Biomedical subjects

M Takao

Publications and source records attributed to M Takao.

At least 91 records · Page 5Linked to original sources

PubMed1998

[Selection criterion of limited operation for lung cancer as a radical operation].

We reviewed partial resection and segmentectomy for 75 cases (6.5%) out of 1,212 cases treated surgically for primary lung cancer between 1957 and 1996. The surgical results of limited operation in radicality group and risk group was comparable to that of standard operation for the stage I lung cancer. Five-year survival of clinical stage I non-small cell lung cancer patients that tumor size is 2.0 cm or less was excellent (88.9%). Although risk group may be the best candidates for limited surgery, careful patient selection and theoretical operative procedure could make limited operation a standard procedure in radicality group.

Adenocarcinoma↗

PubMed1998

[Results of surgical treatment for pT3 primary lung cancer].

We reviewed pT3 lung cancer for 86 cases (13.1%) out of 659 cases treated surgically for primary lung cancer between 1985 and march 1998. Five-year and ten-year survival rates for all pT3 cases were 48% and 40% respectively and those for pT3N0M0 cases were 67.2%. The operative mortality between 1990 and 1998 (2.4%) was better than that between 1985 and 1989 (6.7%). The extensive resection for pT3 lung cancer was evaluated to be appropriate. However, the prognosis of the patients who underwent combined resection of mediastinal pleura, pericardium or diaphragm was very poor. Five-year survival rate was significantly worse in patients with N2 disease (17.3%) than in patients with N0 disease (65.8%) (p < 0.05). Although the surgical indication for the patients with mediastinal pleura, pericardium or diaphragm disease and N2 disease is still controversial, there is not the extensive surgical indication.

Adolescent↗

PubMed1997

Cloning and characterization of mammalian 8-hydroxyguanine-specific DNA glycosylase/apurinic, apyrimidinic lyase, a functional mutM homologue.

8-Hydroxyguanine (8-OH-G) is one of the major DNA oxidation products implicated in mutagenesis induced by oxygen radical-forming agents, including ionizing radiation. It is also believed to be involved in spontaneous mutation induced by metabolically produced oxygen radicals. A mammalian homologue of 8-OH-G glycosylase/apurinic, apyrimidinic lyase (mutM homologue, MMH) has been identified in the EST database (for expressed sequence tags) through a homology search with yeast OGG1 protein. The human MMH protein (hMMH), 34% identical to the yeast OGG1 protein, is a member of the DNA repair protein superfamily. The hMMH gene was composed of seven exons, with the alternate last exon, exon 8, producing three major alternative splicing isoforms, because splicing of the sixth intron was optional. The hMMH protein expressed in Escherichia coli revealed the glycosylase activity and apurinic, apyrimidinic lyase activity on duplex DNA containing 8-OH-G. The hMMH protein can rescue a spontaneous mutator strain of E. coli lacking mutM and mutY. By the introduction of recombinant hMMH, the rate of mutation, the formation of rifampicin-resistant revertants, was reduced by 4-7 fold. Genomic structure analysis showed that 3' exons of the hMMH gene are transcribed on the antisense strand of the calcium-dependent calmodulin kinase 1 gene.

Alternative Splicing↗

PubMed1997

Characterization of the alternative excision repair pathway of UV-damaged DNA in Schizosaccharomyces pombe.

Schizosaccharomyces pombe cells deficient in nucleotide excision repair (NER) are still able to remove photoproducts from cellular DNA, showing that there is a second pathway for repair of UV damage in this organism. We have characterized this repair pathway by cloning and disruption of the genomic gene encoding UV damage endonuclease (UVDE). Although uvde gene disruptant cells are only mildly UV sensitive, a double disruptant of uvde and rad13 (a S. pombe mutant defective in NER) was synergistically more sensitive than either single disruptant and was unable to remove any photoproducts from cellular DNA. Analysis of the kinetics of photoproduct removal in different mutants showed that the UVDE-mediated pathway operates much more rapidly than NER. In contrast to a previous report, our genetic analysis showed that rad12 and uvde are not the same gene. Disruption of the rad2 gene encoding a structure- specific flap endonuclease makes cells UV sensitive, but much of this sensitivity is not observed if the uvde gene is also disrupted. Further genetic and immunochemical analyses suggest that DNA incised by UVDE is processed by two separate mechanisms, one dependent and one independent of flap endonuclease.

Cloning, Molecular↗

PubMed1997

Unstable expression of the multi-drug-resistant phenotype in Chinese hamster ovary cells resistant to okadaic acid.

A Chinese hamster ovary cell line resistant to okadaic acid (OA), OAR2-3 has a mutation of the protein phosphatase (PP) 2A alpha gene and expresses a multi-drug resistance (MDR) phenotype. In the present work, we isolated two additional OA-resistant variants, also showing MDR with a cross-resistance profile similar to that of OAR2-3, and with increased and decreased expressions of the P-glycoprotein (Pgp) and DNA topoisomerase (topo) II protein, respectively. Unlike OAR2-3, however, they had no mutation in the same region of the PP2A alpha gene. Except for OA-resistance in OAR2-3, the MDR was found to decrease in the absence of OA, and this decrease was again associated with changes in topo II- and Pgp-expressions. Thus, we conclude that 1) OA regulates the expressions of Pgp and topo II positively and negatively, respectively, resulting in reversible expression of MDR irrespective of genetic changes and 2) in OAR2-3, the mutation in the PP2A alpha gene confers stable resistance to OA. The MDR was also linked with collateral sensitivity to some drugs, like cisplatin and nitrogen mustard.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Silicone-coated polypropylene hollow-fiber oxygenator: experimental evaluation and preliminary clinical use.

BACKGROUND: A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-microm ultrathin silicone layer (cyclosiloxane) was developed. Animal experimental and preliminary clinical studies evaluated its reliability in bypass procedures. METHODS: Five 24-hour venoarterial bypass periods were conducted on dogs using the oxygenator (group A). In 5 controls, bypass periods were conducted using the same oxygenator without silicone coating (group B). As a preliminary clinical study, 14 patients underwent cardiopulmonary bypass with the silicone-coated oxygenator. RESULTS: Eight to 16 hours (mean, 12.2 hours) after initiation of bypass, plasma leakage occurred in all group B animals, but none in group A. The O2 and CO2 transfer rates after 24 hours in group A were significantly higher than at termination of bypass in group B (p < 0.005 and p < 0.03, respectively). Scanning electron microscopy of silicone-coated fibers after 24 hours of bypass revealed no damage to the silicone coating of the polypropylene hollow fibers. In the clinical study, the oxygenator showed good gas transfer, acceptable pressure loss, low hemolysis, and good durability. CONCLUSIONS: This oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.

Animals↗

PubMed1997

Nature and site of action of endogenous nitric oxide in vasculature of isolated pig lungs.

The site of action of endogenous and exogenous nitric oxide (NO) in isolated pig lungs was investigated by using arterial, double, and venous occlusions, which allowed precapillary, postcapillary, and venous segments to be partitioned into arterial, precapillary, postcapillary, and venous segments. NG-nitro-L-arginine (L-NNA; 10(-5) M) increased resistance in the arterial (35 +/- 6.6%. P = 0.003), precapillary (39.3 +/- 5.1%, P = 0.001), and venous (18.3 +/- 4.8%, P = 0.01) segments, respectively. Sodium nitroprusside (10(-5) M) NO (80 parts/million) reversed the effects of L-NNA. Total pulmonary vascular resistance fell with increasing flow, due to a fall in precapillary resistance and dynamic resistance, and was significantly lower than mean total resistance. L-NNA increased the resistances but did not alter the pattern of the pressure-flow relationships. It is concluded that, in isolated pig lungs, the effect of endogenous NO seems to be dependent on flow in the arterial segment and independent of flow in the precapillary segment, but variation of its release does not appear to be fundamental to accommodation to changes in steady flow.

Animals↗

PubMed1997

Translocation of a UV-damaged DNA binding protein into a tight association with chromatin after treatment of mammalian cells with UV light.

A UV-damaged DNA binding protein (UV-DDB) is the major source of UV-damaged DNA binding activity in mammalian cell extracts. This activity is defective in at least some xeroderma pigmentosum group E (XP-E) patients; microinjection of the UV-DDB protein into their fibroblasts corrects nucleotide excision repair (NER). In an in vitro reconstituted NER system, small amounts of UV-DDB stimulate repair synthesis a few fold. After exposure to UV, mammalian cells show an early dose-dependent inhibition of the extractable UV-DDB activity; this inhibition may reflect a tight association of the binding protein with UV-damaged genomic DNA. To investigate the dynamics and location of UV-DDB with respect to damaged chromatin in vivo, we utilized nuclear fractionation and specific antibodies and detected translocation of the p127 component of UV-DDB from a loose to a tight association with chromatinized DNA immediately after UV treatment. A similar redistribution was found for other NER proteins, i.e. XPA, RP-A and PCNA, suggesting their tighter association with genomic DNA after UV. These studies revealed a specific protein-protein interaction between UV-DDB/p127 and RP-A that appears to enhance binding of both proteins to UV-damaged DNA in vitro, providing evidence for the involvement of UV-DDB in the damage-recognition step of NER. Moreover, the kinetics of the reappearance of extractable UV-DDB activity after UV treatment of human cells with differing repair capacities positively correlate with the cell's capacity to repair 6-4 pyrimidine dimers (6-4 PD) in the whole genome, a result consistent with an in vivo role for UV-DDB in recognizing this type of UV lesion.

Animals↗

PubMed1997

High attenuation lymphadenopathy caused by amyloidosis.

We describe a patient with generalized lymphadenopathy due to amyloidosis which showed on computed tomography as masses with high attenuation. Haemorrhage within lymph nodes caused by vascular amyloid deposition was confirmed at autopsy.

Amyloidosis↗

PubMed1997

Rapid changes in pial arterial diameter and cerebral blood flow caused by ipsilateral carotid artery occlusion in rats.

We investigated rapid changes in pial arterial diameter and in cerebral blood flow (CBF) caused by transient ipsilateral common carotid artery occlusion (CCA-O) in anesthetized rats in order to elucidate how the cerebral circulation reacts to acute stem artery occlusion. In separate groups of rats, pial arterial diameter was recorded through a closed cranial window and CBF was recorded by laser-Doppler flowmetry. CCA-O was performed for 5 minutes under normotension and normocapnia (control) and under graded hypotension, hypercapnia and hypocapnia. In the control condition, pial arterial diameter increased rapidly, triggered by CCA-O. It took 12 +/- 3 s to reach the maximum of 204 +/- 42% of the value before CCA-O, and 60 +/- 24 s to become stable at 131 +/- 11%. CBF decreased rapidly to 66 +/- 11%, then increased reactively to 135 +/- 9%, and again decreased to 91 +/- 3%. The reactive increase in CBF caused by CCA-O decreased in parallel with the degree of hypotension, and also became barely detectable under hypercapnia. Our data suggest that active vascular dilation in the territory of the occluded artery is important for inducing collateral circulation.

Animals↗

PubMed1997

[Treatments for T4 advanced lung cancer with invasion to the superior vena cava].

We discussed on the treatments for T4 lung cancer with invasion to the superior vena cava, whose prognosis has been poor. However, surgical resection may improve the prognosis compared with radiation therapy. The prosthetic replacement of superior vena cava can be done safely, and its patency is good in cases of ring-enforced ePTFE graft. Although superior vena caval obstruction syndrome had been a hard issue in the advanced cases, stenting in superior vena using the interventional radiological technique is a safe and reliable method. We should consider the stenting as the first choice for superior vena cava obstruction syndrome, because it makes the QOL improve so much.

Adult↗

PubMed1997

[Ruptured fusiform aneurysm of the basilar artery with minimal atherosclerosis--report of a case].

We reported a case of ruptured fusiform aneurysm of the basilar artery with minimal atherosclerosis. A 51-year-old man was admitted because of subarachnoid hemorrhage (SAH). He had no previous illness and family history. Computed tomographic scan revealed subarachnoid hemorrhage and a fusiform aneurysm in the basilar artery. Cerebral angiography confirmed the presence of the basilar fusiform aneurysm. After four days, the consciousness level worsened and a respiratory support was initiated. The patient died on the fifth hospital day. Autopsy was permitted only to the brain. The brain weighed 1,700 g. Massive subarachnoid hemorrhage was noted at the base of the brain and in the sylvian fissures. A large fusiform aneurysm (30 x 20 x 17 mm) was located in the proximal portion of the basilar artery. Atherosclerotic changes were minimal in the aneurysmal wall and the major extracerebral arteries. SAH was most severe around the aneurysm. The pons showed focal necrosis due to compression by the aneurysm. Microscopically, the aneurysmal wall revealed diffuse attenuation of the muscularis. The elastica also showed a focal defect. We suggest that in the present case of fusiform aneurysm, the pathogenesis is not atherosclerosis but a congenital defect of the muscularis and elastic lamina.

Aneurysm, Ruptured↗

PubMed1996

Intravascular substance P dilates cerebral parenchymal vessels through a specific tachykinin NK1 receptor in cats.

The role of substance P in the cerebral parenchymal circulation was examined in 19 anesthetized cats. The local cerebral blood volume in the temporoparietal cortex was measured by our photoelectric method. Cerebral blood volume reflects the cumulative dimensions of the parenchymal microvessels. Intravenous injection of 0.01, 0.1, and 1 mg/kg FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl) carbonyl-L-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide) , a selective tachykinin NK1 receptor antagonist, had no significant effects (compared to the vehicle, ethanol) on cerebral blood volume and mean arterial blood pressure. Intracarotid injection of 1, 10, 100 pmol/kg, and 1 nmol/kg substance P increased cerebral blood volume (P < 0.01) in a dose-dependent manner (maximal increase of 6.5% at 5 min). Following injection of 1 nmol/kg substance P, cerebral blood volume was initially reduced, possibly due to the marked fall in mean arterial blood pressure (P < 0.01). The cerebral blood volume increase elicited by 1 nmol/kg substance P was strongly blocked (P < 0.05) by prior injection of 1 mg/kg FK888. However, the depressor effect of 1 nmol/kg substance P (-24 +/- 4 mm Hg at 30 s, P < 0.01) was partially inhibited (P < 0.01) by FK888. We conclude that endogenous substance P may not have a significant role in the maintenance of resting tone of cerebral parenchymal vessels. Intravascular substance P, however, dilates the small microvessels through a specific tachykinin NK1 receptor and could be involved in the development of pathologic processes such as migraine headache.

Animals↗

PubMed1996

Cloning, tissue expression, and mapping of a human photolyase homolog with similarity to plant blue-light receptors.

Enzymatic photoreactivation is a DNA repair mechanism that removes UV-induced pyrimidine dimer lesions by action of a single enzyme, photolyase, and visible light. Its presence has been demonstrated in a wide variety of organisms, ranging from simple prokaryotes to higher eukaryotes. We have isolated a human gene encoding a 66-kDa protein that shows clear overall homology to known bacterial photolyase genes. The human gene product is more similar to plant blue-light receptors within class I photolyases than to higher eukaryote class II photolyases. Northern blot analysis showed two transcripts with constitutive expression in all tissues examined and an elevated expression in testis. In situ hybridization with a cDNA-derived probe localized this human gene to chromosome 12q23-q24.1. Southern analysis of the cloned human gene suggests a wide distribution of the gene family in various species.

Amino Acid Sequence↗

PubMed1996

Production of intense low-energy positron beams with synchrotron radiation.

A low-energy positron beam is a unique probe of Fermi surfaces, defects, surfaces and interfaces. In high-energy electron and positron storage rings (E > 6 GeV) it is possible to generate intense synchrotron radiation with 1-3 MeV photons by installing a high-field superconducting wiggler. The strength of the wiggler should be ~8-12 T. High-energy photons are emitted from the wiggler and converted to low-energy positrons by using a suitable target-moderator system. For an 8 GeV electron storage ring at a beam current of 100 mA, final yields are estimated to be ~10(10)-10(12) (slow-e(+) s(-1)) with the size of positron source ~10(2)-10(3) cm(2). The possibility of increasing the brightness of the low-energy positron beam is discussed. Advantages of using synchrotron radiation for producing positrons are pointed out. The effect of a superconducting wiggler on the stored electron beam is also discussed.

Journal Article↗

PubMed1996

cDNA cloning and genomic structure of human bone morphogenetic protein-3B (BMP-3b).

BMP-3b (also termed GDF-10) is a novel BMP-3 related protein recently discovered in rat femur tissue by molecular cloning. In this paper, we have isolated cDNA and the gene for human BMP-3b and determined their structure. Cloned human BMP-3b cDNA with a size of 2632 base pairs encodes a 478 amino acid precursor protein sharing 83% identity with rat BMP-3b. The human BMP-3b gene is composed of 3 exons and spans approximately 13 kilobases of DNA. The 5' flanking region carries no typical TATA box but G+C rich sequences. Southern blot analysis revealed that the BMP-3b gene is situated in a single locus of chromosome 10. By Northern analysis, human BMP-3b transcripts were detected primarily in femur, brain, lung, skeletal muscle, pancreas and testis.

Amino Acid Sequence↗

PubMed1996

Characterization of a UV endonuclease gene from the fission yeast Schizosaccharomyces pombe and its bacterial homolog.

From the fission yeast Schizosaccharomyces pombe, a cDNA fragment was isolated, which confers UV resistance on repair deficient Escherichia coli host cells. The cloned cDNA encodes a protein of 68,815 Da, which has a 36.6% identity of amino acid sequence with the previously identified 74 kDa UV endonuclease of the filamentous fungus Neurospora crassa. Analysis of several truncated gene constructs shows that only the C-terminal two thirds region, which has 54% identity of amino acid sequence with the C-terminal region of the Neurospora homolog, is necessary for complementing activity of UV-sensitivity in the E. coli host cells. Purified recombinant protein from E. coli host cells incises both UV-induced cyclobutane pyrimidine dimers and (6-4) photoproducts at the sites immediately 5' to the DNA damage in the same fashion as the Neurospora protein. Furthermore, a bacterial homologous sequence was isolated from Bacillus subtilis and shows a similar complementing activity of UV sensitivity in E. coli host cells, indicating a wide distribution of this alternative excision repair mechanism in life.

Amino Acid Sequence↗

PubMed1996

Identification of rat bone morphogenetic protein-3b (BMP-3b), a new member of BMP-3.

Rat bone morphogenetic protein-3 (BMP-3) cDNA and BMP-3b cDNA were isolated from rat femur cDNA library by the RT-PCR method using degenerate oligonucleotide primers corresponding to human BMP-3. The deduced amino acid sequence of rat BMP-3 in the mature region reveals 2 amino acid changes compared to that of human BMP-3 (98% identity). The deduced BMP-3b amino acid sequence shows 81% similarity with the mature region of rat BMP-3 and only 37% similarity with the propeptide region. By Northern blot analysis, rat BMP-3b mRNA was detected in costa, costicartilage, femur, calvaria, trachea, aorta and brain. Among these tissues, BMP-3b transcripts were predominantly expressed in cerebellum. BMP-3 mRNA was found in femur, calvaria, trachea, lung and ovary. Although BMP-3b and BMP-3 are very closely related to each other, their transcripts are distributed in different tissues except that both are found in bone. The distribution pattern of BMP-3b mRNA suggests that BMP-3b plays an important role in the central nervous system as well as in bone formation and remodeling.

Aging↗