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Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 181 records · Page 10Linked to original sources
PubMed2001

Slowing Na+ channel inactivation prolongs QT interval and aggravates adrenaline-induced arrhythmias.

We investigated the effects of prolonged repolarization induced by slowed inactivation of Na+ channel on adrenaline-induced arrhythmias in halothane anesthetized, closed-chest dogs. We used sea anemone toxins (ATX-II and Anthopleurin-A) to prolong ventricular repolarization and examined their effects on adrenaline arrhythmias. Sea anemone toxins prolonged the QTc- and JTc-intervals (P<0.01), but did not affect the PQ interval, QRS duration, heart rate and mean blood pressure. Although sea anemone toxins did not induce any arrhythmias by themselves, under the treatment with these toxins, arrhythmias were induced by non-arrhythmia-inducing doses of adrenaline in four dogs out of seven and the control arrhythmias induced by adrenaline were aggravated. These results indicate that, similar to the inhibition of K+ channels by class III drugs, which we have already reported, slowing Na+ channel inactivation with QTc prolongation also aggravates adrenaline-induced arrhythmias.

Animals↗
PubMed2001

Electrophysiologic effects of an antiarrhythmic agent, bidisomide, on sodium current in isolated rat ventricular myocytes: comparison with mexiletine and disopyramide.

The effects of bidisomide, an antiarrhythmic agent, on sodium current (I(Na)) in isolated rat ventricular myocytes were investigated using a whole cell voltage clamp method. Bidisomide blocked I(Na) with a Ki of 214 microM at a holding potential of -140 mV. The blockade of I(Na) was enhanced at a less negative holding potential of -100 mV with a Ki of 21 microM. Bidisomide shifted the steady state inactivation curve to a negative potential direction by 20 mV without a significant change in the slope factor. Bidisomide slowed the time course of recovery of I(Na) at a holding potential of -140 mV with a slow recovery phase. The time constant of recovery phase for bidisomide, disopyramide and mexiletine were 2703, 1858 and 757 ms, respectively. The development of the block of I(Na) consisted of two phases in the presence of bidisomide. The fast and slow time constants were 11 and 648 ms. Bidisomide produced a use-dependent block of I(Na) when the depolarizing pulse was repeated at 1-3 Hz. Our results indicate that bidisomide binds to rat cardiac sodium channels and that the dissociation kinetics of bidisomide from the inactivated sodium channel is slower than that of disopyramide.

Animals↗
PubMed2001

Mechanism of atropine-resistant contraction induced by Dai-kenchu-to in guinea pig ileum.

To clarify the contractile mechanism of Dai-kenchu-to, the effects of hydroxy beta-sanshool (an ingredient of Zanthoxylum fruit), Zanthoxylum fruit (a constituent herb of Dai-kenchu-to) and Dai-kenchu-to were studied in mucosa-free longitudinal muscle of guinea pig ileum. Hydroxy beta-sanshool at 10(-7)-10(-5) g/ml induced dose-related contractions accompanied by autonomous contraction and produced an initial contraction at a concentration of 10(-4) g/ml or more. The contraction induced by hydroxy beta-sanshool (10(-5) g/ml) was significantly inhibited by tetrodotoxin or the capsaicin-receptor antagonist capsazepine. Although atropine or the substance P antagonist spantide tended to inhibit the contraction, a combination of atropine and spantide almost abolished the contraction by hydroxy beta-sanshool. The P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid did not affect hydroxy beta-sanshool-induced contraction in the presence or absence of spantide. The tonic contractions by Zanthoxylum fruit (2 x 10(-4) g/ml) and Dai-kenchu-to (10(-3) g/ml) were significantly inhibited or tended to be inhibited by atropine, spantide, tetrodotoxin or capsazepine and were remarkably suppressed by the combination of atropine and spantide. These results suggested that acetylcholine release from intrinsic cholinergic nerves and tachykinins from sensory neurons are involved in the contractions induced by hydroxy beta-sanshool and that tachykinins may be involved in the atropine-resistant contraction by Dai-kenchu-to.

Animals↗
PubMed2001

In vivo antiarrhythmic profile of AP-792 assessed in different canine arrhythmia models.

The antiarrhythmic effects of a novel antiarrhythmic drug AP-792, 4-(5H-dibenzo[a,d]cyclohepten-5-ylidene)-1-[4-cyclohexylbutyl]piperidine hydrochloride, were analyzed using the epinephrine-, digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmia models. Intravenous administration of AP-792 (0.3 or 1.0 mg/kg) effectively suppressed each of the ventricular arrhythmias, an action that resembles that of a typical cardioselective Ca2+ channel blocker, AH-1058. The antiarrhythmic action of AP-792 was slow in onset and longer-lasting than those in our previous studies using more than 50 antiarrhythmic drugs, including Na+ and Ca2+ channel blockers. These results suggest that AP-792 can become a unique long-acting antiarrhythmic drug.

Animals↗
PubMed2001

Acute electropharmacological effects of intravenously administered amiodarone assessed in the in vivo canine model.

Acute hemodynamic and electrophysiological effects of amiodarone were assessed simultaneously, using the halothane-anesthetized, closed-chest in vivo canine model in comparison with those of solvent ethanol alone. Intravenous administration of the solvent (n = 8) induced no significant change in any of the cardiovascular parameters. On the other hand, intravenous amiodarone in the canine antiarrhythmic dose of 3.0 mg/kg (n = 6) exerted negative chronotropic, inotropic and dromotropic effects in addition to the transient hypotensive action followed by an increase of the total peripheral vascular resistance. Amiodarone also prolonged both the ventricular repolarization phase and the effective refractory period, where the increment was greater in the latter than in the former, indicating the shortening of the electrical vulnerable period of the ventricle. More importantly, appearance of the electrophysiological effect on repolarization took more time and higher dose compared with the effect on refractoriness, which could be detected at a one tenth the dose. These results support the previous knowledge that intravenously administered amiodarone possesses class I, III and IV actions and suggest that shortening of the electrical vulnerable period may be one of the unique antiarrhythmic properties of intravenous amiodarone against re-entry type arrhythmias.

Action Potentials↗
PubMed2001

H2 production from algal biomass by a mixed culture of Rhodobium marinum A-501 and Lactobacillus amylovorus.

To produce hydrogen from starch accumulated in an algal biomass, we used a mixed culture of the lactic acid bacterium, Lactobacillus amylovorus, and the photosynthetic bacterium, Rhodobium marinum A-501. In this system L. amylovorus, which possesses amylase activity, utilized algal starch for lactic acid production, and R. marinum A-501 produced hydrogen in the presence of light using lactic acid as an electron donor. Algal starch accumulated in the marine green alga Dunaliella tertiolecta, and the freshwater green alga Chlamydomonas reinhardtii, was more suitable for lactic acid fermentation by L. amylovorus than an authentic starch sample. Consequently, the yields of hydrogen obtained from starch contained in D. tertiolecta and C. reinhardtii were 61% and 52%, respectively, in the mixed culture of L. amylovorus and R. marinum A-501. These values were markedly superior to those obtained using a mixed culture of Vibrio fluvialis T-522 and R. marinum A-501 described previously. The yield and production rate of hydrogen by R. marinum A-501 from the lactic acid fermentates were higher than from authentic lactic acid, suggesting that the fermentates contain a factor(s) which promotes H2 production by this bacterium.

Journal Article↗
PubMed2001

Reaction kinetics and modeling of the enzyme-catalyzed production of lactosucrose using beta-fructofuranosidase from Arthrobacter sp. K-1.

Lactosucrose synthesis from sucrose and lactose was carried out by using beta-fructofuranosidase from Arthrobacter sp. K-1. The transfructosylation mechanism was found to be of an ordered bi-bi type in which sucrose was bound first to the enzyme and lactosucrose was released last. Hydrolysis side-reaction experiments indicated that the reactions were uncompetitively inhibited by glucose and lactose, while no inhibition by fructose was apparent. The overall reaction rates were formulated. The reaction rate constants, equilibrium constant, and dissociation and Michaelis constants were determined at 35 degrees C and 50 degrees C by fitting the experimental concentration changes with the calculated values by a nonlinear least-square method. The average relative derivation for the concentrations was 9.67%. The kinetic parameters were also calculated for 43 degrees C and 60 degrees C by assuming the Arrhenius law, and the course of reaction was predicted. The obtained reaction rate equations well represented the concentration changes during the experiment at all temperatures.

Algorithms↗
PubMed2001

Roles of phospholipase Cbeta4 in synapse elimination and plasticity in developing and mature cerebellum.

The beta isoforms of phospholipase C (PLCbetas) are thought to mediate signals from metabotropic glutamate receptor subtype 1 (mGluR1) that is crucial for the modulation of synaptic transmission and plasticity. Among four PLCbeta isoforms, PLCbeta4 is one of the two major isoforms expressed in cerebellar Purkinje cells. The authors have studied the roles of PLCbeta4 by analyzing PLCbeta4 knockout mice, which are viable, but exhibit locomotor ataxia. Their cerebellar histology, parallel fiber synapse formation, and basic electrophysiology appear normal. However, developmental elimination of multiple climbing fiber innervation is clearly impaired in the rostral portion of the cerebellar vermis, where PLCbeta4 mRNA is predominantly expressed in the wild-type mice. In the adult, long-term depression is deficient at parallel fiber to Purkinje cell synapses in the rostral cerebellum of the PLCbeta4 knockout mice. The impairment of climbing fiber synapse elimination and the loss of long-term depression are similar to those seen in mice defective in mGluR1, Galphaq, or protein kinase C. Thus, the authors' results strongly suggest that PLCbeta4 is part of a signaling pathway, including the mGluR1, Galphaq and protein kinase C, which is crucial for both climbing fiber synapse elimination in the developing cerebellum and long-term depression induction in the mature cerebellum.

Animals↗
PubMed2001

Physiological roles of corticotropin-releasing hormone receptor type 2.

Recent investigations of the physiological roles of CRH-R2 are reviewed and summarized in Fig. 5. VMH CRH-R2 is more important than CRH-R1 in mediating anorexic effect of CRH or urocortin (UCN) and stress-induced reduction of food intake. CRH-R2 mediates a central anxiolytic response, opposing the anxiogenic effect of CRH mediated by CRH-R1. Hippocampal CRH-R1 mediates stress-induced enhancement of learning, while CRH-R2 in the lateral intermediate septum may act to impair learning. CRH-R1 mediates CRH-induced blood pressure elevation, while peripheral CRH-R2 mediates the hypotensive effect of systemically administered UCN and CRH. It is likely that CRH-R2 does not play an important role in hypothalamic-pituitary adrenal axis regulation, though it has been reported that CRH-R2-deficient mice showed hyperresponse of ACTH and corticosterone. Peripheral CRH-R2 mediates UCN-induced mast cell degranulation, vascular permeability, and abdominal surgery-induced gastric stasis. These recent investigations have revealed that the existence of two CRH receptors, which mediate some opposite effects, provides the CRH and UCN systems a high flexibility and dynamic role in the adaptation of the body to environmental challenge.

Adrenal Glands↗
PubMed2001

A polymorphism in the promoter region of the glucocorticoid receptor gene is associated with its transcriptional activity.

Since glucocorticoid exerts its biological effects by binding to its receptor, the expression efficiency of the glucocorticoid receptor (GR) gene could influence glucocorticoid sensitivity. We found a polymorphism of cytosine/adenine (-22 C/A) in the upstream region of the GR gene. There was no difference in the allelic frequency between normal and type 2 diabetic subjects. The promoter activity determined by luciferase assay was significantly lower in the -22 A allele than in the -22 C allele in both HepG2 (A allele, 4.19 +/- 0.15; C allele, 6.07 +/- 0.27, p < 0.001) and human embryonic kidney 293 cell lines (A allele, 0.93 +/- 0.16; C allele, 1.51 +/- 0.32, p < 0.001). This polymorphism is associated with transcription of the CR gene, which could be related to glucocorticoid sensitivity through an alteration in tissue GR number.

Adult↗
PubMed2001

Clinical significance of the insulin resistance index as assessed by homeostasis model assessment.

To examine the clinical significance of the insulin resistance index as determined by homeostasis model assessment (HOMA-IR), we investigated the relationship between HOMA-IR and the insulin resistance estimated by the euglycemic-hyperinsulinemic clamp method in various subgroups and compared the significance of HOMA-IR with that of fasting plasma insulin levels (FIRI). HOMA-IR was significantly correlated to the inverse of the glucose infusion rate (1/GIR) in both diabetic and non-diabetic subjects (r=0.747, P<0.0001 and r=0.419, P<0.002, respectively). In the diabetic patients, treatment with sulfonylureas did not weaken this correlation (r=0.833, P<0.0001). HOMA-IR was found to be closely related to FIRI (r=0.932, P<0.0001), but HOMA-IR was more closely associated with 1/GIR than FIRI was. HOMA-IR as well as 1/GIR was correlated with the visceral fat area (VFA) more closely than with the subcutaneous fat area (SFA), while FIRI was correlated almost equally with both of them. In conclusion, HOMA-IR is a convenient and beneficial method for evaluating insulin resistance, especially in subjects with visceral fat accumulation, and reflects insulin resistance obtained by euglycemic clamp more accurately than FIRI alone.

Adipose Tissue↗
PubMed2001

Determination of residual solvents in pharmaceuticals by thermal desorption-GC/MS.

A novel method for the determination of residual solvents in pharmaceuticals by thermal desorption (TD)-GC/MS has been established. A programmed temperature pyrolyzer (double shot pyrolyzer) is applied for the TD. This method does not require any sample pretreatment and allows very small amounts of the sample. Directly desorbed solvents from intact pharmaceuticals (ca. 1 mg) in the desorption cup (5 mm x 3.8 mm i.d.) were cryofocused at the head of a capillary column prior to a GC/MS analysis. The desorption temperature was set at a point about 20 degrees C higher than the melting point of each sample individually, and held for 3 min. The analytical results using 7 different pharmaceuticals were in agreement with those obtained by direct injection (DI) of the solution, followed by USP XXIII. This proposed TD-GC/MS method was demonstrated to be very useful for the identification and quantification of residual solvents. Furthermore, this method was simple, allowed rapid analysis and gave good repeatability.

Adsorption↗
PubMed2001

Morphological character of crystalline components present in saiga horn.

The purpose of this study was to investigate the ultrastructure of saiga-antelope (Saiga tatarica) horn for proposing the mechanism of the initial mineralization. Horn is derived from horny tooth of Cyclostomata. The minerals in saiga horn were identified crystallographically using electron microscopy and X-ray diffraction techniques. Soft X-ray photographs revealed the degree of the mineralization pattern. However, the number of rings did not indicate the age of saiga. Mineral deposites were observed among well banded keratin fibers and composed of powder like crystals. This deposited crystals were found by the X-ray diffraction method to be octacalcium phospate (OCP) by comparing these periodic lattice fringes to JCPDS card data. The chemical formula of OCP is Ca8H2(PO4)6.5H2O. Evidences for the presence of OCP in mature hard tissues have never been obtained. This phenomenon described here may be characteristic of saiga horn because we have found no reports on this type of OCP mineralization in any other animal species. It is possible that OCP is the precursor in the initial mineralization step, indicating in a nucleation of mineral on the keratin fibers.

Animals↗
PubMed2001

[Laparoscopy-assisted total nephroureterectomy for renal pelvic and/or lower ureteral cancer].

PURPOSE: The usefulness of laparoscopy-assisted total nephroureterectomy for patients with renal pelvic and lower ureteral cancer is evaluated. MATERIAL: Seven patients with renal pelvic cancer and four with lower ureteral cancer performed laparoscopy-assisted total nephroureterectomy from May 1997 to December 2000 (Ten males and one female, mean age 68.5 year-old). METHOD: Of the 11 patients, the initial one received preoperative embolization of the renal artery. Under general anesthesia laparoscopy-assisted total nephroureterectomy underwent via transperitoneal approach in three patients and retroperitoneal approach in eight. After the kidney was completely dissected under laparoscopic procedure, it was delivered en bloc with ureter from the skin incision in the lower abdomen. RESULT: Two patients needed conversion to open surgery. The mean operating time of nine patients except for conversion cases was 272 minutes and the mean blood loss was 313 ml. There was no major complication associated with laparoscopic procedure. There was no significant difference in both complication and recurrence rate between laparoscopy-assisted total nephroureterectomy and open surgery. CONCLUSION: Laparoscopy-assisted total nephroureterectomy is an useful procedure for the treatment of patients with renal pelvic and lower ureteral cancer because it enables us to remove out the kidney and ureter from one small lower abdominal incision.

Aged↗
PubMed2001

Two sporadic cases of Liddle's syndrome caused by De novo ENaC mutations.

Liddle's syndrome is a rare form of hereditary hypertension caused by mutations of the epithelial sodium (Na(+)) channel (ENaC). Analysis of the diseased pedigrees indicates an autosomal dominant inheritance, and the identified mutations are heterozygotes of gain-of-function mutations. However, sporadic cases of Liddle's syndrome have been reported in the literature, including one recently reported case caused by a de novo mutation of ENaC. We identified two patients with Liddle's syndrome who did not have family histories of hypertension. Sequence analysis showed a mutation in each case (P616L in betaENaC and W576X in gammaENaC), both confirmed to be de novo mutations. These data indicate that Liddle's syndrome should be considered even in patients without a family history of hypertension.

Adult↗
PubMed2001

[A case of breast cancer 5 cm in diameter treated with a breast preserving approach after preoperative intra-arterial chemotherapy].

The patient was a 59-year-old female with a mass in the right breast (area C). At the initial examination, the mass was 5.0 x 4.5 cm on palpation, aspiration cytology was Class V, and a diagnosis of T2aN1aM0, Stage II breast cancer was made. Since the patient strongly desired a breast preserving treatment, a reduction in the size of the mass was attempted by local intra-arterial chemotherapy. Docetaxel (TXT) was administered at 60 mg into the internal thoracic artery and lateral thoracic artery at a rate of once a month for a total of 5 times. After the fifth treatment, the mass was reduced in size to 2.8 x 2.5 cm on palpation, and breast-preserving resection was then carried out. On histopathological examination, cancer was observed in an area of 3.0 x 2.2 cm. Careful follow-up is still needed, but preoperative intra-arterial chemotherapy is considered to be significant as a step before breast preserving surgery for breast cancer with a diameter of 3-5 cm.

Antineoplastic Agents, Phytogenic↗