Biomedical subjects

M Okazaki

Publications and source records attributed to M Okazaki.

At least 163 records · Page 9Linked to original sources

PubMed1998

Kainic acid-induced neuronal loss and glial changes in the hippocampal CA3 of p53-deficient mouse.

We examined kainic acid (KA)-induced neuronal death and changes in glial cells in p53-deficient (p53-/-) and wild-type (p53+/+) mice which were CBA and C57BL/6 background. The p53-/- mouse exhibited a KA-induced loss of CA3 pyramidal neurons similar to that in wild-type mouse. Before neuronal death, c-Jun protein was expressed, phosphorylated and translocated into several nuclei of CA3 pyramidal neurons. In p53-/- mouse, microglial activation was slightly faster and more continuous after 1-7 days than that in p53+/+ mouse. On the other hand, p53-/- astrocytes were relatively resistant to KA cytotoxicity, and marked astrocytosis also occurred after 7 days. These observations suggest that p53-null mutation may influence the activation and proliferation of glial cells rather than neuronal death.

Animals↗

PubMed1998

Soluble fumarate reductase isoenzymes from Saccharomyces cerevisiae are required for anaerobic growth.

In Saccharomyces cerevisiae, the cytosolic and promitochondrial isoenzymes of fumarate reductase are encoded by the FRDS and OSM1 genes, respectively. The product of the OSM1 gene is reported to be required for growth in hypertonic medium. Simultaneous disruption of the FRDS and OSM1 genes resulted in the inability of the yeasts to grow anaerobically on glucose as a carbon source, and disruption of the OSM1 gene caused poor growth under anaerobic conditions. However, the disruption of both the FRDS and/or OSM1 genes had no effect on aerobic growth or growth under hypertonic conditions. These results suggest that the fumarate reductase isoenzymes in Saccharomyces cerevisiae are essential for anaerobic growth but not for growth under hypertonic conditions.

Anaerobiosis↗

PubMed1998

Quantitative detection method of triglycerides in serum lipoproteins and serum-free glycerol by high-performance liquid chromatography.

We have developed a simple and reliable method for quantitative detection of triglycerides (TG) in serum lipoproteins and serum-free glycerol (FG) by high-performance liquid chromatography (HPLC). After separation of serum constituents using a new gel-permeation column (TSK gel Lipopropak XL, Tosoh) and a new eluent (TSK eluent LP-2, Tosoh), TG and FG were detected by on-line reaction using a modified reagent which contained glycerol kinase, glycerol-3-phosphate oxidase and lipoprotein lipase. HPLC patterns showed five peaks corresponding to chylomicrons, very-low-density, low-density, high-density lipoproteins and FG. Absolute concentrations of TG in each lipoprotein fraction and serum FG were calculated from the corresponding peak areas using standard FG as a calibrator. Due to its very high sensitivity of peak detection, this method has become desirable for the analyses of lipoproteins of very low concentrations such as in cell culture systems. This technique will contribute to a better understanding of lipoprotein TG and serum FG distribution in human and nonhuman subjects.

Animals↗

PubMed1998

A syndrome of peripheral blood T-cell infection with Epstein-Barr virus (EBV) followed by EBV-positive T-cell lymphoma.

The role of Epstein-Barr virus (EBV) in the pathogenesis of severe, chronic active EBV infection and its complications is unclear. We investigated two Japanese patients diagnosed with severe, chronic active EBV infection who subsequently developed EBV-positive T-cell lymphoma. The patients displayed abnormally high antibody titers to EBV antigens, and had evidence of peripheral blood CD4(+) T-cell infection with EBV, 19 months and 3 months, respectively, before the diagnosis of EBV-positive T-cell lymphoma. The lymphomas were infected with monoclonal EBV and expressed the EBV latency genes EBNA-1, LMP-1, and LMP-2. Genetic studies showed that the virus detected in the T-cell lymphoma was indistinguishable, with respect to type and previously defined LMP-1 and EBNA-1 gene variations, from virus detected in the peripheral blood T cells 19 months earlier. These studies support an important pathogenetic role of T-cell infection with EBV in chronic active EBV infection and in the EBV-positive T-cell lymphoma that followed.

Antibodies, Viral↗

PubMed1998

Overexpressed mitochondrial hinge protein, a cytochrome c-binding protein, accelerates apoptosis by enhancing the release of cytochrome c from mitochondria.

Holocytochrome c released from mitochondria has been revealed to be one of the contributors of apoptosis. To investigate how the cytochrome c protein is released from mitochondria, we examined the effects of overexpression of the hinge protein, a cytochrome c-binding protein, or cytochrome c on apoptosis by introducing their cDNAs under a constitutive promoter. Overexpression of the cytochrome c and hinge protein mRNAs was confirmed by Northern blotting, although marked accumulation of the cytochrome c protein was not observed. In transfectants of the hinge protein gene as well as cytochrome c gene, apoptosis was accelerated as judged by FITC-conjugated Annexin V binding to the cell surface and DNA fragmentation. In addition, enhancement of the release of cytochrome c into cytosol was demonstrated in these transfectants by a subcellular fractionation experiment, followed by Western blotting. These findings suggest that the release of the cytochrome c protein from mitochondria is regulated by the hinge protein involved in the respiratory chain in the apoptotic process.

Animals↗

PubMed1998

Preparation of Silica Aerogel from TEOS

Silica alcogels were synthesized by the sol-gel polymerization of tetraethylorthosilicate (TEOS). In the synthesis, HCl and NH3 were used as hydrolysis and condensation catalysts. The gelation time became short and the visible light transmittance increased with increasing the amount of HCl or lengthening the hydrolysis time. The alcogels were dried under supercritical conditions with carbon dioxide, and silica aerogels were obtained. As a result of characterization by visible light transmission and N2 adsorption, the aerogels are mesoporous materials with high surface areas. The experimental results suggest that the aerogel properties are not influenced by the drying conditions such as extraction temperature, extraction time, depressurizing temperature, and depressurizing rate. On the other hand, the properties are changed under the conditions of sol-gel polymerization. In the preparation of highly transparent aerogels with high surface areas and large pore volumes, it is necessary to synthesize highly transparent alcogels. It is found that the visible light transmittance of alcogels is an index for preparing aerogels from TEOS. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

PubMed1998

Endoscopic injection sclerotherapy with n-butyl-2-cyanoacrylate for ruptured duodenal varices.

Duodenal varices are a rare site of hemorrhage in patients with portal hypertension, but their rupture is a serious and often fatal event. We report the case of a 77-year-old woman with cirrhosis who presented with melena. She was admitted to our Department because of prolonged shock although she had received a large blood transfusion. Upper gastrointestinal endoscopy revealed nodular varices in the third portion of the duodenum which were considered to be the source of the bleeding. Endoscopic injection sclerotherapy (EIS) with n-butyl-2-cyanoacrylate (Histoacryl; Braun-Melsungen, Germany), an adhesive agent, was performed. We injected 1.5 ml of Histoacryl with Lipiodol (Laboratoire-Guerbet, France) intravariceally and achieved successful hemostasis. This patient's duodenal varices had almost completely resolved 1 month after EIS. We conclude that EIS with Histoacryl is an effective hemostatic measure for ruptured duodenal varices.

Aged↗

PubMed1998

Hepatocellular carcinoma with obstructive jaundice successfully treated with a self-expandable metallic stent.

We report on a 71-year old man with hepatocellular carcinoma (HCC) whose obstructive jaundice was successfully treated with external irradiation and a self-expandable metallic stent (EMS); Wallstent; Schneider (Europe) AG, Bülach, Switzerland. He was admitted to our hospital because of jaundice. HCC was found in S8; the tumor had invaded the bile duct with growth in the common hepatic duct. Endoscopic nasobiliary drainage was performed with difficulty. Radiation therapy to the stenosis enabled us to place a Wallstent endoscopically. He survived without icterus for 1 year.

Aged↗

PubMed1998

Histological evaluation of the effects of intraarterial chemotherapy for advanced breast cancer: a long-term followup study with respect to the survival rate.

To evaluate the effects of intraarterial infusion chemotherapy (IAIC) for advanced breast cancer, we examined the grade of histological responses of preoperative IAIC on tumors at the time of operation and estimated the patients' prognoses for 19 years. IAIC was done preoperatively using timely epochal anticancer drugs on 105 patients with locally advanced (Stage IIIa, IIIb) and metastatic (Stage IV) breast cancer. The survival rate of the Stage IIIb patients who showed a good histological response (Grade IIb< or =) to IAIC was 68.1% for 5 years, and 62.4% for 10 years, respectively. This was in contrast to that of the patients classified as Stage IIIb who showed a poor histological response (Grade IIa> or =) to IAIC. On the other hand, there was no significant difference in the survival rates between the Stage IIIa and IV patients with good and poor histological responses to IAIC. However, the findings showed that a good histological response to IAIC reflected a prolonged survival while the Stage IIIb and IV patients acquired a "down clinical staging" by IAIC. These results strongly suggest that IAIC thus appears to be a useful modality in the multidisciplinary treatment of advanced breast cancer, especially for Stage IIIb patients.

Adult↗

PubMed1998

High proportion of missense mutations of the BRCA1 and BRCA2 genes in Japanese breast cancer families.

Mutations in either of two recently identified genes, BRCA1 and BRCA2, are thought to be responsible for approximately two-thirds of all cases of autosomal-dominantly inherited breast cancer. To examine the nature and frequency of BRCA1 and BRCA2 mutations in Japanese families exhibiting a high incidence of breast cancer, we screened 78 unrelated families in this category for mutations of these two genes. Examining the entire coding sequences as well as exon-intron boundaries of both genes by polymerase chain reaction (PCR) single-strand conformation polymorphism (SSCP) and multiplex-SSCP analysis, we identified possible disease-causing alterations in BRCA1 among affected members of 15 families and in BRCA2 in another 14 families. In 15 of those 29 families, the affected individuals carried missense mutations, although most germline mutations reported worldwide have been deletions or nonsense mutations. Our results, indicating that missense mutations of BRCA1 and BRCA2 tend to predominate over frameshifts or nonsense mutations in Japanese breast cancer families, will contribute significantly to an understanding of mammary tumorigenesis in Japan, and will be of vital importance for future genetic testing.

BRCA2 Protein↗

PubMed1998

Heterogeneous fluoridated apatites synthesized with a three-step fluoride supply system.

Two types of heterogeneous fluoridated apatite, H-F-H and F-H-F, were synthesized by supplying fluoride during the middle half (H-F-H) or initial and final quarters (F-H-F) of the experimental period. Although X-ray diffraction patterns and SEM photographs of both H-F-H and F-H-F-type apatites were not significantly different, high-resolution transmission electron microscopy showed quite different features; H-F-H-type apatite crystals were elongated hexagons, while those of F-H-F-type apatite were rather wider hexagons with electron damage in three-quarters of the inner core. These results supported the previous speculations on the two different types of heterogeneous fluoridated hydroxyapatites synthesized with fluoride concentrations stoichiometrically equivalent to that of fluorapatite: hydroxyapatite covered with fluorapatite and fluorapatite covered with hydroxyapatite. F-H-F-type apatite was less soluble than that of H-F-H-type apatite.

Apatites↗

PubMed1998

NMDA receptor-mediated inspiratory off-switching in pneumotaxic-disconnected cats.

The pneumotaxic center is thought to govern inspiratory off-switching (IOS), and blockade of N-methyl-D-aspartate (NMDA) receptors by dizocilpine impairs IOS causing apneusis. The present study is to examine whether the NMDA receptor-mediated IOS mechanism functions in the medullary respiratory network after disconnecting the pneumotaxic center. In decerebrate and vagotomized cats, the nucleus parabrachialis medialis (NPBM) and vagus nerves were stimulated to evoke IOS and a dorsal pontine transection was performed while the central respiratory activity was recorded in phrenic neurogram. The transection eliminated the NPBM-stimulated IOS but not the vagally evoked IOS, and developed two types of respiration; eupnea in 12 and apneusis in six out of 18 cats. Apneustic respiration was not changed into eupneic one by changing the end-tidal CO2 level. In animals displaying eupnea after the transection, dizocilpine (0.3 mg/kg i.v.) produced apneusis, characterized by a prolonged inspiration, a shortened stage 1 expiration and an unchanged stage 2 expiration. Dizocilpine caused no further change in the apneustic pattern induced by the transection. The present results suggest that the medullary respiratory network is able to generate a eupneic respiration after disconnecting the pontine pneumotaxic center, and the NMDA mechanism plays an important role in the medullary respiratory network.

Age Factors↗

PubMed1998

Induction chemoradiotherapy for advanced stage III non-small cell lung cancer: long-term follow-up in 42 patients.

This multi-institutional phase II study was designed to assess the feasibility, efficacy, toxicity, and long-term survival of induction chemoradiotherapy followed by surgery in previously untreated patients with advanced stage III non-small cell lung cancer. Chemotherapy regimen included cisplatin 20 mg/m2 on days 1-5 and 29-33, and VP-16 40 mg/m2 on days 1-5 and 29-33. Radiotherapy (50 Gy in 25 fractions) began on day 1. Clinically downstaged patients underwent thoracotomy 3-5 weeks after the completion of radiotherapy. Forty-two eligible patients (ten stage IIIA and 32 IIIB) were followed for a median period of 64 months. The response rate was 81%, and 20 patients had a clinically good response. Twenty-one patients underwent thoracotomy. Nineteen patients had complete resections and there were seven pathologic complete responses. There were four treatment related deaths (all stage IIIBs). There were significant survival differences between stage IIIA versus IIIB patients (P = 0.028; median survivals, 24.9 vs. 11.1 months; 5-year survival rates, 20% vs. 8.3%), and patients that achieved pathologic complete response (CR) versus those that did not (P = 0.045; median survivals 30.1 vs. 11.1 months; 5-year survival rates, 28.6% vs. 8.3%). Although the induction chemoradiotherapy employed in this study was not appropriate for stage IIIB patients, it proved feasible in stage IIIA patients in whom it resulted in good 5-year survival rates. It also provided good survival rates in patients achieving pathologic CR.

Adult↗

PubMed1998

Kainic acid induction of heme oxygenase in vivo and in vitro.

Heme oxygenase, catalyses oxidation of the heme molecule in concert with NADPH-cytochrome P450 reductase and then specifically cleaves heme into biliverdin, carbon monoxide, and iron. Biliverdin and its product, bilirubin, are known to be strong antioxidants. Kainic acid is a potent neurotoxin, and induces selective neuronal loss in the rat hippocampus. Kainic acid acts on the kainate receptors, and kainic acid neurotoxicity may be in part mediated by oxidative stress. In this study, we examined whether or not heme oxygenase was activated in kainic acid-induced neurotoxicity. After intracerebroventricular injection of kainic acid, the heme oxygenase-1 protein level was strongly enhanced, although the constitutive heme oxygenase (heme oxygenase-2) protein level was not changed. One day after treatment, the protein level of heme oxygenase-1 reached a maximum and then gradually decreased over a period of three to seven days. In the rat hippocampus, cells expressing heme oxygenase-1 in vivo were predominately microglia and only a few astrocytes. In addition, heme oxygenase-1 immunoreactivity was predominantly co-localized with major histocompatibility complex class II-, and partly co-localized with class I-immunoreactive microglia. In cultured glial cells in vitro, heme oxygenase- protein was expressed in the microglia even with the vehicle treatment, and was strongly induced in astrocytes by kainic acid treatment. These results suggest that ameboid microglia, which express both heme oxygenase-1 and major histocompatibility complex antigens, may play a key role in a delayed episode of kainic acid-induced microglial activation and neurodegeneration.

Animals↗

PubMed1998

Involvement of calcitonin gene-related peptide (CGRP) receptors in insulin-induced vasodilatation in mesenteric resistance blood vessels of rats.

1. The vascular effect of insulin in the mesenteric resistance blood vessel and the role of calcitonin generelated peptide (CGRP)-receptor in insulin-induced vascular responsiveness were investigated in rats. 2. The mesenteric vascular beds isolated from Wistar rats were perfused with Krebs solution, and perfusion pressure was measured with a pressure transducer. In preparations contracted by perfusion with Krebs solution containing methoxamine in the presence of guanethidine, the perfusion of insulin (from 0.1 to 3000 nM) caused a concentration-dependent decrease in perfusion pressure due to vasodilatation. The pD2 value and maximum relaxation (%) were 6.94+/-0.22 and 43.9+/-5.2, respectively. 3. This vasodilator response to insulin was unaffected by 100 nM propranolol (beta-adrenoceptor antagonist) plus 100 nM atropine (muscarinic cholinoceptor antagonist), 100 microM L-NG-nitroarginine (nitric oxide synthase inhibitor), 1 microM ouabain (Na+-K+ ATPase inhibitor), or 1 microM glibenclamide (ATP sensitive K+-channel inhibitor). 4. In preparations without endothelium, perfusion of insulin produced a marked vasodilatation. The pD2 value and maximum relaxation (%) were 7.62+/-0.21 and 81.0+/-4.6, respectively, significantly greater than in preparations with intact endothelium. 5. The vasodilator responses to insulin in the preparations without endothelium were significantly inhibited by CGRP[8 37], a CGRP receptor antagonist, whereas pretreatment with capsaisin, a toxin for CGRP-containing nerves, did not affect insulin-induced vasodilatation. 6. These results suggest that insulin induces non-adrenergic, non-cholinergic and endothelium-independent vasodilatation, which is partially mediated by CGRP receptors.

Animals↗

PubMed1998

Pigmented primary carcinoma of the breast: a clinical mimic of malignant melanoma.

A 68-year-old man had a pigmented tumour in the breast. Although the clinical picture suggested a malignant melanoma, histology revealed that the tumour was a primary ductal carcinoma of the breast. There was no pagetoid cell proliferation in the epidermis. However, tumour nests contained numerous dendritic melanocytes that could survive in the tumour nests without the existence of epidermal keratinocytes. Further immunohistochemical study employing antibodies to melanocyte growth factors demonstrated that anti-basic fibroblast growth factor (bFGF) antibody was the only reagent to show a positive staining for tumour cells. This indicated that the breast cancer cells produced bFGF, which enabled survival of melanocytes within the tumour mass.

Breast Neoplasms, Male↗

PubMed1998

Avoiding ectropion by using the Mitek Anchor System for flap fixation to the facial bones.

The application of the Mitek Anchor System for bony fixation of the flap in the cheek area is described. The cervicofacial rotation-advancement flap is fixated to the malar bone using Mini Anchors for the purpose of diminishing the downward traction on the lower eyelid. They reduced the tension in the distal part of the flap and avoided distal-edge necrosis and ectropion. In another patient the free vascularized musculocutaneous flap, which had been grafted previously for a surgical defect in the cheek and resulted in ectropion of the lower eyelid, was fixated to the malar bone, and the ectropion was corrected. The Mitek Anchor System is useful in flap fixation to the bone because it provides a simple, fast, and reliable method for flap fixation with minimal dissection and precise placement.

Adolescent↗

PubMed1998

Endoscopic management of subcutaneous gunshot wound with irrigation technique.

The application of the endoscope to the treatment of gunshot wounds has never been reported to our knowledge, with the exception of the laparoscope and the sigmoidscope in abdominal gunshot wounds. We report a patient with a subcutaneous gunshot wound who was treated endoscopically using the irrigation technique. The patient was a 25-year-old man who had been shot in the upper arm. The bullet was found near the thoracic spine via radiograph. At surgery the endoscope was inserted into the wound and irrigation was started. Excellent views could be obtained by irrigation, and the endoscope was advanced along the path of the bullet. The bullet and several fragments were removed with two additional small incisions. The method described herein seems beneficial in that (1) it is less invasive than conventional surgical debridement with a long incision, (2) it may provide information helpful in diagnosing the condition and the location of the bullet and its path, and (3) saline irrigation may have a cleansing effect.

Adult↗