Transplant rejection

Biologicals. Figure 3 Fusion protein construction combination of the molecular component of interest with the constant region (Fc) of an antibody molecule, usually immunoglobulin (lg)G1 Fc, imparts the Fc function on to the molecularcomponentfortherapeutic use. The example given is ofCTLA4-lg, derivatives of which have shown clinical efficacy in the treatment of rheumatoid arthritis and transplant rejection. 

Calcineurin is involved in cardiac hypertrophy and in cognitive and behavioral defects in the brain. Inhibitors of calcineurin such as cyclosporine A and FK 506 are used clinically in transplant rejection and autoimmune diseases. 

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

CCR5 expression likely plays a role in T-cell recruitment and may be involved in the development of autoimmune diseases. There is a negative association between the CCR5A32 mutation and rheumatoid arthritis (Prahalad 2006). Furthermore, additional studies reviewed elsewhere suggest the involvement of CCR5 in multiple sclerosis, diabetes, and transplant rejection (Ribeiro and Horuk 2005). As such, it is likely that CCR5 antagonists developed for the treatment of HIV-1 infection can also be used for other diseases. 

Intestine Fever and Gl symptoms (e.g., bloating, cramping, diarrhea, increased stomal output) There are no reliable biochemical markers for intestine transplant rejection, but biopsies may be helpful... 

Before examining the potential roles of chemokines in the pathophysiology of transplant rejection, it is important to review the biology that underlies the rejection of solid organ allografts. 

Horuk R, Clayberger C, Krensky AM, et al. A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection. J Biol Chem 2001 276 4199-4204. 

Grone HJ, Weber C, Weber KS, et al. Met-RANTES reduces vascular and tubular damage during acute renal transplant rejection blocking monocyte arrest and recruitment. FASEB J 1999 13 1371-1383. 

Segerer S, Cui Y, Eitner F, et al. Expression of chemokines and chemokine receptors during human renal transplant rejection. Am J Kidney Dis 2001 37 518-531. 

Pattison J, Nelson PJ, Huie P, et al. RANTES chemokine expression in cell-mediated transplant rejection of the kidney. Lancet 1994 343 209-211. 

Segerer S, Regele H, Mack M, et al. The duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis. Kidney Int 2000 58 1546-1556. 

ORTHOCLONE OKT 3 Muronomab-CD3 Ortho Biotech Reversal of acute kidney transplant rejection, reversal of heart and liver transplant rejection... 

Zenapax Daclizumab Hoffman-La Roche Prevention of kidney transplant rejection... 

Corticosteroids also exert inhibitory effects on the overall immune process. These drugs impair the function of the leukocytes responsible for antibody production and destruction of foreign cells. As a result, corticosteroids are also used therapeutically in the prevention of organ transplant rejection. 

A 30-year-old male with a two-year history of chronic renal failure requiring dialysis consents to transplantation. A donor kidney becomes available. He is given cyclosporine to prevent transplant rejection just before surgery What is the most likely adverse effect of this drug ... 

Drug-induced allergic interstitial nephritis, renal transplant rejection Tubular necrosis... 

Cyclophosphamide (Cytotoxin) Alkylating agent cancer chemotherapy transplant rejection rheumatoid arthritis Decreased Ts cells, B cells, and NK cells... 

Cyclosporin A Transplant rejections Depresses T cells inhibits IL-2 production... 

Aging (skin and other tissues), myocardial infarct or stroke, inflammation, rheumatoid arthritis, atherosclerosis, pulmonary disorders (asthma and chronic obstructive pulmonary diseases), radiation injury, organ transplant rejection, psoriasis, hypertension, AIDS, multiple types of cancer, neuro-degenerative diseases (Parkinson s), diabetes, muscular dystrophy... 

Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G. (2000). Acute heart transplant rejection due to Saint John s wort. Lancet. 355(9203) 548-49. 

HO-1 is controlled at the level of transcription by oxidative stress and several inducers such as porphyrins, metals, and progesterone (8). The absence of HO-1 is associated with severe growth retardation, anemia, and enhanced endothelial cell injury 156, 157). In addition, HO-1 has been implicated in protection against transplant rejection 158, 159). HO-2 is constitutively expressed, and its presence in brain and the noted similar effects of CO and NO has led to the proposal that CO-generated by HO-2 is involved in signaling processes 8, 160-162). 

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