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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 325 records · Page 18Linked to original sources
PubMed1996

Long-term antiepileptic effects of chronic intake of CNK-602A, a thyrotropin-releasing hormone analogue, on spontaneously epileptic rats.

Spontaneously epileptic rats (SER), which represent a double mutation (zi/zi, tm/tm), spontaneously exhibit both tonic and absence-like seizures. We examine the long-term effects of a thyrotropin-releasing hormone (TRH) analogue, CNK-602A, acute administration of which was effective inhibiting both types of seizures in SER, to determine if this agent could be used to treat epilepsy for long periods. Food pellets containing 0.001% CNK-602A were given ad libitum to SER from age 7 weeks. CNK-602A significantly inhibited tonic convulsions and prolonged survival. There were no alterations in body weight or plasma levels of triiodotHyronine (T3) and thyroxine (T4). These findings indicate that chronic intake of CNK-602A in a dose that does not affect plasma levels of T3 and T4 inhibits tonic convulsions in SER and suggest that this drug may be an effective treatment for convulsive seizures in patients with epilepsy.

Administration, Oral↗
PubMed1996

Characterization of the Treponema denticola prtP gene encoding a prolyl-phenylalanine-specific protease (dentilisin).

A chymotrypsin-like protease from Treponema denticola ATCC 35405 was purified by chromatographic techniques. The purified enzyme consisted of three polypeptides (38, 43, and 72 kDa). The protease exhibited specificity for peptide bonds containing phenylalanine and proline at the P1 and P2 positions, respectively, and was classified as a serine protease on the basis of inhibition studies. Naturally occurring protease inhibitors such as alpha1-antitrypsin and alpha1-antichymotrypsin had no effect on enzymatic activity. The enzyme degraded fibronectin, alpha1-antitrypsin, and gelatin while weakly degrading the immunoglobulin G heavy chain and type IV collagen. N-terminal amino acid sequences were determined for the 43- and 72-kDa proteins. On the basis of these sequences, the genes coding for the 43- and 72-kDa proteins were isolated and sequenced. The open reading frame which codes for the 72-kDa protein was designated prtP. This gene consists of 2,169 bp and codes for a protein with an Mr of 77,471. The protein appeared to be composed of a signal peptide region followed by a prosequence and the mature protein domain. The deduced amino acid sequence exhibited similarity with that of the Bacillus subtilis serine protease subtilisin. The deduced properties of the sequence suggest that the 72-kDa protein is a chymotrypsin-like protease. However, the nature and function of the 43-kDa protein have not yet been determined.

Amino Acid Sequence↗
PubMed1996

An adjustable-current swimming pool for the evaluation of endurance capacity of mice.

A new forced-swimming apparatus for determining maximum swimming time in mice was devised for use in the evaluation of the endurance capacity of Std and ddY and CDF1 mice after various diet and drug treatments. With the apparatus, a water current is generated by circulating water with a pump in a swimming pool. A spout and suction slit were contrived to generate a constant current while the strength of the current is regulated by a valve. The decrease in the leg-kicking intervals of mice accompanying the increase in the current speed confirmed that the workload is adjustable by regulation of the current speed. Compared with the number of forelimb strokes, that of the hindlimb kicks was greater. The swimming time until fatigue was observed to decrease with increasing current speed in the two strains of mice. As biochemical indexes, the blood lactate and muscle glycogen levels corroborated the correlation between current speed and increase in workload. These results indicate that the apparatus employed in the present study is suitable for the evaluation of the endurance capacity of mice and that is useful for detecting the effects of dietary differences and drug pretreatments on this capacity.

Animals↗
PubMed1996

Protein adsorption and platelet adhesion on polymer surfaces having phospholipid polar group connected with oxyethylene chain.

We evaluated the blood compatibility of various amphiphilic polymers, that is, n-butyl methacrylate (BMA) copolymers with methacrylates having a phosphorylcholine (PC), hydroxy (OH) or methoxy (MeO) group as an end polar group in the oxyethylene side chain. The amount of proteins adsorbed on the PC-polymer from human plasma was smaller than that on not only the poly(2-hydroxyethyl methacrylate) and poly(methyl methacrylate) but also the OH-polymer and MeO-polymer. The PC group could weaken the interaction between plasma proteins and polymer surfaces. The amount of adsorbed proteins on the PC-polymer decreased with an increase in the mole fraction of the PC units in the polymers. We could observe an effect of the oxyethylene chain length (n is the number of repeating units of oxyethylene) on protein adsorption between n = 2 and n = 3. The platelet adhesion on these polymer surfaces was evaluated using rabbit platelet-rich plasma. On the polymers without the PC group, that is, poly(BMA), OH-polymer, and MeO-polymer, many platelets adhered and a considerable shape change in the adherent platelets occurred. On the other hand, the PC-polymers could effectively suppress platelet adhesion. The platelet adhesion behavior on the polymers was strongly dependent on the adsorbed proteins. Platelet adhesion was completely inhibited on all of the PC-polymers studied having a 0.3 PC unit mole fraction. However, it was observed that the oxyethylene chains on the PC-polymers with a 0.1 PC unit mole fraction affected platelet adhesion.

Adsorption↗
PubMed1996

Effect of reduced protein adsorption on platelet adhesion at the phospholipid polymer surfaces.

We prepared polymers having a phospholipid polar group, poly [omega-methacryloyloxyalkyl phosphorylcholine (MAPC)-co-n-butyl methacrylate(BMA)], as new biomedical materials and evaluated their blood compatibility with attention to protein adsorption and platelet adhesion. The total amount of proteins adsorbed on the polymer surface from human plasma was determined, and the distribution of adsorbed proteins on the plasma-contacting surface was analyzed. The amount of proteins adsorbed on every poly (MAPC-co-BMA) was small compared with that observed on polymers without the phospholipid polar group. However, there was no significant difference in the amount of adsorbed proteins on the poly(MAPC-co-BMA) even when the methylene chain length between the phospholipid polar group and the backbone in the MAPC moiety was altered. Platelet adhesion on the polymer surface from a platelet suspension in a buffered solution was evaluated with and without plasma treatment on the surface. When a rabbit platelet suspension was brought into contact with the poly(BMA) surface after treatment with plasma, many platelets adhered and aggregated. However, a reduced amount of platelet adhered on the poly(BMA) was found in the case of direct contact with the platelet suspension. On the other hand, the poly(MAPC-co-BMA)s could inhibit platelet adhesion under both conditions. Based on these results, it can be concluded that the proteins adsorbed on the surface play an important role in determining the platelet adhesion and suppression of the protein adsorption on the surface, which is one of the most significant ways of inhibiting platelet adhesion.

Adsorption↗
PubMed1996

Electrophysiological and pharmacological characteristics of ionotropic glutamate receptors in medial vestibular nucleus neurons: a whole cell patch clamp study in acutely dissociated neurons.

A patch clamp study was performed to determine which subtype of ionotropic glutamate receptors is involved in the glutamate-induced excitation of the medial vestibular nucleus (MVN) neurons. Whole cell recording was performed on MVN neurons that were acutely dissociated by enzymatic and mechanical treatments. Application of glutamate at a concentration of 100 microM produced a current with a reversal potential of approximately 0 mV. The glutamate-induced current was completely blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), a non-N-methyl-D-aspartate (NMDA)-receptor antagonist. Application of alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) and kainic acid (KA), non-NMDA-receptor agonists, at concentrations of 30 and 100 microM produced a concentration-dependent depolarization concomitantly with an increase in firing rates during current clamp recording. During voltage clamp recording, glutamate, AMPA and KA elicited a concentration-dependent current with an equilibrium potential of approximately 0 mV. To clarify whether NMDA receptors are present in MVN neurons, the effects of glycine on the glutamate- and NMDA-induced current were examined. Two types of NMDA receptor-mediated current (types 1 and 2) were obtained in terms of the difference in sensitivity to both magnesium ion and MK-801, which act on the NMDA-receptor channel. In the type 1 neurons, the NMDA-induced current was not apparently blocked by magnesium ion or MK-801, although a larger current was obtained in the absence of magnesium ion. In the type 2 neurons, marked blockade of the NMDA-induced current was seen in the presence of magnesium ion and MK-801, as previously reported in other neurons of the central nervous system. These findings indicate the presence of both non-NMDA and NMDA receptors, which are involved in primary afferent transmission, in the MVN neuron, and two distinct types of NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Protein sequences of two keto ester reductases: possible identity as hypothetical proteins.

We determined the amino acid sequences of two keto ester reductases (YKER-V and -VI) purified from a cell-free extract of Saccharomyces cerevisiae. The N-terminal and internal amino acid sequences of YKER-VI (AcKR) were in agreement with the sequence of hypothetical 36.4-kDa protein (S. cerevisiae chromosome X reading frame ORF YJR105w) in yeast. The N-terminal amino acid sequence of YKER-V was also identical with that of the hypothetical protein coded by yeast chromosome XIV or II. These results suggested that two hypothetical proteins were expressed as keto ester reductases in yeast cells.

Alcohol Oxidoreductases↗
PubMed1996

Chemical modification of earthworm fibrinolytic enzyme with human serum albumin fragment and characterization of the protease as a therapeutic enzyme.

The strongest fibrinolytic protease (F-III-2) in the six enzyme proteins purified from earthworm, Lumbricus rubellus [N. Nakajima et al., Biosci. Biotech. Biochem., 57, 1726-1730 (1993)] has been modified chemically with fragmented human serum albumin (mol. wt., 10,000-30,000). The modified enzyme lost the antigenicity of the native enzyme and reacted with the antisera against human serum albumin, the human serum albumin fragments, and the conjugate with the native enzyme to form precipitation lines, which fused with each other. The conjugate was significantly more resistant to inactivation by protease inhibitors in rat plasma. The enzyme was a non-hemorrhagic protein and did not induce platelet aggregation. The enzyme kept potent proteolytic activity for fibrin and fibrinogen than that of human plasmin. The enzyme easily solubilized actual fibrin clots (thrombi) of whole blood induced by thrombin in a rat's vena cava. The continuous fibrinolysis for fibrin suspension in an enzyme reactor system using the modified enzyme immobilized to oxirane-activated acrylic beads has been achieved without any inactivation of the activity at least for more than 1 month. The N-terminal amino acid sequence of the protein was also investigated and the sequence showed local similarity to those of the serine proteases such as plasmin and chymotrypsin.

Amino Acid Sequence↗
PubMed1996

Influence of high dose inhaled steroids on hypothalamo-pituitary-adrenal axis function in Japanese patients with asthma: a comparison over the course of time.

Although the influence of high dose inhaled steroids on hypothalamo-pituitary-adrenal (HPA) function in patients with asthma has been extensively studied worldwide, there has been limited information on Japanese asthmatics, especially in terms of a prospective analysis of HPA function in the course of time. We analyzed the changes in HPA function using 2 serial short tetracosactrin tests (STT) separated by an interval of one year in 11 Japanese asthmatics who were treated with high dose inhaled steroids alone [beclomethasone dipropionate (BDP); mean dose 982 micrograms/day] during the period between 2 STTs. Mean values of plasma cortisol before administration of ACTH, maximum cortisol and the rise in cortisol in response to ACTH in the 2 STTs were 7.8, 20.5 and 12.7 micrograms/dl for the 1st test, and 8.9, 23.6 and 14.7 micrograms/dl for the 2nd test, respectively. Overall, there was no significant change in the course of time in each of these 3 values. Although the results of the 1st STT proved to be abnormal in 3 patients who had been receiving systemic steroids before their 1st STT, they improved uniformly in their 2nd STT. In the remaining 8 patients, who had never received systemic steroids, 4 patients showed improvements while the other 4 showed deterioration in HPA function in their serial STTs over the course of time. The dose of BDP was 800 micrograms/day in the former 4 patients, while it was 1,200 micrograms/day in the latter 4. Furthermore, only one patient, in whom BDP had been increased from 800 micrograms/day to 1,200 micrograms/day between the 2 tests, developed an abnormal response in the 2nd STT. On the other hand, one patient whose BDP dose was increased from 800 micrograms/day to 1,600 micrograms/day showed an improvement in HPA function in the 2nd test. These results indicate that the threshold dose of BDP which may cause HPA suppression in Japanese asthmatics lies between 800-1,200 micrograms/day, although there is a large inter-individual variation in terms of such doses.

Administration, Inhalation↗
PubMed1996

A patient with plaque-stage mycosis fungoides has successfully been treated with long-term administration of IFN-gamma and has been in complete remission for more than 6 years.

We report the successful treatment of a patient with plaque-stage mycosis fungoides with long-term and intravenous administration of recombinant human interferon-gamma (IFN-gamma) and discuss the possible mechanisms of this therapy. A 55-year-old female patient had been resistant to existing treatments and had suffered repeated exacerbations over a 5-year period. Four weeks after initiation of 2 x 10(6) U/day of IFN-gamma, a > 10% decrease in the affected surface area was noted. Twenty-two weeks after the administration of 228 x 10(6) U of IFN-gamma, complete remission (CR) was obtained. The CR continued for 13 weeks, but this was followed by an exacerbation. The second CR was obtained after the IFN-gamma dosage was increased to 16 x 10(6) U/week. The dosage was then gradually reduced by 2-4 x 10(6) U every 2 or 3 months. She was treated with a total dose of 2814 x 10(6) of IFN-gamma. She has been followed up for more than 6 years, and there has been no recurrence of mycotic skin lesions nor any visceral involvement. During therapy, no serious side-effects were noted. Long-term administration of IFN-gamma is useful for the treatment of patients with intractable mycosis fungoides. A gradual decrease in the dose of IFN-gamma is important for maintaining remission.

Antineoplastic Agents↗
PubMed1996

[Inhaled corticosteroid in out-patient management of asthma].

In 1988, we started to change our treatment policy, away from a polypharmaceutical approach including oral bronchodilators and oral anti-allergic agents available in Japan, toward an inhalation therapy including inhaled corticosteroids and inhaled beta-agonist. A marked decline in the number of asthma admission and death from asthma started coincidentally with the increased use of inhaled corticosteroid which were followed by the decreased use of inhaled beta-agonists and oral anti-asthma agents. The intensification of patient education mainly consisting of emphasizing on better understanding of benefits of inhalation therapy and a self-management is likely to play an important role in enhancing a protective effects of inhaled corticosteroids. Despite some limitations of inhaled corticosteroids, such as poorer dose response in elderly asthmatics and/or patients with severe disease, further introduction of guide-line treatment will result in a measurable improvement on asthma control.

Administration, Inhalation↗
PubMed1996

[Concerns about adverse effects of inhaled corticosteroids].

Inhaled corticosteroids (ICS) are mainstay in controlling the symptoms of asthma. Previous studies have demonstrated that ICS have minimal systemic effects, at doses of up to 400 micrograms per day for children and up to 1000 micrograms per day for adults. At higher doses some systemic effects can be seen. But to date there is no convincing evidence that this gives rise to any of the well known clinical sequelae of corticosteroid excess. To determine the dosage of ICS, it is important to weigh up the potential benefits and risks in each patient. The use of spacer devices and mouth rinsing may reduce local and systemic adverse effects.

Administration, Inhalation↗
PubMed1996

[Computed tomographic findings in septic pulmonary emboli secondary to renal abscess].

A 73-year-old woman with diabetes mellitus and hypothyroidism had been well until 4 days before she presented with fever, productive coughing, and general malaise. Dyspnea gradually worsened, and she was admitted to Kobe City General Hospital. She appeared toxic and was in moderate respiratory distress on admission. There were scattered rales in both lung fields. The abdomen was soft with no tenderness. A chest roentgenogram showed peripheral infiltrates in both lung fields. Arterial blood gas analysis showed a Po2 of 48.6 Torr and Pco2 of 27.2 Torr. A blood culture on admission showed Escherichia coli. Computerized tomography of the chest showed multiple nodules of various sizes in the peripheral lung fields. Some nodules had necrotic centers and feeding vessels. Wedge-shaped lesions abutting the pleura were also seen. These findings strongly suggested septic pulmonary emboli. An abscess in the left kidney, which was considered to be the source of the septic pulmonary emboli, was found with Ga scintigraphy, ultrasonography, and computerized tomography of the abdomen. Treatment with antibacterial drugs was effective against the lung lesions but not the renal abscess. A left nephrectomy was done. In the proper clinical setting, characteristic CT features of septic emboli can contribute to early diagnosis of this disease.

Abscess↗
PubMed1996

[A case report of total cavopulmonary connection following total cavopulmonary shunt].

A 20-year-old man underwent total cavopulmonary shunt for univentricular heart type A (A.L.L.) with hemiazygos connection six years ago. Four years later, his condition deteriorated with easy fatigue and cyanosis. Cardiac catheterization showed recanalization of ligated SVC. Chest CT showed tight adhesion between the chest wall and the ascending aorta. We approached the heart through left anterolateral thoracotomy in order to avoid injury of the aorta and the ventricle during redo median sternotomy. Total cavopulmonary connection with intraatrial conduit was performed under circulatory arrest and retrograde cardioplegia without aortic cross clamp. His postoperative course was satisfactory. Left thoracotomy was useful for total cavopulmonary connection following total cavopulmonary shunt associated with postoperative adhesion.

Adult↗
PubMed1995

Effect of nicardipine on abnormal excitability of CA3 pyramidal cells in hippocampal slices of spontaneously epileptic rats.

The effects of nicardipine, a Ca2+ channel antagonist, on the abnormal excitability of hippocampal CA3 neurons in spontaneously epileptic rats (SER), a double mutant (zi/zi, tm/tm), were examined to elucidate whether or not the abnormality was due to that of Ca2+ channels. An intracellular recording study was performed using brain slice preparations of SER 12-15 weeks of age, when SER showed both tonic convulsions and absence-like seizures. Bath application of nicardipine (10 nM) completely inhibited the depolarizing shifts lasting for 60-120 ms and accompanying repetitive firings on mossy fiber stimulation in SER. However, this drug did not affect the single action potential induced by the mossy fiber stimulation in CA3 neurons of SER and normal Wistar rats. In the CA3 pyramidal neurons of SER, the Ca2+ spikes induced by the depolarizing pulse applied in the cell in the presence of tetrodotoxin and tetraethylammonium had a different configuration from that in normal Wistar rats. Nicardipine also inhibited the Ca2+ spikes in SER CA3 neurons at a concentration (1 nM) that had no effect on those in normal Wistar rats, while the Ca2+ spikes in Wistar rat CA3 neurons were inhibited by 10 nM nicardipine. These findings suggest that the abnormal excitability of CA3 pyramidal neurons in SER might be attributed to abnormalities of the Ca2+ channels, and that the Ca2+ channel antagonist may be effective as an antiepileptic drug.

Animals↗
PubMed1995

Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth.

Bone marrow stromal cells regulate B-cell growth and development through their surface molecules and cytokines. In this study, we generated a mAb, RS38, that recognized a novel human membrane protein, BST-2, expressed on bone marrow stromal cell lines and synovial cell lines. We cloned a cDNA encoding BST-2 from a rheumatoid arthritis-derived synovial cell line. BST-2 is a 30- to 36-kDa type II transmembrane protein, consisting of 180 amino acids. The BST-2 gene (HGMW-approved symbol BST2) is located on chromosome 19p13.2. BST-2 is expressed not only on certain bone marrow stromal cell lines but also on various normal tissues, although its expression pattern is different from that of another bone marrow stromal cell surface molecule, BST-1. BST-2 surface expression on fibroblast cell lines facilitated the stromal cell-dependent growth of a murine bone marrow-derived pre-B-cell line, DW34. The results suggest that BST-2 may be involved in pre-B-cell growth.

Amino Acid Sequence↗