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Biomedical subjects

M Fujiwara

Publications and source records attributed to M Fujiwara.

At least 253 records · Page 14Linked to original sources
PubMed1996

Mutations and oxidative DNA damage in phage M13mp2 exposed to N-nitrosomorpholine plus near-ultraviolet light.

Previously we reported that a direct-acting mutagen can be formed from N-nitrosomorpholine (NMOR) on exposure to near-ultraviolet light (UVA, 320-400 nm). We have now studied the spectrum of mutations caused by NMOR plus UVA. M13mp2 phages suspended in a sodium phosphate buffer were treated with NMOR under UVA irradiation and Escherichia coli NR9099 was then infected with the phage. Mutations induced in the phage DNA lacZ alpha region were analyzed. The majority (approximately 50%) of the induced sequence changes were G to T transversions. This suggested that modifications in guanine residues were responsible for these transversions. We explored the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) in the DNA. When the phage were treated with NMOR plus UVA, 8-oxodG/dG in DNA increased up to 12-fold over the value in untreated control. When a mutM-deficient mutant of E. coli CSH50 was used as the host, the mutation level was higher than that observed with CSH50. We conclude that 8-oxodG may be involved in mutations induced by NMOR plus UVA.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

Severe acute metabolic acidosis and Wernicke's encephalopathy following chemotherapy with 5-fluorouracil and cisplatin: case report and review of the literature.

A 28-year-old woman with inoperable gastric carcinoma was given continuous infusion of 5-fluorouracil (5-FU) and low-dose cisplatin (CDDP) for 4 weeks while receiving intravenous hyperalimentation (IVH). Eleven days after her last treatment, she developed acute diplopia, deafness and gait ataxia, followed by severe confusion. She became markedly acidotic and hypotensive with a systolic blood pressure of 60 mmHg, necessitating intubation, dopamine treatment and hemodialysis for 7 h. She was also given thiamine. Thereafter, her blood pressure stabilized, the acidosis improved, and her deafness, diplopia, and confusion were resolved. This case suggests that FP (5-FU/CDDP) therapy toxicity, manifested as acute metabolic acidosis and Wernicke's encephalopathy, may be associated with IVH and thiamine deficiency.

Acidosis↗
PubMed1996

Different properties of wild type and drug-resistant mutants of human immunodeficiency virus type 1 reverse transcriptase in vitro.

Drug-resistant mutants of human immunodeficiency virus type 1 (HIV-1) emerge during treatment with various reverse transcriptase (RT) inhibitors in vitro and in vivo. However, the virological nature and pathogenic importance of these mutants have not been fully elucidated. In this study, we have examined HIV-1 mutants resistant to 3'-azido-3'-deoxythymidine (AZT) and nonnucleoside RT inhibitors (NNRTIs) for their infectivity, RT activity, and replication in MT-4 cells. Although the infectivity of AZT- and NNRTI-resistant mutants was similar, the RT activity of AZT-resistant mutants was much higher than that of NNRTI-resistant mutants and their wild types. Furthermore, the RT activity of NNRTI-resistant mutants was significantly lower than that of the wild types. In contrast, the replication of NNRTI-resistant mutants was found to be greater than that of AZT-resistant mutants and the wild types. When HIV-1 proviral DNA (cDNA) synthesis was examined by PCR in MT-4 cells infected with the wild type, AZT-resistant mutant, or NNRTI-resistant mutant, the PCR signal of the NNRTI-resistant mutant was found to be much higher than those of the wild type and AZT-resistant mutant. These results suggest that the drug-resistant mutants differ from their corresponding wild types not only in drug sensitivity but also in other virological properties.

Antiviral Agents↗
PubMed1996

Long-term follow up of abdominal aortic aneurysm complicating Kawasaki disease: comparison of the effectiveness of different imaging methods.

A 2 month old boy with Kawasaki disease developed the rare complication of abdominal aortic aneurysm (AAA). He was followed up over 7 years by ultrasonography (2D-ECHO) with and without Doppler flow evaluation, angiography and computed tomography. Calcification was noted 33 months after the onset of the disease but the aneurysm did not decrease in size. 2D-ECHO was adequate for evaluating the size of an aneurysm, but did not show thrombus formation or calcification. Doppler flow studies did not show abnormally high blood flow velocities either at the inflow or outlet of aneurysms, which are indicative of stenosis. On the other hand an abdominal aortogram provided information regarding the luminal shape and abnormalities in flow pattern suggestive of thrombus formation. Fluoroscopy cannot demonstrate calcification in the early stages. Computed tomography (CT) was the imaging method of choice for the evaluation of obstructive or calcific changes; an organizing thrombus was clearly demonstrated and early detection of calcification was possible.

Aortic Aneurysm, Abdominal↗
PubMed1996

Mechanism of selective inhibition of human immunodeficiency virus by ingenol triacetate.

Ingenol 3,5,20-triacetate (ITA), one of the ingenol derivatives, is a selective inhibitor of human immunodeficiency virus (HIV) replication in vitro. ITA inhibited the replication of HIV strains in MT-4 cells at concentrations of 0.051 to 0.65 microM. This concentration was approximately 10(3)-fold lower than its cytotoxic threshold. The mechanism of action of ITA is primarily attributed to the inhibition of viral adsorption to the host cells, but it is distinct from the mechanism of inhibition by other adsorption inhibitors.

Antiviral Agents↗
PubMed1996

Hypertriglyceridemia and fatty liver of fasting rats after administration of emeriamine.

The effect of emeriamine, a potent inhibitor of the entry of fatty acids into mitochondria on lipid metabolism, was examined. Emeriamine (10 mg/kg body weight) was orally administered to rats under the two different physiological conditions of a 2-day fast or refeeding with a high-carbohydrate diet after a 2-day fast. When rats were refed with a high-carbohydrate diet, serum and hepatic ketone bodies and the levels of free fatty acids decreased, and triglycerides significantly increased compared with fasting rats. However, no significant effect of emeriamine on serum and hepatic lipids was observed between two refeeding groups with or without emeriamine. Conversely, when emeriamine was administered to fasting rats, the levels of serum and hepatic triglycerides increased about 11- and 5-fold, respectively. However, the increased level of hepatic triglycerides was not accompanied by the activities of fatty acid synthetase and NADPH-generating enzymes. The analysis of serum lipoprotein revealed that very low-density lipoprotein consisted of triglyceride-rich particles and there were less apolipoproteins in the fasting rat given emeriamine. We also determined the 120-kDA protein content, which was probably dependent on lipogenesis. The level of 120-kDa protein was greatly increased with or without the administration of emeriamine after refeeding with a high-carbohydrate diet, but the concentration of 120-kDa protein was slight in the fasting rat with emeriamine. These results suggest that specific inhibition of fatty acid oxidation by emeriamine diverted the exogenous fatty acid to the esterification pathway, and induced fatty liver and hypertriglyceridemia under fasting conditions.

Animals↗
PubMed1996

Effects of refeeding diets on emeriamine-induced fatty liver in fasting rats.

We recently reported that fatty liver and hypertriglyceridemia are easily induced by the administration of an inhibitor of fatty acid oxidation (emeriamine; (R)-3-amino-4-trimethylaminobutyric acid) to fasting rats, and that these conditions are not accompanied by the increased de novo synthesis of fatty acid [J. Nutr. Sci. Vitaminol., 42, 111-120, (1996)]. To study whether emeriamine-induced fatty liver is affected by nutrients during recovery from fatty acid oxidation inhibition, we fed rats with either a high-carbohydrate (HCHO) diet or a high-fat (HFAT) diet. Rats fed an HCHO diet following the administration of emeriamine showed a marked decrease in serum and hepatic triglycerides, and a marked increase in hepatic glycogen. The lower levels of serum and hepatic triglycerides were accompanied by decreased activities of the NADPH-generating enzymes such as malic enzyme and glucose-6-phosphate dehydrogenase. By contrast, rats fed an HFAT diet showed less significant changes in hepatic triglyceride and glycogen levels. These results suggest a reciprocal relationship between the triglyceride level and glycogen accumulation caused by HCHO diet during recovery from emeriamine.

Animals↗
PubMed1996

[Evaluation of the clinical usefulness of super dynamic 99mTc-HM-PAO SPECT in ischemic cerebrovascular disease--detection of hypo- and hyperperfusion area].

The purpose of this study is to assess the clinical usefulness of super dynamic SPECT of 99mTc-HM-PAO. Six patients with unilateral occlusion of middle cerebral artery (MCA) or internal carotid artery (ICA) in the chronic phase, and 5 patients with subacute cerebral infarction were studied. We used a ring-type SPECT "HEADTOME." Two types of collimator were used: a high sensitivity (HS) collimator for super dynamic scan and a high resolution (HR) collimator for static scan. First, the intravenous constant infusion of 99mTc-HM-PAO (925-1480 MBq) for 1 minute was started. After 30 seconds from the beginning of the injection, we performed the 12 seconds/frame super dynamic SPECT for 2 minutes. Then, the static SPECT for 10 minutes was done. For semiquantitative analyses, differential percentage of regional activity between affected and non-affected hemispheres was calculated in the 6th frame image of super dynamic SPECT and static SPECT image. In all 6 patients with unilateral occlusion of MCA and ICA, super dynamic SPECT images showed the better contrast of low perfusion areas in comparison with the static SPECT images. In 5 patients with subacute cerebral infarction who showed focal hyperactivities on static SPECT, focal hyperactivities (hyperperfusion or hyperemia) were displayed in 3 cases, whereas, focal hypo- or isoactivities (hypo- or isoperfusion) were shown in 2 cases on super dynamic SPECT. However, all patients with subacute cerebral infarction showed hyperfixation on static SPECT as compared with super dynamic SPECT. Although the image quality on super dynamic SPECT is not as high as that on static SPECT, cerebral hemodynamics would be detected with less backdiffusion of 99mTc-HM-PAO from the brain to blood, and with less accumulation of hydrophilic components in subacute infarct region. In conclusion, super dynamic SPECT in early distribution of 99mTc-HM-PAO using dedicated SPECT device might be helpful to detect cerebral perfusion close to true cerebral blood flow distribution.

Aged↗
PubMed1996

[Postoperative sore throat--a comparison of standard cuff, gas-barrier cuff and Brandt anesthesia tube cuff].

Excessive intracuff pressure due to nitrous oxide diffusion into the cuff can damage the tracheal mucosa. Several endotracheal tubes have been developed (Trachelon gas barrier type tube, Brandt Anaesthesia tube) to limit nitrous oxide-related intracuff pressure increase. We investigated whether the incidence of postoperative sore throat could be reduced by using these tubes. Endotracheal intubation was performed in 37 adult female patients with either a standard tube (group S, n = 14), a gas barrier type tube (group G, n = 11), or a Brandt tube (group B, n = 12). All patients were interviewed 16-30 h postoperatively by anesthesiologist who did not know which tube had been used. The increase of intracuff pressure was significantly lower in group G (7.6 +/- 5.1 mmHg, mean +/- SD) and in group B (3.4 +/- 1.7 mmHg) than that in group S (24.0 +/- 9.5 mmHg). The incidence of postoperative sore throat was not significantly different among the groups, 36% (5/14) in group S, 45% (5/11) in group G, and 33% (4/12) in Group B. This incidence did not correlate with intracuff pressure increase. In conclusion, specially manufactured endotracheal tubes to limit excessive intracuff pressure did not effectively attenuate the incidence of postoperative sore throat in this patient population.

Adult↗
PubMed1996

[A patient with clinically de novo Ph-positive acute lymphoblastic leukemia had Ph chromosome in all metaphases at the time of hematological remission].

A 58-year-old man was referred to our hospital because of his refractory leukemia. Laboratory examinations showed mild anemia and leukocytosis but no blast was seen in the blood. The patient's bone marrow was hyperplastic and 64.8% of marrow cells were lymphoblastoid cells. They were positive for CD10, CD19, CD34 and HLA-DR antigen. Cytogenetic analysis revealed the Ph chromosome in 17 of 20 metaphases. A Southern blot analysis demonstrated no rearrangement of M-BCR gene. A diagnosis of Ph-positive ALL was made. The patient received chemotherapy and reached a complete remission. At that time, however, his marrow cells had Ph chromosome in 7 of 7 metaphases and rearrangement of m-BCR was positive in PCR analysis. He died of septic shock during the intensive consolidation therapy. Clinically this patient seems to have de novo Ph-positive ALL though his marrow cells had Ph chromosome in all metaphases at the time of complete remission. Recently the rare cases of Ph-positive CML with an m-BCR breakpoint are reported in the literature. This patient may have such a type of CML in blastic phase.

Blast Crisis↗
PubMed1995

Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma. A study of surgical cases among Japanese, and white and African Americans.

BACKGROUND: An association between lymphocytic thyroiditis and thyroid papillary carcinoma is still controversial. To determine a definite statistical relation, a histopathologic study was performed on tissues from in three races, because there is a racial and age-related difference in the susceptibility to thyroiditis. METHODS: The prevalence and severity of thyroiditis combined with adenomatous goiter, follicular adenoma, or papillary carcinoma was defined by examination of surgically resected materials from Japanese (626 patients), and white and African Americans (330 and 90 patients, respectively). RESULTS: The prevalence of lymphocytic infiltrates, which are indicative of autoimmune thyroiditis, was significantly higher in patients with papillary carcinoma than in patients with adenomatous goiter or follicular adenoma among Japanese females (63.0%) and males (50.0%), white females (76.0%), and African American females (46.2%). Lymphocyte infiltration into the follicular adenoma or papillary carcinoma correlated with the severity of combined thyroiditis. CONCLUSION: An association between chronic lymphocytic thyroiditis and papillary carcinoma was confirmed in the Japanese, and white and African American populations. The possibility of autoimmune thyroiditis as a predisposing factor for papillary thyroid carcinoma, is suggested.

Adenoma↗
PubMed1995

Flow cytometric analysis of the DNA content of adenocarcinoma of the lung, especially for patients with stage 1 disease with long term follow-up.

BACKGROUND: To assess the prognostic value of DNA ploidy in adenocarcinoma of the lung, the authors performed a flow cytometric study using paraffin embedded archival material from 160 patients (109 [68%] with aneuploid lesions, 51 [32%] with diploid lesions) who underwent surgical resection from 1982 to 1991. METHODS: The proportion of DNA aneuploid tumors increased as the disease stage advanced, from 35 of 63 (55.5%) with Stage 1 disease to 15 of 20 (75.0%) with Stage 2 disease, to 40 of 53 (75.5%) with Stage 3a disease, to 19 of 24 (79.2%) with Stage 3b disease. However, this trend was not statistically significant. Comparison of the survival time of the 160 patients with adenocarcinoma of the lung with a median follow-up of 7.8 years revealed that patients with diploid tumors had significantly longer survival than did those with aneuploid tumors (P < 0.01). RESULTS: Examination by stage showed that patients with Stage 1 disease with diploid tumors had significantly longer survival times than did those with aneuploid tumors (P < 0.05) but that there were no significant differences in clinical outcome in patients with Stage 2, 3a, and 3b diploid tumors. CONCLUSIONS: Analysis of aneuploid versus diploid DNA content in patients with Stage 1 adenocarcinoma of the lung is concluded to be useful in evaluating clinical outcome and prognosis.

Adenocarcinoma↗
PubMed1995

Preoperative intra-aortic ultrasonography to determine resectability in advanced oesophageal cancer.

This study was designed to evaluate the effectiveness of intra-aortic ultrasonography in the preoperative diagnosis of aortic wall invasion by oesophageal cancer. Twenty-four patients with advanced oesophageal cancer underwent the procedure, and aortic invasion was found in seven. In three of these seven patients, the invasion was diagnosed to be limited to the aortic adventitia, enabling preoperative prediction of the resectability of the tumour. The contact angle of the tumour in relation to the descending aorta was more than 90 degrees in six patients, and aortic invasion to all layers was visualized in four by intra-aortic ultrasonography. On the other hand, aortic invasion to the adventitia was found in three of 14 patients in whom the contact angle was less than 90 degrees. Intra-aortic ultrasonography provides important information to help determine the resectability of advanced oesophageal cancer.

Adult↗
PubMed1995

Olfactory disturbances caused by the anti-cancer drug tegafur.

Olfactory disturbances induced by the anti-cancer drug tegafur were studied in separate clinical and experimental investigations. Five patients with olfactory dysfunction after tegafur were studied and were found to have normal endoscopic findings of the olfactory cleft mucosa. The average period for drug administration was 22 months. Recovery from the olfactory disturbance was poor and biopsy of the olfactory mucosa revealed severely degenerated epithelium. In experimental studies in a guinea pig animal model, effects of oral tegafur on mitotic cells in the olfactory epithelium were examined using bromodeoxyuridine (BrdU) uptake as index. At the conclusion of 3 weeks' treatment, no pronounced morphological changes were seen, but the number of BrdU-incorporating cells decreased in proportion to the dose of tegafur used. Following long-term administration of tegafur 18 months, mitotic cells reacting to BrdU or proliferating cell nuclear antigen had virtually disappeared, indicating persistent inhibition of mitotic cell activity. Morphological changes present included decreased olfactory cell numbers, loss of cells in areas just above basal cells and degeneration of the mucous layer.

Adult↗