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Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 and 4. In order to clarify the role of Phe(3) and Phe(4) in binding to the mu receptor, we synthesized a series of analogs in which Phe(3) and Phe(4) were replaced by various amino acids. It was found that the aromaticity of the Phe-beta-phenyl groups of Phe(3) and Phe(4) is a principal determinant of how strongly it binds to the receptor, although better molecular hydrophobicity reinforces the activity. The receptor binding subsites of Phe(3) and Phe(4) of endomorphin-2 were found to exhibit different structural requirements. The results suggest that [Trp(3)]endomorphin-2 (native endomorphin-1) and endomorphin-2 bind to different receptor subclasses.

Ac-RYYRIK-NH2 is a peptide isolated from the peptide library as an antagonist that inhibits the biological activities of nociceptin, a hyperalgesic neuropeptide. In order to clarify the structural requirements of this peptide for binding to the nociceptin receptor ORL1, systematic structure–activity studies were carried out. The result of Ala-scanning indicated that the N-terminal tripeptide RYY(=Arg-Tyr-Tyr) is crucially important for binding to the ORL1 receptor. Residual truncations from the N- or C-terminus revealed the special importance of the N-terminal Arg residue. The removal of protecting groups indicated that the N-terminal acetyl group is essential, but the C-terminal amide group is insignificant. These results indicated the conspicuous importance of acetyl-Arg at position 1 of Ac-RYYRIK-NH2 as a key structure allowing binding to the receptor. To investigate the binding site of this peptide in the ORL1 receptor, we synthesized and assayed a series of analogues of the nociceptin dibasic repeat region, residues 8–13 of RKSARK. None of the derivatives were active. Ac-RYYRIK-NH2 was inactive for the µ opioid receptor to which nociceptin binds with considerable strength. All the results suggested that the mode of binding between Ac-RYYRIK-NH2 and the ORL1 receptor is different to that between the ORL1 receptor and nociceptin, and that it may consist of interaction with the receptor site to which nociceptin(1–7) or -(14–17) binds. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.

Interleukin 6 (IL-6)/B cell stimulatory factor 2 is a multifunctional cytokine produced by both lymphoid and nonlymphoid cells. IL-6 regulates immune response, acute phase reaction, and hematopoiesis. It was found that IL-6 production by T cells is dependent on macrophages, and IL-6 is one of essential factors for pokeweed mitogen induced immunoglobulin production. Both high- and low-affinity IL-6 receptors were identified. The molecular cloning of IL-6 receptors demonstrated that this receptor is a member of the immunoglobulin superfamily. The deregulated production of IL-6 is suggested to be involved in the pathogenesis of autoimmune diseases and in the development of multiple myeloma.

A case of phycomycosis during the course of acute lymphatic leukemia was reported and host factors inducing mycosis was discussed on the case and literatures. During the therapy of antil-eukemic agents and the corticosteroid, he got acute ileus of a small intestine. The histological examination of the resected intestine after the surgcial operation revealed broad and nonseptate hyphae in blood vessel with invasion into vessel wall. He was successfully treated with Clotrimazole and Amphotericine B for 10 days without dissemination of phycomycosis. Autopsy showed on fungal cells on all organs examined. During his hospitalization, suppression of cellular immunity such as negative skin test for PPD, low response of lymphocytes to PHA and decrease number of rosette forming cells. NBT test was negative. In most of the described cases phycomycosis also occurred in patients in whom the immune defence mechanisms were impaired. These conditions of patients are not specific for phycomycosis, but lowered host defence may relate to the induction of opportunistic infections as well as phycomycosis.

The myeloperoxidase (MPO) activity of patients treated with cytotoxic drugs and/or corticosteroids was lower than that of healthy controls. Cyclophosphamide decreases the number of leukocytes without affecting the MPO activity per cell. At the same dose of anti-inflammatory potency, dexamethasone caused more decrease than other corticosteroids in the MPO level, nitro-blue tetrazolium (NET) and number of polymorphonuclear leukocytes (PMN). However, on successive daily treatment with dexamethasone for 7 days, the MPO level and NET returned to normal, although phagocytosis of Candida by PMN diminished to about 60 % of the normal level. Pretreatment of rats with heat-killed Candida albicans protected the functions of PMN against dexamethasone.

Antibody molecules play an essential role not only in protection against viral or bacterial infections, but also in the induction of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus, and immediate-type hypersensitivity. Therefore, the study of the mechanism regulating the activation, proliferation and immunoglobulin secretion of B lymphocytes is essential for the normal and abnormal regulations in the antibody response.