LONG‐TERM FOLLOW UP OF PATIENTS WITH SMALL GASTROINTESTINAL STROMAL TUMORS IN THE STOMACH USING ENDOSCOPIC ULTRASONOGRAPHY‐GUIDED FINE‐NEEDLE ASPIRATION BIOPSY

Background: Gastrointestinal stromal tumors (GIST) are one of the most common mesenchymal tumors of the gastrointestinal tract. GIST are defined by positive immunohistochemical staining for KIT or CD34 and thus are generally diagnosed after surgery. Because small GIST are rarely diagnosed before surgery, the clinical course of these small tumors is not clear. The aim of the present study was to follow changes in size and configuration of small GIST that were pathologically confirmed using endoscopic ultrasonography‐guided fine‐needle aspiration biopsy (EUS‐FNAB). Methods: Between July 1997 and December 2003, 16 tumors in 16 patients (10 men and 6 women) with an immunohistochemical diagnosis of GIST were regularly followed in our hospital. The median patient age when EUS‐FNAB was performed was 62 years (range 26–82 years) and the median follow‐up period was 4.9 years (range 0.5–9.6 years). Results: Fourteen tumors showed no remarkable changes in size and shape during follow up compared with the initial diagnosis. Two tumors enlarged: one tumor approximately doubled its diameter in 8 years and the other tumor increased from 1.8 cm at diagnosis to up to 10 cm after only 2 years. Doubling time of the latter tumor was calculated as 3.1 months. Conclusions: We conclude that EUS‐FNAB might be a good modality for final diagnosis of GIST without surgery, and that GIST without rapid growth on follow up can be endoscopically followed.     

Nonbacterial thrombotic endocarditis clinically mimicking veno-occlusive disease of the liver complicating autologous bone marrow transplantation.

Nonbacterial thrombotic endocarditis is an uncommon, but well-described, complication of bone marrow transplantation. We describe a case of nonbacterial thrombotic endocarditis following autologous bone marrow transplantation that was marked by weight gain, hepatomegaly, ascites, and extreme hyperbilirubinemia leading to a clinical diagnosis of hepatic veno-occlusive disease. Autopsy revealed nonbacterial thrombotic endocarditis of the tricuspid and pulmonic valves, and passive congestion of the liver, but there was no evidence of veno-occlusive disease. We discuss the pathophysiology and clinical features of nonbacterial thrombotic endocarditis and review its occurrence in association with bone marrow transplantation. Nonbacterial thrombotic endocarditis is often difficult to detect clinically and should be a diagnostic consideration in patients who develop systemic emboli or congestive heart failure after bone marrow transplantation.     

Evaluation of a new enzyme-linked immunosorbent assay test for rotavirus antigen in faeces

A new commercial test for the diagnosis of rotavirus gastroenteritis was assessed. With some modifications it compared favourably with electron microscopy and immunofluorescence.     

Competitive control of the self-renewing T cell repertoire

We develop a mathematical model for the self-renewing part of the T cell repertoire. Assuming that self-renewing T cells have to be stimulated by immunogenic MHC-peptide complexes presented on the surfaces of antigen-presenting cells, we derive a model of T cell growth in which competition for MHC-peptide complexes limits T cell clone sizes and regulates the total number of self-renewing T cells in the animal. We show that for a sufficient diversity and/or degree of cross-reactivity, the total T cell number hardly depends upon the diversity of the T cell repertoire or the diversity of the set of presented peptides. Conversely, for repertoires of lower diversity and/or cross-reactivity, steady-state total T cell numbers may be limited by the diversity of the T cells. This provides a possible explanation for the limited repertoire expansion in some, but not all, mouse T cell re-constitution experiments. We suggest that the competitive interactions described by our model underlie the normal T cells numbers observed in transgenic mice, germ-free mice and various knockout mice.      

Extremely complex repeat shuffling during germline mutation at human minisatellite B6.7

Human minisatellite B6.7 is a highly variable locus showing extensive heterozygosity with alleles ranging from six to >500 repeat units. Paternal and maternal mutation rates to new length alleles were estimated from pedigrees at 7.0 and 3.9% per gamete, respectively, indicating that B6.7 is one of the most unstable minisatellites isolated to date. Mutation at this locus was also analysed by small pool PCR of sperm and blood DNA. Male germline instability varied from <0.8 to 14% per allele and increased with tandem array size. In contrast, the frequency of mutants in somatic (blood) DNA was far lower (<0.5%), consistent with a meiotic origin of germline mutants. Sperm mutants were further characterized by minisatellite variant repeat mapping using four major polymorphic sites within the B6.7 repeats. This highly informative system revealed a wide variety of changes in allele structure, including simple intra-allelic duplications and deletions and more complicated inter- and intra-allelic transfers of repeat blocks, as seen at other human minisatellites. The main mode of sperm mutation, however, resulted in extremely complex allele reorganization with evidence of inter-allelic transfer plus the generation of novel repeats by rearrangement at the sub-repeat level, suggesting that recombinational instability at B6.7 is a complex multistep process.     

Somatic mutation processes at a human minisatellite

Germline instability at human minisatellites frequently involves complex inter-allelic transfers of repeat units usually restricted to one end of the repeat array and apparently regulated by flanking DNA. In contrast, nothing is known about the structural basis of somatic instability at minisatellites. An electrophoretic size-enrichment strategy was therefore developed at minisatellite MS32 (D1S8) to enable rare abnormal-length mutants to be detected, validated and quantitated in blood DNA by single molecule PCR. Structural analysis of rare mutant alleles in blood revealed simple deletions/duplications of repeat unit blocks located at random along the tandem repeat array, a mode of mutation completely different from that seen in sperm. Furthermore, allele-specific suppression of sperm instability at MS32 did not affect somatic instability. These data suggest that conversion-based minisatellite mutation in sperm is completely germline-specific and most likely meiotic in origin. Somatic instability appears to occur by a separate pathway involving replication slippage or, more likely, intra-allelic unequal crossing over.