Treatment with interferon beta-1b has substantial clinical benefit in the demyelinating disease multiple sclerosis, yet the mechanism of action in the disease remains largely unknown. Gelatinase A (matrix metalloproteinase-2, 72-kd gelatinase) and B (matrix metalloproteinase-9, 92-kd gelatinase) are matrix metalloproteinases capable of enzymatic digestion of subendothelial basement membrane constituents. In human T cells, interleukin-2 induces gelatinase secretion and enhances gelatinase-dependent migration across an artificial basement membrane-like layer in vitro. Pretreatment of T cells with interferon beta-1b for 48 hours decreased interleukin-2-induced gelatinase production and secretion as determined by zymography. In parallel to the downregulation of gelatinase secretion, pretreatment with interferon beta-1b inhibited T-cell migration across the basement membrane in vitro by up to 90%, but had only a minor impact on cell locomotion per se. For both gelatinase secretion and T-cell migration, the inhibitory effect mediated by exposure to interferon beta-1b was dose dependent. Fluorescence-activated cell sorter analysis also showed that interferon beta-1b downregulates the interleukin-2 receptor alpha-chain and lowered the affinity of interleukin-2 to the cell surface by 30%, which may represent an additional mechanism for the observed effects of interferon beta-1b. The dramatic effects of interferon beta-1b on gelatinase expression and migration raise the possibility that its beneficial effects in multiple sclerosis may result from interference with the capacity of activated T cells to traverse the basement membrane and migrate to the central nervous system.

Many different pathogens stimulate cells bearing the V gamma 9-V delta 2 T cell receptor (TCR), which represent the most abundant population of human gamma delta cells. The antigens responsible for the stimulation of these gamma delta cells are not well characterized. Here, we describe six non-peptidic molecules which share this property: isopentenylpyrophosphate, dimethylallylpyrophosphate, 2,3-diphosphoglyceric acid, glycerol-3-phosphoric acid, xylose-1-phosphate, and ribose-1-phosphate. All these molecules are naturally occurring metabolites in prokaryotic and eukaryotic cells, and stimulate freshly isolated gamma delta cells from peripheral blood of different donors as well as established gamma delta clones. Comparison of their structure with that of similar but inactive molecules showed that both the number and position of the phosphate groups, as well as the residues connected with the carbon backbone are required for stimulation. The CD3-TCR complex is involved in cell triggering as shown by inhibition with anti-CD3 Fab fragments. However, all gamma delta clones were broadly cross-reactive and we could not isolate cells specific for only one ligand. The capacity of this frequent subset of gamma delta cells to recognize common bacterial metabolites confers the advantage to react rapidly to different invading pathogens.

Pathologic rupture of the spleen in hematologic malignancies is rare. We present two cases of splenic rupture which occurred in a man with a secondary high-grade non-Hodgkin's lymphoma and a woman with chronic lymphocytic leukemia (CLL). In a review of the literature, we have been able to identify 136 cases of pathologic splenic rupture since 1861; 34% have occurred in acute leukemias, 34% in non-Hodgkin's lymphomas, and 18% in chronic myelogenous leukemia (CML). We find a male-to-female ratio of 3:1, with considerable differences for the specific diseases encountered. Pathologic rupture of the spleen has happened almost exclusively in adults and the ruptured spleens are generally moderately to severely enlarged. It seems that, apart from splenic infiltration by a hematologic disease, splenic infarcts and coagulation disorders (which have previously been advanced as the most important pathophysiologic factors leading to rupture), male sex, adulthood, severe splenomegaly, and cytoreductive chemotherapy may increase the risk for pathologic splenic rupture. We briefly discuss symptoms preceding the event, diagnostic possibilities, and the outcome with operative and conservative approaches.

Current non‐invasive screening methods for the prenatal diagnosis of fetal aneuploidies are hampered by low sensitivities and high false positive rates. Attempts to redress this situation include the enrichment of fetal cells from maternal blood, or the use of fetal DNA in the plasma of pregnant women. By the use of real‐time quantitative polymerase chain reaction (PCR) it has recently been shown that circulatory male fetal DNA in maternal plasma is elevated in pregnancies with trisomy 21 fetuses. In this independent study we confirm and extend upon these results by showing that the levels of fetal DNA are also elevated in pregnancies with other chromosomal aneuploidies (mean=185.8 genome equivalents/ml; range=62.2–471.7) when compared to pregnancies with normal male fetuses (mean=81.9 genome equivalents/ml; range=28.8–328.9), p=0.005. This elevation was greatest for fetuses with trisomy 21, whereas it was not significant for fetuses with trisomy 18, p=0.356. These data suggest that a quantitative analysis of such fetal DNA levels may serve as an additional marker for certain fetal chromosomal abnormalities, in particular for trisomy 21. Copyright © 2000 John Wiley & Sons, Ltd.

In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.