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Biomedical subjects

K Takagi

Publications and source records attributed to K Takagi.

At least 487 records · Page 27Linked to original sources
PubMed1991

Pharmacokinetic characteristics of N7-substituted theophylline derivatives and their interaction with quinolone in rats.

Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model-independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50% of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, approximately 13-fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug.

Aminophylline↗
PubMed1991

Monocytoid B-cell lymphoma: a study of 36 cases.

We have studied 36 cases of monocytoid B-cell lymphoma (MBCL). We confirm the predilection for females (30 of 36; ratio, five women to one man). The median age was 65 years (range, 29 to 85 years). Monocytoid B-cell lymphoma characteristically involves peripheral lymph nodes (30 of 36) with a propensity for paraparotid or intraparotid nodes. Salivary glands were affected in five patients. Other extranodal sites of involvement included breast, thyroid, stomach, and soft tissue of chest wall. Eight patients manifested with Sjögren's syndrome, one had systemic lupus erythematosus, one presented initially with Raynaud's phenomenon, and two had a monoclonal gammopathy. "Composite lymphomas" were encountered in seven patients. In addition, association with or progression to a higher-grade lymphoma, ie, mixed small and large cell (one) and large cell (six), was observed in seven patients and was associated with a more aggressive behavior of the lymphoma. Immunohistochemical studies performed on biopsy sections from 20 patients confirmed the B-cell nature of MBCL. An average reactivity of less than 10% of the monocytoid B cells with the proliferation marker Ki-67 was demonstrated, in keeping with the indolent behavior of MBCL. Despite our observation of follicular lymphomas frequently accompanying MBCL, the t(14;18) chromosomal translocation does not appear to play a pathogenetic role for MBCL, as determined by molecular studies for the t(14;18) chromosomal translocation and immunologic studies for the BCL2 protein. Our observations also provide support for the proposal that there is an overlap between MBCL and "MALT lymphomas" (those arising from mucosa-associated lymphoid tissue).

Adult↗
PubMed1991

Cervical spinal epidural hematoma with spontaneous remission.

Spinal epidural hematoma (SEH) is comparatively rare. In most cases, urgent surgical decompression is necessary. Several reports have described spontaneous remission of SEH. The authors present a rare case of spontaneous resolution of cervical SEH.

Epidural Space↗
PubMed1991

Effect of intraportal nitroglycerin on portosystemic hemodynamics in patients with cirrhosis: comparison with i.v. route.

We observed 18 patients with portal hypertension and cirrhosis to compare the effects of intraportal nitroglycerin on portosystemic hemodynamics with the i.v. route. Patients received 1 microgram/kg/min of nitroglycerin intravenously (n = 9) or the same dose of nitroglycerin directly into the portal vein (n = 9). Both routes of nitroglycerin significantly reduced mean arterial pressure and this effect was higher with the i.v. route (-28.0% versus -19.3%, p less than 0.02). The portal pressure, as evaluated by the portal venous pressure gradient or hepatic venous pressure gradient, was also reduced significantly in both groups. The fall in portal pressure was higher in the intraportal group, but the difference was not significant (intravenous versus intraportal, -23.9 versus -25.1% in portal venous pressure gradient, -25.2 versus -33.4% in hepatic venous pressure gradient). The hepatic blood flow was maintained despite the significant reduction in portal pressure by both routes. These results indicate that intraportal nitroglycerin decreases portal pressure with a smaller effect on systemic hemodynamics than the i.v. route. We conclude that the oral administration of nitroglycerin, which is a pathway equivalent to the intraportal route, may be more useful than the i.v. (i.e., sublingual) route in the treatment of portal hypertension.

Administration, Oral↗
PubMed1991

Relationship between fetal hypoxia and endothelin-1 in fetal circulation.

The role of endothelin-1 (ET-1), a potent vasoconstrictor peptide secreted by endothelial cells, in fetal circulation was investigated in relation to fetal hypoxia. Umbilical venous blood was obtained from 23 subjects who delivered between 36 and 41 weeks of gestation. In all cases, pH of umbilical venous blood was measured immediately after the delivery of placenta. ET-1 was extracted from the umbilical venous plasma by an Amprep C2 column and determined by a specific radioimmunoassay. Immunoreactive ET levels in the umbilical cord plasma (pg/ml, mean +/- SEM) from subjects with umbilical venous blood pH levels below 7.30 (n = 9) were 12.53 +/- 2.03, significantly higher than those with pH levels above 7.30 (6.44 +/- 1.11, n = 14). These results indicate that ET-1 in the fetal circulation may be involved in the regulation of the circulation in response to changes in acid-base balance related to fetal hypoxia.

Adult↗
PubMed1991

c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas.

Ductectatic-type mucinous cystic neoplasms of the pancreas constitute a recently recognized new human pancreatic tumor entity. Examination for the presence of point mutations at codon 12 of K-ras by oligonucleotide hybridization in 5 adenomas and 3 carcinomas revealed alteration in 3 and 2, respectively. In 4 of these positive cases, the transition was GGT----GAT (Gly----Asp) with the remaining one, found in a cancer, being GGT----GTT (Gly----Val). In two carcinoma cases, the same point mutation was detected both in the carcinoma area and in a coexisting adenoma component. Thus K-ras point mutation appears to be associated with this particular type of neoplasm in the same manner as observed for typical exocrine pancreas carcinomas. Our study also indicates the possible existence of an adenoma-carcinoma sequence in the evolution of this type of neoplasm and we suggest that K-ras activation may be an important event in the phase of adenoma development.

Adenoma↗
PubMed1991

Inhibition of cyclic GMP phosphodiesterase by xanthine derivatives relaxes guinea-pig trachealis smooth muscle.

1. For the purpose of clarifying the mechanism of the airways smooth muscle relaxant action of xanthines, cyclic guanosine monophosphate (GMP) phosphodiesterase (PDE) from guinea-pig trachealis muscle was purified with diethylaminoethyl ether (DEAE) cellulose column chromatography. 2. Five 3-alkylxanthines (3-methylxanthine, 3-ethylxanthine, 3-n-propylxanthine (enprofylline), 3-n-butylxanthine, and 3-iso-butylxanthine), and five 1-methyl-3-alkylxanthines (1-methyl-3-methyl-xanthine (theophylline), 1-methyl-3-ethylxanthine, 1-methyl-3-n-propylxanthine, 1-methyl-3-n-butylxanthine, and 1-methyl-3-iso-butylxanthine (IBMX] were compared in terms of purified cyclic GMP PDE inhibition. The relationship between the structure and inhibition of cyclic GMP PDE was studied. 3. The -log EC50 values for relaxation of spontaneous tone of isolated guinea-pig trachealis preparations by the 3-alkylxanthines and 1-methyl-3-alkylxanthines were determined. 4. The five 1-methyl-3-alkylxanthines were each more potent in relaxing isolated trachealis smooth muscle than the corresponding 3-alkylxanthines. The 1-methyl-3-alkylxanthines were also more potent than the corresponding 3-alkylxanthines in their cyclic GMP PDE inhibitory effect. There was a strong positive correlation between the concentration of inhibitor which inhibited hydrolysis by 50% (IC50) values for cyclic GMP PDE inhibition by the xanthine derivatives and their EC50 values for trachealis muscle relaxation. 5. It is suggested that the mechanism by which xanthine derivatives relax trachealis smooth muscle involves inhibition of cyclic GMP PDE in addition to inhibition of cyclic adenosine monophosphate PDE.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1991

Etiological role of phagocytes in Kawasaki disease.

The numbers of immature neutrophils and monocytes in the peripheral blood are increased in the acute phase of Kawasaki disease. These phagocytes contain toxic granules and vacuoles in the cytoplasm. Phagocytes are primed and activated to release active oxygen species, lysosome enzymes and chemical mediators, which injure cultured endothelial cells and vascular smooth muscle cells. One of the possible factors causing cardio-vascular complications in Kawasaki disease is these activated phagocytes. Some microbial agents or their products such as toxins may activate neutrophils and monocytes, but the real cause remains unknown.

Cytokines↗
PubMed1991

Structure-related inhibitory effect of quinolones on alkyl-xanthine elimination in rats.

To investigate the relationship between the chemical structures of quinolones, enoxacin (ENX) and its analogues, and their metabolic inhibitory effects on theophylline, a xanthine derivative closely related to theophylline, 1-methyl-3-propylxanthine (MPX), was used as a model of theophylline in rats. The disappearance of MPX from plasma was significantly delayed by treatment with ENX and analogue A (derivatives without substituent group at both 3'- and 5'- carbon atom in the piperazinyl ring): total body clearance of MPX was significantly decreased by approximately 50%. However, analogue A was converted into ENX in the rat body (about 14% of dose). Analogues B and C (derivatives with substituent group at 3'- or 5'-carbon atom in the piperazinyl ring) had little or no effect on MPX disposition. No significant change in the volume of distribution of MPX was observed after coadministration with these quinolones. The results of this study indicate that the substitutions on 3' and 5'-carbon atoms of piperazinyl ring at 7-position of the quinolone molecule may play important role in the inhibition of theophylline metabolism.

Animals↗
PubMed1991

[Enzyme-linked immunosorbent assay using monoclonal antibodies for direct serotyping of enteric adenoviruses in feces].

We were prepared three monoclonal antibodies in which the monoclone 12D was type specific for Adenovirus 40 (Ad40), 1F was type specific for Ad41 and 15D was group specific for Ads. For identification of enteric adenoviruses (EAd) in stool specimens, enzyme-linked immunosorbent assay (ELISA) test using monoclonal antibodies was developed. Results of identification by the ELISA tests using monoclonal antibodies to EAd on 15 fecal samples in which Ad particles were found by electron microscopy showed complete coincidence to those of Sma 1 restriction endonuclease cleavage. From these results, the ELISA tests employing EAds type specific monoclonal antibodies proved to be specific and this was a rapid technique for laboratory diagnosis of EAd in fecal specimens of viral gastroenteritis. Fifty-eight fecal samples with Ad particles positive by EM were serotyped by the ELISA using monoclonal antibodies. Eleven fecal samples were identified as Ad40, 25 as Ad41, 1 as double infection with Ad40 and Ad41, and 4 as non-EAd. These results indicated that Ad41 was more dominant than Ad40 during April, 1986 to January, 1989 in Matsuyama city.

Adenoviruses, Human↗
PubMed1991

Effect of a new quinolone, sparfloxacin, on the pharmacokinetics of theophylline in asthmatic patients.

Recently, it has become evident that some quinolones affect the processing of theophylline in the human system. The effect of a new quinolone, sparfloxacin, on the pharmacokinetics and metabolism of theophylline was investigated in six asthmatic patients receiving chronic theophylline therapy (a sustained-release theophylline tablet formulation of 200 to 300 mg twice daily at 12-h intervals). To these patients, sparfloxacin (200 mg once daily) was coadministered for 1 week. Plasma and urine samples were analyzed by high-performance liquid chromatography for theophylline and its metabolites. Plasma theophylline concentration-time curves and the urinary excretion of theophylline and its major metabolites before and after coadministration of sparfloxacin were compared. The total body clearance of theophylline after coadministration of sparfloxacin, 42.81 +/- 6.64 ml/h/kg (mean +/- standard error of the mean), was not significantly different from that after the administration of theophylline alone, 47.11 +/- 7.61 ml/h/kg. Also, no significant change in the urinary excretion of theophylline and its metabolites was observed for subjects receiving or not receiving sparfloxacin. These findings indicate that a once-daily dose of 200 mg of sparfloxacin has no significant effect on the pharmacokinetics and metabolism of theophylline and that it would be safe to coadminister this quinolone to asthmatic patients receiving chronic theophylline therapy.

4-Quinolones↗
PubMed1991

Changes of plasma concentrations of steroid hormones, prostaglandin F2 alpha-metabolite and pregnant mare serum gonadotropin during pregnancy in thoroughbred mares.

Plasma concentrations of estrogens, gestagens, cortisol (F), 13, 14-dihydro, 15-keto PGF2 alpha (PGFM) and pregnant mare serum gonadotropin (PMSG) in 10 Thoroughbred mares were measured for a 11-month pregnancy period. Estrone (E1) and estradiol-17 beta (E2) levels gradually increased as the pregnancy advanced, showing a peak around Month 8 and decreased thereafter. Progesterone (P) levels increased on Months 3 and 11, and 17 alpha-OH-progesterone (17 alpha-OHP) levels peaked on Month 3, whereas 20 alpha-OH-progesterone (20 alpha-OHP) levels increased sharply after Month 6. PGFM indicated peaks on Months 2 and 11. F and PMSG levels peaked on Months 2 and 3. From factor analysis, Month, E1, E2 and 20 alpha-OHP were discriminated as Factor 1, increasing with the progress of pregnancy, PMSG, 17 alpha-OHP and P as Factor 2, showing a relation with the secondary corpus luteum, and PGFM and F as Factor 3, affecting PGFM change on Month 2 by F. P also related to both Factors 1 and 3, showing an inverse relation against PGFM. In conclusion E1, E2 and 20 alpha-OHP contained in Factor 1 were suggested to be important especially as parameters of placental function after Month 6.

Animals↗
PubMed1991

Erythromycin reduces the severity of bronchial hyperresponsiveness in asthma.

It has been demonstrated that bronchial hyperresponsiveness is a characteristic feature of bronchial asthma, and airway inflammation plays an important role in bronchial hyperresponsiveness. Erythromycin is an antibiotic extensively used worldwide which is also reported to have anti-inflammatory action. This study was designed to clarify whether erythromycin could favorably alter bronchial responsiveness in patients with bronchial asthma. To estimate bronchial responsiveness, histamine challenge was performed in 23 patients with bronchial asthma (atopic type, 11; nonatopic type, 12). All patients were treated for ten weeks with erythromycin, 200 mg three times daily, orally. After ten weeks' treatment, PC20, an index of bronchial sensitivity, was increased significantly. There was no difference between atopic and nonatopic patients in the improvement of PC20. It was concluded that erythromycin reduces the severity of bronchial responsiveness in patients with bronchial asthma.

Adult↗
PubMed1991

Recovery time course of airway hyperresponsiveness to acetylcholine after ovalbumin challenge in guinea pigs.

Sequential changes in airway and adrenergic responsiveness after ovalbumin (OA) challenge were studied in guinea pigs. Airway responsiveness, alpha 1- and beta-adrenoceptor numbers and adenylate cyclase activity was determined after increasing doses of acetylcholine aerosol were administered before, 0, 3, 7, and 14 days after exposure to 2 percent OA or physiologic saline solution for 10 consecutive days. The antiasthmatic agent, azelastine (1 mg/kg/day, intraperitoneal), was administered for 14 days after the tenth exposure to OA in some animals. Airway responsiveness increased significantly after OA exposure, beta-adrenoceptor numbers decreased by 35 percent, and adenylate cyclase activity decreased by 54 percent (p less than 0.01). Values remained significantly different than control animals for 7 days and required 14 days to normalize completely. Azelastine decreased the recovery period to seven days. Azelastine may affect airway responsiveness, at least in part, by increasing beta-adrenergic responsiveness.

Acetylcholine↗
PubMed1991

Studies on vestibulo-spinal reflexes by examination of labyrinthine-evoked EMGs of lower limbs.

Evoked electromyograms (EMGs) induced by galvanic stimulation of the labyrinth were examined in the muscles of the lower limbs. The labyrinthine-evoked EMGs appeared in the muscles of the femoral and gluteal regions and of the legs, and these muscle activities were changed by the head position in spite of the labyrinthine stimulation being the same. The vestibulo-spinal reflexes fulfil these functions in coordination with the neck proprioceptor.

Ear, Inner↗
PubMed1991

[Efficacy and safety of percutaneous endoscopic gastrostomy in the elderly].

Percutaneous endoscopic gastrostomy (PEG) was performed in 32 patients with nasogastric feeding (NGF) or total parenteral nutrition (TPN), who were unable to swallow. Our cases of PEG included 10 with dementia, 8 with cerebral infarction, 8 with cerebral bleeding, 3 with gastric cancer, and others. TPN was performed after PEG for a short time. Because of the combination of TPN and PEG, there was no mortality or major complication related to the procedure. Minor complications included subcutaneous abscess and TPN catheter fever. PEG can be safely and rapidly performed. Furthermore, painless life, better cosmetic features and physical condition can be obtained with this procedure. The majority of the patients are able to return home after PEG. PEG can improve the quality of life of the patients who cannot swallow but have an intact gut.

Abscess↗
PubMed1991

[Clinical analysis of urinary incontinence in the institutionalized elderly].

Urinary incontinence among institutionalized elderly were analyzed from clinical and social viewpoints. The patient group included 25 males and 107 females with an average age of 78 years (ranged from 66 to 92). They had neither highly impaired performance status nor severe dementia. Forty-nine of them (37%) underwent urological examination. Urge incontinence was common among male patients, while urge, stress or mixed incontinence were prevalent in female patients. Thirty-six per cent of the patients had to use pads, diapers and others for their incontinence, while other needed no special protection for their incontinence. Incontinence caused limitation of social activity in 30% of the patients. Many causal factors were assumed for incontinence in elderly; weakness of the pelvic muscles, urinary tract infection, cerebrovascular disorders, neurological disorders and prior pelvic surgery. Prostatic carcinoma or urethral stricture caused overflow incontinence in a few patients. Diuretics or tranquilizers appeared to lead incontinence in some patients. Nine of 18 patients undergoing cystometry had overactive detrusor. Majority of the incontinent elderly showed no intention to visit clinics. Therefore, it recommended to keep staffs in elderly institutions as well as elderly themselves informed that incontinence in the elderly should be treated, which in turn improves the quality of life.

Aged↗