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Biomedical subjects

Kenji Fukui

Publications and source records attributed to Kenji Fukui.

48 records · Page 3Linked to original sources
PubMed2003

[Change in body image of patients with alcohol dependence during treatment process].

In order to find useful information for the establishment of new treatment method to alcohol dependence, we investigated the change of the body image of patients with alcohol dependence before and after the treatment. HABIT (Haga Body Image Test), a questionnaire about body image developed in department of psychiatry in Kyoto Prefectural University of Medicine, was used to examine the change of body image between pre- and post-3-month conventional treatment program in 46 patients with alcohol dependence hospitalized into special institutions for treatment of the disease in Kyoto. Patients with poor outcome of the treatment showed improvement of body image on visceral function, feeling of appetite and outward appearance, while patients with good outcome indicated no significant change in these aspects. This finding likely suggests that the treatment would result in good outcome in patients having stable feeling of physical health, and the cognitive treatment approach about these aspects of body image should be performed on the patients with poor treatment outcome. On the other hand, the body image about motor function showed significantly higher score in the patients approach for the patients with poor outcome to become aware of their physical activity would be effective.

Adult↗
PubMed2002

Cerebral blood flow changes in general paresis following penicillin treatment: a longitudinal single photon emission computed tomography study.

Three cases of general paresis were successfully treated with high-dose penicillin. In all cases, cerebrospinal fluid cell counts decreased to normal and mental status improved rapidly. Cerebrospinal fluid protein concentrations decreased and IQ scores and overall levels of functioning improved gradually over 1 year. Regional cerebral blood flow (CBF) changes were analyzed longitudinally for 1 year using single photon emission computed tomography (SPECT). Autoradiography method and region of interest (ROI) analyses were used for quantitative CBF assessment and 3D stereotactic surface projections (3D-SSP) analyses were used for qualitative CBF pattern assessment. 3D-SSP could not reveal remarkable CBF pattern changes through the courses. The ROI analyses showed remarkable CBF decreases in all brain regions 1 month after the treatment, which recovered to normal levels 1 year after the treatment. These results suggest that remarkable decreases of quantitative CBF counts reflect the disappearance of encephalitis, while their gradual recovery reflects the gradual improvement of cerebral functional activity. As Treponema pallidum infection affects whole brain and CBF changes globally, quantitative CBF assessment may be more efficient than qualitative CBF pattern analyses for the purpose of understanding the pathophysiology of general paresis.

Brain↗
PubMed2002

Relationship between clock drawing test performance and regional cerebral blood flow in Alzheimer's disease: a single photon emission computed tomography study.

The clock drawing test (CDT) is a useful tool for screening cognitive impairment. Previous neuropsychological studies have revealed that CDT performance requires several cognitive functions including semantic memory, visuospatial function and executive function. However, the neural substrates involved remain to be elucidated. The aim of the present study was to identify the brain regions responsible for CDT performance in patients with Alzheimer's disease (AD). Twenty-six patients satisfying the National Institute of Neurological and Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD underwent the CDT and the Mini-Mental State Examination (MMSE), together with a N-isopropyl-p-[123I] iodoamphetamine (IMP) single photon emission computed tomography measurements of the resting regional cerebral blood flow (rCBF). The CDT score correlated significantly with the MMSE score (r=0.582; P < 0.05). Stepwise multiple regression analysis revealed that the MMSE score and the left posterior temporal rCBF were major predictors of CDT score. These findings suggest that the CDT score may reflect the severity of dementia, and that it has a close relationship with the left posterior temporal function. Our findings provide the first functional neuroimaging evidence for the neural substrates involved in CDT performance.

Aged↗
PubMed2002

A behavior therapy program combined with liquid nutrition designed for anorexia nervosa.

We have introduced behavior therapy as standard in-patient treatment for anorexia nervosa and have modified the treatment program. At first, we used Fukamachi's activity restriction therapy (FT), followed by Token economy therapy (TET), which combined token economy with FT. Finally, we have developed Kyoto Prefectural University of Medicine Behavior Therapy (KPT). According to KPT, only liquid formula is given in the early stages of hospitalization and a target weight is not set at admission. We examined the effect of these three programs with respect to bodyweight gain. Thirty-five anorexic patients participated in these three programs in our hospital: seven completed FT, seven completed TET and 21 completed KPT. We compared the effects of these three programs on body mass index (BMI). Furthermore, the effects of these three programs on BMI were compared at admission, 1 month after admission and at discharge, 6 months after discharge. In addition, the rate of increase of BMI for the following three periods was investigated: 1 month after admission, total hospitalization (from admission to discharge) and from admission to 6 months after discharge. The result is that KPT was the most effective of the three programs with regard to both the amount and the rate of increase of BMI at all points and there is a significant difference between KPT and FT. This effectiveness may be attributable to the use of an oral liquid formula, the setting of target weight at a later stage of hospitalization and the release of activity restriction based on weight gain.

Activities of Daily Living↗
PubMed2002

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 1st communication: effects on general behavior and central nervous system.

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on general behavior and the central nervous system were investigated in mice, rats and cats. 1. General behavior: When SNI-2011 was administered orally to mice at 100 mg/kg, mydriasis, a decrease of spontaneous motor activity, tremor, convulsions, salivation, abnormal posture, abnormal gait, reduced grip strength and reduced response against external stimulating were observed, and 2 out of 6 animals died. At 10 mg/kg or lower, no particular sign was observed except mydriasis, which appeared to be caused via the peripheral muscarinic acetylcholine receptors. 2. Central nervous system: SNI-2011 had no effect on the motor coordination in mice. Hypothermia was observed in rats and reduced spontaneous motor activity, analgesia and enhanced maximum electroshock-induced convulsions were observed in mice after oral administration of 30 mg/kg SNI-2011. Slight increase in the rate of theta-wave band in the hippocampal EEG of rats and spinal multisynaptic reflexes in cats were observed after intravenous injection of 10 mg/kg SNI-2011. At an oral dose of 10 mg/kg, prolongation of thiopental-induced sleeping time in mice was observed. The prolongation of sleeping time was inhibited by a peripheral muscarinic antagonist. These results suggest that SNI-2011 has muscarinic effects on general behavior and the central nervous system at the doses approximately 10-fold higher than the effective doses needed for saliva secretion.

Anesthetics, Intravenous↗
PubMed2002

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 2nd communication: effects on somatic nervous system and on autonomic nervous system and smooth muscle.

A novel muscarinic receptor agonist SNI-2011 ((+/-)-cis-2-methylspirol[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on the somatic nervous system and on the autonomic nervous system and smooth muscle were investigated in mice, rats, guinea pigs, rabbits and cats. 1. Somatic nervous system: SNI-2011 had no effect on the neuromuscular junction in rats and no muscle relaxant effect in mice. No surface anesthetic effect was observed in guinea pigs, but infiltration anesthetic effect was found after intracutaneous injection of solution (1% or higher). 2. Autonomic nervous system and smooth muscle: SNI-2011 tended to cause mydriasis at 3 mg/kg i.v. or higher in rabbits and dose-dependently caused mydriasis at 10 mg/kg p.o. or higher in rats. Mydriasis in rats was also observed by ophthalmic instillation, caused via the peripheral muscarinic acetylcholine receptors. SNI-2011 elevated the base line tension of nictitating membrane in cats when it was injected intravenously at 3 mg/kg or higher. In the smooth muscle, SNI-2011 increased the spontaneous movement of isolated rabbit ileum (1 x 10(-6) mol/l or higher), contractions of isolated guinea pig ileum (1 x 10(-6) mol/l or higher) and isolated guinea pig trachea (3 x 10(-6) mol/l or higher). SNI-2011 relaxed the histamine- and noradrenaline-induced contractions of isolated guinea pig aorta and augmented noradrenaline- and phenylephrine-induced contractions of isolated rat vas deferens. These effects were induced by relatively higher concentrations only i.e. 1 x 10(-5) mol/l or higher. From these results, SNI-2011 has muscarinic side effects on the somatic nervous system and on the autonomic nervous system and smooth muscle, however, in the case of oral administration, that is clinical administration route, SNI-2011 caused no muscarinic side effect at the effective doses needed for saliva secretion.

Anesthetics↗
PubMed2002

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 3rd communication: effects on respiratory and cardiovascular systems.

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane- 5,3'-quinuclidine]monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on the respiratory and cardiovascular systems were investigated in guinea pigs and dogs. SNI-2011 reduced the contractile force and beating rate of isolated right guinea pig atrium at 1 x 10(-6) mol/l or higher and 3 x 10(-6) mol/l or higher, respectively. SNI-2011 reduced the contractile force of isolated left atrium induced by electric stimulation at 1 x 10(-6) mol/l or higher. In anesthetized dogs, SNI-2011 caused a transient decrease in blood pressure, tachycardia and an increase in femoral arterial blood flow at 0.01 mg/kg i.v. or higher. At 1 mg/kg it caused continuous bradycardia, a decrease in femoral arterial blood flow and an increase in respiration rate in addition to the changes observed immediately after injection. A transient negative T-wave was observed as the only change in the ECG immediately after injection at 1 mg/kg. However, when SNI-2011 was injected intraduodenally, a decrease in femoral arterial blood flow, bradycardia and a tendency to increase respiration rate were observed at doses of 1 to 3 mg/kg. All these events in dogs were antagonized by atropine. These results suggest that oral administration of SNI-2011, that is the clinical administration route, can distinctly reduce the muscarinic effects on the respiratory and cardiovascular systems compared to intravenous administration.

Animals↗
PubMed2002

General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 4th communication: Effects on gastrointestinal, urinary and reproductive systems and other effects.

A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on the gastrointestinal, urinary and reproductive systems and other tissues were investigated in mice, rats guinea pigs, rabbits and dogs. 1. Gastrointestinal system: SNI-2011 did not cause any effects on the gastrointestinal system, i.e. the intestinal transport of charcoal meal in mice, the secretion of gastric and bile juices, and the formation of ulcer induced by water immersion restraint in rats. 2. Urinary and reproductive systems: SNI-2011 augmented the spontaneous movement of rat pregnant uterus in vivo at 0.3 mg/kg i.v. or higher, and this effect was not observed in the non-pregnant uterus. SNI-2011 increased the spontaneous movement of isolated guinea pig bladder (3 x 10(-6) mol/l or higher) and increased the in vivo spontaneous movement of rat bladder (0.3 mg/kg i.v. or higher). SNI-2011 caused increases in rat urine volume, pH and urinary excretion of Na+ and Cl- at 30 mg/kg p.o. 3. Others: SNI-2011 had no effect on the vascular permeability in mice, hematological parameters and blood coagulation in rats. SNI-2011 had neither hemolytic nor anti-inflammatory effect. These results suggest that SNI-2011 has muscarinic effects on the gastrointestinal, urinary and reproductive systems and other tissues at the doses approximately 10-fold higher than the doses needed for saliva secretion.

Animals↗
PubMed2002

Thyroid hormone receptor interacting protein 3 (trip3) is a novel coactivator of hepatocyte nuclear factor-4alpha.

Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. HNF-4alpha, which is a transcription factor expressed in pancreatic beta-cells, plays an important role in regulating the expression of genes involved in glucose metabolism. Thus, cofactors that interact with HNF-4alpha and modify its transcriptional activity might also play an important role in regulating the metabolic pathways in pancreatic beta-cells, and the genes of such cofactors are plausible candidate genes for MODY. In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. Human Trip3 cDNA contained an open reading frame for a protein of 155 amino acids, and the gene was expressed in both pancreatic islets and MIN6 cells. Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. These results suggest that Trip3 is a coactivator of HNF-4alpha. Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha.

Animals↗
PubMed2002

Hepatocyte nuclear factor-1alpha modulates pancreatic beta-cell growth by regulating the expression of insulin-like growth factor-1 in INS-1 cells.

Maturity-onset diabetes of the young type 3 (MODY3) is characterized by impaired insulin secretion. Heterozygous mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha are the cause of MODY3. Transgenic mice overexpressing dominant-negative HNF-1alpha mutant in pancreatic beta-cells and HNF-1alpha knockout mice are animal models of MODY3. These mice exhibit defective glucose-stimulated insulin secretion and have reduced beta-cell mass and beta-cell proliferation rate. Here we examined the effect of HNF-1alpha on beta-cell proliferation by overexpressing a human naturally occurring dominant- negative mutation P291fsinsC in INS-1 cells under the control of doxycycline-induction system. INS-1 cells overexpressing P291fsinsC showed apparent growth impairment. The proliferation rate estimated by [(3)H]thymidine incorporation was significantly reduced in P291fsinsC-expressing INS-1 cells compared with noninduced or wild-type HNF-1alpha-overexpressing INS-1 cells. Growth inhibition occurred at the transition from G1 to S cell cycle phase, with reduced expression of cyclin E and upregulation of p27. cDNA array analysis revealed that the expression levels of IGF-1, a major growth factor for beta-cells, and macrophage migration inhibitory factor (MIF), a cytokine expressed in pancreatic beta-cells, were reduced in P291fsinsC-HNF-1alpha-expressing INS-1 cells. Although MIF seemed to have proliferative function, blockade of MIF action by anti-MIF antibody stimulated INS-1 cell proliferation, excluding its direct role in the growth impairment. However, addition of IGF-1 to P291fsinsC-expressing INS-1 cells rescued the growth inhibition. Our data suggest that HNF-1alpha is critical for modulating pancreatic beta-cell growth by regulating IGF-1 expression. IGF-1 might be a potential therapeutic target for the treatment of MODY3.

Animals↗
PubMed2001

Chronic high-dose nitrazepam dependence 123I-IMP SPECT and EEG studies.

A patient who took 50-100 mg nitrazepam per day for 25 years is presented. (123)I-IMP SPECT (autoradiography method) and EEG were performed sequentially on the subject during and after the withdrawal syndrome. Severe hypoperfusion of the whole brain on SPECT and diffuse slow activity on EEG were demonstrated during the withdrawal syndrome and subsequently remarkably improved. However, the hypofrontal pattern on both early and delayed images in SPECT was unchanged. The changes observed on SPECT and EEG reflect the pathophysiology of dependence and withdrawal. Additionally, the hypofrontal pattern remained unchanged suggesting that organic brain damage can develop as a result of chronic high-dose benzodiazepine abuse.

Journal Article↗