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Biomedical subjects

S Sawada

Publications and source records attributed to S Sawada.

At least 181 records · Page 10Linked to original sources
PubMed1995

Noninvasive quantification of regional myocardial flow reserve in patients with coronary atherosclerosis using nitrogen-13 ammonia positron emission tomography. Determination of extent of altered vascular reactivity.

OBJECTIVES: The aim of this study was to evaluate patients with coronary artery disease to 1) determine the relation between flow reserve measured by nitrogen-13 (N-13) ammonia kinetic modeling and stenosis severity assessed by quantitative angiography, and 2) examine whether flow reserve is impaired in regions supplied by vessels without significant angiographic disease. BACKGROUND: With the advent of new therapeutic approaches for coronary disease, an accurate noninvasive approach for absolute quantification of flow and flow reserve is needed to evaluate functional severity and extent of atherosclerosis. Nitrogen-13 ammonia kinetic modeling may permit such evaluation. METHODS: Twenty-seven subjects were classified into three groups: group 1 = 5 young volunteers: group 2 = 7 middle-aged volunteers; and group 3 = 15 patients with coronary artery disease. Dynamic N-13 ammonia positron emission tomographic imaging was performed at rest and during adenosine infusion. A three-compartment model was fit to regional N-13 ammonia kinetic data to determine myocardial flow. Group 3 patients underwent quantitative coronary angiography. RESULTS: The regional blood flow results in patients with coronary disease were classified into four subgroups: no significant detectable disease and mild (50% to 69.9% area stenosis), moderate (70% to 94.9% area stenosis) or severe (95% to 100% area stenosis) coronary disease. Flow reserve was 2.95 +/- 0.65; 2.09 +/- 0.47; 2.02 +/- 0.51; 1.3 +/- 0.32, respectively (p < or = 0.01 except mild vs. moderate). Flow reserve was correlated with percent area stenosis (r = -0.56) and minimal lumen diameter (r = 0.75). In volunteers (groups 1 and 2), flow reserves were greater than in segments without detectable disease in group 3 patients (4.10 +/- 0.71 and 3.79 +/- 0.42, respectively, vs. 2.88 +/- 0.56, p < or = 0.02). CONCLUSIONS: The functional severity of coronary disease measured by N-13 ammonia positron emission tomography varied for a given stenosis but was significantly related to angiographic severity. Among patients with coronary disease, myocardial regions without significant angiographic stenoses displayed reduced flow reserve than did regions in control subjects, indicating that vascular reactivity was more diffusely impaired in group 3 than was suggested by angiography. Noninvasive quantification of myocardial flow reserve using dynamic N-13 ammonia positron emission tomography yields important functional data that permit definition of the extent of disease even when disease is not apparent by angiography.

Adenosine↗
PubMed1995

Neurochemical changes related to ageing in the senescence-accelerated mouse brain and the effect of chronic administration of nimodipine.

The levels of neurotransmitters and related metabolic enzyme activities in the brain of young-adult (3 months old), aged (11 months old) and nimodipine-administered (11 months old) senescence-accelerated mouse (SAM) were compared. Nimodipine, a calcium antagonist, was administered orally for 5 months. Acetylcholine (ACh), serotonin (5-HT) and dopamine (DA) levels all decreased with age but this decrease was attenuated by nimodipine. Choline acetyltransferase and choline esterase activities increased with age, and nimodipine enhanced their activities. Tryptophan hydroxylase activity was not affected by age or nimodipine administration. Monoamine oxidase-A activity increased with age, and was decreased by nimodipine administration. These results suggest that SAM rapidly undergoes neurochemical changes which are considered to be part of the normal aging process, and these changes were attenuated by chronic administration of nimodipine.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Baclofen inhibits GABAergic transmission after treatment with type-specific calcium channel blockers in cultured rat hippocampal neurons.

Effects of the GABAB agonist baclofen on GABAergic transmission were examined before and after treatment with N-type (CgTX) and P-type (AGTX) Ca2+ channel blockers in cultured rat hippocampal neurons. Baclofen reduced GABAergic synaptic currents (IPSCs) without affecting the postsynaptic sensitivity to GABA. The presynaptic inhibition by baclofen was not blocked by Ba2+, a K+ channel blocker. IPSCs were reduced by treatment with either CgTX or AGTX, and completely abolished by treatment with both toxins. Both IPSCs after treatment with CgTX and those after AGTX treatment were similarly reduced by baclofen. The results indicate that both the transmission mediated by AGTX-sensitive Ca2+ channels and that by CgTX-sensitive Ca2+ channels are sensitive to baclofen, suggesting that activation of presynaptic GABAB receptors might inhibit both types of Ca2+ channels contributing to the GABAergic transmission in the hippocampus.

Animals↗
PubMed1995

Analysis of genomic polymorphism among herpes simplex virus type 2 isolates from four areas of Japan and three other countries.

Genomic polymorphism of 307 epidemiologically unrelated strains of herpes simplex virus type 2 (HSV-2) from four areas of Japan and three other countries (Korea, Sweden and the U.S.A.) was analysed by using 16 variable markers selected from 97 restriction endonuclease (RE) sites with five REs. In addition to the 16 markers, 26 rare variable RE sites were found in 307 isolates. Five and four of 16 markers (RE sites) were found to differ in the frequency of isolates with the markers between isolates from Japan and Sweden and between those from Japan and the U.S.A., respectively, suggesting that they are genomically different from each other. In this manner, 307 HSV-2 isolates from four countries could be classified into 68 different genotypes (no. of isolates/no. of genotypes = 4.5). Some isolates from one country or more than two countries at times were classified into the same genotypes, which were referred to as predominant genotypes. The most predominant genotypes for isolates from Japan, Sweden and the U.S.A. were genotypes 30, 26 (32) and 3, respectively, indicating that they are different by the country. In genotypes 1 and 6, the frequency of isolates was found to be significantly different between Japan and Sweden and between Japan and the U.S.A., respectively. Nine out of 16 markers differed in the most genomically distant isolates, each of which was obtained in Sweden and Japan. In addition, high correlation coefficients (r) in the Japanese isolates were detected in different pairs of markers from those in the Swedish isolates, suggesting that isolates from these two countries are evolutionarily distant.

Biological Evolution↗
PubMed1995

Clinical implications of metastases to the ovary.

Predictive factors for ovarian metastases were analyzed in 313 autopsy cases of women dying of malignancy. Genital, hematopoietic, brain tumors, and double primaries were excluded. Ovarian metastases were found in 60 of 313 (19.2%) cases. The primary sites of origin were stomach (18 cases), breast (13), pancreas (7), bile duct (7), large intestine (4), kidney (3), liver (2), lung (1), and other (5). The percentages of ovarian metastasis in each primary site were 50% (3/6) in the kidney, 38.3% (18/47) in the stomach, 30.8% (4/13) in the large intestine, 22.9% (13/57) in the breast, 22.6% (7/31) in the bile duct, 19.4% (7/36) in the pancreas, 5.4% (2/37) in the liver, and 3.4% (1/29) in the lung. Seventy-five percent (75%) of ovaries with metastasis were 5 cm or less in the greatest dimension. Seventy-eight percent (78%) of ovarian metastases were bilateral. Fifty-one percent (51%) of the involved ovaries were cystic. Twenty-four percent (24%) of the metastasis were occult in which microscopic disease was present in normal appearing ovaries. The mean age of death in the cases with ovarian metastasis was 53.8 +/- 16.8 years. This was significantly younger than the mean age without ovarian metastasis that mainly was attributable to the younger ages for breast and bile duct cancer. The number of other extraovarian metastatic sites for positive ovarian cases was significantly greater than for the negative ovarian cases (7.6 +/- 2.4 and 5.8 +/- 2.5, respectively). This difference was dominant in gastric and bile duct cancers. The other metastatic sites that accompanied ovarian metastases were the adrenal gland in gastric cancer, the spleen and small intestine in breast cancer, and the adrenal gland and colon in bile duct cancer. The frequency of peritoneal dissemination was essentially the same between cases with positive and negative ovarian metastasis. Scirrhous adenocarcinoma of the stomach more commonly metastasized to the ovary than any other stomach histological type. These findings suggest that although the impact upon outcome of bilateral salpingo-ophorectomy at the initial operation is unknown, the discovery of ovarian metastases in a large proportion of patients may dramatically alter initial management in patients otherwise thought to have only local disease.

Adolescent↗
PubMed1995

Heat-inducible expression system for a foreign gene in cultured tobacco cells using the HSP18.2 promoter of Arabidopsis thaliana.

A system for the controlled expression of a foreign gene in cultured tobacco cells (Nicotiana tabacum, BY2) by temperature shift was constructed. A 925-base-pair (bp) DNA fragment containing the 5'-flanking region of a low-molecular-mass heat-shock protein gene (HSP18.2) of Arabidopsis thaliana was inserted upstream of the beta-glucuronidase reporter gene (GUS). The resulting HSP18.2-GUS construct was introduced into BY2 cells by electroporation or Agrobacterium-mediated transformation. Transient expression of the HSP18.2 promoter in protoplasts was very low regardless of the heat shock. Although expression of the HSP18.2-GUS chimeric gene in the stable transformants of BY2 was hardly detected in culture at 25 degrees C, the expression increased rapidly on the transcriptional level when the incubation temperature was shifted to 35-37 degrees C. The optimal temperature for heat-shock induction was 37 degrees C. After a 2-h incubation at 37 degrees C, GUS activity was about 1000-fold greater than that before heat shock. The amount of GUS mRNA was maximum 2 h after heat shock, and then decreased gradually.

Agrobacterium tumefaciens↗
PubMed1995

Relationship between responsiveness to colony stimulating factors (CSFs) and surface phenotype of leukemic blasts.

We examined the responsiveness of leukemic cells to colony stimulating factors (CSFs) as determined by 3H-TdR incorporation and surface phenotypes of leukemic blasts. In acute myeloid leukemia (AML), CD13 and/or CD33 positive and HLA-DR negative M1 and M3 cases tended to show high response to G-CSF, GM-CSFs and IL-3, however, all HLA-DR positive M1, M2, M4 and M5 cases were unresponsive to CSFs but showed high autonomous growth. In acute lymphocytic leukemia (ALL), no response was observed to any CSFs but high autonomous growth was found in mixed leukemia cases. Sole T or B lineage cases showed low autonomous growth. These results suggest the varied nature of the proliferative state in leukemia and the existence of a subgroup in M1.

Cell Division↗
PubMed1995

Comparison of autoradiography, liquid scintillation counting and immunoenzymatic staining of 5-bromo-2'-deoxyuridine for measurement of unscheduled DNA synthesis and replicative DNA synthesis in rat liver.

Different methods for evaluating unscheduled DNA synthesis (UDS) and replicative DNA synthesis (RDS) were studied in hepatocytes of F344 rats exposed in vivo to dimethylnitrosamine (DMN) or CCl4. Hepatocytes were isolated and incubated in Williams' medium E supplemented with either [3H]thymidine for autoradiography or 5-bromo-2'-deoxyuridine for immunoenzymatic staining. In the method of liquid scintillation counting, the cells were incubated with [3H]thymidine with or without hydroxyurea. The nuclear fraction was isolated and the incorporation of [3H]thymidine into nuclear DNA was determined by a liquid scintillation counter. DMN at doses of 0.625-5 mg/kg body weight induced UDS of 1.6-37.9 (0 dose; -6.9) net grains/nucleus measured by autoradiography and 337-1377 (0 dose; 177) dpm/microgram DNA in the presence of hydroxyurea measured by a liquid scintillation counter. CCl4 at doses of 50-400 mg/kg body weight induced RDS in 1.5-12.1% (0 dose; 0.12%) and 1.8-14.6% (0 dose; 0.16%) of cells with the methods of autoradiography and immunoenzymatic staining, respectively, and of 2991-24256 (0 dose; 324) dpm/microgram DNA in the absence of hydroxyurea with the method of liquid scintillation counting. Similar dose-dependent induction of UDS and RDS was observed with these methods. These results suggest that the methods of liquid scintillation counting and immunoenzymatic staining have almost the same sensitivity for measuring UDS and RDS as that of autoradiography.

Animals↗
PubMed1995

Reaction of the aortic wall to six metallic stent materials.

RATIONALE AND OBJECTIVES: We investigated the effects of various metallic stents on the aortic wall. METHODS: The wires of Gianturco-type expandable metallic stents were plated with gold, silver, or copper or coated with Teflon or silicone. Stents were inserted into the aortas of 15 adult mongrel dogs. The time course of radiologic, macroscopic, and histologic changes in the aorta at the site of the stent was investigated at 1, 2, and 4 weeks after implantation. RESULTS: The gold-plated stent appeared to produce fewer macroscopic and histopathologic changes in the aorta than the other types of stents. The neointima was thinnest with gold (83.9 +/- 40.3 microns), followed by stainless steel (103.6 +/- 57.0 microns), Teflon (115.0 +/- 30.2 microns), silicone (209.6 +/- 25.9 microns), silver (228.6 +/- 33.8 microns), and copper (unmeasurable). With the copper-plated stent, the aorta suffered severe erosion of the vessel wall, marked thrombus formation, and aortic rupture. CONCLUSION: Gold is a useful intravascular material because it reacts only minimally with the vessel wall.

Animals↗
PubMed1995

Radiation-induced apoptotic cell death in human gastric epithelial tumour cells; correlation between mitotic death and apoptosis.

The mode of cell death in cells undergoing mitotic death after gamma-irradiation was studied in seven human gastric epithelial tumour cell lines and two strains of normal gastric fibroblasts. Apoptotic cells were frequently observed in all tumour lines after irradiation, whereas the two fibroblast strains were quite low in apoptosis frequency. The advent of apoptosis depended on the radiation doses and incubation time. Detailed analysis of one of the carcinoma lines, SH101-P4, revealed that G2-phase arrest was maximum at 12 h postirradiation. The cells began to escape G2 arrest by 24 h. Apoptotic cells began to increase at 12 h postirradiation and became maximal from 72 to 96 h. Apoptosis developed in the G1 phase of the cell cycle subsequent to the irradiation. These results suggest that apoptosis is one of the modes of mitotic death after irradiation.

Adenocarcinoma↗
PubMed1995

TNF-alpha regulates IL-4-induced Fc epsilon RII/CD23 gene expression and soluble Fc epsilon RII release by human monocytes.

We examined the regulatory effects of TNF-alpha on IL-4-induced gene expression of the low-affinity receptor for IgE (Fc epsilon RII/CD23) in human monocytes and IL-4-induced soluble Fc epsilon RII (sFc epsilon RII) release from monocytes. IL-4-induced Fc epsilon RII expression on the surface of monocytes was reduced by TNF-alpha as early as 1 day after culture and the effect of TNF-alpha increased with prolonged culture. The present analysis was designed to examine whether or not TNF-alpha could suppress IL-4-induced Fc epsilon RII mRNA expression and enhanced IL-4-induced sFc epsilon RII release. The addition of TNF-alpha to monocyte cultures with IL-4 significantly reduced Fc epsilon RII expression on the surface of monocytes and significantly increased sFc epsilon RII release from monocytes. Over time, there was an inverse relationship between the disappearance of cell surface Fc epsilon RII and the appearance of sFc epsilon RII in culture supernatants. Fc epsilon RII mRNA expression in monocytes cultured with IL-4 was not affected by TNF-alpha when examined at 6 h after cultivation. When the cells were cultured with TNF-alpha for more than 24 h, however, TNF-alpha down-regulated IL-4-induced Fc epsilon RII mRNA levels. This correlated with the kinetics of down-regulation of IL-4-induced Fc epsilon RII expression on the surface of monocytes by TNF-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Neurofibromatosis 2 and neurilemmomatosis gene are identical.

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder characterized by the occurrence of bilateral acoustic neuromas, as well as meningiomas and schwannomas. The gene locus for NF2 resides on chromosome 22q12 and has been cloned recently. Neurilemmomatosis is characterized by multiple cutaneous and spinal neurilemmomas without other signs of NF1 or NF2. Many cases with this disorder include the diagnosis of neurofibromatosis or other rare diseases unexplained by current nosology. In this study, we analyzed the peripheral leukocytes and tissue from cutaneous neurilemmomas of seven patients with neurilemmomatosis using DNA markers for different regions of chromosome 22. We detected allelic losses in three of seven tumors from seven patients with a probe for the NF2 region of the long arm of chromosome 22 and the germ-line mutations in two of three tumors from the same three patients. Mutations in the NF2 gene were a deletion from at least codon 334 to 579 and G insertion at codon 42. We conclude that the neurilemmomatosis locus lies within the NF2 region and that these diseases might be identical.

Adult↗
PubMed1995

Gianturco stent placement in malignant caval obstruction: analysis of factors for predicting the outcome.

PURPOSE: To determine the factors that may be used to predict outcome of stent placement in patients with malignancies obstructing the superior or inferior vena cava. MATERIALS AND METHODS: Gianturco stents were placed in 39 patients with malignant obstruction of the superior (n = 16) or inferior (n = 23) vena cava. Thirteen patients with obstruction of the superior vena cava received radiation therapy and/or chemotherapy at some time in their course of treatment. Computed tomographic (CT) scans were obtained in all patients. The authors analyzed treatment outcome with the location, length, and CT appearance of obstruction. RESULTS: Venous congestive symptoms disappeared after stent placement in 35 patients and remained in four. Symptoms did not recur during 1-13-month follow-up in 32 of the 35 patients in whom the symptoms disappeared. Nonfatal complications were observed in nine patients. Results of multivariate analysis showed that the outcome of stent placement is best predicted by the appearance of obstructions on CT scans irrespective of the location and length of the lesions. CONCLUSION: Good results can be expected from placement of Gianturco stents except when CT shows the obstruction to be totally enveloped by tumor.

Constriction, Pathologic↗
PubMed1995

Partial purification and characterization of an esterase acting on the anticancer pro-drugs, 7-ethylcamptothecin derivatives.

A hydrolytic enzyme which catalyzes hydrolysis of the ester-linkage of a series of 17-O-acyl derivatives of 7-ethylcamptothecin-21-(2-dimethylamino)ethylamide [acyl derivatives of 22E] was purified from rat liver and its properties were characterized. It hydrolyzed the ester-linkage of all 22E derivatives tested as well as p-nitrophenyl acetate at pH 8-9 but had no effect on 7-ethyl-10-[4-(piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11: irinotecan), unlike CPT-11 converting carboxylesterase, which was previously purified from rat serum [Tsuji T. et al., J. Pharmacobio-Dyn., 14, 341 (1991)]. The enzyme had no effect on either acetyl choline or butyrylcholine. It was inhibited by several organophosphorous compounds such as diisopropyl fluorophosphate (DFP), bis-(p-nitrophenyl)phosphate and paraoxon, but was insensitive to inhibitors specific for choline esterases. These results indicate that this liver esterase is clearly distinct from choline esterase and serum CPT-11 converting enzyme and is able to convert pro-drugs, O-acyl derivatives of 22E, to an antitumor agent.

Animals↗
PubMed1995

Neutron generator at Hiroshima University for use in radiobiology study.

A neutron generator (HIRRAC) for use in radiobiology study has been constructed at the Research Institute for Radiation Biology and Medicine, Hiroshima University (RIRBM). Monoenergetic neutrons of which energy is less than 1.3 MeV are generated by the 7Li(p,n)7 Be reaction at proton energies up to 3 MeV. The protons are accelerated by a Schenkel-type-accelerator and are bombared onto the 7Li-target. An apparatus for the irradiation of biological material such as mice, cultured cells and so on, was designed and will be manufactured. Neutron and gamma-ray dose rates were measured by paired (TE-TE and C-CO2) ionization chambers. Contamination of the gamma ray was less than about 6% when using 10-microns-thick 7Li as a target. Maximum dose rates for the tissue equivalent materials was 40 cGy/min at a distance of 10 cm from the target. Energy distributions of the obtained neutrons have been measured by a 3He-gas proportional counter. The monoenergetic neutrons within an energy region from 0.1 to 1.3 MeV produced by thin 7Li or 7LiF targets had a small energy spread of about 50 keV (1 sigma width of gaussian). The energy spread of neutrons was about 10% or less at an incident proton energy of 2.3 MeV. We found that HIRRAC produces small energy spread neutrons and at sufficient dose rates for use in radiobiology studies.

Animals↗
PubMed1995

Human T-lymphotropic virus type I associated myelopathy treated effectively with lymphocytapheresis using a leukocyte removal filter.

The patient, a 61-year-old woman, received a blood transfusion at the age of 33 years. Weakness of the lower extremities developed at the age of 42 and the diagnosis of human T-lymphotropic virus type I (HTLV-I) associated myelopathy was made. Somatosensory evoked potential examination showed that the latency of P27 evoked by peroneal nerve stimulation was 44 msec. Lymphocytapheresis was performed 3 times with one-week intervals using a leukocyte removal filter. The muscle weakness began to improve on the second day after the second lymphocytapheresis and the sensory impairment began to improve on the third day after the third lymphocytapheresis. The delayed latency of P27 improved after the lymphocytapheresis. The effectiveness of lymphocytapheresis in this case suggests that lymphocytes are involved in the pathogenesis of HTLV-I associated myelopathy.

Evoked Potentials, Somatosensory↗