Search PubMed⌕ Search

Biomedical subjects

H Kasai

Publications and source records attributed to H Kasai.

At least 181 records · Page 10Linked to original sources
PubMed1996

Neuronal and glial characteristics of central neurocytoma: electron microscopical analysis of two cases.

We have identified two central neurocytomas which contained cells co-expressing glial fibrillary acidic protein and synaptophysin defined by double-label immunostaining. Dual-positive cells were mostly polygonal in shape and with a morphological appearance similar to that of reactive astrocytes. This distinct morphology could be used to distinguish cells expressing glial fibrillary acidic protein from cells with round and clear cytoplasm which did not express glial fibrillary acidic protein and which composed the majority of the tumor. Samples containing polygonal cells were selected for electron microscopy from toluidine blue-stained semithin sections. Ultrastructural findings were similar in both neurocytomas, with both being composed predominantly of round cells with clear cytoplasm corresponding to the clear cells identified by light microscopy. Dense-core vesicles and clear vesicles were frequently observed in the cell processes. Apart from these clear cells, polygonal cells with electron-dense cytoplasm were noted. Paralleling the result of double immunostaining, these polygonal cells contained both dense-core vesicles and intermediate, presumably glial filaments. Microtubules and lipofuscin granules were also observed. These results suggest that cells expressing glial fibrillary acidic protein in central neurocytoma include tumor cells with both neuronal and glial characteristics.

Adult↗
PubMed1996

Serum Amylase elevation following hepatic resection in patients with chronic liver disease.

BACKGROUND: Factors liable to cause hyperamylasemia after hepatectomy were studied retrospectively in 140 patient with chronic liver disease. METHODS: The pringle maneuver was performed in 113 patients (Pringle group), the hemihepatic vascular occlusion technique in 21 (hemihepatic group), and no vascular occlusion in 6 (no-occlusion group). RESULTS: In the Pringle group, postoperative serum amylase levels were elevated significantly in comparison with the preoperative levels, but were not elevated in hemihepatic and no-occlusions groups. In the Pringle group, there were 4 patients whose postoperative serum amylase levels exceeded 3.5 times the upper limit of the normal range together with serum pancreatic isoamylase or lipase elevation or both. When compared with the other 109 patients, these 4 patients had a significantly longer vascular occlusion time (51 +/-3 minutes versus 94 +/- 8 minutes P<0.005). One of them developed pancreatitis and died from hepatic failure. CONCLUSION: Prolongation of portal congestion carries a potential risk of serum amylase elevation and pancreatitis after hepatectomy in patients with underlying liver disease.

Adult↗
PubMed1996

Increased 8-hydroxyguanine levels in DNA and its repair activity in rat kidney after administration of a renal carcinogen, ferric nitrilotriacetate.

The renal carcinogen, ferric nitrilotriacetate (Fe-NTA), is known to induce oxidative stress and the subsequent formation of a type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), in the rat kidney (Umemura et al., 1990). Using an improved DNA isolation method (Nakae et al., 1995), which reduces the background level of 8-OH-Gua, we found a five-fold increase in the 8-OH-Gua level in kidney DNA after a single i.p. injection of Fe-NTA. On the basis of the report that 8-OH-Gua repair activity is enhanced after cells are exposed to oxidative stress due to ionizing radiation (Bases et al., 1992), the measurement of 8-OH-Gua repair activity will also be useful to assess cellular oxidative stress. The 8-OH-Gua repair enzyme activity was determined with an endonuclease assay using a 22 mer DNA that contains 8-OH-Gua at a specific position. A five-fold increase in the 8-OH-Gua repair activity as compared with the control, was observed in the target organ, the rat kidney, 120 h after Fe-NTA administration. In the non-target organ, the liver, the increase was not as large (two-fold). This simple assay of oxidative DNA damage repair will be useful for evaluating the carcinogenicity of oxygen radical forming chemicals, in addition to chemical analyses of oxidative DNA damage.

Animals↗
PubMed1996

8-hydroxyguanine levels in nuclear DNA and its repair activity in rat organs associated with age.

8-Hydroxyguanine (8-OH-Gua) is one of the most abundant types of oxidative DNA damage. The levels of 8-OH-Gua, and its repair activity, were quantified in 3-week-, 5-month-, and 30-month-old male Sprague-Dawley rat organs such as liver, kidney, spleen, lung, small intestine, and brain. The levels of 8-OH-Gua were significantly higher in the 5-month-old rat kidney and brain and 30-month-old rat spleen when compared to that of the 3-week-old rats. However, no significant differences were found in the organs between 5- and 30-month-old rats that were due to the aging process. The repair activity levels of kidney, spleen, and lung were higher than those of liver, small intestine, and brain. This pattern was consistent for the three age stages.

Aging↗
PubMed1996

Inhibition of nucleolar function and morphological change by adriamycin associated with heat shock protein 70 accumulation.

Adriamycin (ADR) has been considered to target mainly DNA metabolism in the nucleus. Recently, we observed the nuclear translocation of heat shock protein 70 (HSP70) after ADR treatment. We examined which intranuclear changes might be related to this alteration of HSP70 localization. We found considerable alternations in the nucleolar morphology and function in ADR-treated tumor cells, i.e., a ring-shaped segregation of granular components of almost all nucleoli and a dramatic reduction of nucleolar 45S ribosomal precursor RNA biosynthesis in HeLa cells exposed to 100 microM ADR for 2 h. Concomitantly with these changes, HSP70 was concentrated into the nucleoli, as in the case of heat shock treatment. These results indicate a novel anticancer effect of ADR via the suppression of cellular protein biosynthesis, in addition to its effect on DNA.

Antibiotics, Antineoplastic↗
PubMed1996

Fast RARE MR imaging with variable flip angle excitation.

A method was developed for performing T1-weighted magnetic resonance imaging with the rapid acquisition with relaxation enhancement (RARE) sequence by altering the excitation flip angle. This method was called variable flip angle turbo spin-echo (VF-TSE) imaging. When the effective echo time corresponds to the first echo, the resolution worsens as the echo train length becomes longer. For this reason, the echo train length was set at three, the repetition time (TR) was shortened (100- 200 msec) to decrease imaging time, and the initial flip angle was adjusted (120 degrees-140 degrees) to improve image quality. Another advantage of this method is that the initial flip angle can be reduced to below 90 degrees when a longer TR is needed. Measured signal intensities for VF-TSE imaging matched theoretic predictions. VF-TSE imaging yielded high contrast-to-noise and signal-to-noise ratios without sacrificing resolution. The VF-TSE technique was useful for breath-hold, three-dimensional, and cardiac synchronization imaging.

Humans↗
PubMed1996

Increase in the 8-hydroxyguanine repair activity in the rat kidney after the administration of a renal carcinogen, ferric nitrilotriacetate.

One type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), is known to increase in rat kidney DNA after the administration of a renal carcinogen, ferric nitrilotriacetate (Fe-NTA). To determine the involvement of oxygen radicals in Fe-NTA carcinogenesis, we examined whether the 8-OH-Gua repair enzymes are induced in the rat kidney after Fe-NTA administration, in addition to our analysis of the 8-OH-Gua levels in the DNA, because the 8-OH-Gua repair activity is known to be induced in mammalian cells by oxidative stress due to ionizing radiation. The 8-OH-Gua repair enzyme activity was determined with an endonuclease assay using a 22-mer double strand DNA, which contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua repair activity was observed in the rat kidney after a single intraperitoneal injection of Fe-NTA (p < 0.01). This is the first report on the induction of the repair activity for 8-OH-Gua after treatment with a chemical carcinogen. This assay will be useful for evaluating the carcinogenicity of oxygen radical-forming chemicals.

Animals↗
PubMed1996

Immunohistochemical observation of foci of muscle actin-positive tumor cells in meningiomas.

OBJECTIVE: It has been suggested that muscle actin is expressed in some meningiomas. The purpose of this study was to examine this hypothesis in a large number of meningiomas and to examine possible explanations for this expression. DESIGN: Sixty-five meningiomas were examined using immunohistochemistry for muscle actin. Meningiomas with foci of muscle actin-positive cells (n = 6) were further examined using monoclonal antibodies for desmin, epithelial membrane antigen, cytokeratin, and von Willebrand factor. These specimens were also stained for reticulin. SETTING: All tissues were obtained from surgical biopsy specimens at a large academic medical center. MAIN OUTCOME MEASURES: Meningioma cells were considered to express muscle actin if the expression was shown to localize specifically in meningothelial cells and whorls that were also positive for epithelial membrane antigen. RESULTS: Seventeen of 65 meningiomas were shown to contain muscle actin-positive cells. Scattered cells were positive in 11 cases, and in the remaining six cases we observed foci of muscle actin-positive cells, which had a propensity to form cellular whorls. These foci expressed epithelial membrane antigen, but stains for desmin, cytokeratin, von Willebrand factor, and reticulin were negative. CONCLUSIONS: Our findings suggest that meningioma cells elaborate muscle actin without showing differentiation into specific cell types.

Actins↗
PubMed1995

Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose.

Mice carrying a null mutation in the glucokinase (GK) gene in pancreatic beta-cells, but not in the liver, were generated by disrupting the beta-cell-specific exon. Heterozygous mutant mice showed early-onset mild diabetes due to impaired insulin-secretory response to glucose. Homozygotes showed severe diabetes shortly after birth and died within a week. GK-deficient islets isolated from homozygotes showed defective insulin secretion in response to glucose, while they responded to other secretagogues: almost normally to arginine and to some extent to sulfonylureas. These data provide the first direct proof that GK serves as a glucose sensor molecule for insulin secretion and plays a pivotal role in glucose homeostasis. GK-deficient mice serve as an animal model of the insulin-secretory defect in human non-insulin-dependent diabetes mellitus.

Alternative Splicing↗
PubMed1995

Age-associated change of 8-hydroxyguanine repair activity in cultured human fibroblasts.

8-hydroxyguanine (8-OH-Gua) is a major oxidative DNA damage product. Its repair activity was determined in the human fibroblast cell line, TIG-3, during the aging process. The repair activity increased in the first part of the aging process and decreased in the latter part. The highest repair activity was observed at the age of 30 PDL. These results suggest that the defense capacity for replication errors due to oxidative DNA damage increases greatly when the cells are rapidly dividing.

Base Sequence↗
PubMed1995

Formation of 2-hydroxydeoxyadenosine triphosphate, an oxidatively damaged nucleotide, and its incorporation by DNA polymerases. Steady-state kinetics of the incorporation.

We found that hydroxylation occurs at the C-2 position of adenine by oxygen radical treatment (Fe2+-EDTA) of dA, dATP, and single- and double-stranded DNA. This oxidatively damaged base, 2-hydroxyadenine, was produced 3-6-fold and 40-fold less than 8-hydroxyguanine when monomers and polynucleotides, respectively, were treated. To determine whether the damaged nucleotide, 2-hydroxydeoxyadenosine triphosphate (2-OH-dATP), is incorporated into a growing DNA, and to reveal the kinds of nucleotides opposite which 2-OH-dATP is incorporated, calf thymus DNA polymerase alpha and the Klenow fragment of Escherichia coli DNA polymerase I were used in vitro DAN synthesis in the presence of 2-OH-dATP. DNA polymerase alpha incorporated the nucleotide opposite T and C in the DNA template. On the other hand, in an experiment using the Klenow fragment, incorporation of 2-OH-dATP was observed only opposite T. Steady-state kinetic studies indicated that incorporation of 2-OH-dATP by DNA polymerase alpha opposite T was favored over that opposite C by a factor of only 4.5. These results indicate that 2-OH-dATP, an oxidatively damaged nucleotide, is a substrate for DNA polymerases and is incorporated incorrectly by the replicative DNA polymerase.

Adenosine Triphosphate↗
PubMed1995

8-hydroxydeoxyguanosine levels in DNA of human breast cancer are not significantly different from those of non-cancerous breast tissues by the HPLC-ECD method.

8-Hydroxydeoxyguanosine (oh8dG) is a promutagenic DNA lesion produced by oxygen radicals, and a high level of 8-hydroxyguanine in breast cancers was previously demonstrated by the gas chromatography-mass-spectrometry method. To confirm the previous observation, the oh8dG levels of DNA of 22 breast cancers and corresponding adjacent non-cancerous breast tissues were analyzed by high performance liquid chromatography-electrochemical detector (HPLC-ECD) system, and the correlation of the oh8dG levels in breast cancer DNAs with clinical and immunohistochemical parameters was examined. However, the levels of oh8dG in DNA of breast cancers are not significantly different from those of corresponding non-cancerous breast tissues (P = 0.084) by the HPLC-ECD method. Furthermore, the oh8dG levels in breast cancers were not associated with p53 and erbB-2 immunoreactions, with expression of estrogen and progesterone receptors, and with clinical stage and histological grade. Thus, in contrast to the previous data, the present study using the HPLC-ECD method does not indicate an increase of oh8dG levels in breast cancers.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Misincorporation of dAMP opposite 2-hydroxyadenine, an oxidative form of adenine.

Nucleotide incorporation opposite an oxidative form of adenine, 2-hydroxyadenine (2-OH-Ade) was investigated. When a primed template with 2-OH-Ade was treated with an exonuclease-deficient Klenow fragment of Escherichia coli DNA polymerase I (KFexo-), recombinant rat DNA polymerase beta (pol beta) or calf thymus DNA polymerase alpha (pol alpha), incorporation of dTMP and dAMP was observed. In addition, KFexo- inserted dGMP as well. A steady-state kinetic study indicated that the insertion of dAMP and dTMP opposite the DNA lesion occurred with similar frequency with KFexo- and pol beta. Insertion of dTMP opposite 2-OH-Ade was favored to that of dAMP by pol alpha. Chain extension from the A.2-OH-Ade pair is less favored than that from the T.2-OH-Ade pair by all three DNA polymerase. Analysis of full-length products of in vitro DNA synthesis showed that dTMP and dAMP were incorporated by DNA polymerases and that exonuclease-proficient and -deficient Klenow fragments also inserted dGMP opposite 2-OH-Ade. These results suggest that formation of 2-OH-Ade from A in DNA will induce A-->T and A-->C transversions in cells.

Animals↗
PubMed1995

Cloning and characterization of the hrpA gene in the terC region of Escherichia coli that is highly similar to the DEAH family RNA helicase genes of Saccharomyces cerevisiae.

During the course of systematic nucleotide sequence analysis of the terC region of E.coli K-12 by using the ordered lambda phage clones, we found the presence of a gene, termed hrpA, that showed a high degree of sequence similarity to the PRP2, PRP16 and PRP22 genes of Saccharomyces cerevisiae. The products of these yeast genes are known to play their roles in mRNA splicing, and belong to a group of proteins collectively called the DEAH family. The hrpA gene is the first example of a DEAH family gene in prokaryotes. The N-terminal region of the protein it encodes contains conserved sequence stretches characteristic of an RNA helicase. Its molecular mass is calculated to be 146 kDa. Previously, a 135 kDa protein was identified by Moir et al. [J. Bacteriol. (1992) 174, 2102-2110] in this region which is most likely identical to that encoded by hrpA. The C-terminal region of the hrpA gene product seems to contain an RNA binding motif weakly resembling that of ribosomal protein S1 of E.coli. Disruption of the hrpA gene suggested that it is not essential for the growth of E.coli.

Adenosine Triphosphatases↗
PubMed1995

Possible correlation between DNA damage induced by hydrogen peroxide and translocation of heat shock 70 protein into the nucleus.

Oxygen radicals have been implicated as the causative agent in deleterious processes such as gene mutation, cellular transformation and cell death. Cellular response to DNA damage induced by hydrogen peroxide was examined in human amniotic cultured cells (WISH). The content of 8-hydroxydeoxyguanosine in nuclear DNA increased during the early period of exposure to hydrogen peroxide, that is, it peaked at 1 h in the cells treated with 1 mM hydrogen peroxide and then declined, but not to the control levels within 4 h. Interestingly, immunofluorescence staining of treated cells revealed that cytoplasmic hsp70 protein translocated transiently into the nucleus, which was most remarkable around 30 min after the addition of 1 mM hydrogen peroxide into the culture medium. On the other hand, the induction of hsp70 gene mRNA was not significant during the early period of treatment by 0.5 mM hydrogen peroxide and was occurred after 5 h. DNA damage induced by Adriamycin further supported the possible correlation between hydroxyl radical-mediated cleavage of DNA and nuclear translocation of hsp70 protein. These results suggest that preexisting hsp70 protein translocated into the nucleus to either protect chromatin DNA from further damage or to facilitate the repair of DNA damage in some unknown ways.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Pancreatic calcium waves and secretion.

Pancreatic acinar cells display stereotypic Ca2+ waves resulting from Ca2+ release from internal stores during stimulation. The Ca2+ waves are initiated at the luminal pole, and, at high agonist concentrations, spread towards the basal pole. Two key mechanisms behind the generation of Ca2+ waves have been identified. First, the Ca2+ waves are composite, mediated by three distinct Ca2+ release mechanisms with a polarized distribution: high-sensitivity inositol 1,4,5-trisphosphate (InsP3) receptors at a small trigger zone (T zone) in the secretory granule area, Ca(2+)-induced Ca2+ release channels in the granular area and low-sensitivity InsP3 receptors in the basal area. Second, InsP3 can readily diffuse in the cytosol, whereas rises in cytosolic Ca2+ concentration ([Ca2+]i) can be confined through strong buffering and sequestration of Ca2+. InsP3 is thus used as a long-range messenger to transmit agonist signals to the T zone, and [Ca2+]i rises at the T zone are used as a local switch. These mechanisms enable preferential activation of the T zone, irrespective of localization of stimuli and agonist receptors. The secretion of enzymes and fluid is a direct consequence of [Ca2+]i rises at the T zone. The Ca2+ waves and oscillations probably boost the T zone functions.

Animals↗
PubMed1995

Oxidative DNA damage induced by silica in vivo.

Occupational exposure to silica has often been associated with the development of pulmonary fibrosis and, occasionally, lung cancer. Their development may be mediated by oxidant-induced cellular injury. The short- and long-term effects of a single intratracheal instillation of silica in rats (10 mg/200 microliters/saline per rat) was assessed by measuring 8-hydroxy-2'-deoxyguanosine (oh8dG) levels in lung tissue and peripheral blood leukocytes. Cell differentials, reduced glutathione (GSH), and superoxide dismutase (SOD), lipid peroxide, and total phospholipids in peripheral blood and/or bronchoalveolar lavage fluid (BALF) were also measured. The pulmonary oh8dG levels increased approximately 2.24- 2.86-fold from 1 to 5 days after exposure to silica. It was still elevated 1 and 4 weeks after installation, but the difference was no longer statistically significant. The oh8dG levels in peripheral blood leukocytes were never significantly different, but they were generally higher than in the controls. The low SOD levels in the BALF of exposed rats in the early stage and the higher GSH levels in the late stage may represent protective reactions against the generation of oxygen species. A significant increase in oh8dG levels in lung tissue suggested the possible carcinogenicity of silica.

8-Hydroxy-2'-Deoxyguanosine↗