Laboratory investigation; a journal of technical methods and pathology
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Many molecular alterations are known to occur in urothelial carcinoma of the bladder, but their significance for tumor progression is poorly understood. Deletions of chromosome 8p are frequently found in several tumor types and are often associated with progressive disease. In all, 99 bladder tumors were screened for deletions at 8p using loss of heterozygosity (LOH) and multicolor fluorescence in situ hybridization FISH analyses. ⋯ However, promoter methylation was detected using methylation-specific PCR in 29% of cases. In conclusion, we could show a close correlation of chromosome 8p deletions and progression of papillary bladder tumors. The sFRP1 gene on chromosome 8p12-11.1 could be a candidate gene for the predicted, progression-related tumor suppressor gene in bladder cancer and could contribute to urothelial carcinogenesis.
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Composite lymphomas are rare combinations of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma in the same patient, where clonal relatedness has been observed in most of the few cases analyzed. Here, we report a composite classical HL and diffuse large B-cell lymphoma (DLBCL) with interesting molecular features. Micromanipulation of single cells and analysis of V gene rearrangements revealed clonal relatedness with shared and distinct mutations, indicative of derivation from a common germinal center (GC) B-cell precursor and also of further development of both lymphomas in a GC. ⋯ Intriguingly, in the DLBCL precursor somatic hypermutation activity continued after acquisition of destructive V gene mutations, a feature previously found only in Epstein-Barr virus (EBV) infected B-cell expansions. Furthermore, we found evidence of light-chain receptor revision in the lymphoma precursor during a GC reaction. Re-expression of the V(D)J recombination machinery may enhance genomic instability in GC B cells and contribute to lymphomagenesis.
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Glomerular crescents are a major determinant of progression in various renal diseases. Some types of growth factors are known to be involved in the evolution of crescents and the subsequent scar formation. Although glomerular parietal epithelial cells (PECs) are the major component of cellular crescents, the influence of growth factors on PECs is unknown. ⋯ In addition, blockade of endogenous CTGF using an antisense oligodeoxynucleotide significantly attenuated both TGF-beta- and PDGF-BB-induced extracellular matrix synthesis. These results suggest that several growth factors promote cell proliferation and matrix production in PECs. CTGF-mediated matrix production via the TGF-beta or PDGF-BB pathway in PECs may, in part, play a role in the progression of scar formation in crescents.
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Distinction of oligodendrogliomas from other gliomas is clinically important, but the histologic diagnosis of oligodendroglioma has been a difficult and notoriously subjective task. Testing for loss of heterozygosity (LOH) on chromosomal arms 1p and 19q, the genetic signature of oligodendroglioma, has emerged as a useful, objective adjunct to the traditional histologic evaluation. However, LOH testing of glioma specimens has not yet been widely implemented, presumably because of a lack of a practical LOH assay. ⋯ LOH is detected by analysis of the allelic patterns and by integration of data from multiple highly polymorphic microsatellites. In a validation study on 19 gliomas, the results were concordant with results obtained by established methods and correlated well with histologic diagnoses. Because only a paraffin section is required, the pathologist can perform both the traditional histopathologic evaluation and this supporting molecular assay from the material at hand.
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The products of the blood clotting reaction, eg, thrombin and fibrinopeptides, have various proinflammatory activities and are suggested to modulate inflammation. The macrophage expression of tissue factor (TF), the clotting initiator, has been shown to cause clotting in the site of the delayed-type hypersensitivity reaction, a cellular immune response. However, the mechanism of the clotting induction in humoral immune response has been insufficiently studied. ⋯ The number of TF-positive neutrophils were correlated in time with the intensity and extent of fibrin deposition that was visualized with an mAb specific for fibrin and peaked in 24 hours. Interestingly, the fibrin deposit was partially positive for an mAb specific for neutrophil elastase-digested fibrin. These results show in vivo evidence of a close relationship between neutrophils and both clotting and fibrinolysis in the Arthus reaction and may suggest that these neutrophil functions contribute to the pathogenesis of this hypersensitivity inflammation.