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Biomedical subjects

K Kanno

Publications and source records attributed to K Kanno.

At least 73 records · Page 4Linked to original sources
PubMed1992

Increased production of endothelin-1 in patients with inflammatory arthritides.

OBJECTIVE: Endothelin-1 (ET-1) is a potent vasoconstrictive peptide, but its precise mechanism of action in vivo has remained unknown. METHODS: We measured ET-1 activity by radioimmunoassay, in both plasma and synovial fluid from patients with inflammatory arthritides. RESULTS: ET-1-like immunoreactivity was found in synovial fluid, at levels severalfold higher than those in plasma. Reverse-phase high-performance liquid chromatography showed an elution profile corresponding to actual ET-1. A single class of high-affinity binding sites for ET-1 in cultured synovial cells was also detected. Furthermore, ET-1 induced mild DNA synthesis in synovial cells. CONCLUSION: Taken together, these results indicate that ET-1 might contribute to the synovial proliferation seen in inflammatory arthritides, in an autocrine/paracrine manner.

Adult↗
PubMed1992

L-arginine infusion induces hypotension and diuresis/natriuresis with concomitant increased urinary excretion of nitrite/nitrate and cyclic GMP in humans.

1. The vascular endothelium produces endothelium-derived relaxing factor (EDRF) or nitric oxide (NO), which exerts vasodilation through cyclic guanosine monophosphate (cGMP) as a second messenger. To determine whether EDRF has any vasodilating and natriuretic action in man, the present study examined the effects of L-arginine (L-Arg), a substrate for NO, on the responses of mean blood pressure (MBP) and heart rate (HR); plasma concentrations of cGMP, atrial natriuretic factor (ANF) and nitrite/nitrate (NOx); urinary excretion of sodium, cGMP and NOx; and urinary flow in eight normal male subjects. These parameters were compared with those following saline infusion in the same subjects. Clearance of para-aminohippuric acid (PAH) and inulin was studied in five normal subjects. 2. Infusion of L-Arg (30 g) caused a significant fall in MBP (-8 mmHg) with a concomitant rise in HR (10 beats/min), while saline infusion had no effects on these parameters. 3. Neither L-Arg nor saline infusion caused appreciable changes in plasma concentrations of ANF or NOx. Plasma cGMP concentrations increased significantly during (1.7-fold) and after (1.9-fold) L-Arg infusion, but only slightly (1.3-fold) during saline infusion. 4. Urine flow increased more remarkably following L-Arg infusion than that following saline infusion. Remarkable increases in urinary excretion of sodium and fractional excretion of sodium were observed after L-Arg infusion compared with those after saline infusion. Natriuresis was associated with enhanced urinary excretion of cGMP and Nox. Urinary Nox excretion showed positive correlations with urinary flow (r = 0.69, P less than 0.001) and with urinary cGMP excretion (r = 0.60, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of the new angiotensin-converting enzyme inhibitor imidapril on renal hemodynamics and function in anesthetized dogs.

The effects of a new angiotensin-converting enzyme (ACE) inhibitor, imidapril hydrochloride ((-)-(4S)-3-[(2S)-2- [[(1S)-1-ethoxycarbonyl-3-phenylpropyl]amino]propionyl]- 1-methyl-2-oxoimidazolidine-4-carboxylic acid hydrochloride, imidapril, TA-6366, CAS 89396-94-1) and of its active metabolite, 6366 A (CAS 89371-44-8) on renal function were studied in anesthetized dogs and compared to the effects of enalapril and its active metabolite, enalaprilat. Intravenous (i.v.) administration of 6366 A at 30 micrograms/kg strongly inhibited angiotensin I-induced renal vasoconstrictive and pressor responses. 6366 A promptly lowered blood pressure and renal vascular resistance, and caused clear increases in renal blood flow and glomerular filtration rate. It also increased urine volume and urinary excretion of sodium and chloride. These renal effects were also produced by intraduodenal (i.d.) administration of 2 mg/kg of imidapril. However, the effects of i.d. imidapril began later, developed gradually and reached a plateau after 2 to 3 h. Enalaprilat (30 micrograms/kg i.v.) and enalapril (2 mg/kg i.d.) had renal effects similar to 6366 A and imidapril. In conclusion, the ACE inhibitor imidapril has beneficial effects on renal function via its active metabolite, and the effects appear to be essentially identical to those of enalapril.

Anesthesia↗
PubMed1992

[Controversy in the treatment of superficial esophageal carcinoma--indications and problems of the procedures].

In our institution, 152 cases have been treated, which are 24.3% of total 626 cases with esophageal carcinomas. Analysis of these 152 cases revealed that neither intraepithelial cancer (ep), nor mm2 cancer, in which the lesion is limited within the upper two-thirds of the proper mucosal layer, had any vessels invasion and lymph node metastases. In addition, only 25% of the cases with mm3 cancer, limited within the deeper one-third of the proper mucosal layer, had vessels invasion without lymph node metastases. The 5-year survival of the cases less than sm1 was as good as 100%. However, those of sm2 and sm3 patients were 58.9% and 54.2%, respectively. Thus, we made the treatment strategy for superficial esophageal cancer as follows: 1. For ep to mm2 cases, endoscopic mucosal resection could be applied. 2. For the cases whose lesions widely spread in the esophagus, blunt resection would be indicated. 3. For the cases with mm3 to sm3 cancer, thoracotomy and laparotomy with wide lymph node dissection from neck to abdomen should be employed. Since a radical operation for esophageal cancer has high operative risk and poor postoperative quality of life, we should properly pick up and apply more cases with mucosal carcinoma for endoscopic mucosal resection.

Esophageal Neoplasms↗
PubMed1991

Endothelin-3 stimulates production of endothelium-derived nitric oxide via phosphoinositide breakdown.

Cultured bovine endothelial cells (EC) have specific receptors for endothelin (ET)-3 functionally coupled to phosphoinositide breakdown. We studied whether ET-3 stimulates synthesis of nitric oxide (NO), an endothelium-derived relaxing factor that activates soluble guanylate cyclase in EC, and whether the ET-3-induced NO formation involves G-proteins. ET-3 dose-dependently stimulated production of intracellular cGMP in EC, of which effects were abolished by pretreatment with NG-monomethyl L-arginine, an inhibitor of NO synthesis, and methylene blue, an inhibitor of soluble guanylate cyclase. The stimulatory effects of ET-3 on cGMP production, inositol trisphosphate formation and increase in cytosolic free Ca2+ concentration were similarly blocked by pretreatment with pertussis toxin (PTX). These data suggest that ET-3 induces synthesis of NO mediated by phosphoinositide breakdown via PTX-sensitive G-protein in EC.

Animals↗
PubMed1991

Reversible MRI and CT findings in uremic encephalopathy.

In this 35-year-old woman with chronic glomerulonephritis and uremic encephalopathy, the basal ganglia bilaterally, internal capsules and periventricular white matter showed hypodensity on CT, low signal intensity on T1-weighted MRI and high signal intensity on T2-weighted MRI. Following a series of dialyses, her clinical symptoms and blood chemistry improved. The CT and MRI returned to normal. These reversible abnormalities may be caused by reversible ischemic change, but disorders of cerebral metabolism and uremic toxins may contribute.

Adult↗
PubMed1991

Urinary excretion of endothelin-1 in normal subjects and patients with renal disease.

To elucidate the pathophysiological significance of urinary endothelin-1 (ET-1), we measured urinary excretion of ET-1-like immunoreactivity (L1) in 17 patients with renal disease and 9 normal subjects. Twenty-four hour urinary ET-1-L1 excretion in patients with renal disease (358 +/- 68 ng, mean +/- SE) was significantly (P less than 0.005) greater than that of normal subjects (77 +/- 5 ng). In patients with renal disease. ET-1-L1 clearance (CET) exceeded creatinine clearance (CCR); CET/CCR (305 +/- 81%) was significantly (P less than 0.005) greater than that of normal subjects (43 +/- 13%). The 24-hour urinary excretion of ET-1-L1 in patients with renal disease showed significant correlation with that of N-acetyl-beta-D-glucosaminidase (r = 0.587, P less than 0.05), beta 2-microglobulin (r = 0.614, P less than 0.01) and albumin (r = 0.484, P less than 0.05). Intravenous infusion of saline (500 ml) in seven normal subjects did not affect urinary ET-1 excretion rate. These data suggest that urinary excretion of ET-1 derives mainly from renal tubular secretion at least in patients with renal disease, and that degradation and/or reabsorption of ET-1 at the tubular site may also contribute to the renal handling of ET-1. Therefore, urinary excretion of ET-1 should serve as a potential marker for renal injury.

Acetylglucosaminidase↗
PubMed1991

Plasma endothelin-1 levels in patients with diabetes mellitus with or without vascular complication.

Plasma endothelin-1 (ET-1) concentrations were measured in 25 patients with non-insulin-dependent diabetes mellitus (11 with angiopathy and 14 without angiopathy) and 21 normal subjects using radioimmunoassay specific to ET-1. Basal plasma immunoreactive (ir) ET-1 levels in diabetic patients with and without angiopathy were 1.73 +/- 0.29 and 1.68 +/- 0.20 pg/ml, respectively. Although high glucose levels may stimulate ET-1 release from vascular endothelial cells in vitro, our data suggest that circulating ET-1 may not be elevated in most diabetic patients with or without angiopathy.

Adult↗
PubMed1991

Cellular mechanism of endothelin-1 release by angiotensin and vasopressin.

Release of endothelin-1, a novel potent vasoconstrictor peptide originally isolated from endothelial cells, from cultured bovine endothelial cells has been shown to be stimulated by arginine vasopressin and angiotensin II. To elucidate the cellular mechanism by which endothelin-1 is released by these vasoconstrictors, we tested the effects of several compounds on the agonist-induced endothelin-1 release and studied the changes of cytosolic free Ca2+ concentrations and phosphoinositide breakdown by these agonists in cultured bovine endothelial cells. Protein kinase C inhibitors (H-7, staurosporine), an intracellular Ca2+ chelator, and an inhibitor of phospholipase C (neomycin), all abolished the agonist-induced endothelin-1 release, whereas the Ca2+ channel blocker nicardipine was ineffective. Although synthetic 1,2-diglyceride (diolein) dose dependently stimulated endothelin-1 release, downregulation of protein kinase C after pretreatment with phorbol ester resulted in decreased effects to increase endothelin-1 release by the agonists. Both arginine vasopressin and angiotensin II induced immediate and transient increases in intracellular Ca2+ levels of fura-2-loaded endothelial cells as well as formation of inositol trisphosphate; the agonist-induced intracellular Ca2+ increases were not affected either by nicardipine or by chelating extracellular Ca2+. The arginine vasopressin- and angiotensin II-induced intracellular Ca2+ increases, inositol trisphosphate formation, and endothelin-1 release were completely abolished by V1-receptor antagonist and saralasin, respectively. It is concluded that arginine vasopressin and angiotensin II stimulate the release of endothelin-1 by a common mechanism, involving receptor-mediated mobilization of intracellular Ca2+ and activation of protein kinase C in endothelial cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Comparison of cardiorenal and emetic effects of dopamine prodrugs docarpamine (TA-870) and levodopa in dogs.

Positive inotropic and renal vasodilatory effects of a novel dopamine prodrug, docarpamine, [N-(N-acetyl-L-methionyl)-3,4-bis(ethoxycarbonyl)dopamine; TA-870] and those of levodopa were compared in anesthetized dogs, and emetic effects of the two drugs were compared in conscious dogs. Intraduodenal administrations of docarpamine and levodopa at 20 mg/kg produced similar increases in cardiac contractility. The maximal increases in the left ventricular dP/dtmax after docarpamine and levodopa were 36.6 +/- 14.2 and 39.2 +/- 12.1%, respectively. The two drugs also produced similar decreases in renal vascular resistance (21.2 +/- 2.2 and 13.6 +/- 3.4%, respectively) and increases in renal blood flow (27.9 +/- 3.2 and 17.9 +/- 5.2%, respectively), however, the duration of renal vasodilation after docarpamine was longer than that of levodopa. Oral administration of the two drugs in conscious dogs produced vomiting. The ED50 value of the emetic effect for docarpamine was greater than 160 mg/kg, and that for levodopa was 11.0 mg/kg. The emesis was inhibited by pretreatment with a DA2 antagonist, domperidone. In conclusion, docarpamine and levodopa produced similar cardiorenal effects, but the emetic effect of docarpamine was much weaker than that of levodopa. Docarpamine can be used as a selective dopamine prodrug for the peripheral circulation.

Animals↗
PubMed1991

The effect of a protein-bound polysaccharide on T cell subsets of peripheral venous blood and thoracic duct lymph.

To investigate the effect of a protein-polysaccharide preparation, PSK, on immune system function, the ratios of peripheral venous blood and thoracic duct lymphocyte subsets were determined in 6-week-old male SPF Wistar-Imamichi strain rats maintained on a diet containing 2% PSK ad libitum. Peripheral blood and thoracic duct lymph specimens were obtained from pretreatment, 4- and 8-week PSK-treated, and period-matched control groups of rats. The lymphocyte count and percentages of helper/inducer and suppressor/cytotoxic T cells were determined with a laser flow-cytometry system using monoclonal antibodies W3/13, W3/25 and OX8. Compared with the controls, the PSK-treated group showed significantly lower total T cell and helper/inducer T cell counts in the peripheral blood, but showed no difference in the suppressor/cytotoxic T cell count. However, in the thoracic duct, there were significantly increased total T cell and helper/inducer T cell counts, but no difference in suppressor/cytotoxic T cell counts compared with the controls. These data appear to indicate a significant activity of oral PSK, resulting in modulation of lymphocyte distribution in the body by facilitation of the transition of circulating T lymphocytes, especially helper/inducer T cells, into the lymph.

Administration, Oral↗
PubMed1990

Cytokine-induced release of endothelin-1 from porcine renal epithelial cell line.

To elucidate the mechanism by which endothelin-1 (ET-1) is released from renal epithelial cells, we have investigated the effects of several compounds on release of ET-1-like immunoreactivity (LI) from LLCPK1 cell line. Thrombin, transforming growth factor-beta, cytokines (tumor necrotizing factor-alpha, interleukin-1 beta), and phorbol ester stimulated ET-1-LI release in a time- and dose-dependent manner. The cytokine-induced ET-1-LI release was not affected by indomethacin. Northern blot analysis using cDNA for porcine preproET-1 as a probe revealed a single major band corresponding to the size of ET-1 mRNA in LLCPK1. These data indicate that the preproET-1 gene is also expressed in renal epithelial cells and the release of ET-1 from renal cells is regulated by the similar mechanism to that from endothelial cells.

Animals↗
PubMed1990

Receptor binding and vasoconstrictor activity of big endothelin.

We studied the effects of synthetic porcine big endothelin (ET), a putative 39-residue intermediate deduced from cDNA sequence analysis, on receptor binding activity in cultured rat vascular smooth muscle cells as well as its vasoconstrictive activity in rat pulmonary artery. Big ET was about two orders of magnitude less active than ET in the receptor binding and vasoconstriction assays. Our data are consistent with the contention that big ET is an intermediate which can be converted into fully bioactive 21-residue mature ET.

Animals↗