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Biomedical subjects

M Hashimoto

Publications and source records attributed to M Hashimoto.

At least 73 records · Page 4Linked to original sources
PubMed2001

Right hepatic duct emptying into the cystic duct: report of a case.

BACKGROUND: Anomalous insertion of the right hepatic duct into the cystic duct is a rare anatomic variation. At this writing, only nine cases have been reported in the literature. In the patients presenting with this anomaly, the surgeon may accidentally transect the right hepatic duct during cholecystectomy. METHODS: We encountered a case of anomalous insertion of the right hepatic duct into the cystic duct, which was clearly demonstrated in the intraoperative cholangiography during laparoscopic cholecystectomy. RESULTS: As the half-cut point of the cystic duct happened to be on the gallbladder side of the cystic duct, cholecystectomy was accomplished laparoscopically. CONCLUSIONS: In anomalous insertion of the right hepatic duct into the cystic duct, hepatic duct transection could happen. Preoperative precise evaluation of the biliary duct, awareness of potential biliary variations, and identification of all anatomic structures before ligation and division were essential to prevent bile duct injury.

Aged↗
PubMed2001

An inhibitor of inducible nitric oxide synthase decreases forearm blood flow in patients with congestive heart failure.

OBJECTIVES: The functional activation of inducible nitric oxide synthase (iNOS) was evaluated as a source of nitric oxide (NO) in the forearm of patients with heart failure. BACKGROUND: Although endogenous NO is normally produced by constitutive NO synthase (cNOS) in patients with congestive heart failure (CHF), expression of iNOS provides an additional source of NO. However, there are no in vivo studies showing functional activation of iNOS in humans. METHODS: A nonselective NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), and a selective inhibitor of iNOS, aminoguanidine, were administered intra-arterially in graded doses into the brachial arteries of 13 patients with CHF and 10 normal control subjects. Forearm blood flow (FBF) was measured simultaneously in the infused and noninfused arms by plethysmography. Arterial and venous plasma concentrations of nitrite/nitrate (NOx) were measured at baseline and at the highest dose of each drug. RESULTS: L-NMMA significantly reduced the FBF ratio between the infused and noninfused arms in both the control and patient groups (35 +/- 12% and 34 +/- 10%, respectively; both p < 0.001). Aminoguanidine at the same concentration significantly reduced the ratio in the patient group (15 +/- 9%, p < 0.01), with no change in the control group. The arterial NOx concentration was not affected by either drug; however, venous NOx concentrations were significantly decreased in both the control and patient groups by L-NMMA (18 +/- 5% and 18 +/- 17%, respectively; both p < 0.05) and in the patient group only by aminoguanidine (7 +/- 6%, p < 0.05). CONCLUSIONS: These findings suggest that NO production in the forearms of patients with CHF is induced partly by iNOS activation, whereas in normal subjects, it can be ascribed to cNOS activation.

Acetylcholine↗
PubMed2001

beta-Synuclein inhibits alpha-synuclein aggregation: a possible role as an anti-parkinsonian factor.

We characterized beta-synuclein, the non-amyloidogenic homolog of alpha-synuclein, as an inhibitor of aggregation of alpha-synuclein, a molecule implicated in Parkinson's disease. For this, doubly transgenic mice expressing human (h) alpha- and beta-synuclein were generated. In doubly transgenic mice, beta-synuclein ameliorated motor deficits, neurodegenerative alterations, and neuronal alpha-synuclein accumulation seen in halpha-synuclein transgenic mice. Similarly, cell lines transfected with beta-synuclein were resistant to alpha-synuclein accumulation. halpha-synuclein was coimmunoprecipitated with hbeta-synuclein in the brains of doubly transgenic mice and in the double-transfected cell lines. Our results raise the possibility that beta-synuclein might be a natural negative regulator of alpha-synuclein aggregation and that a similar class of endogenous factors might regulate the aggregation state of other molecules involved in neurodegeneration. Such an anti-amyloidogenic property of beta-synuclein might also provide a novel strategy for the treatment of neurodegenerative disorders.

Animals↗
PubMed2001

Apolipoprotein E epsilon 4 and the pattern of regional brain atrophy in Alzheimer's disease.

BACKGROUND: Although the APOE epsilon 4 allele increases the risk of developing AD, the effects of the epsilon 4 allele on brain atrophy in clinical AD patients are controversial. OBJECTIVE: To investigate a possible relationship between the genetic variants of APOE and brain atrophy in patients with AD. METHODS: Using MRI-based volumetry techniques, the authors compared the volumes of the hippocampal formation, amygdaloid complex, and whole brain in probable AD patients (based on criteria of the National Institute for Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association) with different APOE alleles. One group (n = 46) had the epsilon 3/3 allele, one group (n = 46) had the epsilon 3/4 allele, and one group (n = 46) had the epsilon 4/4 allele. The three groups were matched for age, sex, disease duration, education level, and severity of dementia represented by their score of the Mini-Mental State Examination. A possible difference in pattern of cognitive deficits with dose of the APOE epsilon 4 allele was also examined. RESULTS: The normalized hippocampal volume was correlated with the number of APOE epsilon 4 alleles (r = -0.285, p = 0.0007). The amygdalar volume was also correlated with the number of APOE epsilon 4 alleles (r = -0.178, p = 0.037). The number of APOE epsilon 4 alleles was positively correlated with the whole-brain volume (r = 0.185, p = 0.030). It was also correlated with Wechsler Adult Intelligence Scale-Revised performance IQ (r = 0.203, p = 0.017) and with Wechsler Memory Scale-Revised attention/concentration score (r = 0.191, p = 0.025). CONCLUSIONS: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE epsilon 4 allele on the brains of AD patients may have regional specificity.

Aged↗
PubMed2001

beta-amyloid peptides enhance alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease.

Alzheimer's disease and Parkinson's disease are associated with the cerebral accumulation of beta-amyloid and alpha-synuclein, respectively. Some patients have clinical and pathological features of both diseases, raising the possibility of overlapping pathogenetic pathways. We generated transgenic (tg) mice with neuronal expression of human beta-amyloid peptides, alpha-synuclein, or both. The functional and morphological alterations in doubly tg mice resembled the Lewy-body variant of Alzheimer's disease. These mice had severe deficits in learning and memory, developed motor deficits before alpha-synuclein singly tg mice, and showed prominent age-dependent degeneration of cholinergic neurons and presynaptic terminals. They also had more alpha-synuclein-immunoreactive neuronal inclusions than alpha-synuclein singly tg mice. Ultrastructurally, some of these inclusions were fibrillar in doubly tg mice, whereas all inclusions were amorphous in alpha-synuclein singly tg mice. beta-Amyloid peptides promoted aggregation of alpha-synuclein in a cell-free system and intraneuronal accumulation of alpha-synuclein in cell culture. beta-Amyloid peptides may contribute to the development of Lewy-body diseases by promoting the aggregation of alpha-synuclein and exacerbating alpha-synuclein-dependent neuronal pathologies. Therefore, treatments that block the production or accumulation of beta-amyloid peptides could benefit a broader spectrum of disorders than previously anticipated.

Age Factors↗
PubMed2001

Promoter structure and gene expression of the mouse inositol 1,4,5-trisphosphate receptor type 3 gene.

Inositol 1,4,5-trisphosphate receptor type 3 (IP(3)R3) is a ubiquitously expressed IP(3)R gene in the IP(3)R gene family. We identified an upstream region of the mouse IP(3)R3 genomic DNA. Transcription start points for the IP(3)R3 gene were found to be located mainly at four sites between nucleotide position -325 and -285 relative to the first ATG codon. The major start point was mapped around -325. Transcription promotion ability was detected between -325 and -285 in an IP(3)R3 proximal promoter sequence. The promoter had no TATA-box but was highly GC-rich and contained two putative Sp1-binding sites. There was no sequence similarity between promoter regions of IP(3)R3 and IP(3)R2, another ubiquitous gene, except for GC-boxes. By using a series of 5'-truncation versions and a transient luciferase assay, we detected multiple common and cell-type-dependent regulatory regions within the distal promoter sequence downstream from -4.0 kb that function positively or negatively. The IP(3)R3 gene was highly transcribed in the kidney, spleen, heart, and skeletal muscle, and this tissue distribution pattern was nearly complementary to that of IP(3)R2. We found that IP(3)R3 gene expression was repressed in retinoic acid-treated and neural differentiated P19 mouse embryonic carcinoma cells.

3T3 Cells↗
PubMed2001

Effects of candesartan on cough and bronchial hyperresponsiveness in mildly to moderately hypertensive patients with symptomatic asthma.

BACKGROUND: Candesartan, an AT(1) receptor antagonist, has been reported to have no association with persistent cough in subjects with hypertension, but there has been no study on the safety of its administration to hypertensive patients with symptomatic asthma. The aim of this study was to compare the adverse effects of candesartan and calcium antagonists on cough, pulmonary function, and bronchial hyperresponsiveness in these patients. METHODS AND RESULTS: Sixty mildly to moderately hypertensive patients with bronchial asthma received either candesartan (n=30) or the calcium antagonists nifedipine or manidipine (n=30) for 6 months. The candesartan group included 5 subjects with a history of ACE inhibitor-induced cough. There were no differences between the 2 groups in patient characteristics, ACE gene polymorphism, pulmonary function, or bronchial hyperresponsiveness to methacholine. Control of hypertension was the primary end point; new cough detected by self-administrated questionnaire and an increase in cough frequency by visual analog scale were the second end point. No patient complained of persistent cough. Neither mean visual analog scale score nor pulmonary functions changed during this study. Bronchial hyperresponsiveness had a tendency to improve in the candesartan group, but there was no difference between the 2 groups. CONCLUSIONS: Incidence, frequency, and severity of persistent cough, pulmonary functions, and bronchial hyperresponsiveness did not change in either the candesartan or calcium antagonist group. It is suggested that candesartan is as effective and safe as calcium antagonists in the treatment of hypertension associated with symptomatic asthma.

Adult↗
PubMed2001

Purification and characterization of carbaryl hydrolase from Arthrobacter sp. RC100.

A carbaryl hydrolase was purified to homogeneity from Arthrobacter sp. strain RC100 by protamine sulfate treatment, ammonium sulfate precipitation, and hydrophobic, anion-exchange, and gel filtration chromatographies. The native enzyme had a molecular mass of 100 kDa and was composed of two identical subunits with molecular masses of 51 kDa. The hydrolase activity was strongly inhibited by DIFP, PMSF, Hg(2+) and paraoxon but not by EDTA. The optimum pH and temperature for the enzyme activity were 9.0 and 50 degrees C, respectively. The enzyme hydrolyzed four N-methylcarbamate insecticides (carbaryl, xylylcarb, metolcarb and XMC), but was not able to hydrolyze fenobucarb, propoxur, and isoprocarb.

Arthrobacter↗
PubMed2001

Fluorescent pigments of the retinal pigment epithelium and age-related macular degeneration.

The major hydrophobic fluorophore of the retinal pigment epithelium (RPE) is A2E, a pyridinium bis-retinoid derived from all-trans-retinal and phosphatidyl-ethanolamine. The accumulation of fluorophores such as A2E is implicated in the pathogenesis of age-related macular degeneration (AMD), a disease associated with the deterioration of central vision and a leading cause of blindness in the elderly. Recent chemical and biological studies have provided insight into the synthesis and biosynthesis of A2E, the spectroscopic properties of this pigment, and the role of A2E and RPE cell death.

Age Factors↗
PubMed2001

Significant effect of the N-terminal region of the mitochondrial ADP/ATP carrier on its efficient expression in yeast mitochondria.

The low-level expression of the bovine heart mitochondrial ADP/ATP carrier (bovine type 1 ADP/ATP carrier (bAAC1)) in the yeast mitochondrial membrane is significantly improved by replacement of its N-terminal region with corresponding regions of the yeast type 1 and 2 carriers (yAAC1 and yAAC2) (Hashimoto, M., Shinohara, Y., Majima, E., Hatanaka, T., Yamazaki, N., and Terada, H. (1999) Biochim. Biophys. Acta 1409, 113--124). To understand why the bAAC1 chimeras were highly expressed in yeast mitochondria, we examined the effects of the length and sequence of the N-terminal region extending into the cytosol on the expression of bAAC1 and yAAC2 derivatives in yeast mitochondria. For this, their N-terminal regions were replaced with peptide fragments of various lengths and sequences derived from those of bAAC1, yAAC1, and yAAC2. We found that a specific amino acid sequence and a definite length of the N-terminal region of yAAC2 were required for high expression of bAAC1 and yAAC2 in yeast mitochondria. We also examined the steady-state transcript levels and expression of these derivatives in whole yeast cells. Based on our results, we discuss the role of the N-terminal region in efficient expression of bAAC1 and yAAC2 in yeast mitochondria.

Amino Acid Sequence↗
PubMed2001

Altered expression of glutamate transporters under hypoxic conditions in vitro.

Regulation of extracellular excitotoxins by glial and neuronal glutamate transporters is critical to maintain synaptic terminal integrity. Factors interfering with the normal functioning of these transporters might be involved in neurodegeneration. Among them, recent studies have shown that hypoxia alters glutamate transporter function; however, it is unclear if hypoxia has an effect on the expression of glutamate transporters and which intracellular signaling pathways are involved. The C6 rat glial and GT1--7 mouse neuronal cell lines were exposed to hypoxic conditions (5% CO(2), 95% N(2)) and levels of glutamate transporter mRNA were determined by ribonuclease protection assay. After 21 hr, there was a 100% increase in levels of rat excitatory amino acid transporter 3 (EAAT3) mRNA in C6 cells and a 600% increase in levels of murine EAAT2 mRNA in GT1--7 cells. There was a similar increase in mRNA levels after hypoxia in C6 cells transfected with human EAAT2, whereas reoxygenation normalized the expression levels of glutamate transporters. Although the expression of EAATs was associated with increased immunoreactivity by Western blot, functioning of the transporters was decreased as evidenced by D-aspartate uptake. Finally, although the protein kinase C stimulator phorbol-12-myristate-13-acetate enhanced EAAT2 mRNA levels after hypoxia, protein kinase C inhibitor bisindolylmaleimide I had the opposite effect. Taken together, this study suggests that the hypoxia is capable of upregulating levels of EAATs via a protein kinase C-dependent compensatory mechanism. This increased expression is not sufficient to overcome the decreased functioning of the EAATs associated with decreased ATP production and mitochondrial dysfunction.

Amino Acid Transport System X-AG↗
PubMed2001

Trp122 and Trp134 on the surface of the catalytic domain are essential for crystalline chitin hydrolysis by Bacillus circulans chitinase A1.

From the 3D-structural analysis of the catalytic domain of chitinase A1, two exposed tryptophan residues (W122 and W134) are proposed to play an important role in guiding a chitin chain into the catalytic cleft during the crystalline chitin hydrolysis. Mutation of either W122 or W134 to alanine significantly reduced the hydrolyzing activity against highly crystalline beta-chitin microfibrils. Double mutation almost completely abolished the hydrolyzing activity. On the other hand, the hydrolyzing activity against either soluble or amorphous substrate was not reduced. These mutations slightly impaired the binding activity of this enzyme. These results clearly demonstrated that the two exposed aromatic residues play a critical role in hydrolyzing the chitin chain in crystalline chitin.

Bacillus↗
PubMed2001

Nicorandil--induced ATP release in endothelial cells of rat caudal artery is associated with increase in intracellular Ca(2+).

The effect of nicorandil, an ATP-sensitive K(+) channel opener, on the level of intracellular Ca(2+) ([Ca(2+)](i)) and on ATP release in endothelial cells of the rat caudal artery was examined using a fluorescent confocal microscopic imaging system and high-performance liquid chromatography (HPLC) with fluorescent detection, respectively. Nicorandil significantly increased [Ca(2+)](i) and the overflow of ATP and its metabolites. The former reaction was abolished in the absence of extracellular Ca(2+), but it did not change in the presence of thapsigargin or cyclopiazonic acid. The increase in the overflow of ATP and [Ca(2+)](i) induced by nicorandil was markedly suppressed by glibenclamide, an ATP-sensitive K(+) channel blocker. The increase of [Ca(2+)](i) induced by nicorandil was significantly and inversely correlated with the level of intracellular ATP in the endothelial cells, suggesting that activation of ATP-sensitive K(+) channels by nicorandil increases Ca(2+) influx in endothelial cells. The increase of [Ca(2+)](i) might be associated with ATP release.

Adenosine↗
PubMed2001

Synthesis of biotinylated bis(D-glucose) derivatives for glucose transporter photoaffinity labelling.

New diazirine based bis-glucose derivatives for tagging glucose transporters have been synthesised. These included two biotinylated compounds linked either by an aminocaproate or by a cleavable dithiol link. These compounds have been derivatised via a key skeleton compound that can be easily used for introduction of additional tags. Studies on the erythrocyte glucose transporter (GLUT1) and the insulin-stimulated adipose cell transporter (GLUT4) have revealed the biotinylated photoreactive bis-glucose compounds are effective labelling reagents.

Adipocytes↗
PubMed2001

A model of photoprobe docking with beta1,4-galactosyltransferase identifies a possible carboxylate involved in glycosylation steps.

A molecular docking study has been performed on the interaction of beta1,4-galactosyltransferase with an acceptor site photoprobe. This is based on an acceptor site peptide fragment which was recently identified by the use of a photoprobe. The present model strongly suggests that the carboxylate group of Asp318 could be involved in the activation of the acceptor sugar 4-OH for the efficient galactosyltransfer. The result also exemplified that the combination of photoaffinity labeling with crystallography is a powerful method for the detailed structural analysis of ligand protein complex.

Aspartic Acid↗
PubMed2001

Estrogen prevents oxidative stress-induced endothelial cell apoptosis in rats.

BACKGROUND: Estrogen replacement attenuates the increased risk of cardiovascular disease in postmenopausal women. Recent studies using an in vitro culture system have shown that estrogen inhibits endothelial cell (EC) apoptosis. The in vivo relevance of this finding, however, is not defined. To do so, we have developed a rat vascular injury model in which EC apoptosis induced by hydrogen peroxide plays a role. METHODS AND RESULTS: Intracarotid arterial administration of 0.01 mmol/L hydrogen peroxide for 5 minutes evoked EC apoptosis after 6 to 24 hours, determined by nuclear staining with Hoechst 33342, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, and electron microscopy. Apoptosis was associated with EC loss and was followed by EC regeneration at 72 hours and neointima formation at 1 to 2 weeks. Estradiol replacement in ovariectomized female Wistar rats decreased the rate of apoptotic ECs by approximately 50%, assayed by nuclear morphology of en face specimens, resulting in increased remaining ECs and decreased neointima formation. Progesterone did not influence the effects of estradiol on EC apoptosis. CONCLUSIONS: These results provide new insight into the cardioprotective action of estrogen as well as a paradigm of the response-to-injury hypothesis.

Animals↗