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1.
Litman GW; Rast JP; Shamblott MJ; Haire RN; Hulst M; Roess W; Litman RT; Hinds- Frey KR; Zilch A; Amemiya CT 《Molecular biology and evolution》1993,10(1):60-72
Immunoglobulins are encoded by a large multigene system that undergoes
somatic rearrangement and additional genetic change during the development
of immunoglobulin-producing cells. Inducible antibody and antibody-like
responses are found in all vertebrates. However, immunoglobulin possessing
disulfide-bonded heavy and light chains and domain-type organization has
been described only in representatives of the jawed vertebrates. High
degrees of nucleotide and predicted amino acid sequence identity are
evident when the segmental elements that constitute the immunoglobulin gene
loci in phylogenetically divergent vertebrates are compared. However, the
organization of gene loci and the manner in which the independent elements
recombine (and diversify) vary markedly among different taxa. One striking
pattern of gene organization is the "cluster type" that appears to be
restricted to the chondrichthyes (cartilaginous fishes) and limits
segmental rearrangement to closely linked elements. This type of gene
organization is associated with both heavy- and light-chain gene loci. In
some cases, the clusters are "joined" or "partially joined" in the germ
line, in effect predetermining or partially predetermining, respectively,
the encoded specificities (the assumption being that these are expressed)
of the individual loci. By relating the sequences of transcribed gene
products to their respective germ-line genes, it is evident that, in some
cases, joined-type genes are expressed. This raises a question about the
existence and/or nature of allelic exclusion in these species. The
extensive variation in gene organization found throughout the vertebrate
species may relate directly to the role of intersegmental
(V<==>D<==>J) distances in the commitment of the individual
antibody-producing cell to a particular genetic specificity. Thus, the
evolution of this locus, perhaps more so than that of others, may reflect
the interrelationships between genetic organization and function.
相似文献
2.
We investigated the effect of melanocortin 4 receptor (MC4) antagonists on food intake in mice. Food intake during the light phase was significantly increased by ICV administration of mixed MC3/MC4 antagonists (AgRP and SHU9119) or MC4 selective antagonist peptide [(Cyclo (1-5)[Suc-D-Nal-Arg-Trp-Lys]NH2] (MBP10) and the small molecule antagonists THP and NBI-30. Both mixed and selective antagonists significantly reversed anorexia induced by ICV administration of the MC4 agonist (c (1-6) HfRWK-NH2) and the cytokine IL-1beta. These findings provide pharmacological evidence that the MC4 receptor mediates the effects of melanocortin agonists and antagonists on food intake in mice, and support the idea that selective small molecule MC4 antagonists may be useful as therapeutics for cachexia. 相似文献
3.
E Wang Y Zhao A Monaco L Uccellini JM Kirkwood M Spyropoulou-Vlachou MC Panelli FM Marincola H Gogas 《PloS one》2012,7(7):e40805
Purpose
IFNa was the first cytokine to demonstrate anti-tumor activity in advanced melanoma. Despite the ability of high-dose IFNa reducing relapse and mortality by up to 33%, large majority of patients experience side effects and toxicity which outweigh the benefits. The current study attempts to identify genetic markers likely to be associated with benefit from IFN-a2b treatment and predictive for survival.Experimental design
We tested the association of variants in FOXP3 microsatellites, CTLA4 SNPs and HLA genotype in 284 melanoma patients and their association with prognosis and survival of melanoma patients who received IFNa adjuvant therapy.Results
Univariate survival analysis suggested that patients bearing either the DRB1*15 or HLA-Cw7 allele suffered worse OS while patients bearing either HLA-Cw6 or HLA-B44 enjoyed better OS. DRB1*15 positive patients suffered also worse RFS and conversely HLA-Cw6 positive patients had better RFS. Multivariate analysis revealed that a five-marker genotyping signature was prognostic of OS independent of disease stage. In the multivariate Cox regression model, HLA-B38 (p = 0.021), HLA-C15 (p = 0.025), HLA-C3 (p = 0.014), DRB1*15 (p = 0.005) and CT60*G/G (0.081) were significantly associated with OS with risk ratio of 0.097 (95% CI, 0.013–0.709), 0.387 (95% CI, 0.169–0.889), 0.449 (95% CI, 0.237–0.851), 1.948 (95% CI, 1.221–3.109) and 1.484 (95% IC, 0.953–2.312) respectively.Conclusion
These results suggest that gene polymorphisms relevant to a biological occurrence are more likely to be informative when studied in concert to address potential redundant or conflicting functions that may limit each gene individual contribution. The five markers identified here exemplify this concept though prospective validation in independent cohorts is needed. 相似文献4.
Pontillo J Wu D Ching B Hudson S Genicot MJ Gao Y Ewing T Fleck BA Gogas K Aparicio A Wang H Wen J Wade WS 《Bioorganic & medicinal chemistry letters》2008,18(23):6151-6155
The design synthesis and SAR of a series of chiral ring-constrained norepinephrine reuptake inhibitors with improved physicochemical properties is described. Typical compounds are potent (IC(50)s<10 nM), selective against the other monoamine transporters, weak CYP2D6 inhibitors (IC(50)s>1 microM) and stable to oxidation by human liver microsomes. In addition, the compounds exhibit a favorable polarity profile. 相似文献
5.
Hudson S Kiankarimi M Eccles W Mostofi YS Genicot MJ Dwight W Fleck BA Gogas K Wade WS 《Bioorganic & medicinal chemistry letters》2008,18(16):4495-4498
The design, synthesis and SAR of a series of heterocyclic ring-constrained norepinephrine reuptake inhibitors are described. As racemates, the best compounds compare favorably with atomoxetine (IC(50)'s<10 nM) in potency at the transporter. 相似文献
6.
KR Rupesh PL PremKumar Vasanth V Shiva Kumar Seetharaman S Jayachandran 《BMC microbiology》2002,2(1):5-7
Background
Seeds of the legume plant Lathyrus sativus, which is grown in arid and semi arid tropical regions, contain Diamino Propionic acid (DAP). DAP is a neurotoxin, which, when consumed, causes a disease called Lathyrism. Lathryrism may manifest as Neurolathyrism or Osteolathyrism, in which the nervous system, and bone formation respectively, are affected. DAP ammonia lyase is produced by a few microorganisms such as Salmonella typhi, Salmonella typhimurium and Pseudomonas, and is capable of detoxifying DAP. 相似文献7.
Eleni Timotheadou Konstantine T. Kalogeras Georgia-Angeliki Koliou Ralph M. Wirtz Flora Zagouri Angelos Koutras Elke Veltrup Christos Christodoulou George Pentheroudakis Aris Tsiftsoglou Pavlos Papakostas Gerasimos Aravantinos Vasilios Venizelos Dimitrios Pectasides Paris Kosmidis Charisios Karanikiotis Christos Markopoulos Helen Gogas George Fountzilas 《Translational oncology》2017,10(4):589-598
8.
A mathematical model is proposed which systematically investigates complex calcium oscillations in pancreatic acinar cells. This model is based on calcium-induced calcium release via inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR) and includes calcium modulation of inositol (1,4,5) trisphosphate (IP3) levels through feedback regulation of degradation and production. In our model, the apical and the basal regions are separated by a region containing mitochondria, which is capable of restricting Ca2+ responses to the apical region. We were able to reproduce the observed oscillatory patterns, from baseline spikes to sinusoidal oscillations. The model predicts that calcium-dependent production and degradation of IP3 is a key mechanism for complex calcium oscillations in pancreatic acinar cells. A partial bifurcation analysis is performed which explores the dynamic behaviour of the model in both apical and basal regions. 相似文献
9.
Dilek Gogas Yavuz Belgin Kü?ükkaya H. ?nder Ers?z A. Süha Yal?in Kaya Emerk Sema Akalin 《Experimental diabetes research》2002,3(2):145-151
Nonenzymatic glycation of tissue and plasma
proteins may stimulate the production of oxidant
and carbonyl stress in diabetes. The aim
of this study was to evaluate the effects of
aminoguanidine (AG) on lipid peroxidation,
protein oxidation and nitric oxide (NO) release
in diabetic rat kidneys. After induction of diabetes
with streptozotocin, female Wistar rats
were divided into 2 groups. Group DAG (n=9)
rats were given AG hydrogen carbonate (1 g/L)
in drinking water and group D (n=8) was diabetic
control rats given only tap water. Group
H (n=8) was followed as healthy controls. At
the end of an 8 week period, NO release, lipid
and protein oxidation were determined in kidney
tissues. NO release was significantly lower
in diabetic rats compared with healthy controls
(p<0.05). Lipid peroxidation was significantly
high in group D (3.9 ± 0.3 nmol MDA/g tissue)
compared with the group DAG (2.6 ± 0.1 nmol
MDA/g tissue, p<0.01) and group H (2.4 ± 0.2
nmol MDA/g tissue). Protein oxidation was
significantly higher in diabetics than healthy
controls (563.8 ± 23.9, 655.8 ± 7.2 , 431.5 ±
8.8 mmol carbonyl / g tissue for group DAG, D
and H, respectively, p< 0.05). A positive correlation
between albuminuria and thiobarbituric
acid reactive substance (TBARS) levels (r= 0.54,p<0.005) and carbonyl content (r=0.70,
p<0.0005) in kidney homogenate were
observed.
Although AG treatment had no effect on NO
release, it significantly decreased lipid peroxidation
in diabetic rat cortices. Consequently
increased lipid peroxidation -as well as- protein
oxidation could be involved in the pathogenesis
of diabetic albuminuria. 相似文献
10.