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K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 397 records · Page 22Linked to original sources
PubMed1999

E-CELL: software environment for whole-cell simulation.

MOTIVATION: Genome sequencing projects and further systematic functional analyses of complete gene sets are producing an unprecedented mass of molecular information for a wide range of model organisms. This provides us with a detailed account of the cell with which we may begin to build models for simulating intracellular molecular processes to predict the dynamic behavior of living cells. Previous work in biochemical and genetic simulation has isolated well-characterized pathways for detailed analysis, but methods for building integrative models of the cell that incorporate gene regulation, metabolism and signaling have not been established. We, therefore, were motivated to develop a software environment for building such integrative models based on gene sets, and running simulations to conduct experiments in silico. RESULTS: E-CELL, a modeling and simulation environment for biochemical and genetic processes, has been developed. The E-CELL system allows a user to define functions of proteins, protein-protein interactions, protein-DNA interactions, regulation of gene expression and other features of cellular metabolism, as a set of reaction rules. E-CELL simulates cell behavior by numerically integrating the differential equations described implicitly in these reaction rules. The user can observe, through a computer display, dynamic changes in concentrations of proteins, protein complexes and other chemical compounds in the cell. Using this software, we constructed a model of a hypothetical cell with only 127 genes sufficient for transcription, translation, energy production and phospholipid synthesis. Most of the genes are taken from Mycoplasma genitalium, the organism having the smallest known chromosome, whose complete 580 kb genome sequence was determined at TIGR in 1995. We discuss future applications of the E-CELL system with special respect to genome engineering. AVAILABILITY: The E-CELL software is available upon request. SUPPLEMENTARY INFORMATION: The complete list of rules of the developed cell model with kinetic parameters can be obtained via our web site at: http://e-cell.org/.

Adenosine Triphosphate↗
PubMed1999

The factor V Leiden mutation in Japanese couples with recurrent spontaneous abortion.

Thrombosis of placental vessels can be a major cause of recurrent spontaneous abortion (RSA). The factor V Leiden (FVL) mutation, a single point mutation in the factor V gene, is the most common genetic predisposition to thrombosis in European countries and the United States. However, even among Caucasian populations, the association between the FVL mutation and RSA is still controversial. The objectives of the present study were to investigate the prevalence of the FVL mutation in Japanese women who have experienced RSA and to clarify the contribution of the FVL mutation to recurrent miscarriages. A total of 52 Japanese women with a history of three or more consecutive idiopathic first trimester miscarriages and 41 of their male partners were studied. The control group consisted of 55 parous women without obstetric complications. Peripheral blood cell DNA was examined for the presence of the FVL alleles by polymerase chain reaction with Mnl I restriction fragment length polymorphisms. None of the 52 women with RSA and the 41 partners carried the mutation. We also found no subject carrying the FVL alleles in the control group. These results suggest that the FVL alleles are not concentrated in women with RSA at least to clinically significant levels and that there is no apparent association between the FVL mutation and RSA in our Japanese population.

Abortion, Habitual↗
PubMed1999

Pityriasis rubra pilaris with acantholysis and lichenoid histology.

Acantholytic foci have been reported several times in pityriasis rubra pilaris (PRP). Lichenoid tissue reactions were also mentioned in the literature regarding PRP. We report a 58-year-old patient who, after having colon cancer, had PRP with biopsies showing acantholytic lesions and a heavy lichenoid lymphocytic infiltration. Investigation by serial sectioning of the acantholytic lesion suggested an involvement of the intraepidermal eccrine duct and further investigation with carcinoembryonic antigen (CEA) staining demonstrated a CEA-positive eccrine duct in the acantholytic foci. We suggest that acantholysis in PRP is induced by proteolytic enzymes, urea, and other substances in eccrine sweat in keratin-plugged acrosyringia. This patient had a combination of three relatively rare features of PRP-acantholysis, lichenoid reaction, and a cancer background.

Acantholysis↗
PubMed1999

Antiischemic effects of CP-060S, an inhibitor of pathologically modified sodium channels, assessed in the canine experimental model of angina pectoris.

CP-060S is a novel compound that can inhibit the slow inward calcium current as well as the veratridine-induced, noninactivating sodium current. Antiischemic and cardiovascular effects of CP-060S were assessed by using halothane-anesthetized beagle dogs and compared with the effects of semotiadil, a benzothiazine calcium antagonist. The first or second diagonal branch was narrowed. ECG, unipolar electrograms from both ischemic and nonischemic regions, and systemic and left ventricular pressure were monitored. The left ventricle was electrically driven at 190-240 beats/min for 3 min to induce reversible myocardial ischemia. The severity of ischemia was judged by the magnitude of ST-segment depression. CP-060S (0.1 mg/kg, i.v.) significantly attenuated the pacing-induced ST-segment depression in the ischemic region >2 h, whereas during the sinus rhythm, it showed reversible negative chronotropic, inotropic, and dromotropic effects and induced transient depressor response, which would not necessarily be considered favorable (n = 8). A smaller dose of CP-060S (0.03 mg/kg, i.v.) showed a similar antiischemic and cardiovascular profile, but each effect was less potent than that of the higher dose (n = 7). Semotiadil (0.1 and 0.3 mg/kg, i.v.) also showed cardiovascular suppression similar to that of CP-060S; however, the antiischemic effect was not detected during the whole experimental period (n = 6). Thus the inhibition of the noninactivating sodium current may be the primary reason for the antiischemic effect of CP-060S and could become a new cytoprotective principle in the treatment of patients with ischemic heart disease.

Angina Pectoris↗
PubMed1999

Cariporide, a highly selective Na+/H+ exchange inhibitor, suppresses the reperfusion-induced lethal arrhythmias and "overshoot" phenomenon of creatine phosphate in situ rat heart.

The effects of a highly selective Na+/H+ exchange inhibitor cariporide on the reperfused in situ heart were assessed. Male Sprague-Dawley (SD) rats weighing 200-300 g were anesthetized with pentobarbital sodium (60 mg/kg, i.p.) and divided into four groups; sham-operated (n = 6), vehicle (n = 15), 0.1 mg/kg (n = 15), and 1.0 mg/kg (n = 15) groups. The left coronary artery was ligated for 5 min and then released with ECG and blood pressure monitoring. Cariporide was intravenously given as a bolus 2 min before the reperfusion. The heart was rapidly excised and frozen 3 min after the onset of ventricular fibrillation, otherwise 10 min after the reperfusion. The adenosine triphosphate (ATP), creatine phosphate (CP), and glycogen contents were measured in the reperfused ischemic myocardium by using an enzymatic fluorometric assay technique. The incidence of the lethal ventricular fibrillation was 53% in the vehicle, 27% in the low-dose and 7% in the high-dose group. The concentrations (mean+/-SEM) of ATP, CP (nmol/mg protein), and glycogen (nmol as glucose/mg protein) were 74+/-4, 255+/-19, and 164+/-21 in the sham, 23+/-4, 763+/-70, and 61+/-7 in the vehicle, 27+/-4, 180+/-16, and 104+/-14 in the low-dose, and 32+/-4, 178+/-24, and 108+/-8 in the high-dose groups, respectively, indicating that cariporide significantly blunted CP overshoot as well as glycogenolysis during reperfusion. Thus cariporide can be expected to depress arrhythmogenesis and protect the metabolic status of the heart.

Analysis of Variance↗
PubMed1999

Can the MAP technique be applied to detect delayed afterdepolarization? Electrophysiologic and pharmacologic evidence.

The purpose of this study was to assess whether the monophasic action potentials (MAPs) technique can be applied to detect delayed afterdepolarizations (DADs). The canine isolated, blood-perfused ventricular septum preparation was used to obtain stable MAP signals (n = 8). The preparation was electrically driven by trains of 15 stimuli at each cycle length of 600-300 ms under the monitoring of MAP and papillary muscle contraction. In a basal condition, neither DADs nor premature ventricular contractions (PVCs) were induced by the train stimulation, whereas the coupling interval between electrograms of the last driven contraction and the first spontaneously developed contraction was prolonged by shortening the pacing cycle length. Then 40-45 microg of ouabain was intravenously administered into the blood-donor dog. Both DADs and PVCs were induced in all preparations by the pacing protocol 10-15 min after the ouabain injection; however, PVCs did not occur spontaneously. Small aftercontractions also were detected during the electrical pacing in four preparations. By shortening the pacing cycle length, the DADs were enhanced, the coupling interval was shortened, and the number of PVCs increased. After the administration of ryanodine, verapamil, tetrodotoxin, or lidocaine (n = 4--6), the small aftercontractions disappeared, the DADs attenuated, the coupling interval was prolonged, and the number of PVCs decreased. These observations suggest that PVCs observed in this model may be derived from the DAD-related triggered activity, and moreover, show the feasibility of recording DADs and triggered activity by the MAP technique.

Action Potentials↗
PubMed1999

Electrophysiologic, cardiohemodynamic and beta-blocking actions of a new ultra-short-acting beta-blocker, ONO-1101, assessed by the in vivo canine model in comparison with esmolol.

The purpose of this study was to assess the cardiovascular effects of an ultra-short-acting beta-blocker, ONO-1101, by using halothane-anesthetized beagle dogs in comparison with esmolol. ONO-1101 (n = 6) or esmolol (n = 6) was administered at four infusion rates of 0.3, 3, 30, and 300 microg/ kg/min. Each infusion was performed over a 30-min period, and the parameters were measured at 20-30 min after the start of each infusion. ONO-1101 significantly decreased the heart rate, rate-pressure product, left ventricular contraction, cardiac output, and relative refractory period of the right ventricle, suppressed the AV nodal conduction, and increased the effective refractory period of the right ventricle, whereas no significant change was observed in the preload and afterload of the left ventricle, intrinsic sinus nodal automaticity, His-Purkinje-ventricular conduction, and the monophasic action-potential duration of the right ventricle. The cardiovascular effects of esmolol were comparable to those of ONO-1101, except that the preload of the left ventricle was significantly increased, and the ventricular repolarization phase was shortened by 300 microg/kg/min of esmolol infusion. Meanwhile, ONO-1101 as well as esmolol significantly reduced the isoproterenol-induced increase in heart rate and ventricular contraction, but the inhibitory action of ONO-1101 was 6-8 times greater than that of esmolol. These results suggest that the suppressive effects of ONO-1101 on cardiovascular performance are significantly less potent than those of esmolol at equipotent beta-blocking doses.

Adrenergic beta-Agonists↗
PubMed1999

Cardiovascular effects of optical isomers of cibenzoline, assessed in the canine isolated, blood-perfused papillary muscle and sinoatrial node preparations.

A clinically available racemic mixture of the optical isomers of cibenzoline possesses a potent sodium channel-blocking action in addition to the moderate calcium channel-blocking action. It has been reported that the S(-)-isomer inhibits sodium channels more potently than calcium channels, whereas the R(+)-isomer suppresses the sodium channels as well as calcium channels, and that the calcium channel-blocking potency of these isomers is similar. This study was designed to assess the effects of each optical isomer of cibenzoline on ventricular contraction, coronary blood flow, and sinus node automaticity by using the canine isolated, blood-perfused papillary muscle and sinoatrial node preparations. Each isomer showed negative inotropic and chronotropic effects as well as coronary vasodilator action in a dose-dependent manner. The negative inotropic effect of S(-)-cibenzoline was 1.8 times more potent than that of R(+)-cibenzoline, whereas there was no significant difference between the isomers in the negative chronotropic and coronary vasodilator effects. These results suggest that the difference of the inotropic effects between the optical isomers of cibenzoline is mainly derived from the extent of the sodium channel-blocking action, whereas the vasodilator and negative chronotropic effects may chiefly depend on the calcium channel inhibition.

Animals↗
PubMed1999

Direct cardiac effects of a novel vesamicol receptor ligand, m-iodobenzyl-trozamicol, assessed in the canine isolated, blood-perfused heart preparations.

MIBT, m-(iodobenzyl)trozamicol, is a recently discovered vesamicol analogue that can be used as a functional marker of cholinergic activity in the heart as well as the brain. The purpose of this study was to assess the effects of MIBT on sinus node automaticity, ventricular contraction, and coronary blood flow in addition to the action-potential duration of the ventricle by using canine isolated, blood-perfused sinoatrial node and papillary muscle preparations. Intracoronary administration of MIBT (1-300 microg) exerted negative chronotropic, inotropic, and coronary vasodilator effects in a dose-related manner. Pretreatment of the preparations with the muscarinic receptor antagonist atropine did not change these effects of MIBT. Moreover, MIBT had little effect on the repolarization phase of the ventricular action potential. Because the doses of MIBT needed for imaging cardiac cholinergic function were much lower than those affecting the cardiovascular system, MIBT may be used safely in future clinical applications.

Action Potentials↗
PubMed1999

The role of serum imbibition for skin grafts.

Numerous studies of grafted skin suggest that full-thickness skin grafts are nourished by exudate from the recipient bed called a serum imbibition. However, whether serum imbibition by itself is sufficient for nourishment of skin grafts has not been shown definitely and directly. To clarify the role of serum imbibition, we performed a comparative study between 20 skin grafts and 20 musculocutaneous flaps. The nourishment of the cell in the skin graft is by serum imbibition. That in musculocutaneous flaps is mainly derived from blood supply. We evaluated the nourishment by means of the unique characteristics of the cell cycle. Once cells are put into a synthetic phase, they cannot reverse or stop the progress of the cell cycle. To take advantage of this characteristic of the cell cycle, prewounding methods (40 flaps were lifted once and put back to the original sites prior to the evaluation) were intended for the cells in pre-elevated skin to turn into a proliferating phase. Cells were examined by antibody against proliferating cell nuclear antigen immunohistologically, to determine whether they had turned into the proliferating phase or not. After 3 days, all flaps were reelevated; half (20 flaps) had their muscle layer and the neurovascular bundle removed to make a full-thickness skin graft. The rest (20 flaps) were only lifted. They were sutured back to the original sites. Ten skin grafts and musculocutaneous flaps each were harvested at 3 hours (1st day) and at 11 days (11th day) after the second operation. Bromodeoxyuridine, which is a thymidine analog and is taken into the cells in the synthetic phase, was introduced intraperitoneally 2 hours before the harvest. All flaps and grafts were evaluated histologically and immunohistologically. Proliferating cell nuclear antigen analysis showed that the prewounding method induced the cells of skin grafts and musculocutaneous flaps to proliferate before the implantation. Regarding the bromodeoxyuridine uptake, no significant differences could be seen between skin grafts and musculocutaneous flaps irrespective of their different nourishment. No structural changes, such as degenerative or necrotic, could be seen at the hair follicle and other glands even at the 11th day. Almost all of the layers of skin grafts survived as long as they were checked by light microscopy (hematoxylin and eosin stain). No differences could be seen between musculocutaneous flaps and skin grafts or between the 1st and 11th days in this study. We concluded that serum imbibition is sufficient for nourishment of skin grafts, just as blood supply is sufficient for nourishment of musculocutaneous flaps.

Animals↗
PubMed1999

Antral gastric permeability to antigens in mice is altered by infection with Helicobacter felis.

OBJECTIVE: Gastric inflammation is observed not only during Helicobacter pylori infection but also after eradication of the bacterium. The hypothesis that an altered gastric permeability could be involved was tested using a model of mice infected with Helicobacter felis. DESIGN: The antral and corpus gastric permeability during infection and after eradication of bacteria was studied. METHODS: Gastric fragments from the antrum and corpus of healthy mice, mice infected with H. felis, or mice after bacterial eradication, were mounted in Ussing chambers, and fluxes of sodium (JNa), mannitol (JMan) and horseradish peroxidase (HRP) under intact (JHRPi) and degraded (JD) form were measured. RESULTS: In healthy mice, JNa, JMan, JHRPi and JD, respectively, were greater in the antrum (6.5 +/- 0.5 microEq/h.cm2; 0.137 +/- 0.016 micromol/h.cm2; 30.4 +/- 7.4 ng/h.cm2 and 852 +/- 173 ng/h.cm2) than in the corpus (5.0 +/- 0.3 microEq/h.cm2; 0.085 micro 0.013 micromol/h.cm2; 9.5 +/- 2.8 ng/h.cm2 and 434 +/- 139 ng/h.cm2). In H. felis-infected mice, HRP fluxes in the antrum were increased (JHRPi = 182 +/- 86, JD = 948 +/- 94 ng/h.cm2) as compared to controls (JHRPi = 10.3 +/- 2.6, JD = 458 +/- 98 ng/h.cm2). Bacterial eradication led to the reduction of intact (JHRPi = 53 +/- 26 ng/h.cm) but not of degraded (JD = 844 +/- 213 ng/h.cm) HRP fluxes. After eradication, degraded HRP fluxes returned to normal in mice without inflammation (JD = 558 +/- 36 ng/h.cm2) but not in those with persistent inflammation (JD = 987 +/- 310 ng/h.cm2). CONCLUSIONS: The results suggest that during H. felis infection, bacterial colonization and inflammation lead to an increased gastric permeability along the direct and degradative pathways, respectively. Such an increased antigenic load could contribute to the perpetuation of gastric inflammation after bacterial eradication, and possibly to food protein sensitization.

Animals↗
PubMed1999

Generalized atrophic benign epidermolysis bullosa: a case of severe hemidesmosomal deficiency.

A case of generalized atrophic benign epidermolysis bullosa was followed from birth to 14 years of age. Electron microscopy of the blistered skin showed either the absence or greatly reduced hemidesmosomes of a very poorly developed type. In perilesional skin, the frequency of hemidesmosomes was 1/3 to 1/2 of the normal controls. These hemidesmosomes were small and lacked normal ultrastructures. Anchoring filaments did not cluster underneath them, and the anchoring fibrils were also diminished. In view of the published data correlating the genotype to the phenotype, this patient seems to have a homozygous nonsense mutation of the COL17A1 gene encoding collagen XVII. An accumulation of data may eventually enable electron microscopists to estimate the types of gene mutation.

Desmosomes↗
PubMed1999

Spiny keratoderma--a demonstration of hair keratin and hair type keratinization.

Six cases of spiny keratoderma were analyzed with hair specific antikeratin antibodies (AE13, AE14) and by electron microscopy. The keratotic column exhibited a different keratin birefringence and the underlying viable epidermis was less eosinophilic than the surrounding epidermis. AE13, which is specific for hair cortex, was positive in the lower column and variably positive in the viable epidermis, often beyond the columnar lesion. AE14 was negative in the lesion. Electron microscopy demonstrated features of keratinization of normal hair cortex, i.e. by the accretion of keratin filaments without production of keratohyalin or trichohyalin granules. Cementsomes (lamellar granules) and marginal bands were not produced as they are not formed in normal cortical keratinization. It was suggested that spiny keratoderma represents an ectopic hair formation of palms and soles.

Aged↗
PubMed1999

Conservation and diversification of MHC class I and its related molecules in vertebrates.

The elucidation of the complete peptide-binding domains of the highly polymorphic shark MHC class I genes offered us an opportunity to examine the characteristics of their predicted protein products in the light of the latest advance in the structural studies of the MHC class I molecules. The results suggest that the fundamental characteristics in the T-cell recognition of the MHC class I molecule/peptide complex are expected to have been established at the early stage of the vertebrate evolution. The elucidation of the typical classical class I molecules from fishes and also of some MHC class I-related molecules may help us-to explore the common denominator of the ancient class I molecules.

Amino Acid Sequence↗
PubMed1999

Lumped constant for deoxyglucose is decreased when myocardial glucose uptake is enhanced.

Quantification of myocardial glucose uptake by positron emission tomography with [18F]fluorodeoxyglucose (FDG) requires the "lumped constant" (LC), which corrects the difference of affinity between glucose and FDG to glucose transporters and phosphorylating system. Since LC was introduced, it has been considered to be constant. However, this has recently been questioned. To elucidate the constancy of LC by other than radioisotope techniques, the accumulation rate of sugar phosphates (d[SP]/dt) was measured in isolated, perfused rat hearts by 31P NMR spectroscopy with 2-deoxyglucose (DG). We postulate alpha as the affinity of DG to transporters and the phosphorylating system relative to that of glucose. Theoretically, alpha is equivalent to LC. We determined alpha by measuring d[SP]/dt at DG concentration ([DG]) = 10, 7, 5, and 3 mmol/l, keeping the total of glucose concentration ([glucose]) and [DG] to 10 mmol/l. When the glucose uptake was enhanced by insulin (10 mU/ml) or stunning, calculated alpha was reduced (insulin stimulated, 0.15; stunning, 0.19) compared with the control (0.59). These results indicate that LC can be evaluated by methods without radiolabeled tracers and is smaller when glucose uptake is augmented.

Animals↗
PubMed1999

Modulation of AV nodal and Hisian conduction by changes in extracellular space.

Previous studies have demonstrated that the extracellular space (ECS) component of the atrioventricular (AV) node and His bundle region is larger than the ECS in adjacent contractile myocardium. The potential physiological significance of this observation was examined in a canine blood-perfused AV nodal preparation. Mannitol, an ECS osmotic expander, was infused directly into either the AV node or His bundle region. This resulted in a significant dose-dependent increase in the AV nodal or His-ventricular conduction time and in the AV nodal effective refractory period. Mannitol infusion eventually resulted in Wenckebach block (n = 6), which reversed with mannitol washout. The ratio of AV nodal to left ventricular ECS in tissue frozen immediately on the development of heart block (n = 8) was significantly higher in the region of block (4.53 +/- 0.61) compared with that in control preparations (2.23 +/- 0.35, n = 6, P < 0.01) and donor dog hearts (2.45 +/- 0.18, n = 11, P < 0.01) not exposed to mannitol. With lower mannitol rates (10% of total blood flow), AV nodal conduction times increased by 5-10% and the AV node became supersensitive to adenosine, acetylcholine, and carbachol, but not to norepinephrine. We conclude that mannitol-induced changes in AV node and His bundle ECS markedly alter conduction system electrophysiology and the sensitivity of conductive tissues to purinergic and cholinergic agonists.

Acetylcholine↗