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Biomedical subjects

M Koyama

Publications and source records attributed to M Koyama.

At least 109 records · Page 6Linked to original sources
PubMed1997

Preventative and therapeutic effects of AE0047 on renal injury in stroke-prone spontaneously hypertensive rats.

1. The present study was designed to investigate the preventative and therapeutic effects of AE0047 on renal injury compared with those of nitrendipine in stroke-prone spontaneously hypertensive rats (SHRSP). 2. In the preventative study, drug administration was started before the appearance of renal injury, such as proteinuria. Treatment for 6 weeks with AE0047 (1 and 3 mg/kg, p.o.) led to a dose-related reduction in systolic blood pressure (SBP). Nitrendipine, at doses of 10 and 30 mg/kg, also lowered SBP to a similar degree to that seen with AE0047 at 1 and 3 mg/kg, respectively. 3. In the vehicle-administered SHRSP group, urinary excretion of protein (Uprotein V) increased progressively from 14 weeks of age for another 6 weeks. AE0047 at both doses maintained Uprotein V within normal levels throughout the experimental period. However, the elevation of Uprotein V was only inhibited in the 30 mg/kg nitrendipine-treated group. Urinary N-acetyl-beta-D-glucosaminide (NAG) activity in the vehicle-treated SHRSP group was elevated. Urinary NAG activity remained at a low level only in AE0047-treated groups. 4. Histopathological examination revealed severe lesions (i.e. fibrinoid necrosis, proliferative vasculitis and glomerular lesions) of the kidney in SHRSP. AE0047 treatment at each dose attenuated the development of renal lesions in SHRSP. In contrast, nitrendipine, at 10 mg/kg, was ineffective against the development of renal lesions. Although nitrendipine at 30 mg/kg suppressed the development of renal lesions, this effect was still weaker than that seen with AE0047 at 1 mg/kg. 5. In the therapeutic study, drugs were administered to 17-week-old SHRSP with moderate renal damage for 10 days. Treatment with AE0047 (1 and 3 mg/kg) produced dose-dependent decreases in Uprotein V. In the nitrendipine-treated group, Uprotein V tended to decrease but the changes were not significant. 6. Histopathological studies revealed that 3 mg/kg AE0047 improved renal lesions, such as fibrinoid necrosis, proliferative vasculitis and glomerular lesions, whereas 30 mg/kg nitrendipine did not. 7. Taken together, the results indicate that AE0047 is capable of preventing proteinuria as well as renal lesions, in part via a mechanism independent of its depressor action on SBP. Furthermore, AE0047 improves proteinuria and renal lesions in proteinuria-established SHRSP. Thus, AE0047 may have therapeutic potential in suppressing either the development or the progression of renal disease in hypertensive patients.

Animals↗
PubMed1997

SPECT imaging of normal subjects with technetium-99m-HMPAO and technetium-99m-ECD.

UNLABELLED: Technetium-99m-HMPAO and 99mTc-ECD have been used for regional cerebral blood flow (rCBF) studies using SPECT. However, details of the normal perfusion patterns of these agents still remain to be clarified. HMPAO-SPECT and ECD-SPECT images of normal individuals were investigated using an anatomical standardization technique. METHODS: Twenty healthy subjects participated in this study. In 10 of these, regional cerebral perfusion was measured with HMPAO, and in the other 10, ECD was used. All SPECT images were globally normalized to 50 counts/voxel, and then, each SPECT image was transformed into a standard brain anatomy format with the aid of x-ray CT of each subject and a computerized human brain atlas system (HBA). Mean and s.d. images for each tracer were calculated on a voxel-by-voxel basis. For comparison of these SPECT images with blood flow, rCBF images were generated using PET in a separate group of 10 healthy male subjects during an eyes-closed resting state. The PET images were globally normalized to 50 ml/100 g/min and anatomically standardized using each subject's MRI and the HBA for the SPECT images. RESULTS: In the HMPAO-SPECT images, relatively high radioactivities Were observed in the basal ganglia and cerebellum. In the ECD-SPECT images, high levels were observed in the medial aspect of the occipital lobe. These regions with high radioactivity were not apparent in the rCBF-PET images. CONCLUSION: While both HMPAO and ECD have been used to investigate rCBF, their perfusion patterns differ from rCBF-PET images. This presumably reflects differences in the mechanism of accumulation of each agent in the brain. For clinical diagnoses, these patterns must be taken into consideration.

Adult↗
PubMed1997

[An experiment in a new method of nursing education--the problem-based learning for prenatal nursing].

At the opening of lectures in 1995 on the Science of maternity Nursing in the Special Subjects of Nursing, a problem-based learning was tried as a new educating method in the unit of "Prenatal Nursing." In the present paper, reviewing the introduction/implementation of the method, subjects in the future are described. This process contained two major flows, one was the training of tutors in problem-based learning, including participating the workshop held at McMaster University, and the other was the preparation for the class at the introduction of the new educational method, such as the overall subject composition and the development of teaching materials of prenatal nursing and resources, etc. according to the procedures of the problem-based learning. As the results of the actual implementation, various different reactions in comparison with the lecture method were observed both in tutors and students. As the subjects hereafter, the following three points have been clearly elucidated, that is, in order to proceed the problem-based learning under the present condition that it is not in the comprehensive curriculum, to prevent the overload and conflict in the student learning, considering and adjusting the relationship with contents and methods of concurrent subjects and units, to establish the system for tutorial assessment and evaluation, and to insure tutors and fulfill their training system.

Curriculum↗
PubMed1997

[Efficacy and safety of sulbactam/cefoperazone for hepato-biliary infections].

We studied efficacy and safety of sulbactam/cefoperazone (SBT/CPT) in the treatment of biliary tract infections in hospitalized patients at 26 hospitals from February 1993 to March 1995. Secondary to dropout, 273 out of 338 patients entered in the study were evaluated, 127 patients with cholecystitis, 132 patients with cholangitis, and 14 patients with liver abscesses. Of these, 93 patients (34.1% had malignancy as an underlying disease. SBT/CPZ had an efficacy of 79.9% (218 patients; excellent: 52, good: 166), with the efficacy in patients with cholecystitis, cholangitis and liver abscess at 89.0% (113 patients), 77.3% (102 patients and 21.4% (3 patients), respectively. A significant difference (p < 0.05) was observed in the efficacy rates of patients with (59 patients [63.4%]) and without malignancy (159 patients [88.3%]). A total of 84 strains were isolated from bile specimens of 53 patients, and the major isolates were Escherichia coli, Pseudomonas aeruginosa and Enterococcus spp. Two or more bacterial strains were isolated simultaneously in 20 patients. Mild or moderate side effect (allergic reaction including rash etc.) were noted in 4 patients (1.18%), and laboratory abnormalities (increased GOT, etc.) were in 16 patients (4.71%) out of the total 338 patients. This study clearly demonstrated that SBT/CPZ retains its excellent clinical efficacy and safety profile, throughout its use over the past decade.

Adolescent↗
PubMed1996

High-affinity calcium-binding site in the gama-carboxyglutamic acid domain of bovine factor VII.

The calcium-mediated interaction of factor VIIa with tissue factor is considered to be the primary trigger of blood coagulation. To determine the role of calcium ions in the action of factor VII, we prepared monoclonal antibodies whose binding to factor VII was calcium-dependent. A monoclonal antibody designated C6 strongly inhibited factor VII-induced clotting at a molar ratio of factor VII to antibody of 1:1. The half-maximal binding of factor VII to the C6 antibody was observed at a concentration of calcium ions of 80 microM. Proteolytic fragments of factor VII were assayed for their ability to inhibit competitively the binding of 125I-factor VII to immobilized C6 antibody. The binding was inhibited by increasing amounts of factor VII, by a fragment that contained the gamma-carboxyglutamic acid (Gla) domain linked to first epidermal growth factor-like domain, and by a Gla domain peptide (residues 1-41), over a range of concentration of 10(-9) to 10(-7) M. The antigenic site recognized by the monoclonal antibody C6, which was generated upon the high-affinity binding of calcium ions, was located in the Gla domain. The C6 antibody inhibited the activation of factor X and the amidolytic activity of factor VIIa in the presence of tissue factor. These results demonstrate that a high-affinity calcium-binding site(s) is located in the Gla domain of factor VII, which is concerned with the initiation of tissue factor-mediated blood coagulation by factor VIIa.

1-Carboxyglutamic Acid↗
PubMed1996

Functional anatomy of GO/NO-GO discrimination and response selection--a PET study in man.

The purpose of this study was to identify the functional fields activated in relation to the NO-GO decision. Nine healthy subjects participated in the study which consisted of two test positron emission tomography (PET) scans (GO/NO-GO task and response selection task) and one control scan. In the response selection task, subjects were asked to flex their thumb of the right hand when a light emitting diode (LED) placed 60 cm from their eyes turned on red and to flex their index finger of the right hand when LED turned on green. In the GO/NO-GO task, subjects were asked to flex their thumb when the LED turned on red, however, they were asked not to move their fingers when LED turned on green. In the control state, they were asked simply to look at the LED without any movement of finger during the course of the scan. The mean regional cerebral blood flow (rCBF) change images for each task minus control and task minus task were calculated and fields of significant rCBF changes were identified. Several fields in the prefrontal cortex of the right hemisphere were specifically activated in relation to the GO/NO-GO task. The results indicate that the prefrontal cortex of the right hemisphere may be a key structure to make a decision not to move.

Adult↗
PubMed1996

Topographic representation in human intraparietal sulcus of reaching and saccade.

Regional cerebral blood flow was measured by positron emission tomography in seven subjects during reaching with saccade, reaching without saccade, saccade and control tasks. The reaching with saccade task activated two spatially distinct areas in the contralateral intraparietal sulcus (IPS) compared with the control condition. The area located in the anterior part of the IPS was also activated during the reaching without saccade but not during the saccade task. The other area, located in the posterior part of the IPS was, in contrast, active during the saccade but not the reaching without saccade task. The results indicate that the human IPS is functionally heterogeneous, and that functional roles of its anterior and posterior parts include control of reaching movements and eye movements, respectively.

Adolescent↗
PubMed1996

Changes in regional cerebral blood flow during self-paced arm and finger movements. A PET study.

The purpose of this study was to identify the functional fields activated in relation to the self-paced proximal and distal arm movements. The regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET) and 15O-labelled H2O (H2(15)O) in eight healthy subjects. All subjects performed the following three tasks: (1) repetitive opposition of thumb and index finger of the right hand, (2) repetitive co-contraction of biceps and tricepts brachii muscles of the right arm, and (3) rest. The mean rCBF change images for each task minus control was calculated and fields of significant rCBF changes were identified. Each movement activated different fields in the primary motor area (MI), the dorsal aspect of the premotor area (PMA) and the superior part of the prefrontal area (PFA) of the contralateral hemisphere. In these areas, arm fields were located relatively dorsally to the finger fields. In addition, specific fields in the ventral part of the PMA, the supplementary motor area (SMA), the superior parietal lobule (SPL) of the contralateral hemisphere, and the ipsilateral PFA were consistently activated during both movements. Due to a limited a field of view of the PET scanner in the axial direction, the PET scan could not cover the cerebellum. The results indicate that there may be somatotopical organization not only in the MI but also in the dorsal part of the PMA and the PFA, and that the specific fields in the ventral part of the PMA, the SMA, the SPL, and the PFA may be involved in self-paced movement.

Adult↗
PubMed1996

Deficiency of plasma platelet-activating factor acetylhydrolase: roles of blood cells.

Platelet-activating factor (PAF), a potent mediator of inflammation and circulatory shock, is inactivated by the enzyme PAF acetylhydrolase. Plasma PAF acetylhydrolase deficiency occurs even in healthy subjects. We hypothesized that erythrocyte PAF acetylhydrolase could play a supplementary role in this plasma acetylhydrolase deficiency. We examined 1,030 subjects who participated in mass checkups, and assayed plasma and erythrocyte PAF acetylhydrolase. We also investigated the degradation of exogenous PAF by erythrocytes or other blood cells obtained from subjects who exhibited the plasma enzyme deficiency. The incidence of the plasma enzyme deficiency in this general Japanese population was 4.7% (48/1,030). None of the subjects with the deficiency had a history of allergy, circulatory shock, or chronic inflammatory diseases. The mean values for erythrocyte cytosolic PAF acetylhydrolase activity in the normal and deficient subjects were 0.51 +/- 0.15 (SD) and 0.71 +/- 0.28 nkat (nmol/s)/g protein, respectively, and the difference was significant (P < 0.001, Mann-Whitney U-test). The half-life of 10 nmol/l [3H]PAF in plasma from normal subjects was about 5 min, and the half-life in whole blood or erythrocyte suspension in autologous plasma was almost the same as that in plasma. In plasma from deficient subjects, unchanged PAF virtually remained and the degradation in whole blood or erythrocyte suspension was a little faster than in plasma. We conclude that erythrocytes contribute only little to PAF metabolism in normal blood but they account for almost all of the slow PAF degradation in blood from subjects deficient in plasma PAF acetylhydrolase.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1996

P53 protein expression in pancreatic tumors and its relationship to clinicopathological factors and prognosis.

We examined the expression of p53 protein by immunohistochemical method in a series of pancreatic tumors and evaluated its relationships to the clinicopathological factors and prognosis. The study involved 108 cases of pancreatic tumors (79 ductal carcinomas, 1 acinar cell carcinoma, 14 endocrine tumors, 6 solid cystic tumors, 8 benign ductal tumors) and 8 chronic pancreatitides. Thirty-nine cases of pancreatic ductal carcinoma (49.4%) were positive for p53 protein. Analysis of the Cox hazards model identified p53 positivity and stage at the initial operation as an independent prognostic factor. Patients with p53 positive ductal carcinomas had a greater risk of death compared to p53 negative cases (P < 0.05). There was, however, no statistically significant correlation between p53 protein expression and other clinicopathological factors. Cases of stage III and IVb with positive p53 showed a bleak prognosis compared to p53 negative cases (P < 0.05). Our results suggest that p53 expression is common in invasive pancreatic ductal carcinomas and may have a prognostic value.

Adult↗
PubMed1996

A simple method for the quantification of benzodiazepine receptors using iodine-123 iomazenil and single-photon emission tomography.

Iodine-123 iomazenil (Iomazenil) is a ligand for central type benzodiazepine receptors that is suitable for single-photon emission tomography (SPET). The purpose of this study was to develop a simple method for the quantification of its binding potential (BP). The method is based on a two-compartment model (K1, influx rate constant; k2', efflux rate constant; VT' (=K1/k2'), the total distribution volumes relative to the total arterial tracer concentration), and requires two SPET scans and one blood sampling. For a given input function, the radioactivity ratio of the early to delayed scans can be considered to tabulate as a function of k2', and a table look-up procedure provides the corresponding k2' value, from which K1 and VT' values are then calculated. The arterial input function is obtained by calibration of the standard input function by the single blood sampling. SPET studies were performed on 14 patients with cerebrovascular diseases, dementia or brain tumours (mean age+/-SD, 56.0+/-12.2). None of the patients had any heart, renal or liver disease. A dynamic SPET scan was performed following intravenous bolus injection of Iomazenil. A static SPET scan was performed at 180 min after injection. Frequent blood sampling from the brachial artery was performed on all subjects for determination of the arterial input function. Two-compartment model analysis was validated for calculation of the VT' value of Iomazenil. Good correlations were observed between VT' values calculated by three-compartment model analysis and those calculated by the present method, in which the scan time combinations (early scan/delayed scan) used were 15/180 min, 30/180 min or 45/180 min (all combinations: r=0.92), supporting the validity of this method. The present method is simple and applicable for clinical use.

Brain↗
PubMed1996

Internal thoracic artery holder for coronary artery bypass grafting.

An arterial graft holder was designed to facilitate coronary artery bypass grafting using arterial conduits. It is possible to open the heel of the arterial conduit and stitch the most difficult angle of the anastomosis under optimal visualization. This internal thoracic artery holder is atraumatic and protects the arterial conduit wall from crush injuries caused by vascular forceps. Anastomosis without the endothelial injury may provide long-term patency of the coronary artery bypass graft.

Anastomosis, Surgical↗
PubMed1996

Intraoperative implantation of percutaneous left ventricular assist system.

The percutaneous left ventricular assist system, using modified Dennis technique, has been used successfully to treat patients experiencing severe cardiogenic shock in a variety of nonsurgical situations. Fluoroscopy is generally essential for implantation. Our experience with the implantation of the percutaneous left ventricular assist system during operations is described here. The percutaneous left ventricular assist system was applied using transesophageal echocardiographic imaging and by leading with the index finger through the right atrium without fluoroscopy.

Aged↗
PubMed1996

Suppression of humoral immunity by monoclonal antibody to CD79b, an invariant component of antigen receptors on B lymphocytes.

CD79b is an invariant component of antigen receptors on B lymphocytes. Previous data have suggested that monoclonal antibody (mAb) to CD79b would introduce negative signals into B lymphocytes and suppress humoral immunity. We tested this hypothesis in this study using in vitro assay systems, and revealed that anti-CD79b mAb effectively suppressed the antibody response to a T-cell dependent antigen. The speculated mechanisms for this immunosuppression were: (i) down-modulation of antigen receptors, (ii) inhibition of B lymphocyte differentiation, and (iii) induction of B lymphocyte unresponsiveness. Of these three, we confirmed that the first two were actually induced by anti-CD79b mAb treatment, whereas the in vitro system could not induce the unresponsiveness of B lymphocytes.

Antibodies, Monoclonal↗
PubMed1996

Signal transduction through mu kappa B-cell receptors expressed on pre-B cells is different from that through B-cell receptors on mature B cells.

We introduced kappa light chain genes into pre-B cells to increase the surface mu HC expression, and established transfectants expressing mature type of B-cell receptors (BCR) on pre-B-cell surfaces. Since the cytoplasmic conformations of the reconstituted BCR and intrinsic pre-B-cell receptor (pre-BCR) are identical, they would be connected with the identical signal transduction pathways in pre-B cells. By using the transfectants, we revealed that the reconstituted BCR on pre-B cells was functionally equivalent to BCR on mature B cells in terms of the induction of intracellular Ca++ mobilization. However, we found that the signal-transduction pathways through BCR on pre-B cells were quantitatively different from those mature B cells in two ways. First, cross-linkage of the reconstituted BCR on pre-B cells induced preferential tyrosine phosphorylation of p120 and p100, which was not observed when BCR on mature B cells was cross-linked. Second, BCR in pre-B cells was physically associated with a larger amount of phosphatidylinositol-3 kinase (PI-3K) than BCR in mature B cells in spite of the fact that both pre-B and B cells expressed a similar amount of PI-3K in cytoplasm. Signals through pre-BCR and BCR are known to cause distinct biological effects in B-cell development. The biochemical features in the downstream of reconstituted BCR on pre-B cells, which we revealed in this study, will be of help in understanding the mechanism of functional differences between pre-BCR and BCR.

B-Lymphocytes↗
PubMed1996

Reduced renal clearance of furancarboxylic acid, a major albumin-bound organic acid, in undialyzed uremic patients.

3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is accumulated in uremic serum as a major albumin-bound organic acid. We determined both serum and urine levels of total CMPF to calculate renal clearance of CMPF in healthy subjects and undialyzed uremic patients. Urinary excretion of CMPF and renal clearance were significantly decreased in the uremic patients. The relative clearance ratios of CMPF to creatinine were as low as 0.43% in healthy subjects and 0.45% in uremic patients, indicating that only the protein-unbound, free form of serum CMPF (about 0.4%) is ultrafiltrated in the glomeruli and then excreted into urine. In conclusion, CMPF is accumulated in uremic serum as a consequence of its reduced renal clearance. Urinary excretion of CMPF may be explained only by glomerular filtration of free CMPF in the blood.

Blood Urea Nitrogen↗