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The human immunodeficiency virus (HIV) apparently utilizes human chromosome 2, interleukin-1 (IL-1), glucocorticoid hormones, and viral Tat protein to accelerate its replication and the synthesis of all HIV proteins. HIV Tat protein binds to the long terminal repeat (LTR) ribonucleic acid, including the trans-acting responsive (TAR) sequence and the promoter region to increase HIV replication. Tat-TAR transactivation requires a factor encoded on the long arm of chromosome 2. The interaction of HIV with chromosome 2 may also cause the observed inhibition of interleukin-1 receptor antagonist (IL-1RA), thus increasing the production of IL-1. IL-1, in turn, stimulates the HIV-1 enhancer region of the LTR, thus increasing HIV gene expression and replication. IL-1 also induces glucocorticoid hormone synthesis which stimulates HIV in the virion infectivity factor (Vif) region, thus increasing HIV infectivity. It is, thus, proposed that IL-1RA not only may serve to inhibit HIV-induced IL-1, but may be the unidentified human chorionic gonadotropin-associated factor recently found to have anti-HIV and anti-Kaposi's sarcoma activity.

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Human immunodeficiency virus may regulate its replication by stimulating the synthesis of interleukin-1. Interleukin-1, in turn, has the ability to stimulate the human immunodeficiency virus enhancer region. The human genes responsible for interleukin-1 and interleukin-1 receptor antagonist synthesis are located on the long arm of chromosome 2. Coincidentally, the trans-activation responsive ribonucleic acid element in the R region of the long terminal repeat of human immunodeficiency virus-1 has been found to interact directly with a factor present on the long arm of chromosome 2 to facilitate transactivation by the human immunodeficiency virus Tat protein. The human CD26 gene is also located on the long arm of chromosome 2. CD26 is a lymphocyte cell surface antigen that is stimulated by interleukin-1 and serves with CD4 as a coreceptor that interacts with the V3 loop in gp120 of human immunodeficiency virus. The human immunodeficiency virus-induced interleukin-1 excess, thus, serves human immunodeficiency virus by enhancing replication, and by increasing human immunodeficiency virus infectivity via activation of CD26. IL-1 also adversely affects acquired immune deficiency syndrome-related Kaposi's sarcoma. Several genetic treatments for human immunodeficiency virus infection are proposed.

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Documented evidence supports the "cortisol connection' theory of acquired immune deficiency syndrome, linking glucocorticoid metabolism with immune function, and human immunodeficiency virus with them both. The peptide T subregion of gp 120 of human immunodeficiency virus apparently utilizes cellular melanocyte stimulating hormone receptors to competitively inhibit the blocking of interleukin-1 by melanocyte-stimulating hormone. Interleukin-1 stimulates CD8+ T-lymphocyte proliferation, as well as causing the release of corticotropin-releasing hormone, thereby stimulating the release of adrenocorticotrophic hormone and cortisol. Gp 120 also induces upregulation of adrenocorticotrophic hormone-related messenger ribonucleic acid. This apparently separate glucocorticoid metabolic route utilized by human immunodeficiency virus is the basis of the cortisol excess seen in human immunodeficiency virus infection. In vitro glucocorticoid-resistant lymphoid cells are resistant to human immunodeficiency virus infection as well. Viral resistance is also observed in patients who demonstrate glucocorticoid resistance. Glucocorticoid-responsive elements are contained in the human immunodeficiency virus (proviral and viral) genome that appear to regulate human immunodeficiency virus replication. Similarly, lymphoid-cell development and regulation depend on glucocorticoids. One may take advantage of this view of human immunodeficiency virus pathogenesis to create new methods of treatment.

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Recent evidence suggests that HIV infection and the clinical and laboratory manifestations of acquired immunodeficiency syndrome (AIDS) are a result of the genetic influence of the virus on cellular adrenocorticotrophic hormone (ACTH) and cortisol metabolism. Recent genetic studies substantiate this view with the observation that the HIV-1 genome is linked to glucocorticoid inducibility and to glucocorticoid receptor binding, and may explain the strong ability of cortisol to enhance HIV replication. Adrenocortical hyperactivity observed in HIV-infected individuals has been found to be independent of the hypothalamic-pituitary axis, and is apparently a result of increased ACTH production by HIV. It is proposed that the HIV-induced cortisol excess is the foundation of the immunosuppression seen in AIDS, and is the basis for alternative avenues of treatment, including the use of ascorbic acid.

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We describe an 'in vitro' assay which allows rapid quantification of the binding of biotinated-vesicles to streptavidin immobilised on microtitre plates by estimating levels of a liposome encapsulated fluorescent molecule, rhodamine 123. It is shown that optimal vesicle binding to streptavidin occurs when a six carbon biotin spacer arm derivative of distearoylphosphatidylethanolamine (biotin-X-DSPE) is incorporated in liposomes. This alleviates steric hindrance arising due to the inclusion of small amounts of large bulky amphiphiles such as monosialoganglioside (GM1, 5 mol%) in vesicles. In contrast the ability of liposomes containing poly(ethylene glycol) derivatives of DSPE (PEG2000-DSPE, 5 mol%) to bind streptavidin was only marginally better when biotin-X-DSPE was substituted for biotin-DSPE in vesicles. It is further shown that amounts of biotinated-vesicles bound to streptavidin were minimally influenced by the fluidity of the liposome preparation when assayed at 4 degrees C. However, at elevated temperatures (37 degrees C) lipid estimates as determined by vesicle entrapped rhodamine 123 were low due to leakage of this marker from vesicles. This was shown by comparing amounts of biotinated-liposomes bound to streptavidin coated plates using the lipid marker [3H]cholesteryl hexadecyl ether to estimates determined by vesicle entrapped rhodamine 123. The 'in vitro' assay protocol described here is a general method applicable in the optimisation of other targeting protocols. In conclusion our work suggests that liposomes containing GM1 and the spacer arm derivative biotin-X-DSPE bind optimally to immobilised streptavidin which should aid in the use of biotinated-liposomes in 'in vivo' targeted delivery applications.

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Acquired immunodeficiency syndrome (AIDS) and systemic lupus erythematosus (SLE) are two diseases with striking similarities as well as contrasting differences. There is evidence that AIDS and SLE have the same or similar viruses as their etiologic agent. Genetic, clinical and immunological studies suggest that the two diseases are the same, with their only difference being the stimulatory effects of the AIDS virus on cortisol production versus the inhibitory effects of the proposed SLE virus on cortisol production. Possible mechanisms of the disease process for both AIDS and SLE are discussed, as well as proposed treatments for AIDS, including the use of procainamide and ascorbic acid.

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