Aspirin-triggered 15-epi-lipoxin A4 (ATL) generation by human leukocytes and murine peritonitis exudates: development of a specific 15-epi-LXA4 ELISA

Aspirin (ASA) triggers the formation of 15-epi-lipoxins (15-epi-LXs or ATL [ASA-triggered LX]), which are potent bioactive eicosanoids that may contribute to the therapeutic impact of ASA. To elucidate the role of these new compounds in vivo, it is essential to establish quick and sensitive detection methods. To this end, we prepared an enzyme-linked immunosorbent assay specific for 15-epi-LXA4 that proved to be highly sensitive (IC50 approximately 50 pg, minimum detection approximately 3.5 pg) and stereoselective. The amounts of 15-epi-LXA4 generated by human neutrophils from peripheral blood of healthy volunteers using this enzyme-linked immunosorbent assay were in agreement with those values obtained by liquid chromatography. Formation of 15-epi-LXA4 was cell ratio-dependent during THP-1 (a monocytic leukemia cell line)-neutrophil interactions with ASA-treated cells, and 15-epi-LXA4 was not detected with either cell type alone. Generation of 15-epi-LXA4 was also examined in murine peritonitis with ASA administration. Exudates from ASA-treated mice showed increased production of 15-epi-LXA4 that was diminished by indomethacin, a blocker of ASA-dependent acetylation of prostaglandin G/H synthase. A cytochrome P450 inhibitor administered in the presence of ASA did not prevent 15-epi-LXA4 formation, which suggests that P450 does not significantly contribute to formation of 15-epi-LXA4 in this murine model. These results indicate that the new enzyme-linked immunosorbent assay is both sensitive and selective for 15-epi-LXA4 and that 15-epi-LXA4 is produced by human leukocyte-leukocyte interactions. In addition, 15-epi-LXA4 is generated by inflammatory exudates when ASA is administered during murine peritonitis and when prostaglandin G/H synthase is upregulated and acetylated. This assay should provide rapid means to investigate 15-epi-LXA4 generation in both cellular and animal models.     

Outpatient group psychotherapy for the elderly: an alternative to institutionalization

Two case studies illustrate the positive effects of group psychotherapy for elderly outpatients of a municipal hospital in an industrial community of Baltimore. Most of the outpatients were depressed about physical, mental, or social losses. A total of five brief therapy groups were established. Each group had a maximum of 12 members and met in the hospital for an hour and a half once a week for 12 consecutive weeks. Members could continue in subsequent 12-week sessions if they desired. As a result of their participation in groups, many members became involved in volunteer or part-time work, renewed contact with family and friends, and were better able to deal with life's stresses.     

Single-chain immunotoxins targeted to CD40 for the treatment of human B-lineage hematologic malignancies

Immunotoxins, in chemical conjugate form, have shown limited efficacy in clinical trials in patients with hematologic malignancies. Single-chain immunotoxins (SCIT) provide for enhanced therapeutic efficacy over chemical conjugate forms without additional toxicity and thus may result in improved antitumor activity. We have evaluated two SCITs targeted to CD40, a receptor expressed on most B-lineage hematologic malignancies, for the treatment of non-Hodgkin's lymphoma and multiple myeloma. Both SCITs, G28-5 sFv-PE40 and BD1-G28-5 sFv, were highly potent and specifically cytotoxic against non-Hodgkin's lymphoma and multiple myeloma cell lines. G28-5 sFv-PE40 has proven to be efficacious in SCID mice bearing human non-Hodgkin's lymphoma and multiple myeloma xenografts. Antitumor activity has also been noted in preliminary studies using BD1-G28-5 sFv in non-Hodgkin's lymphoma models. The data presented here indicate that these agents should be considered for use in clinical trials in patients with refractive non-Hodgkin's lymphoma, multiple myeloma and other CD40-expressing hematologic malignancies.     

Scar formation and ligament healing

OBJECTIVE: To compare the efficacy of IUI husband in natural versus FSH stimulated cycles. DESIGN: Prospective, controlled study. MATERIALS AND METHODS: IUI were performed in 57 infertile couples with natural cycles, and in 16 under FSH and GnRH stimulation (Short protocol). In stimulated patients also hCG and hydrogesteron were given. Indication in both groups was idiopathic infertility. Duration of infertility and the age were comparable. Semen preparation and ovarian monitoring were the same in 2 groups. RESULTS: Three pregnancies in 57 natural IUI cycles (5.3%) and 5 out of 16 cycles in stimulated women (31.2% per cycle-with one triple pregnancy). CONCLUSION: In couples with idiopathic infertility FSH stimulation significantly increases rate of pregnancy and multiple gestation.