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K Yoshimoto

Publications and source records attributed to K Yoshimoto.

At least 55 records · Page 3Linked to original sources
PubMed2000

Alcohol enhances characteristic releases of dopamine and serotonin in the central nucleus of the amygdala.

The amygdaloid complex (AMY) is implicated in emotional and motivational aspects of behavior, including the formation of positive reinforcement association. AMY may also associated with brain rewarding circuitry. In the present study, the effect of ethanol (EtOH) on the release of dopamine (DA) and serotonin (5-HT) was studied in the central amygdaloid nucleus (CeAMY), and projecting excitatory afferents to the ventral tegmental area (VTA), of freely moving Wistar rats by brain microdialysis. Within 20 min of i.p. injection of EtOH (2 g/kg), the levels of DA and 5-HT in the CeAMY dialysate increased over the baseline value by 270 and 160% (N = 6-7), respectively. Addition of EtOH (25, 50 and 100 mM) to the microdialysis perfusion medium for 1 h caused a 115-150% dose-related increase in the extracellular level of DA in the CeAMY. 100 mM EtOH-induced CeAMY DA release continued to increase for 1 h after the perfusion medium was returned to normal perfusion medium. In contrast, the CeAMY 5-HT level was increased only by the addition of 100 mM EtOH for 1 h to 130% for 80 min. The stimulation of the CeAMY by EtOH through the microdialysis membrane showed delayed responses of DA and 5-HT compared with the i.p. injection of EtOH. Overall, the present findings are not sufficient to conclude whether EtOH acts directly or indirectly on the major monoamine nerve cells in the CeAMY, but the degree of acute EtOH action affected the differences in time at the peak response on EtOH-induced DA and 5-HT releases in the CeAMY via VTA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Age-related dopamine deficiency in the mesostriatal dopamine system of zitter mutant rats: regional fiber vulnerability in the striatum and the olfactory tubercle.

Oxidant stress has been implicated in the pathogenesis of Parkinson's disease. To test the oxidant stress hypothesis of dopaminergic degeneration, age-related changes in the mesostriatal dopamine neuron system were compared between zitter mutant rats which have abnormal metabolism of oxygen species in the brain and Sprague-Dawley rat as a control using the neurochemistry and immunohistochemistry. Dopamine content in the caudate-putamen, nucleus accumbens and olfactory tubercle of zitter rats decreased significantly with age, and was lower than that found in corresponding age-matched controls. In the zitter rats, the reduction of dopamine was more prominent in the caudate-putamen than in the nucleus accumbens and olfactory tubercle. A characteristic decline of tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen of the zitter rat was also observed. In the dorsolateral caudate-putamen, reduction of tyrosine hydroxylase-immunoreactive fibers was observed in the matrix-like area, whereas in the ventromedial caudate-putamen the reduction occurred in the patch-like areas. Degeneration of tyrosine hydroxylase-immunoreactive fibers which was characterized by swollen varicosities and clustered fibers was observed in the caudate-putamen and nucleus accumbens and preceded loss of normal tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen. Thus, the depletion of dopamine in the terminal areas is related to axonal degeneration. However, there was no degenerative tyrosine hydroxylase-immunoreactive fibers in the olfactory tubercle at any examined age, but reductions of tyrosine hydroxylase-immunoreactive fibers and dopamine contents were noted in the olfactory tubercle after four months-of-age. Since the zitter rats have an abnormal oxygen metabolism, the degeneration of tyrosine hydroxylase-immunoreactive fibers could result from an accumulation of superoxide species. The present results provide support for the oxidant stress hypothesis of dopaminergic neuronal degeneration and further indicate the region-specific vulnerability of the nigrostriatal dopamine system.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2000

Involvement of tyrosine phosphorylation in the positive inotropic effect produced by H(1)-receptors with histamine in guinea-pig left atrium.

We investigated the effect of stimulation of H(1)-receptors with histamine on protein tyrosine phosphorylation levels in guinea-pig left atrium and evaluated the influences of tyrosine kinase inhibitors on the positive inotropic effect mediated by H(1)-receptors in this tissue. Histamine induced an increase in tyrosine phosphorylation in four main clusters of proteins with apparent molecular weights of 25, 35, 65 and 150 kDa. Tyrosine phosphorylation of these proteins attained a peak around 2 - 3 min following histamine stimulation and then declined to or below basal levels. Histamine-induced protein tyrosine phosphorylation was antagonized by the H(1)-receptor antagonists mepyramine (1 microM) and chlorpheniramine (1 microM), but not by the H(2)-receptor antagonist cimetidine (10 microM). The positive inotropic effect of histamine was depressed in a concentration-dependent manner by the tyrosine kinase inhibitors tyrphostin A25 (50 to 100 microM) and genistein (10 to 50 microM) but not by the inactive genistein analogue daidzein (50 microM). The positive inotropic effect of isoprenaline was unchanged by tyrphostin A25 and genistein. At a concentration of 1 microM histamine produced a dual-component positive inotropic response composed of an initial increasing phase and a second and late developing, greater positive inotropic phase. Treatment with tyrphostin A25 (100 microM) and genistein (50 microM), but not daidzein (50 microM), significantly attenuated the two components of the inotropic response, although genistein suppressed the initial component more markedly than the late component. We conclude that increased protein tyrosine phosphorylation may play an important role in initiating at least some part of the positive inotropic effect of H(1)-receptor stimulation in guinea-pig left atrium.

Animals↗
PubMed2000

Relation of lifestyle factors to metacarpal bone mineral density was different depending on menstrual condition and years since menopause in Japanese women.

OBJECTIVE: To examine whether the relation between lifestyle and metacarpal bone mineral density (BMD) varied with life-stages. DESIGN: Cross-sectional study. SETTING: Taking questionnaires related to lifestyle and examining metacarpal BMD by computed X-ray densitometry at a local health care center. SUBJECTS: Out of 750 Japanese women aged 40-69 y old who underwent screening for osteoporosis, we selected 535 healthy subjects without medical conditions or lifestyle factors known to affect bone metabolism. RESULTS: A cross-sectional comparison of BMD and years since menopause (YSM) resulted in a logarithmic regression model (BMD=2. 539-0.149xloge YSM, r2=0.418), indicating that a prominent reduction in metacarpal BMD appears up to 4-6 y after menopause. In premenopausal women with regular menstruation, those who engaged in regular physical activity during adolescence showed significantly greater BMD than those who did not. In 1-5-y postmenopausal women, those with current calcium intake of more than 800 mg/d, current milk intake greater than 900 ml/week, daily consumption of milk and/or dairy products, or frequent consumption of small fish showed significantly greater BMD. In 6-15-y postmenopausal women, those who took more than 6000 or 8000 steps/day showed significantly greater BMD. CONCLUSIONS: The relation between lifestyle and BMD differed with life-stages in Japanese women. It was suggested that to perform lifestyle modifications for the prevention of osteoporosis, life-stages should be taken into consideration. SPONSORSHIP: Grant for Research on Health Service from Ministry of Health and Welfare, Japan and grant from The National Dairy Promotion and Research Association of Japan. European Journal of Clinical Nutrition (2000) 54, 9-13

Adult↗
PubMed2000

Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy.

BACKGROUND: We previously described that monocyte chemoattractant protein-1 (MCP-1) plays an important role in progressive glomerular and interstitial damage in inflammatory renal diseases. However, the expression of MCP-1 in diabetic nephropathy remains to be investigated. METHODS: We examined whether locally expressed MCP-1 participates in human diabetic nephropathy via recruiting and activating monocytes/macrophages (Mphi). Urinary and serum MCP-1 levels were measured by enzyme-linked immunosorbent assay in 45 patients with diabetic nephropathy. The presence of MCP-1 in diseased kidneys was determined by immunohistochemical and in situ hybridization analyses. RESULTS: Urinary MCP-1 levels were significantly elevated in patients with diabetic nephrotic syndrome and advanced tubulointerstitial lesions. Moreover, urinary levels of MCP-1 were well correlated with the number of CD68-positive infiltrating cells in the interstitium. In contrast, serum MCP-1 levels remained similar to those of healthy volunteers. Furthermore, we detected the MCP-1-positive cells in the interstitium of diabetic nephropathy via both immunohistochemical and in situ hybridization analyses. CONCLUSION: These observations suggest that locally produced MCP-1 may be involved in the development of advanced diabetic nephropathy, especially in the formation of tubulointerstitial lesions possibly through Mphi recruitment and activation. Moreover, up-regulation of MCP-1 may be a common pathway involved in the progressive tubulointerstitial damage in diabetic nephropathy as well as inflammatory renal diseases.

Adolescent↗
PubMed2000

The rate of cell growth is regulated by purine biosynthesis via ATP production and G(1) to S phase transition.

We recently showed that an increased supply of purine nucleotides increased the growth rate of cultured fibroblasts. To understand the mechanism of the growth rate regulation, CHO K1 (a wild type of Chinese hamster ovary fibroblast cell line) and CHO ade (-)A (a cell line deficient in amidophosphoribosyltransferase, a rate-limiting enzyme of the de novo pathway) were cultured under various conditions. Moreover, a defective de novo pathway in CHO ade (-)A cells was exogenously restored by 5-amino-4-imidazole-carboxamide riboside, a precursor of the de novo pathway. The following parameters were determined: the growth rate of CHO fibroblasts, the metabolic rate of the de novo pathway, the enzyme activities of amidophosphoribosyltransferase and hypoxanthine phosphoribosyltransferase, the content of intracellular nucleotides, and the duration of each cell-cycle phase. We concluded the following: (i) Purine de novo synthesis, rather than purine salvage synthesis or pyrimidine synthesis, limits the growth rate. (ii) Purine nucleotides are synthesized preferentially by the salvage pathway as long as hypoxanthine is available for energy conservation. (iii) The GTP content depends on the intracellular ATP content. (iv) Biosynthesis of purine nucleotides increases the growth rate mainly through ATP production and promotion of the G(1)/S transition.

Adenosine Triphosphate↗
PubMed2000

Developmental changes in cerebrospinal fluid concentrations of monoamine-related substances revealed with a Coulochem electrode array system.

The relationship between age and cerebrospinal fluid concentrations of monoamine-related substances, including kynurenine, were investigated using a Coulochem electrode array system, to clarify developmental changes in monoamine-related substances in the human central nervous system. In neurologically normal children, significant inverse correlations with age were observed for the cerebrospinal fluid concentrations of 5-hydroxytryptophan, 5-hydroxyindole-acetic acid, kynurenine, homovanillic acid, 3-methoxy-4-hydroxyphenyl glycol, and 3-O-methyl-dopamine. The concentrations of their precursors, tryptophan and tyrosine, were not related to age. This is the first comprehensive study revealing developmental changes in monoamine-related substances including their precursors and metabolites.

Age Factors↗
PubMed2000

Changes in dopamine transporter and c-Fos expression in the nucleus accumbens of alcohol-tolerant rats.

BACKGROUND: We have shown that neurochemical functions of 5-HT3 receptors in regulating dopamine (DA) release in the nucleus accumbens (ACC) after alcohol exposure compensate for the dysfunction of serotonergic activity to restore the original properties in processing alcohol tolerance, and that the development of alcohol dependence may be mediated by ACC 5-HT3 receptors. In the present study, the effects of chronic alcohol consumption on the functions of the dopamine transporter (DAT) and the expression of c-Fos proteins were investigated using in vivo brain microdialysis and immunocytochemistry. METHODS: Perfusion of cocaine and 1-(2-Bis-(4-fluorophenyl) methoxy) ethyl)-4-(3-phenylpropyl) piperizine (GBR 12909) through the microdialysis probe membrane increased the extracellular levels of DA in ACC of alcohol-treated rats that had developed alcohol tolerance by drinking 10% EtOH for 30 days. RESULTS: The magnitudes of DA reuptake or DAT inhibitors, cocaine, and GBR 12909 that induced DA availability in the ACC were significantly higher in alcohol-treated rats than in controls. When compared with control rats, the alcohol-treated rats exhibited higher levels of DA and its metabolite, DOPAC, in the ACC. Increased expression of the c-Fos-like protein was found in the ACC of alcohol-treated rats. These results show that (1) chronic alcohol consumption desensitizes or decreases the DAT of DA terminals in the ACC and that (2) EtOH causes cellular hyperexcitability of ACC dopaminergic neurons with increased Fos expression during alcohol tolerance. CONCLUSION: The findings suggested that an abnormality of the dopaminergic neurons in the ACC that are involved with DAT dysfunction is associated with the development of alcohol tolerance.

Alcoholism↗
PubMed2000

Multiple endocrine neoplasia type 1: from bedside to benchside.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic endocrine, and anterior pituitary tumors. MEN1 has two characteristics; a hormone excess and a sometimes lethal outcome due to malignant tumors. The recent identification of the MEN1 gene has opened the door to a much deeper understanding of this syndrome. Germline MEN1 mutations have been identified in most MEN1 families. They were not found, however, in families with familial pituitary tumors. Thus, studies with the MEN1 gene helped to establish that mutation of some other gene(s) is likely causative of the MEN1 phenocopy. These recent advances provide for the identification of mutant MEN1 gene carriers who are at a high risk of developing MEN1. The protein encoded by the MEN1 gene has been shown to function in the regulation of JunD-activated transcription but much still remains to be elucidated.

Genes, Tumor Suppressor↗
PubMed2000

[A case of high-age minimal change nephrotic syndrome relapse after 18-year remission and effective treatment with steroid and cyclosporin combined therapy].

We describe the clinical course of a 69-year-old woman, who suffered from minimal change nephrotic syndrome(MCNS) after long-term remission. In 1979, she was admitted to Kanazawa University Hospital due to MCNS verified by renal biopsy and was treated with oral prednisolone(initially 40 mg/day) for two years. She suffered from edema again in 1999 with massive proteinuria. Renal biopsy revealed minor glomerular abnormality without any deposition of immunoglobulins or complements. Electron microscopic findings showed extensive foot process effacement. Therefore, we diagnosed this case as a recurrence of MCNS. She was treated with the combination of methylprednisolone pulse therapy(500 mg, 3 days), oral prednisolone(20 mg/day) and cyclosporin(CyA, 3 mg/kg/day), which could induce earlier complete remission. These results suggest that recurrence after long-term remission could occur in adult-onset MCNS and that the combination therapy of prednisolone and CyA may be effective for the induction of early remission in MCNS.

Administration, Oral↗
PubMed1999

TRH increases cerebrospinal fluid concentration of kynurenine.

We have analyzed changes in cerebrospinal fluid (CSF) concentrations of monoamine-related substances to clarify the mechanism of the antiepileptic action of thyrotropin-releasing hormone (TRH). TRH-tartrate was administered to 14 patients with intractable epilepsy. Before and 2 weeks after TRH administration, CSF was collected and analyzed for tryptophan and tyrosine metabolites. Among monoamine-related substances, only CSF concentrations of kynurenine were increased after TRH therapy. Considering the fact that kynurenic acid acts as antagonist on the NMDA receptor complex, the results of this study may explain at least one of the mechanisms of the effectiveness of TRH therapy for intractable epilepsy.

Adolescent↗
PubMed1999

Differential regulation of the human insulin gene transcription by GG1 and GG2 elements with GG- and C1-binding factors.

Using a human growth hormone reporter system, the introduced mutations in GG1 alone or both GG elements of GG1 and GG2 in the human insulin promoter abolished 94 or 96% of the beta-cell-specific transcriptional activity in a pancreatic islet beta-cell line of MIN6, while the mutations in GG2 or its total deletion abolished 85 or 86% of the transcriptional activity. When linked to the thymidine kinase promoter, mutations in GG1 or both GG elements abolished 74% of the transcriptional activity in MIN6 cells, while the mutations in GG2 or its total deletion abolished 55 or 54%. In the electrophoretic mobility shift assay (EMSA), one nuclear factor was shown to interact with two GG elements, and another C1-binding factor with GG1 and C1. The differential effects of deletions or selective mutations in the GG2 or GG1 sequence in the oligonucleotide probes on the binding activity of GG- or C1-binding factors in EMSA proved the requirement of both GG1 and GG2 or both GG1 and C1, respectively, for the transaction of these two factors. The molecular size of the GG-binding factor was estimated about 30 kDa. Based on these, we conclude that two GG elements contribute, with GG1 more critically than GG2, to the beta-cell-specific transcription of the human insulin gene through transaction with the GG- and C1-binding factors.

Animals↗
PubMed1999

Interactive binding to the two principal ligand binding sites of human serum albumin: effect of the neutral-to-base transition.

The relationship between the two principal ligand binding sites, sites I and II, on human serum albumin (HSA) was quantitatively and qualitatively examined by equilibrium dialysis and fluorescence spectroscopy. Among the three subsite markers to site I, only the binding of dansyl-L-asparagine (DNSA), which is a subsite Ib marker (K. Yamasaki et al., Biochim. Biophys. Acta 1295 (1996) 147), was inhibited by the simultaneous binding of a site II ligand, such as ibuprofen and diazepam. This indicates that, in contrast to subsite Ib, subsites Ia and Ic do not strongly interact with site II. The thermodynamic characteristics for the coupling reaction between DNSA and ibuprofen and between DNSA and diazepam, which gave positive coupling free energies and negative values for both coupling enthalpy and entropy, indicated that the reaction process was entropically driven. Increase of pH from 6.5 to 8.2 caused an increase in coupling constant and entropy for the mutual antagonism between DNSA and the site II ligands on binding to HSA. The site II ligand-induced red-shift of lambda(max) and solvent accessibility of DNSA in subsite Ib were decreased when the albumin molecule was isomerized from the neutral (N) to the base (B) conformation in the physiological pH region. Based on these findings, we conclude that a 'competitive' like strong allosteric regulation exists for the binding of these two ligands to the N conformer, whereas for the B conformer this interaction can be classified as nearly 'independent'. Since the distance between Trp-214, which resides within the site I subdomain, and Tyr-411, which is involved in site II, is increased by 6 A during the N-B transition (N.G. Hagag et al., Fed. Proc. 41 (1982) 1189), we propose a mechanism for the pH-dependent antagonistic binding between subsite Ib and site II, which involves the transmission of ligand-induced allosteric effects from one site to another site, modified by changes in the spatial relationship of sites I and II caused by the N-B transition.

Acrylamide↗
PubMed1999

Delayed 5-HT release in the developing cortex of microencephalic rats.

Postnatal changes in the fiber distribution and release of 5-HT in the somatosensory cortex (Sm) of methylazoxymethanol acetate (MAM)-induced microencephalic rats were studied. A transient accumulation of serotonergic fibers was observed in the Sm of the control and MAM rats in the first 2 weeks following birth. However, the density of serotonergic fibers was higher in the MAM rats than in the controls, and the distribution pattern of serotonergic fibers was more extensive in the MAM rats. The microdialysis indicated a high basal level and a delayed K+ -evoked 5-HT release in the Sm of MAM rats on postnatal day 10. The present results suggest morphological and functional alterations of serotonergic fibers in the Sm of MAM rats during the critical period of cortical formation.

Abnormalities, Drug-Induced↗
PubMed1999

Apoptosis and remodelling of beta cells by paracrine interferon-gamma without insulitis in transgenic mice.

AIMS/HYPOTHESIS: To examine whether interferon-gamma destroys islet beta cells directly or indirectly through lymphocyte activation, or whether direct action of interferon-gamma on beta cells by itself induces diabetes without insulitis. METHODS: To avoid possible nonspecific breakdown of beta cells by transgenic overexpression of interferon-gamma by the insulin promoter, we generated transgenic mice expressing interferon-gamma under the control of rat glucagon promoter (RGP-IFN-gamma-Tg mice). RESULTS: The absence of insulitis in RGP-IFN-gamma-Tg mice enabled us to investigate the direct effects of paracrine interferon-gamma. In RGP-IFN-gamma-Tg mice, serum concentrations of interferon-gamma and tumour necrosis factor-alpha (TNF-alpha) were 50 and 6 times higher than those in their littermates, respectively, and glucose-responsive insulin secretion decreased to one-half the level of that in the littermates. Transgenic interferon-gamma induced remodelling of beta cells where apoptosis of many beta cells was compensated by their vigorous regeneration and diabetes did not occur in most of the RGP-IFN-gamma-Tg mice. CONCLUSION/INTERPRETATION: Interferon-gamma alone is insufficient for the complete destruction of beta cells in vivo, and factors other than interferon-gamma including activated lymphocytes or other cytokines, are necessary in addition to interferon-gamma for the development of Type I (insulin-dependent) diabetes mellitus.

Animals↗