Biomedical subjects

K Honda

Publications and source records attributed to K Honda.

At least 163 records · Page 9Linked to original sources

PubMed1999

Dopamine D3 agonists into the substantia nigra aggravate cataplexy but do not modify sleep.

We have recently demonstrated that local perfusion of dopaminergic D2/D3 agonists into the ventral tegmental area (VTA) significantly aggravates cataplexy and increases sleep in narcoleptic Dobermans. We further assessed the roles of the mesostriatal dopaminergic system and found that local perfusion of quinpirole and 7-OH-DPAT into the substantia nigra (SN) significantly aggravated cataplexy, while perfusion of a D2/D3 antagonist significantly reduced cataplexy. Neither a D1 agonist nor a D1 antagonist modified cataplexy. SN perfusion of quinpirole did not significantly modify sleep, while VTA perfusion significantly increased the drowsy state. Although autoregulation of the VTA and SN dopaminergic neurons are involved in the regulation of cataplexy, both structures have distinct roles for the regulation of sleep.

Animals↗

PubMed1999

Dopamine D3 agonists into the substantia nigra aggravate cataplexy but do not modify sleep [corrected].

Animals↗

PubMed1999

Cardiovascular and renal effects of conivaptan hydrochloride (YM087), a vasopressin V1A and V2 receptor antagonist, in dogs with pacing-induced congestive heart failure.

The systemic hemodynamic and renal responses to conivaptan hydrochloride (YM087; 4'-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine -6-carbonyl)-2-phenylbenzanilide monohydrochloride), a vasopressin V1A and V2 receptor antagonist, were determined in pentobarbital-anesthetized dogs after 2 to 3 weeks of rapid right ventricular pacing. Congestive heart failure, characterized by decreases in first derivative of left ventricular pressure (left ventricular d P/dt(max)) and cardiac output, and increases in left ventricular end-diastolic pressure and total peripheral vascular resistance, was induced by chronic rapid right ventricular pacing at 260-280 beats/min. Intravenous administration of conivaptan (0.1 mg/kg) significantly increased left ventricular dP/dt(max) and cardiac output and significantly decreased left ventricular end-diastolic pressure and total peripheral vascular resistance. Conivaptan also increased urine flow and reduced urine osmolality by markedly increasing free water clearance. These results indicate that conivaptan produced hemodynamic improvement and marked aquaresis in dogs with congestive heart failure. Therefore, conivaptan may find clinical use in treating patients with congestive heart failure.

Animals↗

PubMed1999

Roles of nitric oxide in the spinal cord in cardiovascular regulation in rats.

The roles of nitric oxide (NO) in the spinal cord in regulation of blood pressure were examined in anesthetized rats. Intrathecal (i.t.) injection of an inhibitor of NO synthase (NOS), N(omega)-nitro-L-arginine methylester (L-NAME), caused marked dose-dependent increase in the blood pressure. The pressor response to L-NAME was attenuated by pretreatment with L-arginine (10 micromol, i.t.). Pretreatment with the ganglionic blocker pentolinium (10 mg/kg, i.v.) and alpha1- and beta-adrenoceptor antagonists significantly inhibited the pressor response induced by L-NAME. The pressor responses to L-NAME was blocked by pretreatment with the selective N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP-5) (50 nmol, i.t.), but not by pretreatment with a non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In addition, the pressor response to L-NAME was reduced by spinal cord transection. These results suggest that L-NAME causes activation of the sympathetic nervous system by reduction of NO in the spinal cord, and that this reduction of NO by L-NAME may activate glutamatergic neurons in the medulla oblongata.

Animals↗

PubMed1999

Recombinant human erythropoietin stimulates vascular endothelial growth factor release by glomerular endothelial cells.

We designed the present study to address the question of whether recombinant human erythropoietin stimulates DNA synthesis and vascular endothelial growth factor (VEGF) secretion in vitro using cultured bovine glomerular endothelial cells (GENs). Recombinant human erythropoietin dose-dependently stimulated the proliferation of GENs in culture, and this proliferative effect was inhibited by 1 microg/ml anti-VEGF antiserum. The increase in VEGF concentrations in the supernatants containing 10 U/ml rHuEpo was abolished by incubation with 10 microg/ml of anti-human rHuEPO antiserum, 0.2 microg/ml actinomycin D or 10 microg/ml cycloheximide. Taken together, rHuEpo stimulates GEN proliferation in vitro and VEGF release from these cells is associated with stimulation of RNA-dependent DNA and protein synthesis.

Animals↗

PubMed1999

Regional differences in genetic subgroup frequency in hereditary cerebellar ataxia, and a morphometrical study of brain MR images in SCA1, MJD and SCA6.

Molecular genetic assessments of 69 individuals in 44 families with hereditary cerebellar ataxia (HCA) were made to determine the relative frequencies of subtypes of HCA in Yamagata, Japan. Fifteen families (34%) had SCA1, none had SCA2, nine (20%) had MJD, five (11%) had SCA6 and nine (20%) had DRPLA. These findings differ markedly from those in other regions of Japan and the rest of the world. A morphometrical study of the brain MR images also was made on 38 individuals with SCA1 (n = 14), MJD (n = 8) or SCA6 (n = 16). In SCA1, the ventral pons was atrophic in proportion to the amount of cerebellar atrophy. In MJD, both the pons and the cerebellum were atrophic, cerebellar atrophy being less pronounced than that in SCA1 and SCA6. While both the major and minor axes of the ventral pons were proportionally decreased in SCA1, the minor axis was more decreased than the major axis in MJD. In SCA6, a mild reduction in the ratio of the ventral pontine area to the posterior fossa area (Pv/PF) was observed as well as obvious cerebellar atrophy. These findings indicate that in MR images SCA1, MJD and SCA6 show different atrophic features of the cerebellum and brainstem.

Adult↗

PubMed1999

Eating problems in female Japanese high school students: a prevalence study.

OBJECTIVES: This study was conducted to estimate the prevalence of eating problems and to identify factors associated with the eating problems among Japanese high school girls. METHODS: This study used a cross-sectional design. The study population was 3,032 female students attending three high schools in Fukushima, Japan. The 26-item version of the Eating Attitudes Test (EAT-26) was administered to assess eating problems. Inquiries were also made regarding possible risk factors for the eating problems. RESULTS: Of the 2,685 subjects, 5.4% had a total EAT-26 score above the cutoff point (20 < or =). Logistic regression analysis demonstrated that older age, higher body mass index, a distorted body image, obsessive-compulsive tendency, and some familial issues were independently related to the eating problems. DISCUSSION: The prevalence of eating problems in the Japanese female population was low compared with reports from Western countries. In addition, distorted body image was suggested to have the greatest influence on eating problems.

Adolescent↗

PubMed1999

Glomerular expression of cell-cycle-regulatory proteins in human crescentic glomerulonephritis.

To elucidate the mechanism underlying crescentic formation, we assessed the phenotypic characterization and cell-cycle protein expression in human crescentic glomerulonephritis (CRGN). Kidney tissue specimens taken from CRGN patients (10 patients with pauci-immune type rapidly progressive glomerulonephritis (RPGN), 2 patients with Henoch-Schönlein purpura nephritis, and 1 patient with IgA nephropathy) were examined immunohistochemically. Most of the cellular components of the crescents expressed cytokeratin, whereas few cells expressed PHM-5. CD68-positive cells were minor components of cellular crescents, indicating that the major principal cellular component of the crescents is made up of cells with the parietal glomerular epithelial cell (PEC) phenotype. Additionally, serial section analysis revealed that Ki-67-positive cells in the crescents were frequently cyclin-A positive and Bcl-2 positive, but seldom cyclin-B(1) positive. Moreover, the expression of cyclin-dependent kinase inhibitor p27(Kip1) was low in the cellular crescents, despite being exclusively positive in podocytes within the same section. We concluded that the major component of the cellular crescents is made up of PECs and that apparent expression of cyclins and Bcl-2 and restrained expression of p27(Kip1) may be synergistically associated with the development of cellular crescents in human CRGN.

Amino Acid Sequence↗

PubMed1999

Four novel mutations of the Fanconi anemia group A gene (FAA) in Japanese patients.

Fanconi anemia (FA) is an autosomal recessive disorder characterized by pancytopenia, predisposition to cancers, and a diverse variety of congenital malformations. At least eight complementation groups, A through H, have been described. Recently, the FA-A gene (FAA) has been isolated, and a large number of distinct mutations reported in ethnically diverse FA-A patients. Here, we report on the mutation analysis of five FA patients by single-strand conformation polymorphism. Out of five patients, at least three were found to have mutations in the FAA gene. The first patient was a compound heterozygote with a 1-bp deletion and a single-base substitution. The second patient had a heterozygous 2-bp deletion, which introduces a premature termination codon, and the third patient had a heterozygous splice donor site mutation in intron 27.

Base Sequence↗

PubMed1999

Suppressive effect of anticardiolipin antibody on the proliferation of human umbilical vein endothelial cells.

OBJECTIVE: To determine whether sera that show a positive anticardiolipin test result have a suppressive effect on the proliferation of endothelial cells collected from human umbilical veins. DESIGN: Retrospective in vitro study. SETTING: University hospital outpatient clinic for the treatment of infertility. PATIENT(S): Thirteen patients with recurrent fetal miscarriages who were positive for anticardiolipin antibody and 14 patients with recurrent miscarriages who were negative for anticardiolipin antibody. INTERVENTION(S): Serum was obtained from each patient. MAIN OUTCOME MEASURE(S): Suppressive effect of the sera on the culture of human umbilical vein endothelial cells. RESULT(S): The proliferation of human umbilical vein endothelial cells decreased significantly in cultures that contained sera showing positive anticardiolipin antibody activity that had been collected from patients with recurrent fetal miscarriages. CONCLUSION(S): The results strongly suggest that anticardiolipin antibody has a suppressive effect on the proliferation of human umbilical vein endothelial cells.

Abortion, Habitual↗

PubMed1999

Ca2+ mobilization and activation of extracellular acidification by carbachol in acutely dispersed cells from guinea pig detrusor: Fura 2 fluorometry and microphysiometry using the cytosensor.

The study aim was to develop a simple in vitro model for pharmacophysiological investigation of urinary bladder smooth muscles. Smooth muscle cells from guinea pig detrusor were dissociated, and the suspended cells were stimulated with carbachol (CCh), an acetylcholine receptor agonist. Cytosolic Ca2+ levels were determined using Fura 2 fluorescence and extracellular acidification rates were monitored by the Cytosensor microphysiometer. CCh dose-dependently increased cytosolic Ca2+ levels and extracellular acidification rates, with EC50 values of approximately 1 microM. Both the acetylcholine muscarinic receptor antagonist atropine and the M3 muscarinic receptor-preferring antagonist 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) inhibited the effects of CCh, three orders of magnitude more potently than the selective M2 muscarinic receptor antagonist, methoctramine. These data indicate the dominant role of M3 receptors in guinea-pig bladder but fail to show clear evidence of any functional role for M2 receptors. Since this finding agrees with a number of other studies using in vivo and in vitro models (1), cell suspensions such as these may prove to be simple tools for the pharmacological study of urinary bladder smooth muscle tissue.

Animals↗

PubMed1999

Trisomy 10 in a child with acute nonlymphocytic leukemia followed by relapse with a different clone.

We report a 2-year-old Japanese boy with acute nonlymphocytic leukemia (ANLL) having trisomy 10 as the sole chromosomal abnormality. The majority of the marrow blasts had lobulated nuclei and Auer rods in their cytoplasm. The blasts were positive for peroxidase, CD13, CD15, and CD33, but negative for esterase, CD3, CD7, CD34, and HLA-DR, indicating a diagnosis of ANLL, atypical M2 in French-American-British (FAB) classification. He was treated with combination chemotherapy, including anthracyclines, etoposide, and cytosine arabinoside. Four months after achieving the first remission, the disease relapsed during the consolidation therapy, and he died 9 months later. Trisomy 10 was not detected at relapse, and blasts showed phenotypes different from those at initial diagnosis. The present case suggests that the prognosis of acute leukemia with trisomy 10 in the pediatric age group may not be good, and that further studies are required to clarify the association of trisomy 10 with leukemogenesis and disease progression.

Bone Marrow↗

PubMed1999

Gene transfer to the rat biliary tract with the HVJ-cationic liposome method.

BACKGROUND/AIMS: The ability to transfer foreign genes into the biliary tract would be useful for the treatment of biliary tract diseases, including cancer, cystic fibrosis and other genetic diseases. To introduce a foreign gene precisely into the rat biliary epithelial cells, we developed a new technique, inserting a polyethylene catheter into the common bile duct through the papilla of Vater by use of a fusigenic cationic liposome with hemagglutinating virus of Japan (HVJ-cationic liposome). METHODS: Transfection efficiency was estimated with the use of FITC-oligonucleotides (FITC-ODNs) and cDNA of beta-galactosidase (pCAG-lacZ). RESULTS: FITC-ODNs encapsulated in HVJ-cationic liposome were effectively transfected into cell nuclei of human cholangiocellular carcinoma in vitro after a 30-min incubation as compared with the simple application of naked FITC-ODNs. After in vivo injection of FITC-ODNs using the HVJ-cationic liposome method through the papilla of Vater, fluorescence accumulation was observed only in the epithelial cells of the biliary tract, but not in the parenchymal cells of the liver. Beta-galactosidase expression was observed in the biliary epithelial cells 3 days after the transfection of pCAG-lacZ and was also detected at 14 days, but not at 28 days, without obvious cytotoxicity. CONCLUSIONS: HVJ-cationic liposome-mediated gene transfer to the biliary tract via the papilla of Vater is a minimally-invasive and an effective gene-delivery method for site-specific targeting to the epithelial cells of the biliary tract, which could be applied to the treatment of human biliary tract diseases.

Animals↗

PubMed1999

An electrophysiological and morphological investigation of the projections of growth hormone-releasing peptide-6-responsive neurons in the rat arcuate nucleus to the median eminence and to the paraventricular nucleus.

Growth hormone-releasing peptide-6 injection induces c-fos messenger RNA expression in many arcuate nucleus neurons, and sub-populations of neurons in this region project to the hypothalamic paraventricular nucleus. We examined electrophysiologically whether arcuate nucleus neurons that project to the paraventricular nucleus also project to the median eminence, and whether these neurons are activated by systemic injection of growth hormone-releasing peptide-6. Of 116 arcuate nucleus neurons tested, 43 were antidromically-identified as projecting to the paraventricular nucleus and a further 30 as projecting to the median eminence; these populations displayed distinct electrophysiological characteristics, and contrasting patterns of orthodromic response to stimulation of the median eminence and paraventricular nucleus, indicating that these two populations are functionally distinct with limited communication between them. Only one cell was antidromically-identified as projecting to both these regions. Three of 10 arcuate nucleus neurons that projected to the paraventricular nucleus were activated by injection of growth hormone-releasing peptide-6. In parallel experiments, we examined whether Fos protein expression is induced in arcuate nucleus neurons that project to the paraventricular nucleus, as identified by retrograde-labelling with FluoroGold. Immunocytochemical studies revealed that 20% of arcuate nucleus neurons that were retrogradely-labelled from the paraventricular nucleus were Fos-positive following growth hormone-releasing peptide-6 injection, although cells that were both Fos-positive and retrogradely-labelled accounted for less than 5% of the total number of Fos-positive arcuate nucleus neurons. These results confirm that there is a direct projection from the arcuate nucleus to the paraventricular nucleus and indicate that growth hormone-releasing peptide-6 activates some of these neurons.

Animals↗

PubMed1999

Excitation of oxytocin cells in the hypothalamic supraoptic nucleus by electrical stimulation of the dorsal penile nerve and tactile stimulation of the penis in the rat.

In urethane-anaesthetized male rats, electrical stimulation of the dorsal penile nerve (DPN) excited 29 of 48 (60%) oxytocin cells in the contralateral supraoptic nucleus, whereas only 5 of 28 (18%) vasopressin cells were excited by the stimulation. The stimulus applied to the ipsilateral DPN to the recorded neurone also excited a similar proportion of oxytocin cells (25 of 43; 58%). Tactile stimulation of the glans penis excited 7 of 12 (58%) oxytocin cells, whereas the same stimulation excited only 3 of 16 (19%) vasopressin cells. The results suggest that sensory information arising from the penis preferentially excites oxytocin cells in the supraoptic nucleus.

Animals↗

PubMed1999

An unusual autopsy case of a victim stabbed during sadomasochistic prostitution.

A 29-year-old male who lived alone was found dead with his back leaning against the wall of his room. He had been stabbed in his abdomen with a survival-type knife. The victim's mouth was plugged with a pink-colored glove and was sealed with packing tape. His wrists were tightly tied behind his back with the same type of packing tape. The cause of death was diagnosed as hemorrhage from the right common iliac artery and vein. Due to the strange circumstances of the crime scene, the police initially considered the possibility of homicide by a group of assassins. Two months later, the police arrested a male suspect who was a member of a vice racketeer. The victim was characterized as a masochist and bisexual. He often hired the male suspect to perform sadomasochistic activities. On the day of the crime, the victim prepared a survival-type knife and packing tape himself to experience fear and pain more strongly. The victim hoped to use the knife to increase sexual excitement. In this case of sadomasochistic prostitution leading to death, the legal issues of homicide for money, malicious request of injury by the victim and accidental death were involved.

Journal Article↗

PubMed1999

Eosinophil activation by eotaxin--eotaxin primes the production of reactive oxygen species from eosinophils.

BACKGROUND: The CC chemokine eotaxin has been shown to possess selective chemotactic activity for eosinophils, the major effector cells in allergic inflammation. Reactive oxygen species (ROS) from eosinophils may damage cells or tissue, such as the mucosal epithelium. In this study, we examined the effect of eotaxin on ROS from eosinophils and compared its activity with RANTES and interleukin (IL)-5. Moreover, we examined the signal transduction of eotaxin and the effect of dexamethasone on ROS from eosinophils. METHODS: Eosinophils were isolated by modified CD16-negative selection. ROS in luminol-dependent or lucigenin-dependent chemiluminescence reaction were examined. Calcium ionophore A23187 was added to the mixture of eosinophils with luminol or lucigenin, and then ROS were determined. RESULTS: Eotaxin primed the production of ROS in a dose-dependent manner. ROS from untreated eosinophils evoked with calcium ionophore A23187 in luminol-dependent chemiluminescence gave a maximal value of 4957+/-1035 intensity counts (IC) (mean+/-SE, n=7) and an integral value of 15.75+/-3.14 IC (x10(-4)), while eosinophils that were treated with eotaxin gave maximal values of 11 142+/-2300 IC (10 nM) and 29165+/-3718 IC (100 nM) and integral values of 41.07+5.44 IC (x10(-4)) (10 nM) and 152.90+/-22.38 IC (x10(-4))(100 nM). Moreover, eotaxin was less effective as a priming agent with lucigenin-sensitive pathways than luminol-sensitive pathways. Among several kinds of eosinophils activating cytokines and chemokines, the priming effect of eotaxin on RO5 was the most potent. Eotaxin-primed ROS were inhibited by pertussis toxin, which ADP-ribolysates G proteins; wortmannin, a phosphatidylinositol-3-kinase inhibitor; and genistein, a tyrosine kinase inhibitor, suggesting the involvement of pertussis toxin-sensitive G proteins, phosphatidylinositol-3-kinase, and tyrosine kinase in the signal transduction of eotaxin. Moreover, dexamethasone inhibited ROS from not only untreated eosinophils but also eosinophils treated with eotaxin. CONCLUSION: Eotaxin may play an important role in the pathogenesis of allergic inflammation through eosinophil activation by priming of eosinophil oxidative metabolism, as well as by involvement in selective eosinophil chemotaxis.

Acridines↗

PubMed1999

Association of CTLA-4 polymorphism with positive anti-GAD antibody in Japanese subjects with type 1 diabetes mellitus.

OBJECTIVE: CTLA-4, expressed on activated T cells, is thought to be a negative regulator of T cell function. Its gene (2q33) may confer genetic susceptibility to type 1 diabetes mellitus (IDDM12). The present study was undertaken to clarify the role of CTLA-4 gene polymorphism in Japanese subjects with type 1 diabetes and its effect on their clinical features. SUBJECTS AND METHODS: In 117 Japanese subjects with type 1 diabetes, the CTLA-4 exon 1 polymorphism (49 A/G) was defined by PCR-RFLP analysis. Anti-GAD antibodies (GAD-Ab) and fasting serum C-peptide were also determined. 141 healthy age- and sex-matched subjects served as controls. RESULTS: The frequency of each polymorphism was not different between the type 1 diabetic subjects and the controls; AA 21, AG 42 and GG 54 for the diabetic subjects, and AA 22, AG 47 and GG 72 for the controls. The frequency of the GG genotype was higher in the diabetic subjects with positive GAD-Ab (greater than 8 U/ml) (67%) than in the GAD-Ab negative subjects (39%) (P < 0.05). The prevalence of positive GAD-Ab declined with the duration of diabetes. In the diabetic subjects with disease duration of less than 5 years (n = 40), the frequency of the GG genotype was also higher in the GAD-Ab positive subjects (71%) (P < 0.05). In the analysis of all the diabetic subjects, there was a strong association between positive GAD-Ab and beta cell function (P < 0.0001). CONCLUSIONS: There was no evidence that the CTLA-4 exon 1 polymorphism (49 A/G) confers genetic susceptibility to type 1 diabetes mellitus in our case-control study in Japanese subjects. However, the frequency of positive GAD-Ab was higher in the GG subjects. CTLA-4 polymorphism might contribute to the clinical heterogeneity of type 1 diabetes mellitus in Japanese subjects.

Abatacept↗