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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 469 records · Page 26Linked to original sources

Effects of the M1 muscarinic receptor antagonist pirenzepine on gastric mucus glycoprotein in rats with or without ethanol-induced gastric damage.

Changes in gastric mucus glycoprotein (mucin) isolated from pirenzepine-treated rats with or without ethanol (50%)-induced gastric damage were studied. The prior administration of pirenzepine inhibited significantly and dose-dependently the occurrence of macroscopically observable hemorrhagic lesions induced by treatment with ethanol. The gastric mucosa was separated into the surface mucosa, including the mucus gel layer, and the deeper mucosa by mechanical scraping, and the mucin in each was isolated. In ethanol-treated animals the mucin content of the deep corpus mucosa was significantly reduced to 68% the control value. This reduction was inhibited by pretreatment with pirenzepine. In the surface mucosa mucin content was also reduced to 48% of control value by ethanol treatment, but pirenzepine pretreatment increased mucin content to 235% the control value. Total mucin content in the entire stomach essentially resumed the control level by pretreatment with 100 mg/kg of pirenzepine. A single oral administration of pirenzepine (100 mg/kg) caused no change in total mucin content, but mucin in the deep corpus mucosa selectively and significantly increased to 124% the control. These and the results of carbohydrate analysis of purified mucin indicate that pirenzepine administration possibly accelerates the secretion of accumulated deep corpus mucus, retains this deep mucus on surface mucosal mucus, and protects the gastric mucosa in ethanol-induced gastric damage. This may be related to the antiulcerogenic effects of pirenzepine.

Animals↗

Effect of rebamipide on mucus secretion by endogenous prostaglandin-independent mechanism in rat gastric mucosa.

The effect of rebamipide (2-(4-chlorobenzoylamino)-3-[2 (1H)-quinolinon-4-yl]-propionic acid, OPC-12759, CAS 11911-87-6), an anti-ulcer agent developed to enhance defensive factors in the gastric mucosa, on gastric mucus secretion was studied by a newly developed biochemical method to measure the gastric mucus glycoprotein content in rats. 1 h after intraperitoneal administration, rebamipide did not produce a significant change in the intramucosal mucus contents (surface mucosal layer and deep mucosal layers of corpus and antral regions) but significantly increased the content of soluble mucus, which recovered from the gastric contents, to about 160% of the control value. Since rebamipide has been shown to increase the biosynthesis of prostaglandins, indometacin was administered to the rats prior to rebamipide administration to examine whether the increase in prostaglandin biosynthesis contributes to the rebamipide-induced increase in gastric mucus secretion. The increase in the soluble mucus was not altered by the pretreatment with indometacin, thus indicating that rebamipide per se has a potential to increase the gastric mucus secretion by a mechanism that is not mediated by the endogenous prostaglandins. The effect of rebamipide on the gastric mucus secretion might contribute to heal and to prevent the recurrence of peptic ulcer diseases as well as to maintain the homeostasis of the gastric mucosa.

Alanine↗

[Surgical correction of atrioventricular discordance--results and follow-up].

Between January 1977 and October 1991, 47 consecutive patients with atrioventricular discordance, ventriculoarterial discordance, and two ventricles underwent intracardiac repair at the Heart Institute of Japan. Their ages at operation ranged from 2 months to 21 years (average 9.2 years) and period of follow-up ranged from 1 month to 168 months (average 65.1 months). There were five basic anatomic types according to the associated anomalies, grouped into (1) situs solitus, ventriculoarterial (V-A) discordance or double-outlet right ventricle (DORV), ventricular septal defect (VSD) and pulmonary outflow tract obstruction (POTO) (31 patients); (2) situs solitus, V-A discordance and VSD (6 patients); (3) situs solitus, V-A discordance and tricuspid regurgitation (TR) (2 patients); (4) situs inversus, V-A discordance or DORV, VSA and POTO (7 patients); (5) situs inversus, V-A discordance and VSD (1 patient). TR was evident preoperatively in 13 patients (28% of 47 patients), one of whom had Ebstein's anomaly. The conventional operation, which consisted of closure of VSD (34 patients), posterolateral pulmonary outflow enlargement (2 patients), tricuspid valvuloplasty (2 patients), and tricuspid replacement (1 patient) using the anatomical right ventricle as the systemic ventricle, was performed in 35 patients (RV group). The anatomic correction (so-called "double switch operation"), the new alternative operation using the anatomical left ventricle as the systemic ventricle, was achieved in 12 patients (LV group). Anatomic correction consisted of Senning and RV-PA ECR in 3, Mustard and RV-PA ECR in 4, Senning and arterial switch in 2, and Mustard and arterial switch in 1 patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Assessment of long-term systemic ventricular function after the surgical repair in patients with atrioventricular discordance].

Long-term systemic ventricular function at rest and during supine bicycle exercise was studied in 12 patients with atrioventricular discordance (AVD group) using multigated radionuclide blood pool imaging. For comparison, similar measurements were made in eight children (control group). The mean age at the exercise test was 12.3 years in AVD group and was 14.8 years in the control group. In AVD group, ages at the operation ranged from three to 21 years (mean 12.3 years), and the exercise test was performed from one to 9.8 years after the operation (mean 5.3 years). The operative procedures in AVD group consisted of closure of the ventricular septal defect in 11 patients, extracardiac conduit between the left ventricle and the pulmonary artery in nine patients, postero-lateral left ventricular outflow reconstruction in two patients, tricuspid annuloplasty in one patient, and tricuspid valve replacement in one patient. Exercise tolerance of AVD group was less than that of the control group. Heart rate and blood pressure were significantly increased during exercise in both groups. In the control group, end-diastolic count index (EDCI) (= end-diastolic volume) remained unchanged and end-systolic count index (ESCI) (= end-systolic volume) decreased during exercise. In contrast, both EDCI and ESCI were decreased in AVD group. As a consequence, systemic right ventricular ejection fraction (RVEF) increased during exercise in the control group, but remained unchanged in AVD group. Although stroke count index (SCI) (= stroke volume index) did not increased during exercise in AVD group, output count index (OCI) (= cardiac index) increased with the increase of heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Two-stage Jatene procedure after Mustard or Senning operation].

We have successfully performed a two-stage Jatene procedure in four patients who showed severe anatomical right ventricular dysfunction after atrial switch (Mustard or Senning) operation for transposition of the great arteries. All four patients developed an adequate left ventricular pressure for the arterial switch operation by one or two-stage pulmonary artery banding. Left ventricular posterior wall thickness increased sufficiently enough after the banding although left ventricular ejection fraction showed significant decrease. After Jatene procedure left ventricular ejection fraction recovered, and RV end-diastolic volume which had been prominently enlarged preoperatively was dramatically normalized. Cardiac index increased from 3.6 +/- 1.6 l/min/m2 preoperatively to 5.3 +/- 6.1 l/min/m2 postoperatively with the decrease in left atrial pressure. Postoperative electrophysiological study revealed the recovery of sinus node function and atrial conduction by means of the take-down of atrial switch operation previously performed. We conclude that the Jatene procedure should be an ideal alternative in patients with right ventricular dysfunction after atrial switch operation. The left ventricle could be prepared by an effective pulmonary artery banding in most instances.

Cardiac Surgical Procedures↗

Left ventricular mechanics and myocyte function after correction of experimental chronic mitral regurgitation by combined mitral valve replacement and preservation of the native mitral valve apparatus.

BACKGROUND: Contractile function improves after correction of experimental mitral regurgitation, but ejection performance becomes depressed when mitral valve replacement involves chordal transection. A role for chordal transection in producing the depressed ejection performance was suspected but uncertain. Therefore, in this study, we tested two specific hypotheses: 1) that contractile function would improve and, in conjunction with chordal preservation, would allow for preserved ejection performance and 2) that improved left ventricular contractile function after surgery would be reflected in the function of myocytes isolated from the affected left ventricles. METHODS AND RESULTS: We examined ventricular contractile function and ejection performance and isolated myocyte function after correction of experimental mitral regurgitation (chordal rupture) with mitral valve replacement that involved chordal preservation. After 3 months of chronic mitral regurgitation, the average regurgitant fraction of seven dogs was 0.77 +/- 0.04. End-diastolic volume had increased from 79 +/- 5 to 132 +/- 10 cm3 (p < 0.05). At that time, all indexes of left ventricular contractile function were depressed. Three months after mitral valve replacement with chordal preservation, end-diastolic volume fell to 100 +/- 4 cm3 (p < 0.05). At this time, all indexes of contractile function had returned to normal. End-systolic stress and ejection fraction after mitral valve replacement were similar to their baseline levels. Viscosity-velocity curves (analogous to force-velocity curves) of myocytes isolated from the affected left ventricles were similar to those of myocytes isolated from normal left ventricles. CONCLUSIONS: We conclude that mitral valve replacement with chordal preservation allows ventricular contractile function to return to normal. Normal global ventricular function, in turn, is associated with normal function of the individual myocytes that compose the left ventricular chamber. Further, chordal preservation allowed for loading and ejection performance to return to premorbid levels.

Animals↗

[Surgical treatment of total anomalous pulmonary venous connection Darling type Ib using pedicled right atrial flap].

A one-month-old baby with total anomalous pulmonary venous connection (TAPVC) type Ib underwent a total correction with a pedicled right atrial (RA) flap, which was made by incising the RA wall in a quadrangular configuration. The common pulmonary vein (PV) was cut back into the left atrium (LA). Then the RA flap was sutured along the limbus of PV recess and atrial septal defect (ASD) to create a new pulmonary venous channel. The defect in the RA wall was directly closed without any prosthetic patch. Absorbable sutures (# 6-0 PDS) were used throughout. Postoperative course was uneventful and echocardiogram showed widely opened PV channel draining into the LA. We think that this procedure could be applied in various types of total and partial anomalous pulmonary venous connection, avoiding pulmonary venous obstruction on the assumption that the RA flap should grow.

Heart Atria↗

[Use of beta-agonist inhalation concomitantly with regular beclomethasone dipropionate in patients with bronchial asthma--as required or on a regular basis].

We investigated whether regular use of beta-agonist inhalation concomitantly with regular beclomethasone dipropionate (BDP) inhalation is necessary in chronic bronchial asthma. Twenty chronic asthmatic patients who were stable on regular BDP and beta-agonist inhalation were studied. After a 2 week observation period, the patients were randomly assigned to two groups. One group received BDP 400 micrograms/day (2 puffs 4 times) and beta-agonist inhalation as required for 4 weeks. This period was followed by 4 weeks of treatment with BDP 400 micrograms/day and regular beta-agonist inhalation. The other group received these treatments in the reverse order. No significant differences among the two groups were observed in attack score, ADL score, sleep score, and %PEFR. In addition, no differences were detected in these parameters between the periods of regular use of beta-agonist and the periods of use as required. The frequency of inhalation of beta-agonist during the use as required period correlated with the sleep score and difference in %PEFR between morning and night, and was significantly lower than the frequency of inhalation during the period of regular. From these results, we conclude that inhalation of beta-agonist on a regular basis is not necessary to achieve the same degree of relief of symptoms as treatment with beta 2-agonist and BDP inhalation on regular basis in patients with chronic asthma.

Administration, Inhalation↗

Effects of L-threo-DOPS, a noradrenaline precursor, on the long-term potentiation in the rat hippocampal mossy fiber-CA3 region.

The effects of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a synthetic precursor of norepinephrine (NE), on the long-term potentiation (LTP) in the hippocampal mossy fiber-CA3 system was examined in urethane-anesthetized rats, the objective being to determine whether or not this drug acts as NE on the LTP. L-threo-DOPS may be effective for treating some type of mental disorders, including dementia. The LTP, induced in CA3 by tetanic stimulation (100 Hz for 1 s) applied to the mossy fiber persisted for more than 4 h. When L-threo-DOPS (50 and 150 micrograms) was injected into the lateral ventricle 30 min prior to the tetanic stimulation, there were no significant alterations in the LTP. However, in animals treated with reserpine (5 mg/kg i.p.) 24 h before the experiment, LTP was not induced with tetanic stimulation alone yet was obtained when tetanic stimulation was preceded by L-threo-DOPS (50 and 150 micrograms) applied to the ventricle. The LTP obtained by L-threo-DOPS in the reserpine-treated animal was inhibited by pretreatment with benserazide and was completely blocked by the simultaneous administration of sotalol. These results suggest that NE converted from L-threo-DOPS plays an important role in inducing LTP in the mossy fiber-CA3 system in the animals deficient in catecholamines.

Anesthesia↗

Characteristics of muscarinic cholinergic, gamma-aminobutyric acid(A) and phencyclidine receptors in spontaneously epileptic rats; in vitro quantitative autoradiographic analysis.

Characteristics of muscarinic cholinergic (mACh), gamma-aminobutyric acid(A) (GABAA) and phencyclidine (PCP) receptors in the spontaneously epileptic rats (SER), which exhibit both absence-like seizures and tonic convulsion, were examined using in vitro quantitative autoradiography. Computer analysis using autoradiographic technique revealed that the amount of the specific binding of [3H]quinuclidinyl benzilate (QNB) to mACh receptors in the striatum of SER was more than that of zitter rats, not exhibiting both seizures and convulsion. However, the specific bindings of [3H]muscimol and [3H]N-(1-[2-thienyl]cyclohexyl)3,4-piperidine (TCP) to GABAA and PCP receptors, respectively, of SER were not different from those of zitter rats in various regions tested. These results suggest that hyperfunction of mACh receptors in the striatum is involved in the appearance of absence-like seizures and tonic convulsion of SER.

Animals↗

Effects of thyrotropin-releasing hormone and a related analog, CNK-602A, on long-term potentiation in the mossy fiber-CA3 pathway of guinea pig hippocampal slices.

The effects of thyrotropin-releasing hormone (TRH) and a related analog, CNK-602A, that induces the release of catecholamines, on long-term potentiation (LTP) of the population spike in mossy fiber-CA3 pathways were investigated in guinea pig hippocampal slices. TRH augmented LTP of the population spike at concentrations of 10(-6)-10(-5) M. CNK-602A also augmented LTP at concentrations of 10(-6)-10(-5) M in a dose-dependent manner. LTP in slices of the hippocampus obtained from animals given 6-hydroxydopamine (6-OHDA) intraventricularly was significantly lower than that in non-treated animals. However, both TRH and CNK-602A (10(-6) M) augmented LTP in slices from 6-OHDA-treated animals. These findings suggest that TRH and CNK-602A augment LTP in the mossy fiber-CA3 pathway without activating noradrenergic and/or dopaminergic fibers.

Animals↗

Inhibition by thyrotropin-releasing hormone of epileptic seizures in spontaneously epileptic rats.

The effects of thyrotropin-releasing hormone (TRH) were investigated on absence-like seizures, which are characterized by the sudden appearance of 5-7 Hz spike-wave-like complexes in the cortical and hippocampal EEG, and on tonic convulsions of spontaneously epileptic rats (SER; zi/zi, tm/tm), a double mutant obtained by mating zitter homozygote (zi/zi) with tremor heterozygote rats (tm/+). TRH (5 and 10 mg/kg i.v.) inhibited the appearance of both absence-like seizures and tonic convulsions of SER without inducing obvious changes in the background EEG. The inhibitory effects were seen 5-20 min after injection of 10 mg/kg TRH and were antagonized by pretreatment with haloperidol (0.5 and 1.0/kg i.p.), although haloperidol alone did not affect the seizures. These results suggest that TRH has an antiepileptic effect in the genetically defined animal model, SER, and that the effect is mediated by the central dopaminergic system.

Animals↗

Protein adsorption from human plasma is reduced on phospholipid polymers.

Protein adsorption from human plasma was investigated on phospholipid polymers, poly (2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA) or glass by radioimmunoassay and immunogold labeling techniques. In the present studies the focus was to determine the composition and distribution of proteins at the surface of these materials after contact with human blood plasma. On all materials, protein adsorption was detected and included identification of albumin, IgG, fibrinogen, fibronectin, Hageman factor (factor XII), factor VIII/von Willebrand factor, high-molecular-weight kininogen (HMWK) and the complement protein C5. The amount of protein adsorbed decreased with an increase in the MPC composition and appeared to adsorb to the surfaces in a uniform and evenly distributed manner. Therefore, we suggest that MPC moieties play an important role in suppression of protein adsorption. From these findings, it is concluded that the reduction of protein adsorption at the blood contacting surface of phospholipid polymers may result in the inhibition of thrombus formation.

Adsorption↗

Y/6 chromosome translocation in a male with triple primary cancers involving the breast.

Cytogenic studies were performed in a 72-year-old male patient with triple primary cancers including breast, skin and lung. Left breast cancer was diagnosed at the age of 46 and he received mastectomy and thoracic irradiation. Squamous cell carcinoma and Bowen's disease were diagnosed from two separated parts of a skin lesion at the age of 70. Small-cell lung cancer was diagnosed 1 year later, and he received chemotherapy and radiotherapy. Chromosome analysis was carried out on both peripheral lymphocyte and skin fibroblast cultures at the age of 72. Out of 30 fibroblast cells karyotyped at the second passage, 7 cells (23%) consistently showed a reciprocal translocation t(Y;6)(q12;p21). The same translocation was found in one of 200 cells from lymphocyte cultures. The findings suggest that the translocation t(Y;6) might be inherent in nature, and that the patient was a mosaic of 46,XY/46,X,t(Y;6)(q12;p21). These results highlight the constitutional chromosomal abnormality as one of the possible high-risk factors for multiple primary cancers.

Breast Neoplasms↗

Platelet-activating factor (PAF) in allergic diseases: inhibitory effects of anti-allergic drugs, ketotifen and three kampo medicines on PAF production.

Platelet-activating factor (PAF) is considered an important mediator in allergic and inflammatory reactions. To further investigate the role of PAF in allergic diseases, we examined the in vitro and ex vivo effect of anti-allergic drugs on PAF production by human neutrophils. Ketotifen and three Kampo medicines, which are widely used in the treatment of allergic diseases in Japan, inhibited PAF production by normal human neutrophils dose-dependently, whereas disodium chromoglycate (DSCG) and tranilast did not have any inhibitory effect. Ketotifen also suppressed ex vivo PAF production by neutrophils from healthy subjects. PAF production decreased from 40.5 +/- 5.0 units to 21.6 +/- 4.7 units after oral administration of 2 mg of ketotifen per day for one week. We also measured the concentration of lysoPAF in serum from patients with Japanese cedar pollinosis during the pollen season and followed the effect of ketotifen on lysoPAF levels in the serum from these patients. We found that the concentration of lysoPAF, a precursor and degradation product of PAF, in patients with cedar pollinosis (87.8 +/- 8.7 units) was significantly higher than in healthy subjects (54.7 +/- 7.7 units). After two weeks, lysoPAF levels decreased significantly (82.6 units to 41.3 units) only in the group treated with nasal aerosol and ketotifen. These results suggest that PAF may play a role in allergic diseases and that the clinical effects of anti-allergic drugs may at least partially be due to their anti-PAF action.

Adult↗

A new method of separation and quantitation of mucus glycoprotein in rat gastric mucus gel layer and its application to mucus secretion induced by 16,16-dimethyl PGE2.

A method was established for recovering the mucus gel layer of rat gastric mucosa without damage to underlying surface epithelium. The mucus gel was solubilized by stirring the gastric mucosa in a solution of N-acetylcysteine (NAC), a mucolytic agent. Optimal mucus gel solubilization was possible by treatment with 2% NAC for 5 minutes at room temperature. Mucus glycoprotein was quantitatively extracted and measured from the mucus gel sample obtained by the NAC treatment. This treatment caused no damage to surface epithelial cells, as observed by a light microscope. Besides NAC, pronase solution was also adequate for solubilizing the mucus gel layer without any damage to the surface epithelium. However, extraction and measurement of mucus glycoprotein from the pronase-treated mucus gel sample was not possible due to contamination by high molecular hexose-containing substances which were eluted along with the mucus glycoprotein from the column of Bio-Gel A-1.5m. This NAC method was used to examine changes in mucus glycoprotein content in the mucus gel at one hour following the oral administration of 16,16-dimethyl prostaglandin E2. A significant increase in mucus glycoprotein of the gel was brought about by the prostaglandin treatment. Thus, the present method was suitable for estimating the amount of mucus secreted in to the mucus gel layer.

Animals↗