Search PubMed⌕ Search

Biomedical subjects

K Mishima

Publications and source records attributed to K Mishima.

At least 163 records · Page 9Linked to original sources

ARD 1, a 64-kDa guanine nucleotide-binding protein with a carboxyl-terminal ADP-ribosylation factor domain.

Clones referred to as ARD 1 were isolated from human and rat cDNA libraries. ARD 1 genes encode a putative 64-kDa protein that contains an 18-kDa ADP-ribosylation factor (ARF) domain at the carboxyl terminus and is much larger than the other monomeric approximately 20-kDa guanine nucleotide-binding ARF proteins thus far identified. ARD 1 mRNAs of 3.7 and 4.1 kilobases were detected in all rat tissues as well as in mouse and rabbit brain, human fibroblasts, and human neuroblastoma cells but not in HL-60 cells. Based on sequence identities, ARD 1 is highly conserved between rat and human. The ARF domain of ARD 1 contains the consensus sequences believed to be involved in guanine nucleotide binding, which are conserved in the ARFs and other GTP-binding proteins. Recombinant ARD 1 or the ARF domain of ARD 1, which lacks the 15 amino acids corresponding to the amino-terminal regions of ARFs stimulated, in a GTP-dependent manner, cholera toxin ADP-ribosyltransferase activity in the presence of 0.3% Tween 20. It had no effect in the presence of SDS, dimyristoylphosphatidylcholine/cholate, or cardiolipin. These observations are consistent with the conclusion that the amino-terminal region of ARF proteins is not required for activation of cholera toxin. In addition, the characteristic features of ARF proteins may be found as domains of larger mammalian proteins.

ADP-Ribosylation Factors↗

Prognostic factors for well-differentiated squamous cell carcinoma in the oral cavity with emphasis on immunohistochemical evaluation.

Histological and immunohistological prognostic factors for well-differentiated oral squamous cell carcinoma (SCC) were examined in 31 patients. They included 18 males and 13 females aged 42-84 (median 63) years. The tumors were located in the tongue in 13 cases, gingiva in 7, floor of the mouth in 5, cheek mucosa in 4, and palate in 2. Advanced disease (stages III and IV) was found in 92% of patients; 22 were treated by radical surgery and nine by excisional or incisional biopsy, followed by adjuvant chemotherapy and external radiation. The 5-year survival rate in patients with stages III and IV disease was 58% and 33%, respectively. Histologic factors evaluated were tumor cell mitotic counts, degree of lymphocyte and eosinophil infiltration around the tumor, mast cell counts, HLA-DR expression on tumor cells, or surrounding lymphocytes. Multivariate analysis revealed that degree of eosinophilic infiltration and expression of HLA-DR antigen on the tumor cells were significant factors for prognosis (P < 0.05); i.e., heavy eosinophilic infiltration and expression of HLA-DR antigen on tumor cells were signs of an unfavorable prognosis. The interpretation of the present findings are discussed with a review of the literature.

Adult↗

Dextrorphan attenuates the behavioral consequences of ischemia and the biochemical consequences of anoxia: possible role of N-methyl-d-aspartate receptor antagonism and ATP replenishing action in its cerebroprotecting profile.

The acute anti-ischemic and anti-anoxic effects of dextrorphan (DX) were compared with those of dizocilpine (MK-801) in a variety of animal models, and in vivo and in vitro testings under anoxic conditions. DX reduced the incidence of death in ischemic mice and improved the rotarod performance of mice with brain ischemia. The ischemically-impaired memory of mice treated with DX markedly improved, as shown in the step-through type passive avoidance test, Morris water maze and in the habituation of exploratory behavior test. MK-801 likewise improved the water maze performance of the ischemically-impaired mice, but to a lesser extent. The step-through type passive avoidance performance of ischemic mice was not improved by MK-801. In the passive avoidance task with normal mice, DX, like MK-801, produced anterograde amnesia at doses higher than those needed to attenuate the behavioral effects of ischemia. DX, intravenously or centrally administered, markedly and dose-dependently reduced the incidence of death in mice receiving potassium cyanide (KCN). DX lessened the reduction in adenosine triphosphate (ATP) and increased lactate contents in mice dosed with KCN and also lessened the reduction in ATP in the TCA cycle and oxidative phosphorylation reactions caused by KCN (0.58 mmol/l), whereas MK-801 failed to show any effect on ATP formation pathways in vivo and in vitro, and failed to protect mice against KCN-induced lethal toxicity in vivo. In the in vitro studies, DX increased the adenylate kinase activity of the rat brain homogenate. DX was found to be a cerebroprotectant with anti-ischemic and anti-anoxic actions, the effects probably stemming from its N-methyl-d-aspartate receptor antagonistic property in cooperation with its ATP replenishing action.

Adenosine Triphosphate↗

Primary malignant lymphoma of the liver.

Clinical and pathologic features of 69 cases with primary hepatic lymphoma, 52 reported from Western countries and 17 cases from Japan, were summarized in terms of clinical findings including age and sex, past history, presenting symptoms, and physical findings, diagnostic procedures including imaging techniques and histopathology, and finally therapy and follow-up. The present cases included four patients with an acquired immunodeficiency syndrome and 12 with a history of chronic liver diseases. Histologically, all cases were non-Hodgkin's lymphoma with diffuse large cell type being the most common immunochemically about 80% were B-cell type. Follow-up showed that hepatic lymphoma had a relatively favourable prognosis provided early detection was possible.

Adolescent↗

Structural studies of DNA and RNA containing AG base pairs by NMR.

Base pairing between A and G residues has been suggested in some ribozymes and the structure derived from this non-standard base pairing could play a crucial role in enzymatic actions of the ribozymes. We have studied the structures of three DNAs and an RNA that base sequences were modeled after the ribozymes by NMR. It was found that the A and G residues can form a basepair in a very unique fashion both in the DNAs and RNA. "Side" instead of "head to head" alignment of the two bases was found, where an amino proton instead of an imino proton of the G residue is involved in the hydrogen bonding. As a result of the unique basepairing, certain bases stack over the bases of the opposite strand instead of over the ones of the same strand. It was also shown that the formation and thermal stability of this unique AG basepair depend on the neighbouring base sequences. Moreover existence of the unique AG basepairs was suggested in a real small metalloribozyme itself.

Adenine↗

[Changes of bone marrow MRI pattern in aplastic anemia before and after bone marrow transplantation].

In order to evaluate the usefulness of magnetic resonance imaging (MRI) in estimating bone marrow cellularity, we performed T1-weighted MRI of the lumbar vertebral marrow in two patients with severe aplastic anemia, before and after bone marrow transplantation (BMT). High signal intensity was detected in the bone marrow before BMT, but the bone marrow pattern of MRI became normal after BMT. MRI seems to be effective for evaluating bone marrow cellularity and recovery, and for monitoring therapeutic effects in patients with aplastic anemia before and after treatment with BMT.

Adult↗

Detection of low copy numbers of Epstein-Barr virus by in situ hybridization using nonradioisotopic probes prepared by the polymerase chain reaction.

A highly sensitive in situ hybridization procedure was established using digoxigenin-11-dUTP-labeled probes that were prepared by the polymerase chain reaction (PCR). By using 12 sets of primers, BamHI-W fragment of the Epstein-Barr Virus (EBV) was amplified with labeled substrate in individual PCRs. Then the 12 probes (average size, 120 base pairs) were mixed and hybridized with cultured and RNase-treated Namalwa cells, which contain two copies of EBV genomes per cell. The strength of the signals was much stronger as compared with random-primed probe. Our results indicate that the size-averaged PCR probes magnified the sensitivity for detecting low copy numbers of virus genomes by in situ hybridization and that this technique has the potential for investigating latent virus infection in other clinical situations.

Base Sequence↗

The occurrence of monocytoid B-lymphocytes in the spleen in gastric cancer.

Occurrence of monocytoid B-lymphocytes (MBL) in spleens of 34 patients with gastric cancer was examined. Histologic findings of gastric cancer including classification, depth of invasion, and stage of disease were defined based on the General Rules for the Gastric Cancer Study (Japan). MBL were defined morphologically as having abundant pale cytoplasm with distinct cell borders and small nucleus often with reniform shape. Immunohistochemically, these cells were B-cell in nature, i.e., CD15-, CD43-, CD45RA+, CD45Ro-, CD68-, CD74+, CDw75+, Mx-PanB(L26)+, MBI+, EMA-, PG-MI-. Clusters of MBL were found in 14 of 34 (41%) patients: they were found to be directly adjoining to the periarterial sheath or apart from the white pulp. In the cases without MBL, zonation of mantle zone and marginal zone was apparent with distinct secondary follicles in 72% of cases. Meanwhile, in spleens with MBL, the mantle zone showed atrophy in a half of cases, resulting in indistinct zonation of the mantle zone and marginal zone. Secondary follicles were distinct in less than 30% of cases. Correlation of the occurrence of MBL, evaluated by Spearman's correlation coefficient, revealed that the age was the most important factor (R = -0.4852, P = 0.00364): the median age of patients with and without MBL was 75.7 and 61.7 yr, respectively. The MBL were increased in gastric cancer as compared with other cancers (P < 0.03) and with noncancer spleens (P < 0.1). The age of gastric cancer patients with MBL was older than those in other cancers and noncancer patients. Therefore occurrence of MBL in spleen might be a function of aging.

Aged↗

Regulation of ADP-ribosylation factor (ARF) expression. Cross-species conservation of the developmental and tissue-specific alternative polyadenylation of ARF 4 mRNA.

ADP-ribosylation factors (ARFs), approximately 20-kDa guanine nucleotide-binding proteins, are involved in protein trafficking and enhance cholera toxin ADP-ribosyltransferase activity. Expression of six ARF genes was examined in mammalian tissues; only ARF 4 mRNA was detected in rat testis in forms considerably shorter than those in other tissues. Testis-specific expression of short forms of ARF 4 mRNA was observed in several mammalian species. On Northern analysis of the developmental expression of rat ARF 4 mRNA, appearance of the shorter species was consistent with its involvement in a late stage of spermatogenesis. Sequences of products of rapid amplification of cDNA ends (RACE-polymerase chain reaction) of rat ARF 4 mRNA revealed that different mRNAs resulted from the use of three polyadenylation signals, one AUUAAA and two AAUAAA. Sequences of 3'-untranslated regions of rat and human ARF 4 mRNA were very similar with identical polyadenylation signals at similar positions. Of the ARF 4 mRNAs identified by RACE-PCR, with sizes of 1.1, 1.3, and 1.8 kb, the 1.1-kb mRNA was predominant in adult testis. By in situ hybridization, the 1.1-kb mRNA was identified primarily in mature sperm, consistent with the developmental studies. Shorter mRNAs, thought to be more stable, may compensate for cessation of transcription at late stages of spermatogenesis.

ADP-Ribosylation Factors↗

p33, an endogenous target protein for arginine-specific ADP-ribosyltransferase in chicken polymorphonuclear leukocytes, is highly homologous to mim-1 protein (myb-induced myeloid protein-1).

We have determined the partial amino acid sequence of p33, an endogenous substrate protein for arginine-specific ADP-ribosyltransferase in chicken polymorphonuclear leukocytes (heterophils), and found that the sequence was completely identical with the regions of amino acid sequences deduced from mim-1 (named for myb-induced myeloid protein-1, which is expressed in chicken promyelocytes) cDNA [(1989) Cell, 59, 1115-1125], except for one amino acid difference (Tyr297-->Ile). These results together with data on cellular and subcellular distributions of p33 in heterophils suggest that mim-1 may encode the precursor protein of p33.

ADP Ribose Transferases↗

Double helix formation of phosphatidylcholine myelin figures.

Double helix formation of phosphatidylcholine myelin figures has been studied by use of optical microscopy. The winding of the double helices was looser than a geometrically possible one and the pitch was related proportionally to the outer radii of helical myelin figures. The regularity in the winding was explained in terms of the intermembrane binding energy and the bending elastic energy.

Molecular Conformation↗

Molecular and immunological characterization of ADP-ribosylarginine hydrolases.

Mono-ADP-ribosylation is a reversible modification of proteins with NAD:arginine ADP-ribosyltransferases and ADP-ribosylarginine hydrolases catalyzing the forward and reverse reactions, respectively. Hydrolase activities were present in a variety of animal species, with the highest specific activities found in rat and mouse brain, spleen, and testis. Rat and mouse hydrolases were dithiothreitol- and Mg(2+)-dependent, whereas the bovine and guinea pig enzymes were dithiothreitol-independent. A rat brain hydrolase was purified approximately 20,000-fold and represented the major approximately 39-kDa protein on denaturing gels. Immunoaffinity-purified rabbit polyclonal antibodies reacted with 39-kDa proteins from turkey erythrocytes and rat, mouse, and calf brains. A rat brain cDNA library was screened using oligonucleotide and polymerase chain reaction-generated cDNA probes. Inserts from two overlapping clones yielded a composite sequence that included a 1086-base pair open reading frame, which contained amino acid sequences found in the purified hydrolase. A hydrolase fusion protein, synthesized in Escherichia coli, reacted with anti-39-kDa polyclonal antibodies and exhibited Mg(2+)- and dithiothreitol-dependent hydrolase activity. A coding region cDNA hybridized readily to a 1.7-kilobase band in rat and mouse poly(A)+ RNA, but poorly to bovine, chicken, rabbit, and human poly(A)+ RNA. The immunological and molecular biological data are consistent with partial conservation of hydrolase structure across animal species.

Amino Acid Sequence↗

Guanine nucleotide-binding proteins in the intestinal parasite Giardia lamblia. Isolation of a gene encoding an approximately 20-kDa ADP-ribosylation factor.

Giardia lamblia is a protozoan intestinal parasite that has characteristics of both eukaryotes and prokaryotes. To determine whether genes for guanine nucleotide-binding proteins are present in Giardia, genomic DNA and cDNA libraries were screened by polymerase chain reaction and by hybridization with mixed oligonucleotide probes complementary to sequences encoding conserved GTP-binding domains. A gene with a high degree of sequence identity with mammalian ADP-ribosylation factors (ARFs), believed to be important in vesicular transport, was identified. The Giardia ARF gene had a 573-base open reading frame encoding 191 amino acids which are 63-70% identical with known mammalian and yeast ARFs. Sequence conservation among ARFs was greatest in putative GTP-binding domains. A single ARF mRNA species of approximately 750 bases was found in two different Giardia isolates. Primer extension and RNA sequencing of the Giardia ARF transcript revealed a short (6-base) 5'-untranslated region similar in size to those found in other Giardia transcripts. Giardia extracts contained ARF activity, as shown by stimulation of cholera toxin-catalyzed ADP-ribosylation and a Giardia ARF expressed in Escherichia coli as a fusion protein likewise exhibited biochemical activity. Its presence in Giardia is consistent with the view that ARF emerged before the divergence of this protozoan from other eukaryotes (approximately 1.5 billion years ago), and that an ARF-like protein may have been the ancestor of several other classes of signal-transducing guanine nucleotide-binding proteins, including the alpha subunits of the heterotrimeric G proteins.

ADP-Ribosylation Factors↗

ADP-ribosylation of actins by arginine-specific ADP-ribosyltransferase purified from chicken heterophils.

We reported the purification and characterization of an arginine-specific ADP-ribosyltransferase and acceptor protein p33 in granules of chicken peripheral polymorphonuclear leukocytes (heterophils) [Mishima, K., Terashima, M., Obara, S., Yamada, K., Imai, K. & Shimoyama, M. (1991) J. Biochem. (Tokyo) 110, 388-394]. In the present study, we obtained evidence that chicken non-muscle beta/gamma-actin, skeletal muscle alpha-actin and smooth-muscle gamma-actin were ADP ribosylated by the heterophil ADP-ribosyltransferase. The stoichiometry of ADP-ribose incorporation into these actins was 1.2 mol, 1.0 mol and 2.0 mol ADP-ribose/mol of beta/gamma-actin, alpha-actin and gamma-actin, respectively. The optimal pH for the ADP ribosylation was at pH 8.5, with the respective actin. Km values for NAD were calculated to be 30 microM with beta/gamma-actin, 35 microM with alpha-actin and 20 microM with gamma-actin. The Km values for the actin isoforms were 15 microM for beta/gamma-actin, 2.5 microM for alpha-actin and 10 microM for gamma-actin. ADP ribosylation of actin inhibited its capacity to polymerize, as determined by the increase in fluorescence intensity with N-(1-pyrenyl)iodoacetamide-labelled actin. Filamentous actin (F-actin) polymerized with the respective actin isoform was also ADP ribosylated, although the extent of the modification of F-actin was lower than that of globular actin (G-actin). In situ ADP ribosylation of beta/gamma-actin was evidenced with chicken peripheral heterophils permeabilized with saponin. Thus, the endogenous ADP ribosylation of actin in the heterophils may be involved in the cellular processes such as phagocytosis, secretion and migration.

Actins↗

Growth rate of myelin figures for phosphatidylcholine and phosphatidylethanolamine.

The growth length of myelin figures (or myelin tubes) was measured for several kinds of phospholipids using optical microscopy. The measurements were done for myelin figures with various thickness of tube wall. In spite of remarkable differences in morphology between the myelin figures of phosphatidylcholine and those of phosphatidylethanolamine, the growth rates for both were adapted to the expression proposed previously. The initial rate and the damping factor of the growth were inversely proportional to the wall thickness of myelin tubes.

In Vitro Techniques↗

Interactions of poly(ethylene glycol)-grafted cellulose membranes with proteins and platelets.

The interactions of proteins and platelets with cellulose membranes grafted with poly(ethylene glycol) were studied. The poly(ethylene glycol) grafting was carried out using poly(ethylene glycol)-monoacid and poly(ethylene glycol)-diacid, which have one and two terminal carboxyl groups, respectively. The grafting operates through esterification between the carboxyl groups of poly(ethylene glycol) and the hydroxyl groups on the membrane surface. Both of the poly(ethylene glycol) grafted membranes reduced the complement activation. Adsorption of bovine serum albumin and gamma-globulin increased when the membrane was grafted with poly(ethylene glycol)-diacid, but did not change when it was grafted with poly(ethylene glycol)-monoacid. When platelets were incubated with serum proteins, the platelet adhesion to the membranes slightly decreased by grafting both the poly(ethylene glycol)-diacid and poly(ethylene glycol)-monoacid. The poly(ethylene glycol)-diacid grafted surface showed more clotting than the poly(ethylene glycol)-monoacid grafted and original surfaces.

Animals↗

[Recurrent case of subacute necrotizing lymphadenitis in young man].

A 10-year-old male was admitted to our hospital because of lymphadenopathy and fever. Biopsy of a cervical lymph node demonstrated nodular necrotic foci containing many macrophages phagocyting the karyorrhexic nuclei. He was diagnosed as subacute necrotizing lymphadenitis (SNL) and all the symptoms disappeared spontaneously within a month. Five year later, lymphadenopathy recurred, and re-biopsy showed the same histological findings and he also recovered spontaneously. Although the prognosis of SNL is generally excellent and the majority of the patients recover without any treatment, recurrences are very rare, especially in young male patient.

Adolescent↗