子宮腺筋症の浸潤におけるMMP-7(PUMP-1,Matrilysin)の関与形態について

We are presently investigating the involvement of matrix metalloproteinases (MMPs), MMP-7 (Pump-1, matrilysin) in particular, in the development of adenomyosis uteri. To examine whether progression of adenomyosis uteri might correlate with an expression of MMP enzyme activity, we initially utilized an animal model for adenomyosis uteri induced in pituitarygrafted mice. Gelatin zymography identified three distinct enzyme activities of MMP (20-30 kDa, 50 kDa, and 70 kDa) in extracts obtained from a uterus with adenomyosis, whereas no enzyme activities of MMP were demonstrated in those obtained from normal uterus. Since MMP enzyme activity of 20-30 kDa corresponds to the reported low molecular weight MMP-7 in an activated form (19 kDa) and an inactive form (28-29 kDa), the expression of MMP-7 mRNA was investigated by RT-PCR combined with Southern blot analysis. The result showed that a band of 440 bp PCR product was demonstrated in comparable amounts in both normal mouse uterus and mouse adenomyosis uteri, suggesting that an enhanced enzyme activity of MMP-7 observed in adenomyosis uteri may not be controlled solely at mRNA level. This suggestion was supported by subsequent human studies, the result of which showed a band of 440 bp PCR product in comparable amounts in both adenomyosis uteri and normal uterine endometrium. To examine the expression of MMP-7 protein in human adenomyosis uteri, Western blot analysis of the immunoreactive MMP-7 was performed in the same samples with those used in the study on the expression of the MMP-7 mRNA. Higher amounts of immunoreactive MMP-7 were observed in the epithelial cells of uterine adenomyosis than in those of normal uterine endometrium. The semi-quantitative scoring for immunoreactive MMP-7 staining showed that MMP-7 expression observed in adenomyosis uteri was menstrual cycle-independent and significantly higher than that in normal uterine endometrium, in which MMP-7 expression was menstrual cycle-dependent with its higher expression during the proliferation phase than during the early to mid secretory phase of the menstrual cycle. The data, taken together, are consistent with an idea that epithelial synthesis of MMP-7 in uterine adenomyosis contributes to its invasion into the myometrium

Net-step exercise and depressive symptoms among the community-dwelling elderly in Japan

Introduction: Leisure-time physical activity (LTPA) and exercise have attracted attention as potential preventive factors against depression in the elderly. The net-step exercise (NSE) was developed in Hokkaido, Japan to assist elderly people with decreased physical functions. NSE is a non-aerobic, low-intensity, and slow balance motion LTPA. In the present study, the relationship between NSE and depressive symptoms among the community-dwelling elderly is examined. Methods: This study employed a cross-sectional design with community-dwelling elderly participants, aged 72?81 years (n = 672; mean age = 76.4 years). Participation in NSE and other LTPA, including walking, jogging, and park golf, a sport popular in Hokkaido, particularly among the elderly, was assessed. Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15). Results: Univariate analysis showed that those participating in NSE more than once a month and those who reported engaging in walking or park golf more than once a week were less likely to report symptoms of depression. Multivariate analysis showed that NSE and walking had marginally significant (odds ratio (OR) = 0.53; 95% CI: 0.27?1.02) and significant (OR = 0.61; 95% CI: 0.40?0.93) inverse associations, respectively, with reports of depressive symptoms even after adjustments for age, sex, years of education, continuous walking for 15 min, experience of a fall in the past year, utilization of various long-term care services provided for the elderly, stroke, frequency of jogging, and park golf. Discussion: This study showed that participants engaging in NSE, which is a non-aerobic, low-intensity, and low frequency activity, had a marginally significantly inverse association with depressive symptoms. Longitudinal research should be conducted in the future

Incidence and associated factors of sudden unexpected death in advanced cancer patients: A multicenter prospective cohort study

[Purpose] A sudden unexpected death has significant negative impacts on patients, family caregivers, and medical staff in hospice/palliative care. This study aimed to clarify the incidence and associated factors of sudden unexpected death according to four definitions in advanced cancer patients. [Methods] We performed a prospective cohort study in 23 inpatient hospices/palliative care units in Japan. Advanced cancer patients aged ≥18 years who were admitted to inpatient hospices/palliative care units were included. The incidence and associated factors of sudden unexpected death were evaluated in all enrolled patients according to four definitions: (a) rapid decline death, defined as a sudden death preceded by functional decline over 1–2 days; (b) surprise death, defined if the primary responsible palliative care physician answered “yes” to the question, “Were you surprised by the timing of the death?”; (c) unexpected death, defined as a death that occurred earlier than the physicians had anticipated; and (d) performance status (PS)-defined sudden death, defined as a death that occurred within 1 week of functional status assessment with an Australia-modified Karnofsky PS ≥50. [Results] Among 1896 patients, the incidence of rapid decline death was the highest (30-day cumulative incidence: 16.8%, 95% CI: 14.8–19.0%), followed by surprise death (9.6%, 8.1–11.4%), unexpected death (9.0%, 7.5–10.8%), and PS-defined sudden death (6.4%, 5.2–8.0%). Male sex, liver metastasis, dyspnea, malignant skin lesion, and fluid retention were significantly associated with the occurrence of sudden unexpected death. [Conclusion] Sudden unexpected death is not uncommon even in inpatient hospices/palliative care units, with range of 6.4–16.8% according to the different definitions

Update on the Keio collection of Escherichia coli single-gene deletion mutants

The Keio collection (Baba et al, 2006) has been established as a set of single‐gene deletion mutants of Escherichia coli K‐12. These mutants have a precisely designed deletion from the second codon from the seventh to the last codon of each predicted ORF. Further information is available at http://sal.cs.purdue.edu:8097/GB7/index.jsp or http://ecoli.naist.jp/. The distribution is now being handled by the National Institute of Genetics of Japan (http://www.shigen.nig.ac.jp/ecoli/pec/index.jsp). To date more than 4 million samples have been distributed worldwide. As we described earlier (Baba et al, 2006), gene amplification during construction is likely to have led to a small number of mutants with genetic duplications

Omega-3 Polyunsaturated Fatty Acids Suppress the Cystic Lesion Formation of Peritoneal Endometriosis in Transgenic Mouse Models

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) play a role in controlling pathological inflammatory reactions. Endometriosis is characterized by the presence of endometrial tissue on the peritoneum and an exaggerated inflammatory environment around ectopic tissues. Here peritoneal endometriosis was reproduced using a mouse model in which murine endometrial fragments were inoculated into the peritoneal cavity of mice. Fat-1 mice, in which omega-6 can be converted to omega-3 PUFAs, or wild type mice, in which it cannot, were used for the endometriosis model to address the actions of omega-3 PUFAs on the development of endometriotic lesions. The number and weight of cystic endometriotic lesions in fat-1 mice two weeks after inoculation were significantly less than half to those of controls. Mediator lipidomics revealed that cystic endometriotic lesions and peritoneal fluids were abundant in 12/15-hydroxyeicosapentaenoic acid (12/15-HEPE), derived from eicosapentaenoic acid (EPA), and their amount in fat-1 mice was significantly larger than that in controls. 12/15-Lipoxygenase (12/15-LOX)-knockout (KO) and control mice with or without EPA administration were assessed for the endometriosis model. EPA administration decreased the number of lesions in controls but not in 12/15-LOX-KO mice. The peritoneal fluids in EPA-fed 12/15-LOX-KO mice contained reduced levels of EPA metabolites such as 12/15-HEPE and EPA-derived resolvin E3 even after EPA administration. cDNA microarrays of endometriotic lesions revealed that Interleukin-6 (IL-6) expression in fat-1 mice was significantly lower than that in controls. These results suggest that both endogenous and exogenous EPA-derived PUFAs protect against the development of endometriosis through their anti-inflammatory effects and, in particular, the 12/15-LOX-pathway products of EPA may be key mediators to suppress endometriosis

Seed-coat protective neolignans are produced by the dirigent protein AtDP1 and the laccase AtLAC5 in Arabidopsis

種子を保護するネオリグナンの生合成機構を解明 --新たな薬効成分の創出に期待--. 京都大学プレスリリース. 2020-12-03.Lignans/neolignans are generally synthesized from coniferyl alcohol (CA) in the cinnamate/monolignol pathway by oxidation to generate the corresponding radicals with subsequent stereoselective dimerization aided by dirigent proteins (DIRs). Genes encoding oxidases and DIRs for neolignan biosynthesis have not been identified previously. In Arabidopsis thaliana, the DIR AtDP1/AtDIR12 plays an essential role in the 8-O-4′ coupling in neolignan biosynthesis by unequivocal structural determination of the compound missing in the atdp1 mutant as a sinapoylcholine (SC)-conjugated neolignan, erythro-3-{4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-hydroxymethylethoxy]-3, 5-dimethoxyphenyl}acryloylcholine. Phylogenetic analyses showed that AtDP1/AtDIR12 belongs to the DIR-a subfamily composed of DIRs for 8-8′ coupling of monolignol radicals. AtDP1/AtDIR12 is specifically expressed in outer integument 1 cells in developing seeds. As a putative oxidase for neolignan biosynthesis, we focused on AtLAC5, a laccase gene coexpressed with AtDP1/AtDIR12. In lac5 mutants, the abundance of feruloylcholine (FC)-conjugated neolignans decreased to a level comparable to those in the atdp1 mutant. In addition, SC/FC-conjugated neolignans were missing in the seeds of mutants defective in SCT/SCPL19, an enzyme that synthesizes SC. These results strongly suggest that AtDP1/AtDIR12 and AtLAC5 are involved in neolignan biosynthesis via SC/FC. A tetrazolium penetration assay showed that seed coat permeability increased in atdp1 mutants, suggesting a protective role of neolignans in A. thaliana seeds

大学コンソーシアム石川における ICT 教育支援体制の充実

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