46 research outputs found

    Laparoscopic vs Open approach for transverse colon cancer. A systematic review and meta-analysis of short and long term outcomes

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    Background: Transverse colon malignancies have been excluded from all randomized controlled trials comparing laparoscopic against open colectomies, potentially due to the advanced laparoscopic skills required for dissecting around the middle colic vessels and the associated morbidity. Concerns have been expressed that the laparospopic approach may compromise the oncological clearance in transverse colon cancer. This study aimed to comprehensively compare the laparoscopic (LPA) to the open (OPA) approach by performing a meta-analysis of long and short term outcomes. Methods: Medline, Embase, Cochrane library, Scopus and Web of Knowledge databases were interrogated. Selected studies were critically appraised and the short-term morbidity and long term oncological outcomes were meta-analyzed. Sensitivity analysis according to the quality of the study, type of procedure (laparoscopic vs laparoscopically assisted) and level of lymphadenectomy was performed. Statistical heterogeneity and publication bias were also investigated. Results: Eleven case control trials (1415 patients) were included in the study. There was no difference between the LPA and the OPA in overall survival [Hazard Ratio (HR)=0.83 (0.56, 1.22); P=0.34], disease free survival (p=0.20), local recurrence (p=0.81) or distant metastases (p=0.24). LPA was found to have longer operative time [Weighted mean difference (WMD)=45.00 (29.48, 60.52);P<0.00001] with earlier establishment of oral intake [WMD=-1.68 (-1.84, -1.53);P<0.00001] and shorter hospital stay [WMD =-2.94 (-4.27, -1.62);P=0.0001]. No difference was found in relation to anastomotic leakage (p=0.39), intra-abdominal abscess (p=0.25), lymph nodes harvested (p=0.17). Conclusions: LPA seems to be safe with equivalent oncological outcomes to OPA and better short term outcomes in selected patient populations. High quality Randomized control trials are required to further investigate the role of laparoscopy in transverse colon cancer

    microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity

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    褐色脂肪細胞の燃焼を促す新たなメカニズムを解明 --体の熱産生にマイクロRNA-33が関与--. 京都大学プレスリリース. 2021-02-17.Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33−/− mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-β-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress

    Filament formation and robust strand exchange activities of the rice DMC1A and DMC1B proteins

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    The DMC1 protein, a meiosis-specific DNA recombinase, catalyzes strand exchange between homologous chromosomes. In rice, two Dmc1 genes, Dmc1A and Dmc1B, have been reported. Although the Oryza sativa DMC1A protein has been partially characterized, however the biochemical properties of the DMC1B protein have not been defined. In the present study, we expressed the Oryza sativa DMC1A and DMC1B proteins in bacteria and purified them. The purified DMC1A and DMC1B proteins formed helical filaments along single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA), and promoted robust strand exchange between ssDNA and dsDNA over five thousand base pairs in the presence of RPA, as a co-factor. The DMC1A and DMC1B proteins also promoted strand exchange in the absence of RPA with long DNA substrates containing several thousand base pairs. In contrast, the human DMC1 protein strictly required RPA to promote strand exchange with these long DNA substrates. The strand-exchange activity of the Oryza sativa DMC1A protein was much higher than that of the DMC1B protein. Consistently, the DNA-binding activity of the DMC1A protein was higher than that of the DMC1B protein. These biochemical differences between the DMC1A and DMC1B proteins may provide important insight into their functional differences during meiosis in rice

    Chemotherapy-resistant osteosarcoma is highly susceptible to IL-15-activated allogeneic and autologous NK cells

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    High-grade osteosarcoma occurs predominantly in adolescents and young adults and has an overall survival rate of about 60%, despite chemotherapy and surgery. Therefore, novel treatment modalities are needed to prevent or treat recurrent disease. Natural killer (NK) cells are lymphocytes with cytotoxic activity toward virus-infected or malignant cells. We explored the feasibility of autologous and allogeneic NK cell–mediated therapies for chemotherapy-resistant and chemotherapy-sensitive high-grade osteosarcoma. The expression by osteosarcoma cells of ligands for activating NK cell receptors was studied in vitro and in vivo, and their contribution to NK cell–mediated cytolysis was studied by specific antibody blockade. Chromium release cytotoxicity assays revealed chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cell lines and osteosarcoma primary cultures to be sensitive to NK cell–mediated cytolysis. Cytolytic activity was strongly enhanced by IL-15 activation and was dependent on DNAM-1 and NKG2D pathways. Autologous and allogeneic activated NK cells lysed osteosarcoma primary cultures equally well. Osteosarcoma patient–derived NK cells were functionally and phenotypically unimpaired. In conclusion, osteosarcoma cells, including chemoresistant variants, are highly susceptible to lysis by IL-15-induced NK cells from both allogeneic and autologous origin. Our data support the exploitation of NK cells or NK cell–activating agents in patients with high-grade osteosarcoma

    ZIP8 Zinc Transporter: Indispensable Role for Both Multiple-Organ Organogenesis and Hematopoiesis In Utero

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    Previously this laboratory characterized Slc39a8-encoded ZIP8 as a Zn2+/(HCO3–)2 symporter; yet, the overall physiological importance of ZIP8 at the whole-organism level remains unclear. Herein we describe the phenotype of the hypomorphic Slc39a8(neo/neo) mouse which has retained the neomycin-resistance gene in intron 3, hence causing significantly decreased ZIP8 mRNA and protein levels in embryo, fetus, placenta, yolk sac, and several tissues of neonates. The Slc39a8(neo) allele is associated with diminished zinc and iron uptake in mouse fetal fibroblast and liver-derived cultures; consequently, Slc39a8(neo/neo) newborns exhibit diminished zinc and iron levels in several tissues. Slc39a8(neo/neo) homozygotes from gestational day(GD)-11.5 onward are pale, growth-stunted, and die between GD18.5 and 48 h postnatally. Defects include: severely hypoplastic spleen; hypoplasia of liver, kidney, lung, and lower limbs. Histologically, Slc39a8(neo/neo) neonates show decreased numbers of hematopoietic islands in yolk sac and liver. Low hemoglobin, hematocrit, red cell count, serum iron, and total iron-binding capacity confirmed severe anemia. Flow cytometry of fetal liver cells revealed the erythroid series strikingly affected in the hypomorph. Zinc-dependent 5-aminolevulinic acid dehydratase, required for heme synthesis, was not different between Slc39a8(+/+) and Slc39a8(neo/neo) offspring. To demonstrate further that the mouse phenotype is due to ZIP8 deficiency, we bred Slc39a8(+/neo) with BAC-transgenic BTZIP8-3 line (carrying three extra copies of the Slc39a8 allele); this cross generated viable Slc39a8(neo/neo)_BTZIP8-3(+/+) pups showing none of the above-mentioned congenital defects–proving Slc39a8(neo/neo) causes the described phenotype. Our study demonstrates that ZIP8-mediated zinc transport plays an unappreciated critical role during in utero and neonatal growth, organ morphogenesis, and hematopoiesis

    Directed differentiation of embryonic stem cells using a bead-based combinatorial screening method

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    We have developed a rapid, bead-based combinatorial screening method to determine optimal combinations of variables that direct stem cell differentiation to produce known or novel cell types having pre-determined characteristics. Here we describe three experiments comprising stepwise exposure of mouse or human embryonic cells to 10,000 combinations of serum-free differentiation media, through which we discovered multiple novel, efficient and robust protocols to generate a number of specific hematopoietic and neural lineages. We further demonstrate that the technology can be used to optimize existing protocols in order to substitute costly growth factors with bioactive small molecules and/or increase cell yield, and to identify in vitro conditions for the production of rare developmental intermediates such as an embryonic lymphoid progenitor cell that has not previously been reported

    Underground behavior of overwintering Tokyo daruma pond frogs in early spring

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    Although Tokyo daruma pond frogs (Pelophylax porosus porosus) were once commonly observed throughout paddy fields in Japan, their populations have recently declined. The mode by which frogs survive during the overwintering period is largely unknown. In this study, we observed the underground behavior of 12 free-living Tokyo daruma pond frogs that overwintered in paddy soil and a dry field by periodically excavating their overwintering positions from late March to early May. The mean overwintering depth of these frogs was similar to 19.8 cm, with 10 having migrated toward the soil surface (mean depth: similar to 8.6 cm) by late March, and finally, all 11 live frogs migrated further upward close to the soil surface. In addition, males tended to emerge earlier in spring than females. One monitored frog in the paddy soil that migrated close to the soil surface died, presumably from plowing. Aside from the 12 study frogs, several other mutilated frog corpses were found in the paddies. This species starts migrating to the soil surface during the same period when human disturbances begin, making the frogs vulnerable to these disturbances during this period. Consequently, it is necessary to facilitate the emergence of frogs to protect them from human disturbances-e.g., by temporarily filling fields with water

    Anemia prevalence and its determinants in Brazilian institutionalized elderly

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    Objective: To estimate the prevalence of anemia and analyze the factors associated with anemia in elderly residents of long-term care institutions. Methods: This cross-sectional study was performed in male and female elderly volunteers selected in a two-stage random sampling from long-term care institutions in the city of Maringa, Brazil (2008). A diagnosis of anemia was based on the plasma hemoglobin concentration. The independent variables analyzed were gender, age, time of residence at an institution, body mass index, and serum iron and albumin concentrations. The association between anemia and the variables was assessed using the Poisson regression with robust variance in unadjusted and adjusted analyses, considering a complex sample and a significance level of 5%. Results: The sample included 124 adults older than 60 y residing in long-term care institutions (53.0% female). The prevalence of anemia was 29% and was not significantly associated with gender, serum iron concentration, time of residence at an institution, or body mass index. Conversely, hypoalbuminemia was considered a risk factor for anemia. Conclusion: There is a high prevalence of anemia in the institutionalized elderly and hypoalbuminemia is a factor associated with this outcome. Interventions are necessary to promote improvements in the health and welfare of this population. (C) 2012 Published by Elsevier Inc
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