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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 127 records · Page 7Linked to original sources

Carotid arterial distensibility is an important determinant of improvement in autonomic balance after successful coronary angioplasty.

OBJECTIVE: To determine whether arterial distensibility influences improvement of autonomic imbalance after left ventricular wall motion (LVWM) abnormality has been improved by percutaneous transluminal angioplasty (PTCA) in patients with ischemic heart disease (IHD). METHODS AND RESULTS: The following variables were assessed before and 3 months after PTCA in 63 patients with IHD who had a successful PTCA: heart rate variability (standard deviation of all normal R-R intervals [SDNN] measured from 24 h Holter electrocardiograms), baroreceptor sensitivity (determined by the phenylephrine injection method), and carotid artery distensibility (determined by ultrasonography). Abnormalities of LVWM were assessed by cineventriculography. In a multivariate analysis, carotid artery distensibility before PTCA and changes in LVWM abnormality before and after PTCA were independently associated with changes in baroreceptor sensitivity and SDNN (P< 0.05). Patients were divided into two groups: one with impaired and one group with unimpaired initial carotid artery distensibility. After PTCA, LVWM was improved significantly in both groups, but baroreceptor sensitivity and SDNN were improved significantly (respectively from 5.0 +/- 3.3 to 5.9 +/- 3.9 ms/mmHg, P< 0.01 and from 111 +/- 47 to 128 +/- 54 ms, P < 0.01) only in patients with well-preserved carotid artery distensibility. CONCLUSIONS: The beneficial effect of PTCA on autonomic balance was greater in patients with well-preserved carotid artery distensibility than in those with impaired carotid artery distensibility. These results suggest that the pathophysiological state of arterial distensibility may modify the autonomic balance even after myocardial ischemia-related LVWM abnormalities are improved.

Adult↗

Significant increase in prostaglandin E-main urinary metabolite by laxative administration: comparison with ulcerative colitis.

OBJECTIVE: To assess the production of prostaglandin E(2), an important chemical mediator in diarrhea induced by laxative administration, a prostaglandin E-main urinary metabolite (7alpha-hydroxy-5,11-diketotetranor-prosta-1,16-dioic acid, PGE-MUM) was measured in healthy volunteers and compared with the values of patients with ulcerative colitis. METHODS: PGE-MUM was determined by a simplified immunoassay of bicyclic PGE-MUM and analyzed for the influence of laxative administration and active/remission phases of ulcerative colitis. RESULTS: Administration of laxatives induced a significant increase in PGE-MUM in healthy volunteers. A significant elevation was also found in the active as compared with the remission phase of ulcerative colitis. The PGE-MUM levels were significantly correlated with our modified Talstad scores, clinical disease activity indices in ulcerative colitis. It was confirmed by time course studies of individual patients that changes in PGE-MUM correlated well with colitis activity. CONCLUSION: Laxative administration induces production of prostaglandin E(2) as one of the chemical mediators, although its production grade is relatively low as compared with ulcerative colitis in the active phase.

Aged↗

NMR structure of ribonuclease HI from Escherichia coli.

The solution structure of ribonuclease HI (RNase HI) from Escherichia coli (E. coli), a protein of 155 residues, was determined. Three-dimensional nuclear Overhauser enhancement spectroscopy (NOESY) was used to obtain 1,424 distance constraints between individually assigned polypeptide chain hydrogen atoms. Supplemental geometric constraints of 90phi angles and 12chi1 angles, and the distance constraints of 66 hydrogen bonds were experimentally derived. Using the DADAS90 program that calculates structures in dihedral angle space, 15 structures satisfying almost all constraints were obtained. The average root mean square deviation (RMSD) from the mean structure was 0.75 A for backbone atoms. The RMSD for backbone atoms between the representative NMR structure with the smallest constraint violation and crystal structures was within 1.2 A. Although the NMR and crystal structures thus resemble one another, a significant discrepancy was observed in a region termed 'basic protrusion.' The discrepancy observed in NMR experiments is explained by fluctuation in this region.

Amino Acid Sequence↗

Preparation and characterization of two crystalline forms of 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrroli dinyl]benzamide (TKS159).

For 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrrolid inyl]benzamide (TKS159), two polymorphs, forms alpha and beta, were prepared and characterized by means of X-ray powder diffractometry, thermal analysis, infrared spectroscopy and 13C-NMR spectroscopy, both in the solution and solid phases. The X-ray powder diffraction analysis gave different patterns for forms alpha and beta. In the thermogravimetry and differential thermal analysis profiles, form beta exhibited characteristic endo- and exothermic peaks at 112.7 degrees C and 116.2 degrees C, respectively, due to the partial melting-induced phase transition to form alpha without accompanying weight loss, and these were followed by an additional endothermic peak at 138.2 degrees C due to fusion. For form alpha, only an endothermic peak at 137.8 degrees C due to fusion was observed. The IR spectroscopic analyses of forms alpha and beta gave different absorption bands assigned to N-H and O-H stretching, N-H bending, and C=O stretching vibrations. From the data obtained by thermal analysis, form alpha was shown to be thermodynamically more stable than form beta.

Benzamides↗

The scopolamine-induced impairment of spatial cognition parallels the acetylcholine release in the ventral hippocampus in rats.

We investigated the relationship between the induction of spatial cognition impairment in the 8-arm radial maze task and regional changes (ventral hippocampus (VH), dorsal hippocampus, frontal cortex, and basolateral amygdala nucleus) in brain acetylcholine (ACh) release using microdialysis in rats treated with muscarinic (M) receptor antagonists. In a behavioral study, two M1 antagonists, scopolamine (0.5 mg/kg, i.p. and 20 microg, i.c.v.) and pirenzepine (80 microg, i.c.v.), but not an M2 antagonist, AF-DX116 (40-80 microg, i.c.v.), disrupted spatial cognition in the 8-arm radial maze task. In brain microdialysis with Ringer's solution containing 0.1 mM eserine sulfate, scopolamine and AF-DX116, but not pirenzepine, increased ACh release in the VH. Moreover, in the bilateral injection of scopolamine (2 microg/side), the VH and dorsomedial thalamus nucleus were important regions for scopolamine-induced impairment of spatial cognition. A simultaneous determination of the behavioral changes revealed that scopolamine (0.5 mg/kg, i.p.) markedly decreased the ACh contents and also increased the ACh release in all regions tested. Especially, the changes in the ACh release of the VH closely paralleled the induction of the scopolamine-induced impairment of spatial cognition. These results suggest that the blocking balance between M1 and M2 muscarinic receptor in the VH therefore plays a major role in the spatial cognition impairment induced by scopolamine in the 8-arm radial maze task.

Acetylcholine↗

Heterogeneous distribution of thrombomodulin and von Willebrand factor in endothelial cells in the human pulmonary microvessels.

Laser scanning confocal fluorescence microscopy techniques were used to study the localization of von Willebrand factor (vWf; Factor VIII-related antigen) and thrombomodulin (transmembrane receptor for thrombin) in the microvascular endothelial cells in the normal human lung. Tissues were obtained from lobectomy specimens resected for solitary nodules (7 adenocarcinomas and 4 hamartomas) from 11 patients. The plasma membranes of the capillary endothelial cells in the alveolar zones (A-zones) showed red linear fluorescence for thrombomodulin. However, their cytoplasm was mostly unreactive for vWf. The microvessels which were located in the connective tissue (C-zones), including peribronchial, and subpleural areas and large vascular walls, consistently demonstrated band-like green fluorescence for vWf in their cytoplasm, and their plasma membranes usually lacked reactivity for thrombomodulin. Only a limited number of peribronchial capillaries measuring <10 microm in diameter showed a mosaic-like appearance, in which red fluorescence along the plasma membranes was found together with green fluorescence in the subjacent cytoplasm. In the juxtaalveolar (J-zones) microvessels located along the borders between A- and C-zones, and measuring up to 40 microm in diameter, the endothelial cells showed a mosaic-like pattern of distribution of the two antigens. However, the localization of thrombomodulin in the J-zone microvessels was separate and independent from that of vWf. The thrombomodulin-reactive cells were directly connected to the alveolar capillary endothelial cells. Heterogeneous patterns of distribution of thrombomodulin and vWf suggest that topographic differences of endothelial function occur to maintain a balance of coagulation and anticoagulation in the normal human lung.

Adult↗

Expression of hnRNP A2/B1 proteins in human cancer cell lines.

The overexpression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is recently reported informative as a marker of lung cancer for early detection. To examine whether the expression of the proteins is specific for lung cancer, immunological analyses were performed both in lung and non-lung cancer cell lines. In immunostaining and Western blotting, the expression of A2/B1 was observed not only in the lung cancer cells but also in non-lung cancer cells. The expression of hnRNP A2/B1 is not specific for lung cancer and quantitative determination of A2/B1 is required to elucidate their significance in carcinogenesis.

Heterogeneous-Nuclear Ribonucleoprotein Group A-B↗

[A case of complete regression of liver metastases by treatment with Futraful supposition].

The patient was a 57-year-old man abnormalities indicated in examinations by X-ray and ultrasonography in February, 1991. X-ray and endoscopic examination revealed a Borrmann type 3 carcinoma in the posterior wall and lesser curvature of the upper body of the stomach. The liver was swollen to 3 fingerbreadths on the right mid-clavicular line. Multiple liver metastases were revealed by computed tomography (CT). Proximal gastrectomy was done. From March 24, 1991, a Futraful suppository (1,500 mg/day) was given daily. After 4 months, CT showed the reduction and partial disappearance of the low-density areas of the liver. After 2 years and 7 months, CT showed very small low-density areas, which completely disappeared by April, 1998. The patient has had a good quality of life. According to the General Rules for Gastric Cancer Study, the patient belongs to the class of complete response.

Adenocarcinoma↗

Cystometric evaluation of bladder function in non-anesthetized mice with and without bladder outlet obstruction.

PURPOSE: To develop a model for cystometric study of bladder function in the awake mouse, and to characterize urodynamically and immunohistochemically the non-obstructed and infravesically obstructed mouse bladder. MATERIALS AND METHODS: Non-obstructed Balb/CJ mice, and mice with bladder outlet obstruction after surgical, partial ligation of the urethra underwent continuous cystometry as previously described for rats. Bladders were also investigated by immunohistochemistry. RESULTS: During the period of cystometry, reproducible micturition patterns were obtained. Marked differences in the urodynamic parameters between non-obstructed and obstructed mice were revealed. In mice subjected to urethral obstruction, micturition pressure (p <0.05), threshold pressure (p <0.05), bladder capacity (p <0.001), micturition volume (p <0.001), and residual volume (p <0.05) increased significantly. There was no difference in basal pressure or compliance between non-obstructed and obstructed mice. Non-voiding bladder activity was consistently recorded in obstructed mice; both frequency and amplitude increased significantly (p <0.01). Compared with non-obstructed bladders, obstructed bladders showed hypertrophy of the bladder wall and various degrees of "patchy denervation" of the detrusor. When tested in non-obstructed mice capsaicin, prostaglandin E2 (intravesical administration) and apomorphine (subcutaneous administration) induced bladder overactivity. CONCLUSIONS: Continuous cystometry can be reproducibly performed in awake, freely moving non-obstructed mice and mice with bladder outflow obstruction. The changes induced by infravesical obstruction in mice were similar to those previously found in rats. This model may be useful for investigations of genetically modified mice.

Animals↗

[Long-term effects of non-supervised home exercise therapy on quality of life in patients with myocardial infarction].

OBJECTIVES: Improvement in exercise tolerance is an important goal in cardiac rehabilitation, but improvement in quality of life (QOL) must also be considered. Therefore, we planned a non-supervised walking exercise program at home for 1 year in patients in the convalescent phase of myocardial infarction to study the exercise tolerance and QOL. METHODS: Thirty-two patients (mean age 60.3 +/- 10 years, 23 men and 9 women) performed our non-supervised home exercise program in which the exercise prescription was based on the rating of perceived exertion. Before discharge, 1 month and 1 year after discharge, exercise tolerance was measured by the cardiopulmonary treadmill exercise test, and QOL was investigated by questionnaire. RESULTS: Anaerobic threshold increased from 15.8 +/- 3.4 ml/kg/min before discharge to 17.5 +/- 3.0 ml/kg/min 1 month after (p < 0.05) and to 18.3 +/- 3.0 ml/min/kg 1 year after (p < 0.05 vs at discharge), and peak oxygen consumption increased from 22.2 +/- 4.3 to 25.2 +/- 5.1 ml/kg/min (p < 0.05) and to 26.4 +/- 5.2 ml/kg/min (p < 0.05 vs at discharge), respectively. QOL score by questionnaire was maintained in 13 patients (improved in 3, same in 10) and decreased in 19 of 32 patients from discharge to 1 month, and the score was maintained in 18 patients (improved in 13, same in 5) and decreased in 14 of 32 patients from 1 month to 1 year after discharge. CONCLUSIONS: In patients with myocardial infarction in the convalescent phase, our non-supervised home exercise program resulted in improvement in exercise tolerance, but QOL score decreased gradually. Therefore, we should not only prescribe an exercise program, but also must give more psychosocial support to the patients. The reasons for the decreased QOL by cardiac rehabilitation must be further investigated.

Anaerobic Threshold↗

[Clinical training and home therapy in our clinic].

Since 1986, we have practiced clinical training. In this training, the physician trainee acts as the head of our clinic, managing programs including the medical teams for outpatient clinics and home therapy. Our home therapy started in 1975 and successive resident trainees have held conferences, cooperation between hospitals and clinics between clinics, and also held home patient and family parties. In our clinical training, therefore, the resident can effectively gain generalized clinical abilities.

Aged↗

[Clinical characteristics of ventricular tachycardia and ventricular fibrillation in exercise stress testing].

OBJECTIVES: Ventricular tachycardia (VT) and ventricular fibrillation (Vf) induced in exercise stress testing should be treated urgently, although the occurrence of arrhythmia is rare. The conditions for the onset of arrhythmia and the clinical characteristics of VT and Vf patients in exercise stress testing were studied. METHODS: Fifty-nine patients (mean age 54 +/- 17 years, 41 males, 18 females) with VT (succession of 3 or more ventricular premature beats) or Vf induced in exercise stress testing were selected from 7,594 patients with consecutive treadmill stress testing in our hospital from January 1993 to February 1998. RESULTS: The incidence of exercise-induced VT or Vf was 0.8%, and there were no fatal accidents in all tests. Among the 59 patients with exercise-induced VT or Vf, 52 patients had non-sustained VT, 5 had sustained VT, and 2 had Vf. Of the 59 patients, 23 had rhythm or conduction disturbances, 14 had coronary artery disease, 13 had cardiomyopathy, and 9 had valvular heart disease. The VT or Vf incidence in coronary artery disease was 0.2%, and in valvular heart disease was 10.8%. VT or Vf occurred at over 80% of maximum heart rate exercise intensity in 40 patients, including 4 with sustained VT and 2 with Vf, of the 59 patients. Also, in 9 VT patients including the 4 sustained VT patients, VT occurred in the exercise recovery period within 2 min after the exercise. Although VT disappeared spontaneously in 52 non-sustained VT and 3 sustained VT patients, intravenous injection of lidocaine was needed in 2 sustained VT patients and direct current defibrillator was needed in 2 Vf patients. Furthermore, only one non-cardiac death was observed in the follow-up period of average 42 months. CONCLUSIONS: Our results showed clinical characteristics and incidence of VT or Vf similar to past reports. Furthermore, all sustained VT and Vf patients, who should be treated urgently, had a past history of ventricular premature beats or VT. Our data suggest that VT and Vf could occur during the recovery period, especially in patients with documented ventricular tachyarrhythmias when the stress intensity has reached the critical level in the exercise tolerance test.

Aged↗

Isolation and characterization of the distal promoter region of mouse Cbfa1.

Cbfa1 is an essential transcription factor for bone formation, and as such little is known about the region responsible for the transcriptional regulation of this gene. Here we report the determination of the transcription start sites, isolation and partial characterization of distal promoter region of this gene. Three transcription start sites were identified by the 5'-Cap site method, recently invented for rapid examination of the 5'-end of genes of interest. A reporter construct containing 1.8 kb of 5' of transcription start sites had approximately 25-fold more luciferase activity than the promoter-less vector in osteoblastic cell lines. Deletion analysis of the reporter construct demonstrated that the minimal region to express promoter activity lies between bp -168 and -99, taking the most downstream transcription start site as +1. By Northern blot analysis, mRNA expression from the distal promoter was detected in the differentiated osteoblastic cell lines, UMR-106, ROS17/2.8 and MC3T3-E1, but not in cell lines of immature phenotype or originated from other organs. Luciferase activity was strongest in UMR-106 and ROS17/2.8, and weakest in COS-1 and HepG2, which are cell lines originating from other organs, corresponding to the level of mRNA expression. These results demonstrated that the distal promoter region examined here is important for tissue- and cell-type-specific gene expression of Cbfa1.

Animals↗

Prognostic utility of myocardial blood flow assessed by N-13 ammonia positron emission tomography in patients with idiopathic dilated cardiomyopathy.

Previous studies in patients with idiopathic dilated cardiomyopathy (IDC) have suggested that myocardial perfusion is impaired and spatially heterogeneous in such cases. Our objective was to identify any association between an abnormality in myocardial perfusion and the prognosis of patients with IDC. We collected data on N-13 ammonia positron emission tomography (PET) studies performed in 26 patients with IDC (9 nonsurvivors, 17 survivors) and in 8 normal control subjects. Regional myocardial blood flow (rMBF) was quantified using N-13 ammonia positron emission tomography and the Simple flow model. The spatial heterogeneity of myocardial perfusion was assessed by calculating the coefficient of variance of rMBF. Mean rMBF of the survivors was significantly lower (0.54 +/- 0.13 ml/min/g) than that of control subjects (0.66 +/- 0.06 ml/min/g) (p = 0.03 vs control), but did not differ significantly between nonsurvivors (0.58 +/- 0.15 ml/min/g) and control subjects. The coefficient of variance of rMBF was significantly higher in nonsurvivors than in either survivors or control subjects (0.24 +/- 0.08 vs 0.15 +/- 0.08, p = 0.007, and 0.16 +/- 0.05, p = 0.03, respectively). The probability of 3-year survival (Kaplan-Meier method) was 33.0% in subjects whose coefficient of variance of rMBF was above the median compared with 90.0% in subjects whose coefficient of variance of rMBF was below the median (p = 0.01). The probability of 3-year survival did not differ among subjects whose mean rMBF was above versus below the median (61.5% vs 62.9%, respectively). The results suggest that the prognosis of patients with IDC is associated with the spatial heterogeneity of myocardial perfusion, not with initial absolute rMBF.

Adult↗

Transglycosylation of cellobiose by partially purified Trichoderma viride cellulase.

A commercial cellulase from Trichoderma viride was fractionated into three fractions, F1, F2, and F3, in order to investigate transglycosylation activities. Among these fractions, F3, which demonstrated highly hydrolytic activity toward p-nitrophenyl beta-D-glucopyranoside and Avicel, most effectively catalyzed the transglycosylation of cellobiose and converted cellobiose into beta-Glc-(1-->6)-beta-glc-(1-->4)-Glc and beta-Glc-(1-->6)-beta-Glc-(1-->6)-beta-Glc(1-->4)-Glc. The F3 fraction contained the enzyme to catalyze beta-glucosyl transfer toward only the C-6 position of the sugar acceptor, and thus it is expected to be of use for syntheses of functional oligosaccharides.

Carbohydrate Sequence↗