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Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 307 records · Page 17Linked to original sources
PubMed1997

[Liver metastases from breast cancer 14 years after radical mastectomy; successful treatment with hepatic arterial infusion chemotherapy and systemic endocrine therapy--a case report].

The patient was a 73-year-old woman who was admitted to our hospital for epigastric discomfort and body weight loss. She had undergone radical right mastectomy in March 1982. Ultrasonography and computed tomography revealed multiple tumors in the liver. Three of the tumor markers (CA-125, CA 19-9, and CA 15-3) were positive. US-guided fine needle aspiration biopsy of the liver tumor showed small atypical cells with solid cell nests. Immunohistochemical tests revealed estrogen receptor was positive. We diagnosed the patient as recurrent breast cancer metastatic to liver, 14 years postoperatively. The liver tumors were successfully controlled with the combination of intra-arterial infusion chemotherapy (5-fluorouracil, epirubicin, and mitomycin C) along with systemic endocrine therapy (medroxyprogesterone acetate and fadrozole hydrochloride hydrate).

Aged↗
PubMed1997

[Extra-arterial dislocation of indwelling catheter in hepatic arterial infusion chemotherapy--special reference to tissue destruction by 5-fluorouracil].

The causes of extra-arterial dislocation of indwelling catheter (EAD), which was one of the serious complications in arterial infusion chemotherapy, were examined. Subjects were six cases of EAD among the 45 cases of gastric cancer with liver metastases treated with hepatic arterial infusion chemotherapy. According to the route of cannulation, EAD occurred more frequently in the cases of cannulation via gastroduodenal artery (18.5%) than in those via subclavian artery (5.5%). Concerning the drugs and their administration, all cases of EAD were treated by continuous injection of 5-fluorouracil (5-FU). Main symptoms of EAD were high fever, abdominal pain and anemia, which developed after administration of total doses from 4.0 g to 30.5 g of 5-FU. In conclusion, it was strongly suggested that arterial destruction due to the toxicity of 5-FU caused EAD in hepatic arterial infusion chemotherapy, especially in cases of cannulation via gastroduodenal artery due to the high concentration of 5-FU in a limited part of the arterial wall.

Aged↗
PubMed1997

[Correlation between anti-tumor effects and serum hepatocyte growth factor level in patients with liver metastases from gastric cancer treated by induced hypertensive chemotherapy with angiotensin II].

To clarify the clinical significance of serum hepatocyte growth factor (HGF), the possible correlation between anti-tumor effect and serum HGF level was examined in six patients with liver metastases from gastric cancer. These patients were treated by induced hypertensive chemotherapy with angiotensin II (IHC). We measured the serum concentration of HGF and compared them with the anti-tumor effect and conventional tumor makers (CEA, CA 19-9). The cut-off level of serum HGF was prescribed at 0.4 ng/ml from healthy volunteer's samples. As the result, anti-tumor effects were one case of CR, two of PR, one of NC and two of PD. Serum HGF levels before IHC were positive in all cases (0.44 to 1.35 ng/ml), whereas the levels were not related to the extent of liver metastases. With regard to the anti-tumor effect, the serum HGF level after IHC was more sensitively reflected compared with conventional tumor markers. In conclusion, it is considered that the serum HGF level might be a useful indicator for the treatment effect in gastric cancer.

Aged↗
PubMed1997

[A case of primary acute pulmonary cavitation in sarcoidosis complicated by multiple nodular lesions in the central nervous system].

A 20-year-old man visited our hospital complaining of headache and a dry cough. Chest X-ray and chest CT showed bilateral hilar and mediastinal lymphadenopathy, multiple cavitations with thin, smooth walls, and diffuse granular shadows. A transbronchial biopsy specimen revealed sarcoid granuloma. Primary acute pulmonary cavitation of sarcoidosis was diagnosed, since there was no evidence of infection, emphysematous change, fibrotic or cystic bronchiectatic change on chest X-ray. EEG, contrast enhancement of brain CT scans and MRI were performed because the patient complained of headache. EEG showed a high voltage paroxysmal slow wave and giant build-up, whereas brain CT showed no abnormalities. T1-weighted MRI with gadolinium enhancement showed multiple high intensity nodules in the convexity, brain stem, and spinal cord. Corticosteroid therapy (60 mg/day) was started. After 1 week of treatment, the headache ceased. After 2 weeks of treatment, both the cavities in the lung field's and the nodules in the central nervous system disappeared. Therefore, the dose of corticosteroids was gradually reduced to a maintenance dose of 5 mg/day, and no relapse was noted. We report a very rare case of primary acute pulmonary cavitation in sarcoidosis complicated by multiple nodular lesions in the central nervous system.

Adult↗
PubMed1996

Extrathymic differentiation of resident T cells in the joints of mice with collagen-induced arthritis.

Murine collagen-induced arthritis (CIA) is known as a T cell-mediated autoimmune disease, although autoantibodies are also suspected to be associated with the onset of the disease. To determine the origin of such T cells in the joints of mice with CIA, their phenotypic properties as well as those of T cells in other immune organs were examined in DBA/1 mice. Since a significant number of mononuclear cells (MNC) was also yielded by the joints of normal DBA/1 mice, the properties of these T cells were examined in parallel. When CIA was induced by an intradermal injection of type II collagen at the base of the tail, the numbers of MNC yielded by the regional lymph nodes and the foot joints were doubled. Interestingly, regardless of the onset of CIA, the joints were always comprised of unique T cell populations, including IL-2(R)alpha- beta+ T cells, gammadelta T cells, CD8alpha+ beta- cells, and CD44+ L-selectin- cells. All these properties coincide with those of extrathymic T cells in liver and intestine. In the case of gammadelta T cells in joints, Vgamma and Vdelta usages were unique and different from those in the other organs. More importantly, Vgamma and Vdelta usages in gammadelta T cells in the joints of normal mice and in those of mice with CIA were essentially the same. Taken together with the expression of recombination-activating gene-1 and -2 mRNAs by MNC in mice with CIA, these findings raise the possibility that the joints have their own resident T cells that are extrathymically generated in situ.

Animals↗
PubMed1996

A fusion protein library: an improved method for rapid screening and characterization of DNA binding or interacting proteins.

A rapid method for screening and characterization of DNA binding or protein-interacting molecules is described. The method relies on a fusion protein library in which randomized DNA fragments are inserted into pGEX-3X and its derivatives to generate collections of GST-fusion proteins. After inducing the expression of the fusion proteins by addition of IPTG, the colonies can be screened either with radioactively labeled DNA/RNA fragment for specific clones encoding DNA/RNA binding proteins or with an antibody for clones encoding proteins of interest. They can also be screened with a radioactively labeled protein for cloning of interacting molecules. The fusion proteins encoded by the isolated clones can be readily purified by conducting the lysis of the cells and an affinity column in the presence of an alkyl anionic detergent, N-laurylsarcosine (sarkosyl), and can be further characterized.

Blotting, Southern↗
PubMed1996

Cloning and mapping of a human RBP56 gene encoding a putative RNA binding protein similar to FUS/TLS and EWS proteins.

The EWS gene was found at the chromosome breakpoints in Ewing sarcoma, and the FUS/TLS gene was found at the breakpoints of myxoid liposarcoma and acute myeloid leukemia. These genes encode proteins that carry a highly homologous RNA binding domain. Fusion proteins made of the N-terminal half of EWS or FUS/TLS and transcriptional regulatory proteins, also derived from genes located at breakpoints, have been suggested to be involved in the pathogenesis of tumors. By PCR amplification of human Namalwa cell cDNA using degenerate primers made from the conserved amino acid sequences in the RNA binding domain of EWS and FUS/TLS, we obtained a cDNA fragment (RBP56 cDNA), the predicted amino acid sequences of which were similar but not identical to those of EWS and FUS/TLS. Using this fragment as a probe, we obtained two isoforms of cDNAs consisting of 2144 and 2153 bp, respectively, which encode proteins consisting of 589 and 592 amino acid residues, respectively. The predicted amino acid sequences of RBP56 protein have a serine-, tyrosine-, glutamine-, and glycine-rich region in the N-terminal region, an RNA binding domain and a C2C2 finger motif in the central region, and degenerate repeats of DR(S)GG(G)-YGG sequences in the C-terminal region. The expression of RBP56 mRNA was observed in all of the human fetal and adult tissues examined, as was the expression of EWS and FUS/TLS mRNAs. The RBP56 gene was mapped to chromosome 17q11.2 to q12.

Amino Acid Sequence↗
PubMed1996

Simultaneous activation of granulocytes and extrathymic T cells in number and function by excessive administration of nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) sometimes show serious side effects such as damage to the gastroduodenal mucosa and dysfunction of the liver. Although many investigators have focused on some types of leukocytes, a comprehensive study concerning all types of leukocytes, especially recently identified extrathymic T cells, remains to be done. When mice were treated with an intraperitoneal injection of indomethacin (50 or 300 microg/mouse), the number of thymocytes decreased while the number of MNC in various peripheral organs increased. This increase in MNC was due mainly to the increase in the numbers of granulocytes and extrathymic T cells. Reflecting thymic atrophy, the proportion of thymus-derived T cells distributed in the periphery decreased. The use of other NSAIDs revealed that granulocytosis seen in the periphery arose from a selective activation of myelomonocytic cells in the bone marrow. Some functional experiments using the Ca2+ influx, iNOS mRNA expression, and autoreactive cytotoxicity as indicators suggested that granulocytes and extrathymic T cells were in activated states not only in number but also in function. Since both granulocytes and extrathymic T cells become cytotoxic effectors against self-tissues or self-cells when overactivated, these activated leukocytes may be intimately related to the etiology of the tissue damage inducible by NSAIDs (i.e., adverse drug reaction).

Animals↗
PubMed1996

Selective determination of chloride and bromide ions in serum by cyclic voltammetry.

Voltammetric determination of chloride and bromide ions in serum was made using a one-body type Ag electrode, whose surface was covered with a dialysis membrane for preventing interference from proteins. This determination was based on measurement of the charge of the reduction wave of silver halide formed on the Ag electrode surface in a halide ion solution during a cathodic potential sweep. In this method, depending on the potential sweep range, the charge of the reduction wave of AgI, AgI + AgBr, or AgI + AgBr + AgCl can be measured. Here, the method was used to determine the chloride and bromide ions in artificial serum. Linear concentration ranges were 1.0 x 10(-2)-2.4 x 10(-1) M for chloride ions and 5.0 x 10(-3)-1.8 x 10(-2) M for bromide ions. The correlation coefficient was 0.999 in each case. The relative standard deviation for chloride ion (1.0 x 10(-1) M) was 1.9% (n = 10), and that for bromide ion (1.5 x 10(-2) M) was 2.5% (n = 10). Bromide ions at a relatively high concentration as the component of serum had no effect on the determination of the chloride ion in the serum. This method is thus useful for the selective determination of chloride and bromide ions in serum.

Blood Substitutes↗
PubMed1996

Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma.

Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is unique in its ability to promote vascular permeability and endothelial cell growth, and its role in tumor development has received considerable attention. In this report, we describe the elevation of VPF/VEGF transcript expression in human hepatocellular carcinoma. Surgical samples of 23 patients with hepatocellular carcinoma were studied using reverse transcription-PCR analysis. The oligonucleotide primers were designed to amplify all four known splicing variants that could be expressed in the samples studied. Sixteen cases showed VPF/VEGF transcript expression in the tumor (16/23, 69.6%), whereas only 9 of the 23 patients showed it in the corresponding nontumoral part. There was no difference between the pattern of expression of VPF/VEGF isoforms in tumoral and nontumoral tissues. VPF/VEGF mRNA expression in the liver tumors was associated with fibrous capsule formation and septal formation (P < 0.05 respectively, Fisher's exact P test). In situ hybridization confirmed the presence of VPF/VEGF mRNA expression in tumor cells and less intensely in hepatocytes of nontumoral liver. We also found that VPF/VEGF expression in the tumor cell was increased in the area adjacent to necrotic regions (presumably hypoxic regions). As a regulator of vascular permeability and endothelial cell growth factor, VPF/VEGF may play an important role in the development of hepatocellular carcinoma.

Adult↗
PubMed1996

The pulmonary alveolar proteinosis in granulocyte macrophage colony-stimulating factor/interleukins 3/5 beta c receptor-deficient mice is reversed by bone marrow transplantation.

Mice mutant for granulocyte macrophage colony-stimulating factor (GM-CSF) or the common receptor component (beta c) for GM-CSF, interleukin (IL)-3, and IL-5 exhibit a lung disorder similar to human pulmonary alveolar proteinosis, a rare disease with congenital, infantile, and adult forms. Bone marrow transplantation and hematopoietic reconstitution of beta c mutant mice with wild-type bone marrow reversed the established disease state in the lungs, defining this disease as hematopoietic in nature. It is likely that the disease involves alveolar macrophages, as donor myeloid cell engraftment into the lungs of mutant recipient mice correlated with reverting both the disease and an abnormal macrophage morphology seen in the lungs of affected animals. Recombination Activating Gene-2 mutant donor bone marrow, which lacks the potential to develop lymphocytes, reversed the pathology in the lungs to the same extent as whole bone marrow. These data establish that certain lung disorders, if of cell-autonomous hematopoietic origin, can be manipulated by bone marrow transplantation.

Animals↗
PubMed1996

JAK2 is essential for activation of c-fos and c-myc promoters and cell proliferation through the human granulocyte-macrophage colony-stimulating factor receptor in BA/F3 cells.

Interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to activate JAK2 in various cells, but the role of JAK2 in IL-3 or GM-CSF receptor signal transduction is largely unknown. We have now examined the role of JAK2 in GM-CSF-induced signaling events in BA/F3 cells. In BA/F3 cells expressing hGMR, activation of JAK2 by hGM-CSF requires the box1 region of hGMR beta. Dominant negative JAK2 (delta JAK2), which lacked the kinase domain suppressed mIL-3 or hGM-CSF-induced c-fos promoter activation as well as c-myc promoter activation/cell proliferation, thereby suggesting that JAK2 is involved in the signaling of both pathways. Further analyses of the role of JAK2 in c-fos gene activation in BA/F3 cells expressing hGMR revealed that delta JAK2 inhibited hGM-CSF-induced phosphorylation of Shc and protein tyrosine phosphatase 1D. Within hGMR beta, the several tyrosine residues which exist are related to activation of Shc or protein tyrosine phosphate 1D, and are phosphorylated in response to hGM-CSF stimulation. In addition, we observed that delta JAK2 inhibited hGM-CSF-induced phosphorylation of hGMR beta. Taken together, our results suggest that JAK2 activated by the box1 region of hGMR mediates hGM-CSF-induced c-fos promoter activation through phosphorylation of hGMR.

Cell Line↗
PubMed1996

CTBP1/RBP1, a Saccharomyces cerevisiae protein which binds to T-rich single-stranded DNA containing the 11-bp core sequence of autonomously replicating sequence, is a poly(deoxypyrimidine)-binding protein.

South-Western screening of a glutathione-S-transferase fusion protein library constructed from the yeast Saccharomyces cerevisiae genomic DNA lead to isolation of core T-rich-strand-binding protein (CTBP) clones that bound to single-stranded DNA containing the T-rich-strand of the 11-bp core sequence of autonomously replicating sequences. One of these clones, CTBP1, contains a portion of previously described RBP1 which is an RNA-binding and single-stranded DNA-binding protein of S. cerevisiae. GST-CTBP1 as well as the full-length fusion protein with RBP1 (GST-RBP1) bind exclusively to the T-rich strand of the core sequence with an apparent dissociation constant of 5 nM, but not to the A-rich strand or double strand of the same sequence. Mutations within the core which reduce the number of T or C residues decrease the affinity of this protein. In keeping with this, binding of GST-CTBP1 to the core sequence is efficiently completed by poly(dT), poly(dT-dC) or poly(dC), but not by poly(dA) or poly(dG) to significant extents. Among polyribonucleic acids, GST-CTBP1 binds to poly(U) and poly(I) with greatest affinity, whereas GST-RBP1 binds to RNA in a rather non-specific manner. In no cases was affinity for RNA greater than that for DNA. Our results indicate that CTBP1/RBP1 is a polydeoxypyrimidine-binding protein of S. cerevisiae. CTBP1 contains two sets of an RNA-recognition motif (RRM) and a glutamine stretch. The binding affinity of the N-terminal or C-terminal set containing one RRM and one glutamine stretch is nearly two orders of magnitude lower than that of the wild-type CTBP1 containing both sets. The isolated N-terminal or C-terminal RRM alone (RRM1 and RRM2, respectively) is sufficient for binding nucleic acids with the binding specificity similar to that of the wild-type RRM, although the binding affinity of the isolated RRM2 is nearly two orders of magnitude lower than that of RRM1. Our results indicate that the two RRMs present in CTBP1/RBP1 have differential binding affinities and that the high affinity of RRM for polydeoxypyrimidine results from synergy between two lower-affinity RRMs.

Alcohol Oxidoreductases↗
PubMed1996

The beta subunit of human granulocyte-macrophage colony-stimulating factor receptor forms a homodimer and is activated via association with the alpha subunit.

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor (hGMR) consists of alpha and beta subunits, and the precise stoichiometry of these subunits has remained to be determined. In this work, oligomerization of the beta subunit was studied using a chemical cross-linker. In Ba/F3, a mouse interleukin-3-dependent cell line expressing both subunits of hGMR (Ba/F3-alpha,beta), a protein with a molecular mass corresponding to that of a homodimer of the beta subunit (beta homodimer) was detected only when cells were treated with the cross-linker. Dimerization of the beta subunit was confirmed by coimmunoprecipitation of a tagged beta subunit with the wild type beta subunit COS7 cells. The beta homodimer had already formed in the absence of hGM-CSF, whereas stimulation with the ligand brought both alpha and beta subunits into a complex, the result being tyrosine phosphorylation of the beta homodimer. Tyrosine phosphorylation of the subunit was impaired by deletion of the cytoplasmic domain of the alpha subunit without interfering with the association of both subunits. These results indicate that the beta homodimer, which alone is insufficient for signaling, forms the functional hGMR with the alpha subunit in response to hGM-CSF.

Cross-Linking Reagents↗
PubMed1996

Granulocyte-macrophage colony-stimulating factor provokes RAS activation and transcription of c-fos through different modes of signaling.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) provokes a proliferative response and induction of early-response genes such as c-fos in target cells. It also induces rapid tyrosine phosphorylation of cellular proteins, including the beta subunit (betac) of its functional receptor. However, locations and functions of phosphorylated tyrosine residues within the betac are unclear. To elucidate the mechanism of the human GM-CSF receptor signal transduction, mutational analyses were made of the cytoplasmic domain of the beta-c, using murine BA/F3 cells. Deletion of the conserved box 1 motif resulted in loss of tyrosine phosphorylation of the betac, thereby indicating an essential role for this motif in activating the tyrosine kinase which phosphorylates betac. A C-terminal truncated mutant at position 589 activated the c-fos promoter, and this activation was diminished by a substitution at tyrosine 577 (Tyr577). However, the same substitution in the full-length betac did not completely abrogate the c-fos promoter activation, hence, redundant signaling pathways probably exist. When we analyzed signaling molecules functioning downstream of the beta-c we found that Tyr577 is essential for Shc phosphorylation, while tyrosine phosphorylation of PTP1D was mediated through Tyr577 as well as through other site(s). We suggest that GM-CSF stimulates at least two modes of signals leading to Ras activation, an event which ultimately gives rise to promoter activation of c-fos.

Amino Acid Sequence↗