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Biomedical subjects

M Kishimoto

Publications and source records attributed to M Kishimoto.

At least 37 records · Page 2Linked to original sources
PubMed2000

Increase in desulfurization activity of Rhodococcus erythropolis KA2-5-1 using ethanol feeding.

Rhodococcus erythropolis KA2-5-1 is one of the best strains for the desulfurization of dibenzothiophene (DBT) via a sulfur-specific pathway in which DBT is converted to the end product, 2-hydroxybiphenyl, by releasing sulfite via DBT-sulfone and 2-(2'-hydroxyphenyl) benzene sulphinate. The objective of this research is to develop a culture method in order to attain a high cell density with a high level of specific desulfurization activity. Compared with glucose or glycerol, ethanol was found to be a preferable carbon source for obtaining a high specific activity (SA) of desulfurization. When the amount of DBT fed was restricted by feeding 2.9 mg-DBT/g-ethanol solution, the maximum SA and final cell concentration were 135.5 (mmol-2HBP/kg-dry cell weight-h) and 37 (g-dry cell weight/l), respectively. On the other hand, when glucose or glycerol was used as a carbon source, the SA was lower than 50 (mM-2HBP/kg-dry cell weight-h) and the final cell concentration was also lower than 27 (g-dry cell weight/l). The activities of the desulfurization enzymes in R. erythropolis KA2-5-1 grown on ethanol were remarkably higher than when the strain was grown on glucose or glycerol. It was also suggested that NADH, which is produced by the biochemical reaction of NAD with ethanol catalyzed by alcohol dehydrogenase, might contribute to the conversion of FMN to FMNH2, which is a coenzyme for the activities of desulfurization enzymes.

Journal Article↗
PubMed2000

Evaluation of gut motility in type II diabetes by the radiopaque marker method.

BACKGROUND: The clinical usefulness of the radiopaque marker method for detecting diabetic gastrointestinal motility disturbances, was evaluated by examining 21 type II diabetes subjects who did not have any neuropathic symptoms. METHODS: After administration of a Sitzmark capsule, markers were located using plain abdominal radiographs, and the transit time of the markers through seven areas of digestive tract was calculated by Arhan's methods. The plasma concentration of acetaminophen at 45 min after oral administration was measured to evaluate gastric emptying time. The coefficient of variation of R-R intervals on the electrocardiograms (CV(R-R)) was measured to evaluate parasympathetic autonomic function. RESULTS: In the diabetics, the average (+/- SD) transit time through upper digestive tracts was slightly but not significantly elongated compared with control subjects (14.4 +/- 8.3 vs 9.9 +/- 6.1 h). Significant elongation was observed in transit time through the lower digestive tracts or the whole gut (44.6 +/- 20.9 and 57.9 +/- 22.3 h, respectively) compared with control subjects (23.3 +/- 8.5 and 33.2 +/- 11.0 h). The transit time of the markers from stomach to small intestine was highly correlated (r = 0.693) with plasma concentration of acetaminophen. The transit time through either the whole colon (r = 0.564) or the whole gut (r = 0.630) was highly correlated with CV(R-R). CONCLUSIONS: These findings suggest that the radiopaque marker method is a useful tool for detecting the sections of the digestive tract responsible for gut motility disturbances. In type II diabetics with no neuropathic symptoms, the lower digestive tracts may deteriorate prior to the impairment of upper digestive tracts.

Acetaminophen↗
PubMed2000

Control of antibody-antigen interaction using anion-induced conformational change in antigen peptide.

The binding of a monoclonal antibody to an epitope peptide was controlled by the conformational change of the epitope peptide induced by anions. We synthesized peptides in which the epitope sequence DTYRYI for the monoclonal antibody AU1 is located between amphiphilic peptides (KKLL)n and (LLKK)n. In the absence of an appropriate anion, the peptide was in a random coil state and the epitope was linear. In contrast, in the presence of an appropriate anion, the peptide exhibited an anti-parallel alpha-helical structure and the epitope was subsequently 'bent'. In the presence of 41 microM triphosphate, the association constant between the antibody and the peptide was decreased by one order of magnitude in the case of n = 3 and at least three orders of magnitude in the case of n = 4 or 5. Oligo-DNAs, as anions, dissociated the antibody-peptide complex, whereas triphosphate did not. The DNA concentrations required for 50% dissociation of the antibody-peptide complex at pH 7.5 were 4x10(-8), 1x10(-7) and 6x10(-6) M for decamer, octamer and hexamer DNA, respectively.

Amino Acid Sequence↗
PubMed2000

L-Lysine production by exponential feeding of L-threonine.

The effect of L-threonine feeding in the production phase on L-lysine production by Brevibacterium flavum, which requires L-homoserine or L-threonine for cell growth, was investigated considering the concerted inhibition by L-threonine plus L-lysine, and the metabolism related to lysine production. Exponential feeding of L-threonine increased L-lysine production to 70 g/l about three times that without feeding. From the analysis of the metabolic flux, carbon flux of L-lysine synthesis pathway in the production phase after L-threonine feeding was higher than that in the growth phase. The results show that feeding of an inhibitory substance may increase the production, especially when the substance is necessary for the continuation of cell growth and/or production.

Journal Article↗
PubMed2000

Multifocal fibrosclerosis as a possible cause of panhypopituitarism with central diabetes insipidus.

Multifocal fibrosclerosis denotes a combination of similar fibrous disorders occurring at different anatomical sites. We encountered a 53-year-old male patient with orbital pseudotumor, chronic paranasal sinusitis, fibrous nodules of the lungs, intracranial pachymeningitis, and panhypopituitarism with central diabetes insipidus (DI) as a possible manifestation of multifocal fibrosclerosis. It has been reported that intracranial pachymeningitis or orbital pseudotumor associated with multifocal fibrosclerosis could invade the sella turcica causing a variety of anterior and/or posterior pituitary dysfunctions. In our case, intracranial pachymeningitis apparently involved the pituitary stalk and gland. Isolated gonadotropin deficiency, in addition to central DI, preceded panhypopituitarism. Although panhypopituitarism with central DI due to multifocal fibrosclerosis is quite rare and only one case has ever been reported, this systemic fibrotic disorder can be a possible cause of panhypopituitarism with central DI.

Diabetes Insipidus↗
PubMed1999

A complementary peptide vaccine that induces T cell anergy and prevents experimental allergic neuritis in Lewis rats.

We have developed and described a new method of altering T cell-mediated autoimmune diseases by immunization with the complementary peptide against T cell epitopes. The complementary peptide (denoted NAE 07-06) to the bovine P2 protein, residues 60-70 (denoted EAN 60-70), was tested in the Lewis rat model of experimental allergic neuritis (EAN). Immunization with NAE 07-06 induced polyclonal and monoclonal Abs that inhibited the proliferation of the P2-specific T cell line, stimulated with EAN 60-70, and recognized Vbeta, but not Valpha, of TCRs. Proliferation of T cells treated with anti-NAE 07-06 Abs could be partially restored by treatment with rIL-2, in accordance with an anergy model. A homologous sequence was found between NAE 07-06 and the VDJ junction of the TCR beta-chain from an EAN 60-70-specific T cell line. Rats preimmunized with NAE 07-06 in vivo before EAN induction showed less disease severity clinically and histologically. These data suggest a new therapeutic approach for T cell-mediated autoimmune disorders through the induction of anti-TCR Abs with complementary peptide Ags.

Animals↗
PubMed1999

Induction of glycation suppresses glucokinase gene expression in HIT-T15 cells.

AIMS/HYPOTHESIS: Chronic hyperglycaemia in patients with Type II (non-insulin-dependent) diabetes mellitus often leads to a decline in glucose-responsive insulin secretion from pancreatic beta cells, a phenomenon called glucose toxicity. Upon hyperglycaemia, glycation reaction occurs in the beta cells and induces oxidative stress. To understand the molecular basis of the beta-cell glucose toxicity, we investigated the possible effects of glycation on the expression and enzymatic activity of glucokinase, which plays a crucial part in glucose-responsive insulin secretion. METHODS: Glycation and reactive oxygen species were induced in HIT-T15 cells by treatment with D-ribose and effects on glucokinase gene transcription, glucokinase protein amount, glucose phosphorylation activity, and DNA-binding activities of putative glucokinase gene transcription factors were evaluated. RESULTS: When glycation was induced in HIT-T15 cells, the activity of the human glucokinase gene beta-cell-type promoter was suppressed substantially (83% reduction at 60 mmol/l D-ribose). Also, similar reductions in mRNA and protein amounts of glucokinase and in the Vmax of its enzymatic activity were observed. In agreement with the reduction in the promoter activity, the two major transcription factors of the glucokinase gene, the Pal-binding factor and PDX-1, reduced their binding to their target sequences in the glucokinase gene promoter in glycation-induced HIT cells. Because these effects of D-ribose were counteracted by aminoguanidine or N-acetylcysteine, reactive oxygen species, generated by the glycation reaction, appears to be involved in the phenomena. CONCLUSION/INTERPRETATION: The induction of the glycation reaction, which is known to occur in pancreatic beta cells in chronic hyperglycaemia, suppresses the glucokinase gene transcription and its enzymatic activity. Thus, hyperglycaemia-dependent inhibition of glucokinase activity could in part explain beta-cell glucose toxicity.

Acetylcysteine↗
PubMed1999

Activation of extracellular signal-regulated kinase in lung tissues of mice treated with carcinogen.

The activation of extracellular signal-regulated kinase (ERK) in lung tissues of mice, as determined by the appearance of phosphorylated form, was observed on day 30 after urethane injection, and the activation also occurred in urethane-induced lung tumors. Immunohistochemical analysis using anti-phosphorylated ERK antibody indicated that the active form of ERK localized in alveolar epithelial cells. Furthermore, we confirmed by immunoprecipitation and immunoblot analysis that other essential components of the ERK cascade, that is, Ras, Raf and MEK (known as ERK kinase) were activated. These results indicate that the activation of the ERK signal in alveolar epithelial cells at the early stage of urethane-induced lung carcinogenesis is an important factor to develop lung tumors.

Animals↗
PubMed1999

Overexpression of the aldose reductase gene induces apoptosis in pancreatic beta-cells by causing a redox imbalance.

To determine the role of the polyol metabolizing pathway under hyperglycemic conditions, the effects of aldose reductase (AR) on the cellular functions of pancreatic beta-cells were examined. Stable transfectants of rat AR cDNA were obtained with a pancreatic beta-cell line, HIT, in which a negligible amount of AR was originally expressed. Overproduction of AR triggered DNA fragmentation, as judged with the TUNEL method and agarose gel electrophoresis. Morphological analysis by electron microscopy also clearly showed apoptosis of the AR-overexpressing HIT cells. Induction by interleukin-1beta of gene expression such as those of an inducible form of nitric oxide synthase (NOS-II) and Mn-superoxide dismutase (Mn-SOD), was much lower in the transfectants than in the control cells, while the expression of constitutively expressed genes such as those for Cu,Zn-superoxide dismutase and insulin was not changed. The susceptibility to interleukin-1beta stimulation of the expression of the NOS II and Mn-SOD genes was due to suppressed NF-kappaB activity, which is essential for the expression of these genes. In addition, the intracellular NADPH/NADP+ ratio was considerably lower in the AR-transfected cells than in control cells. Thus, the overexpression of AR in pancreatic beta-cells induced apoptosis that may be caused by a redox imbalance.

Aldehyde Reductase↗
PubMed1999

[Building aging level indices based on ability to perform personal care and household management activities].

Defining aging as deterioration of the ability required for the activities of daily living with increasing age, we developed a formula for estimating the age of aging. In 1994 and 1995, a questionnaire survey was conducted for 11,592 individuals (4,885 men, mean age 61.6, standard deviation 14.6; and 6,677 women, mean age 63.2, standard deviation 14.8) who were members of 7 cohorts (5 community-based cohorts and 2 cohorts of examiners at a health-promotion center). The questionnaire included three groups of questions related to medical treatment, aging-related symptoms, and personal care (ADL; Activities of Daily Living) and household management (IADL: Instrumental ADL). Multiple regression analysis was made by sex and age group (over 65 years old, under 65 years old) using age as a dependent variable and the three question categories as explanatory variables. Using multiple regression analysis by question category, five items were abstracted from each of the three groups, so that a total of 15 items were abstracted from all questions. Five items were then abstracted from the 15 by multiple regression analysis, and the predicted aging age for an individual is estimated using this statistical model from the results of the questionnaire survey. The predicted aging age is significantly associated with age (r = 0.40-0.49, p = 0.0001). The difference between the predicted aging age and age is greater among the older or younger people. The expected predicted aging age is estimated using regression analysis of the predicted aging age on age. Aging level indices by sex and age groups were determined by the difference between the expected predicted aging age and age. We are planning to carry out an epidemiological study on the risk factor for aging using the aging level indices in seven cohorts.

Activities of Daily Living↗
PubMed1999

Insulin resistance contributes to carotid arterial wall thickness in patients with non-insulin-dependent-diabetes mellitus.

The aim of this study was to clarify whether insulin resistance contributes to atherosclerosis in patients with non-insulin-dependent diabetes mellitus (NIDDM). Fifty-three NIDDM patients (36 males and 17 females, 53+/-10 years old (mean+/-SD)) were studied. As an index of atherosclerosis, we measured the average thickness (IMT) as well as basal thickness excluding the maximum thickness and the height of the maximum thickness of the carotid artery wall. Euglycemic hyperinsulinemic glucose clamp was conducted for 90 min to evaluate average glucose infusion rate (GIR) as an index of insulin sensitivity in the peripheral tissues. For another 180 min after intake of oral glucose load with 0.3 g/kg, the euglycemic hyperinsulinemic clamp was continued to measure ratio of splanchnic glucose uptake (SGU) as an index of insulin sensitivity of the liver. The patients were separated into three activity groups according to the grade of their leisure-time physical activity. GIR (r = -0.32, p < 0.05) but not SGU (r=0.139) showed a significant inverse relationship with IMT. Multivariant regression analysis indicated that age and total cholesterol remain as independent risk factors for basal thickness and GIR as only independent risk factor for the height of the maximum thickness. Paralleling the degrees of habitual exercise (low, moderate, and high active group), GIR was higher (6.19+/-1.02, 6.38+/-1.38, 7.44+/-1.80, respectively) and IMT was lower (1.34+/-0.33 mm, 1.20+/-0.31 mm, and 1.12+/-0.29 mm, respectively) in male NIDDM as well as in female NIDDM. These data suggest that insulin resistance in the peripheral tissues but not the splanchnic tissues may independently contribute to carotid arterial wall thickness and especially to plaque lesion, and that habitual exercise might reduce insulin resistance leading to attenuation of atherosclerosis.

Aged↗
PubMed1999

Impaired diurnal cardiac autonomic function in subjects with type 2 diabetes.

OBJECTIVE: To assess diurnal cardiac sympathetic and parasympathetic nerve functions in diabetic subjects with variable diabetic neuropathy. RESEARCH DESIGN AND METHODS: Frequency domain analysis of 24-h Holter ECG was done for 132 diabetic subjects (84 without any symptomatic neuropathy; 37 with only symptomatic peripheral neuropathy; 11 with symptomatic autonomic neuropathy) and 57 normal volunteers to calculate the low frequency (LF) component representing the beta-adrenoceptor function and the high frequency (HF) component representing the cardiac parasympathetic nerve function. RESULTS: Cardiac LF and HF components in diabetic subjects without peripheral neuropathy showed values comparable to those of normal volunteers and a similar circadian rhythm. Diabetic subjects with peripheral neuropathy or autonomic neuropathy showed significantly depressed LF and HF components and loss of the circadian rhythm of LF and HF components compared with diabetic subjects without neuropathy. Impairment of the LF component in the afternoon could be accounted for by the duration of diabetes and elevated HbA1c level. Impairment of the HF component at night could be accounted for by the duration of diabetes but not an elevated HbA1c level. CONCLUSIONS: These data indicated that diabetic subjects with peripheral neuropathy and diabetic subjects with symptomatic autonomic neuropathy, but not diabetic subjects without neuropathy, showed a marked decrease in cardiac sympathetic and parasympathetic nerve functions and loss of circadian rhythm.

Adult↗
PubMed1998

The inhibitory effect of vitamin E on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis in mice based on the regulation of polyamine metabolism.

The present study was carried out in order to estimate a usefulness of vitamin E against 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in mice. Feeding high doses of vitamin E suppressed the NNK-induced elevation of the activity of ornithine decarboxylase, a key enzyme of polyamine biosynthesis, in the lungs of mice at 4 weeks after injection. In contrast, the vitamin elevated the NNK-induced decrease of the activity of spermidine/spermine N1-acetyltransferase, a key enzyme of polyamine biodegradation. In conjugation with these events, the NNK-increased level of proliferating nuclear cell antigen as a marker of cell proliferation was suppressed by vitamin E treatment. Also, the supply of high doses of vitamin E suppressed NNK-induced lung tumorigenesis in mice. These results suggest that vitamin E inhibits the development of lung tumors in mice treated with NNK, partly due to the regulation of polyamine metabolism.

Animals↗
PubMed1998

The inhibitory effect of vitamin E on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced DNA injury and the fixation of the DNA injury in mouse lungs.

In order to estimate the effect of vitamin E on DNA injury and K-ras point mutation at an early stage of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone(NNK)-induced lung tumorigenesis in mice, the present study was carried out. Presupplement with vitamin E about 15 times more than control for a week significantly inhibited NNK-induced O6-methylguanine formation in the lungs of mice at 4 and 168 h after the injection. At 30 days after the NNK injection. the activation of K-ras oncogene with a 12th codon GC-->AT transition was detected in 56% of lung samples tested by mutant-allele-specific amplification. Vitamin E supplement reduced the frequency of the mutation to 30%. These results suggest that vitamin E suppresses NNK-induced DNA injury and subsequent fixation of the injury during the initiation and post-initiation phases of the lung tumorigenesis in mice.

Animals↗
PubMed1998

Effect of mechanical toothbrush stimulation on gingival microcirculatory functions in inflamed gingiva of dogs.

The effect of mechanical toothbrush stimulation on gingival microcirculatory functions was examined with and without removal of supragingival plaque in inflamed gingiva of 6 dogs. After removal of the ligatures, 4 treatment modalities: mechanical stimulation by vibration (MS), removal of supragingival plaque (PR), combination (MS+PR) and no treatment (NT), were administered to each quadrant for 2 weeks. Both quadrants with plaque removal showed a marked decrease in the gingival index score, while slight and moderate decreases were observed in NT and MS quadrants, respectively. Changes in gingival crevicular fluid flow, pocket oxygen tension and hemoglobin oxygen saturation in the gingiva were significant in the MS, PR and MS+PR quadrants. Significant treatment-by-time effects were found for all of the parameters of microcirculatory function between NT and MS quadrants, and gingival crevicular fluid flow between PR and MS+PR quadrants, respectively. These findings suggest that mechanical stimulation with a toothbrush may offer an additional benefit to gingival microcirculatory functions in inflamed gingiva.

Animals↗
PubMed1998

Relationship between the level of activities of daily living and chronic medical conditions among the elderly.

The purpose of this study is to observe the disease-disability association through a cross-sectional study. Between 1994 and 1995, we conducted a questionnaire survey in 5 towns in Japan. Among the items included in the questionnaire, 5 related to ADL (bathing, feeding, dressing/undressing, toileting, and going out socially) were treated as purpose variables; and 5 related to the history of medical treatment received over the past year (diabetes, heart disease, cerebrovascular disease, neuralgia, and bone fractures) were used as explanatory variables. Multiple logistic models were applied to observe the relationship. The history of medical treatment for cerebrovascular disease greatly and unavoidably affects disability related to ADL. Bone fractures, diabetes, and heart diseases contributed to specific ADL disabilities.

Activities of Daily Living↗