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Biomedical subjects

K Kanno

Publications and source records attributed to K Kanno.

18 recordsLinked to original sources
PubMed1992

Cellular mechanism of thrombin on endothelin-1 biosynthesis and release in bovine endothelial cell.

We have studied the cellular mechanism responsible for induction of preproendothelin (preproET)-1 mRNA and release of ET-1 by thrombin in cultured bovine endothelial cells (ECs). Thrombin induced an immediate and dose-dependent formation of inositol-1,4,5-trisphosphate (IP3) with a concomitant increase in intracellular Ca2+ concentration ([Ca2+]i). The thrombin-induced ET-1 release was abolished either by a phospholipase C inhibitor, a protein kinase C (PKC) inhibitor, or an intracellular Ca(2+)-chelator, whereas a Ca(2+)-channel antagonist was ineffective. A selective thrombin inhibitor (argatroban) decreased IP3 formation and the increase in [Ca2+]i and ET-1 release stimulated by thrombin. Northern blot analysis revealed that thrombin-induced expression of preproET-1 mRNA was inhibited completely by a PKC inhibitor and partially by argatroban. These data suggest that thrombin is involved in the mechanism of preproET-1 mRNA expression and subsequent ET-1 release, possibly through activation PKC and mobilization of intracellular Ca2+ resulting from the receptor-mediated phosphoinositide breakdown in ECs.

Animals↗
PubMed1992

Sulfated alkyl oligosaccharides with potent inhibitory effects on human immunodeficiency virus infection.

Compounds with medium relative molecular masses active against human immunodeficiency virus (HIV) were synthesized. Sulfated alkyl oligosaccharides such as sulfated octadecyl maltohexaoside, sulfated dodecyl laminaripentaoside and sulfated dodecyl laminari-oligomer caused 50% inhibition of virus infection in the EC50 range of 0.4-0.7 microgram/mL in vitro using the MT-4 cell line and HIV-1HTLV-IIIB virus isolate, though sulfated oligosaccharides without alkyl groups showed low anti-HIV activities. This anti-HIV activity was close to the EC50 of 0.43 microgram/mL for a highly active sulfated polysaccharide curdlan sulfate which was reported to inhibit completely the HIV infection at a concentration as low as 3.3 micrograms/mL. These compounds were also active against HIV-2 and a clinically isolated HIV-1 with reduced AZT sensitivity. For such sulfated alkyl oligosaccharides, the mechanism of inhibition of HIV infection was assumed to be the inhibition of HIV binding to the cell and to some extent the interaction of the alkyl portion with the lipid bilayer of the virus.

Amino Acid Sequence↗
PubMed1992

Endothelin receptors in human parathyroid gland.

We studied whether specific receptors for endothelins (ETs) exist in human parathyroid tissues and whether ETs may have any effect on secretion of PTH from parathyroid cells. Binding studies using [125I]ET-1 to the parathyroid membranes obtained from patients with hyperparathyroidism (2 adenomas, 2 hyperplasias) revealed that ET-1 competitively inhibited the binding of [125I]ET-1 to the membranes (the apparent Kd: 62 +/- 18 pM), whereas ET-3 showed biphasic and less steep inhibition curve than ET-1 in all tissue membranes examined. Northern blot analysis of poly(A)+ RNA from the parathyroid adenoma clearly demonstrated gene expression of both ETA and ETB receptors as well as preproET-1. ET-1 inhibited basal PTH secretion from dispersed adenoma cells more potently than ET-3. The present study clearly demonstrates the presence of both ETA and ETB receptor subtypes in human parathyroid tissues through which ETs may modulate PTH secretion in an autocrine and/or paracrine manner.

Adenoma↗
PubMed1992

Concomitant expression of receptor subtype and isopeptide of endothelin by human adrenal gland.

We studied whether specific receptors for endothelin (ET) isopeptide exist in human aldosterone-producing adenoma and normal adrenal cortex, and whether ET isopeptides are produced by human adrenal gland. Competitive binding studies using [125I]ET-1 as a radioligand revealed the presence of a single class of high-affinity binding sites for ET-1 with the apparent KD of 70 +/- 31 pM and Bmax of 226 +/- 139 fmol/mg protein in adenoma membranes almost comparable to those in adjacent normal cortex. The apparent Ki for ET-2 and ET-3 were 89 +/- 33 pM and 82 +/- 16 pM, respectively. Northern blot analysis of poly(A)+ RNA of adenoma and adjacent normal cortex using cDNAs for ET receptor subtype (ETA, ETB) and ET isopeptide (ET-1, ET-3) as probes revealed that ETA and ETB receptors as well as ET isopeptides (preproET-1, preproET-3) are concomitantly expressed in both tissues. Our data demonstrate for the first time that ET receptor subtype (ETA and ETB) and ET isopeptide (ET-1 and ET-3) are concomitantly expressed by human adrenal cortex, suggesting the potential role of ETs as a local mediator in human adrenal gland.

Adenoma↗
PubMed1992

Effects of three distinct natriuretic peptides on receptor binding and guanylate cyclase activities in rat glioma cells.

Receptor binding and cyclic GMP generation by three distinct natriuretic peptides (ANP, BNP, CNP) were studied in a cultured rat glioma cell line (C6). Binding studies revealed the presence of high-affinity binding sites for three natriuretic peptides with almost comparable affinities. In contrast, CNP and BNP were almost equipotent in stimulating intracellular cyclic GMP generation over the low concentration range, but CNP caused further elevation in the high concentration range, whereas ANP was minimally effective. Our data suggest that the glioma cells possess receptors more responsive to CNP than ANP and BNP despite no apparent correlation between receptor binding affinities and cyclic GMP responses.

Animals↗
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

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↗
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↗
PubMed1977

Elastin sub-fraction as binding site for lipids.

Elastin preparations were isolated from human thoracic aorta, from atherosclerotic and from grossly normal regions. A relatively mild procedure was used to avoid hot alkaline extraction and autoclaving. The elastase digest of the aortic elastin was chromatographed on a Sephadex G-100 column and separated into two fractions: A (larger molecular weight) and B (smaller molecular weight). The ratio of fraction A to total aortic elastin increased with age and the development of the atherosclerosis. Amino acid and sugar analyses showed that fraction A consistently contained more polar amino acids, hexose, hexosamine and L-fucose, and less sialic acid, in comparison with fraction B. Part of the elastin preparation was incubated with human low-density lipoprotein; a considerable amount of lipid, especially cholesterol, was transferred from the lipoprotein to the elastin. Estimation of protein and cholesterol in fractions A and B of the elastase hydrolyzate of incubated elastin showed that most of the cholesterol taken up by elastin had been in fraction A. The increased proportion of fraction A in aortic elastin derived from plaque areas appeared responsible for the marked lipid-binding capacity of plaque elastin.

Age Factors↗
PubMed1977

[Hemodynamic and respiratory function following acute spinal cord injury (author's transl)].

Twenty two cases of the cervical and thoracic cord injury were studied to determine hemodynamic and respiratory function within 7 days from the injury. Most patients showed a tendency of bradycardia and hypotension on admission which were more remarkable in the group of lower cervical cord or the upper thoracic cord lesion than the upper cervical cord group. Such a hypotension and bradycardia tended to recover within 7 days. In cervical cord injury, cardiac output remained unchanged, which indicated that initial hypotension was due to decreased total peripheral resistance. Respiratory rate was slightly increased in most patients, but did'nt show any significant difference among the level of the lesion. PaO2 and PaCO2 were within normal range on admission, however PaO2 decreased gradually in 7 days only in cervical cord injury. Increased pulmonary arterial pressure was confirmed during the above hypoxemic period. It suggests that disturbance of neurological control of pulmonary circulation might play a significant role in the respiratory insufficiency of cervical cord injury.

Adolescent↗
PubMed1975

Low serum alpha-1-antitrypsin level as a contributory factor of combined emphysema in silicosis.

In order to evaluate low serum alpha-1-antitrypsin level as a contributory factor of combined emphysema in silicotic patients, serum alpha-1-antitrypsin analysis was carried out in 80 patients with silicosis. Low serum alpha-1-antitrypsin level was found in 5 patients. Large opacities were observed roentgenologically in only 1 out of these 5 cases in contrast to 31 of the other 75 cases. Also the suggestive findings for the emphysema were showed in 4 of these 5 cases while such findings were found on their chest X-ray films in only 43 of the other 75 cases. FEV 1.0% below 50 were calculated in 3 of the 5 cases, on the contrary in 22 of the 75 cases. RV above 50% predicted value was showed by all the 5 low antitrypsin patients, in contrast to only 25 of other 74 cases. The silicotic patients with low serum alpha-1-antitrypsin concentration are most likely to have an association with a high incidence of complicated emphysema.

Adult↗