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Biomedical subjects

O Wada

Publications and source records attributed to O Wada.

At least 19 recordsLinked to original sources
PubMed1998

Altered expression of endothelin-1 and endothelial nitric oxide synthase in the juxtaglomerular apparatus of rats with HgCl2-induced acute renal failure.

A progressive fall in glomerular capillary plasma flow (QA) is observed in mercury chloride (HgCl2)-induced acute renal failure (ARF) although the site of the main lesion of this ARF is the proximal tubule. To elucidate this mechanism, we examined the expression of endothelin (ET)-1 and endothelial nitric oxide synthase (eNOS) protein at the glomerulus level in the kidneys of control rats and rats with HgCl2-induced ARF. Both ET-1 and eNOS protein were detected in the juxtaglomerular cells of afferent arterioles. The expression of ET-1 was significantly increased in ARF rats when compared to control rats. Inversely, the expression of eNOS protein was markedly reduced in ARF rats as opposed to control rats. These observations suggest the participation of the vasoconstrictor, ET-1 and the vasodilator, NO in a reduction in QA observed in HgCl2-induced ARF.

Acute Kidney Injury↗
PubMed1998

Role of angiotensin II, endothelin-1, and nitric oxide in HgCl2-induced acute renal failure.

To elucidate the mechanisms underlying the development of HgCl2-induced acute renal failure (ARF), we examined the expression of endothelin (ET)-1, endothelial (e) nitric oxide synthase (NOS) and inducible (i) NOS, and a role of angiotensin II (ANG II) and tumor necrosis factor (TNF) in glomeruli and cortices from rats at 20 h after exposure of HgCl2. Prepro-ET-1 and iNOS mRNA were significantly increased in glomeruli and cortices from rats with HgCl2-induced ARF. However, eNOS mRNA was markedly decreased in glomeruli of rats with HgCl2-induced ARF. Blockade of the action of endogenous ANG II with TCV-116, an ANG II receptor type 1 antagonist, or prior administration of TNF antibody (Ab) neutralizing TNF bioactivity or aminoguanidine, an iNOS inhibitor, substantially suppressed the increase in the expression of prepro-ET-1 or iNOS mRNA seen in rats with HgCl2-induced ARF. Both TCV-116 and TNF Ab had no effects on the expression of eNOS mRNA. The abundance of ET-1, iNOS, and eNOS proteins was paralleled by the magnitude of each mRNA expression. Additionally, the aggravation of blood urea nitrogen and serum Cr observed in rats with HgCl2-induced ARF were significantly ameliorated together with the alleviation of proximal tubule epithelial cell injury when the expression of prepro-ET-1 or iNOS mRNA was blunted by prior administration of TCV-116 or prior injection of TNF Ab or aminoguanidine. These observations indicate that ANG II, ET-1, and NO may play an important role in the progression of HgCl2-induced ARF through the acceleration of proximal tubule epithelial cell injury and the deterioration of glomerular hemodynamics. In HgCl2-induced ARF, the gene expression of ET-1 or iNOS is at least in part up-regulated at the transcription level by endogenous ANG II or TNF.

Acute Kidney Injury↗
PubMed1998

Zinc deficiency aggravates tubulointerstitial nephropathy caused by ureteral obstruction.

Ureteral ligation causes tubulointerstitial nephropathy characterized by the tubular dilatation, the interstitial expansion, and a leukocyte infiltration into the tubulointerstitium. The present study was designed to explore whether zinc (Zn) deficiency affects the development of unilateral ureteral obstruction (UUO)-induced tubulointerstitial nephropathy. Compared to rats fed a standard diet, rats fed a Zn-deficient diet exhibited a greater influx of leukocytes into the tubulointerstitium of the cortex of the obstructed kidney 3 d following UUO. Furthermore, rats fed a Zn-deficient diet showed a slight invasion of leukocytes into the tubulointerstitium of the cortex of the contralateral nonobstructed kidney (CLK), although there was no infiltration of leukocytes into the CLK of rats fed a standard diet. These histological changes, however, were ameliorated by administration of enalapril, an angiotensin (ANG) I-converting enzyme inhibitor. Thus, it is suggested that Zn deficiency aggravates UUO-induced tubulointerstitial nephropathy via an increase in the action of ANG II.

Animals↗
PubMed1998

Effects of dietary protein on eicosanoid production in rat renal tubules.

The effects of dietary protein on the in vitro production of prostaglandin (PG) E2, 6-keto PGF1alpha, and thromboxane B2 (TxB2) were examined in cortical and medullary tubules from rats fed a low (6% casein) or a high (40% casein) protein diet for approximately 8 weeks. PGE2 was a major eicosanoid produced by rat renal tubules (PGE2 > TxB2 > 6-keto PGF1alpha). Medullary tubules produced significantly greater amounts of PGE2, 6-keto PGF1alpha, and TxB2 than cortical tubules. The activity of phospholipase (PL) A2 and PLC and the levels of cyclooxygenase (COX) were significantly greater in medullary tubules than in cortical tubules. The production of eicosanoids may be increased in medullary versus cortical tubules via the greater activity of these enzymes involved in eicosanoid formation. Although there were no substantial differences in the production of PGE2, 6-keto PGF1alpha, and TxB2 between cortical tubules from rats fed a low- or a high-protein diet, significant increases in the synthesis of the three eicosanoids were observed in medullary tubules from rats fed a high- versus a low-protein diet. The activity of membrane-bound PLA2 and PLC and the levels of COX were not also substantially different between cortical tubules from rats fed a low- or a high-protein diet. However, medullary tubules had significantly greater activity of membrane-associated PLA2 and COX in rats fed a high-protein diet than in those fed a low-protein diet. The activity of PLC was comparable in medullary tubules from rats fed a low- or a high-protein diet. We conclude that a high protein intake selectively enhances eicosanoid production in rat medullary tubules probably via activation of the PLA2-COX pathway.

Animals↗
PubMed1998

Inducible nitric oxide synthase expression in mercury chloride-induced acute tubular necrosis.

To examine the mechanisms involved in the progression of mercury chloride (HgCl2)-induced acute tubular necrosis (ATN), we investigated the histopathological changes and the expression of inducible nitric oxide synthase (iNOS) mRNA and protein in renal cortices of rats at 20 hours after exposure to HgCl2. The expression of iNOS mRNA was significantly augmented in renal cortices of rats with HgCl2-induced acute renal failure (ARF). Likewise, the induction of iNOS protein was observed in damaged proximal tubule epithelial cells of rats with HgCl2-induced ARF. Pretreatment of rats with iNOS inhibitor aminoguanidine, however, suppressed the development of proximal tubule epithelial cell injury and prevented an increase in blood urea nitrogen and serum creatinine as well as resulting in a marked fall in iNOS mRNA and protein in rats with HgCl2-induced ARF. These observations indicate that the induction of iNOS may play a role in the progression of HgCl2-induced ATN through the exacerbation of proximal tubule epithelial cell damage.

Acute Kidney Injury↗
PubMed1997

Quantitative evaluation of blood flow distribution to exercising and resting skeletal muscles in patients with cardiac dysfunction using whole-body thallium-201 scintigraphy.

BACKGROUND AND HYPOTHESIS: Decreased blood flow to working muscles makes an important contribution to exercise intolerance in patients with chronic heart failure. This study was undertaken to examine whether maldistribution of skeletal muscle blood flow is closely related to exercise intolerance in patients with cardiac dysfunction. METHODS: Whole-body thallium scintigraphy was performed during one-leg exercise in 11 patients with left ventricular (LV) dysfunction (LV ejection fraction < 45%). Blood flow distribution to the exercising and resting legs was quantified by expressing regional thallium counts as a percentage of the whole-body counts at rest, at the level of anaerobic threshold, and at peak exercise. RESULTS: At anaerobic threshold, the thallium activity of exercising muscle increased from 4.2 +/- 0.7 to 14.0 +/- 2.5% (p < 0.05) in the thigh and from 1.7 +/- 0.3 to 4.1 +/- 0.9% (p < 0.05) in the calf, compared with the resting value. Consequently, the ratio of thallium activity between exercising and resting legs increased to 2.7 +/- 0.7 (p < 0.05) in the thigh and to 2.3 +/- 0.7 (p < 0.05) in the calf. When plotted as a function of anaerobic threshold, thallium activity of the exercising thigh (r = 0.78, p < 0.05) and the thallium ratio between exercising and resting thigh (r = 0.69, p < 0.05) declined with the reduction of exercise tolerance. These correlations were not observed in calves. CONCLUSION: Whole-body thallium scintigraphy demonstrated a maldistribution of leg blood flow in patients with reduced aerobic exercise capacity, suggesting that this abnormality could play an important role in exercising intolerance in these patients.

Adult↗
PubMed1997

Lithium deficiency reduces thymus weight and alters differential blood count in rats.

Effects of lithium (Li) deficiency and/or immobilization stress on the thymus weight and differential blood count of rats were studied. The thymus weight of the rats fed a low Li diet were lighter than those of rats fed a Li supplemented diet, whether the rats were exposed to stress or not. Of the rats not exposed to stress, those in the low Li diet group showed a significant decrease in the ratios of neutrophils and T helper lymphocytes. However, there was an increase in the total number of lymphocytes in the low Li dietary group. It was shown that Li deficiency altered the responses to stress in rats.

Animals↗
PubMed1997

Ureteral obstruction enhances eicosanoid production in cortical and medullary tubules of rat kidneys.

We examined prostaglandin (PG) E2, 6-keto PGF1alpha, and thromboxane B2 (TxB2) production in cortical and medullary tubules from sham-operated control (SOC) rats and rats with bilateral ureteral obstruction (BUO) of 24 h duration. In SOC rats medullary tubules produced significantly greater amounts of the three eicosanoids than cortical tubules. Again, the production of PGE2, 6-keto PGF1alpha, and TxB2 by cortical and medullary tubules was significantly greater in BUO rats than in SOC rats. To elucidate the mechanisms involved, we examined the activity of phospholipase A2 (PLA2) reactive against phosphatidylcholine or phosphatidylethanolamine (PE), the activity of phospholipase C (PLC), and the levels of cyclooxygenase (COX) in cortical and medullary tubules from SOC and BUO rats. In SOC rats the activity of phosphatidylcholine-PLA2 and PE-PLA2, the activity of PLC, and the mass of COX were significantly greater in medullary tubules than in cortical tubules. On the other hand, the activity of PLC in membranes of cortical tubules and the activity of PE-PLA2 and PLC in membranes of medullary tubules, which were in active location, were significantly greater in BUO rats than in SOC rats. COX levels were also significantly greater in cortical and medullary tubules of BUO rats than in those of SOC rats. Thus, we indicate that medullary tubules from SOC rats have greater production of eicosanoids through increased activity of the PLA2 and PLC-COX pathway than cortical tubules from the same group of rats. Again, in rats with BUO, the tubular eicosanoid production may be enhanced via activation of the PLC-COX pathway in cortical tubules or through activation of the PE-PLA2 and PLC-COX pathway in medullary tubules. The enhanced production of tubular eicosanoids observed in rats with BUO may affect tubular function, particularly sodium and water reabsorption.

6-Ketoprostaglandin F1 alpha↗
PubMed1997

Rapid incorporation of docosahexaenoic acid from dietary sources into brain microsomal, synaptosomal and mitochondrial membranes in adult mice.

This study examined the incorporation of docosahexaenoic acid (DHA) from several dietary sources into the brain tissue and intracellular organelles in mice which had been fed a 5% palm oil (low n-3 fatty acid level) diet for 8 or 11 weeks. The percentages of DHA in the tissues of mice fed 5% representative oils for 30 days or 5% purified n-3 fatty acid diets for 6 days were analyzed using gas chromatography. The percentage of DHA in the brain was ranked in the following order: the salmon oil diet group > the sardine oil diet group > > the perilla oil diet group > > the lard and palm oil diet groups for the 30 day feeding trial; and the DHA diet group > > the eicosapentaenoic acid and alpha-linolenic acid diet groups for the 6 day feeding trial. The percentage of arachidonic acid showed a more dramatic decrease than that of docosapentaenoic acid. These results reflected the plasma fatty acid concentrations, but were not as pronounced as the changes observed in the plasma. The majority of the DHA incorporated into the brain was recovered in microsomal, synaptosomal, and mitochondrial fractions separated by density gradient centrifugation. These membrane fractions took up DHA within several days. These results suggest that the intake of DHA itself increases the DHA level of brain membranes more rapidly than intake of the precursors in animals fed a low n-3 fatty acid level diet.

Animals↗
PubMed1996

Association between family history and gastric carcinoma among young adults.

The relationship between family history of gastric carcinoma and gastric carcinoma in Japanese under 40 years of age was analyzed. The subjects were 108 gastric carcinoma patients (86% were diffuse type) at 9 hospitals in the Kanto area of Japan. Firstly, incidence of gastric carcinoma among the parents of the subjects were compared with that in the general population. Observed/expected (O/E) ratios (P-value) were 1.8 (0.06) for all subjects, 1.3 (0.62) for male subjects, 2.1 (0.04) for female subjects, 0.5 (0.41) for early carcinoma, 2.6 (P<0.01) for advanced carcinoma, 2.3 (0.22) for intestinal-type carcinoma and 1.7 (0.13) for diffuse-type carcinoma. Association between gastric carcinoma and parents' history of gastric carcinoma was strong among women and regarding advanced carcinoma, and the difference in O/E ratios between early and advanced carcinoma was remarkable. Secondly, factors related to advanced-stage gastric carcinoma were analyzed. Histological type (diffuse and intestinal types) was not related, but family history of gastric carcinoma among parents and grandparents was related to advanced stage, and the relationship was independent of other factors. The odds ratio (95% confidence interval) was 3.3 (1.1-9.9). Family history may be related to stage of gastric carcinoma through its relationship to the manner or speed of the tumor's progression. We hypothesis that some genetic factor exists which is involved both in progression from early to advanced stage and in occurrence of gastric carcinoma.

Adolescent↗
PubMed1996

[Trace elements and their physiological roles].

Of 95 naturally occurring elements of the periodic table, no less than 25 perform essential functions in the human body. Eight of these, namely zinc, copper, selenium, cobalt, chromium, molybdenum, manganese and iodine, are required in small amounts and each comprises less than 0.01% of the body weight and termed essential trace elements. In the body, they function in a similar way; most of them are at the active site of enzymes or of physiologically active substances of the body. Dietary deficiency causes a variety of clinical features, which are consistent with the decreased activity of these active substances. Recent topics are the resemblance of these features and their background pathophysiology with those of aging.

Aging↗
PubMed1996

[Intracavitary bacillus Calmette-Guerin therapy for upper tract transitional cell carcinoma].

Four patients with upper urinary tract transitional cell carcinoma were treated with bacillus Calmette-Guerin (BCG) via a percutaneous nephrostomy tube or a retrograde ureteral catheter. A 68-year-old female and an 80-year-old male had carcinoma in situ (CIS) in the left upper urinary tract (cases 1 and 2). A man aged 47 had CIS in the left upper urinary tract, bladder, and prostatic urethra (case 3). CIS in the left upper urinary tract was identified in a woman aged 63 with chronic renal insufficiency (case 4). Two patients (cases 1 and 2) responded to this therapy. In the other two patients nephrectomy was performed due to residual tumor. There were extensive tuberculous granulomas in the kidneys. In one resected kidney (case 4) carcinoma had invaded the renal parenchyma. The reviewed literature showed that BCG perfusion therapy was effective in 71% (27 of 38 renal units) for the upper urinary tract tumors and that there were 5 cases of severe complication, including sepsis in 2, high fever in 2, and ureteral stricture in 1. Based on the fact that the kidney receives a profuse blood supply and that the renal pelvis and ureter have a thin wall, careful management is mandatory to prevent severe adverse effects and insidious tumor progression.

Aged↗
PubMed1996

[Estimation of safety and toxicity of rho-nitrophenol sodium with a physiologically based pharmacokinetics model].

The safety and toxicity of chemicals given first to animals and finally to humans are generally estimated with a method of safe coefficient, which lacks scientific ground. To change the traditional method, we designed a physiologically based pharmacokinetics model (PBPK) for the estimation of safety and toxicity of chemicals. For example, rho-nitrophenol sodium (PNP-Na) was used. The PNP-Na pharmacokinetics in bodies of rat as well as humans were studied, and possibilities of making use of the model in the estimation of safety and toxicity of chemicals were also discussed.

Animals↗
PubMed1995

Loading sequence plays an important role in enhanced load sensitivity of left ventricular relaxation in conscious dogs with tachycardia-induced cardiomyopathy.

BACKGROUND: Left ventricular relaxation rate in the failing heart depends more on the systolic load than in the normal heart. To elucidate the mechanisms for the enhanced load sensitivity of left ventricular relaxation in heart failure, we examined the relative contributions of changes in end-systolic volume and loading sequence to the left ventricular relaxation rate. METHODS AND RESULTS: In seven conscious dogs, the time constant (Td) of left ventricular pressure decay, end-systolic volume, systolic circumferential force, and time to peak force during caval occlusion were compared before and after development of tachycardia-induced heart failure. Rapid ventricular pacing decreased the slope of the end-systolic pressure-volume relation from 4.5 to 2.8 mm Hg/mL (P < .01) and prolonged Td from 33 to 49 ms (P < .01). In normal conditions, caval occlusion reduced end-systolic force (-580 g, P < .01) and end-systolic volume (-7 mL, P < .01) but did not change Td or time to peak force. In heart failure, however, caval occlusion shortened Td (-11 ms, P < .01), with a concomitant decrease in the time to peak force (-30 ms, P < .01), while end-systolic volume and force declined slightly. Consequently, for a comparable reduction in end-systolic force, Td decreased more in heart failure than in normal hearts, suggesting enhanced load sensitivity. Moreover, changes in Td correlated well with those in the time to peak force (r = .79, P < .01) but not with those in end-systolic volume. CONCLUSIONS: Loading sequence rather than elastic recoil seems to play the predominant role in the enhanced load sensitivity of left ventricular relaxation in heart failure.

Animals↗
PubMed1995

Serum anti-Helicobacter pylori antibody and gastric carcinoma among young adults. Research Group on Prevention of Gastric Carcinoma among Young Adults.

BACKGROUND: Helicobacter pylori is recognized as one of the possible causes of gastric carcinoma. There have been few studies on the relationship between H. pylori and gastric carcinoma in patients younger than 40 years. METHODS: Data and sera were collected from the cases (105 hospitalized patients younger than 40 years with gastric carcinoma from 9 hospitals in the Kanto-Shin-Etsu Area in Japan) and controls (102 hospitalized control subjects and 101 screening control subjects) whose sex and age (within 4 years) were matched. The serum anti-H. pylori immunoglobulin G antibody was measured, and the odds ratio (OR) for the association between seropositivity and gastric carcinoma was calculated. RESULTS: The OR (95% confidence interval) was 13.3 (5.3-35.6). For women, the OR was 32.8, whereas for men it was 6.8. The OR for patients with early gastric carcinoma was 20.8, and for patients with advanced disease, it was 10.8. The OR for intestinal-type carcinoma was 18.0, and for diffuse-type carcinoma, it was 12.8. The OR for proximal carcinoma was 11.3, and for distal carcinoma it was 14.8. CONCLUSION: The OR for these young subjects was considerably larger than that for the older subjects in previously published studies. Among those younger than 40 years of age, early stage carcinoma has a stronger association with H. pylori than advanced carcinoma, and intestinal- and diffuse-type carcinomas have an association with H. pylori.

Adolescent↗
PubMed1995

Interaction of atrial natriuretic peptide with its receptors in bovine lung membranes.

In bovine lung membranes, atrial natriuretic peptide (ANP) showed temperature-dependent binding to guanylate cyclase-natriuretic peptide receptor (NPR-GC). Photoaffinity labeling of the receptors with 4-azidobenzoyl (AZB)-125I-ANP and competitive binding studies with 125I-ANP, ANP, and atriopeptin I (API) revealed that NPR-GC was detected as the predominant ANP-binding protein at 0 degrees C, whereas at 37 degrees C natriuretic peptide clearance receptor (NPR-C) was detected as the predominant protein. The ratio of NPR-GC and NPR-C was 89:11 at 0 degrees C for 40 min, respectively, whereas 6:94 at 37 degrees C. AZB-125I-ANP bound to NPR-GC dissociated from the binding site within 5 min at 37 degrees C but not at 0 degrees C, whereas ANP bound to NPR-C did not dissociate from the binding site at 0 and 37 degrees C. The dissociated AZB-125I-ANP rapidly rebound to NPR-GC at 37 degrees C but not to NPR-C, and the dissociated NPR-GC was capable of binding. Some AZB-125I-ANP was hydrolyzed by a membrane-bound proteinase(s). Phosphoramidon inhibited the hydrolysis of AZB-125I-ANP. Thus, the dissociated AZB-125I-ANP rebound to NPR-GC and NPR-C. These results suggest that usually intact ANP repeatedly binds to NPR-GC until hydrolysis. Furthermore, the majority of ANP bind to NPR-GC before binding to NPR-C under physiological temperature.

Affinity Labels↗
PubMed1995

The association of smoking and drinking habits with serum pepsinogens.

BACKGROUND: The influence of smoking on serum pepsinogen I has been assessed. However, still to be assessed are the influences of smoking on pepsinogen II and drinking on serum pepsinogens. METHODS: Data were collected from 13,381 employees by questionnaire and serum tests. Multiple regression analyses were done with logarithms of serum pepsinogen I (LPI), pepsinogen II (LPII) or pepsinogen I/II ratio (LI/II) as a criterion variable and as categorized explanatory variables, sex, age, subjective symptoms in the stomach, past history of peptic ulcer, current smoking dose, past smoking amount, drinking habit and current drinking dose. RESULTS: Current smoking dose showed dose-dependent positive associations with LPI and LI/II: Past smoking amount yielded weakly dose-dependent negative associations with LPI and LI/II: Current drinking dose showed dose-dependent negative associations with LPI and LPII. CONCLUSION: Current smoking elevates pepsinogen I and the I/II ratio, and it may be necessary to consider the effect of smoking when pepsinogens are used as markers for gastric cancer. Drinking reduced pepsinogen I and II, but the effect was not so large.

Adult↗