Search PubMed⌕ Search

Biomedical subjects

M Tsukada

Publications and source records attributed to M Tsukada.

At least 37 records · Page 2Linked to original sources

Fast and stable method for simulating quantum electron dynamics

A fast and stable method is formulated to compute the time evolution of a wave function by numerically solving the time-dependent Schrodinger equation. This method is a real-space-real-time evolution method implemented by several computational techniques such as Suzuki's exponential product, Cayley's form, the finite differential method, and an operator named adhesive operator. This method conserves the norm of the wave function, manages periodic conditions and adaptive mesh refinement technique, and is suitable for vector- and parallel-type supercomputers. Applying this method to some simple electron dynamics, we confirmed the efficiency and accuracy of the method for simulating fast time-dependent quantum phenomena.

Journal Article↗

Enhancement of vasoconstrictor responses to 5-HT but no to methoxamine by cooling in isolated dog lingual and mesenteric arteries.

The effect of temperature on submaximal vasoconstrictions to an intraluminal injection of serotonin (5-HT) and methoxamine was investigated in isolated and perfused canine lingual and mesenteric arteries, using the cannula insertion method. In both arteries cooling (from 37 degrees C to 27 degrees C) caused a remarkable enhancement of vasoconstriction to 5-HT, but did not to methoxamine. In lingual arteries, methoxamine-induced constrictions were strongly depressed, although those were slightly depressed in mesenteric arteries. It is assumed that 5-HT produces an important role to modulate vascular tonicity in low temperature conditions.

Adrenergic alpha-Agonists↗

[Case-control study of risk factors for cedar pollinosis among parents of 3-year-old children].

PURPOSE: To identify risk factors associated with cedar pollinosis among parents of three-year-old children. METHODS: The subjects were parents whose children underwent health examination at the age of three years in September and October 1997 in Tochigi prefecture. We distributed questionnaires to the examinees beforehand with the request that they be filled in and brought to the examination site. Information on parents' environmental factors (place of residence, type and structure of housing, and distance from roads with heavy traffic), and mothers' past history and family history of allergic diseases was obtained. We defined cedar pollinosis in terms of three symptoms, sneezing, nasal discharge, and nasal obstruction, between February and May. Controls were those who did not have any of the three symptoms. Environmental factors were assessed with univariate and multivariate analyses using unconditional logistic models. Maternal genetic factors were also analyzed with odds ratios and 95% confidence intervals calculated for each. We also compared odds ratios of environmental factors between groups with and without genetic factors. RESULTS: Of the parents of children taking the health examination, 90.2% took part (2,968 of 3,291 couples). Information was obtained from 2,846 mothers and 2,905 fathers. Mother and father cases were 312 and 229, and controls were 1,857 and 1,934, respectively. For the univariate analysis of environmental factors, place of residence (residential area/agricultural area), type of housing (apartment complex/solitary house), structure (reinforced concrete building/wooden house), and distance from heavy traffic (< 100 m/100 m+) were positively related to cedar pollinosis. For the multivariate analysis using unconditional logistic models, the odds ratio was significantly high for distance from heavy traffic (< 100 m/100 m+) among fathers. Mothers' past history and family history of allergic diseases showed high odds ratios for cedar pollinosis. We classified groups with and without past and family histories of allergic diseases (group with and without genetic factors) for assessment with multivariate analyses. Odds ratios for the group with an allergic history were higher than for those without such a history, but difference for factors such as, distance from heavy traffic type of housing, and structure were not statistically significant. CONCLUSION: Risk of cedar pollinosis increases with distance from heavy traffic among fathers. Mothers with histories of allergy show slightly elevated odds ratios for environmental factors, but without statistic significance.

Case-Control Studies↗

On the occurrence of neuronal sprouting in the frontal cortex of a patient with Down's syndrome.

We report on the autopsy of a 52-year-old Down's syndrome patient with a 9-year history of progressive dementia. Histologically, there was a marked neuronal loss in the cerebral cortices with numerous neurofibrillary tangles and senile plaques and congophilic angiopathy. The second cortical layer was spongy in appearance and the frontal and temporal white matter showed marked myelin pallor. Immunohistochemistry for MAP2 of the frontal and temporal cortices revealed great reduction in the number of large pyramidal neurons. On the other hand, a much stronger MAP2 immunoreactivity than that seen in the controls was observed in the second layer, which consisted of many small pyramidal neurons with features of aberrant sprouting. They were recognized in the frontal cortices but not in the temporal cortices, and were not immunolabeled with phosphorylated-tau nor MAP5. On double immunolabeling with MAP2 and beta-amyloid antibodies, these neurons were found to be not directly associated with the formation of senile plaques. Ultrastructurally, MAP2 was immunolocalized in an amorphous granular form in the neuronal somata and processes, and paired helical filaments were not immunolabeled. The observation may indicate the occurrence of a remarkable plastic response of small pyramidal cortical neurons in this patient with Down's syndrome.

Amyloid beta-Peptides↗

Structural and functional analysis of a novel coiled-coil protein involved in Ypt6 GTPase-regulated protein transport in yeast.

The yeast transport GTPase Ypt6p is dispensable for cell growth and secretion, but its lack results in temperature sensitivity and missorting of vacuolar carboxypeptidase Y. We previously identified four yeast genes (SYS1, 2, 3, and 5) that on high expression suppressed these phenotypic alterations. SYS3 encodes a 105-kDa protein with a predicted high alpha-helical content. It is related to a variety of mammalian Golgi-associated proteins and to the yeast Uso1p, an essential protein involved in docking of endoplasmic reticulum-derived vesicles to the cis-Golgi. Like Uso1p, Sys3p is predominatly cytosolic. According to gel chromatographic, two-hybrid, and chemical cross-linking analyses, Sys3p forms dimers and larger protein complexes. Its loss of function results in partial missorting of carboxypeptidase Y. Double disruptions of SYS3 and YPT6 lead to a significant growth inhibition of the mutant cells, to a massive accumulation of 40- to 50-nm vesicles, to an aggravation of vacuolar protein missorting, and to a defect in alpha-pheromone processing apparently attributable to a perturbation of protease Kex2p cycling between the Golgi and a post-Golgi compartment. The results of this study suggest that Sys3p, like Ypt6p, acts in vesicular transport (presumably at a vesicle-docking stage) between an endosomal compartment and the most distal Golgi compartment.

Amino Acid Sequence↗

[Relationship between breast milk and atopic dermatitis in children].

OBJECTIVE: To determine whether or not dioxins and furans in breast milk have a role in the prevalence of atopic dermatitis among children. METHODS: The target population of the study was all children participating in health check-up program for 3-year-old children in Tochigi Prefecture in September and October 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. RESULTS: Questionnaires from 2,968 children (85.3% of those who were to participate in the programs, and 90.2% of children who participated them) were analyzed. The risk of atopic dermatitis was higher among children with breast milk (odds ratio [OR] = 1.37 with 95% confidence interval [CI] 1.02-1.83) and those with mixed nutrition (OR = 1.21, 95% CI: 0.94-1.57) in comparison with children with only bottled milk. Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.27; 95% CI, 1.01-1.62) and those with second or later parity orders (OR = 1.32, 95% CI; 1.04-1.67) were also risk factors of the dermatitis after the adjustment for some potential confounding factors. CONCLUSION: Breast milk elevates the risk of atopic dermatitis slightly; the risk is, however, higher in children in second or later parity orders. If the PCDDs and PCDFs in breast milk cause the dermatitis, this would contradict the assumed metabolism of these chemicals in human bodies.

Adult↗

Use of Bombyx mori silk fibroin as a substratum for cultivation of animal cells.

The growth of animal cells on silk fibroin-coated plates was examined. The anchorage-dependent cells showed almost the same growth on both fibroin- and collagen-coated plates, and it was 30-50% higher than that on polystyrene plates coated with hydrophilic groups. On the other hand, the growth of the anchorage-independent hybridomas on the three different plates did not show a significant difference. The cells grown on the respective plates produced their products with the same efficiency despite the difference in the chemical properties of the plates. In this paper, it is demonstrated that silk fibroin can be used as the substratum for the culture of animal cells in place of collagen.

Animals↗

Effect of the chemical modification of the arginyl residue in Bombyx mori silk fibroin on the attachment and growth of fibroblast cells.

We prepared matrices of Bombyx mori silk fibroin (SF) with different degrees of modification of arginyl residues by reaction between 1,2-cyclohexanedione (CHD) and SF. Two kinds of SF, namely native SF (NSF), obtained from the silk gland of silkworm larvae, and regenerated SF (RSF), prepared from cocoons of the same silkworm, were used in this study because their amino acid compositions were slightly different from each other. The attachment and growth of mouse fibroblast (L-929) cells on the matrices of the NSF and RSF, in which half or almost all of the arginyl residues were modified (NSF50, RSF50, NSF100, and RSF100), were studied using a cell culture method. Both NSF50 and NSF100 exhibited higher cell attachment than did the unmodified NSF. While the cell growth on NSF50 was not significantly different from that on NSF and NSF100, the growth on NSF100 was higher than that on NSF. The cells attached to NSF50 and NSF100 were extensively spread out and their filopodia were visible by SEM. The cell attachment and growth on RSF were comparable to those on NSF100. Although RSF50 exhibited almost the same cell attachment as did the unmodified RSF, RSF100 exhibited a lower cell attachment than did the unmodified RSF and RSF50. There were no significant differences in the cell growth among RSF series. The cells attached to RSF50 and RSF100 aggregated to form masses, and their filopodia could not be found. The relationship of cell attachment to the basicity of the substrate is considered because the modification of the positively charged arginyl residue changed the basicity of the substrate and the cell attachment on the substrate.

Amino Acids↗

Effects of recombinant human serum albumin on ascites in rats with puromycin aminonucleoside-induced nephropathy.

1. Recombinant human serum albumin (rHSA) (1 g/kg) significantly decreased the weight of ascites in rats with puromycin aminonucleoside-induced nephropathy. 2. Furosemide (1-30 mg/kg) did not significantly reduce the weight of ascites in this model. 3. A combination of rHSA (1 g/kg) with furosemide (5 mg/kg) significantly decreased the weight of ascites in this model compared with furosemide alone. 4. In consideration of these results, rHSA can be a substitute for human serum albumin products prepared from human plasma in therapy for ascites or edema in furosemide-resistant nephrotic syndrome.

Animals↗

Evidence on N-acetyltransferase allele-associated metabolism of hydrazine in Japanese workers.

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Adult↗

A cross-sectional observation of the health effects of hydrazine hydrate and differences of its metabolism by NAT2 polymorphism.

OBJECTIVES: To summarize the results of two studies that attempted to clarify: (1) the health effects of hydrazine hydrate (HH) (N2H4 x H2O: CAS No. 7803-57-8); and (2) the influence of allelic polymorphism of N-acetyltransferase (NAT2) on the metabolism of HH. METHODS: A cross-sectional survey was carried out on 172 male HH-exposed workers and 125 male referent workers at five factories in Japan. The biological half-lives of HH after 1 h of exposure were determined in 12 workers, four workers in each of three NAT2 phenotypes. Clinical examinations were performed and acute and chronic subjective symptoms related to HH were examined by self-administered questionnaires. NAT2 phenotypes were assessed. RESULTS: No hydrazine was detected in either the breathing zones or the urine of the referent workers. The mean hydrazine concentration in the breathing zones, hydrazine and acetylhydrazine in urine, and the cumulative exposure level were 0.0109 ppm, 0.8660 micromol/g x Cr, and 2.80 ppm-years, respectively. There was no difference and no dose-dependent change in the health examination items between HH-exposed and referent workers after adjusting confounding factors, nor in terms of the differences of NAT2 phenotypes. Of 90 subjective symptoms, complaints of nightmares were significantly related to HH exposure. The half-life of urinary hydrazine and acetylhydrazine on rapid, intermediate, and slow phenotypes was 1.68, 3.01, and 4.46 h, respectively. CONCLUSION: This study suggested that current and cumulative exposure to HH did not affect the workers' health, and the half-life of the slow phenotype was longer than those of the rapid and intermediate phenotypes.

Adolescent↗

Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae.

Autophagic protein degradation includes bulk protein turnover with dynamic membrane reorganization, in which formation of novel organelles autophagosomes play key roles. We have shown that Saccharomyces cerevisiae performs the autophagy in the vacuole, a lytic compartment of yeast, in response to various kinds of nutrient starvation. Here we show that the APG1 gene, involved in the autophagic process in yeast, encodes a novel type of Ser/Thr protein kinase. Our results provide direct evidence for involvement of protein phosphorylation in regulation of the autophagic process. We found overall homology of Apglp with C. elegans Unc-51 protein, suggesting that homologous molecular mechanisms, conserved from unicellular to multicellular organisms, are involved in dynamic membrane flow.

Amino Acid Sequence↗

Mechanisms for histamine H1 receptor-mediated vasodilation in isolated canine lingual arteries.

Histamine and selective histamine receptor subtype agonists' effects on isolated and perfused canine lingual arteries were investigated with the cannula insertion method. In preparations preconstricted with phenylephrine, histamine and a selective histamine H1 receptor agonist, 2-pyridylethylamine induced a biphasic vascular response in a dose-related manner, i.e., vasoconstriction followed by vasodilatation. The biphasic responses to histamine and 2-pyridylethylamine were inhibited by diphenhydramine, a selective histamine H1 receptor antagonist, but were not influenced by cimetidine, a selective histamine H2 receptor antagonist. Dimaprit, a selective histamine H2 receptor agonist, induced only a slight vasoconstriction which was not modified by cimetidine. Dimaprit never induced vasodilation even at a large dose. A histamine H3 receptor agonist, R-alpha-methylhistamine, did not produce any significant vascular responses. Moreover, histamine-induced vasodilation was in part inhibited by removal of the endothelium, and the vasodilation remaining was abolished by H1 blockade. Thus, it is concluded that in canine lingual arteries there are abundant histamine H1 receptors which mediate both vasoconstriction and vasodilation, and that the histamine-induced vasodilation is in part due to endothelium-dependent mechanisms.

Animals↗

Stimulus-dependent induction of long-term potentiation in CA1 area of the hippocampus: experiment and model.

In the CA1 area of the hippocampus, the magnitude of long-term potentiation (LTP) depends not only on the frequency of applied stimuli, but also on their number. With a slice preparation using extracellular recording in the hippocampus CA1 of a guinea pig, we investigate the magnitude of LTP induced by electrical stimuli with a range of frequencies and the number of applied stimuli. We find that the magnitude of the saturated potentiation obtained with periodic stimuli largely depends on the frequency and is insensitive to the number of stimuli, once the saturation level has been obtained. Furthermore, we investigated nonperiodic stimuli and found that the magnitude of the saturated potentiation is also sensitive to the statistical correlation between successive interstimulus intervals, even when their average frequency is held constant. In order to explain the LTP dependence on these various experimental parameters, we propose a simple mathematical model for the induction of LTP. In the model, an exponentially decaying element released as a result of previous stimuli is coupled with a new stimulus to act as the potentiation force, and the magnitude of potentiation is determined by this potentiation force. We can determine the decaying time constant of this hypothetical element as a model parameter by fitting the model to the experimental data. The time scale is found to be of the order of 200 msc. A molecular or cellular factor with this decaying time constant is likely to be induced in LTP induction.

Animals↗

Electrophysiological evidence of an increase in cold tolerance of cardiac muscles in mice after energy restriction.

Life-prolonging energy restriction (ER) has been known to extend longevity. The heart was selected as the target organ of ER and the electrophysiological properties of ER on the heart were investigated. Action potential parameters were measured on ventricular papillary muscles of C57BL/6 mice (2-6 months of age). Resting membrane potential (Rm) did not change even when the temperature was lowered to 20 degrees C in ER mice (-67.5 +/- 0.8 mV), however, the membrane was depolarized in the control (-61.1 +/- 1.1 mV). Action potential duration measured at 30 and 50% repolarization was significantly prolonged in ER mice at 20-35 degrees C. Ouabain (10 microM) decreased Rm in ER mice at 20 degrees C (-68.6 +/- 1.0 to -63.6 +/- 0.8 mV), but failed to decrease Rm in the control (-60.6 +/- 1.8 to -62.1 +/- 1.2 mV). There were no significant differences in extracted Na, K-ATPase activity or affinity and binding capacity of ouabain between ER and control hearts. These results indicate that in ER mice the lack of effect of temperature on Rm was not due to a change in the physicochemical properties of Na, K-ATPase. The present study collectively suggests that ER increases cold tolerance in the heart of mice.

Acclimatization↗

Synthesis of poly(ethylene glycol)-silk fibroin conjugates and surface interaction between L-929 cells and the conjugates.

Poly(ethylene glycol) (PEG)-silk fibroin (SF) conjugates (PEG2-SF) were prepared by the chemical modification of solubilized SF with 2,4-bis[O-methoxypoly(ethylene glycol)]-6-chloro-s-triazine (actPEG2) in borate buffer at 37 degrees C. The IR spectra and DSC curves of PEG2-SF and SF suggested the introduction of PEG into SF by the modification and the beta-sheet structure of both SF and PEG2-SF induced by the treatment with methanol aqueous solutions. The content of the PEG component in PEG2-SF was evaluated to be 67% by weight from the melting enthalpy change of PEG observed on the DSC thermogram of PEG2-SF. Water content and contact angle measurements of SF before and after the modification indicated that the hydrophilicity of the PEG2-SF surface increased compared with that of SF. The attachment and growth of fibroblast cells (L-929) on the matrix of PEG2-SF were studied by a cell culture method. PEG2-SF exhibited very low cell attachment and growth, though SF exhibited high cell attachment and growth. The filopodium of the cells attached to PEG2-SF could not be found, and the cells aggregated to form masses in scanning electron microscopy images. These results could be explained in terms of the increased hydrophilicity of the PEG2-SF surface.

Animals↗