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Biomedical subjects

N Shimada

Publications and source records attributed to N Shimada.

At least 91 records · Page 5Linked to original sources
PubMed1999

Bacillus thuringiensis insecticidal Cry1Aa toxin binds to a highly conserved region of aminopeptidase N in the host insect leading to its evolutionary success.

Bacillus thuringiensis insecticidal protein, Cry1Aa toxin, binds to a specific receptor in insect midguts and has insecticidal activity. Therefore, the structure of the receptor molecule is probably a key factor in determining the binding affinity of the toxin and insect susceptibility. The cDNA fragment (PX frg1) encoding the Cry1Aa toxin-binding region of an aminopeptidase N (APN) or an APN family protein from diamondback moth, Plutella xylostella midgut was cloned and sequenced. A comparison between the deduced amino acid sequence of PX frg1 and other insect APN sequences shows that Cry1Aa toxin binds to a highly conserved region of APN family protein. In this paper, we propose a model to explain the mechanism that causes B. thuringiensis evolutionary success and differing insect susceptibility to Cry1Aa toxin.

Amino Acid Sequence↗
PubMed1999

Overexpression of nucleoside diphosphate kinases induces neurite outgrowth and their substitution to inactive forms leads to suppression of nerve growth factor- and dibutyryl cyclic AMP-induced effects in PC12D cells.

Whether nucleoside diphosphate kinase (NDPK) is involved in neuronal differentiation was investigated with special reference to its enzyme activity. Neurite outgrowth of PC12D cells induced by nerve growth factor or a cyclic AMP analog was suppressed to some extent when inactive NDPKs (the active site histidine 118 was replaced with alanine), not active forms, were transiently overexpressed. This suppression was more definite in their stably expressed clones. NDPKbeta-transfected clones and, to a lesser extent, NDPKalpha-transfected clones, but not inactive NDPK-transfected clones, extended neurites without differentiation inducers. These results imply that NDPKs may play a role by exerting their enzyme activity during differentiation of PC12 cells.

Alanine↗
PubMed1999

Association between duration of obesity and risk of non-insulin-dependent diabetes mellitus. The Sotetsu Study.

The authors investigated the association between duration of obesity (ordinary obesity as body mass index (BMI) (kg/m2) > or = 25.0 and extreme obesity as BMI > or = 27.8) and the risk of diabetes mellitus. Male employees of a railway company, aged 30 years or older, observed for 10 years or more, free from serious disease conditions, with initial BMI <25.0, aged 30 years or more at the time diabetes was diagnosed, and with complete data, were examined by univariate and multivariate analyses (n = 1,598). Age-adjusted odds ratios for diabetes were significantly increased among males who were obese for 10-19.9 years and >20 years (odds ratios = 2.10 and 2.84 for ordinary obesity and 6.14 and 4.15 for extreme obesity, respectively). Additional adjustment for current obesity, physical activity, smoking, drinking, family history, and observation period did not change the findings remarkably. In conclusion, > or = 10 years duration of ordinary obesity or > or = 1 year of extreme obesity was an important predictor for diabetes independent of age, current obesity, physical activity, smoking, drinking, family history, and observation period.

Adult↗
PubMed1999

Enantioselectivity of bunitrolol 4-hydroxylation is reversed by the change of an amino acid residue from valine to methionine at position 374 of cytochrome P450-2D6.

The enantioselectivity of 4-hydroxylation of bunitrolol (BTL), a beta-adrenoceptor blocking drug, was studied in microsomes from human liver, human hepatoma (Hep G2) cells expressing CYP2D6, and lymphoblastoid cells expressing CYP2D6. Kinetics in human liver microsomes showed that the Vmax value for (+)-BTL was 2.1-fold that of (-)-BTL, and that the Km value for (+)-BTL was lower than that for the (-)-antipode, resulting in the intrinsic clearance (Vmax/Km) of (+)-BTL being 2.1-fold over its (-)-antipode. CYP2D6 (CYP2D6-met) expressed in Hep G2 cells had a methionine residue at position 373 of the amino acid sequence and a rat-type N-terminal peptide (MELLNGTGLWSM) instead of the human-type (MGLEALVPLAVIV), and showed enantioselectivity of [(+)-BTL < (-)-BTL] for the rate of BTL 4-hydroxylation. In contrast, enantioselectivity [(+)-BTL > (-)-BTL] for Hep G2-CYP2D6 (CYP2D6-val) with a human-type N-terminal peptide that had a valine residue at 374, which corresponds to the methionine of the CYP2D6-met variant, was the same as that for human liver microsomes. We further confirmed that CYP2D6-met and CYP2D6-val expressed in human lymphoblastoid cells, both of which have methionine and valine, respectively, at position 374 and a human-type N-terminal peptide, exhibited the same enantioselectivities as those obtained from CYP2D6-met and CYP2D6-val expressed in the Hep G2 cell system. These results indicate that the amino acid at 374 of CYP2D6 is one of the key factors influencing the enantioselectivity of BTL 4-hydroxylation.

Adrenergic beta-Antagonists↗
PubMed1999

Economic evaluation of alternative indicators for screening for diabetes mellitus.

BACKGROUND: the optimal indicator for screening for diabetes mellitus without relying on fasting conditions was clarified. METHODS: the subjects were 891 men ages 26 through 80 years (48.5 +/- 8.5). The objectives of this study were (1) to elucidate the efficacy of 1,5-anhydroglucitol (1,5-AG), glycosylated hemoglobin, and fructosamine (FRA) as screening tests for non-insulin-dependent diabetes mellitus (NIDDM) or for impaired glucose tolerance (IGT) and (2) to perform an economic evaluation for each indicator. The efficacy of each indicator was evaluated by drawing the receiver operating characteristic curves and calculating the areas under these curves (AUCs). An original model was developed for the pur pose of cost-effectiveness analysis. RESULTS: each indicator was evaluated as a screening test for NIDDM alone and for both IGT and NIDDM. The AUCs of 1,5-AG and fasting plasma glucose were the largest in the case of the detection of NIDDM alone and the detection of both IGT and NIDDM, respectively. FRA was, however, the most cost-effective in Japan. CONCLUSION: using equations, we indicated the equi librium points at which the cost-effectiveness ratios of each indicator intersected in order to generalize the results. By calculating the appropriate-actual ratios of costs for each indicator, we could ascertain the optimal indicator for each country.

Adult↗
PubMed1999

Isoform selective inhibition and inactivation of human cytochrome P450s by methylenedioxyphenyl compounds.

1. A series of methylenedioxyphenyl compounds were evaluated for their inhibitory and inactivation effects on nine human cytochrome P450 (CYP) activities using microsomes from human B-lymphoblast cells expressing specific human CYP isoforms. 2. Methylenedioxyphenyl compounds which possess a bulky structure such as 1,4-benzothiazine showed substantial inhibition of S-warfarin 7-hydroxylation catalysed by CYP2C9, S-mephenytoin 4'-hydroxylation by CYP2C19, bufuralol 1'-hydroxylation by CYP2D6, and testosterone 6beta-hydroxylation by CYP3A4. Regarding ethoxyresorufin O-deethylation catalysed by CYP1A1 and benzyloxyresorufin O-dealkylation by CYP2B6, the subtle change of a substitution of the 1,4-benzothiazine structure affected the inhibition selectivity. Ethoxyresorufin O-deethylation by CYP1A2, coumarin 7-hydroxylation by CYP2A6, and chlorzoxazone 6-hydroxylation by CYP2E1 were not inhibited by almost any of the methylenedioxyphenyl compounds. The inhibitory effects of methylenedioxyphenyl compounds that possess a short chain amino group on the human CYP isoforms were not significant. 3. The methylenedioxyphenyl compounds inactivated CYP1A1 (k(inact) = 0.034 min(-1) and K(i) = 0.81 microM), CYP2C9 (k(inact) = 0.041 and 0.042 min(-1) and K(i) = 0.56 and 0.15 microM), CYP2D6 (k(inact) = 0.044-0.339 min(-1) and K(i) = 0.21-19.88 microM), and CYP3A4 (k(inact) = 0.076-0.251 min(-1) and K(i) = 0.25-0.69 microM). These results suggested that the methylenedioxyphenyl compounds investigated in this study would be potent mechanism-based inactivators of these human CYP isoforms. In contrast, CYP2B6 and CYP2C19 were not inactivated. 4. The present study suggested that the selectivity of inhibition or inactivation of human CYP isoforms by methylenedioxyphenyl compounds may vary according to the structure of the side chain.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Activation of phenacetin O-deethylase activity by alpha-naphthoflavone in human liver microsomes.

1. The roles of different human cytochrome P450s (CYP) in phenacetin O-deethylation were investigated using human liver microsomes and recombinant proteins. Phenacetin O-deethylase (POD) activities in human liver microsomes at substrate concentrations of 10 and 500 microM were inhibited by 0.1 and 1 microM alpha-naphthoflavone and activated by 10 and 100 microM alpha-naphthoflavone. The activation of POD activity in human liver microsomes by alphanaphthoflavone was inhibited by 100 microM aniline, anti-CYP2E1 antibody, 1 microM ketoconazole and anti-CYP3A4 antibody. 2. In recombinant CYP from human B-lymphoblast cells, POD activities at a phenacetin concentration of 500 microM were detected for CYP2E1 and CYP3A4, as well as CYP1A2, CYP1A1, CYP2C19, CYP2C9 and CYP2A6. In recombinant CYP from human B-lymphoblast cells or baculovirus-infected insect cells and in reconstituted systems, a requirement of cytochrome b5 (b5) for POD activities catalysed by CYP2E1 and CYP3A4 was observed. The activation of POD activity by alpha-naphthoflavone was observed for CYP3A4, but not for CYP2E1. Co-expression of b5 with CYP3A4 enhanced the activation of POD activity by alpha-naphthoflavone. 3. In the absence of alpha-naphthoflavone, the POD activity in pooled human liver microsomes at 500 microM phenacetin was significantly inhibited (p<0.0001) by 10 microM fluvoxamine, but not by 1 microM ketoconazole. In the presence of alpha-naphthoflavone, the activity was significantly inhibited (p<0.0001) by 1 microM ketoconazole, but not by 10 microM fluvoxamine. 4. Inter-individual differences in the effects of alpha-naphthoflavone on POD activity in human liver microsomes were observed, and the involvement of CYP3A4 as well as CYP1A2 in POD activity in human liver was identified even at a low substrate concentration.

Aniline Compounds↗
PubMed1999

New approach in the evaluation of a fitness program at a worksite.

The most common methods for the economic evaluation of a fitness program at a worksite are cost-effectiveness, cost-benefit, and cost-utility analyses. In this study, we applied a basic microeconomic theory, "neoclassical firm's problems," as the new approach for it. The optimal number of physical-exercise classes that constitute the core of the fitness program are determined using the cubic health production function. The optimal number is defined as the number that maximizes the profit of the program. The optimal number corresponding to any willingness-to-pay amount of the participants for the effectiveness of the program is presented using a graph. For example, if the willingness-to-pay is $800, the optimal number of classes is 23. Our method can be applied to the evaluation of any health care program if the health production function can be estimated.

Cost-Benefit Analysis↗
PubMed1999

Colour vision of the foraging swallowtail butterfly papilio xuthus

This paper demonstrates that foraging summer-form females of the Japanese yellow swallowtail butterfly Papilio xuthus have colour vision. The butterflies were trained to feed on sucrose solution placed on a disk of a particular colour in a cage set in the laboratory. After a few such training runs, a butterfly was presented with the training colour randomly positioned within an array of disks of other colours, but with no sucrose solution. The results indicate that the butterflies learn rapidly to select the training colour reliably among different colours. The training colour was also correctly selected when it was covered with neutral density filters to reduce its brightness, or even when the colour was presented together with disks of a variety of shades of grey. These results demonstrate convincingly, for the first time, that a butterfly has true colour vision.

Journal Article↗
PubMed1999

Preparation and application of anti-idiotypic antibody against anti-gibberellin A4 antibody.

A monoclonal anti-idiotypic antibody was raised against anti-gibberellin A4 (GA4) antibody, which recognizes biologically active gibberellins such as GA1 and GA4 specifically. Amino acid sequences of variable regions of both anti-GA4 and anti-idiotypic antibodies were analyzed. By using the property of the anti-idiotypic antibody to compete with GA1/4 in binding to the anti-GA4 antibody, we successfully applied the anti-idiotypic antibody to ELISA as a tracer for measuring GA1/4. The single-chain Fv (scFv) gene of the anti-idiotypic antibody was constructed, and scFv expressed in E. coli showed binding activity to anti-GA4 antibody. These results suggest the possible application of anti-idiotypic antibody as a handy and stable source of an enzymatic tracer for ELISA by production of fusion protein of the scFv and an appropriate enzyme.

Amino Acid Sequence↗
PubMed1999

Expression of a functional single-chain antibody against GA24/19 in transgenic tobacco.

An anti-gibberellin A24/19 single-chain Fv gene was constructed from gamma and kappa genes cloned from a hybridoma cell line producing monoclonal antibody against gibberellin A24/19, biosynthetic precursors of gibberellin A4/1 which are biologically active per se. The single-chain Fv gene was introduced into tobacco plants after the binding activity of the single-chain Fv expressed in Escherichia coli was confirmed. When the single-chain Fv expression is targeted to endoplasmic reticulum, the plants could accumulate the single-chain Fv protein with the antigen binding activity up to 3.6% of the total soluble protein. On the other hand, when the expression is targeted to cytosol, accumulation of the single-chain Fv protein was not detected at all. The dwarf phenotype of the transgenic plants expressing the single-chain Fv protein, together with the preliminary analytical data indicating a decreased level of gibberellin A1 in the dwarf transgenics, suggested that the single-chain Fv decreased the concentration of bioactive gibberellins by trapping and inhibiting the metabolism of gibberellin A24 and/or A19 to gibberellin A4 and/or A1.

Antibodies, Monoclonal↗
PubMed1999

Association between alcohol intake and subjective health: the Sotetsu Study.

Subjective health and alcohol intake are important predictors of mortality. There have been few epidemiological studies, however, of the relationship between alcohol consumption and subjective health among the Japanese. The purpose of this study is to investigate the association between alcohol consumption and subjective health. The study subjects were 2,020 Japanese male employees, who were free from serious disease conditions. The data on subjective health and alcohol consumption were obtained by means of self-reported questionnaire. The subjects who responded "poor health" in the answer to the question about the subjective health status were considered to be in ill-health. Ethanol intake per day was calculated by multiplying the frequency of drinking by the ethanol intake per drinking occasion and summing up for each alcoholic beverage. Age, smoking status, physical activity, and sleeping hours were treated as confounding factors. As a result, subjects who consumed 25-36 or 49 g ethanol or more per day had a significantly lower risk of self-rated ill-health compared with those who had never drunk, and a significantly inverse trend was found independent of age, smoking status, physical activity, and sleeping hours. In conclusion, moderate drinkers have a lower risk of self-rated ill-health among Japanese male employees investigated.

Adolescent↗
PubMed1999

Plasma, urinary, and erythrocyte concentrations of guanidino compounds in patients with chronic renal failure.

Guanidino compounds are among the most likely candidates for uremic toxins. We determined the plasma, erythrocyte, and urinary concentration of guanidino compounds in 30 hemodialysis patients and 15 patients with chronic renal failure who had not undergone hemodialysis. Guanidino compounds were measured by high-performance liquid chromatography. Plasma levels of taurocyamine, guanidinosuccinic acid, alpha-N-acetyl-L-arginine, creatine, guanidinobutyric acid, guanidine, and methylguanidine were significantly increased in patients with chronic renal failure with or without hemodialysis. In contrast, plasma guanidinoacetic acid concentrations were significantly decreased. Erythrocyte concentrations of creatinine, guanidinosuccinic acid, guanidine and methylguanidine were also markedly elevated. No correlation was observed between plasma creatinine concentration and erythrocyte concentration of guanidinosuccinic acid or methylguanidine. However, there was a significant correlation between plasma and erythrocyte methylguanidine, and between plasma and erythrocyte guanidinosuccinic acid.

Adult↗
PubMed1999

Application of a rigid endoscope to the microsurgical management of 54 cerebral aneurysms: results in 48 patients.

OBJECT: To enhance visual confirmation of regional anatomy, endoscopy was introduced during microsurgery for cerebral aneurysms. The risks and benefits are analyzed in the present study. METHODS: The endoscopic technique was used during microsurgery for 54 aneurysms in 48 patients. Forty-three aneurysms were located in the anterior circulation and 11 were in the posterior circulation. Thirty-eight aneurysms (70.4%) had not ruptured. All ruptured aneurysms in the present series produced Hunt and Hess Grade I or II subarachnoid hemorrhage. After initial exposure achieved with the aid of a microscope, the rigid endoscope was introduced to confirm the regional anatomy, including the aneurysm neck and adjacent structures. The necks of 43 aneurysms were clipped using microscopic control or simultaneous microscopic/endoscopic control. After clipping, the positions of the clip and nearby structures were inspected using the endoscope. Use of the neuroendoscope provided useful information that further clarified the regional anatomy in 44 cases (81.5%) either before or after neck clipping. In nine cases (16.7%), these details were available only with the use of the endoscope. In five cases (9.3%), the surgeons reapplied the clip on the basis of endoscopic information obtained after the initial clipping. There were two cases in which surgical complications were possibly related to the endoscopic procedures (one patient with asymptomatic cerebral contusion and another with transient oculomotor palsy). CONCLUSIONS: It is the authors' impression that the use of the endoscope in the microsurgical management of cerebral aneurysms enhanced the safety and reliability of the surgery. However, there is a prerequisite for the surgeon to be familiar with this instrumentation and fully prepared for the risks and inconveniences of endoscopic procedures.

Adult↗
PubMed1999

[A case of atypical polypoid adenomyoma with intramural myoma-like growth].

We encountered a case of a large atypical polypoid adenomyoma (APA) which showed characteristic intramural appearance. As many cases of APA of the uterus have been reported in recent years, macro- and microscopic findings of the lesion and its clinical characteristics have been investigated. However the pathogenesis and the natural history of the lesion remained to be solved owing to still limited number of the cases. We report this case to discuss the macroscopic findings and clinicopathologic characteristics of the lesion.

Adenomyoma↗
PubMed1999

Sertraline N-demethylation is catalyzed by multiple isoforms of human cytochrome P-450 in vitro.

Sertraline, a new antidepressant of the selective serotonin reuptake inhibitor class, is extensively metabolized to desmethylsertraline in humans. We identified the cytochrome P-450 (CYP) isoforms involved in sertraline N-demethylation using pooled human liver microsomes and cDNA-expressed CYP isoforms. Eadie-Hofstee plots for the sertraline N-demethylation in human liver microsomes were monophasic. The estimated Michaelis-Menten kinetic parameters were: KM = 18.1 +/- 2.0 microM, Vmax = 0.45 +/- 0.03 nmol/min/mg of protein, and Vmax/KM = 25.2 +/- 4.3 microl/min/mg of protein. At the substrate concentration of 20 microM, which approximated the apparent KM value, sulfaphenazole (CYP2C9 inhibitor) and triazolam (CYP3A substrate) reduced the N-demethylation activities by 20 to 35% in human liver microsomes, whereas the inhibition induced by mephenytoin (CYP2C19 substrate) or quinidine (CYP2D6 inhibitor) was marginal. The anti-CYP2B6 antibody inhibited the sertraline N-demethylation activities by 35%. Sertraline N-demethylation activities were detected in all cDNA-expressed CYP isoforms studied. In particular, CYP2C19, CYP2B6, CYP2C9-Arg, CYP2D6-Val, and CYP3A4 all showed relatively high activity. When the contributions of CYP2D6, CYP2C9, CYP2B6, CYP2C19, and CYP3A4 were estimated from the Vmax/KM of cDNA-expressed CYP isoforms and from their contents in pooled human liver microsomes, the values were found to be 35, 29, 14, 13, and 9%, respectively. The results suggest that at least five isoforms of CYP (CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4) are involved in the sertraline N-demethylation in human liver microsomes and that the contribution of any individual isoform does not exceed 40% of overall metabolism. Therefore, concurrent administration of a drug that inhibits a specific CYP isoform is unlikely to cause a marked increase in the plasma concentration of sertraline.

Antidepressive Agents↗