Disease relevance of IGKV6D-21

• Here, we show in four melanoma patients that ex vivo detectable T-cells and thus strong T-cell responses can also be induced against the more universal cancer-testis antigens NY-ESO-1 and Mage-A10 [1].
• Melanoma-associated antigens in esophageal adenocarcinoma: identification of novel MAGE-A10 splice variants [2].
• However, this monoclonal antibody did not neutralize the porcine rotavirus AT/76, also of serotype G3, nor mutants of SA-11 virus (serotype G3) which were selected with monoclonal antibody A10/N3 and are known to have mutations affecting the C antigenic region [3].
• RESULTS: A 10-gene signature set that could be used to accurately determine the HIV-1 serostatus was identified [4].
• Observed patterns for all possible clade combinations (among HPV clades A3, A5, A6, A7, A9, and A10) in two-genotype infections did not significantly differ from those expected in the entire sample, across HIV, Pap smear, and age strata (all goodness-of-fit exact P > 0.20) [5].

High impact information on IGKV6D-21

• In previous studies, added parathyroid hormone-related protein (PTHrP) inhibits whereas transfected PTHrP stimulates the proliferation of A10 aortic smooth muscle cells by nuclear translocation of the peptide [6].
• The loss of dopaminergic neurons in the mesencephalon of the MPTP-intoxicated monkeys was severe in the substantia nigra, intermediate in cell groups A8 and A10, and almost undetectable in the central gray substance [7].
• Perforated patch-clamp experiments further showed in two vascular smooth muscle cell lines (A10 and A7r5), a reversible, dose-dependent inhibitory effect of farnesol on L-type Ca2+ currents (IC50 = 2.2 microM) [8].
• Our results demonstrate that the 2'-hydroxyl groups at A10, G11, A24, and C25 provide essential functions for catalysis, possibly forming important tertiary contacts or magnesium coordination sites that are necessary for active site architecture [9].
• Moreover, in the haplotype analysis with G2319A- and VNTR-polymorphisms, a positive gene dose efffect on the risk with the A10 allele (P = 0.044, linearity tendency test) and a negative gene dose effect with the G10 allele (P = 0.010, linearity tendency test) for alcoholism were significantly detected [10].

Chemical compound and disease context of IGKV6D-21

• Twenty-nine type 2 diabetic patients with dyslipidemia were enrolled and randomly assigned to receive atorvastatin orally at 10 mg (A10; n = 10), 20 mg (A20; n = 10), or 40 mg (A40; n = 9) daily for 12 weeks [11].

Biological context of IGKV6D-21

• According to their DNA sequences and the derived amino-acid sequences A10 and A14 do not fit well into the subgroup classification [12].
• Analysis of transgenic TgH alpha2[-798]CAT rats demonstrated sodium activation of human alpha2[-798]CAT transgene expression in aorta parallel to observations made in rat A10 aortic tissue culture cells [13].
• RNA blot analysis of rat A10 cells revealed a dose-specific (0.022 to 30 micromol/L monensin) upregulation of alpha1-, alpha2-, and beta1-subunit Na,K-ATPase RNA levels [13].
• With the use of chloramphenicol acetyltransferase (CAT) as reporter gene, CAT assays of rat alpha1[-1288]CAT and human alpha2[-798]CAT promoter constructs exhibited induction of CAT activity in monensin (10 micromol/L)-treated A10 cells compared with untreated A10 cells [13].
• Flow cytometry analysis revealed that treatment of A10 cells with 80 muM Avn-c arrested the cell cycle in G1 phase as indicated by an increase in the number of cells in G1 phase and a decrease in the number of cells in S phase [14].

Anatomical context of IGKV6D-21

• Rat embryonic aortic smooth muscle cell line A10 was used in this study [14].
• The human striatum, which receives dopaminergic innervation from the substantia nigra and ventral tegmental area (cell groups A8, A9 and A10), has structural and functional subdivisions both rostrocaudally and dorsoventrally [15].
• Together with area A10 it influences the strial efflux via SNZR to thalamus and from there to prefrontal cortex [16].
• Fields of dense labeling in both the caudate nucleus and the putamen, interrupted by pockets of sparse labeling, were observed with deposits involving cell group A8, cell group A10 and/or the dorsally situated 'pars mixta' of the substantia nigra [17].
• The B cell line FLEB-14 and the erythroid cell line K562, which both express p120 as determined by flow cytometry, but no IL-2R alpha or beta chains showed only slight proliferation changes at high 7 x A10 concentrations [18].

Associations of IGKV6D-21 with chemical compounds

• Atorvastatin dose-dependently decreased HL (A10, -11%; A80, -22%; both P < 0.001) [19].
• The postprandial increment in area under the curve above baseline concentrations in type IIB subjects was significantly decreased by atorvastatin for plasma triglyceride (A10: -42% and A40: -55%, P < 0.01), chylomicrons (CMs) (A10: -24% and A40: -40%, P < 0.03) and VLDL-1 (A10: -54% and A40: -52%, P < 0.02) [20].
• These results indicate that VGLUT2 is expressed in subsets of A10 and A11 dopamine neurons, which might release dopamine and glutamate separately from different varicosities in the majority of their single axons [21].
• We find that < or =1 microM lovastatin potently inhibits the proliferation of A10 cultures, and higher concentrations (> or =3 microM) induce apoptosis [22].
• At a concentration of 120 microM, avenanthramide-2c inhibited more than 50% of SMC proliferation, as measured by [3H] thymidine incorporation, and increased the doubling time of rat SMC line (A10) from 28 to 48 h [23].

Analytical, diagnostic and therapeutic context of IGKV6D-21

• To further evaluate MAGE-A10 expression, reverse transcription-polymerase chain reaction (RT-PCR) products were sequenced, and protein expression was determined using a specific antibody [2].
• Immunohistochemistry on tissue microarray revealed MAGE-A proteins in 20.3% (12 of 59) of EAs and MAGE-A10 staining in 16.9% (10 of 59) of EAs [2].
• CONCLUSIONS: This is the first report of these MAGE-A10 alternative splice sequences, and characterization of MAGE-A expression may provide potential targets for immunotherapy in patients with EA [2].
• MAGE-A expression was confirmed by Western blot in several esophageal tumors and in two EA cell lines, Flo-1 and Seg-1, whereas Flo-1 also expressed MAGE-A10 [2].
• However, the 35 kDa, deglycosylated A subunit was clearly visible on immunoprecipitation with mAb A10 to the TSHR amino terminus, but not with the anti-myc mAb, indicating loss of the c-myc epitope at residues 338-349 [24].

References