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Biomedical subjects

T Hayakawa

Publications and source records attributed to T Hayakawa.

At least 127 records · Page 7Linked to original sources
PubMed2001

Altered expression of prostacyclin synthase in a subset of the thick ascending limb cells and mesangial cells in 5/6-nephrectomized rats.

The aim of this study was to evaluate the possible role of prostacyclin (PGl2) in the onset and development of hypertension and chronic renal failure in 5/6-nephrectomized rats (5/6NX). We measured the systolic blood pressure, 24-h urinary excretion levels of 6-keto-PGF1alpha, which was a stable metabolite of PGI2, and levels of PGI2 synthase (PCS) mRNA in the kidneys. Immunostaining for PCS in the kidneys was also evaluated. Systolic blood pressure was higher in 5/6NX than in sham-operated rats. The 24-h urinary excretion levels of 6-keto-PGF1alpha in 5/6NX at 1 week postsurgery were lower than in sham-operated rats. In renal morphology, tubulointerstitial injury was observed at 2 weeks postsurgery, and glomerulosclerosis at 4 weeks. Levels of PCS mRNA in 5/6NX decreased significantly at 1 and 2 weeks postsurgery compared with those in sham-operated rats, but at 8 weeks these levels showed a tendency to increase. Immunostaining for PCS was positive in a subset of the cortical thick ascending limb of Henle's loop cells, including macula densa in both groups. Moreover, in 5/6NX at 8 weeks postsurgery, mesangial cells also stained positive for PCS. In conclusion, our findings suggest that PCS might play an important role in mitigating glomerular hemodynamic changes associated with reduction of renal mass.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Tissue inhibitor of metalloproteinases 1 and 2 directly stimulate the bone-resorbing activity of isolated mature osteoclasts.

Tissue inhibitor metalloproteinases 1 (TIMP-1) and 2 have been reported to inhibit bone resorption. However, here, we report the direct action of both TIMP-1 and TIMP-2 on isolated rabbit mature osteoclasts to stimulate their bone-resorbing activity at significantly lower concentrations (approximately ng/ml) than those (approximately microg/ml) required for the inhibition of bone resorption. The cell population used in this study consisted of a mature osteoclast population with >95% purity. TIMP-1 (approximately 50 ng/ml) and TIMP-2 (approximately 8-10 ng/ml) increased the pit area excavated by the isolated mature osteoclasts. The stimulatory effects of TIMPs were abolished by simultaneous addition of anti-TIMP antibodies. At higher concentrations, the stimulation of bone resorption decreased reversely to the control level. The magnitude of the stimulatory effect of TIMP-2 was more than that of TIMP-1. Metalloproteinase inhibitors such as BE16627B and R94138 could not replace TIMPs with respect to the bone-resorbing activity, suggesting that the osteoclast-stimulating activity of TIMPs was independent of the inhibitory activity on matrix metalloproteinases (MMPs). TIMPs stimulated tyrosine phosphorylation of cellular proteins in the isolated mature osteoclasts. Both herbimycin A, an inhibitor of tyrosine kinases, and PD98059 and U0126, inhibitors of mitogen-activated protein kinase (MAPK), completely blocked the TIMP-induced stimulation of osteoclastic bone-resorbing activity. On the plasma membrane of osteoclasts, some TIMP-2-binding proteins were detected by a cross-linking experiment. These findings show that TIMPs directly stimulate the bone-resorbing activity of isolated mature osteoclasts at their physiological concentrations and that the stimulatory action of TIMPs is likely to be independent of their activities as inhibitors of MMPs.

Acetamides↗
PubMed2001

Distribution and properties of rat intestinal alkaline phosphatase isoenzymes.

The ALP activities and properties of rat intestine cut into 20 segments were examined, and we were able to demonstrate that the ALP activity of upper intestine is high compared to that of lower intestine. This result coincided with those of other reports. However, we newly clarified that there is an ALP isoenzyme found in the lower intestine which can be inhibited by L-homoarginine. The molecular weight of the ALP isoenzyme was 136 kDa. In addition, it was clarified that there are several isoenzymes from upper to lower intestine. This study demonstrates that there exist isoenzymes, which are inhibited by L-HArg, in the intestine which are similar to the isoenzymes in the liver, bone and kidney.

Alkaline Phosphatase↗
PubMed2001

Insulinoma with subsequent association of Zollinger-Ellison syndrome.

We report a patient with insulinoma associated with Zollinger-Ellison syndrome. A 67-year-old woman was first admitted to our hospital for an abdominal mass. Abdominal computed tomography (CT) revealed a large pancreatic tumor, which was then diagnosed as an unresectable pancreatic adenocarcinoma. At the age of 71, she presented symptoms of hypoglycemia. Fasting blood glucose was 21 mg/dl and plasma immunoreactive insulin level was 846 microU/ ml. Plasma gastrin, glucagon, vasoactive intestinal polypeptide and somatostatin levels were all normal. At the age of 73, hypoglycemic attacks occurred more frequently and she was admitted to our hospital. Abdominal CT scan showed multiple liver metastases. Chemotherapy with 5-fluorouracil and doxorubicin was performed. Three months later, she had an emergency laparotomy because of a perforated duodenal ulcer. Plasma gastrin level was 1,960 pg/ml at that time. Gastric hypersecretion was well controlled with a proton pump inhibitor (lansoprazole) but she died of widespread cancer dissemination 8 years after her first admission. On autopsy, histologic examination revealed a mixed acinar-endocrine carcinoma of the pancreas. Immunohistochemical stains were positive for insulin, gastrin, and alpha1-antitrypsin.

Aged↗
PubMed2001

Effect of vitamin B6 deficiency on the synthesis and accumulation of S-adenosylhomocysteine and S-adenosylmethionine in rat tissues.

The effect of vitamin B6-deficiency on the B6-vitamer concentrations, level of S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) were studied in rat tissues. The plasma pyridoxal 5'-phosphate (PLP) and, pyridoxal (PL) levels were lower in the B6-deficient group compared to the control group. After 5 weeks of feeding the experimental diets, tissue PLP, pyridoxamine 5'-phosphate (PMP) and PL concentrations were significantly lower in the B6-deficient group compared to the control and the pair-fed control groups. Thymus PLP and PL levels were lower in the B6-deficient group. The concentration of SAM in the B6-deficient group decreased to approximately 50% and 25% in liver and thymus, respectively. However SAH concentration was 3.5 and 2 fold higher compared to the control and the pair-fed control groups. Thus, the ratio of SAM/SAH was significantly decreased in the B6-deficient group compared to the control or the pair fed-control group. In addition, the S-adenosylhomocysteine hydrolase (EC 3.3.1.1) activity increased by 45% and 15% in liver and thymus, respectively, in the B6-deficient group compared to the pair-fed control and the control groups. However, the activity of L-methionine S-adenosyltransferase (EC 2.5.1.6) was also unaffected. Concentrations of SAH and SAM, SAM/SAH ratio and activities of S-adenosylhomocysteine hydrolase and L-methionine S-adenosyltrasferase in rat brain were not affected by the B6-deficiency. We infer that the alteration of B6 metabolism, especially the reduction of PLP contents in liver and thymus, caused by the B6 deficiency, resulted in accumulation of SAH as well as reduction of SAM and the SAM/SAH ratio. The reduction of the SAM/SAH ratio was due to a block in the catabolism of methionine via the trans-sulfuration pathway. These may lead to inhibition of transmethylation reaction of DNA, RNA and protein, the synthesis and function of thymic lymphocyte and result in damage to tissues.

Animals↗
PubMed2001

Conformational and quantum analysis of dental adhesive carboxylic acid and carboxylic acid anhydride monomers.

The conformational and quantum analyses of dental adhesive carboxylic acid and carboxylic acid anhydride monomers were preformed. Conformational analyses were carried out by a molecular mechanics calculation. 4-META and 4-AETA showed more compact conformation than 4-MET. Quantum analyses were performed by semi-empirical molecular orbital calculation. 4-MET had a higher dipole moment, polarizability, and HOMO and LUMO energy than 4-META and 4-AETA. The bond lengths and bond orders of the carbonyl groups of the trimellitic acid moiety of 4-MET were different from those of carbonyl groups of the trimellitate anhydride moieties of 4-META and 4-AETA. Oxygen of the methacryloyl or acryloyl groups showed the highest electron densities among the oxygen atoms for all monomers. The superdelocalizabilities of oxygen atoms of the trimellitic acid moiety of 4-MET were greater than that of oxygen of the methacryloyl group. A small change in the bond length of the Ca-O bond showed a large difference in the steric energies of 4-MET/Ca salt.

Adhesives↗
PubMed2001

[Age-related changes in lower urinary tract symptoms and urodynamic parameters in patients with benign prostatic hyperplasia treated by transurethral resection of the prostate].

PURPOSE: To characterize age-related clinical and urodynamic features of patients with benign prostatic hyperplasia (BPH) treated by transurethral resection of the prostate (TUR-P). MATERIALS AND METHODS: Between July 1994 and March 2000, a total number of 451 patients underwent TUR-P in Nagoya Urology Hospital. Out of these 451 patients, 15 (3.3%) were diagnosed as having an incidental prostate cancer on pathological examination of resected prostate tissue. The remaining 436 patients (48-92 years, 69.8 +/- 7.4 years), in whom 196 (45.0%), 208 (47.7%) and 32 (7.3%) were < or = 69, 70-79 and > or = 80 years, respectively, were subjects for the present study. Their clinical features before and after TUR-P and the therapeutic effects of the treatment were evaluated in terms of aging. RESULTS: Among preoperative variables evaluated, IPSS in patients aged < or = 69 years was significantly higher than in those aged 70-79 years (p < 0.05). The QOL index was significantly higher in patients aged > or = 80 years than in those aged 70-79 years (p < 0.05). The maximum bladder capacity decreased with age from 276 ml in patients aged < or = 69 years to 211 ml in those aged > or = 80 years. Postoperatively, both maximum and mean flow rates were significantly lower in patients aged 70-79 and > or = 80 years compared to those aged < or = 69 years. There was, however, no significant age-related difference in IPSS and QOL index. The assessment of treatment effects at 3 months following TUR-P revealed that the outcomes in function as evaluated by uroflowmetry, anatomy and ultrasonic measurement of prostate volume were significantly worse in patients aged > or = 80 years compared to those in younger patients. However, there was no significant age-related difference in outcomes in subjective symptoms and QOL. CONCLUSIONS: TUR-P could be performed safely even in patients aged > or = 80 years. It is concluded that although postoperative urinary condition might be worse in older patients, they would nevertheless be satisfied with the results of TUR-P in the same way as less aged patients. As long as subjects are selected properly based on the correct diagnosis of BPH and a sufficient evaluation of operation risks, TUR-P can be expected to be performed safely and be followed by satisfaction with the treatment effects.

Aged↗
PubMed2001

Selective dopamine receptor stimulation differentially affects [3H]arachidonic acid incorporation, a surrogate marker for phospholipase A2-mediated neurotransmitter signal transduction, in a rodent model of Parkinson's disease.

Our laboratory has developed a technique whereby radiolabeled long-chain fatty acids are injected intravenously in awake rats to pulse-label brain lipids, mainly phospholipids, to measure regional brain lipid metabolism by autoradiography. The brain incorporation of [(3)H]arachidonic acid ([(3)H]AA), a polyunsaturated fatty acid, may reflect regional changes in neurotransmitter signal transduction using phospholipase A(2). Using this radiotracer, we examined the brain dopamine system in rats with a chronic unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta, a model of Parkinson's disease. Four weeks after lesioning, rats received either vehicle; SKF38393 or quinpirole (LY-171,555) (D(1)- and D(2)-dopamine-like agonists, respectively); or (+)-butaclamol (D(1)/D(2) antagonist) followed by either vehicle, SKF38393, or quinpirole. They then were infused with [(3)H]AA and their brains processed for autoradiography. SKF38393 increased [(3)H]AA incorporation into the lesioned side compared with the intact side in the caudate putamen, somatosensory and motor cortices and subthalamic nucleus, but decreased incorporation in the ipsilateral ventrolateral thalamus. Quinpirole increased ipsilateral [(3)H]AA incorporation in the caudate putamen and somatosensory and motor cortices, and decreased it in the ventrolateral thalamus. (+)-Butaclamol blocked this effect. The data suggest up-regulation in basal ganglia and cortical dopamine circuits mediated by phospholipase A(2) ipsilateral to the substantia nigra lesion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

[A case of infravesical obstruction caused by prostatic stones as diagnosed by transrectal ultrasonography at voiding].

A 69-year-old patient, who had been treated using alpha 1-blocker for benign prostatic hyperplasia (BPH) at another clinic, visited our clinic due to persistent difficulty in urination. Total International Prostate Symptom Score (IPSS) was 32 points and quality of life (QOL) index was 5. Uroflowmetry demonstrated maximum urinary flow rate and average urinary flow rate to be 9.2 ml/sec and 5.1 ml/sec, respectively, with 3 ml of residual urine volume. Transrectal ultrasonography (TRUS) revealed prostatic stones but not BPH. Retrograde urethrography demonstrated nothing abnormal other than prostatic stones. TRUS at voiding phase using linear probe (voiding TRUS) revealed poor opening of the urethra surrounded by prostatic stones. As a result, the cause of urinary disturbance was diagnosed to be due to urethral obstruction caused by prostatic stones, and transurethral resection of prostatic tissue with stones was performed. Postoperatively, IPSS decreased to 10 points and QOL index to 2. Maximum urinary flow rate also improved to 18.1 ml/sec and mean urinary flow to 8.4 ml/sec. Thus, voiding TRUS is likely the best urodynamic test for clinical use in determining the etiology of obstruction at posterior urethra.

Aged↗
PubMed2001

The apolipoprotein E genotype influences the risk for vasospastic angina.

It has been suggested that people with the epsilon4 allele of the apolipoprotein E (apoE) polymorphism and the deletion (D) allele of the insertion (I/D) polymorphism of angiotensin-converting enzymes, are at a greater risk for coronary artery disease. However, only a few studies have examined the relationships between vasospastic angina (VSA) and genotype, especially with the apoE polymorphism. In the present study, 76 patients with VSA without significant fixed coronary artery stenosis, 149 patients with ischemic heart disease (IHD) who had 75% or more luminal diameter narrowing and 213 healthy subjects were enrolled. The odds ratio for VSA of the epsilon4 allele carriers relative to the epsilon3/3 allele subjects compared with subjects with IHD and control subjects combined was 0.44 (95% CI 0.21 to 0.93, P=0.021), and that compared with control subjects alone was 0.36 (95% CI 0.17 to 0.78, P=0.005), implying that the presence of the epsilon4 allele indicates resistance to the development of VSA. In contrast, people with the epsilon2 allele showed a tendency to develop VSA more frequently than did patients with IHD (P=0.009), although the frequency of the epsilon2 allele did not differ between patients with VSA and control subjects. On the other hand, no recessive and dominant effects of the D alleles on VSA were found. These findings suggest that the risk of the occurrence of VSA may be reduced by the epsilon4 allele and increased by the epsilon2 allele. The ApoE polymorphism may be associated with IHD and VSA, probably due to the modulation of lipid metabolism.

Adult↗
PubMed2001

[A case of advanced gastric cancer that was resectable after asctic fluid had disappeared following administration of TS-1].

A 60-year-old man who had suffered from epigastic pain and general malaise from November 1999 was admitted to our hospital due to Borrmann type 3 gastric cancer with ascites on December 7, 1999. We considered a radical B operation impossible, and placed the patient on neoadjuvant TS-1 chemotherapy consisting of 1 M tegafur, 0.4 M gimestat, and 1 M otastat potassium. There were no side effects other than Grade 1 nausea and mild loss of appetite throughout the chemotherapy. After 8 weeks of administration, the primary lesion was reduced in size, and ascitic fluid had disappeared on abdominal computed tomography images. Therefore, a total gastrectomy with splenectomy and D2 lymph node dissection was performed on March 31, 2000. This was a radical B operation that was not possible earlier. The pathological diagnosis was tub2, SE, N1, CY0, H0, P0, M0, INF gamma, ly1, v1, PM (-), DM (-) and the antitumor efficacy of TS-1 was Grade 2 histologically. The patient remains alive and in good condition with no relapse of the gastric cancer 8 months after surgery.

Antimetabolites, Antineoplastic↗
PubMed2001

Calcineurin inhibitor attenuates cardiac hypertrophy due to energy metabolic disorder.

BACKGROUND: Several studies have shown that calcineurin may play a critical role in the signalling of cardiac hypertrophy in various experimental models. OBJECTIVE: To elucidate whether calcineurin is involved in cardiac hypertrophy due to energy metabolic disorder by using the juvenile visceral steatosis (JVS) mouse, which is a murine model of systemic carnitine deficiency. METHODS AND RESULTS: Cardiac hypertrophy in JVS mice (C3H strain) progresses gradually after birth and is present until eight weeks of age. In this study, calcineurin activity in JVS mice increased significantly at four weeks of age (the developing stage of cardiac hypertrophy) compared with age-matched control mice. Treatment with calcineurin inhibitor FK506 (0.5 or 1.0 mg/kg/day) from the age of four to eight weeks attenuated cardiac hypertrophy without beneficially affecting cardiac function. Gene expression, accompanied by cardiac hypertrophy, was also suppressed by the FK506 treatment. CONCLUSIONS: The activation of calcineurin is involved in the development of cardiac hypertrophy in the JVS mouse, and calcineurin inhibition may be useful for reducing cardiac hypertrophy.

Animals↗
PubMed2001

[Estimated relative and absolute risk for cardiovascular disease according to alcohol consumption increase in Japanese general population].

To calculate the estimated relative and absolute risks for cardiovascular diseases according to alcohol consumption increase, we performed a cross-sectional study of men aged 40-79 years using the data from the National Survey of Circulatory Disorders 1990 in Japan. First, we investigated the association between alcohol intake and two types of biochemical variables: serum lipids and blood pressure, by using analysis of variance. Then, concerning the subjects aged 40-59 years, linear regression analyses between alcohol intake and these biochemical markers were done to calculate regression coefficients adjusted for confounding factors. Finally, we substituted these regression coefficients for previously reported regression coefficients in Cox proportional hazard models to calculate relative and absolute risks for coronary heart disease and stroke. Alcohol intake positively correlated to systolic and diastolic blood pressure (SBP and DBP) and high-density lipoprotein cholesterol (HDLC). However, there was no relation between alcohol intake and serum total cholesterol. Linear regression coefficients of SBP, DBP and HDLC were 2.25, 1.43, 2.70, respectively. We used two proportional hazard regression formulas of Japanese population: one for coronary disease (Circulation 89, 2533-39) and the other for stroke (NIPPON DATA80, a 14-year cohort study of randomly selected Japanese). The estimated relative risks of coronary heart disease and stroke were 0.89 and 1.06 for 1 "go" (23 g of ethanol) increment of alcohol intake. The results indicate that the mortality rates shift from 0.44 to 0.39 per 1,000 person-years for coronary heart disease and from 0.76 to 0.81 per 1,000 person-years for stroke in the representative Japanese population aged 40-59 years. The absolute risk of cardiovascular disease may be unchanged if we assume 23 g increment of ethanol intake in Japan because the risk reduction in coronary heart disease was nearly equal to the risk increment in stroke.

Adult↗