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Y Ishihara

Publications and source records attributed to Y Ishihara.

At least 37 records · Page 2Linked to original sources
PubMed2000

3D localized 1H-13C heteronuclear single-quantum coherence correlation spectroscopy in vivo.

A method for spatially three-dimensional (3D) localized two-dimensional (2D) 1H-13C correlation spectroscopy, localized HSQC, is proposed. This method has the following special feature in the preparation period. The 180 degrees (13C) and 180 degrees (1H) pulses are separated in time, and the 180 degrees (13C) pulse is applied at 1/4 1JCH) before the 90 degrees (1H) polarization transfer pulse. The preparation (echo) period 2tau can then be set substantially longer than 1/(2 1JCH), so that even in a whole-body system, slice-selective 90 degrees (1H) pulses and gradient pulses can be applied in that period. The localization capabilities of this method were confirmed in a phantom experiment. The 3D localized 2D 1H-13C correlation spectra from a monkey brain in vivo were obtained after [1-13C]glucose injection, and amino acid metabolism was detected; that is, [4-13C]glutamate appeared immediately after the injection, followed by the appearance of [2-13C]glutamate, [3-13C]glutamate, and [4-13C]glutamine.

Animals↗
PubMed2000

Human brain glucose metabolism mapping using multislice 2D (1)H-(13)C correlation HSQC spectroscopy.

A method for multivolume 2D (1)H-(13)C correlation spectroscopy, multislice heteronuclear single quantum coherence (HSQC), is proposed. This permits human brain metabolism from glucose to amino acids to be followed using a 2-T whole-body scanner. The modifications from the conventional HSQC are that the 180 degrees ((13)C) and 180 degrees ((1)H) pulses are separated in time in the preparation period and that the 180 degrees ((13)C) pulse is applied at 1/(4J(CH)) before the 90 degrees ((1)H) polarization transfer (PT) pulse. The preparation (echo) time can be set longer than 1/(2J(CH)) so that, even in a whole-body system, slice-selective pulses and gradients can be applied. Another modification is that the 90 degrees ((1)H) reverse PT pulses after the creation of 2I(z)S(z) are used as multislice pulses. The time-course of glutamate C4 could be followed with 15-min temporal resolution from the HSQC spectra obtained from the brains of volunteers after the oral administration of glucose C1, and the maximum S/N was 3.

Adult↗
PubMed2000

Temperature monitoring of internal body heating induced by decoupling pulses in animal (13)C-MRS experiments.

A temperature monitoring method to promote safety with regard to tissue heating induced by RF irradiation during MRI procedures, especially carbon-13 magnetic resonance spectroscopy ((13)C-MRS), is proposed. The method is based on the temperature dependence of the water proton chemical shift (-0.01 ppm/ degrees C) combined with phase mapping. Using this method, temperature changes were measured in rats (n = 4) employing practical (1)H-decoupled (13)C-MRS pulse sequences for 1D projections (TR = 1000 ms, acquisition time = 15 ms, matrix = 256, spatial resolution = 0.2 mm) and 2D images (TR = 1500 ms, acquisition time = 840 ms, matrix = 128x32, spatial resolution = 0.8x1.5 mm). Measurement error was 0.18 degrees C (SD) for 1D acquisition and 0.39 degrees C (SD) for 2D acquisition, demonstrating the feasibility of this temperature mapping method. Further studies should be conducted in human subjects to monitor patient safety and to optimize the pulse sequences employed. Magn Reson Med 43:796-803, 2000.

Animals↗
PubMed2000

Effects of acute and chronic cigarette smoking on the expression of endothelin-1 mRNA of the cardiovascular tissues in rats.

Although smoking has been suggested to be involved in the development of cardiovascular diseases, details of the mechanism still need to be revealed. We investigated the effects of cigarette smoking on the tissue mRNA expression of endothelin-1 (ET-1). Male Wistar rats of 4 weeks of age were exposed to smoke from six cigarettes for 30 min (acute exposure) and six cigarettes for 30 min/day, 5 days a week for 6 months (chronic exposure). Half of the rats exposed to 6 months smoking were kept in clean-air conditions for a further 3 months to clear the effects. Tissue expression of ET-1 mRNA in the kidney, aorta, heart and lung was determined by reverse transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot analysis. There was no significant difference in body and organ weight of the heart and kidney between the control and smoking group in either the acute or chronic experiment. In the acute-exposure experiment, expression of ET-1 mRNA was increased in the heart and lung, while that in the kidney and aorta was unchanged. In the chronic-exposure experiment, however, there was no significant difference in the expression of ET-1 mRNA in all the tissues between the smoking and control groups. These results suggest that cigarette smoking could cause cardiovascular and pulmonary diseases by modulating ET-1 mRNA expression in the tissues.

Animals↗
PubMed2000

Regulation of immunoglobulin G2 production by prostaglandin E(2) and platelet-activating factor.

Patients with localized juvenile periodontitis (LJP) have elevated levels of immunoglobulin G2 (IgG2) in their sera. This is also observed in vitro when peripheral blood leukocytes from LJP patients are stimulated with pokeweed mitogen. In previous studies, we showed that lymphocytes from subjects with no periodontitis (NP subjects) produced substantial amounts of IgG2 when they were cultured with monocytes from LJP patients (LJP monocytes). These observations indicate that monocytes or monocyte-derived mediators are positive regulators of the production of IgG2. The present study was initiated to determine if secreted factors from LJP monocytes were capable of enhancing IgG2 production and to determine if prostaglandin E2 (PGE(2)), which LJP monocytes produce at elevated levels, enhances IgG2 production. Experiments in a transwell system and with monocyte-conditioned media indicated that cell-cell contact was not necessary for LJP monocytes to augment the production of IgG2 by T and B cells from NP subjects. Moreover, the production of IgG2 was selectively induced by the addition of PGE(2) or platelet-activating factor (PAF), another lipid cytokine, which can elevate PGE(2) synthesis. Furthermore, IgG2 production was abrogated when cells were treated with indomethacin, a cyclooxygenase inhibitor that blocks the synthesis of PGE(2), or the PAF antagonists CV3988 and TEPC-15. The effects of indomethacin were completely reversed by PGE(2), indicating that this is the only prostanoid that is essential for the production of IgG2. Similarly, PGE(2) reversed the effects of a PAF antagonist, suggesting that the effects of PAF are mediated through the induction of PGE(2) synthesis. Together, these data indicate that PGE(2) and PAF are essential for the production of IgG2.

Aggressive Periodontitis↗
PubMed2000

Exocytosis and movement of zymogen granules observed by VEC-DIC microscopy in the pancreatic tissue en bloc.

The dynamic aspects of exocytosis, especially in the normal acinar tissue en bloc, have remained unclear. We visualized exocytosis directly in the tissue of the exocrine pancreas of rodents by video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy to investigate various exocytosis-related rates and the relationship between the movement of granules and exocytotic responses. Stimulation of the tissue with bethanechol or cholecystokinin caused many of the zymogen granules in the apical pole to disappear abruptly. The exocytotic transients of individual granules were completed in 0.48-0.65 s. Granules destined to participate in the exocytotic response moved randomly at velocities of approximately 0.06 microm/s or less during stimulation. In the tissue preparation, granules located far from the apical pole frequently moved back and forth for 1-7 microm without showing exocytosis. Colchicine suppressed this movement and the late phase of the secretory response. Real-time (VEC-DIC) observation of granule dynamics revealed that the initial step of exocytosis was not coupled directly with the microtubule-dependent translocation but with a continuous, slow Brownian fluctuation of granules.

Animals↗
PubMed2000

Abnormal functional and morphological regulation of the gastric mucosa in histamine H2 receptor-deficient mice.

To clarify the physiological roles of histamine H2 receptor (H2R), we have generated histamine H2R-deficient mice by gene targeting. Homozygous mutant mice were viable and fertile without apparent abnormalities and, unexpectedly, showed normal basal gastric pH. However, the H2R-deficient mice exhibited a marked hypertrophy with enlarged folds in gastric mucosa and an elevated serum gastrin level. Immunohistochemical analysis revealed increased numbers of parietal and enterochromaffin-like (ECL) cells. Despite this hypertrophy, parietal cells in mutant mice were significantly smaller than in wild-type mice and contained enlarged secretory canaliculi with a lower density of microvilli and few typical tubulovesicles in the narrow cytoplasm. Induction of gastric acid secretion by histamine or gastrin was completely abolished in the mutant mice, but carbachol still induced acid secretion. The present study clearly demonstrates that H2R-mediated signal(s) are required for cellular homeostasis of the gastric mucosa and normally formed secretory membranes in parietal cells. Moreover, impaired acid secretion due to the absence of H2R could be overcome by the signals from cholinergic receptors.

Animals↗
PubMed2000

Frequency of facial angiofibromas in Japanese patients with multiple endocrine neoplasia type 1.

The high frequency of cutaneous manifestations in patients with multiple endocrine neoplasia type 1 (MEN 1) has recently been reported. Since prevalence of some cutaneous diseases varies among different ethnic groups, we examined the frequency of facial angiofibromas in Japanese patients with familial MEN 1. Among 27 patients with germline MEN1 gene mutation and one asymptomatic gene carrier, angiofibromas were identified in 43% (12/28) of the subjects. This frequency was significantly lower than that of Caucasian patients, but nonetheless almost equaled those of pituitary tumors and pancreas endocrine tumors. Angiofibromas should be considered as one of major manifestations in MEN 1 regardless of patients' ethnic origin, and clinicians should pay careful attention to the cutaneous lesions in patients with endocrine tumors.

Adult↗
PubMed2000

Central selective acetylcholinesterase inhibitor with neurotrophic activity: structure-activity relationships of TAK-147 and related compounds.

A series of benzylamino inhibitors of acetylcholinesterase (AChE) have been designed based on a working hypothesis of the enzyme s active site. These compounds were tested for their inhibitory activities on AChE and potent inhibitors were further evaluated in terms of central selectivity. These studies led to a discovery of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4, 5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (TAK-147). Pharmacokinetic study has shown that the compound has high central selectivity, as demonstrated by rapid elimination from plasma and long-term existence in the brain. As a consequence, TAK-147 ameliorates impairments of learning and memory in various animal models without producing peripheral side effects. TAK-147 also activates the monoaminergic systems and energy metabolism. Furthermore, TAK-147 was revealed to have NGF-like neurotrophic activity on central cholinergic neurons at concentrations where it inhibits AChE activity. Therefore, TAK-147 is expected not only to ameliorate the clinical symptoms in Alzheimer s disease via AChE inhibition but to prevent or slow the progression of the disease via its neurotrophic action. TAK-147 is now under clinical trial as a therapeutic drug for Alzheimer s disease. This article reviews design and structure-activity relationships of TAK-147 and related compounds. Preclinical pharmacology of TAK-147 is also summarized.

Alzheimer Disease↗
PubMed1999

1,3-Disubstituted benzazepines as novel, potent, selective neuropeptide Y Y1 receptor antagonists.

A novel series of potent and selective non-peptide neuropeptide Y (NPY) Y1 receptor antagonists, having benzazepine nuclei, have been designed, synthesized, and evaluated for activity. Chemical modification of the R(1) and R(3) substituents in structure 1 (Chart 1) yields several compounds that show high affinity for the Y1 receptor (K(i) values of less than 10 nM). SAR studies revealed that introduction of an isopropylurea group at R(1) and a 3-(benzo-condensed-urea) group, 3-(fluorophenylurea) group, or a 3-(N-(4-hydroxyphenyl)guanidine) group at R(3) in structure 1 afforded potent and subtype-selective NPY Y1 receptor antagonists. 3-(3-(Benzothiazol-6-yl)ureido)-1-N-(3-(N'-(3-isopropylureido++ +))benzyl )-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (21), which was one of the most potent derivatives, competitively inhibited specific [(125)I]peptide YY (PYY) binding to Y1 receptors in human neuroblastoma SK-N-MC cells (K(i) = 5.1 nM). 21 not only inhibited the Y1 receptor-mediated increase in cytosolic free Ca(2+) concentration in SK-N-MC cells but also antagonized the Y1 receptor-mediated inhibitory effect of peptide YY on gastrin-induced histamine release in rat enterochromaffin-like cells. 21 showed no significant affinity in 17 receptor binding assays including Y2, Y4, and Y5 receptors.

Animals↗
PubMed1999

Wernicke encephalopathy-like symptoms as an early manifestation of Creutzfeldt-Jakob disease in a chronic alcoholic.

A case of Creutzfeldt-Jakob disease (CJD) with presenting Wernicke encephalopathy (WE)-like symptoms and severe insomnia is presented. An 80-year-old alcoholic man with a 6 month history of tremors, ataxia, memory loss and confabulation, developed profound insomnia, confusion, and delirium with vivid hallucinations. Polysomnography revealed a marked reduction of sleep time, with central-type sleep apnea. Neither myoclonus nor periodic synchronous discharge (PSD) was observed. An autopsy revealed diffuse spongiform changes and astrocytosis throughout the cerebral gray matter, with severe involvement of the mammillary bodies and thalamus. Prion protein (PrP) immunostaining was positive in kuru plaques in the cerebellum, PrP polymorphism at codon 129 was heterozygous Met/Val, and proteinase K resistant PrP (PrP(res)) was demonstrated by Western blotting. The lack of necrotizing lesions in the mammillary bodies, thalamus, and periaqueductal gray matter could rule out WE. The data suggest that the present case of CJD is consistent with PrP(res) type 2 (CJD M/V 2), but was unique in the lack of some typical CJD signs and the presence of signs of WE and sleep abnormalities.

Aged↗
PubMed1999

IgG subclass switching is associated with the severity of experimental autoimmune encephalomyelitis induced with myelin oligodendrocyte glycoprotein peptide in NOD mice.

We have recently shown that a single dose of the myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 produces a relapsing-remitting demyelinating disease similar to multiple sclerosis (MS) in Lewis rats. In this study we have assessed the possibility that a subclass of anti-MOG35-55 antibodies influences the clinical outcome of these diseases by examining the classes and isotypes of anti-MOG35-55 antibody produced during the course of MOG35-55-induced demyelinating disease in NOD mice. Following immunization, 7 of the 21 injected mice had only mild diseases, while the 14 others had severe progressive and/or relapsing-remitting diseases. There were no differences in anti-MOG35-55 IgG, IgA, IgM, IgG1, IgG2a, and IgG3 antibody titers between the severe and mild symptoms groups. High levels of IgG2b antibody to MOG35-55 were detected in all mice with severe symptoms. In contrast, none of the mice which contracted a mild disease produced anti-MOG35-55 IgG2b. These results suggest that in NOD mice, the IgG2b antibody response to MOG35-55 is associated with the severity of this MS-like demyelinating disease.

Amino Acid Sequence↗
PubMed1999

TAK-147, an acetylcholinesterase inhibitor, increases choline acetyltransferase activity in cultured rat septal cholinergic neurons.

TAK-147, a potent acetylcholinesterase (AChE) inhibitor, potentiated choline acetyltransferase (ChAT) activity in cultured rat septal cholinergic neurons in a concentration-dependent manner with an EC50 value of 4.47 nM. Donepezil, another potent AChE inhibitor, also increased ChAT activity although its potency was less than that of TAK-147. Other AChE inhibitors (rivastigmine, tacrine, physostigmine and neostigmine) showed no effect. The effects of TAK-147 were greater in the presence of NGF, suggesting a synergistic action of TAK-147 and NGF. TAK-147 and donepezil showed high affinity for sigma receptors, whereas tacrine and physostigmine did not. Haloperidol and ifenprodil, high-affinity sigma ligands, potently enhanced ChAT activity in the septal neurons. These results suggest that TAK-147 may have neurotrophic activity on central cholinergic neurons, not via AChE inhibition but possibly via an effect on tau receptors.

Animals↗
PubMed1999

A case of endolymphatic sac tumor with long-term survival.

A 72-year-old man developed left facial palsy at age 14 and left-sided hearing loss at age 20. At the age of 59, he presented with gait disturbance, and a large left cerebellopontine angle tumor was detected, which had markedly destroyed the pyramidal bone. The tumor was subtotally resected, but he required two more operations at the ages of 64 and 69 because of tumor regrowth. At the present time, recurrent tumor has destroyed the occipital bone and is invading the scalp. However, even though he has several cranial nerve palsies and cerebellar ataxia, he remains in stable condition and demonstrates long-term survival. The patient's surgical specimens revealed a papillary adenoma, which was recently thought to be of endolymphatic sac origin, although the origin of this kind of tumor, whether arising from the middle ear or from the endolymphatic sac, has not been established with certainty so far. In this paper, we provide further evidence that this tumor originates from the endolymphatic sac, based on anatomical, histopathological, and embryological evidence.

Adenoma↗
PubMed1999

Inhibition of experimental bone resorption and osteoclast formation and survival by 2-aminoethanesulphonic acid.

It is known that bone resorption is mediated by osteoclasts, and lipopolysaccharide (LPS) and inflammatory mediators such as interleukin-1 (IL-1) and prostaglandin E2 (PGE2) induce osteoclast differentiation from haemopoietic cells, 2-aminoethanesulphonic acid, which is known as taurine, is an important nutrient and is added to most synthetic human infant milk formulas. In this study, it was found that 2-aminoethanesulphonic acid inhibits the stimulation of bone resorption mediated by LPS of the periodontopathic microorganism Actinobacillus actinomycetemcomitans Y4 in organ cultures of newborn mouse calvaria. The effect of 2-aminoethanesulphonic acid on the development and survival of osteoclast-like multinucleated cells produced in a mouse bone-marrow culture system was also examined. 2-aminoethanesulphonic acid (100 microg/ml) suppressed the formation of these osteoclast-like cells in the presence of LPS of A. actinomycetemcomitans Y4, IL-1alpha or PGE2 in mouse marrow cultures. On the other hand, 2-aminoethanesulphonic acid did not inhibit 1alpha, 25-dihydroxyvitamin D3-mediated osteoclast differentiation. Although IL-1alpha elongated the survival of the osteoclast-like cells, 2-aminoethanesulphonic acid blocked the supportive effect of IL-1alpha on osteoclast survival. 2-aminoethanesulphonic acid showed no effect on the growth of mouse osteoblasts. Finally, it was found that 2-aminoethanesulphonic acid inhibited alveolar bone resorption in experimental periodontitis in hamsters. These results suggest that 2-aminoethanesulphonic acid is an effective agent in preventing inflammatory bone resorption in periodontal diseases.

Aggregatibacter actinomycetemcomitans↗
PubMed1999

Proton nuclear magnetic resonance spectroscopy of urine for rapid multicomponent analysis of intraoperative cellular metabolites.

We serially measured the proton nuclear magnetic resonance spectra of the urine of intraoperative patients over time to assess their potential use for rapid multicomponent analysis of cellular metabolites. Within a few minutes, the spectra provided signals of many low molecular weight urinary metabolites, including amino acids, ketone bodies, lactate, and glucose. The proton magnetic resonance spectra of the urine of most of the intraoperative patients showed large increases in urinary excretion of alanine, ketone bodies, and lactate and/or glucose, confirming alterations in energy substrate-endocrine relationships during the perioperative period. These metabolic changes appeared to be roughly proportional to the degree of surgical stress, but they were not consistent among patients who underwent the same operation. The study suggests that routine intraoperative metabolic monitoring is necessary to prevent critical metabolic disorders and that proton nuclear magnetic resonance spectroscopy of urine may meet this need by allowing rapid multicomponent analysis of cellular metabolites.

Adult↗