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1.
Harit Kapoor Kush Raj Lohani Tommy H. Lee Devendra K. Agrawal Sumeet K. Mittal 《CTS Clinical and Translational Science》2015,8(6):841-847
Esophageal adenocarcinoma is the fastest rising cancer in the United States. It develops from long‐standing gastroesophageal reflux disease which affects >20% of the general population. It carries a very poor prognosis with 5‐year survival <20%. The disease is known to sequentially progress from reflux esophagitis to a metaplastic precursor, Barrett''s esophagus and then onto dysplasia and esophageal adenocarcinoma. However, only few patients with reflux develop Barrett''s esophagus and only a minority of these turn malignant. The reason for this heterogeneity in clinical progression is unknown. To improve patient management, molecular changes which facilitate disease progression must be identified. Animal models can provide a comprehensive functional and anatomic platform for such a study. Rats and mice have been the most widely studied but disease homology with humans has been questioned. No animal model naturally simulates the inflammation to adenocarcinoma progression as in humans, with all models requiring surgical bypass or destruction of existing antireflux mechanisms. Valuable properties of individual models could be utilized to holistically evaluate disease progression. In this review paper, we critically examined the current animal models of Barrett''s esophagus, their differences and homologies with human disease and how they have shaped our current understanding of Barrett''s carcinogenesis. 相似文献
2.
ARH missense polymorphisms and plasma cholesterol levels. 总被引:1,自引:0,他引:1
Mutations in a putative low-density lipoprotein (LDL) receptor adaptor protein called ARH have been recently described in patients with autosomal recessive hypercholesterolemia (ARH). ARH plays a tissue-specific role in determination of LDL receptor function. In the ARH gene three mismatched polymorphisms have been detected: Pro202Ser, Pro202His and Arg238Trp. These are of putative interest in plasma cholesterol level determination. To evaluate the effect of polymorphisms on plasma cholesterol levels, all polymorphisms were analyzed by PCR and restriction enzyme analysis by MnII, HpyCH4IV and SacII in 100 Caucasian males with high (>90%, 6.29 +/- 0.89 mmol/l), and 100 males with low (<10%, 3.60 +/- 0.57 mmol/l), total plasma cholesterol levels. No significant differences were observed in frequencies of ARH genotypes or alleles between these two extreme groups. These results suggest that ARH polymorphisms are unlikely to be important genetic determinants of plasma cholesterol levels. 相似文献
3.
Increase in membrane uptake of long-chain fatty acids early during preadipocyte differentiation. 总被引:5,自引:1,他引:4
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N A Abumrad C C Forest D M Regen S Sanders 《Proceedings of the National Academy of Sciences of the United States of America》1991,88(14):6008-6012
An increase in early rates of oleate uptake, which reflected fatty acid (FA) entry into the cells, was apparent 2-3 days after confluence of differentiating BFC-1 preadipocytes. The increase was measured in cells kept without glucose and with arsenate, where greater than 95% of intracellular radioactivity was recovered as free unesterified oleate. Uptake of retinoic acid, a molecule structurally similar to long-chain FA, remained unaltered during cell differentiation. Increase in oleate transport was related to increase in transport Vmax (determined under arsenate treatment) from 0.2 to 2 nmol/min per 10(6) cells, whereas Km remained unchanged (2 x 10(-7) M). Oleate transport was maximal at about day 6 after cell confluence (day 0), as FA metabolism (incorporation into lipids) began to gradually increase. The increase in transport preceded induction of mRNAs for both cytosolic FA-binding protein, which appeared at day 6, and for the FA synthase, which appeared at day 10. Data indicated that increases in activities of FA transport and of lipoprotein lipase, early during cell differentiation, favored increased availability of exogenous FA at a stage when endogenous FA synthesis is limited. This result would promote FA esterification and lipid deposition by supplying a rate-limiting substrate. Furthermore, oleate addition to BFC-1 preadipocytes at confluence potentiated the effect of dexamethasone in inducing mRNA for cytosolic FA-binding protein. In adipocytes, FA from exogenous or endogenous sources was necessary to maintain levels of cytosolic FA-binding protein mRNA. Thus, the increase in FA availability might contribute to, or modulate, induction of proteins necessary for preadipocyte differentiation. 相似文献
4.
John R. Graybill Laura K. Najvar Annette Fothergill Thomas Hardin Michael Rinaldi Chris Lambros Steven L. Regen 《Antimicrobial agents and chemotherapy》1998,42(1):147-150
KY-62 is a water-soluble analog of amphotericin B. In vitro testing of five clinical isolates of Candida albicans showed KY-62 to have potency similar to that of amphotericin B. KY-62 was administered to mice infected intravenously with C. albicans. In vivo, KY-62 was effective in immunocompetent mice, with potency similar to that of amphotericin B. KY-62 was well tolerated up to 30 mg/kg of body weight per dose, an amount that would be lethal with amphotericin B. KY-62 was less effective in mice rendered neutropenic with 5-fluorouracil. The addition of flucytosine had little effect. KY-62 may have potential for clinical development. 相似文献
5.
Mothers' Anticipation and Prevention of Unintentional Injury to Young Children in the Home 总被引:4,自引:3,他引:1
Investigated anticipation and prevention of children's unintentionalinjuries in the home. 150 mothers of 1-, 2-, and 3-year-oldchildren kept weekly diaries of anticipated injuries and unanticipatedinjuries/near injuries to their child. Mothers anticipated between57 and 67% of all injury events, a majority when the child wasin the same room as the injury-causing agent prior to interactingwith it. Few anticipated injuries led to injury. In these casesno significant differences were found depending on child's ageand sex. In contrast, mothers of younger children most frequentlyreported preventing injury by physically restricting or movingthe child away and by changing the environment, whereas mothersof older children more frequently engaged in teaching. 相似文献
6.
Agneta Johansson Eva Särndahl Tommy Andersson Torbjörn Bengtsson Helen Lundqvist Claes Dahlgren 《Inflammation》1995,19(2):179-191
When the chemotactic peptide formylmethionyl-leucyl-phenylalanine binds to its cell surface receptor, a transmembrane signal is generated that activates the superoxide-producing NADPH oxidase of human phagocytes. Comparing monocytes and neutrophils with regard to the production of superoxide anion induced by the peptide, we found a similar time-course for both types of cells. In neutrophils, ligand binding induced a conversion of the receptor to a high-affinity form, a change suggested to be due to an association of the receptor-ligand complex to the Triton X-100-insoluble cytoskeleton. This event has been hypothesized to terminate the signal that activates the NADPH oxidase and thereby results in cessation of the cellular production of superoxide anion. Neutrophils preincubated with the cytoskeleton-disrupting drug cytochalasin B showed an increased and prolonged superoxide anion production after activation with the peptide, thus indicating that the cytoskeleton is involved in terminating this response. Formylmethionyl-leucyl-phenylalanine was also found to induce polymerization of actin in monocytes; however, cytochalasin B had no effect on the peptide-induced generation of superoxide anion in these cells. Furthermore, also in monocytes, ligand binding induced a conversion of the receptor to a high-affinity form; however, the receptor-ligand complex did not coisolate with the Triton X-100-insoluble cytoskeleton. These results indicate that, in monocytes, the NADPH oxidase activating pathway is terminated without any association of the receptor-ligand complex to the Triton X-100-insoluble cytoskeleton. 相似文献
7.
Elliott DE Setiawan T Metwali A Blum A Urban JF Weinstock JV 《European journal of immunology》2004,34(10):2690-2698
Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less-developed countries. Helminths, common in less-developed countries, may induce immunoregulatory circuits protective against IBD. IL-10(-/-) mice given piroxicam develop severe and persistent colitis. Lamina propria mononuclear cells from colitic IL-10(-/-) mice released IFN-gamma and IL-12. The ongoing piroxicam-induced colitis could be partially blocked with anti-IL-12 monoclonal antibody suggesting that the inflammation was at least partly IL-12 dependent. Colonization of piroxicam-treated colitic IL-10(-/-) mice with Heligmosomoides polygyrus (an intestinal helminth) suppressed established inflammation and inhibited mucosal IL-12 and IFN-gamma production. H. polygyrus augmented mucosal IL-13, but not IL-4 or IL-5 production. Transfer of mesenteric lymph node (MLN) T cells from IL-10(-/-) animals harboring H. polygyrus into colitic IL-10(-/-) recipients inhibited colitis. MLN T cells from worm-free mice did not. Foxp3 (scurfin) drives regulatory T cell function. H. polygyrus enhanced Foxp3 mRNA expression in MLN T cells that had regulatory activity. This suggests that H. polygyrus inhibits ongoing IL-10(-/-) colitis in part through blocking mucosal Th1 cytokine production. Resolution of inflammation is associated with increased IL-13 production and can be adoptively transferred by MLN T cells. 相似文献
8.
Paul Kruszka Tommy Hu Sungkook Hong Rebecca Signer Benjamin Cogné Betrand Isidor Sarah E. Mazzola Jacques C. Giltay Koen L. I. van Gassen Eleina M. England Lynn Pais Charlotte W. Ockeloen Pedro A. Sanchez‐Lara Esther Kinning Darius J. Adams Kayla Treat Wilfredo Torres‐Martinez Maria F. Bedeschi Maria Iascone Stephanie Blaney Oliver Bell Tiong Y. Tan Marie‐Ange Delrue Julie Jurgens Brenda J. Barry Elizabeth C. Engle Sarah K. Savage Nicole Fleischer Julian A. Martinez‐Agosto Kym Boycott Elaine H. Zackai Maximilian Muenke 《American journal of medical genetics. Part A》2019,179(10):2075-2082
Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features. 相似文献
9.
Alterations in female gonadal hormones are associated with anxiety and mood changes. The aim of the present study was to determine influences of chronic gonadal hormone supplementation on 5-HT(2A) and 5-HT(2C) receptor mRNA levels in the ventral hippocampus and the frontal cerebral cortex. Ovariectomized adult female Sprague-Dawley rats (n=37) received implantation of subcutaneous pellets containing different dosages of 17beta-estradiol alone or in combination with progesterone, or placebo pellets, for 2 weeks. Serotonin receptor mRNA levels were analyzed by in situ hybridization in the ventral hippocampus and 5-HT(2A) receptor mRNA also in the frontal cortex. Estradiol treatment in combination with low-dose progesterone increased 5-HT(2A) receptor mRNA by 43% in the CA2 region of the ventral hippocampus, while estradiol combined with high-dose progesterone increased the expression of this gene by 84% in ventral CA1. 5-HT(2A) mRNA expression in the frontal cortex was not influenced by hormone manipulation. 5-HT(2C) receptor gene expression was in the ventral hippocampus decreased in the CA2, ventral CA1 and the subiculum subregions by high-dose estradiol treatment (8-20% decreases). Effects on mood by gonadal hormones can be mediated, at least partly, through influences on 5-HT(2A) and 5-HT(2C) receptor expression. 相似文献
10.
Gerdes T Kirchhoff M Lind AM Larsen GV Schwartz M Lundsteen C 《European journal of human genetics : EJHG》2005,13(2):171-175
In routine prenatal diagnostics we used a commercial multiplex ligation-dependent probe amplification (MLPA) kit for aneuploidy screening for chromosomes 13, 18, 21, X and Y. We present the results of 1593 consecutive prenatal samples analysed and diagnosed prior to knowledge of the G-banding analysis during 8-month routine use of computer-assisted MLPA aneuploidy screening. In total, 27 aneuploidies were detected. There were no false positive results while two false negative results could be explained by a placental mosaicism and a partial monosomy, respectively. In total, 3.2% of the samples were inconclusive. We conclude that automatic computer assisted MLPA is a rapid, simple and reliable method for detection of aneuploidies in prenatal diagnostics. 相似文献