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Diffuse large B-cell lymphoma (DLBCL) is a common type of non-Hodgkin's lymphoma (NHL) that is highly heterogeneous from both clinical and histopathologic viewpoints. The immunoglobulin (Ig) heavy (H) chain variable region genes were examined in 71 patients with untreated primary DLBCL. Fifty-eight potentially functional VH genes were detected in 53 DLBCL cases; VHgenes were nonfunctional in 9 cases and were not detected in an additional 9 cases. The use of VH gene families by DLBCL tumors was unbiased without overrepresentation of any particular VH gene or gene family. Analysis of Ig mutations in comparison to the most closely related germline gene disclosed mutated VH genes in all but 1 DLBCL case. More than 2% difference from the most similar germline sequence was detected in 52 potentially functional and the 8 nonfunctional VH gene sequences, whereas less than 2% difference from the germline sequence was observed in 3 VH gene isolates. Only 3 VH gene isolates were unmutated. No correlation was found between VH gene use, mutation level, and International Prognostic Index (IPI) or survival. Six of 8 tested tumors showed evidence of ongoing somatic mutations. Evidence for positive or negative antigen selection pressure was observed in 65% of mutated DLBCL cases. Our findings indicate that the etiology and the driving forces for clonal expansion are heterogeneous, which may explain the well-known clinical and pathologic heterogeneity of DLBCL.

Serial changes in splenic volume of 25 patients (18 men and seven women; 53.4 +/- 20.8 years old, range 25-83) with acute pancreatitis who underwent CT examinations were retrospectively studied. Abdominal CT was performed within 3 days after the onset and there was at least one follow-up CT examination after this time. The percentage changes of splenic volume in the first (4-30 days) and second (31-100 days) follow-up CT were calculated. Splenic volume increased in the first follow-up CT (mean +/- SD: 197.8 +/- 121.0 cm3) compared with the initial CT (124.8 +/- 70.0; p < 0.0001), and then decreased in the second follow-up CT (179.7 +/- 100.7; p < 0.002). The average splenic volume increased 65.5 +/- 88.7% (range -10.4-377.4%) between the initial and first follow-up CT examinations. Five of 25 cases (20%) in whom size of spleen increased more than twice had severe acute pancreatitis (p < 0.05), complicated pseudocyst requiring surgical drainage (p < 0.05), pleural effusion (p < 0.01), splenic vein thrombosis or compression (p < 0.05) and longer hospital stay (p < 0.02) compared with patients with a smaller increase in splenic volume. In conclusion, transient splenomegaly was commonly seen in acute pancreatitis, especially in severe or complicated cases. Congestive splenomegaly caused by obstruction or stenosis of the splenic vein and non-specified acute splenitis were suspected of contributing to the transient splenomegaly.

We investigated the effect of WEB 2086, a selective platelet-activating factor (PAF) receptor antagonist, on PAF-induced eosinophil chemotaxis and LTC4 production. WEB 2086 inhibited PAF-induced eosinophil chemotaxis in normals and asthmatics. To further determine if WEB 2086 is a selective PAF receptor antagonist, we examined the effect of WEB 2086 against formyl-methionyl-leucyl-phenylalanine (fMLP)-induced or eosinophil chemotactic factor of anaphylaxis (ECF-A)-induced eosinophil chemotaxis. WEB 2086 did not have a significant inhibition against fMLP or ECF-A-induced eosinophil chemotaxis. These results suggest that WEB 2086 is a selective and potent inhibitor of PAF-induced eosinophil chemotaxis and LTC4 production from eosinophils, due to its antagonism of PAF-receptors.

The role of cytotoxic cells in in vivo immune functions such as allograft rejection is unknown. To begin to assess the function of cytolytic cells in vivo we have begun with cytolytic cell-specific functional molecules: we have isolated and characterized cytolytic cell-specific cDNA clones from cytolytic T cell clones, both encoding distinct serine esterases. The HF gene encodes a trypsin-like enzyme while the C11 gene encodes an enzyme with likely specificity for acidic residues. Here we demonstrate, using in situ hybridization with RNA probe, that both genes are expressed selectively in a subset of T lymphocytes that have infiltrated cardiac allografts. The phenotype of these cells is consistent with the most frequent phenotype of active CTL raised in vitro: they are predominantly CD4-, CD8+, MEL-14- T cell blasts. Thus the expression of these genes, each of which encodes serine esterase found in killer cell granules in vitro, is a valid marker for these cells in vivo as well. The kinetics of their accumulation is consistent with, but not proof of, a putative role in allograft rejection. It is likely that HF and C11 gene expression will be of diagnostic value.

We have measured the relative levels of transcripts for 15 of the 22 known V beta gene segments. The level of transcripts for the highest and lowest expressed V beta gene segment differed by greater than 20-fold in the thymus and an even larger difference was observed in the periphery. The levels of expressions were unrelated to the order of the V beta genes on the chromosome. For most of the V beta gene segments, the relative transcript levels were the same in the thymus and periphery, suggesting that thymic selection in general does not act solely upon the V beta gene segment. One V beta gene segment in the BALB and B10 mice strains was an exception to this rule. V beta 5.2 expression in the periphery of BALB and B10 mice inversely correlated with the expression of the MHC class II molecule I-E. Five V beta gene segments had reduced transcript levels in the periphery of Mls-1a mice compared with their thymic levels or to the levels found in Mls-1b mice. The peripheral level of V beta 3 transcripts vary with MHC and Mls-2 haplotypes. The observation that certain V beta transcript levels are reduced in the periphery when compared with the thymus favors the hypothesis that self tolerance at the T cell level results in the elimination of self-reactive T cells, rather than paralysis by a block at some post-transcriptional step. Finally, the wide variability of V beta gene segment expression in the thymus suggests mechanisms exist to import an early bias to the repertoire. Whether this bias results from differential V beta segment rearrangement rates, differential V beta expression rates, or events occurring after TCR-alpha/beta expression on immature/nonmature thymocyte cell surfaces is yet to be determined.

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