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Biomedical subjects

Kazuo Nakajima

Publications and source records attributed to Kazuo Nakajima.

13 recordsLinked to original sources

Mitochondrial complex I activity is significantly decreased in a patient with maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy associated with mitochondrial DNA C3310T mutation: a cybrid study.

Mitochondrial respiratory function in a patient with maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy associated with heteroplasmic mitochondrial DNA (mtDNA) C3310T mutation, which replaces the second amino acid of NADH dehydrogenase 1 (ND1) from a hydrophobic Proline to a hydrophilic Serine, was investigated. Mitochondrial respiratory function solely due to mtDNA C3310T mutation was investigated in cybrid system by the fusion of mtDNA-deleted (rho(0)) HeLa cells and exogenous mtDNA either from the proband or from controls. Total oxygen consumption of the proband cybrid cells was significantly decreased compared with those of controls (2.468+/-0.475 versus 2.871+/-0.484 micromol/h/10(7) cells, p=0.0392). Mitochondrial respiratory chain complex I activity of the proband cybrid cells was also significantly decreased compared with those of controls (0.191+/-0.080 versus 0.288+/-0.113 micromol/h/mg protein, p=0.0223). Furthermore, ATP content in the proband cybrid cells was also significantly decreased compared with those in controls (1.119+/-0.344 versus 1.419+/-0.378 pmol/10(5) cells, p=0.044). The present study indicates that mtDNA C3310T mutation may be a pathogenic mutation of maternally inherited type 2 diabetes mellitus and hypertrophic cardiomyopathy in the proband and the family.

Blotting, Southern↗

Construct validity of the Frenchay Activities Index for community-dwelling elderly in Japan.

Many researchers have developed various measures to evaluate the functional status of community-dwelling elderly. The Frenchay Activities Index (FAI) was developed to measure instrumental activities of daily living in stroke populations. The FAI has undergone the most intensive evaluation, but its factor structure has not been examined in Japan. The primary purpose of this study was to investigate the construct validity of the FAI for non-stroke community-dwelling elderly in Japan. The study subjects were 1,323 randomly selected community older residents in Hojo city, Ehime prefecture, the southern part of Japan. In order to investigate the construct validation, we performed factor analyses, i.e., exploratory factor analysis and confirmatory factor analysis. Furthermore, we examined the influences of age and gender on the FAI constructs. In the results, the FAI had a two-factor structure consisting of domestic chores, including washing clothes and preparing meals, and work and leisure, including gardening, driving and outings. Younger age was significantly related to increased performance on both factors. In addition, relative to females, males had a lower performance on the domestic chores and a greater performance on the work and leisure. These results suggest that the FAI satisfies the construct validity in the Japanese community-dwelling elderly. The FAI and its two factors provide important and clinically valuable information for understanding the patterns of functional status in the Japanese community-dwelling elderly.

Activities of Daily Living↗

[Factors affecting WHOQOL-26 in community-dwelling patients with schizophrenia].

OBJECTIVE: Schizophrenic patients' quality of life (QOL) has become increasingly important due to shift of mental health care from hospitals to communities. This paper describes a longitudinal study conducted to clarify relationships among the QOL, self-esteem, depressive mood, and uncooperativeness of schizophrenic patients identified in the authors' previous crosssectional study. METHODS: Subjects were 61 schizophrenic patients attending day care at mental hospitals. They were assessed initially, and again after a 12-month follow-up. The assessment was carried out using the Rosenberg Self-Esteem Scale, WHOQOL-26 Scale, and the Brief Psychiatric Rating Scale, and included personal characteristics. Covariance structure analysis (Synchronous Effects Model) was conducted to clarify the relationships between self-esteem and the WHOQOL-26 Scale, and between psychiatric states (depressive mood and uncooperativeness) and self-esteem, while controlling for subjects' individual characteristics and use of antipsychotics as confounding factors. RESULTS: The results indicated that self-esteem had a significantly positive effect on the WHOQOL-26 Scale while depressive mood and uncooperativeness were without significant effects. CONCLUSIONS: The results provide evidence that the enhancement and maintenance of self-esteem may be an effective method of improving WHOQOL-26 in schizophrenic patients.

Adult↗

High-pressure acceleration of the growth kinetics of glucose isomerase crystals.

The growth and dissolution rates of glucose isomerase crystals ({1 0 1} face) were measured in situ at 0.1 and 100 MPa. From these data, we determined that the solubilities at 25 degrees C were C(e) = 3.1 +/- 0.9 and 2.6 +/- 0.5 mg mL(-1) at 0.1 and 100 MPa, respectively. At the same supersaturation of sigma = 2.5 (sigma identical with ln(C/C(e)), C = the concentration of glucose isomerase, C(e) = the solubility) and temperature (T = 25 degrees C), the growth rate under 100 MPa was 7.6 times larger than that under 0.1 MPa. This result shows, for the first time, a kinetic acceleration of the growth rates of protein crystals with increasing pressure. The growth rates vs sigma data fitted well with a two-dimensional nucleation growth model of a polynucleation type. The fitting results indicate that the acceleration is mainly due to the decrease in the molecular surface energy of the glucose isomerase crystal with pressure.

Aldose-Ketose Isomerases↗

Structural consequences of hen egg-white lysozyme orthorhombic crystal growth in a high magnetic field: validation of X-ray diffraction intensity, conformational energy searching and quantitative analysis of B factors and mosaicity.

A novel method has been developed to improve protein-crystal perfection during crystallization in a high magnetic field and structural studies have been undertaken. The three-dimensional structure of orthorhombic hen egg-white (HEW) lysozyme crystals grown in a homogeneous and static magnetic field of 10 T has been determined and refined to a resolution of 1.13 angstroms and an R factor of 17.0%. The 10 T crystals belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 56.54 (3), b = 73.86 (6), c = 30.50 (2) angstroms and one molecule per asymmetric unit. A comparison of the structures of the 0 T and 10 T crystals has been carried out. The magnitude of the structural changes, with a root-mean-square deviation value of 0.75 angstroms for the positions of all protein atoms, is similar to that observed when an identical protein structure is resolved in two different crystalline lattices. The structures remain similar, with the exception of a few residues e.g. Arg68, Arg73, Arg128 and Gln121. The shifts of the arginine residues result in very significant structural fluctuations, which can have large effects on a protein's crystallization properties. The high magnetic field contributed to an improvement in diffraction intensity by (i) the displacement of the charged side chains of Arg68 and Arg73 in the flexible loop and of Arg128 at the C-terminus and (ii) the removal of the alternate conformations of the charged side chains of Arg21, Lys97 or Arg114. The improvement in crystal perfection might arise from the magnetic effect on molecular orientation without structural change and differences in molecular interactions. X-ray diffraction and molecular-modelling studies of lysozyme crystals grown in a 10 T field have indicated that the field contributes to the stability of the dihedral angle. The average difference in conformational energy has a value of -578 kJ mol(-1) per charged residue in favour of the crystal grown in the magnetic field. For most protein atoms, the average B factor in the 10 T crystal shows an improvement of 1.8 angstroms(2) over that for the 0 T control; subsequently, the difference in diffraction intensity between the 10 T and 0 T crystals corresponds to an increase of 22.6% at the resolution limit. The mosaicity of the 10 T crystal was better than that of the 0 T crystal. More highly isotropic values of 0.0065, 0.0049 and 0.0048 degrees were recorded along the a, b and c axes, respectively. Anisotropic mosaicity analysis indicated that crystal growth is most perfect in the direction that corresponds to the favoured growth direction of the crystal, and that the crystal grown in the magnetic field had domains that were three times the volume of those of the control crystal. Overall, the magnetic field has improved the quality of these crystals and the diffracted intensity has increased significantly with the magnetic field, leading to a higher resolution.

Animals↗

Quality of life of schizophrenic patients living in the community: the relationships with personal characteristics, objective indicators and self-esteem.

The relationship of personal characteristics, objective indicators, and self-esteem to quality of life (QOL) was investigated cross-sectionally in 73 Japanese schizophrenic patients, and the question of how objective conditions affect subjective evaluation was evaluated. Depressive mood and uncooperativeness were negatively correlated with self-esteem, and self-esteem was positively correlated with QOL. Self-esteem was considered to directly affect QOL, and depressive mood and uncooperativeness to affect QOL via self-esteem. Findings suggest that, in order to improve the QOL of schizophrenia patients, interventions to help alleviate psychiatric symptoms (e.g. depressive mood, uncooperativeness) must be utilized. A change in Japanese society itself must occur so that the consequences of stigma may be reduced and patient coping skills improved.

Adaptation, Psychological↗

Validity and utility of the Craig Hospital Inventory of Environmental Factors for Korean community-dwelling elderly with or without stroke.

The social environmental barriers are considered to be important because the "social participation" of people with impairments would be facilitated by the prevention and reduction of environmental barriers. The Craig Hospital Inventory of Environmental Factors (CHIEF) is one of the few scales to assess the environmental barriers. In this study, we developed the Korean version of CHIEF and evaluated its construct validity and utility in a sample of Korean community-dwelling elderly with or without stroke. We evaluated the construct validity of the CHIEF by testing the original five-factor structure using a confirmatory factor analysis in 400 elderly in Seoul, Korea. The utility of the CHIEF was then assessed by examining the relationships between individual characteristics, Barthel Index and perceived environmental barriers, measured by the CHIEF, using a structural equation modeling approach. The confirmatory factor analysis result demonstrated the validity of a second-order factor model of the CHIEF comprising the five factors as first-order factors. The perceived environmental barrier was a second-order factor when provided acceptable fit indices after two modifications. The structural equation modeling indicates that perceived environmental barriers are significantly related to activities of daily life but not age, gender, and the episode of stroke. The CHIEF is useful in measuring environmental factors for Korean older adults with or without stroke.

Aged↗

Chlorpropham induces mitochondrial dysfunction in rat hepatocytes.

The metabolism and action of chlorpropham (isopropyl N-(3-chlorophenyl)carbamate; CIPC, a post-harvest agent) and its metabolites were studied in freshly isolated rat hepatocytes and isolated rat hepatic mitochondria, respectively. The exposure of hepatocytes to CIPC caused a concentration (0.25-1.0 mM)- and time (0-3h)-dependent cell death accompanied by loss of cellular ATP and adenine nucleotides. CIPC at a weakly toxic level (0.5 mM) was metabolized to isopropyl N-(3-chloro-4-hydroxyphenyl)carbamate (4OH-CIPC) and subsequently to its glucuronide and sulfate conjugates (major metabolites) or alternatively to a minor metabolite 3-chloroaniline (3CA). The addition of SKF-525A (50 microM), an inhibitor of microsomal monooxygenase, enhanced the CIPC (0.5 mM)-induced cytotoxicity accompanied by loss of ATP and 4OH-CIPC and inhibited the decrease in the concentration of the parent compound. CIPC led to a strong decrease in cellular ATP content compared to its metabolites, 4OH-CIPC and 3CA. On the other hand, the exposure of isolated hepatic mitochondria to CIPC reduced State 3 respiration with a FAD-linked substrate (succinate plus rotenone) and/or with a NAD+ -linked substrate (pyruvate plus malate), whereas State 3 respiration with ascorbate plus tetramethyl-p-phenylendiamine (cytochrome oxidase-linked respiration) was not affected markedly by CIPC. Further, the addition of CIPC caused an increase in the rate of State 4 oxygen consumption, indicating an uncoupling effect, and a decrease in the rate of State 3 oxygen consumption in a concentration-dependent manner, respectively. In contrast, the addition of neither 4OH-CIPC nor 3CA markedly affected the rate of states 3 and/or 4 oxygen consumption. These results indicate that CIPC-induced cytotoxicity is mediated by the parent compound rather than by its metabolites such as 4OH-CIPC and 3CA, and that the toxicity is associated with a rapid depletion of ATP via impairment of mitochondrial function related to oxidative phosphorylation.

Adenine Nucleotides↗

Development and construct validation of the Korean competence scale (KCS).

A comprehensive Korean competence scale (KCS) designed for Korean older adults, was developed and its construct validity evaluated. KCS assesses their higher levels of functional competence than activities of daily livings (ADL), necessary for independence in the home and community. The internal structure of the scale was tested using an exploratory and confirmatory factor analysis with two elderly Korean sample groups. As expected, the exploratory factor analysis result demonstrated a three-factor solution comprised of the following three domains: instrumental self-maintenance, intellectual activity, and social role. The confirmatory factor analysis results showed that an acceptable solution could be estimated for a second-order factor model comprised of these factors. These findings provide evidence for the construct validity of the instrument and have implications for future research on factorial invariance.

Activities of Daily Living↗

Development of the chronic obstructive pulmonary disease activity rating scale: reliability, validity and factorial structure.

The purpose of the present study was to develop the Chronic Obstructive Pulmonary Disease (COPD) Activity Rating Scale (CARS) to measure life-related activity in patients with COPD, and to confirm its reliability and constructive validity in a factorial structure model. The subjects consisted of 114 patients with COPD. An 88-item life-related activity list, generated previously from a literature review, was administered. The secondary structural model consisted of four factors with 12 items. The results of the confirmatory factor analysis by structural equation modeling showed the fit criteria to be statistically significant. The internal consistency of the 12 items was highly reliable (Cronbach's alpha = 0.924). The CARS score was correlated with pulmonary function tests, breathlessness, and the health-related quality of life (QOL) scales in Pearson correlation coefficient. The results suggest that the COPD Activity Rating Scale is a valid scale for the assessment of life-related activity in patients with COPD.

Activities of Daily Living↗

The effect of aging on the results of the rat micronucleus assay.

We conducted the micronucleus assay in 3-, 5-, 7-, 9-, 11- and 13-week-old male rats to determine whether the results varied with age. We administered cyclophosphamide orally at 0 (vehicle), 5, 10 or 20 mg/kg, twice, 24 h apart, to five rats per dosage group and collected bone marrow and peripheral blood 24 h after the second treatment. We observed an age-related decrease in micronucleus-inducing activity in both polychromatic erythrocytes (bone marrow) and reticulocytes (peripheral blood), which we attributed to an age-related decrease in hematopoiesis. In spite of the age-related decrease in sensitivity to the model chemical studied here, all age groups tested showed positive responses. We concluded that the rat is suitable for the micronucleus assay regardless of age.

Age Factors↗

Molecular motor KIF1C is not essential for mouse survival and motor-dependent retrograde Golgi apparatus-to-endoplasmic reticulum transport.

KIF1C is a new member of the kinesin superfamily of proteins (KIFs), which act as microtubule-based molecular motors involved in intracellular transport. We cloned full-length mouse kif1C cDNA, which turned out to have a high homology to a mitochondrial motor KIF1Balpha and to be expressed ubiquitously. To investigate the in vivo significance of KIF1C, we generated kif1C(-/-) mice by knocking in the beta-galactosidase gene into the motor domain of kif1C gene. On staining of LacZ, we detected its expression in the heart, liver, hippocampus, and cerebellum. Unexpectedly, kif1C(-/-) mice were viable and showed no obvious abnormalities. Because immunocytochemistry showed partial colocalization of KIF1C with the Golgi marker protein, we compared the organelle distribution in primary lung fibroblasts from kif1C(+/+) and kif1C(-/-) mice. We found that there was no significant difference in the distribution of the Golgi apparatus or in the transport from the Golgi apparatus to the endoplasmic reticulum (ER) facilitated by brefeldin A between the two cells. This retrograde membrane transport was further confirmed to be normal by time-lapse analysis. Consequently, KIF1C is dispensable for the motor-dependent retrograde transport from the Golgi apparatus to the ER.

Amino Acid Sequence↗