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Biomedical subjects

A Oikawa

Publications and source records attributed to A Oikawa.

At least 37 records · Page 2Linked to original sources

Evolution of chronic subdural hematoma after burr-hole exploration for subdural effusion--case report.

A 57-year-old male developed subdural effusion after head trauma, which remained asymptomatic and unchanged in volume during a follow-up period of 3 months. A typical chronic subdural hematoma (CSDH) developed 6 weeks after burr-hole exploration in spite of the absence of hematoma capsule or blood components in the effusion. The CSDH was successfully treated by irrigation and drainage. This case suggests that the presence of blood in subdural effusion may be the trigger for evolution of CSDH. We recommend that asymptomatic subdural effusion should be followed up without surgical intervention.

Brain↗

Identification of cellular defect in UVS1, a UV-sensitive Chinese hamster ovary mutant cell line.

UVS1 is an intermediately UV-sensitive Chinese hamster ovary mutant originally isolated by its hypersensitivity to an anticancer drug, 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride. By cell fusion analysis, UVS1 complemented the UV sensitivity of the mouse lymphoma cell line US31 from the eighth complementation group of UV-sensitive rodent cell lines. By enzyme-linked immunosorbent assay we found that within 3 h after UV irradiation both pyrimidine dimers and (6-4)photoproducts in UVS1 were not removed from chromosomal DNA in UVS1 at all. Twenty-four h after UV irradiation the removal rate of (6-4)photoproducts was intermediate between CHO9, the parental cell line, and 43-3B, a UV-hypersensitive Chinese hamster ovary mutant of the complementation group 1, whereas the pyrimidine dimers in UVS1 were removed less efficiently as 43-3B. Alkaline elution assay showed that the incising activity to damaged DNA after UV irradiation of UVS1 was as low as that of 43-3B. The number of 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride-induced DNA interstrand cross-links of UVS1 was almost equal to that of 43-3B and about 1.5 times more than that of CHO9, suggesting that the gene products defective in UVS1 and 43-3B are essential for the excision repair of DNA damages produced by 1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3-nitrosour ea hydrochloride.

Animals↗

Okadaic acid, a protein phosphatase inhibitor, induces sister-chromatid exchanges depending on the presence of bromodeoxyuridine.

Okadaic acid (OA), a potent tumor promoter and an inhibitor of protein phosphatase 1 and 2A, induced sister-chromatid exchanges (SCEs) in human lymphoblastoid cells and Chinese hamster ovary cells at low concentrations of 2-10 nM, when the cells were grown for two cell cycles in the presence of OA and bromodeoxyuridine (BrdUrd). Prolonged treatment with OA prior to addition of BrdUrd did not induce SCEs, indicating an essential role of BrdUrd. A similar important role of BrdUrd in SCE induction has been reported in the cases of benzamide (BA) (Natarajan et al., 1981) and camptothecin (CPT) (Zhao et al., 1992), which are inhibitors of poly(ADP-ribose)polymerase and DNA topoisomerase I (topo I), respectively. Unlike many DNA-damaging agents, they are required to be present during S phase along with BrdUrd in the medium and/or in the parental DNA as BrdUMP. Thus OA, like BA and CPT, is a new type of SCE inducer. Exposing cells to a combined treatment with OA, BA and CPT, a significantly higher level of SCEs was induced than that expected if the numbers of SCE caused by these three inhibitors were additive, while no such synergistic increase was seen in every combination of two agents. Since both phosphorylation and poly(ADP-ribosyl)ation have been known to modify topo I activity, the results suggest a common involvement of topo I for SCE formation by OA, BA and CPT. In addition to SCE induction, OA resulted in an increase of mitotic cells which were characterized by a marked chromosome condensation. OA also induced chromosome fragmentation/pulverization in human lymphoblastoid cells and fragmented nuclei in Chinese hamster cells.

Animals↗

Arteriovenous malformation presenting as acute subdural haematoma.

A case of acute subdural haematoma caused by ruptured arteriovenous malformation is reported. At surgery, there was no association with intracerebral haematoma or definite subarachnoid haemorrhage. The mechanism of acute subdural haematoma in the present case was considered to be rupture of an arteriolized bridging vein drained by arteriovenous malformation.

Acute Disease↗

Clinical analysis of incidentally discovered unruptured aneurysms.

BACKGROUND AND PURPOSE: We analyzed the risk factors for rupture of an intracranial aneurysm based on a retrospective angiographic study of ruptured and unruptured aneurysms. METHODS: The 44 cases of asymptomatic aneurysms were selected from 1612 patients whose lesions had been discovered fortuitously by angiography (2.7%) during the period from 1980 to 1989. All these patients were free from any sign of intracranial aneurysm. The variations in age, sex, and location of the aneurysms were analyzed compared with 638 ruptured aneurysms that had been treated in our institute during the same period. The size, shape, and arterial geometry of the unruptured aneurysms were examined angiographically. RESULTS: Unruptured aneurysm was discovered fortuitously in 44 (2.7%) of 1612 patients, with greater incidence in women aged older than 60 years. Unruptured aneurysms were less likely to occur in the anterior communicating artery (12.8%) and the middle cerebral artery (6.4%). However, they were frequently found in the internal carotid artery, with an incidence of 10.6% in cavernous portion of the internal carotid artery, 19.1% in the internal carotid-ophthalmic artery, 19.1% in the internal carotid-posterior communicating artery, and 12.8% in the internal carotid-anterior choroidal artery. Seven of the nine internal carotid-posterior communicating artery aneurysms showed a hypoplastic or aplastic posterior communicating artery. The mean diameter of the unruptured aneurysms was 4.8 mm, and 80% were smaller than 6 mm. CONCLUSIONS: Intracranial aneurysms are formed not only at the bifurcation of an artery but also at its branching and bending points. However, an aneurysm located at the bifurcation, such as the anterior communicating artery and the middle cerebral artery, bleeds easily in contrast with lateral aneurysms such as those found at the branching and bending points on the internal carotid artery.

Adolescent↗

Vertebral artery aneurysm at the level of the cervicomedullary junction--case report.

A 39-year-old male presented with a ruptured vertebral artery aneurysm at the level of the cervicomedullary junction. Neuroradiological imaging demonstrated the aneurysm but not the anatomical relationships. Surgery in the chronic stage revealed that the aneurysm arose from the lowest part of the intradural vertebral artery. No vertebral artery proximal to the aneurysmal neck was identified in the intradural space. Clipping was difficult through the intradural approach. Acute treatment of such aneurysms requires control of the extradural vertebral artery with temporary clipping.

Adult↗

Patterning in hydra cell aggregates without the sorting of cells from different axial origins.

Aggregates of Hydra cells were studied to find out how the primary centers that form new heads are generated in a system of cells in which the original pattern has been destroyed. Since cells that originate near the heads (apical cells) temporarily maintain a high level of head activation potential during aggregate formation and may contribute to pattern formation, their distribution in the aggregates was investigated. The mutual distances between labeled epithelial cells were followed by vitally staining apical cells with DAPI. The distribution was random during early regeneration stages (3, 6, 24 hr). These results show that epithelial cells originating from apical regions do not sort. That is, dynamic cell movement to generate rudiments of new heads is not necessary for head formation in aggregates. A possible explanation of the mechanism is discussed.

Animals↗

Camptothecin-induced sister-chromatid exchange dependent on the presence of bromodeoxyuridine and the phase of the cell cycle.

Camptothecin (CPT), a DNA topoisomerase I inhibitor, dose-dependently induced sister-chromatid exchanges (SCEs) in human lymphoblastoid cells NL3 when added with bromodeoxyuridine (BrdUrd) for 2 cell cycles. CPT given prior to the addition of BrdUrd scarcely induced SCEs. When cells with BrdUrd present for 2 cell cycles were treated with CPT in the first cell cycle, the SCE induction was evident, though its frequency was considerably lower than in cells treated in the second cell cycle, indicating that BrdUrd is essential for SCE induction by CPT. The replacement of BrdUrd with thymidine in the second cell cycle gave the same results in SCE induction and its removal without replacement resulted in a reduced but still clear induction by CPT treatment in the second cell cycle. These results indicate that BrdUrd, not only incorporated into DNA but also in the culture medium, plays an essential role in SCE induction by CPT. CPT treatment in the G1 phase of the second cell cycle also induced SCEs, as did treatment in the S phase. In phytohemagglutinin-stimulated peripheral lymphocytes, CPT given in the G1 phase of the second cell cycle, but not of the first one, also induced SCEs though to a lesser degree. These findings suggest that CPT is capable of inducing DNA lesions during the G1 phase when chromosomes contain BrdUrd-substituted DNA. The lesions are presumably formed in connection with transcription, which requires topoisomerase I activity, and are believed to be long-lived enough to induce SCEs in the following S phase.

Bromodeoxyuridine↗

Mitochondrial DNA repair by photolyase.

Photolyase genes of Saccharomyces cerevisiae and Escherichia coli were expressed in S. cerevisiae and photoreactivation in nuclei and mitochondria of the host cells was analyzed by determination of survival and petit rates. Yeast photolyase was able to repair mitochondrial DNA effectively, whereas E. coli photolyase could reduce only a small fraction of the petit rate produced by UV irradiation. Analysis using fusion between yeast photolyase and E. coli lacZ genes as well as a chimeric gene between yeast and E. coli photolyase genes suggests the importance of the protruding amino terminal region of the yeast photolyase for its transport into mitochondria. A significant similarity between the protruding amino termini of yeast photolyase and yeast uracil-DNA-glycosylase suggests a common functional importance of the terminal sequences for both DNA repair enzymes.

Amino Acid Sequence↗

DNA repair pathways in mammalian cells analyzed by isolation of ACNU-sensitive Chinese hamster ovary cells.

1-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU) causes chloroethylation of DNA strand followed by cross linking through an ethylene bridge. We recently isolated two ACNU sensitive mutants from mutagenized Chinese hamster ovary cells, and found them to be new drug sensitive recessive mutants (Hata et al. 1991). The O6-methyl guanine DNA methyl transferase (MT) activities of these cells were undetectable as the parental cell line, indicating that the sensitivity of the mutant cell lines to ACNU was not due to the decreased cellular level of this enzyme. By complementation analysis with the 7 established UV-sensitive CHO cell lines, one of the mutants, UVS1, turned out to complement their UV-sensitivity and, therefore, build a new complementation group among all the CHO cell lines ever reported. The other mutant, CNU1 showed hypersensitivity only to chlorethylating agents (ACNU, CCNU) and exhibited a slightly reduced unscheduled DNA synthesis (UDS) induced by UV. It is, therefore, suggestive that this mutant is defective in a specific step of DNA repair systems, which is important for the processing of DNA damages produced by ACNU. Only cell lines from the complementation group 1 and 4 out of 7 established complementation groups of UV-sensitive CHO mutants were more sensitive to ACNU than UVS1 and CNU1, indicating some steps of excision repair pathways as well as specific repair system play important roles in repairing ACNU-induced DNA damages.

Animals↗

A possible involvement of DNA topoisomerase I in "caffeine effect" after ultraviolet irradiation.

Caffeine has been known to enhance lethal and chromosome damaging effects of chemical and physical mutagens. In spite of numerous investigations, the mechanism is not fully elucidated. In this paper, we describe that 1) post-treatment with camptothecin (CPT), a specific inhibitor of DNA topoisomerase (topo) I, enhances SCE-induction by ultraviolet light (UV), as post-UV caffeine treatment does, 2) the lethal effect of UV is also enhanced but to a lesser degree than by post-UV caffeine treatment, and 3) caffeine, like CPT, inhibits calf thymus topo I activity, as determined by relaxation of pBR322 supercoiled DNA. These results suggest that the mechanism(s) of lethal and SCE enhancement involves the ability of caffeine to inhibit topo I.

Caffeine↗

Cloning and functional characterization of a eucaryotic DNA photolyase gene from Neurospora crassa.

We cloned a genomic fragment of a photolyase gene from Neurospora crassa by polymerase chain reaction using synthesized oligonucleotide primers designed from the most conserved amino acid sequences among photolyases of various organisms. Using the cloned fragment as a hybridization probe we isolated a genomic fragment and cDNA clones encoding the complete photolyase gene of this organism. The amino acid sequence of the photolyase deduced from the determined nucleotide sequence indicates a protein consisting of 615 amino acid residues (Mr 69,971), which is most similar to that of Saccharomyces cerevisiae. Like yeast photolyase it contains a protruding amino terminus which is missing in photolyases of bacterial origin. Comparison of amino acids sequences among six photolyases suggests that the Neurospora crassa photolyase is more similar to photolyases of pterin type than those of deazaflavin type.

Amino Acid Sequence↗

Role of cysteine residues in the activity of rat glutathione transferase P (7-7): elucidation by oligonucleotide site-directed mutagenesis.

To clarify the role(s) of thiol (sulfhydryl) groups of cysteine (Cys) residues in the activity of the rat glutathione transferase P (7-7) form (GST-P), a cDNA clone, pGP5, containing the entire coding sequence of GST-P (Y. Sugioka et al., (1985) Nucleic Acids Res. 13, 6044-6057) was inserted into the expression vector pKK233-2 and the recombinant GST-P (rGST-P) expressed in E. coli JM109. All four Cys residues in rGST-P were independently substituted with alanine (Ala) by site-directed mutagenesis, the resultant mutants as well as the rGST-P being identical to GST-P purified from liver preneoplastic nodules with regard to molecular weight and immunochemical staining. Since all mutants proved as enzymatically active towards 1-chloro-2,4-dinitrobenzene as liver GST-P, it was indicated that none of the four Cys residues is essential for GST-P activity. However, the mutant with Ala at the 47th position from the N-terminus (Ala47) became resistant to irreversible inactivation by 0.1 mM N-ethylmaleimide (NEM), whereas the other three mutants remained as sensitive as the nonmutant type (rGST-P). Ala47 was also resistant to inactivation by the physiological disulfides, cystamine or cystine, which cause mixed disulfide and/or intra- or inter-subunit disulfide bond formation. These results suggest that the 47-Cys residue of GST-P may be located near the glutathione binding site, and modulation of this residue by thiol/disulfide exchange may play an important role in regulation of activity.

Animals↗

Unique characteristics of superoxide dismutase of a strictly anaerobic archaebacterium Methanobacterium thermoautotrophicum.

The superoxide dismutase (SOD) gene of Methanobacterium thermoautotrophicum (Takao, M., Oikawa, A., and Yasui, A. (1990) Arch. Biochem. Biophys. 283, 210-216), a strictly anaerobic archaebacterium, was expressed in Escherichia coli. The gene product accounted for more than 30% of the host's soluble protein. The purified protein was an active iron-containing tetrameric SOD with specific activity similar to known manganese-containing SODs (MnSODs) of aerobic archaebacteria. Although M. thermoautotrophicum SOD is an iron-containing SOD (FeSOD), it resembles MnSODs in amino acid sequence as judged by criteria distinguishing FeSODs from MnSODs. Moreover, M. thermoautotrophicum SOD is resistant to azide and hydrogen peroxide as MnSODs are, suggesting that its evolution is distinct from known eubacterial FeSODs.

Amino Acid Sequence↗

Isolation of two chloroethylnitrosourea-sensitive Chinese hamster cell lines.

1-[(4-Amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU), a cancer chemotherapeutic bifunctional alkylating agent, causes chloroethylation of DNA and subsequent DNA strand cross-linking through an ethylene bridge. We isolated and characterized two ACNU-sensitive mutants from mutagenized Chinese hamster ovary cells and found them to be new drug-sensitive recessive Chinese hamster mutants. Both mutants were sensitive to various monofunctional alkylating agents in a way similar to that of the parental cell lines CHO9. One mutant (UVS1) was cross-sensitive to UV and complemented the UV sensitivity of all Chinese hamster cell lines of 7 established complementation groups. Since UV-induced unscheduled DNA synthesis was very low, a new locus related to excision repair is thought to be defective in this cell line. Another ACNU-sensitive mutant, CNU1, was slightly more sensitive to UV than the parent cell line. CNU1 was cross-sensitive to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and slightly more sensitive to mitomycin C. No increased accumulation of ACNU and a low level of UV-induced unscheduled DNA synthesis in this cell as compared with the parental cell line suggest that there is abnormality in a repair response of this mutant cell to some types of DNA cross-links.

Animals↗

Acute subdural haematoma successfully treated by percutaneous subdural tapping in an elderly patient.

An elderly patient suffering acute subdural haematoma associated with cerebral contusion was treated by percutaneous subdural tapping while preparing for craniotomy. Most of the subdural haematoma, though of high density on computed tomography scanning, proved to be semiliquid. Drainage of the haematoma yielded resolution of the mass effect, and was followed by a rapid improvement of consciousness. This observation suggests the significance of trial subdural tapping for the treatment of acute traumatic subdural haematoma prior to craniotomy.

Acute Disease↗

Intracranial arteriovenous fistula manifesting as progressive neurological deterioration in an infant: case report.

This 1-year-old male infant had been diagnosed with cerebral degenerative disease because he developed psychomotor regression, and brain atrophy was demonstrated on computed tomography. He underwent magnetic resonance imaging, which suggested a cerebrovascular malformation. Cerebral angiography disclosed an arteriovenous fistula, fed by an anterior cerebral artery and directly draining into a cortical vein. The occlusion of the feeding artery was followed by a satisfactory recovery. The mechanism of the neurological symptoms in this patient is thought to be caused by a steal phenomenon and compression of the brain stem by venous engorgement in the posterior fossa.

Arteriovenous Fistula↗

Characterization of a superoxide dismutase gene from the archaebacterium Methanobacterium thermoautotrophicum.

A gene encoding superoxide dismutase (SOD) was cloned from the archaebacterium Methanobacterium thermoautotrophicum, the first example from an anaerobic bacterium. The deduced amino acid sequence showed overall similarity to sequences of known Mn- and Fe-SODs from aerobic organisms. Judging from a detailed sequence comparison, the cloned SOD gene is classified as Mn-SOD. By comparison of Mn-SOD sequences among various species it was suggested that archaebacterial superoxide dismutase is a direct descendant of a primordial enzyme. Between a putative promoter and the start codon there is an inverted repeat sequence which is also found in the counterpart of Halobacterium halobium.

Amino Acid Sequence↗