Structural analysis of the factors pertaining to attitudes toward and consciousness of organ donation : Comparison between Japanese and Americans

The purpose of this study is to analyze the background factors relating to opinions on organ donation through factorial and structural comparisons between Japanese and Americans. The data were obtained from responses to a questionnaire (371 Japanese and 41 Americans). The main findings are as follows: 1. Most of the factors, ‘a will for organ donation depending on a recipient’, ‘view of remains’, ‘understanding of brain death’ and so on showed significant differences between Japanese and Americans. 2. Japanese had a better understanding of brain death. On the other hand, the ratio of Americans who were willing to donate an organ was higher than that of Japanese. 3. It was revealed that “the approval of organ donation for the third person, not only for one's family” had an impact for having donor card showing the approval for organ donation. Furthermore, as underlying factors generating differences on organ transplant opinions, differences were found among Japanese between “approval of organ transplant” and the attitude assuming that oneself or a member of one's family was the person concerned with organ transplantation. There were also differences between Japanese and Americans on ideas about a view for life and death such as soul existence or view of remains. The argument for transplantation in Japan should consider these structural differences

Nonlinearity of Mechanochemical Motions in Motor Proteins

The assumption of linear response of protein molecules to thermal noise or structural perturbations, such as ligand binding or detachment, is broadly used in the studies of protein dynamics. Conformational motions in proteins are traditionally analyzed in terms of normal modes and experimental data on thermal fluctuations in such macromolecules is also usually interpreted in terms of the excitation of normal modes. We have chosen two important protein motors - myosin V and kinesin KIF1A - and performed numerical investigations of their conformational relaxation properties within the coarse-grained elastic network approximation. We have found that the linearity assumption is deficient for ligand-induced conformational motions and can even be violated for characteristic thermal fluctuations. The deficiency is particularly pronounced in KIF1A where the normal mode description fails completely in describing functional mechanochemical motions. These results indicate that important assumptions of the theory of protein dynamics may need to be reconsidered. Neither a single normal mode, nor a superposition of such modes yield an approximation of strongly nonlinear dynamics.Comment: 10 pages, 6 figure

Combination of p53AIP1 and survivin expression is a powerful prognostic marker in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>p53AIP1 is a potential mediator of apoptosis depending on p53, which is mutated in many kinds of carcinoma. High survivin expression in non-small cell lung cancer is related with poor prognosis. To investigate the role of these genes in non-small cell lung cancer, we compared the relationship between p53AIP1 or survivin gene expression and the clinicopathological status of lung cancer.</p> <p>Materials and methods</p> <p>Forty-seven samples from non-small cell lung cancer patients were obtained between 1997 and 2003. For quantitative evaluation of RNA expression by PCR, we used Taqman PCR methods.</p> <p>Results</p> <p>Although no correlation between p53AIP1 or survivin gene expression and clinicopathological factors was found, the relationship between survivin gene expression and nodal status was significant (p = 0.03). Overall survival in the p53AIP1-negative group was significantly worse than in the positive group (p = 0.04); however, although survivin expression was not a prognostic factor, the combination of p53AIP1 and survivin was a significant prognostic predictor (p = 0.04). In the multivariate cox proportional hazard model, the combination was an independent predictor of overall survival (p53AIP1 (+) survivin (+), HR 0.21, 95%CI = [0.01–1.66]; p53AIP1 (+) survivin (-), HR 0.01, 95%CI = [0.002–0.28]; p53AIP1 (-) survivin (-), HR 0.01, 95%CI = [0.002–3.1], against p53AIP1 (-) survivin (+), p = 0.03).</p> <p>Conclusion</p> <p>These data suggest that the combination of p53AIP1 and survivin gene expression may be a powerful tool to stratify subgroups with better or worse prognosis from the variable non-small cell lung cancer population.</p

Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer

Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers—carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 healthy subjects. The serum concentrations of IL-6, CEA and CA 19-9 were determined using immunoenzyme assays, whereas CRP using immunoturbidimetric method. We defined the diagnostic criteria and prognostic value for proteins tested. In GC patients, the serum concentrations of all the proteins tested were significantly higher than in healthy subjects. The IL-6, CEA and CA 19-9 levels correlated with nodal metastases, while CRP with tumor stage, gastric wall invasion, presence of nodal and distant metastases. Diagnostic sensitivity of IL-6 was higher (85%) than those of other markers (CRP 66%, CA 19-9 34%, CEA 22%) and increased in combined use with CRP or CEA (88%). The area under ROC curve for IL-6 was larger than those of CRP and classic tumor markers (CEA and CA 19-9). None of the proteins tested was independent prognostic factor for the survival of GC patients. Our findings indicate better usefulness of serum proinflammatory proteins—IL-6 and CRP than classic tumor markers—CEA and CA 19-9 in the diagnosis of GC

Analysis of circulating hem-endothelial marker RNA levels in preterm infants

<p>Abstract</p> <p>Background</p> <p>Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications.</p> <p>Methods</p> <p>Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30). Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (<it>AC133, Tie-2, Flk-1 (VEGFR2) and Scl/Tal1</it>) in association with characteristics of prematurity and preterm morbidity.</p> <p>Results</p> <p>Circulating <it>Tie-2 </it>and <it>SCL/Tal1 </it>RNA levels displayed an inverse correlation to gestational age (GA). We observed significantly elevated <it>Tie-2 </it>levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations.</p> <p>Conclusion</p> <p>These preliminary findings suggest that circulating RNA levels especially <it>Tie2 </it>and <it>SCL </it>decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.</p

The expression of thymidine phosphorylase correlates with angiogenesis and the efficacy of chemotherapy using fluorouracil derivatives in advanced gastric carcinoma

The expression of thymidine phosphorylase (TP) and the density of microvessel in advanced gastric carcinoma were examined by immunohistochemistry to evaluate the significance of TP. The expression of TP was negative in 72 cases, positive in 54. The microvessel density correlated with the expression of TP. In total cases, patients with TP-positive tumours survived longer than those with TP-negative tumours. In patients treated with fluorouracil derivatives (FUs), the expression of TP significantly correlated with favourable prognosis and with unfavourable prognosis in those not treated with FUs. The patients with TP-positive tumours, the prognosis of patients treated with FUs was significantly better than that of those not treated with FUs. In patients with TP-positive tumours, treatment with FUs and lymph node metastasis were independent prognostic factors according to the Cox proportional hazards model. Depth of invasion and lymph node metastasis were independent prognostic factors in patients with TP-negative tumours. The determination of the expression of TP might be useful for predicting the efficacy of post-operative chemotherapy using FUs to prevent recurrence in advanced gastric carcinoma patients who undergo curative gastrectomy. © 1999 Cancer Research Campaig

Polyamine metabolism is involved in adipogenesis of 3T3-L1 cells

Polyamines spermidine and spermine are known to be required for mammalian cell proliferation and for embryonic development. Alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (ODC) a limiting enzyme of polyamine biosynthesis, depleted the cellular polyamines and prevented triglyceride accumulation and differentiation in 3T3-L1 cells. In this study, to explore the function of polyamines in adipogenesis, we examined the effect of polyamine biosynthesis inhibitors on adipocyte differentiation and lipid accumulation of 3T3-L1 cells. The spermidine synthase inhibitor trans-4-methylcyclohexylamine (MCHA) increased spermine/spermidine ratios, whereas the spermine synthase inhibitor N-(3-aminopropyl)-cyclohexylamine (APCHA) decreased the ratios in the cells. MCHA was found to decrease lipid accumulation and GPDH activity during differentiation, while APCHA increased lipid accumulation and GPDH activity indicating the enhancement of differentiation. The polyamine-acetylating enzyme, spermidine/spermine N1-acetyltransferase (SSAT) activity was increased within a few hours after stimulus for differentiation, and was found to be elevated by APCHA. In mature adipocytes APCHA decreased lipid accumulation while MCHA had the opposite effect. An acetylpolyamine oxidase and spermine oxidase inhibitor MDL72527 or an antioxidant N-acetylcysteine prevented the promoting effect of APCHA on adipogenesis. These results suggest that not only spermine/spermidine ratios but also polyamine catabolic enzyme activity may contribute to adipogenesis

The Aquaporin Gene Family of the Yellow Fever Mosquito, Aedes aegypti

The mosquito, Aedes aegypti, is the principal vector of the Dengue and yellow fever viruses. During feeding, an adult female can take up more than its own body weight in vertebrate blood. After a blood meal females excrete large amounts of urine through their excretion system, the Malpighian tubules (MT). Diuresis starts within seconds after the mosquito starts feeding. Aquaporins (AQPs) are a family of membrane transporters that regulate the flow of water, glycerol and other small molecules across cellular membranes in both prokaryotic and eukaryotic cells. Our aim was to identify aquaporins that function as water channels, mediating transcellular water transport in MTs of adult female Ae. aegypti.Using a bioinformatics approach we screened genome databases and identified six putative AQPs in the genome of Ae. aegypti. Phylogenetic analysis showed that five of the six Ae. aegypti AQPs have high similarity to classical water-transporting AQPs of vertebrates. Using microarray, reverse transcription and real time PCR analysis we found that all six AQPs are expressed in distinct patterns in mosquito tissues/body parts. AaAQP1, 4, and 5 are strongly expressed in the adult female MT. RNAi-mediated knockdown of the MT-expressed mosquito AQPs resulted in significantly reduced diuresis.Our results support the notion that AQP1, 4, and 5 function as water transporters in the MTs of adult female Ae. aegypti mosquitoes. Our results demonstrate the importance of these AQPs for mosquito diuresis after blood ingestion and highlight their potential as targets for the development of novel vector control strategies