Retinopathy Associated with Other Forms of Human Cancer

Retinopathy is associated also with other neoplasms such as breast and cervical tumours (Holz et al. 1997) and metastatic melanoma (Kirati et al. 1997). Again, this has been attributed to autoimmune responses to retinal proteins.

RCN is expressed in cell cultures derived from retinoblastoma. Using antibodies raised against recombinant RCN, Weichman (1996) demonstrated that RCN is expressed in the cytoplasm of retinoblastoma cell line Y79. The expression was greatly increased by treating cells with 2 mM butyrate, and to a lesser degree by db-cAMP, together with the formation of neurite-like cellular processes indicating a state of induced differentiation. This possible link-up between RCN expression and differentiation is worthy of further investigation.

In the sera of patients with CAR, heat shock protein (HSP) 70 has been detected in addition to recoverin (Ohguro et al. 1999). The involvement of bacterial HSPs in the induction of autoimmunity has been recognised with the demonstration that HSP65 from the tubercle bacillus mycobacterium can induce autoimmune disease in certain animal tumour models. Certain peptides derived from mycobacterial HSP65 and their homologous peptide obtained from patients with Behcet's uveitis or iridocyclitis induce uveitis in Lewis rats. High antibody titres against these peptides are found in rats that developed uveitis as compared with those that had not (Uchio et al. 1998). This suggests that HSPs do function as autoantigens. Therefore, the detection of HSP70, together with recoverin, might suggest that both these antigens stimulate humoral autoimmunity in the pathogenesis of CAR. This view would be in line with the implication of HSPs in other autoimmune diseases such as rheumatoid arthritis (RA) (Winfield, 1989) and SLE (Minota et al. 1988; Conroy et al. 1994). Antibodies against human HSP60 and E. coli HSP60 have been found in patients with RA and SLE and in Reiter's syndrome which combines arthritis with conjunctivitis, but the antibody titres are far higher than the titres of antibodies against mycobacterium HSP65 (Handley et al. 1996). This seems to suggest that the immune system recognises certain epitopes of these HSPs (Van der Zee et al. 1998). Although these observations suggest that HSPs might play a role in autoimmune conditions, they do not explain the coexpression of RCN with HSPs. It may be that some other HSP function, such as protein folding, may be involved here. As we have seen above, certain critical conformational changes are required in the proper functioning of RCN. Although, in the realms of speculation, the possibility that HSPs influence RCN conformation in such a way that sequestered autoimmune epitopes might be exposed cannot be excluded.

It is unclear whether RCN forms complexes with HSPs. This is an interesting avenue to approach; one can envisage a situation where HSPs regulate RCN function by forming a complex. HSPs are known to form complexes with important biological macromolecules such as p53, rb proteins, and S100A4, and possibly influence their function as regulators of the cell cycle (Sherbet and Lakshmi, 1997b).

Arthritis Joint Pain

Arthritis Joint Pain

Arthritis is a general term which is commonly associated with a number of painful conditions affecting the joints and bones. The term arthritis literally translates to joint inflammation.

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