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Biomedical subjects

I Yoshida

Publications and source records attributed to I Yoshida.

At least 37 records · Page 2Linked to original sources
PubMed2001

Nephron distribution of total low Km cyclic AMP phosphodiesterase in mouse, rat and rabbit kidney.

The activity of cAMP degradation enzyme, cAMP phosphodiesterase (cAMP PDE), in renal tubules is a critically important factor in determining cellular cAMP levels, particularly in response to hormones. In this study we examine the nephron distribution of cAMP PDE activity in the mouse, rat and rabbit kidney and important cellular regulators of cAMP PDE, namely calmodulin and adenosine triphosphate (ATP). We assayed total low Km cAMP PDE in microdissected tubule segments, using 10(-6) M (3H) cAMP as a substrate. Activities were expressed in fentomol cAMP hydrolyzed per minute per mm tubular length or per one glomerulus. The content of ATP was measured in outer medullary collecting duct and medullary thick ascending limb of Henle's loop with microbioluminescence assay using firefly luciferase. In mouse kidney, cAMP PDE was significantly higher in all tubular segments compared to glomerulus. Proximal convoluted tubule, proximal straight tubule, medullary thick ascending limb of Henle's loop (mTAL), and outer medullary collecting duct (OMCD) had intermediated activity. Greater cAMP PDE activity was detected in cortical ascending limb of Henle's loop (cTAL), cortical collecting duct and in distal convoluted tubule (DCT). The highest activity was found in connecting tubules. In rat, nephron distribution of cAMP PDE activities was similar to mouse, except that activity in glomeruli was higher than in mouse glomeruli. In rabbit, nephron distribution of cAMP PDE activities was different from those of mouse and rat. There was no single prominent segment with high cAMP PDE activity. DCT and cTAL showed low enzyme activity. Overall, the highest cAMP PDE activities were measured in the mouse and the lowest were measured in the rabbit nephrons, with those of rat nephron showing an intermediate activity. The maximum effective dose of the calmodulin antagonist, trifluoperazine (200 microM), inhibited cAMP PDE in all nephron segments from the rat kidney. However, there is no statistical significance of its inhibition among nephron segments. In OMCD and mTAL of the rat kidney, cAMP PDE activity was inhibited by ATP (5 mM to approximately 10 mM) which is far beyond the physiological concentartion of ATP in normal epithelial cell. Actual determinations of ATP in mTAL and OMCD were 0.1 mM and 0.17 mM, respectively. These observations show that distal segments of tubules have more active catabolism of cAMP than proximal segments. cAMP PDE in each nephron segment appear to be almost equally dependent on trifluoperazine-sensitive pathway that may reflect the Ca2+-calmodulin system. Cellular concentration of ATP might not be involved in the regulation of the total low Km cAMP PDE activity in rat mTAL and OMCD.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2001

[Toxicity study of cefmatilen hydrochloride hydrate (S-1090) (5)--Six-month repeated oral dose toxicity study and supplement study in rats].

Cefmatilen hydrochloride hydrate (S-1090) was orally administered to rats at dose levels of 100, 300 and 1000 mg potency/kg once daily for 6 months. All the S-1090 treated groups showed soft feces, reddish-brown feces (due to chelated products of S-1090 or its decomposition products with Fe3+ in the diet), abdominal distention, increased food and water consumption, lower urine pH, and a decrease of white blood cells counts (except for males of the 100 mg potency/kg group). One male in the 300 mg potency/kg group showed mucous feces and marked decrease in body weight, and diet in the middle stage of the administration period. In necropsy of the survivors of all treated groups, marked cecal enlargement was noted. No remarkable changes were observed in the other examination items. From the early stage of the withdrawal period, animals in the 1000 mg potency/kg group showed again soft or mucous feces and a marked decrease in body weight. Of these animals, one male died and another male was sacrificed in a moribund state at about 2 weeks of the withdrawal period. Enterocolitis was observed in these cases. Almost all animals recovered within 3 weeks of withdrawal. A supplemental study of the 6-month toxicity study was conducted to examine the mechanisms of enterocolitis and the changes observable in the 100 or 300 mg potency/kg groups after drug withdrawal. As a reference, cefdinir (CFDN), an oral cephem antibiotic the same as S-1090, was added in the 1000 mg potency/kg group. No deaths occurred in any groups. Decreased intestinal flora were noted in all the groups treated with S-1090 or CFDN at the end of the dosing period. At 2 weeks of the withdrawal period, C. difficile and its D-1 toxin in the cecal contents were highly detected in the S-1090 300 and 1000 mg potency/kg groups and CFDN group. Inflammatory changes in the cecum and colon were observed in these groups. At 4 weeks of the withdrawal period, intestinal flora in the S-1090 groups almost returned to the condition before dosing, but those in the CFDN group were retained highly. Cecal D-1 toxin in the CFDN group was positive and higher than in the S-1090 groups. It was thus considered that the critical condition with enterocolitis resulted from C. difficile, which proliferated more rapidly than the other bacteria and D-1 toxin produced by this bacteria in the withdrawal period. Above changes were commonly observed in the CFDN group. The NOAEL of S-1090 was assessed to be 100 mg potency/kg/day which induced no enteritis.

Administration, Oral↗
PubMed2001

[A case of acute renal failure and liver dysfunction induced by carbamazepine(CBZ)].

A 56-year-old female with symptomatic epilepsy was admitted to our hospital because of acute renal failure(ARF) and liver dysfunction(LD) after receiving CBZ for two months. She had suffered a drug eruption caused by phenobarbital and valproate six months previously. Renal and liver biopsies presented acute interstitial nephritis and active chronic hepatitis, respectively. Drug-induced lymphocyte stimulating test showed CBZ positivity. Steroid therapy resulted in recovery from ARF and LD. CBZ sometimes causes ARF or LD, but rarely induces both simultaneously, especially in adults. Pathological evidence of two lesions other than from autopsy seems to be the first step in this case. Cross reaction with other antiepileptic agents was also of interest, suggesting that one member of the cytochrome P450 subfamily, CYP3A, participated in the mechanism.

Acute Kidney Injury↗
PubMed2001

Activity of anthocyanins from fruit extract of Ribes nigrum L. against influenza A and B viruses.

Earlier, we have detected antiviral activity in an extract from Ribes nigrum L. fruits ("Kurokarin", name of the one species of black currant in Japanese) against influenza A and B viruses, and herpes simplex virus 1 (Knox et al., Food Processing 33, 21-23, 1998). In the present study, the antiviral activity of constituents of a Kurokarin extract and the mechanism of its antiviral action were examined. Kurokarin extracts were separated to fractions A to D by column chromatography. The major constituents of the fraction D were estimated as anthocyanins. The fraction D was further fractionated by thin-layer chromatography (TLC) to fractions A' to G'. The fraction E' consisted of 3-O-alpha-L-rhamnopyranosyl-beta-D-glucopyranosyl-cyanidin and 3-O-beta-D-glucopyranosyl-cyanidin, and the fraction F' consisted of 3-O-alpha-L-rhamnopyranosyl-beta-D-glucopyranosyl-delphinidin and 3-O-beta-D-glucopyranosyl-delphinidin, identified by high performance liquid chromatography (HPLC) with standards and by high resolution mass spectrometry. The fractions D' to G' showed potent antiviral activity against influenza viruses A and B. The additive antiviral effect of a combination of the fractions E' and F' was assessed. Anthocyanins in the fraction F' did not directly inactivate influenza viruses A and B, but they inhibited virus adsorption to cells and also virus release from infected cells.

Animals↗
PubMed2000

Complex formation between hepatitis C virus core protein and p21Waf1/Cip1/Sdi1.

The core protein (Core) of hepatitis C virus (HCV) has been known to play an important role in hepatocarcinogenesis. By using glutathione S-transferase (GST) pull-down assay, we show here that Core formed a complex with p21Waf1/Cip1/Sdi1 (p21) cell cycle regulator. The deletion-mapping analysis revealed that a portion near the N-terminus of Core (amino acids 24-52) and a C-terminal portion of p21 (amino acids 139-164) were involved in the complex formation. The complex formation was not impaired by point mutations of p21 at residues 147, 149, and 150, which have been reported to abrogate interaction of p21 with proliferating cell nuclear antigen (PCNA), discriminating the Core-binding sequence from the PCNA-binding sequence. Due to the close vicinity of the binding sites, however, Core and PCNA competed with each other when interacting with p21. The distinct interaction between Core and p21 may provide a new aspect to the studies of HCV pathogenesis.

Base Sequence↗
PubMed2000

Molecular and biochemical characterization of a serine proteinase predominantly expressed in the medulla oblongata and cerebellar white matter of mouse brain.

A full-length cDNA clone of a serine proteinase, mouse brain serine proteinase (mBSP), was isolated from a mouse brain cDNA library. mBSP, which has been recently reported to be expressed in the hair follicles of nude mice, is most similar (88% identical) in sequence to rat myelencephalon-specific protease. The mBSP mRNA was steadily expressed in the brain of adult mice with a transient expression in the early fetal stage during development. The genomic structure of the mouse gene for mBSP was determined. The gene, which is mapped to chromosome 7B4-B5, is about 7.4 kilobases in size and contains 7 exons. Interestingly, the 5'-untranslated region of the mBSP gene was interrupted by two introns. In situ hybridization analyses revealed that mBSP is expressed in the white matter of the cerebellum, medulla oblongata, and capsula interna and capsula interna pars retrolenticularis of mouse brain. Further, mBSP was immunolocalized to the neuroglial cells in the white matter of the cerebellum. Recombinant mBSP was produced in the bacterial expression system and activated by lysyl endopeptidase digestion, and the activated enzyme was purified for characterization. The enzyme showed amidolytic activities preferentially cleaving Arg-X bonds when 4-methylcoumaryl-7-amide-containing peptide substrates were used. Typical serine proteinase inhibitors, such as diisopropyl fluorophosphates, phenylmethanesulfonyl fluoride, soybean trypsin inhibitor, aprotinin, leupeptin, antipain, and benzamidine, strongly inhibited the enzyme activity. The recombinant mBSP effectively hydrolyzed fibronectin and gelatin, but not laminin, collagens I and IV, or elastin. These results suggest that mBSP plays an important role in association with the function of the adult mouse brain.

Animals↗
PubMed2000

Inhibition of A beta fibril formation and A beta-induced cytotoxicity by senile plaque-associated proteins.

A beta neurotoxicity is generally believed to require A beta fibril formation. The prevention of A beta fibril formation thus seems to be a promising strategy for the treatment of AD. Recent studies have shown senile plaque-associated proteins such as laminin to have an inhibitory effect on both A beta40 and A beta42 fibril formation in vitro. In the present study, we thus investigated whether or not midkine (MK) and alpha2-macroglobulin (alpha2M), both of which are also senile plaque-associated proteins like laminin, affect A beta fibril formation and A beta-induced cytotoxicity. The present study demonstrated that both MK and alpha2M inhibit both A beta fibril formation and A beta-induced cytotoxicity in PC12 cells. The confirmation of the present results based on in vivo experiments is called for in future studies to clarify whether or not senile plaque-associated proteins such as MK and alpha2M can be a model for therapeutic agents in the treatment of AD.

Alzheimer Disease↗
PubMed2000

Thoracoscopic treatment of primary chylopericardium.

The development of video-assisted thoracoscopy has changed the practice of thoracic surgery. This report describes a 20-year-old man who successfully underwent thoracoscopic thoracic duct ligation and partial pericardiectomy for primary chylopericardium. We recommend a right-sided thoracoscopic approach to the thoracic duct in the lower thoracic cavity.

Adult↗
PubMed2000

Gender-dependent effect of L-NAME on polycystic kidney disease in Han:SPRD rats.

To determine whether the renal nitric oxide (NO) system has a role in the pathogenesis of polycystic kidney disease (PKD) in Han:Sprague-Dawley (SPRD) rats, the NO synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), 70 mg/L, or L-arginine, 0.5 g/L, was administered to heterozygous diseased (cy/+) and homozygous normal animals. Urine nitrate and nitrite excretion was reduced by L-NAME treatment and, in the male cy/+ rats, increased by L-arginine administration. The administration of L-NAME significantly increased blood pressure in all groups, whereas L-arginine had no effect. L-NAME and L-arginine had a modest but significant overall effect on the severity of cystic disease in male rats, reflected by relative kidney weights and cyst volume densities. This effect was gender dependent because it was not observed in female animals. The administration of L-NAME resulted in a significant increase in plasma creatinine concentration of the cy/+ rats, which was more marked in male than female animals. These observations support the recently reported gender differences in the renal NO system and a small role for NO synthesis that can be inhibited by L-NAME in the pathogenesis of PKD in Han:SPRD rats. These observations do not exclude a more important role for the endogenous renal NO production in the pathogenesis of PKD in view of a recent report of a major NOS resistant to conventional inhibitors in the rat kidney.

Animals↗
PubMed2000

The role of the UL41 gene of herpes simplex virus type 1 in evasion of non-specific host defence mechanisms during primary infection.

The UL41 gene product (vhs) of herpes simplex virus (HSV) is packaged in the virion, and mediates host protein synthesis shutoff at the early stage of the virus replication cycle. In order to clarify the role of vhs in virus replication and virulence, we isolated a completely UL41-deficient mutant (the VRDelta41 strain) and its revertant (the VRDelta41R strain). In the mouse encephalitis model, the replication of strain VRDelta41 was inhibited after 2 days post-infection, resulting in low virulence, by gamma-ray-sensitive cells such as lymphocytes and/or neutrophils. The result suggested that some cytokines, produced in VRDelta41-inoculated brains, activate and induce the migration of gamma-ray-sensitive cells to the infection site. Therefore, cytokines produced by HSV-1-infected human cells were screened, and potent inductions of interleukin (IL)-1beta, IL-8 and macrophage inflammatory protein-1alpha by VRDelta41 infection were observed. Moreover, the VRDelta41 strain showed 20- and 5-fold higher sensitivity to interferon-alpha and -beta compared to the wild-type strain, respectively. These results indicate that one important role of vhs in vivo is evasion from non-specific host defence mechanisms during primary infection through suppression of cytokine production in HSV-infected cells and reduction of the anti-HSV activity of interferon-alpha and -beta.

Animals↗
PubMed2000

Herpesvirus alkaline deoxyribonuclease; a possible candidate as a novel target for anti-herpesvirus therapy.

Herpesvirus alkaline deoxyribonucrease (DNase) is coded in the genome of all herpesvirus species determined total sequence and is conserved in structure. In order to determine whether the enzyme could be a target for a novel antiherpesvirus therapy, the anti-herpes simplex virus type 1 (HSV-1) activity of antisense oligonucleotide for HSV-1 alkaline DNase was studied. Six antisense phosphorothioate oligonucleotides, targeted to an internal AUG start codon, were designed and evaluated. One of the oligonucleotides, UL12-4, inhibited wild type and thymidine kinase-deficient HSV-1 replication to 21.5 and 19.5% at 40 microM, respectively. The quantity of alkaline DNase mRNA and DNase activity in HSV-1-infected Vero cells was reduced to one eighth and 66.9% of control, respectively, by treatment with 40 microM of UL12-4, but no effect was observed on the quantity of HSV-1 glycoprotein H mRNA (gamma2 gene) or on the replication of Vero cells. These results indicate that UL12-4 inhibits HSV-1 replication by decreasing the amount of alkaline DNase mRNA. The herpesvirus alkaline DNase could be a novel target for anti-herpesvirus drug.

Animals↗