Biomedical subjects

S Iwata

Publications and source records attributed to S Iwata.

At least 19 recordsLinked to original sources

PubMed2002

Modulation of intracellular glutathione concentration alters dehydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells.

Dehydropyrimidine dehydrogenase (DPD) is the initial key enzyme in the regulation of 5-fluorouracil catabolism and thus controls availability of 5-fluorouracil for anabolism. Modulation of DPD activity may increase the antitumor effect and avoid toxic side effects in 5-fluo-rouracil-based chemotherapy. We measured DPD activity in peripheral blood mononuclear cells from cancer patients and simultaneously monitored intracellular glutathione (GSH) and plasma GSH levels. There was a significant linear relationship between DPD activity and intracellular GSH levels in peripheral blood mononuclear cells obtained from cancer patients. Suppression of intracellular GSH level by buthionine sulfoximine decreased DPD activity, while enhancement of intracellular GSH level by 2-mercaptoethanol increased DPD activity. This study indicated that alteration of intracellular GSH concentration may modulate DPD activity.

Adult↗

PubMed2002

Prooxidant action of gallic acid compounds: copper-dependent strand breaks and the formation of 8-hydroxy-2'-deoxyguanosine in DNA.

Gallic acid and its alkylesters, polyphenolic compounds with antioxidative activity, acted as a prooxidant causing a copper-dependent DNA damage. Treatment of DNA from plasmid pBR322 and calf thymus with gallic acid plus copper ion caused strand scission and the formation of 8-hydroxy-2'-deoxyguanosine in DNA. Addition of catalase protected DNA from the gallic acid/copper-dependent strand breaks and the formation of 8-hydroxy-2'-deoxyguanosine, indicating that hydroxyl radical may participate in the DNA damage. Ethyl-, propyl- and butylgallates showed only a little DNA damage. Octyl- and laurylgallates caused negligible damage of DNA. DNA strand breaks and formation of 8-hydroxy-2'-deoxyguanosine were closely related to the reduction of copper by gallate compounds. These results imply that cuprous ion reduced by gallate derivatives may play a key role in the oxidative cleavage of DNA and the formation of base adduct. The cytotoxic effect of gallate compounds can be explained by their prooxidant action dependent on the reducing activity.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed2002

Enamel tensile bond strength and morphology of resin-enamel interface created by acid etching system with or without moisture and self-etching priming system.

The purpose of this study was to estimate the effect of three types of different adhesive systems on enamel adhesion. Scotchbond Multi-Purpose (MP) as a traditional system, Single Bond (SB) as a wet-bonding system and Clearfil SE Bond (SE) and Unifil Bond (UB) as self-etching priming systems were used. Bovine enamel was treated with each system and tensile bond strength (TBS) of resin to the enamel was measured. The conditioned enamel surfaces and resin-enamel interfaces were also morphologically observed with scanning electron microscope (SEM). The mean TBS for MP, SB, SE and UB were 15.3, 13.7, 14.3 and 11.6 MPa, respectively. There was no significant difference in mean TBS among all products but the traditional system showed the most stable TBS. In SEM observations, self-etching primer created a weaker etched pattern on the enamel surface than phosphoric acid. At the resin-enamel interfaces, thick tag-like extensions penetrated into the enamel etched with phosphoric acid regardless of using the wet-bonding technique, while self-etching primer created thin lamina-like resin penetrations. These results indicate that the traditional system with phosphoric acid etching exhibits the most stable enamel adhesion although the enamel-bonding promoting abilities of these adhesive systems are equivalent to each other.

Acid Etching, Dental↗

PubMed2002

Surgical clipping of basilar aneurysms: relationship between the different approaches and the surgical corridors.

BACKGROUND: Surgical clipping for basilar artery aneurysm (BAA) is a technically demanding procedure due to the depth of the surgical field and the presence of vital perforating arteries in the vicinity. The incorporation of various modifications in the conventional approaches has expanded the surgical armamentarium in dealing with these difficult lesions. METHODS AND FINDINGS: 87 patients of BAA were operated at our center, out of which in 48 patients, a pterional transsylvian approach was used. In 12 patients, this approach had to be extended to incorporate the anterior temporal approach in 6 cases, transzygomatic subtemporal approach in 2 cases and transcavernous approach in 4 cases. The surgical indications for the additional approaches and the relationships between the surgical corridors gained by their inclusion were studied. The use of neuroendoscopy facilitated adequate clipping in one case of high BAA without the incorporation of bone drilling, thus opening new surgical corridors. INTERPRETATION: The variable situation of the BAA makes it mandatory for the surgeon to be prepared to simultaneously work through multiple surgical corridors. Neuroendoscopic-assisted microneurosurgery occasionally utilizes a narrow surgical corridor to facilitate BAA clipping using the conventional approaches and eliminates the need to gain access using additional surgical corridors.

Basilar Artery↗

PubMed2001

Soluble CD26/dipeptidyl peptidase IV induces T cell proliferation through CD86 up-regulation on APCs.

CD26 is a T cell costimulatory molecule with dipeptidyl peptidase IV enzyme activity in its extracellular region. We have previously reported that the addition of soluble CD26 (sCD26) resulted in enhanced proliferation of peripheral blood T lymphocytes induced by the recall Ag, tetanus toxoid (TT). However, the mechanism involved in this immune enhancement has not yet been elucidated. In this paper, we demonstrate that the enhancing effect of sCD26 on TT-induced T cell proliferation occurred in the early stages of immune response. The cells directly affected by exogenously added sCD26 are the CD14-positive monocytes in the peripheral blood. Mannose-6 phosphate interfered with the uptake of sCD26 into monocytes, suggesting that mannose-6 phosphate/insulin-like growth factor II receptor plays a role in the transportation of sCD26 into monocytes. When sCD26 was added after Ag presentation had taken place, enhancement in TT-induced T cell proliferation was not observed. In addition, enhancement of TT-mediated T cell proliferation by sCD26 does not result from trimming of the MHC-bound peptide on the surface of monocytes. Importantly, we also showed that exogenously added sCD26 up-regulated the expression of the costimulatory molecule CD86 on monocytes through its dipeptidyl peptidase IV activity, and that this increased expression of CD86 was observed at both protein and mRNA level. Therefore, our findings suggest that sCD26 enhances T cell immune response to recall Ag via its direct effect on APCs.

Abatacept↗

PubMed2001

Structures of F420H2:NADP+ oxidoreductase with and without its substrates bound.

Cofactor F420 is a 5'-deazaflavin derivative first discovered in methanogenic archaea but later found also to be present in some bacteria. As a coenzyme, it is involved in hydride transfer reactions and as a prosthetic group in the DNA photolyase reaction. We report here for the first time on the crystal structure of an F420-dependent oxidoreductase bound with F420. The structure of F420H2:NADP+ oxidoreductase resolved to 1.65 A contains two domains: an N-terminal domain characteristic of a dinucleotide-binding Rossmann fold and a smaller C-terminal domain. The nicotinamide and the deazaflavin part of the two coenzymes are bound in the cleft between the domains such that the Si-faces of both face each other at a distance of 3.1 A, which is optimal for hydride transfer. Comparison of the structures bound with and without substrates reveals that of the two substrates NADP has to bind first, the binding being associated with an induced fit.

Binding Sites↗

PubMed2001

Novel marine-derived halogen-containing gramine analogues induce vasorelaxation in isolated rat aorta.

We examined the effects of 2,5,6-tribromo-1-methylgramine (TBG), isolated from bryozoan, and its derivative, 5,6-dibromo-1,2-dimethylgramine (DBG), on the contraction of rat aorta. TBG and DBG decreased the high-K(+)-induced increase in muscle contraction and cytosolic Ca(2+) level ([Ca(2+)](i)), respectively. The inhibitory effects of TBG and DBG on high-K(+)-induced contraction were antagonized by increasing the external Ca(2+) concentration or by 1,4-dihydro2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]pyridine-3-carboxylic acid (Bay k8644). The high-K(+)-induced increase of Mn(2+) influx was completely blocked by 10 microM TBG or 10 microM DBG. In the Ca(2+)-free solution, 30 microM TBG or 30 microM DBG inhibited the phenylephrine-induced transient increase in [Ca(2+)](i) and muscle tension, while scarcely affecting caffeine-induced transient changes. TBG and DBG significantly increased the cyclic AMP content at 30 microM, but not at 10 microM. These results suggest that TBG and DBG inhibit the smooth muscle contraction by inhibiting Ca(2+) entry, and at higher concentrations, the increase in intracellular cyclic AMP content also contributes to their inhibitory effect.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2001

Application of 2-(3,5,6-trifluoro-2-hydroxy-4-methoxyphenyl)benzoxazole and -benzothiazole to fluorescent probes sensing pH and metal cations.

2-(3,5,6-Trifluoro-2-hydroxy-4-methoxyphenyl)benzoxazole (3) and benzothiazole analogue (4) are prepared by the two-step procedures from the corresponding 2-(pentafluorophenyl)benzazoles. Benzoxazole 3 is applicable to a fluorescent probe sensing magnesium cation, and 4 is suitable for sensing zinc cation. Both fluorophores 3 and 4 are sensitive to the pH change at pH 7-8, resulting in large fluorescence enhancement under basic conditions. Their high sensitivity to pH and selectivity in metal cations are ascribed to the high acidity of the fluorophenol moiety.

Benzothiazoles↗

PubMed2001

Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice.

This study was conducted to confirm the hypothesis that intestinal microflora are required for the development of adenocarcinoma in the colon of the TCRbeta and p53 double-knockout (TCRbeta-/- p53-/-) mouse. Germ-free TCRbeta-/- p53-/- mice were produced. At 7 weeks of age, the animals were divided into two groups (n = 10/group), and one of these groups was conventionalized. Animals of both groups were subjected to histopathological examination for adenocarcinoma of the colon at 4 months of age. There was no development of adenocarcinoma of the colon among the germ-free mice, whereas in the conventionalized group, adenocarcinomas of the ileocecum and cecum were detected in 70% of animals. These results indicate the usefulness of the TCRbeta-/- p53-/- mouse as a colon cancer animal model that develops spontaneous adenocarcinoma of the colon early in life, and suggest that intestinal microflora play a major role in the development of adenocarcinoma of the colon in this animal model.

Adenocarcinoma↗

PubMed2001

Expression of thioredoxin in bleomycin-injured airway epithelium: possible role of protection against bleomycin induced epithelial injury.

Bleomycin (BLM) is an anticancer drug, administration of which leads to severe lung injury, in which the generation of intracellular reactive oxygen species (ROS) is thought to participate in that. Thioredoxin (TRX) has been found to function as a powerful antioxidant by reducing ROS, and thus protecting against ROS-mediated cytotoxicity. However, a protective role of TRX in BLM-induced lung injury has not been determined. In the present study, we therefore attempted to clarify this issue. Human TRX-transfected L929 murine fibrosarcoma cells were more resistant to BLM-induced cytotoxicity than the parental and the control transfected cells, indicating that TRX plays the protective role in BLM-induced cytotoxicity. Next, we examined TRX expression in the lung of in vivo model of BLM-induced lung injury and BLM-stimulated bronchial epithelial cells in vitro to clarify the role of TRX in BLM-induced lung injury. In the lungs of BLM-treated mice, the expression of TRX was strongly induced in bronchial epithelial cells. TRX expression was also up-regulated at both the mRNA and protein levels in cultured BEC with the treatment with BLM. However, the expression of other major antioxidants, such as Cu/Zn-SOD, Mn-SOD, catalase and glutathione peroxidase, was not affected by BLM. These observations suggest that the cellular reduction and oxidation (redox) state modified by TRX is involved in the BLM resistancy and the induction of TRX in bronchial epithelial cells might play a protective role in BLM-induced lung injury.

Animals↗

PubMed2001

Structure of cytochrome c oxidase: a comparison of the bacterial and mitochondrial enzymes.

It has been almost 5 years since the first structures of cytochrome c oxidase, from Paracoccus denitrificans and bovine heart mitochondria, were revealed. Since then many different proton pumping mechanisms have been proposed for the enzyme; however, no definitive conclusion has been achieved. In this article, we revisit the original structures of bacterial and mitochondrial oxidases and try to clarify similarities as well as differences between the two structures.

Animals↗

PubMed2001

Recognition of cell surface GD3 by monoclonal antibody anti-6C2 in rheumatoid arthritis synovial fluid: expression on human T cells with transendothelial migratory activity.

OBJECTIVE: We have previously reported that the anti-6C2 monoclonal antibody (mAb) defines a subset of human CD4+ memory T cells. The present study sought to determine the nature of the 6C2 molecule and the function associated with 6C2+ T cells, and to examine whether this T cell subset is involved in the pathophysiology of rheumatoid arthritis (RA). METHODS: Cytofluorographic analysis was performed for identification of T cell surface molecules displaying a distribution similar to that of the 6C2 molecule. T cells in the synovial fluid of RA patients were examined for expression of the 6C2 molecule. Transendothelial migratory activity was assessed by assay using monolayers of human endothelial cells. Specific reactivity of the anti-6C2 mAb was determined by immunoblotting on gangliosides separated by thin-layer chromatography, and flow cytometric analysis of the cells transfected with complementary DNA (cDNA) was performed for determination of the glycosyltransferases involved in biosynthesis of the gangliosides. RESULTS: On human peripheral T cells, the 6C2 molecule was distributed, by and large, in a pattern similar to that of CDw60, or O-acetyl-GD3. The majority (>70%) of synovial fluid T cells from patients with RA were found to be 6C2 positive, and those 6C2+ T cells exhibited a transendothelial migratory capacity that was inhibited by pretreatment of T cells with anti-6C2 mAb. Moreover, treatment of T cells with neuraminidase resulted in a loss of 6C2 expression as well as a reduction in the transendothelial migratory activity. Anti-6C2 mAb reacted specifically with GD3, but not with O-acetyl-GD3. The reactivity of anti-6C2 mAb was induced on the cell surface only by transfection with cDNA for GD3 synthase. CONCLUSION: The 6C2 molecule is a disialoganglioside, GD3, and is present on a subset of T cells with transendothelial migratory capacity. The 6C2/GD3 molecules, as well as 6C2/GD3+ T cells, appear to play a role in T cell migration and in the inflammation of RA.

Antibodies, Monoclonal↗

PubMed2001

Treatment of unruptured intracranial aneurysms--a clinicopathological correlation.

OBJECT: Brain check-up is very important for detecting the incidence and prevalence of aneurysms in the population and to get the definite strategy for the treatment of intracranial aneurysms. METHODS: This is a retrospective study of 116 aneurysms detected by brain check-up between 1998-1999 which were treated either by clipping or endovascular coiling. In some cases the aneurysmal wall was resected for histopathological examination and compared with five normal autopsy cases. CONCLUSIONS: Direct surgery is the primary option for a patient with an aneurysm in the anterior circulation especially in young patients. Intravascular therapy is suitable for aneurysms in the posterior circulation and in intracavernous site.

Aged↗

PubMed2001

Macular fold after limited macular translocation treated with scleral shortening release and intravitreal gas.

PURPOSE: To describe a case developing a macular fold as a complication of limited macular translocation, which was successfully managed without repeat vitrectomy. METHODS: Interventional case report. A 34-year-old woman who underwent limited macular translocation for subfoveal choroidal neovascularization secondary to myopic degeneration developed a postoperative macular fold. Her visual acuity deteriorated from 20/100 to 20/200 postoperatively. RESULTS: She underwent scleral shortening release and intravitreal gas injection 4 days after the initial surgery and had a resolution of macular fold with adequate foveal displacement. Her visual acuity had improved to 20/40 3 months postoperatively. CONCLUSION: Scleral shortening release and intravitreal gas injection may be considered for the management of severe macular fold caused by limited macular translocation.

Adult↗

PubMed2001

Recommended method of the Japanese Association of Medical Technologists for the determination of protein in urine by HPLC.

A recommended method for the determination of total urinary proteins as a designated comparative method (DCM) is described. The method is based on gel permeation high performance liquid chromatography (HPLC). A total of 20 microl of urine diluted 5-fold with saline solution were applied to a column, eluted with 0.13 mol/l phosphate buffer (pH 7.0) at a flow rate of 1.0 ml/min at 35 degrees C, and the absorbance is monitored at 220 nm. The fraction eluted in the void volume was quantified for urinary protein, using bovine serum albumin (NIST SRM 927) as the standard. The linear range of the assay was 10--5000 mg/l, and the precision was 1.5% in two samples with concentrations of 1037 and 4338, respectively. The analytical recovery was 96--104%. Low molecular weight substances such as glucose, ascorbic acid and bilirubin did not interfere the assay. The assay was satisfactorily applied to a variety of proteins regardless of their nature or molecular weights (12.4 kDa) including beta2-microglobulin and Bence Jones Proteins. Surveys in five clinical laboratories, employing different types of HPLC apparatus with the same column type, showed satisfactory measurement precision (CV 2.1%) for three urine samples with different protein concentrations.

Artifacts↗

PubMed2001

Improved nasal absorption of drugs using poly-L-arginine: effects of concentration and molecular weight of poly-L-arginine on the nasal absorption of fluorescein isothiocyanate-dextran in rats.

The effects of the concentration and molecular weight of poly-L-arginine (poly-L-Arg) on the in vivo nasal absorption of fluorescein isothiocyanate-labeled dextran (MW, 4 kDa, FD-4) in rats were studied. When poly-L-Arg with a range of different molecular weights (MW, 8.9, 45.5 and 92.0 kDa) was applied intranasally at various concentrations, the bioavailability (F(0-9 h)) of FD-4 increased with the increasing concentration of poly-L-Arg. The enhanced absorption was also dependent on the molar concentration, in that the poly-L-Arg with a higher molecular weight increased F(0-9 h) at a lower molar concentration. In addition, for each applied concentration, the poly-L-Arg exhibited a molecular weight-dependence as far as the enhancement of FD-4 absorption was concerned. On the other hand, the maximum absorption rate (MAR) of FD-4, calculated by means of a deconvolution method, tended to reach a maximum plateau level at a lower applied concentration for the poly-L-Arg with the highest molecular weight, but this plateau level was almost the same for poly-L-Arg with molecular weights of 45.5 and 92.0 kDa. Moreover, the simulated absorption profiles of FD-4 indicate that the degree of enhancement (the level of MAR and the subsequent reduction in the absorption rate) was dependent on the molecular weight of poly-L-Arg, while the effect of poly-L-Arg was maintained for a longer period, depending on the applied concentration, although the MAR was relatively similar. These results indicate that the molecular weight of poly-L-Arg appears to affect both the enhancing efficiency (absorption rate) and the time-frame of this enhancing effect, whereas the concentrations of each poly-L-Arg system applied only have an effect on the time-frame. These effects may also be associated with the charge density of a poly-L-Arg molecule.

Absorption↗

PubMed2001

[The trend of childhood bacterial meningitis in Japan (1997.7-2000.6)].

We surveyed the epidemiology of purulent meningitis in pediatrics for 3 years between July 1997 and June 2000 in Japan and obtained the following results. The number of cases of purulent meningitis was 428, which was equivalent of 1.1-1.7 children out of 1,000 hospitalized those in pediatrics per year. The age-distribution for the infections was the highest under 1 year of age and it decreased as the age increased. Under 1 year of age, the highest distribution was observed in one month of age and under 1 month of age, the highest distribution was observed in 7 days of or younger ages. Haemophilus influenzae was the most common pathogen causing the infections, followed by Streptococcus pneumoniae, group B streptococcus, and Escherichia coli. Relationship between causing pathogens and age-distribution was as follows: group B streptococcus and E. coli were major pathogens under 4 months of age and H. influenzae and S. pneumoniae were major pathogens over 3 months of age. Susceptibility tests performed at each facility demonstrated that 25.3% of H. influenzae isolates and 38.7% of S. pneumoniae isolates were drug-resistant. Analysis of resistant genes for H. influenzae and S. pneumoniae isolates, which were stored and sent, demonstrated higher rates of resistance than those observed in susceptibility tests. These results suggest that the increase in insufficient efficacy of usual treatment with combination of ampicillin and cefotaxime is predictable against the infections. Therefore, the treatment for the infections should be reconsidered.

Female↗

PubMed2001

[Pharmacological treatments of Parkinson's disease].

Antiparkinsonian agents applied or under the investigation for the treatment of patients with Parkinson's disease were reviewed. Tremor, akinesia, rigidity and postual instability are key signs of Parkinson's disease. The most important one is akinesia, which includes decreased spontaneous locomotor activity, slowness of movement, awkwardness and freezing. The main pathophysiology of Parkinson's disease is neurodegeneration of nigrostriatal dopaminergic neurons. Neurotoxins or oxidative stress to the dopaminergic neurons have been discussed as one of the etiologies of degeneration. Antioxidant or neuroprotective agents will be the future drugs for Parkinson's disease. At present, supplement of dopamine by levodopa administration, retarding the metabolism of levodopa or dopamine by a dopa decarboxylase inhibitor (DCI), MAO-B (monoamine oxidase inhibitor type B) inhibitor or catechol-O-methyltransferase (COMT) inhibitor, dopamine receptor agonists, anticholinergic agents, dopamine release enhancer/uptake inhibitor, N-methyl-D-aspartate (NMDA) receptor antagonists are applied for the treatment of Parkinson's disease. New agents such as adenosine receptor antagonists, serotonergic agents and nicotinic receptor agonists are under investigation. Agents to facilitate the growth of nerves or to inhibit degeneration of nerves are also studied and will be developed for the treatment of Parkinson's disease in the future. In the case of familial Parkinson's disease, abnormal genes were identified. Gene therapy might be another future treatment for these cases.

Amantadine↗