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Biomedical subjects

M Matsuo

Publications and source records attributed to M Matsuo.

At least 109 records · Page 6Linked to original sources
PubMed2000

(9-[4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido [1,2-a] pyrimidin-4-one), AS-35, inhibits leukotriene synthesis.

AS-35, (9-[4-acetyl-3-hydroxy-2-n-propylphenoxy) methyl]-3-(1H-tetrazol-5-yl)-4H-pyrido[1, 2-a] pyrimidin-4-one), was developed as a leukotriene (LT) receptor antagonist, which also inhibited IgE-mediated release of leukotrienes (LTs). We have investigated the action of AS-35 on the enzyme activities which are involved in the synthesis of LTC(4) and LTB(4) (LT-synthesizing enzymes); cytosolic phospholipase A(2) (cPLA(2)), 5-lipoxygenase (5-LO), leukotriene (LT)C(4) synthase and LTA(4) hydrolase. AS-35 dose-dependently inhibited IgE- and A23187-stimulated production of LTC(4) by up to 71.5-84.8% and that of LTB(4) by 48.3-49.2% at 2. 5x10(-5) M. The assays for cPLA(2)(-), 5-LO-, LTC(4) synthase- and LTA(4) hydrolase-activities revealed that the inhibition is attributable to suppression of cPLA(2), 5-LO and LTC(4) synthase but not LTA(4) hydrolase. We have also studied the action of AS-35 on the release of beta-hexosaminidase (beta-HEX) as a marker of preformed mediators. AS-35 had only weak inhibitory action on the release of beta-HEX. The results indicate that anti-allergic action of AS-35 is predominantly attributable to its inhibition of LT synthesis by suppressing three consecutive enzymes for LTC(4) synthesis.

Animals↗
PubMed2000

Complete skipping of exon 66 due to novel mutations of the dystrophin gene was identified in two Japanese families of Duchenne muscular dystrophy with severe mental retardation.

Severe mental retardation is a rare complication of Duchenne muscular dystrophy (DMD). Here we report that two DMD cases showing severe mental retardation exhibit the same exon skipping event induced by different intron mutations. In the two Japanese DMD patients studied, the complete sequence of exon 66 of the dystrophin gene was found to be absent from the dystrophin mRNA, creating a premature stop codon in exon 67. Novel point mutations at the consensus sequence of the splice donor site of intron 66 (T9857(+2) to C in one case and G9857(+5) to T in the other case) were found to be the cause of complete exon skipping. Remarkably, severe mental retardation cosegregated with an exon 66-skipping event in their families. Furthermore, pachygyria was disclosed by magnetic resonance imaging (MRI) examination of the brain of one case. Our results suggested that exon 66 skipping should be examined in DMD cases with a severe form of mental retardation.

Adult↗
PubMed2000

Ulinastatin, an elastase inhibitor, inhibits the increased mRNA expression of prostaglandin H2 synthase-type 2 in Kawasaki disease.

Kawasaki disease is an inflammatory disease of unknown cause that causes panvasculitis, including coronary arteritis. Polymorphonucleocytosis in the early stage of the illness suggests the implication of neutrophils in the pathogenesis of the disease. In the acute phase of Kawasaki disease, mRNA expression of prostaglandin H2 synthase (PHS)-2, as determined by reverse transcription-polymerase chain reaction, was markedly enhanced, and thromboxane A2 (TXA2)-synthesizing activity was increased in polymorphonuclear leukocytes (PMNL). This up-regulation of PHS-2 was suppressed by ulinastatin (a neutrophil-elastase inhibitor) treatment. Lipopolysaccharide-induced enhancement of PHS-2 mRNA was also inhibited by therapeutic doses of ulinastatin in vitro by use of PMNL from healthy volunteers. Thus, ulinastatin inhibits arachidonate PHS metabolism by inhibiting new induction of PHS-2 at the mRNA level, which is a novel pharmacologic action of this substance. Ulinastatin treatment is possibly an additional therapeutic approach to Kawasaki disease.

Aspirin↗
PubMed2000

Comparative evaluation of a 5-day Hershberger assay utilizing mature male rats and a pubertal male assay for detection of flutamide's antiandrogenic activity.

A 5-day Hershberger assay utilizing mature male rats and a pubertal male assay were evaluated for the ability to detect antiandrogenic compounds such as flutamide, an androgen receptor antagonist. Six days after the operation, implantation with two silicon capsules containing testosterone (T) (30 mg/capsule) in castrated rats provided the ventral prostate and seminal vesicle weights as well as serum T and luteinizing hormone (LH) levels equivalent to those of the controls (non-castrated, non-implanted rats). Castrated rats implanted with two T-capsules (6 rats/dose) were treated by gavage for 5 days with vehicle (0.5% carboxymethylcellulose) or flutamide (0.15, 0.6, 2.5, or 10 mg/kg/day). Flutamide produced significant decreases in weights of the seminal vesicles and the levator ani plus bulbocavernosus muscles (> or =0.6 mg/kg/day) and ventral prostate (> or =2.5 mg/kg/day), and an increase in serum LH levels (> or =2.5 mg/kg/day), but no changes in serum T levels. When age-matched intact male rats were treated with 10-mg/kg/day flutamide, a significant increase in serum T levels was observed concomitant with a tendency of increased LH. The organ weights were also decreased; however, the changes were less than those in the castrated, T-implanted rats. Immature intact male rats (10 rats/dose) were treated for 20 days with flutamide (0, 0.15, 0.6, 2.5, or 10 mg/kg/day). Flutamide produced significant decreases in weights of the seminal vesicles, ventral prostate, and levator ani plus bulbocavernosus muscles at 2.5 and 10 mg/kg/day. Serum LH levels, but not T levels, were increased at 10 mg/kg/day. Statistical significance of some of these changes was not observed in the 6 animals/dose examined. Our findings support that the Hershberger assay, in the current conditions, is the most sensitive among the assays examined and a useful short-term screening method for the detection of antiandrogenic compounds.

Androgen Antagonists↗
PubMed2000

Pancreas and peripancreatic vessels: effect of imaging delay on gadolinium enhancement at dynamic gradient-recalled-echo MR imaging.

PURPOSE: To investigate the effect of imaging delay on gadolinium enhancement of the pancreas and peripancreatic vessels at dynamic gradient-recalled-echo magnetic resonance (MR) imaging of the pancreas. MATERIALS AND METHODS: Dynamic MR images were obtained after intravenous bolus injection of gadopentetate dimeglumine in 75 patients with no pancreatic malignancies. Test-bolus imaging was performed to determine aortic transit time in individual patients. Patients were randomly assigned so that the middle of k space was acquired at 5, 15, 25, 35, or 45 seconds after arrival of contrast material in the abdominal aorta. Mean signal intensities of pancreas, liver, and peripancreatic vessels were measured, and images were qualitatively assessed by two radiologists. RESULTS: The best pancreatic enhancement occurred at a delay of 15 seconds (P <.05). The best enhancement of the liver and peripancreatic vessels occurred at 25 seconds or later (P <.05). Qualitatively, the best images of the pancreas were obtained at 15 seconds, and the best images of the liver and peripancreatic vessels were obtained at 25 seconds or later. CONCLUSION: Biphasic imaging at 15 and 45 seconds or later after arrival of contrast material in the abdominal aorta is a practical method for acquisition of high-quality dynamic gradient-recalled-echo MR images of the pancreas.

Adult↗
PubMed2000

Estrogenicity of fissure sealants and adhesive resins determined by reporter gene assay.

It is controversial whether the dental resinous materials containing 2,2-bis[4-(2-hydroxy-3-methacryloyloxypropoxy)phenyl]propane (Bis-GMA), which is synthesized from the estrogenic compound bisphenol A (BPA), include unreacted BPA and/or can mimic the effects of natural steroid hormones. In the present study, the estrogenic activities of 3 fissure sealants and 5 adhesive resins, which were all unpolymerized, were determined by means of a reporter gene assay, and the relevance of the components to the estrogenicity was investigated. Two commercially available sealants were confirmed to have estrogenic activity, although none of the tested materials contained BPA. In contrast, hydrophobic monomer bisphenol A dimethacrylate (BPA-DMA), which is also estrogenic, was found to be included in these estrogenic sealants in an amount greater than the minimum concentration to show estrogenicity. This suggests that the estrogenicity of the two proprietary sealants was associated with BPA-DMA rather than with BPA.

Analysis of Variance↗
PubMed2000

Struma ovarii: MRI findings.

We describe the MRI findings in three cases of struma ovarii. In all three cases, MRI showed a multilocular cystic mass with a variable signal intensity within loculi. Some loculi or small cysts within septations showed low signal intensity on T1 weighted images and very low signal intensity on T2 weighted images, corresponding pathologically to gelatinous colloid material in large follicles. In one case, with Gd-DTPA enhanced T1 weighted images, the thick septations and locally thickened wall showed marked enhancement, corresponding microscopically to thyroid tissue.

Adult↗
PubMed2000

MR findings of subarachnoid dissemination of a pituitary adenoma.

Although pituitary adenoma is a benign tumour, subarachnoid dissemination occurs rarely. We describe a case of pituitary adenoma with subarachnoid dissemination. After the third operation for pituitary adenoma, an extraaxial mass was demonstrated on MR images. On T1 and T2 weighted images, the signal intensities of the extraaxial mass were similar to those of the primary pituitary adenoma. On dynamic contrast T1 weighted images, the time-intensity curve of the extraaxial mass, which showed early and persistent signal intensity, was also similar to that of the primary pituitary adenoma. These MR findings are considered to reflect the similar vascularity and stroma of the extraaxial mass and the primary pituitary adenoma.

Adenoma↗
PubMed2000

Protective effect of phenolic antioxidants on the cytotoxicity induced by phosphatidylcholine hydroperoxide.

Phosphatidylcholine hydroperoxides show weak but distinct toxicity toward cultured human umbilical vein endothelial cells. The protective effect of phenolic antioxidants against the cytotoxicity of phosphatidylcholine hydroperoxides was examined. Probucol depressed the toxicity most effectively among the antioxidants studied under both pretreatment and concurrent treatment conditions. alpha-Tocopherol showed a protective effect in the case of concurrent treatment. Protection by phenolic antioxidants against the cytotoxicity of phosphatidylcholine hydroperoxides seems to depend on their incorporation rate into cells, their affinity for phospholipids, their antioxidative activity, and their orientation in membranes.

Antioxidants↗
PubMed2000

Evaluation of a 5-day Hershberger assay using young mature male rats: methyltestosterone and p,p'-DDE, but not fenitrothion, exhibited androgenic or antiandrogenic activity in vivo.

A 5-day Hershberger assay using young mature male rats to detect compounds interfering with androgen receptor (AR)-mediated mechanisms was evaluated for ability to identify p,p'-DDE (a weak AR antagonist) and methyltestosterone (MT, an AR agonist). Fenitrothion, an organophosphate pesticide, was also evaluated in this validated assay. Castrated male Crj:CD(SD)IGS rats (1 week after castration, 11 weeks of age) were subjected to experiments. To determine a suitable value of testosterone propionate (TP) as a reference androgen for detection of antiandrogenic chemicals, castrated male rats were treated daily with TP (0, 0.06, 0.25, 1, 4, or 16 mg/kg/day, s.c.). TP produced increases in weights of ventral prostate, seminal vesicles and levator ani plus bulbocavernosus muscles. Serum androgen level measured by RIA kit (mostly TP) were elevated in a dose-related manner, while the weights of organs with 1 mg/kg/day of TP were nearly equivalent to the maximum responses (i.e., sub-maximal). One hundred mg/kg/day of p,p'-DDE significantly attenuated TP 0.1 mg/kg-induced increases in weights of seminal vesicles and muscles, and TP 1 mg/kg-induced increases in weights of ventral prostate, seminal vesicles and muscles, but did not affect the weight of these organs in either TP 16 mg/kg-treated or intact rats, demonstrating that the dose range of 0.1-1 mg/kg TP is suitable for reference androgen. Oral treatment with 100 mg/kg of MT increased the weights of ventral prostate, seminal vesicles and muscles as strongly as did subcutaneous injection of 1 mg/kg of TP. These findings demonstrate that the 5-day Hershberger assay using young mature as well as immature male rats is a sensitive and valid short-term screening method for the detection of chemicals interfering with AR-mediated mechanisms. To determine whether fenitrothion interferes with AR-mediated mechanisms in vivo, fenitrothion (0, 0.75, 1.5 or 3 mg/kg/day) was administered by gavage for 5 days to castrated rats for androgenicity, or to castrated rats treated with 1 mg/kg TP for antiandrogenicity. Treatment with fenitrothion had no adverse effects on clinical signs, body weight, or liver or kidney weights, but cholinesterase activities in the brain and erythrocytes were significantly suppressed by fenitrothion to, respectively, 77-81% and 66-67% of control levels. In the antiandrogenicity experiment, serum androgen levels of TP-treated, castrated rats did not differ among groups. Treatment with 100 mg/kg of p,p'-DDE as a positive control again significantly attenuated TP-induced increases in weights of the ventral prostate and seminal vesicles, while fenitrothion had no effect on the weights of any organs. In the androgenicity experiment, treatment with 100 mg/kg of MT significantly increased weights of ventral prostate, seminal vesicles and muscles, but fenitrothion had no effects on the weights of any of these organs. These findings yield no evidence that fenitrothion interferes with AR-mediated mechanisms in vivo, consistent with the result of several toxicological bioassays.

Androgen Antagonists↗
PubMed2000

Preoperative detection of malignant hepatic tumors: comparison of combined methods of MR imaging with combined methods of CT.

OBJECTIVE: We compared radiologists' performance on combined unenhanced, gadolinium-enhanced, and ferumoxides-enhanced MR imaging with their performance on helical CT during arterial portography (CTAP) and biphasic CT during hepatic arteriography (CTHA) for the preoperative detection of malignant hepatic tumors. SUBJECTS AND METHODS: MR images and CT scans obtained in 33 patients were retrospectively analyzed. Images of the liver were reviewed on a segment-by-segment basis; a total of 261 segments with 39 hepatocellular carcinomas and 21 metastases were independently reviewed by three radiologists who were invited from outside institutions. Unenhanced and gadolinium-enhanced MR images were reviewed first, then ferumoxides-enhanced MR images were added for combined review. CTAP images and biphasic CTHA images were reviewed together. RESULTS: Sensitivity for the detection of hepatic tumors was analogous for combined unenhanced, gadolinium-enhanced, and ferumoxides-enhanced MR images (86%) and for combined CTAP images and biphasic CTHA images (87%). Specificity was higher with MR images (95%, p < 0.01) than with CT images (91%). Radiologists' performances were improved (Az = 0.962, p = 0.0502) by combining ferumoxides-enhanced MR images with unenhanced and gadolinium-enhanced MR images (Az = 0.950), and were analogous for combined unenhanced, gadolinium-enhanced, and ferumoxides-enhanced MR images and for combined CTAP images and biphasic CTHA images (Az = 0.959). CONCLUSION: Radiologists' performances on combined unenhanced, gadolinium-enhanced, and ferumoxides-enhanced MR imaging compared with their performances on combined helical CTAP and biphasic CTHA are analogous for the preoperative detection of malignant hepatic tumors. Such a dedicated combination of MR imaging may obviate the need for more invasive angiographically assisted helical CT for the preoperative detection of malignant hepatic tumors.

Aged↗
PubMed2000

Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy: nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to sulfonylurea receptor 1.

To elucidate the genetic etiology of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in the Japanese population, we conducted a polymerase chain reaction-single-strand conformation polymorphism analysis of the sulfonylurea receptor 1 (SUR1) and Kir6.2 genes in 17 Japanese PHHI patients, including a pair of siblings from a consanguineous family. We also analyzed the glutamate dehydrogenase gene for the exons encoding an allosteric regulatory domain of the enzyme. In the SUR1 gene, we identified one frameshift (I446fsdelT) and two missense (R1420C, R1436Q) mutations. None of these mutations were found in control Japanese subjects. Siblings homozygous for the R1420C mutation had a mild form, whereas two patients heterozygous for the I446fsdelT and R1436Q mutations, respectively, exhibited a severe form of PHHI. Functional consequences of these mutations on K(ATP) function were evaluated using 86Rb+ efflux studies in COS-7 cells. SUR1-446fsdelT and SUR1-1436Q did not form a functional K(ATP). Western blot analysis after transient expression in COS-7 cells revealed the expression of SUR1-1436Q protein to be markedly reduced, suggesting SUR1-1436Q to be unstable in these cells. K(ATP)(SUR1-1420C) showed reduced responses to metabolic inhibition by oligomycin and 2-deoxyglucose. K(ATP) channels are under complex regulation by intracellular ATP and ADP. ATP both inhibits and activates these channels. The inhibition is probably mediated through direct ATP interaction with a pore-forming subunit Kir6.2, whereas the activation is likely to be through a regulatory subunit SUR1. There is a cooperative regulation of ATP and ADP binding to SUR1, and this cooperativity may be involved in regulating the K(ATP) channel. In SUR1-1420C, high-affinity binding of ATP to the nucleotide-binding fold (NBF)-1 was indistinguishable from that of wild-type SUR1. However, stabilization of ATP binding to NBF-1 by MgATP or MgADP was impaired, suggesting that this defect may account for impaired K(ATP)(SUR1-1420C) function. This is the first direct biochemical evidence that the cooperativity of nucleotide binding to SUR1 is impaired in a SUR1 mutant causing PHHI. No mutations were identified in the Kir6.2 and glutamate dehydrogenase genes. The genetic etiology of PHHI appears to be heterogeneous. SUR1 mutations may account for no more than 20% of PHHI cases in Japanese patients. Mutations of Kir6.2 and glutamate dehydrogenase genes are likely to be even less common.

ATP-Binding Cassette Transporters↗
PubMed2000

Preference of female students for "tempe" preparations composed of glandless cottonseed and defatted soybean or corn at various ratios.

Cottonseed kernels are rich in protein, but they have not been effectively utilized as a foodstuff because of the occurrence of glands that secrete gossypol. a toxic yellow pigment. Glandless cottonseeds (GLCS) are now available. and their kernels or flour are sold as a foodstuff. For this reason, a GLCS-tempe was prepared after the pattern of a traditional food called "Tempe" in Indonesia (fermented with Rhizopus oligosporus), and any gossypol remaining in GLCS proved to be lost in the process. Corn has not yet been used for tempe because of its difficulty to dehull: nevertheless, corn tempe was satisfactorily made from corn grits. Although GLCS-tempe was good. it smelled slightly unique just at swallowing. The preference for GLCS-tempe was correlated to the smell and taste. A combination of GLCS and defatted soybeans or corn at ratio of 1 : 1 led to many good effects on GLCS-tempe: e.g., favorable improvement in smell, taste, amino acid score, nutrient balance, and decrease of oligosaccharides related to the flatulence of the GLCS-tempe. Thus GLCS-tempe containing defatted soybeans or corn half of what can be expected to serve as a nutritious tasty food.

Cottonseed Oil↗
PubMed2000

Plasma cholesterol reduction by defatted soy ontjom (fermented with Neurospora intermedia) in rats fed a cholesterol-free diet.

To popularize defatted soy ontjom (DSB-ontjom, soy product fermented with Neurospora intermedia) as a new food, I examined the plasma cholesterol-reducing effects of DSB-ontjom and DSB in rats fed cholesterol-free diets and compared the efficiencies of these effects. DSB-ontjom greatly reduced the plasma cholesterol level and increased fecal steroid excretion as compared to DSB. DSB-ontjom was rich in pepsin-resistant protein having a high bile acid binding capacity and was abundant in isoflavone-aglycones, especially daizein. The dietary fiber (DF) of DSB-ontjom stimulated the production of short-chain fatty acids (SCFAs) by intestinal microflora. The effect of DSB-ontjom on plasma cholesterol reduction was attributed to the collaborative effects of pepsin-resistant-protein, isoflavone-aglycones and SCFA-producing DF in DSB-ontjom.

Animals↗
PubMed2000

Estrogen affects vascular tone differently according to vasoactive substances in ovariectomized Sprague-Dawley rat.

The favorable effects of estrogen on cardiovascular diseases can be explained by several mechanisms such as changes in serum lipid profiles and thrombogenecity. Estrogen also affects the vascular tone, but there has been no report in which the effect of estrogen was tested comprehensively for several vasoactive substances, especially after long-term administration. Two weeks after bilateral ovariectomy in 8-week old female Sprague-Dawley rats, placebo or 17 beta-estradiol (E2) pellets (0.5 mg; released over 3 weeks) were implanted subcutaneously. Two weeks after pellet implantation, organ chamber experiments were performed using aortae. Compared with control, E2-treated vessels showed impaired endothelium-dependent relaxation to acetylcholine. E2 enhanced the contraction to norepinephrine and U46619 and had no effect on endothelin-1-induced contraction. In contrast, the contraction to angiotensin (AT)-II was inhibited by E2. Northern blot analysis for AT1 receptor expression using cultured aortic smooth muscle cells showed no difference between control and E2-treated cells, suggesting that AT1 receptor downregulation is not the likely mechanism. These results suggest that E2 affects the vascular tone variably according to vasoactive substances.

Animals↗
PubMed2000

Probable involvement of the 5-hydroxytryptamine(4) receptor in methotrexate-induced delayed emesis in dogs.

Delayed emesis in cancer patients undergoing chemotherapy remains a significant problem. The pathogenesis of delayed emesis is still obscure. It was recently demonstrated that methotrexate (MTX), an anticancer drug, evoked delayed emesis in dogs in a manner similar to its actions in humans. We evaluated the antiemetic activity of FK1052, a potent antagonist for both the 5-hydroxytryptamine (HT)(3) and 5-HT(4) receptors, on delayed emesis induced by MTX in beagle dogs. Animal behavior was recorded for 3 days using a video camera. Delayed emesis lasting up to 72 h was observed in dogs treated with MTX (2.5 mg/kg i.v.), but acute emesis did not occur. The following antiemetics, at the dose that prevents cisplatin-induced acute emesis in dogs, were administered i.v. as multiple injections every 12 h during days 2 to 3. FK1052 (1 and 3.2 mg/kg) significantly reduced the emetic episodes caused by MTX, whereas ondansetron (1 mg/kg), a selective 5-HT(3) receptor antagonist, was not effective. The emetic episodes induced by MTX were also inhibited by another 5-HT(3/4) receptor antagonist, tropisetron (1 mg/kg). CP-122,721 (0. 1 mg/kg), a potent selective tachykinin NK(1) receptor antagonist, significantly reduced the emetic responses to MTX. Copper sulfate-induced emesis in dogs was also prevented by FK1052, tropisetron, and CP-122,721 but not by ondansetron. FK1052, tropisetron, and ondansetron had negligible affinity for the NK(1) receptor at 1 microM. These results suggest that the 5-HT(4) receptor may be in part involved in the production of delayed emesis induced by MTX in dogs and that FK1052 may be a useful drug against both acute and delayed emesis induced by cancer chemotherapy.

Animals↗