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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 343 records · Page 19Linked to original sources
PubMed1998

Spiro-substituted piperidines as neurokinin receptor antagonists. I. Design and synthesis of (+/-)-N-[2-(3,4-dichlorophenyl)-4-(spiro [isobenzofuran-1(3H),4'piperidin]-1'-yl)butyl]-N-methylbenzamide, YM-35375, as a new lead compound for novel neurokinin receptor antagonists.

Analysis of the structural requirements of compound 1 (SR48968), a potent NK2 receptor antagonist, revealed that the 4-phenyl group of the piperidine is essential for binding with the NK2 receptor and occupies an equatorial position. Energy calculation of a variety of substituted 4-phenyl piperidines revealed that spiro[isobenzofuran-1(3H),4'-piperidine] possesses a conformationally restricted equatorial phenyl group. Our compound 12 (YM-35375) possessing this spiro-substituted piperidine bound to the NK2 receptor with an IC50 value of 84 nM and to the NK1 receptor with an IC50 value of 710 nM. It showed more potent inhibitory activity (ID50 41 micrograms/kg (i.v.)) against [beta-Ala8]-NKA(4-10)-induced bronchoconstriction in guinea pigs than (+/-)-SR48968 (ID50 68 micrograms/kg (i.v.)). YM-35375 may be a new lead compound for novel NK2 receptor antagonists or NK1-NK2 dual antagonists.

Animals↗
PubMed1998

Apoptosis induced by niacin-related compounds in HL-60 cells.

We have investigated whether niacin-related compounds act as inducers of apoptosis in HL-60 cells. In this study, we found that picolinic acid, dipicolinic acid, and isonicotinamide strongly induce apoptosis. After treatments with these compounds, apoptosis started within 4 h and was induced in about 50% of the cells within 8 h. These compounds induced apoptosis at 5-10 mM, but did not at 1 mM. An ICE-like protease inhibitor (Z-Asp-CH2-DCB) completely blocked the apoptosis, but a caspase-1 inhibitor (Ac-YVAD-CHO) and a caspase-3 inhibitor (Ac-DEVD-CHO) did not block the apoptosis, suggesting that other caspases have the critical roles in the execution process of apoptosis induced by niacin-related compounds.

Apoptosis↗
PubMed1998

[Hypoparathyroidism in maintenance dialysis patients (Pts)--a clinical study].

With the recent development of measurement in intact PTH, increases of hypoparathyroidism and adynamic bone disease have been reported in patients on chronic maintenance dialysis. To clarify the frequency of hypoparathyroidism in maintenance dialysis patients, the present study investigates the relationship between the occurrence of hypoparathyroidism and clinical background, several bone metabolic markers and the bone mineral density. We divided 298 maintenance dialysis patients (HD 270, CAPD 28) without parathyroidectomy into 4 groups based on intact PTH. Group A was absolutely hypo (intact PTH < 60 pg/ml), group B was relatively hypo (60 < or = intact PTH < 160), group C was normal (160 < or = intact PTH < 300), and group D was hyperparathyroidic (300 < or = intact PTH). Groups A and B together accounted for 71.8% of the patients. The mean age in groups A and B was higher than in group D (p < 0.05), and the dialysis duration was shorter (p < 0.01). The concentration of 1, 25 (OH)2D was significantly higher in groups A and B than in group D (p < 0.01), and remarkably higher in group A than in group C. The level of Ca, i-P did not differ among the groups. In our investigation of bone metabolic markers, group D was found to have significantly higher Al-p, intact-BGP, and P 1 PC compared with the other 3 groups (p < 0.01), and the concentration of intact BGP was lower in group A than in groups B and C (p < 0.01). The bone mineral density measured by DEXA did not differ among the groups. The results suggest that, due to multiple factors, the actual occurrence of hypoparathyroidism in maintenance dialysis patients is higher than the predicted occurrence.

Alkaline Phosphatase↗
PubMed1998

Is dobutamine-induced sinus node deceleration a marker of significant stenosis of the right coronary artery?

STUDY OBJECTIVES: Sinus node deceleration during exercise is a highly specific marker for significant stenosis of the right coronary artery. Prior studies of dobutamine-induced sinus node deceleration have contained relatively few patients, and the purpose of this study was to determine if sinus node deceleration is an accurate marker of right coronary artery disease in a much larger study population. DESIGN: Dobutamine stress echocardiography was performed in a cohort of patients, and submaximal exercise testing and coronary angiography were performed in most of the patients. SETTING: A university hospital. PATIENTS AND INTERVENTIONS: Dobutamine stress echocardiography was performed in 757 patients, and symptom-limited submaximal treadmill ECG was also performed in 571 of those patients. Sinus node deceleration was defined as a decrease in the heart rate at peak stress compared with that at the previous stage. Coronary angiography was performed in 631 patients, 184 of whom were found to have significant right coronary artery stenosis. MEASUREMENTS AND RESULTS: The prevalence of dobutamine-induced sinus node deceleration (54 [7%] of 757 patients) was significantly higher than that induced during treadmill ECG (3 [0.5%] of 571 patients; p<0.001). The prevalence of inferior ischemia by echocardiography did not differ between patients with dobutamine-induced sinus node deceleration (26%) and those without (30%). There was also no significant difference in the prevalence of right coronary artery stenosis between the two groups (27% vs 29%). The specificity of dobutamine-induced sinus node deceleration for detecting significant stenosis of the right coronary artery (92%) was higher than that of echocardiography (84%; p<0.00), but the positive predictive value was lower (28% vs 64%; p<0.001). CONCLUSIONS: Although sinus node deceleration during dobutamine stress echocardiography is a relatively more common finding, it does not always accompany significant stenosis in the right coronary artery. The mechanism for its induction is postulated to be vagal activation caused by multiple factors.

Adrenergic beta-Agonists↗
PubMed1998

Effect of 4-phenyl-1,3-dithia-2-thioxo-cyclopent-4-ene on liver injury induced by repeated exposure to galactosamine plus carbon tetrachloride in rats.

The protective effects of 1,3-dithia-2-thioxo-cyclopent-4-ene (DT827A),4-phenyl-1,3-dithia-2-thioxo-cyclopent- 4-ene (DT827B) and 4-(4-fluorophenyl)-1,3-dithia-2-thioxo-cyclopent-4-ene (DT827C) on liver injury induced by D-galactosamine plus carbon tetrachloride (D-GalN + CCl4) and that of DT827B on liver injury induced by thioacetamide were studied using male rats. Out of the three DT827 series of compounds, DT827B was more effective on liver injury induced by the combination exposure to D-GalN + CCl4 for 4 weeks, and accordingly the following two experiments were carried out using DT827B only. Twelve-week administration of DT827B at dose levels of 5, 10 and 20 mg/kg/day revealed a therapeutic effect against liver injury induced by D-GalN + CCl4 dose-dependently, and another twelve-week administration of DT827B at the same three dose levels also revealed a therapeutic effect against liver injury induced by thioacetamide dose-dependently. A hepatoprotective potential of DT827B was suggested under the conditions of these studies.

Animals↗
PubMed1998

Evaluation of rat sperm by flow cytometry: simultaneous analysis of sperm count and sperm viability.

In this study, we conducted a simultaneous analysis of sperm count and viability in rats by flow cytometry (FCM). Epididymal fluids were taken from the caudal epididymis of 12 to 13 week-old Sprague-Dawley rats. The fluids were weighed and mixed with Dulbecco's phosphate buffered saline (D-PBS). Propidium iodide, which can stain only dead sperm, was used to distinguish viable and dead sperm. The sperm count and viability analyzed by FCM were 1.28 x 10(6)/mg and 78.0%, respectively. These values were consistent with the corresponding values (1.39 x 10(6)/mg and 81.0%) that were directly determined microscopically in the fluids of the same sample. In addition, when the original mixture containing sperm was diluted two times and four times with D-PBS, or was diluted two times with D-PBS containing only killed sperm, the sperm count and viability determined by FCM also correlated well with the sperm count (r = 0.96, P < 0.01) and sperm motility (r = 0.99, P < 0.01) by direct microscopic observation, respectively. In conclusion, the present flow cytometric analysis would be practical for the simultaneous determination of sperm count and viability in rat epididymal fluids.

Animals↗
PubMed1998

Suppressive effects of antihistaminic and/or anti-PAF agents on passive anaphylactic shock in mice sensitized with allogeneic monoclonal IgE and IgG1 antibodies and hyperimmune serum.

For the immunopharmacological characterization of murine passive anaphylactic shock, the effects of antihistaminics and/or anti-platelet-activating factor (anti-PAF) agents were studied on the shock mediated by allogeneic monoclonal IgE and IgG1 antibodies and hyperimmune serum. IgE antibody-mediated shock was strongly suppressed by cyproheptadine (10 mg/kg, ip) in every strain regardless of the age and sex of the mice and the presence or absence of a shock potentiator. As far as tested with CTS, DS, and B6D2F1 mice, IgE antibody-mediated shock was also suppressed by the other two antihistamines, triprolidine (10 mg/kg, ip) and oxatomide (100 mg/kg, po). This type of shock was not suppressed by an anti-PAF agent, CV-6209 (3.3 mg/kg, iv), when tested on aged CTS mice given no shock potentiator and young DS mice given a potentiator such as Bordetella pertussis organisms or DL-propranolol. IgG1 antibody-mediated shock was also suppressed by cyproheptadine in general except for CTS mice. Suppression in the DL-propranolol-treated DS and C3H/He mice was not very marked on sensitization with undiluted or slightly diluted IgG1 ascites but quite striking on sensitization with properly diluted ascites. In contrast with the effect of cyproheptadine, suppression by CV-6209 was obvious in aged CTS mice but not in young DL-propranolol-treated DS mice. The shock in DL-propranolol-treated DS mice sensitized with undiluted or slightly diluted ascites was completely abolished by the combined use of these two agents. These results suggest that histamine and/or PAF play a major role in IgE antibody- and IgG1 antibody-mediated shock. However, so far as tested in young DS mice, the shock mediated by hyperimmune serum differed in drug susceptibility from that mediated by the monoclonal antibodies. In the absence of shock potentiators, prevention was produced by cyproheptadine in the males which had been sensitized with the 1:4 or 1:8 dilution of the immune serum. In the presence of DL-propranolol, prevention was not produced even by the combined treatment with cyproheptadine and CV-6209. Therefore, it is likely that some mediators other than histamine and PAF, whose release is triggered by antibody isotypes other than IgE and IgG1, play a greater role for the shock mediated by hyperimmune serum than for the shock mediated by IgE or IgG1 antibody, especially in the presence of shock potentiators.

Anaphylaxis↗
PubMed1998

Relapsed acute promyelocytic leukemia previously treated with all-trans retinoic acid: clinical experience with a new synthetic retinoid, Am-80.

All-trans retinoic acid (ATRA), a potent differentiating drug for acute promyelocytic leukemia (APL), induces a high incidence of complete remission (CR) in patients with APL and is now established as a first-line therapy. However, ATRA resistance has become a clinical problem. Patients who relapsed after ATRA-induced CR have had difficulty in obtaining a second CR with ATRA therapy. Although several mechanisms have been postulated, treatment strategies to overcome resistance have not been established. We used a new synthetic retinoid, Am-80, as reinduction therapy for APL relapse after from ATRA-induced CR. Am-80 was several times more potent than ATRA in inducing differentiation in vitro. At a 6 mg/m2 dose, there were 24 evaluable patients; 14 (58%) achieved CR between days 20 and 58 (median, 37 days). Clinical response correlated with the in vitro response to Am-80. Adverse effects included retinoic acid syndrome (n = 1), hyperleukocytosis (n = 1), xerosis (n = 9), cheilitis (n = 8), hypertriglyceridemia (n = 16), and hypercholesterolemia (n = 15). Am-80 is active in APL after relapse from ATRA-induced CR. Further clinical trials are needed to establish strategies to overcome ATRA resistance.

Adult↗
PubMed1998

[Obesity as one of the risk factors for urolithiasis].

BACKGROUND: It is well known that many diseases may be associated with obesity resulting from an energy-rich diet, and that a westernized diet may increase the incidence of urinary stone formation. To evaluate degree of obesity, we investigated body mass index (BMI) in patients with calcium containing upper urinary stones and examined their blood with regard to lipid metabolism. METHODS: Between July 1994 and December 1995, we analyzed 332 fresh renal-stone formers (253 males and 79 females) who visited 7 hospitals located in Ehime prefecture. As a control, 949 residents older than 20 years (387 males and 562 females) of the same prefecture were also examined by the annual Ehime prefecture office report of 1994. Body mass index as degree of obesity, stone-recurrence, blood test and other complicated diseases were examined. RESULTS: In male stone formers the rate of obesity was significantly higher than that of control males (p < 0.001). The differences were seen only in their twenties and fifties. Furthermore, among male stone formers the rate of obesity was significantly higher in recurrent stone formers than in single stone formers (p < 0.05). On the other hand, in female, there was no significant difference in the rate of obesity between stone formers and controls. No difference was seen between recurrent stone formers and single stone formers. In the blood test, there was no differences in the level of calcium, phosphate and uric acid between stone formers and controls. The level of cholesterol and triglyceride in male were significantly higher in controls (p < 0.01) and there was no difference in the level of high density lipoprotein (HDL) between stone formers and controls. Among the stone formers, 48 males (20.0%) and 17 females (21.5%) had other diseases. The rate of complicated diseases was similar to that of controls and no specific diseases in the stone formers were identified. CONCLUSION: Our report suggested that obesity in male should be considered as a risk factor for calcium containing stone formation.

Adult↗
PubMed1998

Stereoselective uptake of an organic anion across the renal basolateral membrane in isolated perfused rat kidney.

To clarify which process in renal secretion is responsible for the stereoselective renal secretion of organic anions, the renal handling of enantiomers of 5-monomethylsulfamoyl-6,7-dichloro-2, 3-dihydrobenzofuran-2-carboxylic acid (MBCA) was studied by the multiple-indicator dilution method, using isolated perfused rat kidney. After bolus injection of (R)-(+)-[14C]MBCA or (S)-(-)-[14C]MBCA into the renal artery, the outflow patterns for the perfusate and the urinary excretion rate profiles were estimated by statistical moment analysis. AUC values and mean transit times in kidney for the MBCA enantiomers indicated that (R)-(+)-MBCA was excreted much more extensively in urine and that it had a higher affinity for renal tissue than did (S)-(-)-MBCA. A significantly larger intrinsic clearance of secretion for (R)-(+)-MBCA attested to the R-(+)-preferential renal secretion. The uptake rate constant across the basolateral membrane, the ratio of the uptake rate constant to the free fraction in the perfusate, and the intracellular distribution volume were significantly larger for (R)-(+)-MBCA than for (S)-(-)-MBCA, indicating that uptake across the basolateral membrane and intracellular distribution were R-(+)-preferential. However, the mean time across renal epithelial cells for secreted molecules, the single-pass mean residence time in renal epithelial cells, and the rate constant for secretion across the brush-border membrane were not significantly different between enantiomers. The simultaneous presence of (R)-(+)-MBCA decreased the intrinsic clearance of secretion, the ratio of the uptake rate constant to the free fraction in the perfusate, and the intracellular distribution volume for (S)-(-)-[14C]MBCA, although the secretion rate constant, the mean time across renal epithelial cells for secreted molecules, and the single-pass mean residence time in renal epithelial cells were not influenced by (R)-(+)-MBCA, confirming that uptake across the basolateral membrane and intracellular distribution were stereoselective processes.

Animals↗
PubMed1998

[A case of intrathoracic chronic expanding hematoma].

A chronic expanding hematoma in the thoracic cavity is very rare and is clinically included in a category of chronic hemorrhagic empyemas as a special type of chronic empyemas in Japan. In this paper, we report a case of this disease. The patient was a 69-year-old female, who was underwent bilateral artificial pneumothorax for pulmonary tuberculosis 35 years ago. On 25. Nov. 1996, she admitted into Nagoya University Hospital for a diagnosis of intrathoracic tumor. On 2. Dec. 1996, we removed the tumor with combined resection of left lower lobe. The tumor was diagnosed pathologically as an intrathoracic chronic expanding hematoma. This disease is benign, but progressive clinically. In progressive case it is dangerous to remove the tumor for a risk of excessive bleeding and hard adhesion to the chest wall. So we think the earlier is a surgical treatment, the better is a management for this disease.

Aged↗
PubMed1998

[Pilot study of relapsed osteosarcoma and brain tumor with ifosfamide, carboplatin and etoposide (ICE therapy)].

Ifosfamide, Carboplatin and Etoposide (ICE) therapy was used to treat 4 patients, 2 with refractory osteosarcoma, and one each with relapsed brain tumor and newly diagnosed brain tumor. ICE therapy was administered in doses of Ifosfamide 1,800 mg/m2 x 5, Carboplatin 400 mg/m2 x 2 and Etoposide 100 mg/m2 x 5. A total of 30 courses were administered. Two cases of osteosarcoma had a stable disease (range, 3-9 months) and 2 cases of brain tumor had a complete response by magnetic resonance imaging. Moderate or severe toxicity evaluated on a per course basis included: neutropenia 83%, thrombocytopenia 93%, fever 30%, hepatotoxicity 3%, and hemorrhagic cystitis 3%. The median time to hematologic recovery was 20 days. ICE therapy is highly effective for the treatment of refractory or recurrent solid tumors with acceptable toxicity.

Adolescent↗
PubMed1998

[A case report: inhaled nitric oxide improves respiratory function in an infant with pulmonary hypertension].

Nitric oxide (NO) was administered to an infant in a near fatal crisis of pulmonary hypertension after total correction of double outlet right ventricle. Inhaled NO of 4 parts per million reduced pulmonary arterial pressure (PAP) and increased tidal volume during pressure limit ventilation. Both respiratory system compliance and resistance were improved with NO inhalation. There was a significant negative correlation between mean PAP and respiratory system compliance. We speculated that a reduction in PAP with NO inhalation resulted in the improvement of respiratory function. He was successfully weaned from mechanical ventilation.

Double Outlet Right Ventricle↗
PubMed1998

[A case of central sleep-apnea syndrome accompanied by bilateral paralysis of the diaphragma after pediatric cardiac surgery].

Sleep-apnea syndrome is a serious problem in respiratory care. Considerable attention has been paid to it, because it sometimes produces severe hypoxia and hypercapnia, and can cause death. We present a case of a six-year-old girl who showed sleep-apnea syndrome. She suffered from bilateral paralysis of the diaphragm after cardiac surgery and had to be managed under mechanical ventilation for three months. When weaning was tried from mechanical ventilation, she frequently showed apnea lasting over 15 seconds at night, and she was diagnosed as having sleep apnea. She was medicated with theophylline to stimulate the so-called respiratory center. Next day she was successfully weaned from mechanical ventilation. After she had been weaned from mechanical ventilation, hypoxia, hypercapnia, and tachycardia were detected by respiratory monitor at night. The respiratory monitor enabled us to identify the clinical appearance of sleep-apnea, and theophylline may have contributed to its improvement.

Cardiac Surgical Procedures↗
PubMed1998

Relationship between disc displacement and morphologic features of skeletal Class III malocclusion.

The present study assessed the relationship between disc displacement and facial morphologic features in 48 patients with skeletal Class III malocclusion. Clinical examination, standardized lateral oblique temporomandibular joint radiographs, and cephalographs were used to investigate this relationship. Disc displacement was evaluated by the presence of joint sounds (clicking and crepitation) or restricted condylar translation at maximal mouth opening. Thirty-two patients with signs of disc displacement were compared with 16 patients without signs of disc displacement. Results showed that patients with signs of disc displacement had a significantly larger gonial angle and/or SN-MP of the mandible. Thus, morphologic features of patients with skeletal Class III malocclusion may represent a risk factor for the development of disc displacement.

Adult↗
PubMed1998

[Evaluation of antibacterial activities of various antibiotics against glucose non-fermentative gram-negative rods other than Pseudomonas aeruginosa].

MICs of piperacillin, sulbactam/cefoperazone, minocycline (MINO), gentamicin, amikacin, flomoxef, ceftazidime, cefozopran, cefsulodin and imipenem were determined, against 189 clinical isolated strains of glucose non-fermentative Gram-negative Rods (NFGNR; Acinetobacter baumannii (44), Alcaligenes faecalis (5), Alcaligenes xylosoxidans (25), Burkholderia cepacia (12), Chryseobacterium indologenes (23), Chryseobacterium meningosepticum (9), Pseudomonas fluorescens (8), Pseudomonas putida (12), Stenotrophomonas maltophilia (51). Most species of these NFGNR show resistance to many antibiotics tested. Among the antibiotics used in this study, the only antibiotic effective against all species of NFGNR tested is MINO. The spectrums of antibacterial activities of various antibiotics determined by MICs may be useful in preliminary test for identification of these NFGNR.

Anti-Bacterial Agents↗
PubMed1998

[Desmoid tumor of the chest wall: a case report].

A 45-year-old man was referred to our hospital for recurrent desmoid tumor of the chest wall. He underwent chest wall resection with reconstruction of Marlex mesh. But we could not resect it enough widely, because the tumor invaded beside left subclavian artery and subclavian vein, brachioflexus. So he had additional radiation therapy (50 gry). The patient is now doing well without recurrence 1 year after the operation.

Fibromatosis, Abdominal↗