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Biomedical subjects

S Takada

Publications and source records attributed to S Takada.

At least 73 records · Page 4Linked to original sources
PubMed1999

Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability.

Axin forms a complex with glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin, thereby stimulating the degradation of beta-catenin. Because GSK-3beta also phosphorylates Axin in the complex, the physiological significance of the phosphorylation of Axin was examined. Treatment of COS cells with LiCl, a GSK-3beta inhibitor, and okadaic acid, a protein phosphatase inhibitor, decreased and increased, respectively, the cellular protein level of Axin. Pulse-chase analyses showed that the phosphorylated form of Axin was more stable than the unphosphorylated form and that an Axin mutant, in which the possible phosphorylation sites for GSK-3beta were mutated, exhibited a shorter half-life than wild type Axin. Dvl-1, which was genetically shown to function upstream of GSK-3beta, inhibited the phosphorylation of Axin by GSK-3beta in vitro. Furthermore, Wnt-3a-containing conditioned medium down-regulated Axin and accumulated beta-catenin in L cells and expression of Dvl-1(DeltaPDZ), in which the PDZ domain was deleted, suppressed this action of Wnt-3a. These results suggest that the phosphorylation of Axin is important for the regulation of its stability and that Wnt down-regulates Axin through Dvl.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Axin prevents Wnt-3a-induced accumulation of beta-catenin.

When Axin, a negative regulator of the Wnt signaling pathway, was expressed in COS cells, it coeluted with glycogen synthase kinase-3beta (GSK-3beta), beta-catenin, and adenomatous polyposis coli protein (APC) in a high molecular weight fraction on gel filtration column chromatography. In this fraction, GSK-3beta, beta-catenin, and APC were co-precipitated with Axin. Although beta-catenin was detected in the high molecular weight fraction in L cells on gel filtration column chromatography, addition of conditioned medium expressing Wnt-3a to the cells increased beta-catenin in the low molecular weight fraction. However, Wnt-3a-dependent accumulation of beta-catenin was greatly inhibited in L cells stably expressing Axin. Axin also suppressed Wnt-3a-dependent activation of Tcf-4 which binds to beta-catenin and acts as a transcription factor. These results suggest that Axin forms a complex with GSK-3beta, beta-catenin, and APC, resulting in the stimulation of the degradation of beta-catenin and that Wnt-3a induces the dissociation of beta-catenin from the Axin complex and accumulates beta-catenin.

Adenomatous Polyposis Coli Protein↗
PubMed1999

A new simple technique for performing intraoperative endoscopic resection of small-bowel polyps in patients with Peutz-Jeghers syndrome.

We describe herein a simple method for performing intraoperative endoscopic resection of small-bowel polyps associated with Peutz-Jeghers syndrome, using a corrugated anesthetic tube. A 34-year-old man with Peutz-Jeghers syndrome underwent emergency surgery for an ileo-ileo-colic intussusception. A sterile corrugated anesthetic tube was inserted into the small-bowel, proximal to the affected lesion. The small bowel was then telescoped sequentially over the tube using a pleating technique. Consequently, a colonoscope inserted through the tube was easily able to reach the duodeno-jejunal junction, and ten small-bowel polyps were removed using a wire snare and electrocauterization. All resected specimens were washed out by the instillation of saline through a nasogastric tube, then collected on gauze placed near the outlet of the tube. Our technique has the following merits: it is feasible even in emergency surgery; it prevents contamination of the surgical field; and it facilitates the easy collection of polypectomized specimens.

Adult↗
PubMed1999

Effect of hepatocyte growth factor on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats.

Renal toxicity is a serious side effect of therapy with tacrolimus (FK506), an immunosuppressive agent administered to renal transplant recipients. We investigated the effect of hepatocyte growth factor (HGF) on tacrolimus-induced nephrotoxicity in spontaneously hypertensive rats (SHR). After a right nephrectomy, rats received a continuous perfusion of either HGF in a dose of 5 microg/kg daily (tacrolimus + HGF group) or normal saline (tacrolimus group) into the left renal artery at a rate of 1 microl/h for 7 days after surgery. Tacrolimus was injected intramuscularly in a dose of 4 mg/kg daily for 10 days after surgery. HGF significantly inhibited the tacrolimus-induced increase in the serum creatinine (SCr) level (P < 0.05). HGF also prevented the tacrolimus-induced loss in body weight. The bromodeoxyuridine (BrdU) index was significantly higher in kidney specimens from the tacrolimus + HGF group. These findings suggest that HGF induces the regeneration of renal tubular cells and suppresses tacrolimus-induced renal toxicity in SHR.

Animals↗
PubMed1999

High incidence of a survival motor neuron gene/cBCD541 gene ratio of 2 in Japanese parents of spinal muscular atrophy patients: a characteristic background of spinal muscular atrophy in Japan?

Most spinal muscular atrophy (SMA) patients lack the survival motor neuron gene (SMN). However, the patients retain at least one copy of the cBCD541 gene (BCD), which is highly homologous with SMN. Here, we determined the SMN/BCD copy number ratios (the S/B ratios) of 12 parents of Japanese SMA patients with a homozygous SMN deletion, using competitive oligonucleotide priming polymerase chain reaction. We identified an S/B ratio of 2 in 25% of the parents examined, whereas less than 2% of parents of SMA patients in Western populations have an S/B ratio of 2. The high incidence of an S/B ratio of 2 in Japanese parents of SMA patients may reflect the characteristic genetic background of SMA in Japan.

Female↗
PubMed1999

Urinary lead as a possible surrogate of blood lead among workers occupationally exposed to lead.

OBJECTIVES: The aim of the present study is to investigate whether lead (Pb) in urine (Pb-U) can be a valid surrogate of lead in blood (Pb-B), the traditional biomarker of exposure to lead in occupational health. METHODS: Blood and spot urine samples were collected from 258 workers of both sexes occupationally exposed to lead. The samples were analyzed for lead by graphite furnace atomic absorption spectrometry, and the correlation between Pb-B and Pb-U was examined by linear regression analysis before and after logarithmic conversion. RESULTS: The correlation coefficient (0.824; P < 0.01) was largest when the relationship between Pb-B and Pb-U was examined with 214 cases of one sex (i.e., men) after Pb-U was corrected for a specific gravity (1.016) of urine (Pb-Usg) and both Pb-B and Pb-Usg were converted to logarithms. The geometric means (GMs) of Pb-B and Pb-Usg for the 214 men were 489 microG/l and 81 microg/l, respectively. When Pb-Usg was assumed to be 100 microg/l in this set of correlations, the 95% confidence range of Pb-B for the group mean was narrow, i.e., 543-575 microg/l (with GM of 559 microg/l), whereas that for individual Pb-B values was as wide as 355-881 microg/l. CONCLUSIONS: The correlation of Pb-U with Pb-B among workers occupationally exposed to Pb was close enough to suggest that Pb-U may be a good alternative to Pb-B on a group basis, but not close enough to allow Pb-U to predict Pb-B on an individual basis.

Bias↗
PubMed1999

Laparoscopic gastropexy for acute gastric volvulus: a case report.

A 7-year-old girl presented with an acute gastric volvulus that was reduced with a nasogastric catheter. An anterior gastropexy was undertaken laparoscopically. The gastrocolic omentum was deficient along most of the greater curvature, which had allowed organoaxial volvulus. Two years later, gastric volvulus has not recurred. Laparoscopy is an acceptable approach for the evaluation and treatment of children with acute gastric volvulus.

Acute Disease↗
PubMed1999

Radioimmunoassay for a novel benzodiazepine inverse agonist, S-8510, in human plasma and urine.

A radioimmunoassay (RIA) was developed for a new benzodiazepine inverse agonist, 2-(isoxazol-3-yl)-3,6,7,9-tetrahydroimidazo [4,5-d] pyrano [4,3-b] pyridine monophosphate monohydrate (S-8510), in human plasma and urine. For competitive RIA, three amino derivatives of S-8510 were labelled by the Bolton and Hunter method and rabbit antisera were prepared using three immunogens, conjugates of three carboxyl derivatives of S-8510 with bovine serum albumin. All combinations of the labelled antigens and antisera were examined and homologous combinations were selected for the competitive RIA. One of the three homologous combinations had the best selectivity after investigations of cross-reactivity using 12 related compounds and was very sensitive for S-8510. Next, a pretreatment for biological samples was developed using mixed mode solid-phase extraction (SPE) column followed by the RIA (SPE/RIA). The assay recoveries for human plasma and urine were both excellent and the limits of quantitation were extremely low, 80 and 200 pg ml(-1), respectively. Human plasma samples and urine samples after administration of this drug were successfully measured by the SPE/RIA. No cross-reactive metabolites were detected in any fractions after RP-HPLC separation of the plasma samples. The RIA using carefully selected antiserum and labelled antigen was highly specific for unchanged S-8510. To simplify the RIA procedure, a scintillation proximity assay (SPA) using the same labelled antigen and antiserum was developed for analyzing S-8510 in human plasma and found to be very promising.

Antibody Specificity↗
PubMed1999

Three AML patients with existing or pre-existing intracerebral granulocytic sarcomas who were successfully treated with allogeneic bone marrow transplantations.

We report three acute myelogenous leukemia (AML) patients who developed intracerebral granulocytic sarcomas (GS) and were successfully treated with allogeneic BMT (allo-BMT). The diagnosis of one patient was AML M2 with myelofibrosis, and the other two patients were AML M4 with eosinophilia (AML M4 Eo), according to the FAB classification. Two patients first experienced a relapse in the brain that resulted in the formation of GS, followed by a relapse in the bone marrow. The remaining patient developed an optic nerve GS after suffering a bone marrow relapse. All three patients received irradiation for the GS and systemic chemotherapy before the allo-BMT. TBI was used for conditioning, and GVHD prophylaxis was with cyclosporine (CsA) and short-term MTX in all three cases. These patients are currently 9 to 37 months post-BMT without relapse. Thus, our experience suggests that allo-BMT is an effective treatment for AML patients with existing or pre-existing intracerebral GS.

Adult↗
PubMed1999

[Cystic renal cell carcinoma diagnosed as a simple cyst preoperatively with incidental renal tumor: a case report].

A 54-year-old man visited our hospital with right incidentally-found renal tumor detected by ultrasonography. Computed tomography, magnetic resonance imaging and angiography showed a small tumor, 1.5 cm in size, at the upper portion and a simple cyst, 4 cm in size, at the lower pole of the right kidney. We enucleated the small tumor and aspirated the cyst with outer part resection of the cyst wall. Pathological findings of the tumor showed renal cell carcinoma, alveolar type, common type, clear cell subtype, G1, pT1, INF-alpha. Microscopic appearance of the excised cyst wall also revealed sheets of renal cell carcinoma inside the wall. Therefore, two weeks after the first operation, we performed right radical nephrectomy. The resected specimen had severe inflammation without any evidence of residual tumor. Eight months after the nephrectomy, no recurrence has occurred.

Carcinoma, Renal Cell↗
PubMed1999

Sweet's syndrome followed by retinoic acid syndrome during the treatment of acute promyelocytic leukemia with all-trans retinoic acid.

We present here the case of a 49-year-old female with acute promyelocytic leukemia (APL) who, after first developing all-trans retinoic acid (ATRA)-related Sweet's syndrome, was later diagnosed as having retinoic acid (RA) syndrome. Preceding the RA syndrome diagnosis, she developed a fever as well as erythematous nodules on her upper arms. These symptoms were observed on day 18 of treatment with ATRA. Ten days later, she began to develop respiratory distress. There was no indication of infection, and her condition did not improve with empiric therapy. At this time, the diagnosis of RA syndrome was made, resulting in the initiation of steroid pulse therapy, and within 24 hours her elevated fever and respiratory distress improved markedly. In addition, the erythematous nodules gradually began disappearing. A skin biopsy revealed a dense dermal infiltrate consisting of neutrophils.

Adrenal Cortex Hormones↗
PubMed1999

Coupling of the expressed cannabinoid CB1 and CB2 receptors to phospholipase C and G protein-coupled inwardly rectifying K+ channels.

Signaling of the cannabinoid CB1 and CB2 receptors through phospholipase C (PLC) and G protein-coupled inwardly rectifying K+ channels (GIRK) was studied after their expression in COS7 cells and Xenopus oocytes. The CB1 or CB2 receptor was co-expressed with alpha subunits of the Galphaq family (Galphaq, Galpha11, Galpha14, Galpha15 and Galpha16) in COS7 cells. Receptor-dependent activation of PLC was observed after co-expressing the CB1 receptor with Galpha14, Galpha15 or Galpha16 but not with Galphaq or Galpha11. Co-expression of Gbeta1 and Ggamma2 abolished the activation, indicating that the activation was mediated by Galpha. PLC activation was not observed when the CB2 receptor was expressed alone or co-expressed with any of the above Galpha subunits. Coupling to GIRK was observed with both CB1 and CB2 receptors after expression in Xenopus oocytes. Significantly larger currents were induced when the receptor was co-expressed with both GIRK1 and GIRK4 than with either GIRK alone. Co-expression of Galpha transducin with the receptor significantly reduced the K+ currents, indicating that GIRK activation was mediated by Gbetagamma but not by Galpha. These findings suggest two new signaling pathways for the cannabinoid receptors.

Animals↗
PubMed1999

A chronic myelogenous leukemia-like myeloproliferative disorder accompanied by T-cell lymphoblastic lymphoma with chromosome translocation t(8;13)(p11;q12): a Japanese case.

A 40-year-old male patient presented with leukocytosis and mild splenomegaly. Bone marrow aspirate showed myeloid hyperplasia and eosinophilia resembling chronic myelogenous leukemia in the chronic phase. Cytogenetic examination of bone marrow cells revealed an unusual karyotype, t(8;13)(p11;q12), in 20/20 metaphases. Not the BCR/ABL, but the ZNF198/FGFR1 chimeric mRNA was detected by reverse transcription-polymerase chain reaction. Since 1992, 12 patients with a similar atypical myeloproliferative disorder with T-cell non-Hodgkin's lymphoma or eosinophilia, associated with a t(8;13) translocation in both bone marrow and lymph node specimens, have been described. The present case is an additional one that should be classified into this new clinicopathologic entity.

Adult↗
PubMed1999

[Recurrence of bladder cancer in fossa navicularis 12 years after total cystectomy: a case report].

We report a case of urothelial cancer recurrence in fossa navicularis of urethra 12 years after total cystourethrectomy for bladder cancer. A 73-year-old man had undergone total cystourethrectomy and ureterocutancostomy for multiple bladder cancer on June 13, 1986. Histopathological findings showed transitional cell carcinoma, G3, pT4 with carcinoma in situ. Twelve years after the cystectomy, he was admitted to our hospital complaining of the induration of the glans penis. Magnetic resonance imaging showed a high intensity tumor in T1-WI and low intensity tumor in T2-WI, which had invaded fossa navicularis of urethra to glans penis. Aspiration biopsy of the penile tumor revealed transitional cell carcinoma. Therefore, we performed partial penectomy on July 16, 1998, since computed tomography showed no lymph node swelling in the inguinal region. Five months after the second operation, he was diagnosed with bilateral inguinal lymph node metastasis. Then we performed 2-course M-VAC (methotrexate, vinblastine, doxorubicin cisplatin) therapy, which showed partial response. Thereafter, bilateral inguinal lymphadenectomy with one-course postoperative M-VAC therapy was performed.

Aged↗
PubMed1999

[CBDCA, etoposide and epirubicin high-dose combination chemotherapy supported by peripheral blood stem cell transplantation (PBSCT) in metastatic breast cancer].

Six metastatic breast cancer patients, including one brain metastasis, one lung metastasis, three local recurrences and one bone metastasis, underwent multidrug chemotherapy with CBDCA, Etoposide (ETP) and Epirubicin (EPI). Each patient received two courses of PBSC mobilization chemotherapies and subsequently received high-dose chemotherapies for at least two courses. CBDCA AUC 4, ETP 300 mg/m2 and EPI 40 mg/m2 were administered intravenously as a PBSC mobilization chemotherapy, and high-dose chemotherapies were performed under the regimen of CBDCA AUC 8, ETP 900 mg/m2 and EPI 60 mg/m2. Severe bone marrow suppression due to high-dose chemotherapies was off sct by autologous peripheral blood stem cell transplantation (PBSCT). The PBSC mobilization chemotherapies resulted in one CR, three PR, one NC and one PD in the six patients. The PD patient died before high-dose chemotherapy. Consequently, the remaining five patients received the high-dose chemotherapies, which achieved three CR, one PR and one PD in the five patients. The response rate of high-dose chemotherapy was 80% (4/5 cases). In overall outcome, three patients have continued 16, 12 and 10 months tumor-free survival, and three patients died of cancer progression. High-dose chemotherapy with CBDCA, ETP and EPI has led to increased CR rates in metastatic breast cancer, and such therapy has desirable effect on the patient's prognosis.

Adult↗
PubMed1998

Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite.

Embryonic patterning in vertebrates is dependent upon the balance of inductive signals and their specific antagonists. We show that Noggin, which encodes a bone morphogenetic protein (BMP) antagonist expressed in the node, notochord, and dorsal somite, is required for normal mouse development. Although Noggin has been implicated in neural induction, examination of null mutants in the mouse indicates that Noggin is not essential for this process. However, Noggin is required for subsequent growth and patterning of the neural tube. Early BMP-dependent dorsal cell fates, the roof plate and neural crest, form in the absence of Noggin. However, there is a progressive loss of early, Sonic hedgehog (Shh)-dependent ventral cell fates despite the normal expression of Shh in the notochord. Further, somite differentiation is deficient in both muscle and sclerotomal precursors. Addition of BMP2 or BMP4 to paraxial mesoderm explants blocks Shh-mediated induction of Pax-1, a sclerotomal marker, whereas addition of Noggin is sufficient to induce Pax-1. Noggin and Shh induce Pax-1 synergistically. Use of protein kinase A stimulators blocks Shh-mediated induction of Pax-1, but not induction by Noggin, suggesting that induction is mediated by different pathways. Together these data demonstrate that inhibition of BMP signaling by axially secreted Noggin is an important requirement for normal patterning of the vertebrate neural tube and somite.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Variation in the ratio of respirable particulates over inhalable particulates by type of dust workplace.

OBJECTIVE: The aim of the present study was to clarify the quantitative relationship between respirable particulates and inhalable particulates in various dust workplaces. METHODS: Both respirable particulate and inhalable particulate concentrations were measured in 1644 dust workplaces by means of elutriation, and the ratio of respirable particulate mass over that of inhalable particulate (R/I ratio) was calculated for each workplace. RESULTS: Statistical analyses showed that the R/I ratio varied substantially, depending on the type of dust work. The ratio was highest in welding workplaces (mean +/- SD: 53 +/- 19%) and lowest in foundries (23 +/- 16%); the former value suggests that respirable particulate exposure may be underestimated in substantial parts of welding work when only the occupational exposure limit for inhalable particulates is taken for compliance testing. CONCLUSIONS: Simple compliance with the limit for inhalable particulates is not sufficient, and the limit for respirable particulates should also be simultaneously cleared.

Dust↗