Ion-exchanged waveguide lasers in Er3+/Yb3+ codoped silicate glass.

We investigated an Er(3+)/Yb(3+) codoped silicate glass as a host material for waveguide lasers operating near 1.5 microm. Spectroscopic properties of the glass are reported. Waveguide lasers were fabricated by K(+)-ion exchange from a nitrate melt. The waveguides support a single transverse mode at 1.5 microm. An investigation of the laser performance as a function of the Yb:Er ratio was performed, indicating an optimal ratio of approximately 5:1. Slope efficiencies of as great as 6.5% and output powers as high as 19.6 mW at 1.54 microm were realized. The experimental results are compared with a waveguide laser model that is used to extract the Er(3+) upconversion coefficients and the Yb(3+)-Er(3+) cross-relaxation coefficients. The results indicate the possibility of obtaining high-performance waveguide lasers from a durable silicate host glass.

Development of partial tolerance to the gastrointestinal effects of high doses of recombinant tumor necrosis factor-alpha in rodents.

Treatment of healthy rats and mice with a single intravenous injection of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) caused a dose-dependent gastrointestinal inflammation. Within 30 min gastric emptying was blocked and tissue edema occurred in the small and large intestine. In the cecum hemorrhage occurred after 4 h at doses greater than or equal to 250 micrograms/kg. The cecum exhibited an acute inflammatory response following rHuTNF-alpha treatment similar to that seen in tumor necrosis at the same dose. The vascular endothelium became swollen, increased numbers of neutrophils and other leukocytes attached to and penetrated the endothelium, and finally hemorrhage occurred. Treatment of rats with daily injections of rHuTNF-alpha (250 micrograms/kg per d) for 3 wk failed to produce cachexia. Within 24-48 h rats became resistant to the hemorrhagic effect of rHuTNF-alpha, however, the cytokine still caused a transitory block of gastric emptying after 10 d of treatment. Treatment at 5- or 10-d intervals produced results similar to the initial injection. These results suggest that maximum hemorrhagic response will occur when rHuTNF-alpha is administered at intervals of 5-10 d rather than daily.

Natural killer-sensitive targets stimulate production of TNF-alpha but not TNF-beta (lymphotoxin) by highly purified human peripheral blood large granular lymphocytes.

Highly purified populations of large granular lymphocytes (LGL) have been shown to mediate natural killer (NK) cell activity. The mechanism of target cell killing by NK cells is as yet undefined; however, it has been postulated that such killing may involve soluble cytotoxic factors produced and secreted by NK cells. The data presented show that NK-sensitive, but not NK-resistant, tumor cell lines induce highly purified populations of human LGL to produce factors with cytotoxic and/or cytostatic activities. We have identified one of these factors as tumor necrosis factor-alpha (TNF-alpha), and have shown that production of this factor is enhanced by recombinant human interferon-gamma (rHuIFN-gamma). We have also examined the role of TNF-alpha in the cytotoxic function of NK cells. The data show that although highly purified LGL populations produce low levels of TNF-alpha, the cytotoxic/cytostatic activity of this lymphokine on tumor target cells does not correlate with the cytotoxic activity of highly purified populations of LGL on tumor target cells. Furthermore, NK cell-mediated cytotoxicity is not reliably inhibited by antibodies directed against various epitopes of recombinant human TNF-alpha and/or recombinant TNF-beta (lymphotoxin) or rHuIFN-gamma. These data show that although TNF-alpha is produced by highly purified NK-containing LGL cell populations, this factor does not appear to be responsible for NK cell cytotoxicity against classical NK target cells such as Molt-4 or K562. We suggest that NK function can be attributed to a combination of factors rather than to a single factor alone, and that at least two major phenomena are involved in LGL function: the rapid cytotoxic events which lead to the cell lysis measured in classical in vitro NK assays such as against K562; and the release of factors such as TNF-alpha with cytotoxic/cytostatic activities which would inhibit the growth of invading tumor cells in vivo.

Interferon gamma: more than a MAF.

The precise immunoregulatory activities of particular lymphokines have been difficult to define due to the presence of contaminating molecules in the purified natural preparations under study. Thus, the application of recombinant DNA technologies to lymphokine research has been instrumental in elucidating the biologic properties of many of these factors. In particular, with the availability of recombinant gamma interferon (rIFN-gamma) a variety of immuno-regulatory functions, including natural killer activation, enhancement of lymphokine production, macrophage activation, and cell surface Ia expression, have been clearly shown to be mediated by this lymphokine. Recently we have compared the properties of macrophage activating factor (MAF) to those of natural and rIFN-gamma. This article reviews our evidence suggesting that IFN-gamma is a major MAF. In addition, we present evidence for another activity of IFN-gamma, namely, its ability to regulate the growth of certain interleukin 2 (IL-2)-dependent cytotoxic T cell lines.

Genetic and biochemical characterization of human lymphocyte cell surface antigens. The A-1A5 and A-3A4 determinants.

The genes that code for the human lymphocyte cell surface determinants defined by monoclonal antibodies A- 1A5 and A- 3A4 have been genetically mapped. All human chromosomes, except Y, were included in a series of human less than mouse lymphocyte hybrid populations that retained expression of lymphocyte-specific surface markers. Expression of the A- 1A5 and A- 3A4 antigens was quantitated by indirect immunofluorescence and fluorescence-activated cell sorter (FACS) analysis. Hybrid populations heterogeneous for antigen expression were sorted to yield antigenically homogeneous subpopulations. Isozyme analysis indicated concordant segregation of the A- 1A5 determinant with chromosome 10, and the A- 3A4 determinant with chromosome 4. In contrast to the unhybridized human parent cell line (MOLT-4), from which A- 1A5 immunoprecipitated two proteins (160,000 and 125,000 Mr), A- 1A5 only immunoprecipitated a single band (125,000 Mr) from an A- 1A5 -expressing human less than mouse hybrid. The genetic disassociation of these two proteins from the A- 1A5 -reactive complex suggests that the appearance of the 160,000 Mr protein requires a gene locus that is unlinked to the locus for the 125,000 Mr protein on chromosome 10. A third component of the A- 1A5 -reactive protein complex (210,000 Mr), which is recognized by the monoclonal antibody TS2/7, was not expressed on the parent MOLT-4 cells, but was weakly expressed on MOLT-4 less than mouse BW5147 hybrids. This allowed preliminary mapping of that determinant to either chromosome 10 or 15. The A- 3A4 antigen (approximately 45,000 Mr) is a novel cell surface structure expressed on all hematopoietic cell lines tested, and represents the first cell surface marker mapped to chromosome 4.