Studies on the structure and function of the MAP kinase family in Arabidopsis thaliana

Thesis (Ph.D. in Science)--University of Tsukuba, (A), no. 1328, 1995.3.2

Characteristics of breast cancer support groups within hospitals in Japan

施設内の乳がん患者会の有無とその特徴を明らかにする目的で,日本乳癌学会参加564施設(認定347施設,非認定217施設)を対象に郵送質問紙調査を行った.236施設(回収率41.8%)から回答があり,以下の結果を得た.1)乳がん患者会がある施設は,236施設中52施設(22.0%)であった.2)乳がん患者会がある施設の設置主体,規模及び日本乳癌学会認定の有無に違いは見られなかった.しかし,年間乳がん手術件数は,患者会がある施設が有意に多かった.3)患者会は,医療者が発起している会が52施設中22施設(42.3%),患者が発起している会が17施設(32.7%),患者と医療者で発起している会が8施設(15.4%)であった.施設内の患者会は,医療者と患者がコミュニケーションを図る場所,退院直後や外来で活発な治療を受けている時期の患者にとっては利用しやすい身近なサポート資源であると考えられた.4)施設内の患者会は会の内容,運営など,医療者主導の会が多く,セルフヘルプ性は低かった.また,患者の年齢,術後年数など幅があるため,患者個々のニーズには対応できない部分もあり,術後経過と共に支援の内容や必要性が変化してきた際には,施設外の患者会も利用していくシステムも今後必要ではないかと示唆された.The purpose of this study was to determine the number of breast cancer support groups withinhospitals and to describe their characteristics. A questionnaire was mailed to 564 member hospitals of theJapanese Breast Cancer Society (347 accredited, 217 non-accredited). 236 hospitals responded (a responserate of 41.8 percent), and we obtained the following results.1) 52 of 236 hospitals (22.0 percent) had a breast cancer support group.2) No significant differences were found among the hospitals concerning their administrative entity, size,or accredited versus non-accredited status by the Japanese Breast Cancer Society. However, thehospitals with a support group performed a significantly larger number of breast cancer operationsannually than those without a group.3) 22 (42.3 percent), 17 (32.7 percent) and 8 (15.4 percent) of the 52 hospitals had a support groupestablished by physicians, patients, or by both physicians and patients, respectively. A support groupwithin a hospital is considered to provide opportunities for physicians and patients to communicate, aswell as a patient-friendly support resource for those who have just left the hospital and those who areunder intensive treatment on an outpatient basis.4) Many of the support groups were headed by physicians in content and administration and played arather small role as a self-help resource. Additionally, some support groups could not cover patients'individual needs because the ages and postoperative periods of patients varied widely. Therefore, it issuggested that a system be devised where patients can utilize outside support groups when the contentand requirements of needed support change during the postoperative period

Ubiquitin carboxyl-terminal hydrolases are required for period maintenance of the circadian clock at high temperature in Arabidopsis

Protein ubiquitylation participates in a number of essential cellular processes including signal transduction and transcription, often by initiating the degradation of specific substrates through the 26S proteasome. Within the ubiquitin-proteasome system, deubiquitylating enzymes (DUBs) not only help generate and maintain the supply of free ubiquitin monomers, they also directly control functions and activities of specific target proteins by modulating the pool of ubiquitylated species. Ubiquitin carboxyl-terminal hydrolases (UCHs) belong to an enzymatic subclass of DUBs, and are represented by three members in Arabidopsis, UCH1, UCH2 and UCH3. UCH1 and UCH2 influence auxin-dependent developmental pathways in Arabidopsis through their deubiquitylation activities, whereas biological and enzymatic functions of UCH3 remain unclear. Here, we demonstrate that Arabidopsis UCH3 acts to maintain the period of the circadian clock at high temperatures redundantly with UCH1 and UCH2. Whereas single uch1, uch2 and uch3 mutants have weak circadian phenotypes, the triple uch mutant displays a drastic lengthening of period at high temperatures that is more extreme than the uch1 uch2 double mutant. UCH3 also possesses a broad deubiquitylation activity against a range of substrates that link ubiquitin via peptide and isopeptide linkages. While the protein target(s) of UCH1-3 are not yet known, we propose that these DUBs act on one or more factors that control period length of the circadian clock through removal of their bound ubiquitin moieties, thus ensuring that the clock oscillates with a proper period even at elevated temperature

Serial MRI Features of Canine GM1 Gangliosidosis: A Possible Imaging Biomarker for Diagnosis and Progression of the Disease

GM1 gangliosidosis is a fatal neurodegenerative lysosomal storage disease caused by an autosomal recessively inherited deficiency of β-galactosidase activity. Effective therapies need to be developed to treat the disease. In Shiba Inu dogs, one of the canine GM1 gangliosidosis models, neurological signs of the disease, including ataxia, start at approximately 5 months of age and progress until the terminal stage at 12 to 15 months of age. In the present study, serial MR images were taken of an affected dog from a model colony of GM1 gangliosidosis and 4 sporadic clinical cases demonstrating the same mutation in order to characterize the MRI features of this canine GM1 gangliosidosis. By 2 months of age at the latest and persisting until the terminal stage of the disease, the MR findings consistently displayed diffuse hyperintensity in the white matter of the entire cerebrum on T2-weighted images. In addition, brain atrophy manifested at 9 months of age and progressed thereafter. Although a definitive diagnosis depends on biochemical and genetic analyses, these MR characteristics could serve as a diagnostic marker in suspect animals with or without neurological signs. Furthermore, serial changes in MR images could be used as a biomarker to noninvasively monitor the efficacy of newly developed therapeutic strategies

Synoviocyte-targeted therapy synergizes with TNF inhibition in arthritis reversal

Fibroblast-like synoviocytes (FLS) are joint-lining cells that promote rheumatoid arthritis (RA) pathology. Current disease-modifying antirheumatic agents (DMARDs) operate through systemic immunosuppression. FLS-targeted approaches could potentially be combined with DMARDs to improve control of RA without increasing immunosuppression. Here, we assessed the potential of immunoglobulin-like domains 1 and 2 (Ig1&2), a decoy protein that activates the receptor tyrosine phosphatase sigma (PTPRS) on FLS, for RA therapy. We report that PTPRS expression is enriched in synovial lining RA FLS and that Ig1&2 reduces migration of RA but not osteoarthritis FLS. Administration of an Fc-fusion Ig1&2 attenuated arthritis in mice without affecting innate or adaptive immunity. Furthermore, PTPRS was down-regulated in FLS by tumor necrosis factor (TNF) via a phosphatidylinositol 3-kinase–mediated pathway, and TNF inhibition enhanced PTPRS expression in arthritic joints. Combination of ineffective doses of TNF inhibitor and Fc-Ig1&2 reversed arthritis in mice, providing an example of synergy between FLS-targeted and immunosuppressive DMARD therapies.publishedVersio

Tomato TILLING Technology: Development of a Reverse Genetics Tool for the Efficient Isolation of Mutants from Micro-Tom Mutant Libraries

To accelerate functional genomic research in tomato, we developed a Micro-Tom TILLING (Targeting Induced Local Lesions In Genomes) platform. DNA pools were constructed from 3,052 ethyl methanesulfonate (EMS) mutant lines treated with 0.5 or 1.0% EMS. The mutation frequency was calculated by screening 10 genes. The 0.5% EMS population had a mild mutation frequency of one mutation per 1,710 kb, whereas the 1.0% EMS population had a frequency of one mutation per 737 kb, a frequency suitable for producing an allelic series of mutations in the target genes. The overall mutation frequency was one mutation per 1,237 kb, which affected an average of three alleles per kilobase screened. To assess whether a Micro-Tom TILLING platform could be used for efficient mutant isolation, six ethylene receptor genes in tomato (SlETR1–SlETR6) were screened. Two allelic mutants of SlETR1 (Sletr1-1 and Sletr1-2) that resulted in reduced ethylene responses were identified, indicating that our Micro-Tom TILLING platform provides a powerful tool for the rapid detection of mutations in an EMS mutant library. This work provides a practical and publicly accessible tool for the study of fruit biology and for obtaining novel genetic material that can be used to improve important agronomic traits in tomato

TOMATOMA: A Novel Tomato Mutant Database Distributing Micro-Tom Mutant Collections

The tomato is an excellent model for studies of plants bearing berry-type fruits and for experimental studies of the Solanaceae family of plants due to its conserved genetic organization. In this study, a comprehensive mutant tomato population was generated in the background of Micro-Tom, a dwarf, rapid-growth variety. In this and previous studies, a family including 8,598 and 6,422 M2 mutagenized lines was produced by ethylmethane sulfonate (EMS) mutagenesis and γ-ray irradiation, and this study developed and investigated these M2 plants for alteration of visible phenotypes. A total of 9,183 independent M2 families comprising 91,830 M2 plants were inspected for phenotypic alteration, and 1,048 individual mutants were isolated. Subsequently, the observed mutant phenotypes were classified into 15 major categories and 48 subcategories. Overall, 1,819 phenotypic categories were found in 1,048 mutants. Of these mutants, 549 were pleiotropic, whereas 499 were non-pleiotropic. Multiple different mutant alleles per locus were found in the mutant libraries, suggesting that the mutagenized populations were nearly saturated. Additionally, genetic analysis of backcrosses indicated the successful inheritance of the mutations in BC1F2 populations, confirming the reproducibility in the morphological phenotyping of the M2 plants. To integrate and manage the visible phenotypes of mutants and other associated data, we developed the in silico database TOMATOMA, a relational system interfacing modules between mutant line names and phenotypic categories. TOMATOMA is a freely accessible database, and these mutant recourses are available through the TOMATOMA (http://tomatoma.nbrp.jp/index.jsp)

Review Article : Feudalism or Absolute Monarchism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68809/2/10.1177_009770049001600304.pd