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S Hatakeyama

Publications and source records attributed to S Hatakeyama.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Fibrosing alveolitis following Legionella pneumonia].

We reported a case of fibrosing alveolitis following Legionella pneumonia. A 62-year-old man was admitted to our hospital with fever after a visit to a hot spring. Chest X-ray films on admission demonstrated air-space consolidation in the right lower lung. Legionella pneumonia was diagnosed because the patient had elevated serum antibody to Legionella pneumophila serogroup Ia and tested positive for urinary antigen. Although he was initially treated with rifampicin and erythromycin, he experienced drug-induced eruptions. Antibiotic therapy was accordingly changed to clarithromycin, levofloxacin, and minocycline, which together alleviated the patient's clinical symptoms but delayed radiologic regression. Chest X-ray films 2 months after the onset of illness revealed diffuse ground-glass opacities and progressive reduction of volume in the right lung. Long-term corticosteroid treatment was required. Three and half months after disease onset, fever recurred with the appearance of interstitial shadows in the left lung and positive tests for urinary antigen. Increasing the corticosteroid dose resolved the patient's symptoms.

Anti-Inflammatory Agents↗
PubMed2000

[Respiratory failure due to diaphragmatic dysfunction in Charcot-Marie-Tooth disease: a case report].

A 56-year-woman with type 2 respiratory failure due to diaphragmatic dysfunction in Charcot-Marie-Tooth disease (CMT) is reported. The patient, who had a 50-year history of CMT, was referred to our hospital because of nocturnal dyspnea. Arterial blood gas analysis on admission showed marked hypoxia with hypercapnia, and physical examination revealed thoracoabdominal paradoxus in the supine position. Chest radiography revealed elevation of both sides of the diaphragm. The vital capacity and arterial blood gas pressure in the sitting position were markedly higher than those in the supine position. Electrical phrenic nerve stimulation failed to produce any convincing muscle action potential in the diaphragm. These findings suggested that her respiratory failure was induced by both diaphragmatic dysfunction caused by bilateral phrenic nerve palsy due to CMT. Treatment of this patient was started at home with a pressure support ventilator, resulting in satisfactory clinical improvement. In general, respiratory muscle impairment is a rare phenomenon in a patient with CMT. However when a patient with CMT complains of dyspnea or if unexpected heart failure develops, it is important to keep in mind that CMT may be associated with phrenic nerve palsy.

Charcot-Marie-Tooth Disease↗
PubMed2000

Nephrotic syndrome due to focal glomerulosclerosis and undifferentiated carcinoma.

In neoplastic disorder-related nephrotic syndrome, focal glomerulosclerosis (FGS) has been reported mainly in hematological disorders like minimal change nephrotic syndrome (MCNS) in association with presumed T lymphocyte dysfunction. The association of FGS with cancer or solid tumor is rare. We report a case of nephrotic syndrome due to FGS in a patient with undifferentiated adenocarcinoma of the cystic duct. Although the underlying mechanism is unclear, the development of FGS seemed to be related to the poor histological differentiation of the cancer in the possibility of production of an active peptide.

Adenocarcinoma↗
PubMed1999

Structure and expression of the gene encoding mouse F-box protein, Fwd2.

A novel class of ubiquitin ligases, termed the SCF complex, consists of invariable components, Skp1 and Cullin, and variable components called F-box proteins, which have a primary role in determining substrate specificity. We have isolated a cDNA encoding the mouse F-box protein Fwd2 (also known as MD6) as a possible constituent of an SCF-type ubiquitin ligase. Fwd2 cDNA contains 1890 bp with a 1362-bp open reading frame and encodes an approximately 51.5-kDa protein. Fwd2 is expressed predominantly in liver and, to a lesser extent, in the testis, lung, heart, and skeletal muscle. Immunofluorescence staining for Fwd2 protein shows a pattern with the cytoplasm. A coimmunoprecipitation assay has revealed the in vivo interaction between Skp1 and Fwd2 through the F-box domain. Fwd2 also interacts with Cul1 through Skp1, suggesting that Skp1, Cul1, and the F-box protein Fwd2 form an SCF complex (SCF(Fwd2)). We have also isolated and determined the nucleotide sequence and genomic organization of the gene that encodes mouse Fwd2. This gene spans approximately 17 kb and consists of six exons and five introns. Our results suggest that Fwd2 is an F-box protein that constitutes an SCF ubiquitin ligase complex and that it plays a critical role in the ubiquitin-dependent degradation of proteins expressed in the liver.

Amino Acid Sequence↗
PubMed1999

Molecular dissection of the interactions among IkappaBalpha, FWD1, and Skp1 required for ubiquitin-mediated proteolysis of IkappaBalpha.

The SCF complex containing Skp1, Cul1, and the F-box protein FWD1 (the mouse homologue of Drosophila Slimb and Xenopus beta-TrCP) functions as the ubiquitin ligase for IkappaBalpha. FWD1 associates with Skp1 through the F-box domain and also recognizes the conserved DSGXXS motif of IkappaBalpha. The structural requirements for the interactions of FWD1 with IkappaBalpha and with Skp1 have now been investigated further. The D31A mutation (but not the G33A mutation) in the DSGXXS motif of IkappaBalpha abolished the binding of IkappaBalpha to FWD1 and its subsequent ubiquitination without affecting the phosphorylation of IkappaBalpha. The IkappaBalpha mutant D31E still exhibited binding to FWD1 and underwent ubiquitination. These results suggest that, in addition to site-specific phosphorylation at Ser(32) and Ser(36), an acidic amino acid at position 31 is required for FWD1-mediated ubiquitination of IkappaBalpha. Deletion analysis of Skp1 revealed that residues 61-143 of this protein are required for binding to FWD1. On the other hand, the highly conserved residues Pro(149), Ile(160), and Leu(164) in the F-box domain of FWD1 were dispensable for binding to Skp1. Together, these data delineate the structural requirements for the interactions among IkappaBalpha, FWD1, and Skp1 that underlie substrate recognition by the SCF ubiquitin ligase complex.

Amino Acid Sequence↗
PubMed1999

Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and IkappaBepsilon mediated by the F-box protein FWD1.

FWD1 (the mouse homolog of Drosophila Slimb and Xenopus betaTrCP, a member of the F-box- and WD40 repeat-containing family of proteins, and a component of the SCF ubiquitin ligase complex) was recently shown to interact with IkappaBalpha and thereby to promote its ubiquitination and degradation. This protein has now been shown also to bind to IkappaBbeta and IkappaBepsilon as well as to induce their ubiquitination and proteolysis. FWD1 was shown to recognize the conserved DSGPsiXS motif (where Psi represents the hydrophobic residue) present in the NH(2)-terminal regions of these three IkappaB proteins only when the component serine residues are phosphorylated. However, in contrast to IkappaBalpha and IkappaBbeta, the recognition site in IkappaBepsilon for FWD1 is not restricted to the DSGPsiXS motif; FWD1 also interacts with other sites in the NH(2)-terminal region of IkappaBepsilon. Substitution of the critical serine residues in the NH(2)-terminal regions of IkappaBalpha, IkappaBbeta, and IkappaBepsilon with alanines also markedly reduced the extent of FWD1-mediated ubiquitination of these proteins and increased their stability. These data indicate that the three IkappaB proteins, despite their substantial structural and functional differences, all undergo ubiquitination mediated by the SCF(FWD1) complex. FWD1 may thus play an important role in NF-kappaB signal transduction through regulation of the stability of multiple IkappaB proteins.

Amino Acid Sequence↗
PubMed1999

RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination.

A RING finger-containing protein (AO7) that binds ubiquitin-conjugating enzymes (E2s) and is a substrate for E2-dependent ubiquitination was identified. Mutations of cation-coordinating residues within AO7's RING finger abolished ubiquitination, as did chelation of zinc. Several otherwise-unrelated RING finger proteins, including BRCA1, Siah-1, TRC8, NF-X1, kf-1, and Praja1, were assessed for their ability to facilitate E2-dependent ubiquitination. In all cases, ubiquitination was observed. The RING fingers were implicated directly in this activity through mutations of metal-coordinating residues or chelation of zinc. These findings suggest that a large number of RING finger-containing proteins, with otherwise diverse structures and functions, may play previously unappreciated roles in modulating protein levels via ubiquitination.

Amino Acid Sequence↗
PubMed1999

The small GTP-binding protein rac is a regulator of cell death in plants.

Cell death plays important roles in the development and defense of plants as in other multicellular organisms. Rapid production of reactive oxygen species often is associated with plant defense against pathogens, but their molecular mechanisms are not known. We introduced the constitutively active and the dominant negative forms of the small GTP-binding protein OsRac1, a rice homolog of human Rac, into the wild type and a lesion mimic mutant of rice and analyzed H(2)O(2) production and cell death in transformed cell cultures and plants. The results indicate that Rac is a regulator of reactive oxygen species production as well as cell death in rice.

Amino Acid Sequence↗
PubMed1999

Induction of lacZ mutation by 7,12-dimethylbenz[a]anthracene in various tissues of transgenic mice.

The induction of gene mutations was examined in MutaMouse after an intraperitoneal injection of 7, 8-dimethylbenz[a]anthracene (DMBA) at 20 mg/kg in a collaborative study participated by four laboratories. Although the DMBA dose used was lower than the level that has been reported to induce micronucleated erythrocytes maximally in several mouse strains, a killing effect appeared after day 9 of the post-treatment interval. Mutations in lacZ transgene were detected by the positive selection assay following in vitro packaging of phage lambda from the genomic DNA of the transgenic animals that survived. The mutant induction was evaluated in the bone marrow, liver, skin, colon, kidney, thymus, and testis 7 to 28 days after the treatment. In the bone marrow, the mutant frequency reached a maximum, approximately a 30-fold increase, 14 days after the treatment and the increased frequency persisted at least up to day 28 of the post-treatment. Induction of mutants was detected in the liver, colon, thymus, and skin to lesser extents. Marginal responses were obtained in the kidney and testis. The slight increases in the mutant frequencies in the kidney and testis observed in some laboratories were within laboratory-to-laboratory or animal-to-animal variations. In contrast to the gene mutation induction in the bone marrow, the frequency of micronucleated reticulocytes increased transiently 3 days after the treatment and returned to a control level before day 8 of the post-treatment. It was suggested that DMBA induced gene mutation is fixed in stem cells depending on cell proliferation while DNA damages responsible for chromosome breakage are not transmitted to progeny cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1999

Down-regulation of p27(Kip1) by two mechanisms, ubiquitin-mediated degradation and proteolytic processing.

The intracellular level of p27(Kip1), a cyclin-dependent kinase (CDK) inhibitory protein, is rapidly reduced at the G1/S transition phase when the cell cycle pause ceases. In this study, we demonstrated that two posttranslational mechanisms were involved in p27(Kip1) breakdown: degradation via the ubiquitin (Ub)-proteasome pathway and proteolytic processing that rapidly eliminates the cyclin-binding domain. We confirmed that p27(Kip1) was ubiquitinated in vitro as well as in vivo. The p27(Kip1) -ubiquitination activity was higher at the G1/S boundary than during the G0/G1 phase, and p27(Kip1) ubiquitination was reduced significantly when the lysine residues at positions 134, 153, and 165 were replaced by arginine, suggesting that these lysine residues are the targets for Ub conjugation. In parallel with its Ub-dependent degradation, p27(Kip1) was processed rapidly at its N terminus, reducing its molecular mass from 27 to 22 kDa, by a ubiquitination-independent but adenosine triphosphate (ATP)-dependent mechanism with higher activity during the S than the G0/G1 phase. This 22-kDa intermediate had no cyclin-binding domain at its N terminus and virtually no CDK2 kinase inhibitory activity. These results suggest that p27(Kip1) is eliminated by two independent mechanisms, ubiquitin-mediated degradation and ubiquitin-independent processing, during progression from the G1 to S phase.

3T3 Cells↗
PubMed1999

An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.

beta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen synthase kinase-3beta (GSK-3beta)/Axin kinase complex. Here we show that FWD1 (the mouse homologue of Slimb/betaTrCP), an F-box/WD40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, Axin, GSK-3beta and APC. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with FWD1. FWD1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels. In contrast, a dominant-negative mutant form of FWD1 inhibited the ubiquitination process and stabilized beta-catenin. These results suggest that the Skp1/Cullin/F-box protein FWD1 (SCFFWD1)-ubiquitin ligase complex is involved in beta-catenin ubiquitination and that FWD1 serves as an intracellular receptor for phosphorylated beta-catenin. FWD1 also links the phosphorylation machinery to the ubiquitin-proteasome pathway to ensure prompt and efficient proteolysis of beta-catenin in response to external signals. SCFFWD1 may be critical for tumor development and suppression through regulation of beta-catenin protein stability.

Adenomatous Polyposis Coli Protein↗
PubMed1999

Ubiquitin-dependent degradation of IkappaBalpha is mediated by a ubiquitin ligase Skp1/Cul 1/F-box protein FWD1.

Activation of the transcription factor nuclear factor kappa B (NF-kappaB) is controlled by proteolysis of its inhibitory subunit (IkappaB) via the ubiquitin-proteasome pathway. Signal-induced phosphorylation of IkappaBalpha by a large multisubunit complex containing IkappaB kinases is a prerequisite for ubiquitination. Here, we show that FWD1 (a mouse homologue of Slimb/betaTrCP), a member of the F-box/WD40-repeat proteins, is associated specifically with IkappaBalpha only when IkappaBalpha is phosphorylated. The introduction of FWD1 into cells significantly promotes ubiquitination and degradation of IkappaBalpha in concert with IkappaB kinases, resulting in nuclear translocation of NF-kappaB. In addition, FWD1 strikingly evoked the ubiquitination of IkappaBalpha in the in vitro system. In contrast, a dominant-negative form of FWD1 inhibits the ubiquitination, leading to stabilization of IkappaBalpha. These results suggest that the substrate-specific degradation of IkappaBalpha is mediated by a Skp1/Cull 1/F-box protein (SCF) FWD1 ubiquitin-ligase complex and that FWD1 serves as an intracellular receptor for phosphorylated IkappaBalpha. Skp1/Cullin/F-box protein FWD1 might play a critical role in transcriptional regulation of NF-kappaB through control of IkappaB protein stability.

Amino Acid Sequence↗
PubMed1999

JTB: a novel membrane protein gene at 1q21 rearranged in a jumping translocation.

1q21 is frequently involved in different types of translocation in many types of cancers. Jumping translocation (JT) is an unbalanced translocation that comprises amplified chromosomal segments jumping to various telomeres. In this study, we identified a novel gene human JTB (Jumping Translocation Breakpoint) at 1q21, which fused with the telomeric repeats of acceptor telomeres in a case of JT. hJTB (human JTB) encodes a trans-membrane protein that is highly conserved among divergent eukaryotic species. JT results in a hJTB truncation, which potentially produces an hJTB product devoid of the trans-membrane domain. hJTB is located in a gene-rich region at 1q21, called EDC (Epidermal Differentiation Complex). This is the first report identifying the gene involved in unbalanced translocations at 1q21.

Amino Acid Sequence↗
PubMed1999

Incidence of intrahepatic biliary cysts in biliary atresia after hepatic portoenterostomy and associated histopathologic findings in the liver and porta hepatis at diagnosis.

BACKGROUND/PURPOSE: The association of intrahepatic biliary cysts in biliary atresia (BA) after hepatic portoenterostomy has drawn the attention of many pediatric surgeons and has become an important subject in clinical management, but the incidence and causes of this association are not well known. METHODS: During the last 14 years, we operated on 33 BA patients by hepatic portoenterostomy. Five patients could not be followed up over a 1-year period, so the remaining 28 patients had their intrahepatic structure investigated by periodic magnetic resonance imaging (MRI), and were confirmed at autopsy. The authors also reviewed the preoperative conditions of these patients and the histopathologic changes in the liver biopsy and the porta hepatis specimens taken at portoenterostomy. RESULTS: (1) Intrahepatic biliary cysts were found in 6 of the 28 patients studied (21%). Of 16 patients who were operated on after 1989 and are undergoing follow-up by MRI, 4 (25%) had cysts. (2) Five of the 6 patients with cysts had episodes of cholangitis before or at the time of discovery of the cysts, and 4 of them have had their jaundice reappear since the discovery of the cysts. (3) The intralobular spaces (ILS) with fibrosis and the number of bile ducts had increased in the group with cysts compared with those in the group without cysts. (4) The bile duct maximum size in the porta hepatis (PH) was similar in the groups with and without cysts, but a denudation of the mucosal lining cells in the duct, and a fibrosis and inflammation around the duct had increased in the group with cysts compared with those in the group without cysts. (5) Statistically, the fibrosis found in the ILS and the inflammation around the bile duct found in the PH were induced as a correlative factor affecting cyst formation. CONCLUSIONS: The association of intrahepatic biliary cysts in BA after portoenterostomy is frequent. The fibrous change in the ILS and the inflammatory process around the bile ducts might be potential causes of cyst formation.

Bile Ducts↗
PubMed1999

Presence of telomeric G-strand tails in the telomerase catalytic subunit TERT knockout mice.

BACKGROUND: Telomerase consists of two essential subunits, the template RNA (TR; telomerase RNA) and the catalytic subunit TERT (telomerase reverse transcriptase). Knockout mice with a mTR (mouse TR) deletion have been described and well characterized. However, mice with a mTERT (mouse TERT) deletion have not been reported. RESULTS: mTERT-knockout mice have been constructed. The first generation mTERT -/- mice were fertile, and did not show any noticeable macroscopic or microscopic phenotypic change. All tissue cells derived from mTERT -/- mice that were examined lacked telomerase activity, indicating that mTERT is the only gene encoding the telomerase catalytic subunit. Pulse field gel electrophoresis (PFGE) and nondenaturing in-gel hybridization analyses showed that mouse telomeric DNA has G-strand 5'-overhangs, as demonstrated for human and yeast cells. This telomeric single-stranded G-tail was also observed in MEF (mouse embryonic fibroblast) and liver cells derived from mTERT -/- mice. CONCLUSIONS: mTERT-knockout mice show phenotypes that are apparently normal at least during the early generations. This observation is similar to that obtained with the mTR-knockout mice. The presence of the telomeric G-strand tails in mTERT -/- mice suggests that these telomeric 5'-overhangs are produced by telomerase-independent mechanisms, as has been proposed for yeast and human.

Amino Acid Sequence↗
PubMed1999

Esophageal undifferentiated carcinoma displaying marked chondroid differentiation at metastatic foci.

A report of an unusual esophageal tumor in an 81-year-old man is presented. The primary tumor was diagnosed as undifferentiated carcinoma at biopsy and had disappeared after irradiation treatment. However, multiple metastases were noted in the brain, lungs, kidneys, adrenals and spleen at autopsy. Histologically, metastases showed marked cartilaginous metaplasia as demonstrated by light microscopy, histochemical and immunohistochemical studies, although the initial biopsy sample did not possess chondroid matrix. Furthermore, an apparent transition could be traced from carcinomatous to chondroid cells, suggesting that the chondroid cells were derived from carcinoma cells. The carcinomatous area partially showed both squamous and glandular differentiation, although they were poorly differentiated. A retrospective immunohistochemical study that used a panel of antibodies suggested a phenotypic relevance between primary and metastatic tumors.

Aged↗
PubMed1999

New metabolic pathway of (24R)-24,25-dihydroxyvitamin D3: epimerization of the 3-hydroxy group.

A new metabolic pathway of (24R)-24,25-dihydroxyvitamin D3 [24,25(OH)2D3] was clarified in the in vivo experiments. After the administration of 24,25(OH)2D3 to rats, a new monoglucuronide of a vitamin D metabolite was obtained from the bile together with 24,25(OH)2D3 3- and 24-glucuronides. The genin of the metabolite was identified as 3-epi-24,25(OH)2D3 in comparison with the synthetic sample based on the data from 1H-NMR, GC/MS, and LC/atmospheric pressure chemical ionization-MS. The conjugation position was determined to be the 24-hydroxy group by the LC/electrospray ionization-MS and -MS/MS/MS combined with derivatization. To our knowledge, this is the first reported instance of the epimerization of the 3-hydroxy group of vitamin D compound with no hydroxy group at the 1alpha-position.

24,25-Dihydroxyvitamin D 3↗