Search PubMed⌕ Search

Biomedical subjects

N Aoki

Publications and source records attributed to N Aoki.

At least 217 records · Page 12Linked to original sources
PubMed1995

Determination of a common clonal origin of gastric and pulmonary mucosa-associated lymphoid tissue lymphomas presenting five years apart.

Mucosa-associated lymphoid tissue (MALT) lymphoma is often mis-diagnosed as a benign tumor. Dissemination to other sites occurs in MALT lymphoma. We report a 60-year-old man with gastric and pulmonary tumors of MALT lymphoma which occurred 5 years apart. Initially, the gastric tumor had been diagnosed as reactive lymphoreticular hyperplasia. To determine whether the two tumors arose from the same malignant clone, we amplified and sequenced the complementarity-determining region 3 of the immunoglobulin heavy chain gene using the polymerase chain reaction (PCR). The sequences were identical except for 11-nucleotide difference, suggesting identical clonality.

Base Sequence↗
PubMed1995

Wegener's granulomatosis complicated by arterial aneurysm.

Wegener's granulomatosis is a distinct clinicopathologic entity characterized by granulomatous vasculitis of the upper and lower respiratory tract and kidneys. A 56-year-old Japanese man with Wegener's granulomatosis died of intraperitoneal hemorrhage from a ruptured aneurysm of his left gastric artery. Histological findings revealed necrotizing granulomatous vasculitis involving this artery. No previously published reports have described Wegener's granulomatosis patients with aneurysms in such a large artery. We conclude that this case represents either an atypical form of Wegener's granulomatosis or a polyangiitis overlap syndrome of Wegener's granulomatosis and classic polyarteritis nodosa.

Aneurysm↗
PubMed1995

[Pharmacokinetic study of sparfloxacin in patients receiving regular hemodialysis].

We investigated the in vivo kinetics of sparfloxacin (SPFX), an oral quinolone, in the hemodialytic patients. SPFX was orally administrated in a single dose of 200 mg to each of five hemodialytic patients, on a day that they were not receiving hemodialysis therapy. After dosing, the blood samples were collected periodically at 2, 4, 6, 8, 12, 24, 25, 27, 29, 48, 72 hours. Concentration of the unchanged SPFX in the plasma samples were measured by HPLC. The peak plasma levels of SPFX in the hemodialytic patients did not differ greatly from patients with renal failure (5 < Ccr<20 ml/min). Average T 1/2 beta of SPFX was 25.7 hours, and it was prolonged compared to the patients with renal failure (who were not receiving hemodialysis) and a group of young healthy volunteers. Based on these results, we believe those hemodialytic patients may be administrated with the drug once every other day, as long as normal doses are used.

Administration, Oral↗
PubMed1995

Slit ventricle syndrome successfully treated by a lumboperitoneal shunt.

The authors present the case of a 17-year old man with slit ventricle syndrome, presenting as progressive neurological deterioration after head trauma. Serial computed tomography scans revealed slight ventricular enlargement, suggesting shunt malfunction. Communication between the lumbar subarachnoid space and the lateral ventricles was confirmed by computed tomography cisternography. He underwent a lumboperitoneal shunt, resulting in complete resolution of the symptoms. A lumboperitoneal shunt is considered to be a promising option for the treatment of slit ventricle syndrome.

Adolescent↗
PubMed1994

Induction of tyrosine phosphorylation of Vav and expression of Pim-1 correlates with Jak2-mediated growth signaling from the erythropoietin receptor.

The receptor for erythropoietin (Epo) belongs to the cytokine receptor family and lacks a tyrosine kinase domain. However, it has been hypothesized that a tyrosine kinase, Jak2, associates with the membrane proximal cytoplasmic region of Epo receptor (EpoR) and mediates the growth signaling from the receptor through tyrosine phosphorylation of cellular substrates. To explore the growth signaling pathways from the EpoR, we analyzed substrates of tyrosine phosphorylation induced by Epo stimulation in cells expressing various mutant EpoRs. The vav proto-oncogene product was found to be tyrosine phosphorylated after Epo stimulation in cells expressing the wild-type EpoR or a truncated receptor, H mutant, that retains the growth signaling function. In these cells, Epo also induced the expression of a serine/threonine kinase, Pim-1. However, Epo stimulation did not have any effect on Vav or Pim-1 in cells expressing a mutant EpoR, PM4 mutant, inactivated by a point mutation, Trp282 to Arg, in the membrane proximal region, which abrogates the interaction with Jak2. On the other hand, both tyrosine phosphorylation of Vav and expression of Pim-1 were observed constitutively in cells expressing a mutant EpoR that is constitutively activated by a point mutation, Arg 129 to Cys, in the extracellular domain. Jak2 was also constitutively tyrosine phosphorylated and activated in cells expressing this mutant, which confirms the crucial role of Jak2 in growth signaling from the EpoR. Taken together, these observations suggest that the tyrosine phosphorylation of Vav and the expression of Pim-1 may play important roles in growth signaling from the EpoR.

Amino Acid Sequence↗
PubMed1994

Activation of the mitogen-activated protein kinase pathway by the erythropoietin receptor.

The erythropoietin receptor (EpoR) belongs to the cytokine receptor family, members of which lack a tyrosine kinase domain. Recent studies, however, have shown that a cytoplasmic tyrosine kinase, JAK2, interacts with the cytoplasmic domain of the EpoR and becomes activated upon binding of Epo to the receptor. Epo has also been shown to stimulate activation of Ras and Raf-1. The present studies were undertaken to examine the possible involvement of Epo-induced tyrosine phosphorylation in activation of the Ras/mitogen-activated protein kinase (MAP kinase) pathway and to determine its significance on the growth signaling from the EpoR. In an interleukin (IL)-3-dependent cell line expressing the transfected wild-type EpoR, Epo, or IL-3 induced tyrosine phosphorylation of Shc and its association with Grb2. These cytokines also induced tyrosine phosphorylation and activation of MAP kinase isoforms ERK1 and ERK2. A mutant EpoR with a carboxyl-terminal deletion of 108 amino acids (H mutant), which is mitogenically functional but lacks tyrosine phosphorylation sites in the carboxyl-terminal region, showed markedly diminished abilities to induce tyrosine phosphorylation of Shc and to phosphorylate and activate MAP kinases. A mutant receptor (PM4 mutant) inactivated by a point mutation, Trp282 to Arg, which abrogates the interaction with JAK2, failed to induce any effect on Shc or MAP kinases. In cells expressing a mutant EpoR that is constitutively activated by a point mutation, Arg129 to Cys, in the extracellular portion of the receptor, neither tyrosine phosphorylation of Shc nor activation of MAP kinases by phosphorylation was detectable without stimulation with Epo or IL-3. These results suggest that the carboxyl-terminal region of EpoR may play a crucial role in activation of MAP kinases through the Ras signaling pathway which may be activated by tyrosine phosphorylation of Shc and its association with Grb2. The activation of MAP kinases, however, failed to correlate with the mitogenic activity of mutant EpoRs and thus may not be required for growth signaling from the EpoR.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Initial clinical experiences with rescue unipolar radiofrequency thermal balloon angioplasty after abrupt or threatened vessel closure complicating elective conventional balloon coronary angioplasty.

OBJECTIVES: The purpose of this study was to evaluate the effectiveness of radiofrequency thermal balloon angioplasty and rescue procedure after abrupt or threatened vessel closure complicating elective percutaneous transluminal coronary angioplasty. BACKGROUND: Coronary angioplasty is an established therapy for ischemic heart disease. However, abrupt closure after successful angioplasty remains a serious problem. METHOD: We utilized a unipolar radiofrequency balloon in which a radiofrequency potential of 13.56 MHz was transmitted between the coil within the balloon and a plate electrode attached to the patient's body. The temperature within the balloon could be monitored through a thermistor within the balloon. From October 1991 through December 1993, 31 patients who had abrupt or threatened vessel closure during 1,005 consecutive elective coronary angioplasty procedures were randomly assigned to radiofrequency balloon angioplasty or to other procedures as rescue RESULTS: Fifteen patients were assigned to radiofrequency balloon angioplasty (5 with abrupt vessel closure and 10 with threatened closure). The average balloon temperature and inflation time were 62 +/- 9 degrees C and 129 +/- 62 s, respectively. Percent diameter stenosis decreased from 87 +/- 14% to 36 +/- 25% (p < 0.01). The procedure was successful in 14 patients. The rate of restenosis was 67%, but the success rate of repeat conventional coronary angioplasty for restenosed lesions was 86%. CONCLUSIONS: Radiofrequency balloon angioplasty is effective in the treatment of abrupt or threatened vessel closure complicating elective coronary angioplasty even though the procedure is associated with a relatively high rate of restenosis.

Aged↗
PubMed1994

All-trans retinoic acid upregulates thrombomodulin and downregulates tissue-factor expression in acute promyelocytic leukemia cells: distinct expression of thrombomodulin and tissue factor in human leukemic cells.

The expressions of thrombomodulin (TM) and tissue factor (TF) by all-trans retinoic acid (ATRA) were studied in human leukemic cell lines including NB4 (acute promyelocytic leukemia) and U937 (monoblastic leukemia). ATRA remarkably upregulated TM antigen expression in cell lysates as well as TM cofactor activity on the cell surfaces of NB4. The level of TM mRNA in NB4 cells was increased by ATRA. Inherently procoagulant NB4 cells contained markedly higher content of TF, which was efficiently reduced by ATRA. Modest increase of TM and decrease of TF were observed when NB4 cells were treated with dibutyryl cyclic adenosine monophosphate (dbcAMP). On the other hand, both ATRA and dbcAMP showed dramatic increase of TM antigen level and modest decrease of TF antigen in U937 cells. These results suggest that ATRA regulates expressions of TM and TF antigens and activity in NB4 and U937 cell lines, and provide evidence for a potential efficiency of ATRA as a preventive and therapeutic agent for disseminated intravascular coagulation in promyelocytic and monocytic leukemia.

Bucladesine↗
PubMed1994

Recognition DNA sequence of a novel putative transcription factor, BCL6.

The BCL6 gene involved in the 3q27 translocation associated with B-cell lymphomas encodes a novel Cys2-His2 zinc finger protein. We generated a fusion protein of glutathione S-transferase and zinc finger domain of BCL6 to determine recognition sequences of BCL6 with polymerase chain reaction using random oligonucleotides of 26 bases as a ligand. A consensus of 14 nucleotides consisting of (T/A)NCTTTCNAGG(A/G)AT was identified in the recognition sequences. In a gel mobility shift assay, the probe containing the 14-nucleotide recognition sequence formed a complex with the fusion protein and nuclear proteins from Burkitt's cell lines overexpressing the BCL6 transcripts. The consensus sequence was protected from the digestion by nuclease in a DNase I footprinting assay. In conclusion, BCL6 may be involved in tumorigenesis by binding to the consensus sequences of the other genes.

Base Sequence↗
PubMed1994

Erythropoietin induces association of the JAK2 protein tyrosine kinase with the erythropoietin receptor in vivo.

Protein tyrosine phosphorylation has been hypothesized to play a key role in the growth signaling induced by erythropoietin (Epo), although the Epo receptor (EpoR), a member of the cytokine receptor superfamily, lacks a tyrosine kinase domain. Recently, the JAK2 tyrosine kinase was shown to be activated on Epo stimulation and to bind to the cytoplasmic domain of EpoR in vitro. To further explore the mechanisms of activation of JAK2 in EpoR-mediated signal transduction, we assessed the conditions for association of JAK2 with EpoR in vivo. Epo stimulation rapidly induced association of JAK2 with the EpoR in an interleukin 3 (IL-3)-dependent cell line transfected with the wild-type EpoR. On Epo stimulation JAK2 also associated with a truncated mutant EpoR (H-mutant), which is mitogenetically active but not tyrosine phosphorylated, indicating that association does not require receptor phosphorylation and occurs in the membrane proximal region. However, association was not detected with mutant receptors inactivated by an internal deletion or a point mutation, Trp282 to Arg, in a membrane-proximal cytoplasmic region (PB or PM4 mutant, respectively). Immune complex kinase assays of anti-EpoR immunoprecipitates also revealed that activated JAK2 associates with the EpoR in Epo-stimulated cells. By this approach, association also occurred with the mitogenically active H mutant but not with the mitogenically inactive PB or PM4 mutants. In the immune complex kinases assays, EpoR, JAK2, and a 150-kD protein were phosphorylated on tyrosine. Taken together, the results further support the hypothesis that, on Epo stimulation, JAK2 associates with the membrane-proximal cytoplasmic region of the EpoR to be activated and induces tyrosine phosphorylation of cellular substrates, including the EpoR, to transduce a growth signal.

Animals↗
PubMed1994

Immunologically cross-reactive 57 kDa and 53 kDa glycoprotein antigens of bovine milk fat globule membrane: isoforms with different N-linked sugar chains and differential glycosylation at early stages of lactation.

Two glycoprotein antigens with molecular masses of 57 kDa (MGP57) and 53 kDa (MGP53) were co-purified from bovine milk fat globule membrane (MFGM) by immunoaffinity chromatography using a monoclonal antibody raised against the MFGM. Their N-terminal sequences of 22 amino acids determined were identical, and the sequence was homologous (about 60% identical) to the deduced amino acid sequence of mouse milk fat globule epidermal growth factor (EGF) factor 8 (MFG-E8) (Ref. [12], Stubbs, J.D. et al., Proc. Natl. Acad. Sci. USA, 87, 8417-8421, 1990). This suggests that MGP57/53 are bovine MFGM components 15/16 (PAS-6 and PAS-7), which have recently been reported to be bovine homologs of MFG-E8. N-Glycanase treatment of these glycoproteins reduced their molecular masses, and consequently the enzymatically deglycosylated MGP57 and MGP53 converged on a single band of 50 kDa as measured by SDS-PAGE, indicating that the polypeptide portions of these two distinct glycoprotein antigens are very similar or identical and that their N-linked sugar chains contributed to minor difference in their molecular masses. Western blot analyses using lectins also revealed that they were differentially glycosylated; MGP57 was stained with concanavalin A (Con A) more strongly than MGP53, whereas MGP 53 was stained well with soybean agglutinin (SBA). Reactivity with SBA remarkably increased during early stages of lactation. Two-dimensional gel electrophoresis showed that MGP57 and MGP53 were electrically heterogeneous; from day 9 after parturition, both glycoproteins fell in almost the same range of isoelectric points between 6.4 and 7.6, also, such glycoproteins from day 1 after parturition were more acidic, probably due to terminal sialylation of their sugar chains.

Amino Acid Sequence↗
PubMed1994

Presence of functional cyclic AMP responsive element in the 3'-untranslated region of the human thrombomodulin gene.

We characterized the transcriptional regulatory function of the 3'-untranslated region of the thrombomodulin gene by transient transfection assays in human umbilical endothelial cells. Deletion analyses of the 3'-untranslated region indicated that the region containing the consensus sequence of the cyclic AMP (cAMP) responsive element (position 2092) showed an increased transcriptional activity in response to cAMP. Gel-shift analysis showed that a band representing the fragment containing position 2092 was retarded when incubated with nuclear extracts from the cells treated with cAMP. In addition, the region downstream of the cAMP responsive element was found to function negatively in the gene expression. These results indicate that the 3'-untranslated region has a functional cAMP responsive element and plays an important role in the regulation of the thrombomodulin gene expression.

Base Sequence↗
PubMed1994

Different NH2-terminal form with 12 additional residues of alpha 2-plasmin inhibitor from human plasma and culture media of Hep G2 cells.

alpha 2-Plasmin inhibitor (alpha 2PI) was purified from plasma or from the culture media of Hep G2 cells by one-step immunoaffinity chromatography procedure. Majority of alpha 2PI purified from plasma was the previously recognized plasma alpha 2PI with NH2-terminal Asn (Asn-alpha 2PI), whereas majority of alpha 2PI purified from the culture media was retaining the "pro" peptide of 12 amino acids with NH2-terminal Met (Met-alpha 2PI). When Hep G2 cells were cultured in serum-free media, the alpha 2PI secreted to the media was totally in a form of Met-alpha 2PI. Incubation of Met-alpha 2PI with human plasma induced the complete conversion of Met-alpha 2PI to Asn-alpha 2PI. The results indicate that alpha 2PI is synthesized and secreted from liver cells as Met-alpha 2PI and Met-alpha 2PI is converted to Asn-alpha 2PI by proteolytic cleavage in plasma during the circulation.

Amino Acid Sequence↗
PubMed1994

Erythropoietin-dependent association of phosphatidylinositol 3-kinase with tyrosine-phosphorylated erythropoietin receptor.

Erythropoietin (Epo) regulates the proliferation and differentiation of erythroid precursors. The Epo receptor (EpoR) belongs to the cytokine receptor family and lacks a tyrosine kinase domain. However, Epo induces tyrosine phosphorylation of cellular substrates including the EpoR. To explore the functional significance of receptor tyrosine phosphorylation, we examined the possible interaction of the receptor with the 85-kDa regulatory subunit (p85) of phosphatidylinositol (PI) 3-kinase. After Epo stimulation, p85 was found to associate with the tyrosine-phosphorylated 72-kDa form of EpoR as well as a 92-kDa phosphotyrosyl protein, and PI 3-kinase activity was detectable in anti-EpoR immunoprecipitates. Anti-EpoR blotting of anti-p85 immunoprecipitates revealed that p85 binds specifically to the 72-kDa form of the EpoR and not to unphosphorylated 66- and 64-kDa forms. Association of p85 with the EpoR was Epo dose- and time-dependent and correlated with tyrosine phosphorylation of the receptor. Consistent with a role for tyrosine phosphorylation of the EpoR, PI 3-kinase did not associate with a mitogenically active receptor mutant that lacked tyrosine-phosphorylation sites in the carboxyl-terminal region. A recombinant fusion protein containing the carboxyl-terminal SH-2 domain of p85 was shown to bind to tyrosine-phosphorylated EpoR in vitro. Taken together, these results indicate that, following Epo stimulation, the EpoR recruits PI 3-kinase to the cell membrane by binding between the carboxyl-terminal SH-2 domain of p85 and the tyrosine-phosphorylated carboxyl-terminal region of the receptor. The association with PI 3-kinase is, however, not required for the growth signal transduction from the EpoR.

Binding Sites↗
PubMed1994

Production and characterization of monoclonal antibodies directed against bovine milk fat globule membrane (MFGM).

Nine hybridomas secreting monoclonal antibodies (mAbs) to bovine milk fat globule membrane (MFGM) were produced from spleen cells of three immunized BALB/c mice. Several MFGM antigens recognized by some mAbs were identified as a 120 kDa protein and 67 kDa (butyrophilin), 57 kDa (PAS-6), 53 kDa (PAS-7), 33 kDa glycoproteins. The other mAbs secreted by four independent hybridoma clones recognized many broad bands ranging from 20 to 200 kDa. The 120 kDa protein and 67 kDa, 57 kDa, 53 kDa glycoproteins were detected by each mAb in the plasma membrane fraction prepared from a lactating bovine mammary gland. Moreover, mammary gland epithelium of a thin section was specifically stained with these mAbs, indicating that these mAbs directed against MFGM recognized membrane proteins and glycoproteins of lactating mammary epithelial cells. Upon heating of the MFGM in phosphate buffer, pH 7.4 at 100 degrees C for 10 min, the antigens still retained most of its reactivity to these mAbs, whereas, proteolytic cleavage by trypsin and chymotrypsin strongly reduced its reactivity to these mAbs by 60% or more except for two mAbs which recognized the 57 and 53 kDa glycoproteins, respectively.

Animals↗
PubMed1994

Molecular cloning of the breakpoint for 3q27 translocation in B-cell lymphomas and leukemias.

Reciprocal exchanges between chromosomal region 3q27 and three loci of the Ig genes have been reported in cases of B-cell type non-Hodgkin's lymphoma. We have cloned a region containing a breakpoint junction of 3q27 from a cell line established from a patient with Burkitt's lymphoma carrying t(3;22)(q27;q11). The region cloned was shown to contain an Ig lambda light chain gene fused to a gene on chromosome 3q27. This finding was subsequently confirmed by fluorescence in situ hybridization. Extra nucleotides were present at the joining site. The heptamer-like and nonamer-like sequences separated by an intervening 24 bp were present in the region corresponding to the breakpoint of 3q27, suggesting that a misrecombination in Ig gene rearrangement may be involved in the translocation. Southern blot analysis with a 3q27-specific probe showed rearrangements in three additional patients with B-cell malignancies with the t(3;14)(q27;q32). The breakpoints of all four cases clustered within a limited 3-kb region on chromosome 3q27. The region of 3q27 involved in the translocation was designated as the BCL5 locus. The transcripts from the BCL5 locus were detected in normal tissues and hematopoietic cell lines, and the increased expression of transcript of aberrant size was detected in the established cell line carrying t(3;22). These observations suggest that a gene located at 3q27 is involved in the translocation and that its deregulation plays a role in the malignant transformation of B cells.

Base Sequence↗
PubMed1994

Gene involved in the 3q27 translocation associated with B-cell lymphoma, BCL5, encodes a Krüppel-like zinc-finger protein.

Chromosomal translocations involving band 3q27 are the recently described nonrandom cytogenetic abnormalities in B-cell malignancies. We have previously cloned the breakpoint region of 3q27, designated as the BCL5 locus, from the B-cell line carrying the t(3;22). The cDNA for the BCL5 gene was cloned from the human liver cDNA library. The nucleotide sequencing analysis showed that the BCL5 gene encodes a potential transcription factor containing six repeats of the Cys2-His2 zinc-finger motif resembling the Drosophila segmentation gene Krüppel. The calculated molecular weight was 78.8 kD, which was supported by an in vitro transcription and translation experiment. A part of the sequence was essentially identical to that of a genomic fragment, ZNF51, previously reported to be located at 3qter. The translocation occurred in the 5' region of the BCL5 gene, and the protein-coding exons were fused to the Ig-lambda gene in a head-to-head configuration in the cell line carrying t(3;22). The BCL5 cDNA probe detected a major transcript of 3.8 kb in Burkitt's lymphoma cell lines and an aberrant transcript in the t(3;22) cell line, whereas no transcript was detected in myeloid, monocytoid, erythroid, T-lymphoid, and Epstein-Barr virus-immortalized B-lymphoblastoid cell lines.

Amino Acid Sequence↗