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Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 595 records · Page 33Linked to original sources
PubMed1996

Long-term acceptance of major histocompatibility complex-mismatched cardiac allograft induced by a low dose of CTLA4IgM plus FK506.

The immunosuppressant FK506 prolongs allograft survival. However, at therapeutic doses it has significant side effects. A fusion protein consisting of the extracellular portion of CTLA4 and the Fc portion of human IgG (CTLA4IgG) also prolongs allograft survival, but large doses of CTLA4IgG are required for the induction of cardiac allograft acceptance. Therefore, we constructed a pentameric form of a new CTLA4 fusion protein, CTLA4IgM. We tested whether low doses of CTLA4IgG or CTLA4IgM in combination with subtherapeutic doses of FK506 can prolong allograft survival in a synergistic fashion. C57BL/6 (H-2b) neonatal hearts were transplanted to CBA/J (H-2b) mice in a heterotopic, nonvascularized cardiac allograft model. The findings demonstrate that a combination of low doses of FK506 plus a pentameric form of CTLA4Ig, CTLA4IgM, leads to significant graft survival, while a combination of FK506 plus CTLA4IgG does not.

Abatacept↗
PubMed1996

Aortic intimal sarcoma with acute myocardial infarction.

An autopsy case of aortic sarcoma who died of acute myocardial infarction caused by coronary involvement is reported. The patient was a 54 year old woman who was admitted because of an undiagnosed fever and general fatigue of 6 months duration. Magnetic resonance imaging (MRI) showed a tumor in the aortic arch. Total aortic arch replacement was performed. It was diagnosed as a malignant mesenchymal tumor of the aorta. The patient died of acute myocardial infarction 10 months after the operation. At autopsy, the tumor had invaded the luminal surface and intima of the proximal anastomosis (the remnant ascending aorta and the graft), the aortic valves, the distal anastomosis (surgical line of the thoracic aorta plus the graft), and the coronary arteries. The left main coronary artery showed complete obstruction by fibrin thrombus with tumor invasion in the intima, which was responsible for acute myocardial infarction. Primitive and bizarre tumor cells proliferated with many slit-like tissue spaces. Most of the tumor except for its luminal surface showed necrosis. Ultrastructurally, there were spaces between tumor cells, suggesting lumen formation, and some of them had microvilli. This sarcoma was considered to be the so-called aortic intimal sarcoma.

Aortic Diseases↗
PubMed1996

Phantom gastric mucosa for evaluating computed radiography in double-constrast upper gastrointestinal examinations.

PURPOSE: To test the clinical usefulness of computed radiography (CR) with a storage phosphor plate in upper gastrointestinal radiographic examinations, a newly devised phantom gastric mucosa was used. MATERIAL AND METHODS: Simulated small elevated and depressed lesions were created on a phantom gastric mucosa made from a styrofoam "plate". Twenty-four sets of each CR and screen-film radiographs (SR) were obtained using phototimed exposures. Receiver operating characteristic (ROC) study and visual ranking using these images were performed. RESULTS: There was no significant difference between the ROC curves of CR and SR. By visual ranking, CR was equal to or better than SR in most cases. In no case was SR definitely superior to CR. CONCLUSION: CR can be safely applied to upper gastrointestinal roentgenologic examinations.

Gastric Mucosa↗
PubMed1996

Discrete characteristics of antibodies raised against thyrotropin receptor-related peptides whose sequences are not conserved in the luteinizing hormone/chorionic gonadotropin receptor.

In order to identify the specific regions in the human TSH receptor for TSAb and thyroid stimulation-blocking antibody (TSBAb), we produced rabbit antibodies raised against several peptides of the extracellular domain of the human TSH receptor, where sequences are not conserved in the LH/CG receptor, and measured the TSAb activity and TSBAb activity of those antibodies using Chinese hamster ovary cells expressing human TSH receptors. Only antisera from rabbits that were immunized with a peptide of amino acid 32-56, including the small insertion near the N-terminal end of the extracellular domain, showed apparent TSAb activities and have been shown to be significantly precipitated by IgG of patients with Graves' disease. TSAb activity positively correlated with the antibody titers against the peptide in those rabbits. In contrast, antisera from rabbits immunized with a peptide of amino acid 352-378, including a part of the large insertion near the C-terminal end of the extracellular domain, showed the obvious TSBAb activities. TSBAb activity also positively correlated with the degree of antibody titers against the peptide in those rabbits. Moreover, this peptide was significantly immunoprecipitated by the IgG from hypothyroid patients who had TSBAb, and the immunoprecipitation of this peptide positively correlated with TSBAb activities. These results suggest that the epitope responsible for TSAb is quite different from that for TSBAb in the extracellular domain of the human TSH receptor.

Amino Acid Sequence↗
PubMed1996

Lysophosphatidylserine enhances exogenous type II phospholipase A2-induced activation of rat serosal mast cells.

We have previously shown that exogenous type II phospholipase A2 (PLA2) alone elicits degranulation of mast cells, including rat serosal mast cells (SMC) and mouse bone marrow-derived mast cells (BMMC). Here we report that lysophosphatidylserine (lysoPS), a co-factor for activation of rodent SMC in response to some tyrosine kinase-coupled agonists, enhanced type II PLA2-elicited histamine release from rat SMC. In contrast, mouse BMMC was insensitive to lysoPS. Our findings demonstrate a novel route for activation of SMC in that type II PLA2 can act as a direct activator of SMC with enhancement by lysoPS, which is generated from membrane phosphatidylserine possibly by the action of the same enzyme.

Animals↗
PubMed1996

[Problems related to organ transplantation as an allocation of scarce medical resources: a review].

The criteria for allocation of medical resources at three different stages which lead to organ transplantation are discussed, along with advantages and disadvantages. When each criterion was examined individually, it was difficult to determine the best criterion for selection of recipients of donated organs in the most ethically desirable fashion. However, when we examined the suggested criteria on the basis of an actual case, the efficacy of transplantation or expected length of the survival years was most often used as a criterion to select the recipients of donated organs. To increase more support for organ transplantation in our society, it is necessary to more fully discuss how scarce donated organs should be allocated to recipients in a fair and equitable manner.

Decision Making↗
PubMed1996

Chronological changes and inter-regional differences in dietary fiber intakes among middle-aged Japanese women.

Dietary fiber intake was estimated by the total food duplicate method, using a computerized system for fiber calculation recently developed by this study group. Collection of food duplicates were conducted twice, once in 1979-83 and then in 1990-95, in 20 sites across Japan. Altogether 294 and 384 nonsmoking, nonhabitually drinking adult women offered the samples, in the first and second survey, respectively. The average intake of total fiber was 20.7 g/day in the first study, and it was 18.7 g/day in the second survey with a significant reduction. Soluble fiber accounted for 18 to 19%, and the reduction was more marked in soluble fiber than in insoluble fiber. There was an inter-regional difference in fiber intake which was more evident in the first survey than in the second; farmers in Okinawa took less soluble, insoluble and total fiber than in Hokkaido and Honshu farmers and also urban residents. Throughout the four groups, the leading fiber sources were vegetables, followed by cereals, fruits and pulse in the decreasing order. Intakes of these foods diminished during the two survey period, and the reduction of fiber from cereals was most evident in Honshu and Okinawa farmers. International comparison showed that the current level of fiber intake in Japan is essentially similar to the levels in Europe and USA, despite the long-term trend of reduction.

Adult↗
PubMed1996

Diffusion of water in rat sciatic nerve measured by 1H pulsed field gradient NMR: compartmentation and anisotropy.

Diffusion of water was measured in rat sciatic nerve at 22.5 +/- 0.5 degrees C using the spinecho pulsed-field gradient sequence. Three effective diffusion coefficients (ca. 1.1, 0.23, and 0.02 x 10(-9) m2/s) were obtained at a diffusion time of 10 ms in fresh nerve and they showed minimal orientation dependency. The extracellular water signal was quenched by 10 mM MnCl2, and 10% of the water signal remained. Two diffusion coefficients of water were now observed at a diffusion time of 10 ms. The faster coefficient (65% of the remaining signal) was 0.8 x 10(9) m2/s when the axis of the nerve fiber was set parallel to the gradient (D0), and was 0.3 x 10(9) m2/s when the axis of the nerve fiber was set perpendicular to the gradient (D90). The values of D90 and D0 decreased when the diffusion time was increased from 3 ms to 50 ms. A cylinder diameter of 5.4 microns was obtained on the assumption of restricted diffusion in a cylindrical geometry. This agrees with the average inner diameter of axons in the rat sciatic nerve. The slower diffusion component (0.02 x 10(-9) m2/s, 35% of the remaining signal) did not show orientation or diffusion time dependency, and may be attributed to the intracellular water of the Schwann cell body.

Animals↗
PubMed1996

Lymphatic transfer of macromolecules after intrapulmonary administration in the presence or absence of various absorption enhancers in rats.

We have developed a new method to evaluate the transfer of macromolecular drugs to intrapulmonary lymph nodes in rats after intrapulmonary administration. The transfer of fluorescein isothiocyanate dextrans (FDs) to the intrapulmonary lymph nodes was markedly higher than that to iliac lymph node, a non-intrapulmonary lymph node. The transfer of FDs to the intrapulmonary lymph nodes increased with increasing their molecular weights and the threshold for a high lymph node-to-blood level ratio (CLN/CP) was between 10 and 20 kDa. The effects of absorption enhancers on the transfer of FDs to intrapulmonary lymph nodes were also examined in rats. Absorption enhancers used in this study were EDTA, sodium glycocholate (Na-GC), mixed micelles (MM), N-lauryl-beta-D-maltopyranoside (LM), sodium caprate (Na-Cap). The transfer of FD-20, FD-40 and FD-70 to intrapulmonary lymph nodes after intrapulmonary administration increased in the presence of LM. In particular, the lymphatic transfer of FD-40 was remarkably increased in the presence of LM. Similarly, Na-GC and MM improved the transfer of FD-40 to intrapulmonary lymph nodes. These results suggest that absorption enhancers such as LM, Na-GC and MM are effective for improving the transfer of macromolecular drugs to intrapulmonary lymph nodes.

Absorption↗
PubMed1996

[Changes in serum lipoprotein (a) levels related to hyperlipidemia during pregnancy--comparing normal pregnancy and toxemia of pregnancy].

In this study, we investigated fluctuations in serum lipoprotein (a) (Lp(a)) levels in normal and toxemic pregnancy. We measured serum total cholesterol (TC), triglyceride (TG), phospholipid (PL), high-density lipoprotein (HDL), apolipoprotein and Lp(a) levels in 33 normal pregnant and 11 toxemic pregnant women at delivery and in 47 normal pregnant women throughout gestation. Lp(a) and apolipoproteins were detected by turbidimetric immunoassay. The levels of serum lipids, HDL and apolipoproteins were all increased in pregnancy. In toxemia of pregnancy, serum TC and PL levels were lower (p < 0.05) and the apolipoprotein C-III level was higher (p < 0.005) than in normal pregnancy. Serum Lp(a) levels increased until the 20th week and reached a value which was 1.5 times higher than at the 10th week. Thereafter Lp(a) levels were constant until the late stage of pregnancy. In contrast, serum TC and TG levels increased steadily throughout gestation. The serum Lp(a) level was 18.1 +/- 27.5mg/dl in normal pregnancy and 17.8 +/- 17.9mg/dl in toxemia of pregnancy. These results revealed changes in serum Lp(a) levels during pregnancy. Further studies will be required to clarify the metabolic control of Lp(a) in pregnancy and the matabolic disorders of lipids and lipoproteins in toxemia of pregnancy.

Adult↗
PubMed1996

[Hemocirculation and metabolism in intraventricular tumors: kinetic analysis of glucose metabolism].

To estimate hemocirculation and proliferating activity of intraventricular tumor, we measured kinetic rate constants (k1, k2, k3) and glucose metabolic rate (kinetic-rCMRGl) using dynamic positron emission tomography (PET), as well as regional cerebral blood flow (rCBF), blood volume (rCBV), oxygen extraction fraction (rOEF), oxygen metabolic rate (rCMRO2) and autoradiographic rCMRGl (arg-rCMRGl), in patients with intraventricular tumor. The subjects included ten patients, five males and five females, aged from 13 to 53 years with a mean age of 32 years old. Eight tumors were located in the lateral ventricle and two extended into the third ventricle through the foramen of Monro. Another two tumors were located in the fourth ventricle. Histological diagnosis was as follows: five cases of central neurocytoma, one subependymal giant cell astrocytoma, one ependymoma, one choroid plexus carcinoma, one subependymoma, and one meningioma. Tumor lesion on the PET images was determined using CT or MRI, which was performed at levels equivalent to those for the PET scans. For quantitative analysis, regions of interest (ROI) on PET images were delineated on the tumor and the contralateral gray matter. Hemocirculation (rCBF, rCBV) of the tumor was similar to or higher than that of the contralateral gray matter, which corresponded to neuroradiological findings of abundant tumor vessels. Oxygen metabolic parameters (rOEF, rCMRO2) were significantly lower than those of the contralateral gray matter. Especially, low rOEF resulted in an excessive blood flow beyond oxygen demand of the tumor. The raised metabolic rate (rCMRO2/rCMRGl), as compared with that of meningiomas or malignant gliomas, suggested aerobic glycolysis. The kinetic rate constants of tracer transport from blood to brain (k1), reverse transport from brain to blood (k2), and phosphorylation (k3) were analyzed according to the three-compartment model of 18F-fluorodeoxyglucose (18FDG). Tumor k1 and k2 values were similar to or higher than those of the contralateral gray matter, suggesting high permeability due to lack of blood-brain barrier and an abundant blood supply. Tumor k3 value, an indicator of hexokinase activity, and kinetic-rCMRGl were lower in six of eight patients. These six patients have been free from tumor recurrence or regrowth, postoperatively. In the other two patients, tumor kinetic-rCMRGl was similar to or higher than that of the contralateral gray matter, suggesting high activity of proliferation. However, one patient received irradiation and has been followed up, and the other received total resection and has shown no recurrence. Functional information concerning intraventricular tumor is obtained by PET analysis, and kinetic analysis of the rate constants is useful for interpreting a detailed metabolic process of glucose, and provides additional information on intraventricular tumor aggressiveness.

Adolescent↗
PubMed1996

[Positron emission tomographic evaluation for frontal hypertrophic cranial pachymeningitis using 11C-methyl-L-methionine].

A case of frontal hypertrophic cranial pachymeningitis was presented with positron emission tomography (PET) using (11C-methyl)-L-methionine (11C-Met). A 55-year-old male developed right hemiparesis after generalized tonic convulsion one month prior to admission. MR images revealed patchy enhancement extending from the dura mater to the cerebral parenchyma surrounding high T2-weighted signal in the left frontal region. Left carotid angiogram showed atresia of the rostral superior sagittal sinus and obliteration of the cortical veins associated with compensatory venous channels coursing in the frontal deep white matter. PET demonstrated high 11C-Met uptake in the area corresponding to the enhancing lesion on the MR images. The ratio of lesion/normal cortex was 1.58 as an indicator of selective uptake in the lesion. The contralateral temporal gray matter was representative of a normal cortex. In contrast, 11C-Met did not accumulate in the frontal white matter where T2-weighted MR images showed abnormal high intensity lesion. This suggested that the frontal white matter lesion was derived from vasogenic edema due to venous infarction. The patient underwent an uneventful exploratory biopsy. The dura mater had proliferated to a thickness of 3.5mm and was tightly adherent to the left middle frontal gyrus. Microscopically, the thickened dura mater where the tracers had accumulated was composed of abundant collagenous fibers together with diffuse infiltration of inflammatory cells, including predominantly lymphocytes, plasma cells, and neutrocytes. The lymphocytes, which proved positive in both UCHL-1 and L26 staining, had no atypism. Histological findings corresponded to hypertrophic pachymeningitis. Met-PET clearly represented viable and infiltrative zones of inflammatory cells. The patient's neurological symptoms and signs gradually improved. Follow-up MR images three months after the surgery showed the enhancing lesion to be diminished and a marked regression of the vasogenic edema. Spatial determination of viable lesions permitting differentiation from biological inactive or vasogenic edema is an important guideline in selecting an appropriate surgical procedure in the diagnosis and treatment of hypertrophic cranial pachymeningitis. Met-PET would appear useful in delineating inflammatory lesions such as hypertrophic cranial pachymeningitis.

Carbon Radioisotopes↗
PubMed1996

[Prognosis of hepatic metastasis from colorectal cancer following arterial infusion chemotherapy--assessment from the percentage of tumor involved area and tumor markers].

Prognosis of hepatic metastasis from colorectal cancer following arterial infusion chemotherapy was studied from the percentage of tumor involved area (PTIA) and tumor markers. The PTIA was calculated by the following formula: sigma S'/ sigma S, with S' as the tumor area and S as the liver area on each CT slice. The PTIA was 0.76 to 31.1%, and the average was 6.84%. As for the correlation between the PTIA and the prognosis, a statistically significant reverse correlation was found in the cases of death (r = -0.455, p < 0.05, n = 22). In the tumor regression effect of NC cases, the 50% survival time was 24.4 months in cases showing a decrease in CEA or CA19-9 and 18.7 months in the cases showing an increase. Prognosis of the former cases was significantly better than that of the latter cases (p < 0.05). Therefore, PTIA and the decrease in CEA or CA19-9 in the cases of hepatic arterial infusion chemotherapy for metastasis from colorectal cancer seemed important factors reflecting prognosis.

Antineoplastic Agents↗
PubMed1996

Effects of the new class I antiarrhythmic agent Ro 22-9194, (2R)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate, on ischemia- and reperfusion-induced arrhythmias in dogs: involvement of thromboxane A2 synthase inhibitory activity.

We investigated the effects of (2R)-2-amino-N-(2,6-dimethylphenyl)-N-[3-(3-pyridyl)propyl]propionamide D-tartrate (Ro 22-9194), a novel class I antiarrhythmic agent, on myocardial ischemia- and reperfusion-induced arrhythmias in dogs. The incidence of ventricular fibrillation induced by reperfusion after a 30-min coronary ligation was significantly reduced by an i.v. infusion of Ro 22-9194 (10 mg/kg for 5 min before and an additional 20 mg/kg for 30 min during coronary ligation: total, 30 mg/kg) from 73% in the vehicle-treated group to 13%. Ro 22-9194 (20 and 30 mg/kg) also dose-dependently reduced the incidence of ventricular arrhythmias, including ventricular tachycardia and ventricular fibrillation, after coronary reperfusion. Other class I antiarrhythmic agents, mexiletine (15 mg/kg) and disopyramide (7.5 mg/kg), did not inhibit the development of ventricular fibrillation. In in vitro studies, Ro 22-9194, but neither mexiletine nor disopyramide (approximately 10(-3) M), inhibited thromboxane A2 synthase and arachidonic acid-induced aggregation of human platelets (IC50: 1.2 x 10(-5) M and 3.4 x 10(-5) M, respectively). Furthermore, Ro 22-9194 (30 mg/kg) attenuated the increase in venous thromboxane B2 concentrations in the local coronary vein during coronary ligation in dogs. A thromboxane A2 synthase inhibitor, OKY-046 (2.5 mg/kg administered for 5 min before coronary ligation) also showed no evident increases in thromboxane B2 concentrations as well as an antifibrillatory effect. Venous 6-keto-prostaglandin F1 alpha concentrations were not affected by either Ro 22-9194 or OKY-046. These results demonstrate that, unlike mexiletine and disopyramide, Ro 22-9194 protects against reperfusion-induced fatal ventricular arrhythmias in dogs. They also suggest that, in addition to the class I antiarrhythmic effect, the thromboxane A2 synthase inhibitory activity may contribute to the antiarrhythmic properties of Ro 22-9194.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

[Analysis of maternal and fetal risk in 594 pregnancies with heart disease].

The purpose of this study was to estimate the risk of heart diseases in pregnancy. A total of 594 patients with heart diseases treated at the National Cardiovascular Center between 1982 and 1993 were evaluated. The heart diseases were classified into eight categories: congenital heart disease with or without pulmonary hypertension (8 cases (1%) and 219 cases (37%), respectively), mitral valve prolapse (38 cases (6%)), valvular heart disease with or without valve replacement (9 cases (2%) and 54 cases (9%), respectively), arrhythmia (222 cases (37%)), cardiomyotitis (15 cases (3%)) and miscellaneous (29 cases (5%)). Maternal risk was estimated from the incidence of maternal mortality and artificial preterm delivery. Maternal death within two years after delivery was observed in 7 cases (1.2%): 4 cases with cardiomyotitis (3 DCM and 1 HCH), 2 cases with heart disease with pulmonary hypertension (1 PPH and 1 PDA), and a single case with valvular heart disease with aortic valve replacement. Artificial preterm delivery was carried out in 32 cases (5.4%), most frequently in cases with congenital heart disease with pulmonary hypertension (6/8, 75%) which follows cardiomyotitis (4/15, 27%) and cases with valvular heart disease with valve replacement (2/9, 22%). Fetal risk was measured by the incidence of fetal death, fetal growth retardation and congential heart disease of the fetus. IUFD because of maternal heart disease was observed in 4 cases: two cases with valvular heart disease with valve replacement, a single case with Marfan's syndrome and a single case with DCM. Fetal growth retardation was observed in 59 cases, most frequently in cases with congenital heart disease with pulmonary hypertension and cases with valvular heart disease with valve replacement (3/8 (38%) and 3/9 (33%), respectively). Neonatal congenital heart disease was found in 8 of 228 neonates (3.5%) whose mothers also had congenital heart disease. It is therefore suggested that intensive medical care be recommended in pregnancies complicated with congenital heart disease with pulmonary hypertension or with valvular heart disease with valve replacement, which increase both maternal and fetal risk, and in pregnancies complicated with cardiomyotitis which significantly increases the maternal risk.

Arrhythmias, Cardiac↗
PubMed1996

Clinical positron emission tomography for brain tumors: comparison of fludeoxyglucose F 18 and L-methyl-11C-methionine.

PURPOSE: To evaluate the differences between fludeoxyglucose F 18 (FDG) and L-methyl-11C-methionine (11C-methionine) as tracers for positron emission tomography (PET) in the evaluation of brain tumors. METHODS: We analyzed 10 patients with histologically verified cerebral glioma or meningioma and 1 patient with a neuroradiologic diagnosis of low-grade glioma by using FDG, 11C-methionine, and PET. We qualitatively and quantitatively evaluated the extent and degree of accumulation of FDG and 11C-methionine in the tumor tissue. RESULTS: Although PET with FDG depicted malignant tumors as a hot spot in all cases, it was not able to delineate the extent of the tumor. Conversely, PET with 11C-methionine outlined the tumors as areas of increased accumulation of 11C-methionine, regardless of the degree of malignancy. CONCLUSION: PET with FDG and with 11C-methionine can play complementary roles in the evaluation of brain tumors.

Blood Glucose↗
PubMed1996

Nephrotoxicity of thioformamide, a proximate toxicant of nephrotoxic thiazoles, in mice depleted of glutathione.

Administration of thioformamide (TFA) (> 2 mmol/kg, sc) in combination with DL-buthionine sulfoximine (BSO) (4 mmol/kg, i.p.), an inhibitor of glutathione (GSH) synthesis, caused kidney injury in male mice. The injury was characterized by tubular necrosis, increases in relative kidney weight and serum urea nitrogen concentration, and a decrease in renal GSH concentration. In contrast to results in male mice, no overt nephrotoxic effects were observed in female mice given TFA in combination with BSO. These features of nephrotoxicity were very similar to those reported for thiabendazole and other nephrotoxic thiazoles in mice depleted of GSH by treatment with BSO; this resemblance supports the suggestion that TFA as a ring cleavage metabolite, or a further metabolite thereof, is responsible for the toxicity of the nephrotoxic thiazoles (Mizutani, T., Yoshida, K., and Kawazoe, S. (1993) Chem. Res. Toxicol. 6, 174-179).

Animals↗