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Biomedical subjects

M Shibuya

Publications and source records attributed to M Shibuya.

At least 343 records · Page 19Linked to original sources
PubMed1990

Effects of STA-MCA anastomosis for ischaemic oculopathy due to occlusion of the internal carotid artery.

Effects of STA-MCA anastomosis on two patients with neovascular glaucoma due to occlusion of the internal carotid artery are presented. Both patients improved in visual acuity and central retinal artery pressure as well as in signs of transient ischaemic attack. Postoperative angiography showed a marked decrease in collateral flow through the ophthalmic artery, which is reversed from the normal direction, with the development of blood flow through the anastomosis. Discussion is offered indicating that the lack of collateral flow through both the anterior and posterior communicating arteries is important in addition to occlusion of the internal carotid artery in order to produce full-blown ischaemic oculopathy such as venous stasis retinopathy, neovascular glaucoma or rubeosis iridis. It is stressed that EC-IC bypass surgery should be performed soon after the appearance of ischaemia and before the development of neovascular glaucoma or rubeosis iridis in order to obtain normal vision. In ischaemic oculopathy the results of EC-IC bypass can be evaluated objectively and quantitatively by many noninvasive neuroophthalmological tests which are important in discussing the efficacy of the bypass surgery.

Arterial Occlusive Diseases↗
PubMed1990

Antimetastatic effect of defibrinogenation with batroxobin depends on the natural killer activity of host in mice.

Using batroxobin, a thrombin-like enzyme found in snake venom, the effects of defibrinogenation on artificial lung metastasis in mice were studied. The role of natural killer (NK) cells in the inhibitory effects of defibrinogenation on metastasis was also investigated. Artificial lung metastasis experiments were performed by inoculating either B16-F10 cells or B16-BL/6 cells, highly metastatic strains of B16 melanoma cells, into C57BL/6 mice via the tail vein. The administration of batroxobin significantly inhibited lung metastasis, as did NK activity augmented by poly (I).poly (C) were administered, lung metastasis was more markedly inhibited. When NK activity was suppressed by administration of anti-(asialo GM1) antibody, lung metastasis was markedly increased. When batroxobin was administered with anti-(asialo GM1) antibody, no inhibitory effects on lung metastasis, such as those seen with batroxobin alone, were observed. The administration of batroxobin had no effect at all on spleen lymphocyte NK activity. These results indicated that defibrinogenation due to batroxobin inhibits lung metastasis, and these effects depend on NK activity of the host.

Animals↗
PubMed1990

Endothelin causes contraction of canine and bovine arterial smooth muscle in vitro and in vivo.

We have studied the effect of endothelin, an endothelium-derived peptide, on isolated canine and bovine cerebral arteries in vitro and on canine vertebral blood flow (VBF) in vivo. Endothelin produced a dose-dependent contraction of canine and bovine arterial smooth muscle with ED50 values ranging from 4 to 8 nM. The response to endothelin developed slowly and persisted as a sustained contraction. Maximal contraction by endothelin required the presence of extracellular calcium and was independent of the presence of endothelium. The maximal contraction produced by endothelin was approximately 2-3 times greater than that produced by neuropeptide Y or angiotensin II. The injection of endothelin into the vertebral artery decreased vertebral blood flow (VBF) dose-dependently without affecting systemic blood pressure or heart rate. The decrease in VBF produced by endothelin was long-lasting, like that produced by neuropeptide Y, but more potent. The present data, together with our previous study demonstrating that the intracisternal injection of endothelin induces an unusually long-lasting decrease in the basilar artery diameter angiographically, suggests that endothelin may act as a long-lasting vasoconstrictor in cerebral vascular disease.

Angiotensin II↗
PubMed1990

Blood component induction of cerebral vasospasm.

The role of blood components in cerebral vasospasm was evaluated using an in vivo canine model. An intracisternal injection of 5 ml of washed red blood cells (RBCs) and platelet-rich plasma (PRP) resulted in acute vasospasm of the basilar artery as seen by angiography. This was comparable with the degree of vasospasm induced by an injection of the same amount of whole blood. Repeated injections of blood components or whole blood on Days 1 and 3 induced chronic vasospasm, as shown by angiography on Day 7. Results clearly indicate that chronic vasospasm was produced by RBCs and PRP, and it was in a dose-dependent manner with increasing concentrations of RBCs (hematocrit: 30, 50, and 70%). The vasospasm induced by both components closely reproduced that seen with whole blood. Neither acute nor chronic vasospasm induced by blood component injection was associated with clot formation in the subarachnoid space, as confirmed by an autopsy. These results suggest that the extravasation of RBCs and PRP into the subarachnoid space produces cerebral vasospasm by mechanisms independent of blood clot formation.

Animals↗
PubMed1990

Alterations of mouse proto-oncogenes in sarcomas induced after transplantation of human tumors in athymic nude mice.

During serial subcutaneous transplantation of several types of human tumors into nude mice, the local development of malignant mouse-specific sarcomas has been observed. Although the frequency of sarcoma induction is low, this phenomenon is very important because the mouse-specific sarcomas completely replaced the human tumors during serial transplantation. The DNA of five independently induced mouse-specific sarcomas was transfected into NIH/3T3 cells in order to detect oncogenes associated with mouse-specific sarcoma induction. Two of these DNAs were found to carry activated mouse c-N-ras and c-Ki-ras genes. The sequence analysis of the molecularly cloned mouse c-N-ras oncogene showed a single nucleotide transition from G to A at the 12th codon. This results in substitution of aspartic acid for glycine at this position. The mouse c-myc gene was also found to be amplified in a sarcoma. In these mouse sarcoma DNAs, human Alu sequences were not detected. These data strongly suggest that the mouse-specific sarcomas were not induced by the transfer of human transforming sequences but by the alterations of mouse proto-oncogenes.

Amino Acid Sequence↗
PubMed1990

A deletion mutation within the ligand binding domain is responsible for activation of epidermal growth factor receptor gene in human brain tumors.

Two transplantable cell lines of human glioblastoma multiforme GL-3 and GL-5 carried an amplification and overexpression of structurally altered epidermal growth factor (EGF) receptor gene: the 140 kilodalton EGF receptors in these cases exhibited a constitutively expressed tyrosine kinase activity without the ligand. Here, we isolated the abnormal EGF receptor cDNA from GL-5 cell line, and demonstrated that this cDNA bears a single large intramolecular deletion mutation 801 base pairs long within the ligand binding domain of EGF receptor. In other regions no amino acid substitution was observed. At the level of genomic DNA, this deletion appeared to start from the 1st intron and terminate in the 6th intron of the EGF receptor gene. However, in the two lines of glioblastoma, GL-3 and GL-5, the positions of the start or the end of the deletion mutation in these introns were not identical, suggesting an involvement of a unique recombination mechanism in the formation of deletion mutation. A weak but ligand-independent transforming activity was observed in the deletion-carrying EGF receptor cDNA.

Animals↗
PubMed1990

Tissue-specific expression of rat c-ros-1 gene and partial structural similarity of its predicted products with sev protein of Drosophila melanogaster.

The expression and predicted products of rat c-ros-1 gene, the proto-oncogene of v-ros in UR2 sarcoma virus, were characterized. The c-ros-1 gene was found to be expressed in a tissue-specific manner, and the sizes of its transcripts were heterogeneous: 8.2 kilobases (kb) long in lung and kidney tissues, 6.9 kb in heart tissue, and 2.4 kb and 1.9 kb in testis tissue. The c-ros-1 cDNAs were isolated from lung and heart tissues. The predicted product of the c-ros-1 gene in lung tissue was a receptor-type tyrosine kinase 2,317 amino acids long (including a very large extracellular domain of approximately 1,800 amino acids) which showed a partial but significant structural homology with the sev gene product of Drosophila melanogaster. An alternatively sliced lung transcript was found to encode a protein with external and transmembrane domains but not a tyrosine kinase catalytic domain. The predicted product in heart tissue was essentially identical to that in lung tissue except for a shorter amino-terminal region and a 21-amino-acid insertion in the extracellular domain. On the basis of these results, the c-ros-1 gene appears to be active in the lungs and kidneys and probably in the hearts of rats.

Amino Acid Sequence↗
PubMed1990

A novel mammalian protein kinase gene (mak) is highly expressed in testicular germ cells at and after meiosis.

We isolated a novel gene designated mak (male germ cell-associated kinase) by using weak cross-hybridization with a tyrosine kinase gene (v-ros). Sequence analysis of the cDNA corresponding to the 2.6-kilobase transcript revealed that the predicted product of rat mak consisted of 622 amino acids and contained protein kinase consensus motifs in its amino-terminal region. Comparison of the deduced amino acid sequence of mak in the kinase domain with those of other protein kinase genes demonstrated that mak was approximately 40% identical to the cdc2-CDC28 gene family in Schizosaccharomyces pombe, Saccharomyces cerevisiae, and humans but less identical to most other protein kinase gene products. Expression of mak was highly tissue specific, and its transcripts were detected almost exclusively in testicular cells entering and after meiosis but hardly detectable in ovarian cells including oocytes, after the dictyotene stage. These results suggest that the mak gene plays an important role in spermatogenesis.

Amino Acid Sequence↗
PubMed1990

Nonlethal G0-ts mutant tsJT60 becomes lethal at the nonpermissive temperature after transformation: a hint for new cancer chemotherapeutics.

tsJT60 is a nonlethal temperature-sensitive (ts) mutant of a Fischer rat cell line (3Y1) classified as a G0 mutant; i.e., the ts defect is not expressed within the cell growth cycle but is expressed only between the G0 and S phase. tsJT60 clones transformed with oncogenes such as adenovirus E1A, polyoma large T, polyoma middle T, v-Ki-ras, and LTR activated c-myc, or with a chemical carcinogen N-methyl-N'-nitro-N-nitrosoguanidine, grew well at 34 degrees C. However, most of these clones grew slowly at 40 degrees C, producing many floating dead cells, and some clones were killed at 40 degrees C. When they were cultured under conditions inadequate for growth of untransformed cells, such as high cell density or serum restriction, they were killed at 40 degrees C. These and previous results from SV40- and adenovirus-transformed tsJT60 clones favour the idea that transformed tsJT60 cells occasionally enter the G0 phase and are metabolically imbalanced at 40 degrees C during self-stimulation from the G0 to S phase. We propose that a drug which exclusively block, G0-G1 transition would be cytocidal to transformed cells but cytostatic to normal cells.

Adenovirus Early Proteins↗
PubMed1990

[New treatments for urogenital toxicity of anti-neoplastic chemotherapy].

Renal dysfunction and urinary disorders are the most troublesome adverse reaction to anticancer agents such as cisplatin (CDDP) and ifosfamide (IFM). A number of antidotes such as sodium thiosulfate (STS), WR-2721, thiourea, diethyldithiocarbamate and bismuth subnitrate have been tested to reduce the nephrotoxicity of CDDP. One notable method previously reported by Baba et al. and Pfeifle et al involves the i.v. administration of STS to prevent the nephrotoxicity of CDDP given locally. Since STS has been proven clinically effective in reducing such side effects, we initiated a study of STS in patients with advanced non-small-cell lung carcinoma who were given a combination of CDDP and vindesine (VDS) systemically. Urinary levels of beta 2-microglobulin (BMG) and N-acetyl-beta-D-glucosaminidase (NAG) were measured as an index of proximal tubular function. Analysis of both levels indicated that STS suppressed CDDP nephrotoxicity to a minimal level. Therefore, the present study clearly demonstrates that systemic administration of STS reduces the side effects of CDDP to a minimal level without impairing its antitumor activity and that STS treatment is applicable in a repeated chemotherapy using CDDP alone or in combination with other antitumor agents. Furthermore, it has been reported that urinastatin and fosfomycin may exert potent effects to reduce untoward nephrotoxicity of CDDP. IFM causes urinary disorders such as hematuria, reducing its clinical usefulness, Sodium 2-mercaptoethane sulfonate (mesna) is the thiol compound which binds specifically to the urinary toxic metabolites of IFM, and thereby decreases the undesirable effect of IFM on the lower urinary tract, especially on the bladder. Recently, it was reported by a Osaka mesna study group that mesna is useful for the prevention of IMF-induced urinary disorders. It was considered that above new treatments were required in repeating chemotherapy which induced urogenital toxicity.

Antidotes↗
PubMed1990

SDS-polyacrylamide gel electrophoretic patterns of human parotid saliva treated with polyvinylpyrrolidone-iodine in vitro.

In the intraoral application of polyvinylpyrrolidone-iodine (PVP-I) as an antimicrobial agent, a color fading phenomenon is observed that might be caused by the binding of iodine with saliva. We have investigated the binding of iodine with saliva as iodine binding factor (IBF). The presence and characteristics of the IBF were investigated in parotid saliva stimulated by sour lemon drops, unstimulated parotid saliva, and whole saliva. A high level of the binding ability with iodine was observed in stimulated parotid saliva with the treatment of PVP-I compared with the unstimulated, but there were no significant differences in the amounts of total proteins between the stimulated and unstimulated. Electrophoretic patterns of saliva treated with PVP-I and untreated were examined to detect the IBF. The protein band of SDS-polyacrylamide gel electrophoresis near M.W. 60,000 of stimulated parotid saliva disappeared after treatment of PVP-I. This evidence indicates that the color fading phenomenon of PVP-I is associated with a polypeptide level in saliva.

Adult↗
PubMed1990

Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family.

A new human gene encoding a receptor-type tyrosine kinase was isolated by a weak cross-hybridization with v-ros oncogene. A cDNA of about 7.7 kb carried a 4.2 kb open reading frame, and the predicted amino acid sequence of 1338 residues contained extracellular, transmembrane and tyrosine kinase domains. Although its extracellular domain is approximately 220 amino acids longer than those of the products of the fms family, i.e. c-fms, c-kit and platelet-derived growth factor receptor genes, the overall structure including cysteine motifs in its extracellular domain and a long peptide insertion in its tyrosine kinase domain indicates that this new gene is closely related to the fms family. Consequently, the gene was designated as flt (fms-like tyrosine kinase) gene. The expression of the flt gene was strongly suppressed in most of the tumor cell lines examined so far, whereas this mRNA was expressed in a variety of normal tissues of adult rat.

Amino Acid Sequence↗
PubMed1989

Endothelin and the production of cerebral vasospasm in dogs.

We attempted to determine whether or not endothelin (ET) plays a physiological role in cerebral vasospasm. ET (10(-11) - 3 x 10(-8) M) induced a concentration-dependent contraction in isolated canine basilar arteries. Intracisternal injection of 10 to 1,000 pmol ET into dogs induced a dose-dependent decrease in the basilar artery diameter, as measured angiographically on the 1st day. On the 3rd day after the injection of ET (10 pmol), the diameter of the basilar artery had diminished to 76% of the value seen in the control. There were no effects on blood pressure or heart rate. Thus, ET seems to be a potent constrictor of cerebral arteries in vivo, and these effects are long-lasting.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Multi-copy introduction and high-level expression of interleukin-3 genes by retroviral vector superinfection.

We constructed a retroviral expression vector carrying multiple cloning sites. This vector was found to express efficiently the cloned gene. Using this vector and a helper virus-free system, a murine interleukin-3 (mlL-3) high-producing cell line was established by multiple cycles of infection with recombinant retroviruses carrying mlL-3 cDNA. The infected cells produced a considerable amount of mlL-3 and the concentration of mlL-3 in culture media increased as a function of the frequency of infection. High levels of mlL-3 cDNA, mRNA and protein in this cell line were confirmed by Southern, Northern and biological assays, respectively. These results suggest that artificial gene amplification is possible in a helper-free retroviral system. This should be applicable to efficient expression of bioactive molecules in a wide variety of mammalian cells including suspension cells.

Animals↗
PubMed1989

Effects of calcitonin gene-related peptide on canine cerebral artery strips and the in-vivo vertebral blood flow in dogs.

The effects of calcitonin gene-related peptide (CGRP) on canine cerebral arteries and on vertebral blood flow were investigated in-vivo and in-vitro and the findings compared with the effects of vasoactive intestinal peptide (VIP) and substance P. Administration of CGRP into the vertebral artery caused a dose-dependent and long-lasting increase in blood flow. The in-vivo vasodilatory effects of substance P and VIP were short-lasting. CGRP (0.1 to 100 nmol/l) elicited a concentration-dependent relaxation of the isolated middle cerebral and basilar arteries when the tissues were precontracted by exposure to prostaglandin F2 alpha (PGF2 alpha). This effect was not antagonized by propranolol, atropine, tetrodotoxin, (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor(1-29)-NH2 or (D-Pro2, D-Trp7,9) substance P. CGRP also reduced concentration-dependently the contraction of cerebral arteries induced by KCl or 9,11-epithio-11,12-metano-thromboxane A2 (STXA2). Mechanical removal of the endothelium did not abolish the vasodilatory response to CGRP. In PGF2 alpha-contracted canine cerebral arteries, VIP (0.1 to 100 nmol/l) was less potent a vasodilator than CGRP. At low concentrations (0.01 to 1 nmol/l) substance P elicited a rapid and short-lasting relaxation, and in the absence of endothelium this relaxation disappeared. These findings are clear evidence that CGRP modulates vascular tone.

Animals↗
PubMed1989

Molecular cloning of a feline leukemia provirus integrated adjacent to the c-myc gene in a feline T-cell leukemia cell line and the unique structure of its long terminal repeat.

This paper reports the molecular cloning of a rearranged c-myc region from the FT-1 cell line, which was derived from a spontaneous feline T-cell leukemia carrying the feline leukemia virus (FeLV). An abnormal c-myc EcoRI fragment of about 18 kilobases, detected by Southern blotting, was molecularly cloned from the DNA of the FT-1 cell line. The c-myc rearrangement in FT-1 was due to direct integration of the FeLV provirus genome immediately upstream of the c-myc gene in the opposite transcriptional orientation. Nucleotide sequencing showed that the LTR of this provirus had three copies of an enhancer-like sequence, unlike the sequences of FeLVs reported previously, which have only a single copy of this enhancer-like sequence.

Base Sequence↗
PubMed1989

Effects of neuropeptide Y and calcitonin gene-related peptide on local cerebral blood flow in rat striatum.

The effects of neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) on local cerebral blood flow (LCBF) were studied in vivo in rat striatum. Administration of 1 and 5 nmol NPY as a bolus into the internal carotid artery caused a dose-dependent decrease in the ipsilateral striatal LCBF. This decrease developed slowly and persisted for at least 2 h, without affecting mean blood pressure. In contrast, CGRP, at a concentration of 10 pmol, increased striatal LCBF by about 30%, and the duration of the increase was about 1 h. However, at higher doses of CGRP no increase in LCBF was observed. These results suggest that NPY and CGRP released from nerve fibers innervating blood vessels can function as long-acting modulators of CBF.

Animals↗