Biomedical subjects

H Itoh

Publications and source records attributed to H Itoh.

At least 631 records · Page 35Linked to original sources

PubMed1996

Increased serum interleukin-6 level and reduction of hepatic acute-phase response after major hepatectomy.

It has been proposed that a major hepatectomy impairs the liver-related host defense mechanism. The changes in the levels of serum inflammatory cytokines and plasma acute-phase proteins synthesized in the liver were measured after partial hepatectomy. Peak levels of serum interleukin-6 were significantly higher after extended lobectomy than after lobectomy or segmentectomy (p < 0.01). Serum interleukin-1 beta and tumor necrosis factor alpha levels showed no significant changes. Plasma levels of acute-phase proteins were significantly lower after lobectomy or extended lobectomy (p < 0.05). A reduced hepatic acute-phase response probably renders patients liable to infection after major hepatectomy.

Acute-Phase Proteins↗

PubMed1996

Genetic mapping of the mouse stromal cell-derived factor gene (Sdf1) to mouse and rat chromosomes.

Stromal cell-derived factor 1 (SDF1) is a new member of the Cys-X-Cys chemokine family. The chromosomal location of Sdf1, the gene coding mouse SDF1, was determined by fluorescence in situ hybridization (FISH) and molecular linkage analysis. The mouse Sdf1 gene was localized to the R-band-positive F1 band of chromosome 6 by direct R-banding FISH. Interspecific backcross analysis identified the mouse Sdf1 gene locus at 0.8 cM terminal to D6Nit55 and 3.0 cM proximal to D6Mit12. With in situ hybridization using a mouse cDNA clone as a probe, the rat Sdf1 gene was localized to the R-band-positive band 4q42.1, where conserved linkage homology to mouse chromosome 6 has been identified. Although other Cys-X-Cys chemokine genes have been mapped on human chromosome 4, the chromosomal segment where the mouse and rat Sdf1 gene reside have no conserved linkage homology to human chromosome 4. This result suggests that SDF1 is a new chemokine class.

Amino Acid Sequence↗

PubMed1996

Blunted pressure natriuresis in ovariectomized Dahl-Iwai salt-sensitive rats.

Our objective was to determine whether increased salt sensitivity after menopause precedes the development of overt hypertension. We investigated the effect of ovariectomy on pressure natriuresis in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats by in vivo perfusion studies. Differences in the neural and hormonal backgrounds of the kidney were minimized by renal denervation and by holding plasma vasopressin, aldosterone, corticosterone, and norepinephrine levels constant by intravenous infusion. The pressure-natriuresis relationship was blunted in DS rats compared with DR rats (slope, 0.30 versus 0.63 mumol.min-1.g kidney wt-1.mm Hg-1, P < .01). The impaired pressure-natriuresis response of DS rats was further blunted by ovariectomy (from 0.30 to 0.14 mumol.min-1.g kidney wt-1.mm Hg-1, P < .05), and that of DR rats was not. The ovariectomized DS rats developed hypertension earlier than sham-operated DS rats by salt loading. These results show that ovariectomy enhances genetic salt sensitivity by blunting the pressure-natriuresis relationship, which precedes the development of overt hypertension in female DS rats.

Animals↗

PubMed1996

cDNA cloning and gene expression of human type Ialpha cGMP-dependent protein kinase.

The type I cGMP-dependent protein kinase (cGK) is one of the major pathways for the cGMP cascade and has been demonstrated to inhibit platelet aggregation, relax smooth muscle cells, and control cardiocyte contractility. There are two subtypes of the type I cGK, cGKIalpha and cGKIbeta. The former is more sensitive to cGMP than the latter. In humans, cGKIbeta cDNA was isolated, but the full structure and tissue-specific gene expression of cGKIalpha have not been determined. The significance of cGK in human cardiovascular diseases has not been investigated at the molecular level. In the present study, we isolated the full-length human CGKIalpha cDNA (-36 to +2177; the translation start site: +1) enclosing the 671-amino acid protein. Nucleotides +267 to +2177 of the isolated cDNA were identical to the corresponding nucleotides of human cGKIbeta cDNA. Southern blot analysis suggested that human cGKIalpha and cGKIbeta are generated by alternative splicing of a single gene assigned to chromosome 10. By Northern blot analysis, we detected abundant human cGKIalpha mRNA (7.0 kb) in the aorta, heart, kidneys, and adrenals. In contrast, human cGKIbeta mRNA (7.0 kb) was detected abundantly only in the uterus. In cultured vascular smooth muscle cells, the type I cGK mRNA concentration was reduced to 10% of the basal level by 4 x 10(-10) mol/L platelet-derived growth factor. Angiotensin II (10(-8) mol/L), transforming growth factor-beta (4 x 10(-11) mol/L), and tumor necrosis factor-alpha (6 x 10(-6) mol/L) also exhibited an inhibitory effect on type I cGK gene expression. These findings suggest a pathophysiological implication of the type I cGK in cardiovascular diseases, including hypertension and atherosclerosis.

Amino Acid Sequence↗

PubMed1996

Vascular endothelial growth factor suppresses C-type natriuretic peptide secretion.

Angiogenesis plays a pivotal role not only in wound healing and tumor progression but also in diabetic angiopathy, arteriosclerosis, and collateral formation of obstructive vascular diseases. Vascular endothelial growth factor (VEGF) is now thought to be an endothelium-specific and potent angiogenic factor. We previously demonstrated that C-type natriuretic peptide (CNP), originally isolated from porcine brain, is produced by endothelial cells and proposed that CNP can exert control over vascular tone and growth as a local vascular regulator. In the present study, we examined the effect of VEGF on CNP secretion from endothelial cells using the specific radioimmunoassay for CNP we developed. VEGF (1 to 100 ng/mL) dose-dependently suppressed CNP secretion from cultured bovine endothelial cells, and 100 ng/mL VEGF suppressed endothelial CNP secretion to 28% of control levels (31.7 +/- 5.5 versus 8.9 +/- 0.8 fmol/mL, vehicle versus VEGF). VEGF also suppressed CNP mRNA expression in endothelial cells 9 hours after administration. In contrast, basic fibroblast growth factor (20 ng/mL), an endothelium-nonspecific angiogenic factor, significantly stimulated CNP secretion by 290%. These results indicate that VEGF can regulate vascular tone and growth in the process of angiogenesis through suppression of endothelial secretion of CNP, which is an endothelium-derived vasorelaxing and growth-inhibitory peptide.

Animals↗

PubMed1996

Natriuretic peptide receptors in human artery and vein and rabbit vein graft.

Natriuretic peptides elicit their biological effects by elevation of cGMP through activation of two biologically active receptors: natriuretic peptide A receptor, which shows high affinity to atrial and brain natriuretic peptides, and natriuretic peptide B receptor, which is specific to C-type natriuretic peptide. To elucidate the implications of the natriuretic peptide system in arteries and veins, we examined the cGMP production in response to atrial and C-type natriuretic peptide and gene expressions of biologically active natriuretic peptide receptors in human gastroepiploic artery, internal mammary artery, and saphenous vein. Atrial natriuretic peptide augmented cGMP production more potently by one order of magnitude in arteries than in veins. C-type natriuretic peptide stimulated cGMP production weakly and equally in these vessels. Analyzed by reverse transcription-polymerase chain reaction, gene expression of natriuretic peptide A receptor was four times more abundant in arteries than in veins. Gene expression of natriuretic peptide B receptor was approximately the same between these vessels. We also studied the responsiveness to atrial and C-type natriuretic peptide in rabbit jugular vein grafted into carotid artery. In arterialized vein grafts 4 weeks after operation, the effects of atrial and C-type natriuretic peptides on cGMP production did not change from those in jugular veins. In conclusion, atrial natriuretic peptide stimulates cGMP production more potently in arteries than in veins due to the preferential expression of natriuretic peptide A receptor in arteries. These observations support the distinct roles of natriuretic peptides in cardiovascular homeostasis.

Aged↗

PubMed1996

Regulation of endothelial production of C-type natriuretic peptide in coculture with vascular smooth muscle cells. Role of the vascular natriuretic peptide system in vascular growth inhibition.

Recently, we have demonstrated that C-type natriuretic peptide (CNP) is produced in vascular endothelial cells (ECs). In the present study, we investigated the interaction of ECs and vascular smooth muscle cells (SMCs) for endothelial production of CNP and its action on vascular growth, using the EC/SMC coculture system. The concentration of CNP-like immunoreactivity in the medium was increased 60-fold within 48 hours in the EC/SMC coculture with direct contact compared with that in EC alone. Northern blot analysis revealed the augmented expression of CNP mRNA in the EC/SMC coculture. The accumulation of intracellular cGMP in the coculture was concomitantly increased, and this response was blocked by anti-CNP monoclonal antibody and HS-142-1, a nonpeptide atrial natriuretic peptide receptor antagonist. The concentration of biologically active transforming growth factor-beta (TGF-beta) in the culture medium of the coculture with direct contact of ECs and SMCs was elevated to the level to stimulate endothelial production of CNP. Actually, the neutralizing antibody against TGF-beta abrogated the cGMP accumulation in the coculture. These results show that endothelial production of CNP in the EC/SMC coculture is at least in part regulated by TGF-beta. Furthermore, the conditioned medium from ECs stimulated by TGF-beta was demonstrated to have a growth-inhibitory effect on SMCs, which was abolished by anti-CNP monoclonal antibody and HS-142-1. The treatment with anti-CNP monoclonal antibody and HS-142-1 also significantly increased the cell number of the EC/SMC coculture. The present study reveals the pathophysiological significance of endothelial CNP as a paracrine/autocrine vascular regulator for vascular growth in the interaction of ECs and SMCs.

Animals↗

PubMed1996

Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy.

Angiotensin II (Ang II) acts on at least two receptor subtypes, type 1 (AT1) and type 2 (AT2). The AT2 receptor is abundant in the fetus and decreases rapidly after birth. The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role in reproduction. To explore the roles and regulation of the AT2 receptor in human uterus and to examine whether its expression is related to the proliferative characteristics of leiomyoma, we studied Ang II receptor gene expressions in nonpregnant and pregnant myometrium and in uterine leiomyomas obtained from patients who underwent gynecological surgery. Receptor binding studies revealed that all samples exhibited high-affinity binding for [Sar1, Ile5]Ang II, most (> 90%) of which was of the AT2 subtype. In nonpregnant myometrium (n = 5), receptor density [maximum binding capacity (Bmax)] and dissociation constant (Kd) for AT2-selective CGP42112A were 287 +/- 46 fmol/mg protein and 0.48 +/- 0.09 nM, respectively. In the myometrium of early (n = 6) and late pregnancy (n = 3), Bmax for the AT2 receptor was significantly decreased (62 +/- 17 and 25 +/- 6 fmol/mg protein, respectively). Furthermore, administration of combined oral contraceptive pills induced a comparable reduction in AT2 Bmax (54 +/- 12 fmol/mg protein, n = 4). AT2 Bmax or Kd values in uterine leiomyomas from nonpregnant women showed no significant differences from those in nonpregnant myometrium. Changes of AT2 Bmax in uterine leiomyomas during pregnancy or with oral contraceptive were similar to those in the myometrium. Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter. Although the AT1 receptor mRNA expression did not change significantly, the AT2 receptor mRNA level was significantly decreased during pregnancy or with oral contraceptives. These results indicate that AT1 and AT2 receptors are expressed in human myometrium and uterine leiomyoma, in which the AT2 receptor is predominant. AT2 receptor gene expression is down-regulated during pregnancy, possibly mediated by sex steroids.

Adult↗

PubMed1996

Effects of cilazapril on exercise tolerance in the chronic phase of acute myocardial infarction.

The present study was conducted to investigate the effects of cilazapril on exercise tolerance and the hormone kinetics of catecholamines, the reninangiotensin-aldosterone system and alpha-atrial natriuretic peptide (ANP) in patients in the chronic phase of acute myocardial infarction (AMI). The subjects consisted of 19 cases of AMI. Cardiopulmonary exercise testing was performed 1 month after the onset of AMI, and patients were randomly assigned to either a group treated with 1 mg/day of cilazapril (9 cases) and or an untreated group (10 cases). After the completion of 2 months of exercise training at the anaerobic threshold (AT), blood samples were taken during a cardiopulmonary exercise test and various hormones were measured. In comparing the parameters of exercise tolerance before and after the completion of exercise training there were no significant differences between the 2 groups with respect to oxygen uptake, oxygen pulse, or exercise time at AT or at peak exercise. With regard to temporal changes in exercise tolerance, oxygen uptake, oxygen pulse and exercise time all tended to increase in both groups. With regard to hormone kinetics, the alpha-ANP concentration at peak exercise was significantly lower, and the noradrenaline secretions also tended to be lower, in the cilazapril-treated group, even though the peak exercise time was similar in both groups. These results may be support the hypothesis that cilazapril mitigates the left ventricular load during exercise therapy in patients in the chronic phase of AMI.

Aldosterone↗

PubMed1996

Novel beta-D-galactofuranose-containing high-mannose type oligosaccharides in ascorbate oxidase from Acremonium sp. HI-25.

Ascorbate oxidase from the fungus Acremonium sp. HI-25 is a copper-containing glycoprotein that catalyzes the oxidation of ascorbic acid to dehydroascorbic acid. Monosaccharide composition analysis showed that the enzyme contains exclusively N-linked oligosaccharide chains. Following liberation by hydrazinolysis/re-N-acetylation, and fractionation by HPLC on anion exchange. Amide-80 and/or octadecyl silica columns after derivatization with p-aminobenzoic ethyl ester, the structures of the twelve major neutral oligosaccharides were identified by FAB-MS, 400 MHz 1H-NMR, methylation analysis, mild acid hydrolysis, and/or sequential exoglycosidase digestions. Acremonium sp. ascorbate oxidase was found to consist of high-mannose type oligosaccharides (76.3%) having 4 to 9 mannose residues and a series of novel D-galactofuranose-containing high-mannose type oligosaccharides (18.6%) with the following structure.

Acremonium↗

PubMed1996

Endothelin-1-like immunoreactivity and endothelin receptors in the human placenta from normotensive and hypertensive pregnancies.

The levels of endothelin-1-like immunoreactivity (ET-1-LI) and characteristics of endothelin receptors in the chorionic villous tissue of human placenta were determined. The ET-1-LI level in chorionic villous tissue obtained from normal term placenta was 2,450 +/- 940 pg/g wet weight (mean +/- SD, n = 4). Further analysis using gel permeation chromatography and reverse-phase high performance liquid chromatography showed that the main ET-1-LI constituent of ET-1-LI in this tissue was ET-1. Scatchard analysis of [125I]ET-1 binding to the membrane fraction of chorionic villous tissue obtained from term placenta showed high affinity receptor sites with an apparent dissociation constant (Kd) of 23.6 +/- 11.1 pM and a Bmax value of 388 +/- 238 fmol/mg protein (n = 5). The same binding study with [125I]ET 3 showed a Kd of 13.9 +/- 3.8 pM and a Bmax value of 176 +/- 78 fmol/mg protein (n = 5). These results suggest that both ET-A and ET-B receptors (ET-AR and ET-BR) are expressed in chorionic villous tissue. This finding was further confirmed by Northern blot analysis showing the expression of both ET-AR and ET-BR mRNAs in this tissue. ET-1-LI in the umbilical venous plasma of the newborns from women with pregnancy-induced hypertension (PIH) (38.3 +/- 10.4 pg/mL, n = 5) was significantly (P < 0.05) higher than that in the normal newborns from normotensive pregnant women (26.3 +/- 5.2 pg/mL, n = 12). However, in placental chorionic villous tissue obtained from PIH women, both ET-1-LI level and ET binding profile were not different from those in chorionic villous tissue from normotensive pregnant women. These results suggest that the abundant ET-ET receptor system is present in the placental chorionic villous tissue and that this system is not the major factor of the pathogenesis of placental dysfunction occurring in PIH because these systems are similar in normotensive and hypertensive pregnancies.

Chorionic Villi↗

PubMed1996

The RET proto-oncogene in sporadic pheochromocytomas.

In order to evaluate the role of RET proto-oncogene in the development and growth of pheochromocytomas, we examined mutations in RET and expression of RET in 7 cases of sporadic pheochromocytomas. Tumors were screened for mutations in exons 10 and 11 and codon 918 which are identified in multiple endocrine neoplasia types 2A and 2B. No mutations were found in these regions in all of the sporadic pheochromocytomas examined. On the other hand, RET mRNA was detected in all pheochromocytomas and the levels of RET expression were higher in 5 of 7 pheochromocytomas than in normal adrenal medulla, indicating that RET is overexpressed in a sizable portion of sporadic pheochromocytomas. These results suggest that high levels of expression of RET may have relevance to the development or growth of sporadic pheochromocytomas.

Adrenal Gland Neoplasms↗

PubMed1996

Simple obesity with cardiomyopathy of obesity.

A 32-year-old obese female was hospitalized with dyspnea. Echocardiogram revealed left ventricular dilatation. Chest X-ray film showed enlarged heart size and prominent pulmonary congestion. Simple obesity with congestive heart failure (CHF) due to cardiomyopathy of obesity was diagnosed according to the absence of obvious disease that caused obesity or CHF. After diet therapy and medication, subjective symptoms disappeared and body weight was reduced from 137 kg to 85 kg. Although few reports of cardiomyopathy of obesity have been reported in Japan, we propose the possibility that similar cases will be on the increase because Japanese dietary habits are now becoming more similar to those of Caucasians.

Adult↗

PubMed1996

Insulin suppresses endothelial secretion of C-type natriuretic peptide, a novel endothelium-derived relaxing peptide.

We have previously reported that C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family, is produced in vascular endothelial cells (ECs) and acts as an endothelium-derived relaxing peptide. We further demonstrated the detection of the gene transcripts of CNP and atrial natriuretic peptide (ANP) B receptor, a specific receptor for CNP, in human blood vessels. We thus propose the existence of a vascular natriuretic peptide system (NPS). CNP secretion was also demonstrated to be stimulated by various growth factors and cytokines. To clarify the significance of vascular NPS in proliferative vascular complications associated with diabetes, hypertension, or atherosclerosis, in the present study we examined the effect of insulin on CNP secretion from cultured ECs. Insulin at a concentration in the physiological range (10(-10)-10(-7) mol/l) potently suppressed CNP secretion, whereas insulin at the same concentration did not suppress endothelin (ET) secretion from EC. IGF-I had no significant effect on CNP secretion. Insulin, therefore, can be a potent inhibitor of CNP secretion through the activation of insulin receptor. Since CNP has been shown to be a potent inhibitor of vascular smooth muscle cell proliferation, the present study suggests the possibility that attenuated activity of vascular NPS is associated with hyperinsulinemia, which might result in proliferative vascular lesions.

Animals↗

PubMed1996

Walking patterns and finger rhythm of older adults.

Walking patterns and rhythmic movement of the fingers were examined in a total of 1,134 male and female community residents 65 years of age and over. Walking patterns were characterized according to the ratio of step length divided by step rate (cadence), called the Walk Ratio, during level walking at preferred and maximum speeds. The walking pattern tended to change according to age; older subjects walked with shorter steps (smaller Walk Ratio). Rhythmic movement was examined using the finger-tapping test in time to the sound of a 4-Hz metronome. Hastened tapping or finger festination, in which the subject tapped faster than requested (constant error of 3 msec. and over in the intertap interval), was characteristic of aging; 16.8% of the subjects exhibited finger festination and the occurrence increased with age, especially among those in their eighties (29.3%). Finger festination was accompanied by walking patterns with an increased step rate, or a smaller Walk Ratio. These characteristics of aging were discussed as similar to extrapyramidal symptoms of walking and rhythm production in patients with Parkinson's disease.

Acceleration↗

PubMed1996

Does combined therapy of Ca-channel blocker and angiotensin converting enzyme inhibitor exceed monotherapy in renal protection against hypertensive injury in rats?

Either calcium channel blocker (CCB) or angiotensin converting enzyme inhibitor (ACEi) is used as an antihypertensive agent, and we are recommended to use them in combination to refractory hypertension with evidence dependent on clinical observations. We examined the renal protective effect of the combined therapy with calcium channel blocker (amlodipine) and angiotensin converting enzyme inhibitor (enalapril) against hypertensive renal injury in 5/6 nephrectomized spontaneously hypertensive rats (SHRs) with salt loading, comparing with monotherapy of each drug. Forty males SHRs with 5/6 nephrectomy and salt loading were divided to five groups: group 1 as control (n = 8), group 2 received 0.2 mg/kg/day of amlodipine (n = 8), group 3 received 0.2 mg/kg/day of enalapril (n = 8), group 4 (n = 8) and group 5 (n = 8) that were treated with 0.1 mg/kg/day and 0.2 mg/kg/day of each drug in combination respectively. Either amlodipine or enalapril had remarkable effects on reducing the increases in blood pressure and urinary protein excretion. In histopathological examination, it also suppressed renal injury significantly. Additional significant effect of combined therapy was not observed in blood pressure and urinary protein. There were not remarkable, additional effects of the combination of CCB and ACEi on protecting the remnant kidney in 5/6 nephrectomized SHRs fed a high-salt diet, possibly because sodium retention was not alleviated by the combination.

Amlodipine↗

PubMed1996

[Clinical experience of total prostatectomy using DDV-L (deep dorsal venous ligator].

BACKGROUND: We evaluated blood loss in operation and postoperative urinary incontinence to total prostatectomy using the DDV-L. METHODS: We performed total retropubic prostatectomy for 38 patients from May 1979 to May 1995. In 14 patients from October 1994 to May 1995 the DDV-L was used. The DDV-L is used in transurethral approach, disposable device to ligate the deep dorsal vein complex by delivering the needle to lateral of deep dorsal vein complex. RESULTS: We composed the 14 patients which was used the DDV-L with the 14 patients which was from April 1990 to July 1994 was not used that. The mean operating time of 14 patients which was used the DDV-L was 178.5 min, 14 patients which was not used that was 188.0 min. The mean blood loss of 14 patients which was used th DDV-L was 735.7 ml, 14 patients which was not used that was 1250.2 ml. We transfused blood into 2 of 14 patients which was used the DDV-L (14.0%), 10 of 14 patients which was not used that (71.4%). The one of 14 patients which was used the DDV-L (7.5%) and 5 of 14 patients which was not used that (35.7%) had postoperative urinary incontinence needing pad. CONCLUSION: Accordingly the operating results of 14 patients which was used the DDV-L was undoubtedly better that of 14 patients which was as regards blood loss in operation, postoperative urinary incontinence. We can perform easily the management of deep dorsal vein complex by DDV-L, so we can cut of urethra without excess hemostasis and electronic coagulation, and leave enough long membranous urethra. We consider the DDV-L is helpful to total prostatectomy.

Aged↗

PubMed1996

Increased levels of human hepatocyte growth factor in serum and peritoneal fluid after partial hepatectomy.

OBJECTIVE/METHOD: It has been reported that inflammatory cytokines up-regulate human hepatocyte growth factor synthesis in vitro. To demonstrate the relation of this growth factor to interleukin-6 and tumor necrosis factor alpha, the changes in the levels of these cytokines were measured in serum and peritoneal fluid in 22 patients after partial hepatectomy. RESULTS: Serum and fluids levels of cytokines showed a maximum within 3 days after surgery. Cytokines concentrations were much higher in fluid than in serum (p < 0.05). The maximum serum levels of human hepatocyte growth factor were significantly correlated with those of interleukin-6, intraoperative blood loss, and operating time (p < 0.05) but not resected liver weights. In fluid level, the growth factor was also correlated with interleukin-6 (p < 0.05) but with tumor necrosis factor alpha. CONCLUSIONS: These results suggest that human hepatocyte growth factor might be locally produced in the injured tissue associated with interleukin-6 and independently of resected liver weights.

Aged↗