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Bull trout (Salvelinus confluentus) is a char listed as threatened under the United States Endangered Species Act throughout its range in the coterminous United States. Substantial morphological similarities between bull trout and Dolly Varden (S. malma) make field identification difficult. This has resulted in an incomplete understanding of their distribution and abundance in Washington State where these two species occur sympatrically. We used three diagnostic nuclear loci to determine the species of char collected at a trap on the White River in southern Puget Sound (Washington State, USA). Each of the 104 samples revealed the expected bull trout genotype at all three loci. This work presents three principle results: (i) the presence of a migratory bull trout population in southern Puget Sound; (ii) no evidence of migratory Dolly Varden over 3 years; and (iii) no evidence of hybridization was detected. These results also demonstrate how molecular markers can provide information essential to the conservation and management of these species.
Mol Ecol 2003 Feb
PMID:Nuclear DNA identification of migrating bull trout captured at the Puget Sound Energy diversion dam on the White River, Washington State. 1253 6

Bacterial superantigens (SAGs) bind to cognate Vbeta elements of T-cell receptors on T-cells and to major histocompatibility complex (MHC) class II molecules on antigen-presenting cells to activate T-cell subsets expressing the Vbeta elements. We examined the possibility that the direct binding of SAGs (staphylococcal enterotoxins B [SEB] and A [SEA]) to tumor cells decreases the toxicity of SAGs, and that antitumor immunity can be induced with the aid of T-helper-1 (Th1)-type cytokines and monokines released from T-cells and monocytes, respectively, by activation with SAGs. In this context, we have developed a general method for conjugating SEB and SEA directly to tumor cells with a heterobifunctional cross linking agent, N-(gamma- maleimidobutyryloxy) sulfosuccinimide sodium salt. Using this method, we have succeeded in conjugating SEB to a sufficient extent as to induce strong tumor immunity. Both in vitro T-cell culture with SEB-bearing Meth A cells and in vivo immunization with SEB-bearing Meth A cells induce strong antitumor activity. These results suggest that the direct conjugation of SAGs including SEB and SEA to tumor cells is a powerful and useful method for immunotherapy of cancer.
Mol Biotechnol 2003 Sep
PMID:A novel method for modification of tumor cells with bacterial superantigen with a heterobifunctional cross-linking agent in immunotherapy of cancer. 1367 39

This is a continuation of the series of articles (C.R. Rao, D.N. Shanbhag (Eds.), Handbook of Statistics 19: Stochastic Processes: Theory and Methods, Elsevier Science, Amsterdam, 2001 (Chapter 8); Math. Biosci. 175 (2002) 83; Math. Meth. Appl. Sci. 26 (2003) 1587; Adv. Appl. Probab. 36 (2004) 57) devoted to a study of the interplay between two of the main forces of population genetics, mutations and drift, in the Fisher-Wright model. We provide discrete-time versions of theorems describing asymptotic behavior of joint distributions of characteristics of a pair of individuals in this model; their continuous-time counterparts were presented in the previous papers. Furthermore, we show that imbalance index, introduced in Kimmel et al. (Genetics 148 (1998) 1921) and King et al. (Mol. Biol. Evol. 17(12) (2000) 1895) in the context of continuous-time models, may also be used in discrete-time models to detect past population growth.
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PMID:Asymptotic behavior of joint distributions of characteristics of a pair of randomly chosen individuals in discrete-time Fisher-Wright models with mutations and drift. 1556 Sep 13

Although AIMP1 (previously known as p43) is one of three auxiliary proteins bound to a macromolecular aminoacyl tRNA complex, it is also secreted as a cytokine controlling both angiogenesis and immune responses. Here we show that systemically administered purified recombinant human AIMP1 had anti-tumor activity in mouse xenograft models. In Meth A-bearing Balb/c mice, tumor volume increased about 28 fold in the vehicle treatment group, while an increase of about 16.7 fold was observed in the AIMP1-treated group. We also evaluated the anti-tumor activity of AIMP1 in combination with a sub-clinical dose of the cytotoxic anti-tumor drug, paclitaxel. The growth of NUGC-3 human stomach cancer cells was suppressed by 84% and 94% by the combinations of 5 mg/kg paclitaxel + 25 mg/kg AIMP1 (p = 0.03), and 5 mg/kg paclitaxel + 50 mg/kg AIMP1 (p = 0.02), respectively, while 5 mg/kg paclitaxel alone suppressed growth by only 54% (p = 0.02). A similar cooperative effect of AIMP1 and paclitaxel was observed in a lung cancer xenograft model. These results suggest that AIMP1 may be useful as a novel anti-tumor agent.
Mol Cells 2006 Apr 30
PMID:Antitumor activity of the novel human cytokine AIMP1 in an in vivo tumor model. 1668 15

Aspirin displays, at millimolar concentrations, several mechanisms independent from its ability to inhibit cyclooxygenases. Occasionally, the mechanisms displayed in vitro have been clearly related to an effect of clinical relevance in vivo. An expanding literature has been focusing on the cytoprotective effect of aspirin in neurodegenerative disorders and the activation of AKT pathway in neuroprotection and induction of resistance to anticancer drugs. In this work, we tested the ability of aspirin to activate the AKT survival pathway in methylcholanthrene-induced fibrosarcoma cells (Meth A) transplanted into BALB/c nude mice and the clinical effect of aspirin cotreatment during etoposide (VP-16)-based anticancer therapy. We found that cotreatment with aspirin reduced VP-16-induced apoptosis and activated AKT in vitro and in vivo. In Meth A-bearing mice, aspirin administration also activated glycogen synthase kinase-3 and reduced the activity and the efficacy of anticancer therapy in VP-16 cotreated animals. Our data suggest that the antiapoptotic effect of aspirin operates in vivo through the activation of AKT-glycogen synthase kinase pathway causing a decrease in the outcome of VP-16-based therapy. These findings could have clinical relevance in treatment of human malignancies.
Mol Cancer Ther 2006 May
PMID:Aspirin reduces the outcome of anticancer therapy in Meth A-bearing mice through activation of AKT-glycogen synthase kinase signaling. 1673 65

Isolation by distance is usually tested by the correlation of genetic and geographic distances separating all pairwise populations' combinations. However, this method can be significantly biased by only a few highly diverged populations and lose the information of individual population. To detect outlier populations and investigate the relative strengths of gene flow and genetic drift for each population, we propose a decomposed pairwise regression analysis. This analysis was applied to the well-described one-dimensional stepping-stone system of stream-dwelling Dolly Varden charr (Salvelinus malma). When genetic and geographic distances were plotted for all pairs of 17 tributary populations, the correlation was significant but weak (r(2) = 0.184). Seven outlier populations were determined based on the systematic bias of the regression residuals, followed by Akaike's information criteria. The best model, 10 populations included, showed a strong pattern of isolation by distance (r(2) = 0.758), suggesting equilibrium between gene flow and genetic drift in these populations. Each outlier population was also analysed by plotting pairwise genetic and geographic distances against the 10 nonoutlier populations, and categorized into one of the three patterns: strong genetic drift, genetic drift with a limited gene flow and a high level of gene flow. These classifications were generally consistent with a priori predictions for each population (physical barrier, population size, anthropogenic impacts). Combined the genetic analysis with field observations, Dolly Varden in this river appeared to form a mainland-island or source-sink metapopulation structure. The generality of the method will merit many types of spatial genetic analyses.
Mol Ecol 2006 Oct
PMID:Decomposed pairwise regression analysis of genetic and geographic distances reveals a metapopulation structure of stream-dwelling Dolly Varden charr. 1696 63

A food and drink intake survey was carried out among university students and staff members. Consumption data were collected on days when the participants took hot lunch in a university canteen. The dietary acrylamide exposure was calculated through a probabilistic approach and revealed a median intake of 0.40 microg/kg bw/day [90% confidence interval: 0.36-0.44], which is in accordance with previous exposure calculations. Biscuits (35.4%), French fries (29.9%), bread (23.5%), and chocolate (11.2%) were identified to be the main sources of dietary acrylamide. Foodstuffs consumed in between the three main meals of the day (so called snack type foods) contributed the most to the intake (42.2%). The exposure was lower in an intervention group which received free portions of fruit and vegetables, indicating that a nutritionally balanced diet may contribute to a decreased acrylamide intake. French fries had a significant impact on the acrylamide intake, due to the frequent consumption in the canteen. This demonstrates the important responsibility of caterers and canteen kitchens in the mitigation of acrylamide exposure through reduction of acrylamide in their prepared products, in particular in French fries.
Mol Nutr Food Res 2007 May
PMID:Importance of a canteen lunch on the dietary intake of acrylamide. 1744 Sep 97

The expression of tumor suppressor gene DBC2 causes certain breast cancer cells to stop growing [M. Hamaguchi, J.L. Meth, C. Von Klitzing, W. Wei, D. Esposito, L. Rodgers, T. Walsh, P. Welcsh, M.C. King, M.H. Wigler, DBC2, a candidate for a tumor suppressor gene involved in breast cancer, Proc. Natl. Acad. Sci. USA 99 (2002) 13647-13652]. Recently, DBC2 was found to participate in diverse cellular functions such as protein transport, cytoskeleton regulation, apoptosis, and cell cycle control [V. Siripurapu, J.L. Meth, N. Kobayashi, M. Hamaguchi, DBC2 significantly influences cell cycle, apoptosis, cytoskeleton, and membrane trafficking pathways. J. Mol. Biol. 346 (2005) 83-89]. Its tumor suppression mechanism, however, remains unclear. In this paper, we demonstrate that DBC2 suppresses breast cancer proliferation through down-regulation of Cyclin D1 (CCND1). Additionally, the constitutional overexpression of CCND1 prevented the negative impact of DBC2 expression on their growth. Under a CCND1 promoter, the expression of CCNE1 exhibited the same protective effect. Our results indicate that the down-regulation of CCND1 is an essential step for DBC2's growth suppression of cancer cells. We believe that this discovery contributes to a better understanding of DBC2's tumor suppressor function.
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PMID:Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function. 1751 69

We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV) and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly. UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.
Cell Mol Immunol 2007 Aug
PMID:Enhancement of antitumor effect of tegafur/uracil (UFT) plus leucovorin by combined treatment with protein-bound polysaccharide, PSK, in mouse models. 1776 20

Somatic cell nuclear transfer (SCNT) is a technique by which the nucleus of a differentiated cell is introduced into an oocyte from which its genetic material has been removed by a process called enucleation. In mammals, the reconstructed embryo is artificially induced to initiate embryonic development (activation). The oocyte turns the somatic cell nucleus into an embryonic nucleus. This process is called nuclear reprogramming and involves an important change of cell fate, by which the somatic cell nucleus becomes capable of generating all the cell types required for the formation of a new individual, including extraembryonic tissues. Therefore, after transfer of a cloned embryo to a surrogate mother, an offspring genetically identical to the animal from which the somatic cells where isolated, is born. Cloning by nuclear transfer has potential applications in agriculture and biomedicine, but is limited by low efficiency. Cattle were the second mammalian species to be cloned after Dolly the sheep, and it is probably the most widely used species for SCNT experiments. This is, in part due to the high availability of bovine oocytes and the relatively higher efficiency levels usually obtained in cattle. Given the wide utilization of this species for cloning, several alternatives to this basic protocol can be found in the literature. Here we describe a basic protocol for bovine SCNT currently being used in our laboratory, which is amenable for the use of the nuclear transplantation technique for research or commercial purposes.
Methods Mol Biol 2010
PMID:Bovine somatic cell nuclear transfer. 2033 22


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