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Biomedical subjects

Kenji Fukui

Publications and source records attributed to Kenji Fukui.

At least 19 recordsLinked to original sources
PubMed2007

Nuclease activity of the MutS homologue MutS2 from Thermus thermophilus is confined to the Smr domain.

MutS homologues are highly conserved enzymes engaged in DNA mismatch repair (MMR), meiotic recombination and other DNA modifications. Genome sequencing projects have revealed that bacteria and plants possess a MutS homologue, MutS2. MutS2 lacks the mismatch-recognition domain of MutS, but contains an extra C-terminal region called the small MutS-related (Smr) domain. Sequences homologous to the Smr domain are annotated as 'proteins of unknown function' in various organisms ranging from bacteria to human. Although recent in vivo studies indicate that MutS2 plays an important role in recombinational events, there had been only limited characterization of the biochemical function of MutS2 and the Smr domain. We previously established that Thermus thermophilus MutS2 (ttMutS2) possesses endonuclease activity. In this study, we report that a Smr-deleted ttMutS2 mutant retains the dimerization, ATPase and DNA-binding activities, but has no endonuclease activity. Furthermore, the Smr domain alone was stable and functional in binding and incising DNA. It is noteworthy that an endonuclease activity is associated with a MutS homologue, which is generally thought to recognize specific DNA structures.

Adenosine Triphosphatases↗
PubMed2006

Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines.

mRNA localization has an essential role in localizing cytoplasmic determinants, controlling the direction of protein secretion, and allowing the local control of protein synthesis in neurons. In neuronal dendrites, the localization and translocation of mRNA is considered as one of the molecular bases of synaptic plasticity. Recent imaging and functional studies revealed that several RNA-binding proteins form a large messenger ribonucleoprotein (mRNP) complex that is involved in transport and translation of mRNA in dendrites. However, the mechanism of mRNA translocation into dendritic spines is unknown. Here, we show that an actin-based motor, myosin-Va, plays a significant role in mRNP transport in neuronal dendrites and spines. Myosin-Va was Ca2+-dependently associated with TLS, an RNA-binding protein, and its target RNA Nd1-L, an actin stabilizer. A dominant-negative mutant or RNAi of myosin-Va in neurons suppressed TLS accumulation in spines and further impaired TLS dynamics upon activation of mGluRs. The TLS translocation into spines was impeded also in neurons prepared from myosin-Va-null dilute-lethal (dl) mice, which exhibit neurological defects. Our results demonstrate that myosin-Va facilitates the transport of TLS-containing mRNP complexes in spines and may function in synaptic plasticity through Ca2+ signaling.

Animals↗
PubMed2006

Relationship between limbic and cortical 5-HT neurotransmission and acquisition and reversal learning in a go/no-go task in rats.

RATIONALE: Specific brain structures have been suggested to be involved in impulsive responding assessed by a variety of operant tasks. Central serotonin (5-HT) function has also been widely implicated in impulsivity; however, little research has addressed the regional aspect of 5-HT roles in different impulsive indices of task performance. OBJECTIVE: We analyzed the relationships between acquisition and reversal learning in a go/no-go task as different behavioral measures of impulsivity and focal concentrations of 5-HT and its metabolites in the brain. MATERIALS AND METHODS: Rats administered with parachloroamphetamine (PCA) and vehicle were tested in both acquisition and reversal phases in a go/no-go visual discrimination task. Neurochemical analysis was performed to determine 5-HT concentrations in micropunched brain tissues. RESULTS: PCA administration induced regionally 5-HT depletion in the brain and impaired learning performance in both tests. For both tests, significant negative correlations between learning performance and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were observed in the medial prefrontal cortex (mPFC) and amygdala (Amyg). In contrast, significant negative correlations between learning performance and 5-HT and 5-HIAA concentrations were observed for the orbitofrontal cortex (OFC) exclusively in the reversal learning phase. CONCLUSIONS: The present data indicate that 5-HT neurotransmission to the mPFC and Amyg is involved in inhibitory control over responses to discriminated stimuli associated with the go/no-go paradigm common to both tests. In contrast, 5-HT neurotransmission to the OFC is especially involved in additional processes associated with reversal learning.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2006

Regional cerebral blood flow changes associated with interoceptive awareness in the recovery process of anorexia nervosa.

BACKGROUND: An abnormality in regional cerebral blood flow (rCBF) in anorexia nervosa (AN) patients has been reported. There are very few studies that have investigated the rCBF changes in the recovery process of AN. METHODS: For eight female AN patients, we performed (123)I-IMP single photon emission computed tomography (SPECT) and four psychological assessments (Eating Disorder Inventory (EDI), Eating Attitude Test (EAT), Self-Rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI)) both before and after inpatient-behavioral therapy. SPECT images were analyzed using statistical parametric mapping software. We also performed correlational analysis between rCBF and clinical variables. RESULTS: Following treatment, the patients showed significant body weight recovery. They showed significant improvement in EAT, SDS, STAI and a subscale of EDI - interoceptive awareness (IA) - but not in total EDI or other EDI subscales. Significant rCBF increases were observed in the precuneus, posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC) by the treatment. Significant correlation was observed between rCBF of right DLPFC and IA score before treatment. CONCLUSIONS: Changes of rCBF in right DLPFC, ACC, MPFC, PCC and precuneus were related to the AN recovery process and might be associated with improvement of IA following treatment.

Adolescent↗
PubMed2006

Regional cerebral blood flow changes in a patient with delusional parasitosis before and after successful treatment with risperidone: a case report.

The pathophysiology and appropriate pharmacological interventions for delusional parasitosis (DP) remain unknown. Here, we present a case of DP following brain infarction of the right temporoparietal region. Pharmacotherapy with risperidone resulted in a dramatic therapeutic response over a short period. In a sequential N-isopropyl-p-[(123)I]-iodoamphetamine single photon emission computed tomography ([(123)I]-IMP SPECT) study, post-treatment SPECT images revealed a marked increase of rCBF in the large areas including the bilateral frontal and left temporoparietal regions, the right parietal operculum and the bilateral basal ganglia, in contrast to pre-treatment SPECT images showing a global decrease of rCBF. Our clinical outcome suggests the efficacy and safety of risperidone for treatment of DP and that both dopaminergic and serotonergic dysfunction may play a role in DP. Our sequential SPECT findings suggest that psychiatric improvement of DP is associated with increased rCBF.

Aged, 80 and over↗
PubMed2006

JTE-607, a multiple cytokine production inhibitor, ameliorates disease in a SCID mouse xenograft acute myeloid leukemia model.

OBJECTIVE: Accumulating findings suggest that in acute myeloid leukemia (AML) patients, proinflammatory cytokines and growth factors play important roles in the proliferation and survival of AML cells in an autocrine and paracrine manner, leading to deterioration of AML. JTE-607 is a multiple cytokine inhibitor that potently suppresses production of proinflammatory cytokines. In the present study, we investigated the potency of JTE-607 as an antileukemic agent by exploiting a SCID mouse acute leukemia model. METHODS: SCID mice injected with anti-asialo-GM1 antibody were exposed to sublethal total-body irradiation at a dose of 3 Gy and then inoculated intravenously with AML cells. JTE-607 was administered using osmotic minipumps. The effects of JTE-607 on mouse survival time, human interleukin (IL)-8 levels in mouse plasma, and proportion of human CD45(+) cells in the bone marrow were studied. RESULTS: The survival time of the mice was strictly dependent on the number of U-937 cells proliferating in vivo. Administration of JTE-607 during the initial 7 days significantly prolonged survival of the mice, suggesting killing activity of JTE-607 against AML cells in vivo. Delayed administration of JTE-607 also prolonged the survival of mice bearing established leukemia with an effect comparable to the maximum tolerable dose of cytarabine. Flow cytometer analysis of bone marrow cells revealed decreased number of human CD45(+) cells. Human IL-8 level was also reduced by JTE-607. CONCLUSION: Our results indicate that JTE-607 has potential to be a new class of antileukemic drug that exerts inhibitory activities against both the proliferation and proinflammatory cytokine production of AML cells.

Animals↗
PubMed2006

Body mass index among Japanese inpatients with schizophrenia.

BACKGROUND: Many studies have emphasized the high frequency of obesity in schizophrenic patients. However, the characteristics of the Body Mass Index (BMI) distribution in Japanese schizophrenic patients remain unknown, and the aim of this study was to clarify these characteristics in a Japanese schizophrenic inpatient population. METHODS: The subjects were 273 inpatients (males: 141, females: 132) with schizophrenia. The patient BMI distribution was compared with normal control data obtained from the 2003 Japanese National Health and Nutrition Survey. RESULTS: The mean patient BMI was 23.0 +/- 4.3, and the BMI showed a normal distribution. The proportion of patients who were obese, of normal weight and underweight was 30.8%, 53.1%, and 16.1%, respectively. No statistical evidence of a higher frequency of obesity was found in male patients, compared to normal controls, but a higher frequency of underweight patients and a lower frequency of normal-weight patients were apparent in most decades of age. In female schizophrenia patients, a higher prevalence of obesity occurred in patients aged 50-59 years old, compared to controls. A higher rate of underweight elderly patients and a lower rate of normal-weight patients aged 40 to more than 70 years old were also apparent. CONCLUSIONS: The results suggest that not only obesity but also weight problems related to an underweight condition occur more frequently in Japanese schizophrenic inpatients than in normal controls. The deviation of the BMI distribution in Japanese schizophrenic inpatients may have a relationship with higher mortality and sudden death in schizophrenia.

Body Mass Index↗
PubMed2006

Effect of institutional smoking prohibition on Japanese inpatients with chronic schizophrenia.

OBJECTIVE: A higher prevalence of smoking among schizophrenic patients has been well documented in Japan and other countries. Smoking reduction or cessation is desirable to reduce various physical complications in schizophrenic patients, but the effect of smoking reduction on psychiatric status and BMI remains ambiguous. The aim of this study was to determine the effect of an institutional smoking prohibition on smoking status, psychiatric status and BMI in Japanese inpatients with schizophrenia. METHOD: Smoking status, psychiatric status (Clinical Global Impression (CGI) scores: global severity score and global change score) and BMI were investigated in 256 chronic schizophrenic inpatients before and 3 months after prohibition of smoking in a Japanese psychiatric hospital building. RESULTS: Following prohibition, the smoking rate decreased from 36.3% to 22.2%. A weak positive correlation was found between decreased cigarette consumption and the CGI global change score (r=0.140, p=0.025), but the mean global change scores in the smoking groups were less than 6 (minimally worse). No significant increase in BMI was observed. CONCLUSION: Institutional smoking prohibition is effective in reducing the smoking rate, while having only a minor unfavorable effect on psychiatric status and BMI in chronic schizophrenic inpatients.

Body Mass Index↗
PubMed2005

Hepatocyte nuclear factor-4alpha is essential for glucose-stimulated insulin secretion by pancreatic beta-cells.

Mutations in the hepatocyte nuclear factor (HNF)-4alpha gene cause a form of maturity-onset diabetes of the young (MODY1) that is characterized by impairment of glucose-stimulated insulin secretion by pancreatic beta-cells. HNF-4alpha, a transcription factor belonging to the nuclear receptor superfamily, is expressed in pancreatic islets as well as in the liver, kidney, and intestine. However, the role of HNF-4alpha in pancreatic beta-cell is unclear. To clarify the role of HNF-4alpha in beta-cells, we generated beta-cell-specific HNF-4alpha knock-out (betaHNF-4alphaKO) mice using the Cre-LoxP system. The betaHNF-4alphaKO mice exhibited impairment of glucose-stimulated insulin secretion, which is a characteristic of MODY1. Pancreatic islet morphology, beta-cell mass, and insulin content were normal in the HNF-4alpha mutant mice. Insulin secretion by betaHNF-4alphaKO islets and the intracellular calcium response were impaired after stimulation by glucose or sulfonylurea but were normal after stimulation with KCl or arginine. Both NAD(P)H generation and ATP content at high glucose concentrations were normal in the betaHNF-4alphaKO mice. Expression levels of Kir6.2 and SUR1 proteins in the betaHNF-4alphaKO mice were unchanged as compared with control mice. Patch clamp experiments revealed that the current density was significantly increased in betaHNF-4alphaKO mice compared with control mice. These results are suggestive of the dysfunction of K(ATP) channel activity in the pancreatic beta-cells of HNF-4alpha-deficient mice. Because the K(ATP) channel is important for proper insulin secretion in beta-cells, altered K(ATP) channel activity could be related to the impaired insulin secretion in the betaHNF-4alphaKO mice.

ATP-Binding Cassette Transporters↗
PubMed2005

Immunological and Psychological Benefits of Aromatherapy Massage.

This preliminary investigation compares peripheral blood cell counts including red blood cells (RBCs), white blood cells (WBCs), neutrophils, peripheral blood lymphocytes (PBLs), CD4(+), CD8(+) and CD16(+) lymphocytes, CD4(+)/CD8(+) ratio, hematocrit, humoral parameters including serum interferon-gamma and interleukin-6, salivary secretory immunoglobulin A (IgA). Psychological measures including the State-Trait Anxiety Inventory (STAI) questionnaire and the Self-rating Depression Scale (SDS) between recipients (n = 11) of carrier oil massage and aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil and sweet marjoram oil. Though both STAI and SDS showed a significant reduction (P < 0.01) after treatment with aromatherapy and carrier massage, no difference between the aromatherapy and control massage was observed for STAI and SDS. Aromatherapy, in contrast to control massage, did not significantly reduce RBC count or hematocrit. However, aromatherapy massage showed a significant (P > 0.05) increase in PBLs, possibly due to an increase in CD8(+) and CD16(+) lymphocytes, which had significantly increased post-treatment (P < 0.01). Consequently, the CD4(+)/CD8(+) ratio decreased significantly (P < 0.01). The paucity of such differences after carrier oil massage suggests that aromatherapy massage could be beneficial in disease states that require augmentation of CD8(+) lymphocytes. While this study identifies the immunological benefits of aromatherapy massage, there is a need to validate the findings prospectively in a larger cohort of patients.

Journal Article↗
PubMed2005

Spatiotemporal patterns of expression of IGSF4 in developing mouse nervous system.

IGSF4 is a novel immunoglobulin (Ig)-like intercellular adhesion molecule. Since IGSF4 has been characterized by several independent research groups, this molecule is called by three names, TSLC1, SgIGSF and SynCAM. In the experiments to study global changes of gene expression in fetal murine brains after prenatal exposure to low-doses of X-rays, we have found IGSF4 as one of down-regulated genes after X-irradiation. In order to elucidate the expression of spatiotemporal expression of IGSF4 in the developing brain, we have produced polyclonal antibody against IGSF4 and studied the expression of IGSF4 with immunohistochemistry and Western blot analysis. At embryonic day (E) 12.5, IGSF4-immunoreactivity (IR) was observed diffusely in the telencephalic wall, whereas it became rather confined to the subplate, the cortical plate and the subventricular zone as the development proceeded. Noteworthy was a distinct radial pattern found in the cortical plate of E16.5. IGSF4-IR gradually decreased after birth and disappeared in adulthood. In the cerebellum, IGSF4 was expressed in the molecular layer at postnatal day (P) 0 through P14. By Western blot analysis, IGSF4 remained at low levels throughout embryonic stage, whereas it increased after birth. These spatiotemporal patterns of the expression suggest that IGSF4 plays crucial roles in the development of both telencephalon and cerebellum.

Animals↗
PubMed2005

The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation.

Defective glucose-stimulated insulin secretion is the main cause of hyperglycemia in type 2 diabetes mellitus. Mutations in HNF-1alpha cause a monogenic form of type 2 diabetes, maturity-onset diabetes of the young (MODY), characterized by impaired insulin secretion. Here we report that collectrin, a recently cloned kidney-specific gene of unknown function, is a target of HNF-1alpha in pancreatic beta cells. Expression of collectrin was decreased in the islets of HNF-1alpha (-/-) mice, but was increased in obese hyperglycemic mice. Overexpression of collectrin in rat insulinoma INS-1 cells or in the beta cells of transgenic mice enhanced glucose-stimulated insulin exocytosis, without affecting Ca(2+) influx. Conversely, suppression of collectrin attenuated insulin secretion. Collectrin bound to SNARE complexes by interacting with snapin, a SNAP-25 binding protein, and facilitated SNARE complex formation. Therefore, collectrin is a regulator of SNARE complex function, which thereby controls insulin exocytosis.

Animals↗