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Y Kanda

Publications and source records attributed to Y Kanda.

At least 37 records · Page 2Linked to original sources
PubMed1997

Mapping of the catalytic and epitopic sites of human CD38/NAD+ glycohydrolase to a functional domain in the carboxyl terminus.

We reported that 1) ecto-NAD+ glycohydrolase (NADase) activity induced upon differentiation of HL-60 cells is localized on the extracellular carboxyl-terminal side of CD38 and that 2) CD38 ligation by specific mAbs is followed by protein tyrosine phosphorylation in the cells. The strategy selected for identifying the relevant catalytic domains of the molecule relies upon the production in COS-7 cells of carboxyl-terminal deletion mutants of CD38. The mutants with fewer than 15 amino acids deleted at the carboxyl terminus of the 300-amino acid wild-type molecule maintained NADase activity, whereas those with more than 27 amino acids deleted did not. The general inference is that the carboxyl-terminal 273-285 sequence bears the site of enzyme activity. Introduction of site-directed mutation of a conserved cysteine residue (Cys275), located in the 273-285 sequence, completely abolished NADase activity. The second issue resolved in this work is the definition of an epitope of the agonistic anti-CD38 mAbs. To this aim, a panel of selected anti-CD38 mAbs was tested using these mutants and various CD38 fragments as the target in immunoblot analyses. All of the epitopes recognized by mAbs inducing protein tyrosine phosphorylation were mapped on an identical site containing the carboxyl-terminal sequence of 273-285. The conclusion is that the discrete carboxyl-terminal sequence identified in the present study not only plays a key role in its ecto-NADase activity, but actually constitutes the epitopes exploited by the agonistic anti-CD38 mAbs for transmembrane signaling.

ADP-ribosyl Cyclase↗
PubMed1997

Signal transduction via the CD38/NAD+ glycohydrolase.

The human cell surface CD38 molecule is a 46-kDa type-II transmembrane glycoprotein with a short N-terminal cytoplasmic domain and a long Cys-rich C-terminal extracellular one. We previously demonstrated that an ecto-form NAD+ glycohydrolase (NADase) activity induced by all-trans retinoic acid in HL-60 cells is due to the extracellular domain of CD38. In the present study, we investigated a possible signal transduction mediated through CD38 in the retinoic acid-differentiated HL-60 cells with anti-CD38 monoclonal antibodies (mAbs). The addition of selected anti-CD38 mAbs to the cells induced rapid tyrosine phosphorylation of the cellular proteins with the molecular weights of 120,000, 87,000 and 77,000; the phosphorylated 120-kDa protein was identified as the c-cbl proto-oncogene product, p120c-cbl. Furthermore, the phosphorylated p 120c-cbl associated with the 85-kDa subunit of phosphatidylinositol 3-kinase. To determine the relationship between the amino acid sequence responsible for the NADase activity and epitopes recognized by the stimulatory mAbs, we produced its carboxy-terminal deletion mutants in COS-7 cells. The mutants with less than 15 amino acids deleted from the carboxyl terminus of the 300-amino acid wild-type molecule still maintained NADase activity, but those with more than 27 amino acids deleted did not. Introduction of site-directed mutation of a cysteine residue (Cys275), located in the 273-285 sequence, completely abolished the NADase activity. These CD38 mutants were also used for an epitope mapping of anti-CD38 mAbs. All the epitopes recognized by the mAbs inducing the tyrosine phosphorylation were mapped on the same Cys275-containing sequence of 273-285. Thus, the discrete carboxy-terminal sequence not only plays a key role in its ecto-NADase activity, but also contains the epitopes of the agonistic anti-CD38 mAbs for the transmembrane signaling. We also found that the agonistic mAbs markedly potentiate superoxide generation induced by the stimulation of G protein-coupled chemotactic receptors. Our results suggested that the stimulation of CD38 might generate an accessory signal(s) to enhance the G protein-mediated signaling, probably though the protein-tyrosine phosphorylation.

ADP-ribosyl Cyclase↗
PubMed1997

The pituitary folliculo-stellate cell line TtT/GF augments basal and TRH-induced prolactin secretion by GH3 cell.

Numerous functions have been ascribed to anterior pituitary folliculo-stellate (FS) cells. Recently, we established a pituitary FS-like cell line (TtT/GF) from an isologously transplantable pituitary thyrotropic tumor. Here we investigated the effect of FS cells on prolactin (PRL) secretion by using a co-culture system between TtT/GF cells and GH3 cells. We observed that co-culture with TtT/GF cells significantly increased basal PRL secretion without affecting the growth rate of GH3 cells. Further, addition of anti-cytokine-induced neutrophil chemoattractant (CINC) antibody partially reduced PRL secretion in co-culture of GH3 cells with 10% TtT/GF cells. Co-culture with 5% TtT/GF cells also markedly enhanced the PRL response to thyrotropin-releasing hormone (TRH) by GH3 cells, while addition of anti-CINC antibody had no effects on the enhanced PRL response to TRH. These results suggest that FS cells augment basal PRL secretion and enhance the secretory response of PRL to TRH by a paracrine mechanism.

Animals↗
PubMed1997

Pituitary folliculo-stellate-like cell line produces a cytokine-induced neutrophil chemoattractant.

In previous studies, we reported that cytokine-induced neutrophil chemoattractant (CINC) was produced in the pituitary gland. Here we investigated the possibility of detection of CINC immunoreactivity in the pituitary folliculo-stellate (FS)-like cell line (TtT/GF). Intense immunoreactivity was observed by immunocytochemistry in the cytoplasm and cell processes of TtT/GF cells. CINC immunoreactivity was detected by an enzyme-linked immunosorbent assay in as little as 3 h after conditioning the medium with TtT/GF cells, and it increased significantly in a time-dependent manner during the first 24 h of the culture. This immunoreactivity could be induced by lipopolysaccharide and tumor necrosis factor-alpha in a time- and dose-dependent manner. We also observed the expression of CINC mRNA in TtT/GF cells and LPS increased CINC mRNA accumulation in TtT/GF cells. These findings indicate that CINC produced by FS cells may play a role as a paracrine factor of the anterior pituitary gland, and TtT/GF will provide a useful model system for studying the regulation of CINC secretion by FS cells.

Animals↗
PubMed1997

Subcellular localization of the MEN, MLL/MEN and truncated MLL proteins expressed in leukemic cells carrying the t(11;19)(q23;p13.1) translocation.

The t(11;19)(q23;p13.1) translocation is exclusively associated with myeloid leukemias. Previously, we cloned several species of MLL/MEN chimeric cDNAs in a patient with myeloid leukemia carrying the t(11;19)(q23;p13.1) translocation. The MEN sequence directly followed the 5' region of MLL cDNA in some species and otherwise there presented an inserted sequence of 120 bp between the MLL and MEN sequences in others. Because the insertion sequence contained an in-frame termination codon, they coded only for the NH2-terminal part of MLL (truncated MLL). We also cloned the normal MEN cDNA in full-length with a cDNA library derived from K562 cells. We expressed the normal MEN, MLL/MEN chimeric and truncated MLL proteins in COS7 cells with the corresponding cDNAs and detected them with antibodies raised against the MEN and MLL peptides. Immunostaining and subcellular fractionation showed nuclear localization of all these proteins. These findings suggested that MLL/MEN chimeric cDNAs were actually translated into both MLL/MEN fusion and truncated MLL proteins and that they were localized in the nucleus of leukemic cells. Recently, Conaway et al. reported that MEN is an RNA polymerase II elongation factor. The leukemogenesis by the t(11;19)(q23;p13.1) translocation may have resulted from the alteration of transcription regulation induced by the MLL/MEN fusion protein and/or the truncated MLL protein.

Animals↗
PubMed1997

Rapid progression of chronic myelomonocytic leukemia following diaminodiphenyl sulphone treatment for dermatitis herpetiformis.

A 41-year-old patient with dermatitis herpetiformis (DH) developed steroid-resistant blebs as a sign of exacerbating DH. The skin symptoms were resolved after 2 weeks of oral administration of diaminodiphenyl sulphone (DDS). However, 3 weeks after the start of DDS, he suffered from edematous eruption on the cheeks and neck, enlargement of the pharynx, systemic lymphoadenopathy and hepatomegaly. In addition, his leukocyte count increased rapidly from 10.1 x 10(9)/l with 13% monocytes just before the start of DDS, to 24.6 x 10(9)/l with 28% monocytes. Bone marrow aspirate showed trilineage dysplasia and chronic myelomonocytic leukemia (CMML) was diagnosed. The patient died from septic shock during neutropenia following cytotoxic chemotherapy. In this case, CMML was complicated with DH and the administration of DDS accelerated the progression of CMML with the manifestations of DDS syndrome. Although DDS is a well-established drug for DH, DDS should be used with great caution when a hematological malignancy coexists.

Adult↗
PubMed1997

Synthesis and pharmacological properties of ureidomethylcarbamoylphenylketone derivatives. A new potent and subtype-selective nonpeptide CCK-B/gastrin receptor antagonist, S-0509.

A novel series of CCK-B/gastrin receptor antagonists-ureidomethylcarbamoylphenylketone derivatives-were designed, synthesized, and evaluated for activity. Structure-activity relationship studies revealed the importance of a carboxylic acid at substituent R2 and tert-butoxycarbonyl group at R1 in structure A. Compound 7a (S-0509) showed remarkable affinity for the CCK-B/gastrin receptor and a subtype selectivity profile in vitro. Administration (id) of 7a led to excellent inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats with an ED50 value of 0.014 mg/kg. Furthermore, 7a proved to have poor blood-brain permeability by its small effect on enhancement of morphine analgesia. Thus, S-0509 has an increase in selectivity for the peripheral effects of gastrin antagonism from the central effects of CCK-B antagonism.

Animals↗
PubMed1997

Malignant hyperthermia induced by general anesthesia for bone marrow harvesting.

We present a case of a bone marrow donor who developed rhabdomyolysis, acute renal failure and pulmonary edema following an apparently uneventful general anesthesia for bone marrow harvesting. Because malignant hyperthermia (MH) was suspected, he was treated with dantrolene, fluid loading, and continuous hemodiafiltration along with symptomatic supportive care. He made a full recovery and was discharged 3 weeks after harvest. Although the incidence of MH is low, marrow donation involves the risks of anesthesia as is seen in this case. Close monitoring is required to prevent life-threatening complications associated with the bone marrow harvesting procedure.

Adult↗
PubMed1997

Bronchiolitis obliterans organizing pneumonia after syngeneic bone marrow transplantation for acute lymphoblastic leukemia.

We report a patient who developed bronchiolitis obliterans organizing pneumonia (BOOP) after syngeneic BMT for ALL. The patient complained of persistent low-grade fever and non-productive cough after engraftment. Chest CT scan showed patchy infiltration bilaterally in the lower lung fields. Antibiotics were ineffective. Cultures, serological studies and polymerase chain reaction detected no infectious pathogens. We finally made a diagnosis of BOOP by thoracoscopical lung biopsy. The lung lesion disappeared in a month with corticosteroid therapy. While BOOP following allogeneic BMT has been reported, this is the first report after syngeneic transplantation.

Adult↗
PubMed1997

No concomitant occurrence of the N-ras and p53 gene mutations in myelodysplastic syndromes.

Mutations of the N-ras oncogene and p53 tumor suppressor gene were simultaneously investigated in bone marrow cells from 44 patients with myelodysplastic syndrome (MDS) or MDS-derived leukemia by single-strand conformation polymorphism (SSCP) analysis followed by direct sequencing. The mutations of the N-ras gene were detected only in two cases with MDS-derived leukemia. Three patients with MDS-derived leukemia and one with refractory anemia with excess of blasts exhibited five mutations of the p53 gene. No concomitant mutations of both genes were observed in our study, suggesting that alterations of both genes could play an important role in the progression of MDS in a non-cooperative manner.

Anemia, Refractory↗
PubMed1997

GRO-alpha in human serum: differences related to age and sex.

PROBLEM: Human GRO-alpha (GRO-alpha) is a new member of the chemokine family that is supposed to play an important role in inflammatory and immune reactions. We established a sandwich enzyme-linked immunoassay (ELISA) system with polyclonal antibodies against human GRO-alpha and investigated the serum level of healthy donors to establish normal ranges for this chemokine in adults. METHODS: GRO-alpha concentrations were measured cross-sectionally in the sera of 240 healthy adults. The variability of serum GRO-alpha levels was also measured in normal volunteers, samples from whom were obtained by sequential venipunctures or by a small plastic cannula with a heparin-saline lock, to determine short-term variability. RESULTS: Whereas there was no difference between the concentration of human GRO-alpha from men (logarithmic mean, 77.6 pg/ml, n = 120) and that from women with normal menstrual cycles (log mean, 71.6 pg/ml, n = 73), the concentration from postmenopausal women (log mean 45.0 pg/ml, n = 31) was lower than that from women with normal menstrual cycles (log mean 71.6 pg/ml, n = 73). However, we could not detect any significant difference between healthy donors' serum levels and those of donors with acute inflammation. Fewer variations were recognized in the case of the sequential venipunctures method than in that of the heparin-saline lock method. CONCLUSION: We found that the GRO-alpha concentration of postmenopausal women was significantly lower than that of women with normal menstrual cycles. These results suggest the GRO-alpha serum levels of normal healthy women may have some correlation with sex hormones.

Acute Disease↗
PubMed1997

Aspergillus endocarditis in a leukemia patient diagnosed by a PCR assay.

A patient in a blastic phase of chronic myelocytic leukemia developed multiple arterial emboli that originated from mitral valve vegetation. The diagnosis of infective endocarditis was not confirmed because blood cultures, serological assays and other examinations detected no pathogens. He died of intracranial hemorrhage after thrombolytic manipulation for embolization of the abdominal aorta and an autopsy was performed. Polymerase chain reaction analysis and Southern blot analysis of tissues from the mitral valve revealed Aspergillus species as the cause of the endocarditis, although none of the tissue specimens were culture-positive. These molecular analyses will be useful in the diagnosis of various types of Aspergillus infections.

Aspergillosis↗
PubMed1997

Triple synergism of human T-lymphotropic virus type 1-encoded tax, GATA-binding protein, and AP-1 is required for constitutive expression of the interleukin-5 gene in adult T-cell leukemia cells.

Accumulated evidence demonstrates that adult T-cell leukemia (ATL) is frequently associated with eosinophilia, and human T-lymphotropic virus type 1 (HTLV-1)-infected cells frequently express interleukin-5 (IL-5). However, the molecular mechanism of constitutive IL-5 expression in HTLV-1-infected cells remains unclear. To clarify the mechanism of aberrant IL-5 expression in HTLV-1-infected cells, we investigated the response of the human IL-5 promoter to the HTLV-1-encoded protein Tax. Cotransfection experiments using Jurkat cells revealed that Tax is incapable of activating the IL-5 promoter by itself but that it synergistically transactivates the promoter with GATA-binding protein (GATA-4) and 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation. By introducing a series of mutations within the IL-5 promoter, we found that conserved lymphokine element 0 (CLE0) is responsible for mediating the signal induced by Tax-TPA. A deletion construct of the promoter indicated that the -75 GATA element and CLE0 are sufficient to mediate synergistic activation of the IL-5 promoter. Electrophoretic mobility shift assays using Jurkat cell nuclear extracts demonstrated that TPA induces a transcription factor to bind CLE0, and an experiment using JPX-9 cell nuclear extracts showed that Tax enhances this binding activity. An antibody supershift experiment revealed that this band consists of c-Jun and JunD. However, among the Jun family members, only c-Jun is able to cooperate with Tax and GATA-4 to activate the IL-5 promoter. We have determined the minimum factors required for IL-5 gene activation by reconstituting the IL-5 promoter activity in F9 cells. This is the first report to demonstrate the functional involvement of Tax protein in IL-5 gene regulation and to suggest the functional triple synergism among Tax, GATA-4, and AP-1, which disrupts regulated control of the gene and leads to constitutive expression of the IL-5 gene.

Calcimycin↗
PubMed1997

Norepinephrine stimulates mitogen-activated protein kinase activity in GT1-1 gonadotropin-releasing hormone neuronal cell lines.

The GT1-1 GnRH neuronal cell lines exhibit highly differentiated properties of GnRH neurons. We have used GT1-1 cells to study the roles of norepinephrine (NE), membrane depolarization, calcium influx, and phorbol esters in the regulation of mitogen-activated protein (MAP) kinase. NE, which is known to stimulate the release of GnRH, induced MAP kinase activity, the tyrosine phosphorylation of MAP kinase, and MAP kinase kinase activity. Forskolin led to activation of MAP kinase comparable with that induced by NE, and a selective inhibitor of cAMP-dependent protein kinase, H8, attenuated the NE-induced activation of MAP kinase. On the other hand, elimination of extracellular calcium by EGTA completely blocked NE-induced tyrosine phosphorylation of MAP kinase, and a selective inhibitor of calcium/calmodulin-dependent protein kinase, KN-62, attenuated the NE-induced activation of MAP kinase. Furthermore, depolarization of GT1-1 cells with 75 mM KCl, 10 microM BayK 8644, or 1 microM calcium ionophore (A23187) induced rapid tyrosine phosphorylation of MAP kinase. The omission of calcium from the extracellular medium completely abolished these effects of tyrosine phosphorylation of MAP kinase. Phorbol 12-myristate 13-acetate (PMA) also induced MAP kinase activity, but pretreatment of the cultured cells with PMA to down-regulate protein kinase C did not abolish the activation of MAP kinase by NE. In addition, although phosphorylation of Raf-1 kinase was stimulated by PMA, this phosphorylation was not induced by either NE or A23187. These results demonstrate that NE activates MAP kinase directly in GT1-1 cells, and that the effect of NE is mediated by increase in the cAMP level and by calcium influx, but not by PMA-sensitive protein kinase C or Raf-1 kinase.

Animals↗
PubMed1997

High-performance liquid chromatographic analysis of bilirubin and biliverdin from jaundiced broilers.

A sensitive and rapid high-performance liquid chromatographic (HPLC) method was developed and used for the simultaneous determination of bilirubin and biliverdin in pericardial fluid samples collected from broilers at a poultry inspection site. A photodiode array detector distinguishing the bilirubin (UV 450 nm) and biliverdin (365 nm) was used as an analytical detector for HPLC system. An internal-surface reversed-phase silica support column was used, and the mobile phase consisted of acetonitrile: 0.5 M Tris HCl buffer (20:80, pH 7.2). Bilirubin was detected from all of the jaundiced pericardial fluid samples, and a small amount of biliverdin was detected with bilirubin in some samples. These jaundiced broilers had hepatic or bile duct lesions similar to those found in edible animals. From these results, a working definition of jaundiced broilers for poultry inspection sites was suggested: bilirubin is detectable from pericardial fluid and the carcass is in a state of yellow color change.

Animals↗
PubMed1997

[Ifosfamide chemotherapy ineffective for advanced pancreatic carcinoma].

Ifosfamide chemotherapy was studied in 20 patients with advanced pancreatic carcinoma. It was administered at a dose of 1.2-1.5 g/body/day for 5 consecutive days every 3-4 weeks, and the patients treated over 2 courses were registered in our trial. Eleven patients had not received prior chemotherapy. Results achieved were as follows: PR in one patient, NC in 9 patients, and PD in 10 patients. The response rate was 5% and the median survival time was 17 weeks. Toxic effects included anorexia (80%), nausea and vomiting (65%), alopecia (20%), mental disturbance (20%), granulocytopenia (20%), thrombocytopenia (5%), and no renalurological disturbance. We concluded that ifosfamide was not effective for chemotherapy of advanced pancreatic carcinoma.

Adult↗
PubMed1996

Induction of CD38/NADase and its monoclonal antibody-induced tyrosine phosphorylation in human leukemia cell lines.

We previously reported that CD38 characterized as an ecto-enzyme of NAD+ glycohydrolase (NADase) was specifically induced by retinoic acid (RA) in human promyelocytic leukemia HL-60 cells and that anti-CD38 monoclonal antibody (mAb) induced tyrosine phosphorylation of cellular proteins in the RA-differentiated cells. In the present study, we found that CD38/NADase was induced in human monocytic leukemia THP-1 cells not only by RA but also by dibutyryl cAMP, which had no effect on the induction of CD38 in HL-60 cells. Similarly in the RA-differentiated HL-60 cells, tyrosine phosphorylation by anti-CD38 mAb was also observed in the CD38-expressing THP-1 cells, regardless of whether CD38 was induced by RA or dibutyryl cAMP. Such tyrosine phosphorylation was, however, not observed in human lymphoblastic leukemia Jurkat cells which had been treated by RA to produce CD38. Thus, the induction of CD38/NADase appeared to be not limited for RA-dependent differentiation and not always linked to protein-tyrosine phosphorylation in human leukemic cell lines.

ADP-ribosyl Cyclase↗