Faculty Opinions recommendation of Alteration of intra-pancreatic target-organ specificity by abrogation of Aire in NOD mice.

2006 ◽  
Author(s):  
Peter Van Endert
Keyword(s):  
Nod Mice ◽  
Target Organ ◽  
Organ Specificity

scholarly journals Register shifting of an insulin peptide–MHC complex allows diabetogenic T cells to escape thymic deletion

2011 ◽  
Vol 208 (12) ◽  
pp. 2375-2383 ◽  
Author(s):  
James F. Mohan ◽  
Shirley J. Petzold ◽  
Emil R. Unanue
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
Islets Of Langerhans ◽  
Nod Mice ◽  
Target Organ ◽  
Single Amino Acid ◽  
Type B ◽  
Nonobese Diabetic ◽  
High Concentrations ◽  
Antigen Presenting

In nonobese diabetic (NOD) mice, two sets of autoreactive CD4+ T cells recognize the B:9–23 segment of the insulin B chain. One set, type A, recognizes insulin presented by antigen-presenting cells (APCs). These T cells are highly deleted in the thymus. The second set, type B, does not recognize insulin protein but reacts with soluble B chain peptide. This set is not deleted in the thymus but is activated in the islets of Langerhans. In this study, we examine the specificity of these two types of T cells. The protein-reactive set recognizes the stretch of residues 13–21 of the insulin B chain. The set reactive to peptide only recognizes the stretch from residues 12–20. A single amino acid shift of the B chain peptide bound to I-Ag7 determines whether T cells recognize peptides generated by the processing of insulin, and consequently their escape from thymic purging. Biochemical experiments indicate that peptides bound in the 13–21 register interact more favorably with I-Ag7 than peptides that bind in the 12–20 register. Thus, self-reactive T cells can become pathogenic in the target organ where high concentrations of antigen and/or differences in intracellular processing present peptides in registers distinct from those found in the thymus.

Target Organ Specificity For N-Heterocyclic Aromatics

1994 ◽  
Vol 6 (1-4) ◽  
pp. 27-34 ◽  
Author(s):  
David Warshawsky ◽  
Susan Fremont ◽  
Weiling Xue ◽  
Joanne Schneider ◽  
Marlene Jaeger ◽  
...  
Keyword(s):  
Target Organ ◽  
Organ Specificity ◽  
Heterocyclic Aromatics

Target Organ Specificity: Diethylnitrosamine-and Dibenzylnitrosamine-induced Single-strand Breaks Plus Alkali-labile Bonds

1984 ◽  
Vol 3 (2) ◽  
pp. 207-216
Author(s):  
Douglas E. Brash ◽  
Cheng M. Su ◽  
Hani A. Nabi ◽  
Kathleen S. Reuter ◽  
Judith Ortman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Chronic Administration ◽  
Target Organ ◽  
Single Strand ◽  
Organ Specificity ◽  
Tumor Promoters ◽  
Sprague Dawley ◽  
Strand Breaks ◽  
Single Strand Breaks ◽  
Sprague Dawley Rats

Quantitative dose response measurements of diethylnitrosamine-and dibenzylnitrosamine-induced DNA single-strand breaks plus alkali-labile bonds (SSB + ALB) (single-strand breaks, apurinic/apyrimidinic sites, and phosphotriesters) were performed on samples of 100,000 nuclei from Sprague-Dawley rats. Twenty-four hours after diethylnitrosamine injection, there were no SSB + ALB in brain (nontarget), SSB + ALB in kidney (target), and SSB + ALB in liver (target only after partial hepatectomy, tumor promoters, or chronic administration). Seven days after diethylnitrosamine injection, liver SSB + ALB had declined. The noncarcinogenic diethylnitrosamine analog, dibenzylnitrosamine, induced no SSB + ALB at 6 hours or 7 days postinjection. Induction of DNA damage, therefore, correlates well with target organ specificity of tumorigenesis when specificity is broadened to include those organs that exhibit tumors only when DNA damage is followed by additional treatments.

Target Organ Specificity of Cell Proliferation Induced by Various Carcinogens

1993 ◽  
Vol 21 (5) ◽  
pp. 436-442 ◽  
Author(s):  
Yasunori Yoshida ◽  
Masae Tatematsu ◽  
Katsumi Takaba ◽  
Shogo Iwasaki ◽  
Nobuyuki Ito
Keyword(s):  
Cell Proliferation ◽  
Target Organ ◽  
Organ Specificity

Hepatocyte Alterations in Guinea Pigs FED Polychlorinated Biphenyls (PCBs), Dibenzodioxins (PCDD), AND DIBENZOFURANS (PCDF)

1982 ◽  
Vol 40 ◽  
pp. 56-57
Author(s):  
J. N. Turner ◽  
D. N. Collins
Keyword(s):  
Guinea Pigs ◽  
Room Temperature ◽  
Dose Group ◽  
Methyl Cellulose ◽  
Uranyl Acetate ◽  
Target Organ ◽  
Office Building ◽  
Lead Citrate ◽  
Control Groups ◽  
Cooling Fluid

A fire involving an electric service transformer and its cooling fluid, a mixture of PCBs and chlorinated benzenes, contaminated an office building with a fine soot. Chemical analysis showed PCDDs and PCDFs including the highly toxic tetra isomers. Guinea pigs were chosen as an experimental animal to test the soot's toxicity because of their sensitivity to these compounds, and the liver was examined because it is a target organ. The soot was suspended in 0.75% methyl cellulose and administered in a single dose by gavage at levels of 1,10,100, and 500mgm soot/kgm body weight. Each dose group was composed of 6 males and 6 females. Control groups included 12 (6 male, 6 female) animals fed activated carbon in methyl cellulose, 6 males fed methyl cellulose, and 16 males and 10 females untreated. The guinea pigs were sacrificed at 42 days by suffocation in CO2. Liver samples were immediately immersed and minced in 2% gluteraldehyde in cacadylate buffer at pH 7.4 and 4°C. After overnight fixation, samples were postfixed in 1% OsO4 in cacodylate for 1 hr at room temperature, embedded in epon, sectioned and stained with uranyl acetate and lead citrate.

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