transfer assay. Significant bystander tumoricidal effect was observed in lung-cancer cell lines when cultured cells contained only 10% HSV-tk expressing cells. This was also observed to occur with cell lines of different origin or from different species. Although gap-junctional intercellular communication characterized by rapid transfer of Lucifer Yellow was not observed, we did detect gap-junctional communication marked by the slow transfer of calcein-AM in lung-cancer cell lines. However, neither an inhibitor (1-octanol) nor an enhancer (all trans-retinoic acid [ATRA]) of gap-junctional communication affected the extent of the bystander effect. These findings suggest that low levels of gap-junctional communication may be efficient for producing the bystander effect in lung-cancer cells, or that other mechanisms may underlie this effect. Although gap-junctional communication may play an important role in generating the bystander effect in tumor cells expressing the HSV-tk gene, further knowledge of the mechanism of this effect may help improve the treatment of lung cancer with an HSV-tk system.

1-Octanol↗

Potentiation of natriuretic peptide action by the beta-adrenergic blocker carvedilol in hypertensive rats: a new antihypertensive mechanism.

Treatment with a beta-adrenergic blocker (beta-blocker) in hypertension is associated with increased plasma atrial natriuretic peptide (ANP) levels despite a decrease in cardiac overload. The mechanism and pathophysiological significance of the phenomenon remain unclear. To clarify the role of the ANP system in the antihypertensive effects of the beta-blocker, we investigated the effects of carvedilol (30 mg/kg x day, orally, for 4 weeks) on the ANP system in stroke-prone spontaneously hypertensive rats (SHR-SP/Izm). Plasma ANP levels showed a significant increase despite a significant decrease in blood pressure and heart rate in the carvedilol group. Although ANP messenger RNA levels in the heart did not change, messenger RNA levels of the natriuretic peptide-C (NP-C) receptor as a clearance receptor showed a significant decrease in both the aorta and lung in the carvedilol group. NP-C receptor densities were also significantly decreased in the lung in this group. The biological half-life of exogenous ANP in circulating blood was prolonged in the carvedilol group compared with that in the control group. Administration of the ANP receptor antagonist, HS-142-1, resulted in a greater increase in systolic blood pressure in the carvedilol group than in the control group. In addition, both basal and ANP-stimulated cGMP contents in the aorta were significantly higher in the carvedilol group. These results suggest that carvedilol potentiates the hypotensive action of ANP by increasing plasma ANP levels and enhancing the vascular response to ANP. These effects were closely related to the down-regulation of the NP-C receptor. The newly found mechanism seems to account for a sizable portion of the antihypertensive effects of carvedilol and could be of potential importance in the treatment of cardiovascular disease with beta-blockers.

Adrenergic beta-Antagonists↗