Biomedical subjects

K Kurosawa

Publications and source records attributed to K Kurosawa.

At least 19 recordsLinked to original sources

PubMed2001

Dissecting pulmonary arterial aneurysm associated with chromosome 22q11 deletion.

Explore the source record for details and available documents.

Aortic Dissection↗

PubMed2001

Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death.

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) were identified as signal transducers for the TNF receptor superfamily. However, the exact roles of TRAF2 and TRAF5 in TNF-induced NF-kappaB activation still remain controversial. To address this issue, we generated TRAF2 and TRAF5 double knockout (DKO) mice. TNF- but not interleukin-1-induced nuclear translocation of NF-kappaB was severely impaired in murine embryonic fibroblasts (MEFs) derived from DKO mice. Moreover, DKO MEFs were more susceptible to TNF-induced cytotoxicity than TRAF2 knockout MEFs. Collectively, these results indicate that both TRAF2 and TRAF5 are involved in TNF-induced NF-kappaB activation and protection from cell death.

Animals↗

PubMed2001

Essential role of nuclear factor (NF)-kappaB-inducing kinase and inhibitor of kappaB (IkappaB) kinase alpha in NF-kappaB activation through lymphotoxin beta receptor, but not through tumor necrosis factor receptor I.

Both nuclear factor (NF)-kappaB-inducing kinase (NIK) and inhibitor of kappaB (IkappaB) kinase (IKK) have been implicated as essential components for NF-kappaB activation in response to many external stimuli. However, the exact roles of NIK and IKKalpha in cytokine signaling still remain controversial. With the use of in vivo mouse models, rather than with enforced gene-expression systems, we have investigated the role of NIK and IKKalpha in signaling through the type I tumor necrosis factor (TNF) receptor (TNFR-I) and the lymphotoxin beta receptor (LTbetaR), a receptor essential for lymphoid organogenesis. TNF stimulation induced similar levels of phosphorylation and degradation of IkappaBalpha in embryonic fibroblasts from either wild-type or NIK-mutant mice. In contrast, LTbetaR stimulation induced NF-kappaB activation in wild-type mice, but the response was impaired in embryonic fibroblasts from NIK-mutant and IKKalpha-deficient mice. Consistent with the essential role of IKKalpha in LTbetaR signaling, we found that development of Peyer's patches was defective in IKKalpha-deficient mice. These results demonstrate that both NIK and IKKalpha are essential for the induction of NF-kappaB through LTbetaR, whereas the NIK-IKKalpha pathway is dispensable in TNFR-I signaling.

Animals↗

PubMed2001

Molecular analysis of Japanese patients with Rett syndrome: Identification of five novel mutations and genotype-phenotype correlation.

Rett syndrome is an X-linked dominant neurodevelopmental disorder that affects females almost exclusively. The recent identification of mutations of the methyl-CpG-binding protein 2 gene (MECP2) in patients with RTT, encouraged us to analyze the gene in 37 Japanese patients divided into classical RTT (14 cases), variant RTT (13 cases), and mentally retarded patients with Rett-like features (10 cases). Mutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases). Six reported common mutations were detected in 17 cases, and rare single nucleotide substitutions were found in 3 patients. In addition, one insertion mutation (1189insA) and four deletion mutations including one double deletion mutant (451delG, 100del4, 1124del53 and 881del289 plus 1187del8) were newly identified. In the 10 mentally retarded patients with Rett-like features, however, no mutation was detected in the coding region of MECP2. The finding of MECP2 mutations in 92.5% of patients with RTT indicates that RTT fulfilling the diagnostic criteria are due to genetic alteration.

Amino Acid Substitution↗

PubMed2001

Graves' disease in patients with 22q11.2 deletion.

We report 4 female patients and 1 male patient with a 22q11.2 deletion and Graves' disease diagnosed at age 27 months, 7, 10, 17, and 16 years, respectively. The clinical presentations were typical for hyperthyroidism, but 1 female infant had seizures in addition to symptoms of hyperthyroidism. All patients had elevated serum levels of thyroid hormones in association with suppressed thyroid-stimulating hormone levels. From these observations, we suggest that Graves' disease may be a part of the clinical spectrum associated with the 22q11.2 deletion syndrome.

Adolescent↗

PubMed2001

Reversal of multidrug resistance by novel nitrophenyl pyrones, SNF4435C and D.

SNF4435C and D, novel immunosuppressants produced by a strain of Streptomyces spectabilis, were examined for their reversing effects in vitro on various multidrug-resistant (MDR) tumor cells overexpressing P-glycoprotein. These two compounds in the range of 3-10 microM completely reversed the resistance of MDR variant cells, mouse leukemia P388 cells [vincristine (VCR)-resistant P388/VCR and adriamycin (ADM)-resistant P388/ADM], human myelogenous leukemia K562 cells (VCR-resistant K562/VCR and ADM-resistant K562/ADM) and human ovarian cancer A2780 cells (ADM-resistant AD(10)), against VCR. Both compounds moderately potentiated the sensitivity of the MDR cells to ADM but the reversal was not complete. SNF4435C and D significantly increased the intracellular accumulation of VCR in AD(10) cells as potently as verapamil, cyclosporin A (CysA) and FK506, whereas the compounds exerted no effect on the accumulation of VCR in the drug-sensitive parent cells. Moreover, SNF4435C improved the chemotherapeutic efficacy of VCR in the treatment of P388/VCR-bearing mice. When 10 mg/kg SNF4435C was administered intraperitoneally to the mice concurrently with 0.2 mg/kg VCR for every 5 days, a treated/control (T/C) value of 143% was obtained. These results suggest that the compounds are useful candidates or tools for MDR modification in cancer chemotherapy.

Animals↗

PubMed2001

SNF4435C and D, novel immunosuppressants produced by a strain of Streptomyces spectabilis. I. Taxonomy, fermentation, isolation and biological activities.

SNF4435C and D, novel nitrophenyl pyrones, have been isolated from the culture broth of an actinomycete strain SNF4435. The strain was identified as Streptomyces spectabilis from its morphological and cultural characteristics. SNF4435C and D showed a potent immunosuppressive activity in vitro and selectively suppressed B-cell proliferation induced by LPS versus T-cell proliferation induced by Con A.

Animals↗

PubMed2001

SNF4435C and D, novel immunosuppressants produced by a strain of Streptomyces spectabilis. II. Structure elucidation.

SNF4435C and D are new immunosuppressants isolated from the culture broth of a strain of Streptomyces spectabilis. Their molecular formulas were determined as C28H31NO6 based on the HRFAB-MS analyses. The structures of SNF4435C and D were elucidated to be novel nitrophenyl pyrones having an intriguing tricyclic ring system and diastereoisomers of each other by spectroscopic analyses including various NMR measurements.

Fermentation↗

PubMed2001

SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. I. Taxonomy, fermentation, isolation and biological activities.

Novel depsipeptides, SW-163C and E were isolated from the culture broth of an actinomycete strain. The producing organism, designated as SNA15896, was identified as a member of Streptomyces from its morphological and cultural characteristics. SW-163C and E exhibited potent antitumor activities against various tumor cell lines in vitro and against murine leukemia P388 in vivo. The compounds also showed antimicrobial activities.

Animals↗

PubMed2001

SW-163C and E, novel antitumor depsipeptides produced by Streptomyces sp. II. Structure elucidation.

SW-163C and E are novel antitumor antibiotics, which belong to quinomycin family, isolated from the culture broth of Streptomyces sp. SNA15896. These compounds were determined to be cyclic depsipeptides having 3-hydroxyquinaldic acid as a chromophore and a sulfur-containing intramolecular cross linkage through various spectroscopic analyses.

Antibiotics, Antineoplastic↗

PubMed2001

SW-163A and B, novel immunosuppressants produced by Streptomyces sp.

SW-163A and B, novel immunosuppressants, were isolated from the culture broth of Streptomyces sp. SNA15896. The molecular formulas of SW-163A and B were determined as C34H42N2O12 and C33H40N2O12 based on the HRFAB-MS analysis, respectively. Both compounds were elucidated to be a large ring ester structure through spectroscopic analyses including various NMR measurements. SW-163A and B showed immunosuppressive and antimicrobial activities in vitro.

Amino Acids↗

PubMed2001