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K Mihara

Publications and source records attributed to K Mihara.

At least 199 records · Page 11Linked to original sources
PubMed1987

c-yes and bcl-2 genes located on 18q21.3 in a follicular lymphoma cell line carrying a t(14;18) chromosomal translocation.

The c-yes-1 and bcl-2 genes have been independently mapped at the same position of the chromosome band, 18q21.3, which is a breakpoint in the t(14;18) chromosomal translocation. High-molecular-weight genomic DNAs and mRNA isolated from a follicular lymphoma cell line FL-18 and an Epstein-Barr virus harboring FL-18EB cell line, which carried the t(14;18), were analyzed. Although there was no detectable c-yes rearrangement, the chromosome 18-specific probe b (bcl-2) revealed one rearranged fragment after EcoRI, BamHI, PstI and SstI digestion. Therefore, breakage of chromosome 18 in the t(14;18) occurred at the SstI fragment containing the probe b sequence on the bcl-2 gene. The transcript of c-yes was undetectable, whereas active transcription of bcl-2 was observed in the FL-18 and FL-18EB cell lines at a higher level than in other types of lymphoma cell line. These data suggest that the c-yes-1 is not involved in the t(14;18), and the 2 genes located at 18q21.3 are independent sequences.

Aged↗
PubMed1987

A short amino-terminal segment of microsomal cytochrome P-450 functions both as an insertion signal and as a stop-transfer sequence.

Co-translational insertion of liver microsomal cytochrome P-450 into the endoplasmic reticulum membrane is mediated by the signal recognition particle (SRP) and the presence in the cytochrome molecule of a signal sequence that can be recognized by SRP has been postulated. To locate this signal sequence, six hybrid cDNAs were constructed in which various segments of a cDNA for a rabbit liver cytochrome P-450 are fused with a cDNA or its fragment encoding yeast porin (an outer mitochondrial membrane protein) or with a cDNA for pre-interleukin 2 (a secretory protein) from which the 5'-terminal portion encoding most of its signal sequence had been removed. These hybrid cDNAs were inserted into an SP-6 transcription vector and transcribed in vitro. The mRNAs thus synthesized were translated in a cell-free system in the presence of rough microsomes. It was thus found that only those chimeric proteins containing (at their amino-terminal end) the amino-terminal cytochrome P-450 segments consisting of greater than or equal to 29 amino acid residues were co-translationally inserted into the membrane in an SRP-dependent fashion. These proteins were, however, neither processed nor translocated across the membrane. These findings, coupled with the observation that the major portion of these proteins, when inserted into the membrane, was degraded by trypsin, led to the conclusion that a short amino-terminal segment (less than 29 residues) of the cytochrome P-450 functions not only as an insertion signal but also as a stop-transfer sequence. This segment is, therefore, similar to the internal signal of type II plasma membrane proteins, but differs from the latter in the topogenic function.

Amino Acid Sequence↗
PubMed1987

Structural analysis of cloned cDNAs for polycyclic hydrocarbon-inducible forms of rabbit liver microsomal cytochrome P-450.

Two cDNA clones, pHPah1 and pHPah2, encoding polycyclic hydrocarbon-inducible forms of rabbit liver microsomal cytochrome P-450 were isolated and their nucleotide sequences were determined. The inserts of pHPah1 and pHPah2 contained open reading frames specifying the entire primary structures of cytochrome P-450s, consisting of 518 and 516 amino acid residues, respectively. The deduced amino acid sequences for pHPah1 and pHPah2 are 76 and 73% homologous with rat P-450c and P-450d, respectively, and 96% homologous with rabbit P-450 forms 6 and 4, respectively. We conclude that pHPah1 and pHPah2 encode the rabbit counterparts of rat P-450c and P-450d, respectively. A region highly conserved in all species of cytochrome P-450 so far examined, called the HR2 region, can be detected in the pHPah1 and pHPah2 primary structures, but another conserved region, HR1, cannot be observed. Northern hybridization analysis of total RNAs from livers of untreated and drug-treated rabbits demonstrated that the pHPah1 and pHPah2 genes are expressed in untreated animals, induced considerably by administration of 3-methylcholanthrene or beta-naphthoflavone, and suppressed by phenobarbital and isosafrole.

Amino Acid Sequence↗
PubMed1986

Secondary activation of c-abl may be related to translocation to the nucleolar organizer region in an in vitro cultured rat leukemia cell line (K3D).

Localization of cellular oncogenes (c-onc) near the break points of translocations in tumor cells has indicated involvement of these genes in neoplastic growth. Enhanced transcription of the cellular homolog (c-abl) of the transforming sequence of Abelson murine leukemia virus was observed in K3D, which was one of the cloned cell lines of 7,12-dimethylbenz[a]anthracene-induced rat erythroblastic leukemia. Since the c-abl activation was not observed in the parent cell line (K2D) from which K3D was derived and the latter was different from the former in the presence of a new marker chromosome, t(3;12), this marker may play a role in the expression of c-abl in K3D cells. In contrast to the human c-onc assignments, few rat c-onc assignments have been reported. In situ molecular hybridization studies assigned c-abl to the 3q12 site of the normal chromosome 3 and to the break point of the translocation t(3;12) in K3D cells. Another break point in this translocation chromosome 12p11 involves the nucleolar region, and the 3;12 translocation may involve c-abl and nucleolar cistrons. These results provide evidence of secondary c-onc activation during karyotypic evolution of cloned malignant cells.

Abelson murine leukemia virus↗
PubMed1986

Immunohistochemical study of lysozyme in lupus miliaris disseminatus faciei.

The lysozyme activity in tissue samples from patients with lupus miliaris disseminatus faciei (LMDF), sarcoidosis and foreign body granuloma was investigated using the immunoperoxidase technique. The majority of epithelioid cells and giant cells in LMDF and sarcoidosis showed strong lysozyme staining in their cytoplasm. However, most macrophages and giant cells in foreign body granulomas, including granulomatous reactions to epidermal cysts and other foreign materials, stained weakly for lysozyme or were negative. These results suggest that LMDF is different from the foreign body reaction to inert substances, and may be induced by an immunological mechanism associated with cell-mediated immunity.

Adult↗
PubMed1986

1,25-Dihydroxyvitamin D3-regulated expression of genes involved in human T-lymphocyte proliferation and differentiation.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited the secretion of gamma-interferon from human T-lymphocytes activated by the calcium ionophore, A23187, or phytohemagglutinin with or without 12-O-tetradecanoylphorbol-13-acetate. The agent also inhibited cell proliferation and interleukin 2 secretion by these cells. The inhibition of gamma-interferon secretion was time and dose dependent and partially abolished by the addition of exogenous human recombinant interleukin 2. To elucidate the molecular events by which 1,25-(OH)2D3 inhibits cell proliferation and lymphokine secretion, complementary DNA probes were used to follow the expression of genes involved in human T-lymphocyte proliferation and differentiation. 1,25-(OH)2D3 inhibited the expression of interleukin 2 and gamma-interferon messenger RNA in human lymphocytes activated by phytohemagglutinin and 12-O-tetradecanoylphorbol-13-acetate. It also inhibited the accumulation of c-myc protooncogene messenger RNA and, to a lesser extent, interleukin 2 receptor messenger RNA in these cells. However, it did not affect the expression of the HLA-DR gene. These results suggest that 1,25-(OH)2D3 selectively regulates T-lymphocyte activation-related genes at the level of messenger RNA.

Calcimycin↗
PubMed1985

Molecular cloning and sequencing of cDNA for yeast porin, an outer mitochondrial membrane protein: a search for targeting signal in the primary structure.

We have cloned a full-length cDNA for yeast porin, the major outer mitochondrial membrane protein from Saccharomyces cerevisiae, and determined its nucleotide sequence. The primary structure of the protein, deduced from the nucleotide sequence, consisted of 283 amino acid residues and its NH2-terminal sequence, Met-Ser-Pro-Pro-Val-Tyr-Ser, coincided with that determined by Edman degradation for yeast porin, except that the initiator methionine was missing in the mature protein. The deduced sequence had an overall polarity index of 46.3%, a value which falls in the normal range for soluble proteins. An evaluation of hydropathy of the protein indicated that the NH2-terminal one third was relatively hydrophilic and the rest of the molecule was rather hydrophobic. An interesting finding was that the NH2-terminal region of yeast porin (consisting of some 50 amino acid residues) shows structural features that resemble those of the corresponding portion of 70-kd protein, which is also a yeast outer mitochondrial membrane protein. We postulate that this NH2-terminal sequence, like that of 70-kd protein, is required for targeting the porin to the outer mitochondrial membrane.

Bacterial Outer Membrane Proteins↗
PubMed1985

Cooperative regulation of c-myc expression in differentiation of human promyelocytic leukemia induced by recombinant gamma-interferon and 1,25-dihydroxyvitamin D3.

The biological activity of recombinant human gamma-interferon (IFN-gamma) to induce the phenotypic differentiation of human promyelocytic leukemia cell line HL-60 and to regulate c-myc expression was evaluated. Treatment with IFN-gamma increased monocyte-associated cell surface antigens detected by monocyte-specific monoclonal antibodies in a dose- and time-dependent manner. These antigenic changes were accompanied by a functional differentiation, determined by the increase of phagocytic capability and superoxide generation. IFN-gamma was also found to suppress the growth of HL-60 cells and reduce expression of a c-myc oncogene. These phenotypic and morphological changes to macrophage-like cells induced by IFN-gamma were similar to those by 1,25-dihydroxyvitamin D3, whereas the plasma membrane antigenic changes were different. Moreover, the combination of IFN-gamma and suboptimal doses of 1,25-dihydroxyvitamin D3 have synergistic effects in augmenting mature monocyte specific antigens (Mo2, 63D3, OKM1, and OKM5). In the reduction of c-myc expression by these drugs, a cooperative effect was observed with the inhibition of transferrin receptor expression and cell growth. These results indicate that human recombinant IFN-gamma induces a monocyte phenotype in the HL-60 cells via a mechanism different from the action of 1,25-dihydroxyvitamin D3.

Antigens, Surface↗
PubMed1984

Comparative metabolism of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) in mice and rats.

In male and female DDY/Slc mice given single oral doses (20 or 500 mg/kg body weight) of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) labelled with 14C at the p-methyl group, 14C was distributed mainly in the stomach, intestines, liver and kidney, and then excreted in the urine, faeces and expired air. During the 7 days after treatment, 41-65, 26-50 and 6-9% of the 14C dose was excreted in faeces, urine and expired air, respectively, and the total recovery was 96-98%. Levels of 14C in 21 male and 22 female tissues 7 days after treatment were less than 1 microgram BHT equivalents/g tissue (ppm) in mice given 20 mg/kg and less than 11 ppm in mice given 500 mg/kg. When [14C]BHT was given orally to male mice at 20 mg/kg/day for 10 days, 14C was rapidly excreted and did not exhibit any tendency to accumulate in any tissues. Thin-layer chromatography and high-performance liquid chromatography analyses showed that more than 43 metabolites were present in the urine and faeces of both species, and all of these were identified to determine metabolic pathways for BHT in mice and rats. Major metabolic reactions of [14C]BHT in mice were the oxidation of the p-methyl group attached to the benzene ring and of the tert-butyl groups. The products from the latter reaction were cyclized to some extent by reacting with the adjacent phenolic OH group to give hemiacetals or lactones. The carboxyl derivatives from the p-methyl oxidation were conjugated with glucuronic acid. When single oral doses of 20 or 500 mg [14C]BHT/kg were given to male Sprague-Dawley rats, metabolites similar to those in mice were found. However, the major biotransformation was oxidation of the p-methyl group, and oxidation of the tert-butyl groups was a minor reaction in rats.

Animals↗
PubMed1984

Signal recognition particle is required for co-translational insertion of cytochrome P-450 into microsomal membranes.

Insertion of newly synthesized P-450(1), the major phenobarbital-inducible form of rabbit liver microsomal cytochrome P-450, into microsomal membranes was studied in a wheat germ cell-free translation system programed with total RNA from the liver of a phenobarbital-treated rabbit. P-450(1) synthesized in vitro had the same molecular weight as the mature molecule and was co-translationally inserted into dog pancreas rough microsomal membranes. In the presence of salt-washed microsomes, instead of unwashed ones, the insertion was greatly diminished. It could, however, be restored by supplementation of the system with purified signal recognition particle (SRP), a known component of the membrane translocation machinery for secretory proteins. In the absence of microsomes, SRP inhibited the translation of mRNA encoding P-450(1) and this translation arrest was released by the addition of salt-washed microsomes. On the other hand, SRP did not affect the translation of mRNAs encoding yeast porin and reticulocyte globin, which are mitochondrial and cytosolic proteins, respectively. We conclude that co-translational insertion of P-450(1) into microsomal membranes requires SRP and postulate that P-450(1) possesses an uncleavable signal sequence that can be recognized by SRP.

Cytochrome P-450 Enzyme System↗
PubMed1984

[Multiple anomalies of cerebral vessels. A case of multiple aneurysms associated with fenestration of the middle cerebral artery and persistent primitive trigeminal artery].

A case of multiple intracranial anomalies was reported. They consisted of fenestration of the middle cerebral artery (MCA), persistent primitive trigeminal artery and four intracranial aneurysms. The patient, 45-year-old male, had an attack of subarachnoid hemorrhage on July 15, 1982. He was transferred and admitted to our Dept. of Neurosurgery on July 27. On admission neurological examinations revealed retinal hemorrhage, bilateral papilledema and abducens nerve paresis on the left. Cerebral angiography demonstrated multiple aneurysms, one in the left vertebral artery, one in the left MCA, one in the right IC-PC junction and one in the fenestrated right MCA and persistent primitive trigeminal artery. Computed tomography (CT) demonstrated high density areas in the basal cistern and bilateral sylvian fissures, and cavum septi pellucidi and cavum Vergae as well. Surgical intervention was done and all aneurysms were clipped or coated successfully. The aneurysm in the fenestrated right MCA had originated from the proximal end of the fenestration of the MCA. The cavum septi pellucidi and cavum Vergae were asymptomatic. The postoperative course was uneventful. The authors discussed the pathogenesis and clinical meanings of fenestration of the MCA and persistent primitive trigeminal artery, and inferred that the genetic abnormality at the stage of development of cerebral vessels could play one part of the formation of intracranial aneurysms, because of the fact that the cerebrovascular anomalies showed high incidence of coexistence of intracranial aneurysms.

Cerebral Angiography↗