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991.
Molecular genetics of gastrointestinal non-Hodgkin's lymphomas: unusual prevalence and pattern of c-myc rearrangements in aggressive lymphomas 总被引:4,自引:0,他引:4
Thirty-two extranodal lymphomas of the gastrointestinal (GI) tract underwent molecular genetic analysis by Southern blotting using probes for the immunoglobulin genes and the bcl-1, bcl-2, and c-myc loci, commonly involved in lymphomagenesis. No bcl-1 rearrangements were found. There was only one large-cell lymphoma with a bcl-2 rearrangement. A rearrangement of the c-myc gene was found in six of eight Burkittlike lymphomas of the intestine. In five of these six cases, a chromosomal translocation t(8;14) with an unusual breakpoint was demonstrated by comigration of the rearranged c-myc and a rearranged JH sequence. This pattern of rearrangement has not been previously associated with a specific group of non-Hodgkin's lymphomas. In contrast to all six low-grade lymphomas, c-myc rearrangements were found in 6 of 12 large-cell or high-grade mucosa-associated lymphomas of the stomach. No comigration of c-myc and immunoglobulin heavy-chain gene sequences were found. We conclude that primary GI lymphomas have different molecular genetic characteristics compared with node-based follicle center-cell lymphoma and as a group are not related to these lymphomas. In addition, the prevalence and patterns of c-myc rearrangements in the gastric large-cell lymphomas and ileocecal Burkittlike lymphomas are noteworthy and suggest a different and distinct pathogenesis for these tumors. 相似文献
992.
Differential regulation by cytokines of constitutive and stimulated secretion of von Willebrand factor from endothelial cells 总被引:8,自引:2,他引:6
We examined the effect of cytokines on basal and agonist-stimulated release of von Willebrand factor (vWf) by human endothelial cells. Treatment of endothelial cells for up to 48 hours with human recombinant or purified interleukin 1 (IL-1) or human recombinant tumor necrosis factor-alpha (TNF-alpha) did not significantly affect constitutive secretion of vWf or intracellular levels of vWf, although basal prostacyclin (PGI2) production was markedly enhanced. In contrast, both IL-1 and TNF-alpha modulated vWf release in response to thrombin or phorbol ester. Pretreatment of endothelial cells for 2 hours with either cytokine enhanced by up to threefold the stimulatory effect of a subsequent 60-minute exposure to thrombin. Addition of cycloheximide (5 micrograms/mL) during the preincubation abolished this enhancement. Moreover, if the cytokine pretreatment time was extended to 24 hours, agonist-stimulated vWf release was significantly suppressed. Cytokine treatment for 2 or 24 hours had no detectable effect on levels of vWf messenger RNA. The effects of cytokines were not the result of contamination with bacterial lipopolysaccharide and were not attributable to endothelial cell injury. These results show that cytokines have little or no direct effect on vWf release from endothelial cells but can significantly modulate its acute release in response to other stimuli in a complex time- and dose-dependent manner. 相似文献
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Computed tomography has acquired an increasingly central role in the evaluation of asbestos-exposed individuals. The advantages of increased contrast resolution and axial image display have extended our ability to interrogate areas of the pulmonary parenchyma and pleura that are inadequately seen on chest radiographs. The additional information to be gained from CT evaluation must be balanced by the additional expense and time required, particularly in view of the large numbers of asbestos-exposed individuals who will undergo screening over the coming decades. Ideally, imaging strategies that include CT should emphasize those problematic situations in which additional information will serve a differential or diagnostic function, alter the management or habits of the individuals, modify the working environment, or improve our understanding of asbestos-induced diseases. The chest radiograph is the mainstay in the imaging evaluation of asbestos-exposed individuals, providing an inexpensive and rapid appraisal of the presence of both focal and diffuse abnormalities of the pleura and lung parenchyma. Conventional (whole-thorax) CT may be an important adjunct in the following situations: (1) to clarify the presence of pleural thickening, particularly in distinguishing pleural disease from normal extrapleural soft tissues; (2) to stage and determine tumor extent in malignant pleural mesothelioma; (3) to identify optimal sites for biopsy of suspicious pleural changes; and (4) to detect and characterize lung cancers or other focal masses that may be obscured by extensive pleural or parenchymal fibrosis. Limited HRCT studies are roughly competitive in time and cost with four-view radiographic examinations. There is growing evidence that HRCT can detect interstitial disease in advance of conventional clinical or radiographic studies. However, the application of limited HRCT for large-scale screening is controversial. This issue will be resolved as we gain greater understanding of the specificity of HRCT and establish guidelines for standardizing the technique and image interpretation. At present, limited HRCT scans can supplement the evaluation of subjects in whom there is equivocal parenchymal or pleural disease on radiographs or unexplained abnormalities on pulmonary function tests. In individuals with significant pleural disease, HRCT can effectively define the presence and extent of interstitial fibrosis. In individuals with combined cigarette smoking-asbestos exposure in whom symptoms or functional abnormalities are present, HRCT may play a central role in distinguishing emphysematous lung destruction from the peripheral interstitial changes of asbestosis. 相似文献
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The development of assays for the detection of fibrin(ogen)olysis based on COOH-terminal A alpha chain epitopes 总被引:1,自引:0,他引:1
The COOH-terminal two-thirds of the fibrinogen A alpha chain is a substrate for both factor XIIIa and plasmin and is, therefore, a source of structural markers for the clinical detection of fibrin(ogen)olysis. Monoclonal antibodies (MoAbs) that bind to epitopes within this region (F-102, A alpha 563-578; F-103, A alpha 259-276) have been applied towards the development of two sensitive and specific enzyme-linked immunosorbent assays (ELISAs). The first assay, a capture (F-102)-tag (F-103) ELISA, measures plasma fibrinogen molecules whose A alpha chains are intact. The second assay, a solution phase competitive ELISA based on MoAb F-102, quantifies circulating COOH-terminal A alpha chain degradation products (A alpha FDPs), among the earliest peptides released from fibrinogen during plasmin-mediated fragment X formation. This assay features a novel preliminary plasma absorption step on concanavalin A to recover A alpha FDPs (if present in the sample) in a milieu free of immunologically cross-reactive fibrinogen. Both ELISAs use highly purified fibrinogen as the assay standard for quantitation. In control plasmas, circulating A alpha FDPs accounted for less than 2% of their respective intact fibrinogen A alpha chain concentration, suggesting a physiologic low level of proteolysis occurring at the extreme COOH-terminal portion of the molecule. Plasma A alpha FDPs were elevated (2.3% to 7.8% of their respective intact fibrinogen A alpha chain concentration) in a group of plasma from patients with documented, high serum FDPs (21 to 41 micrograms/mL). Application of the two ELISAs to characterize the course of A alpha chain proteolysis during thrombolytic therapy (TIMI phase 1) indicated that A alpha FDPs were a very early marker of the lytic state (detectable 15 minutes after treatment had been initiated), and that streptokinase and recombinant tissue plasminogen activator appeared to produce significantly different A alpha chain degradation profiles. 相似文献