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T Shikano

Publications and source records attributed to T Shikano.

At least 37 records · Page 2Linked to original sources
PubMed1996

Pharmacological profile of T-0632, a novel potent and selective CCKA receptor antagonist, in vivo.

The pharmacological profile of a new CCKA receptor antagonist, T-0632 [sodium (S)-1-(2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolinylcarbonyl) amino]-6-methoxy-2-oxo-1H-indole-3-propanoate], was examined in in vivo studies and compared with those of L-364, 718 [3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepine-3-yl)-1 H-indole-2-carboxamide] and loxiglumide [D.L-4-(3,4-dichlorobenzoylamino)-5-(N-3-methoxypropyl-pentylam ino)-5- oxopentanoic acid]. In rats, intravenously administered T-0632, L-364,718 and loxiglumide dose dependently inhibited cholecystokinin octapeptide (CCK-8)-stimulated pancreatic exocrine secretion with estimated ED50 values of 0.025, 0.016 and 1.8 mg/kg, respectively. The ED50 values for intraduodenal administration of these compounds were 0.040, 0.26 and 3.0 mg/kg, respectively. In mice, orally administered T-0632 prevented caerulein-induced pancreatitis, CCK-8-induced inhibition of gastric emptying and CCK-8-induced gallbladder emptying in dose-dependent manners with ED50 values of 0.028, 0.04, and 0.12 mg/kg, respectively. The effect of T-0632 for caerulein-induced pancreatitis was 4-fold more potent than that for gallbladder emptying. In contrast, the effects of L-364,718 and loxiglumide for caerulein-induced pancreatitis were 2-4-fold weaker than those for gallbladder emptying. In dogs, T-0632 and loxiglumide maximally inhibited CCK-8-stimulated pancreatic amylase secretion at doses of 0.01 and 10 mg/kg, respectively. At these doses, the effect of T-0632 on CCK-8-induced increase in the gallbladder intraluminal pressure was weaker than that of loxiglumide. These results suggest that T-0632 has a potent antagonistic action on CCKA receptors in several animal species and the effects of T-0632 are more selective for the pancreas over the gallbladder compared with L-364,718 and loxiglumide.

Animals↗
PubMed1996

Atrial natriuretic peptide induces the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in glomerular mesangial cells.

Atrial natriuretic peptide (ANP) has been shown to inhibit the proliferation of various types of cells including glomerular mesangial cells. The activation of mitogen-activated protein kinase (MAPK) is one of the main signal transduction systems leading to cell proliferation. MAPK is tightly regulated by the activating kinase, MEK, and specific phosphatase MKP-1. Constitutive expression of MKP-1 has been shown to inhibit cell proliferation by suppressing MAPK activity. In order to understand the mechanism of the anti-proliferative effect of ANP, we examined whether ANP could inhibit MAPK by inducing MKP-1 in cultured rat glomerular mesangial cells. ANP increased the expression of MKP-1 mRNA in a dose-dependent (10 nM maximum) and time-dependent, with a peak stimulation at 30 min, manner. Receptor for ANP is a transmembrane guanylyl cyclase. Activation of guanylyl cyclase of ANP receptor by ligand plays an essential role in ANP signal transduction. 8-Bromo-cGMP, a cell permeable analogue of cyclic GMP, and sodium nitroprusside, an activator of soluble guanylyl cyclase, could mimic the effects of ANP and were able to induce the expression of MKP-1 in a similar time course as ANP. The protein expression of MKP-1 was maximally stimulated by ANP at 120 min. Treatment of the cells with ANP for 120 min resulted in an inhibition of phorbol ester-induced activation of MAPK, while the activation of MEK was not affected by ANP. These results indicate that ANP might inhibit the proliferation of mesangial cells by inactivating MAPK through the induction of MKP-1.

Amino Acid Sequence↗
PubMed1996

[Tyrosine phosphorylation of focal adhesion kinase (p125FAK) and paxillin in glomeruli from diabetic rats].

Focal adhesion kinase (p125FAK) is a novel non-receptor cytosolic tyrosine kinase which is activated through the phosphorylation of its tyrosine residue by ligands that bind to integrins and ligands that activate protein kinase C (PKC). In diabetic glomeruli, extracellular matrix proteins such as fibronectin, laminin and type IV collagen, which bind to integrins, were found to be increased in the mesangial area. Furthermore, PKC was shown to be activated in diabetic glomeruli. These changes might be able to cause the activation of p125FAK in diabetic glomeruli. To test this hypothesis, we examined tyrosine phosphorylation of p125FAK and paxillin, a proposed substrate of p125FAK, in glomeruli isolated from streptozotocin (STZ)-induced diabetic rats. Tyrosine phosphorylation of p125FAK or paxillin was evaluated by immunoblot analysis using anti-phosphotyrosine antibody after immunoprecipitation with anti-p125FAK or anti-paxillin antibody. Three and seven weeks after STZ injection, tyrosine phosphorylation of both p125FAK and paxillin was increased in diabetic glomeruli. The increase in tyrosine phosphorylation of p125FAK and paxillin was not observed in glomeruli from diabetic rats treated with insulin. To investigate the mechanism of increase in tyrosine phosphorylation of p125FAK, we examined tyrosine phosphorylation of p125FAK in mesangial cells plated on a fibronectin-coated dish or cultured under conditions of high glucose concentration (conditions under which PKC can be activated). Attachment of the cells to fibronectin induced tyrosine phosphorylation of p125FAK, while a high glucose concentration did not modulate tyrosine phosphorylation of p125FAK. In conclusion, tyrosine phosphorylation of p125FAK and paxillin was increased in diabetic glomeruli and these alternations may have been caused by changes in extracellular matrix proteins in diabetes.

Animals↗
PubMed1996

[Childhood acute promyelocytic leukemia treated with all-trans retinoic acid].

We treated two children with acute promyelocytic leukemia (APL) in whom complete remission was successfully induced by oral administration of all-trans retinoic acid (ATRA). We followed these patients with conventional chemotherapy. The first patient has remained in continuous complete remission. However, the other patient relapsed during the maintenance therapy and died of progressive disease in spite of a second treatment with ATRA and chemotherapy. From a clinical point of view, the latter case had a hyperleukocytosis on admission. Also morphologically speaking, this patient had a different M3 variant than the first case. There are two major isoforms of PML/RAR alpha transcripts, so called short and long type transcripts, according to the breakpoints in the PML genes. In the first case the "long type' isoform was detected by reverse transcriptase polymerase chain reaction (RT/PCR) amplification. On the other hand the "short type' isoform was observed in the latter case. Also the second case became PCR positive at relapse, although the detectable isoform was negative during remission. The "short type' isoform may be related to the poor prognosis and RT/PCR analyses may be a powerful to detect early relapse.

Adolescent↗
PubMed1995

Mutations of the p53 and ras genes in childhood t(1;19)-acute lymphoblastic leukemia.

We have investigated the alterations of p53 and ras genes including H-, K-, and N-ras genes in 22 acute lymphoblastic leukemia (ALL) cases and five cell lines carrying t(1;19) by use of polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis and direct sequencing. The mutations of the p53 gene were found in 2 of 20 t(1;19)-ALL cases at diagnosis (10%), all of 4 cases at relapse (100%), and 4 of the 5 cell lines (80%). Four of the five patients who died had missense mutations at codons 49, 177, 179, and 248. In cases examined sequentially, one had the same point mutation at codon 179 at both diagnosis and relapse, and another had the same p53 gene mutation at codon 240 both in leukemic cells at relapse and in a cell line derived at that time. The other case had no mutation at diagnosis but had the mutation at codon 177 at relapse and cell lines derived from blast cells at diagnosis, suggesting that a small number of leukemic cells with the p53 gene mutation at diagnosis might have escaped PCR-SSCP analysis. In cell lines, SCMC-L9 had three point mutations in the p53 gene at codons 175, 248, and 358, whereas SCMC-L10 had frame shift at codons 209-211. One case had a rare polymorphism at codon 11. We found only one mutation of the N-ras gene that was a 2-bp substitution of GGT(Gly) to GTC(Val) at codon 13 among 22 t(1;19)-ALL cases and five cell lines. This case showed no mutation of the p53 gene and has had a good course. These results suggest that in t(1;19)-ALL, mutations of the p53 and ras genes are infrequent at diagnosis and that p53 gene alterations may be associated with relapse phase or progression of t(1;19)-ALL.

Adolescent↗
PubMed1995

A t(11;14)(p13;q11) specific for T-cell malignancies in acute megakaryoblastic leukemia.

A 2-year-old girl with a very rare form of acute megakaryoblastic leukemia (AMKL), having the 11p13;14q11 translocation specific for T-cell malignancies, is reported. She was diagnosed as having AMKL on the basis of her bone marrow, which contained 30% megakaryoblasts identified by characteristic morphology on May-Giemsa stain, positive for platelet peroxidase activity and for the surface marker of platelet glycoprotein IIb/IIIa, CD41. Cytogenetic studies of marrow cells revealed 47,XX,i(7q), +der(11)t(11;14)(p13;q11), -14, +21. She achieved hematologic remission after two courses of chemotherapy including behenoyl cytarabine, acracinorubicin, 6 mercaptopurine, and prednisolone, but soon relapsed and died 11 months after admission. This case suggests that adequate diagnostic assessments of morphology, surface markers, and cytogenetics are necessary for proper diagnosis in leukemia and lymphoma, and that an important, though as-yet unidentified, gene in megakaryopoiesis may reside in the 14q11 chromosomal region.

Chromosomes, Human, Pair 11↗
PubMed1995

Endothelin-1 stimulates tyrosine phosphorylation of p125 focal adhesion kinase in mesangial cells.

Endothelin-1 (ET-1) is known to induce the contraction and proliferation of glomerular mesangial cells. Because ET-1 was found to stimulate the tyrosine phosphorylation of unidentified cellular proteins in cultured mesangial cells, protein tyrosine kinase might serve as one of the important signals leading to various functions of ET-1. Focal adhesion kinase (p125FAK) is a newly identified cytoplasmic protein tyrosine kinase that is activated by the phosphorylation of its own tyrosine residue. Because p125FAK was found to play a role in the signal transduction of not only integrins but also various neurotransmitters, including bombesin, endothelin, and vasopressin in Swiss 3T3 cells and Rat-1 fibroblasts, whether ET-1 could stimulate the tyrosine phosphorylation of p125FAK in glomerular mesangial cells was examined. ET-1 stimulated the tyrosine phosphorylation of p125FAK by threefold to fourfold in cultured mesangial cells. This effect of ET-1 was detected at 1 min and reached a maximum within 5 min and was blocked by BQ-123, an antagonist for ETA receptor. A23187, a calcium ionophore, failed to stimulate the tyrosine phosphorylation of p125FAK, and ET-1 was able to stimulate the tyrosine phosphorylation of p125FAK, even in a calcium-free medium. The activation of protein kinase C (PKC) by phorbol 12, 13-dibutyrate resulted in a stimulation of the tyrosine phosphorylation of p125FAK, and an inhibition of PKC by calphostin C or staurosporine significantly reduced the effect of ET-1. Furthermore, prolonged treatment of the cells with phorbol 12, 13-dibutyrate markedly inhibited the ET-1-induced tyrosine phosphorylation of p125FAK. These results indicate that p125FAK might play a role in a signal transduction system of ET-1 in glomerular mesangial cells and that the ET-1-induced tyrosine phosphorylation of p125FAK is largely dependent on the PKC pathway.

Animals↗
PubMed1994

Acute lymphoblastic leukemia and non-Hodgkin's lymphoma with mediastinal mass--a study of 23 children; different disorders or different stages?

Mediastinal tumor was found in both acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). Most cases showed the T-cell phenotype. We query whether these two diseases are in fact different disorders or merely different stages of the same disease. Twelve ALL patients with a mediastinal mass and eleven NHL patients with a mediastinal mass under 15 years of age were studied with respect to cytogenetics, immunophenotype, genotype and clinical features. Clonal chromosome abnormalities were found in 75% (9/12) of the ALL patients and 100% (11/11) of the NHL patients. Of the 20 patients with chromosome abnormalities, 12 (60%) had translocations involving 14q11-13 and 7q35 (8 ALL, 4 NHL). t(9;17)(q34;q23) was found only in 3 patients with NHL. All showed the T-cell phenotype except two, who had none of the chromosomal abnormalities frequently detected in T cell ALL/NHL. In T-cell patients, immunophenotypical staging of ALL showed a predominance of early and common thymocyte phenotypes while that of NHL showed a predominance of common thymocyte phenotypes. All 7 of the T-cell patients examined showed rearrangements of the T-cell receptor beta chain gene. On the other hand, two non-T-cell, non-B-cell patients showed no rearrangement. There were no apparent clinical differences between ALL and NHL patients in age (median 8.6 vs 8.9 years), sex ratio (F/M 9/3 vs 7/4) or in the rate of complete remission (90% vs 100%). Our study demonstrated no relevant clinical, prognostic, or immunophenotypic differences between ALL and NHL with mediastinal mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[A study of E2A gene in childhood acute lymphoblastic leukemia].

E2A gene rearrangements and E2A-PBX1 chimeric mRNA produced by t(1;19) were examined in 50 cases with acute lymphoblastic leukemia (ALL). Nine of 10 ALL cases with t(1;19) showed the rearrangement by Southern blotting using the E2A gene probe when digested with Xba I, Bgl II, and Eco RI, and the remaining one having hyperdiploidy which was considered to be a sign of good prognosis, lacked E2A rearrangement. Six of 7 ALL cases with t(1;19) that were tested showed the predicted 164 bps band of E2A-PBX1 chimeric mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR), while a case having t(1;19) without E2A rearrangement and 10 cases lacking t(1;19) did not. Three ALL cases tested did not have E2A-PBX1 mRNA at the time complete remission 4 months after diagnosis. Forty ALL cases lacking t(1;19), including 4 cases with t(11;19), did not reveal rearrangement of E2A. We conclude that t(1;19)-ALL can be molecularly diagnosed, and minimal residual disease could be detected by the RT-PCR method.

Adolescent↗
PubMed1994

[Three cases of hematologic malignancies with jumping translocation].

We treated three cases of hematologic malignancies (Burkitt's lymphoma, ALL (L3), AML (M0)) with jumping translocations. Tumor formation was easily occurred in all three cases. The location of the jumping translocation was 1q21 in all three cases. Hematologic malignancies with jumping translocation tend to be B-cell lineage and have poor prognosis. The significance of jumping translocation is unknown yet, but it seems that jumping translocation is related to the tumor progression, rather than tumorigenesis. So that the intensive therapy including bone marrow transplantation must be considered.

Adolescent↗
PubMed1993

Antagonist for atrial natriuretic peptide receptors ameliorates glomerular hyperfiltration in diabetic rats.

To evaluate the possible contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration, we examined the effect of non-peptide competitive antagonist for biological receptors of ANP, HS-142-1, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in diabetic rats. Increased GFR and RPF in diabetic rats were significantly ameliorated by the injection of HS-142-1, while blood pressure remained unchanged. Urinary cyclic GMP excretion was significantly higher in diabetic rats than in control rats and HS-142-1 decreased urinary cGMP excretion significantly. These results indicate that atrial natriuretic peptide contributes to the development of glomerular hyperfiltration and hyperperfusion in diabetes and HS-142-1 might be useful in the treatment of them.

Animals↗
PubMed1993

Jumping translocations of 1q in Burkitt lymphoma and acute nonlymphocytic leukemia.

"Jumping translocations" have been observed mostly in cultured cells. Reports of such translocations in hematologic malignancies are few, and the associated clinical picture is unclear. We report three cases of hematologic malignancies with various unbalanced translocations (so-called jumping translocation) involving trisomy of the long arm of chromosome 1. The first case was a 13-year-old boy with Burkitt lymphoma who showed a very aggressive clinical course. The second case was a 10-month-old girl with acute nonlymphocytic leukemia [ANNL, French-American-British (FAB) classification M0] who had high risk factors, including hyperleukocytosis with a peripheral white blood cell (WBC) count of 300,000/microliters, and who died 7 months after diagnosis. The third case was a 6-year-old boy with Burkitt-like leukemia whose first remission lasted only 1 month. Only 10 cases with jumping translocations, including two cases with Burkitt-like leukemia/lymphoma, have been reported previously. This rare phenomenon may occur with increased frequency in Burkitt-like leukemia/lymphoma and may be an adverse prognostic factor.

Adolescent↗
PubMed1992

Cytogenetic characteristics of childhood non-Hodgkin lymphoma.

Cytogenetic studies were performed successfully on 24 patients with non-Hodgkin lymphoma (NHL) who were younger than 15 years of age. Of these, 22 patients (92%) had abnormal clones. With respect to histologic findings, 3 (25%) of the 12 patients with lymphoblastic lymphoma had 14q11 translocations and 2 (17%) had t(9;17) (q34;q23). Four (80%) of the five patients with small non-cleaved cell lymphoma had t(8;14)(q24;q32). With respect to immunologic findings, four (44%) of the nine patients with T-cell lymphoma had abnormalities consisting of 14q11 and 7q36 translocations, in which the T-cell receptor genes resided. Three (33%) of the patients with T-cell lymphoma had t(9;17)(q34;q23). However, three (43%) of the seven patients with B-cell lymphoma had t(8;14) (q23;q32), and two (29%) of the patients with B-cell lymphoma had an extra i(11q) chromosome with a resultant 11q tetrasomy. Non-T-cell non-B-cell lymphomas, which occurred in 21% of all patients, showed various chromosomal abnormalities. This study demonstrated that, in childhood NHL, karyotype correlates closely with immunophenotype, clinical features, and histologic findings.

Adolescent↗
PubMed1992

Myelodysplastic syndrome with partial deletion of the long arm of chromosome 5: first report of a case in a child.

A childhood case of myelodysplastic syndrome (MDS) with a deletion of the long arm of chromosome 5 (5q-) is reported. The patient was an 8 year old boy who has recurrent angina. Laboratory evaluation revealed the following: hemoglobin 8.1 gm/dl, white blood cell count 4.9 x 10(3)/l with 3% atypical lymphocytes, and platelet count 17.7 x 10(4)/l. A bone marrow aspirate revealed 20% blast cells and dysmyelopoietic changes involving all three marrow cell lines. Karyotype analysis of marrow cells revealed 46,XY,5q- in 100% of the metaphases. These findings led to a diagnosis of MDS with 5q-, which is most commonly found in adult MDS. This case seems to represent an exceedingly rare childhood case of MDS with 5q-.

Bone Marrow Examination↗
PubMed1992

[Chromosome abnormalities and prognosis in childhood acute leukemia].

The chromosomal classification system of childhood acute leukemia according to ploidy or structural chromosomal changes of leukemia cells is clinically useful for the prediction of the treatment outcome. While patients with hyperdiploid (greater than 50 chromosomes) ALL enjoy the best prognosis, those with hypodiploid or pseudodiploid ALL are expected to have unfavorable clinical outcome. Among various translocations or deletions in ALL, t(4;11), t(9;22) and t(8;14) predict the worst clinical outcome. AML patients with t(8;21) or inv (16) have better 50% survival than those with other chromosome changes or normal diploidy. Chromosome analysis of leukemia cells should be included in the diagnostic workup of childhood acute leukemia.

Age Factors↗
PubMed1992

[Alveolar rhabdomyosarcoma with massive bone marrow involvement and 2;13 chromosome translocation].

We report a 9-year-old girl who had massive bone marrow infiltration of tumor cells at the onset of alveolar rhabdomyosarcoma. She was admitted to a surgical hospital because of abdominal pain and tumor in the buttock. Computerized tomographic scans of the pelvis revealed an abnormal mass. She was referred to our department. Hematological examination showed pancytopenia. Blood chemistry revealed hypercalcemia and hyperuricemia. Bone marrow was occupied with 100% tumor cells. Chromosome analysis of tumor cells in bone marrow revealed a specific translocation, t(2;13) (q37;q14). This finding enabled the diagnosis of a disseminated alveolar rhabdomyosarcoma to be established. She was treated with vincristine, cyclophosphamide and epirubicin, achieved a complete remission, but died of relapse 3 months after diagnosis.

Bone Marrow Diseases↗
PubMed1991

Detection of tyrosine hydroxylase mRNA and minimal neuroblastoma cells by the reverse transcription-polymerase chain reaction.

To facilitate the diagnosis of bone marrow metastasis in neuroblastoma, we have developed a method of amplifying and detecting the tyrosine hydroxylase (TH) mRNA sequence in bone marrow cells using a combination of reverse transcription and the polymerase chain reaction (RT/PCR). By this method, the sequence of TH was detected clearly in the neuroblastoma tissues of all 6 patients and not detected in the bone marrow cells of any of the 9 negative control children. In a reconstitution experiment, 1 neuroblastoma cell per 100,000 normal bone marrow cells could be detected, thus indicating the great sensitivity of this method. Based on these results, this technique may be of value in the diagnosis and treatment follow-up of bone marrow metastasis of neuroblastoma.

Adult↗