Hematopathology and molecular hematology最新文献

{"title":"An anti-LFA-1 monoclonal antibody (LDA-8) induces cellular aggregation of human lymphoblastoid cell lines and peripheral blood lymphocytes.","authors":"J S Yang,&nbsp;G Mathioudakis,&nbsp;E Kruzel,&nbsp;L S Angelo,&nbsp;L I Sakkas,&nbsp;J E Lee,&nbsp;E L Oleszak,&nbsp;C D Platsoucas","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The human leukocyte-function-associated antigen-1 (LFA-1) plays a key role in intercellular adhesion interactions of the immune response. A monoclonal antibody (mab), designated LDA-8, is described that recognizes LFA-1. In contrast to nearly all other anti-LFA-1 mabs, which inhibit cellular aggregation, LDA-8 induces cell-cell aggregation. The LDA-8 mab was generated by immunizing mice with membrane fragments from the Jurkat T-cell line. The LDA-8 mab stained peripheral blood mononuclear cells (PBMC), monocyte-depleted peripheral blood lymphocytes, purified monocytes, and a number of T and B tumor cell lines. The LDA-8 mab induced aggregation of PBMC from normal donors, as well as of cells from T-cell lines (MOLT4 and CEM). Control mabs directed against HLA class 1 or CD4 did not induce aggregation. Aggregation was concentration- and time-dependent. EDTA added to the cultures 1 hour prior to or together with the LDA-8 mab did not inhibit LDA-8-induced aggregate formation. Anti LFA-1 alpha-chain mab added to the cells 1 hour prior to LDA-8 mab, or together with the LDA-8 mab, also did not inhibit LDA-8-induced aggregation. In contrast, anti-LFA-1 beta-chain mab, added to the cells together with or 1 hour prior to the LDA-8 mab, significantly inhibited LDA-8-induced aggregate formation. The LDA-8 mab immunoprecipitated two polypeptide chains of 110 kDa and 160 kDa under non-reducing conditions and of 92 kDa and 162 kDa under reducing conditions, from cells of the MOLT-4 or CEM T-cell lines or phytohemagglutinin (PHA)-stimulated PBMC. The molecular mass of these polypeptides was identical to that of polypeptides immunoprecipitated by the anti-LFA-1 TS1.22 mab, suggesting that the LDA-8 mab and the anti-LFA-1 mab recognize the same molecule. This was confirmed by sequential immunoprecipitation. The LDA-8 mab recognizes a unique epitope on LFA-1 and induces cell aggregation that is blocked by mabs recognizing the beta-chain, but not the alpha-chain of the LDA-1 molecule.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20368071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rearrangement, hypermutation, and possible preferential use of a VH5 gene, VH32, in a Hodgkin's cell line.","authors":"C Messineo,&nbsp;R Coupland,&nbsp;A Bakhshi,&nbsp;M Raffeld,&nbsp;S G Irving,&nbsp;A Bagg,&nbsp;J Cossman","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nonrandom use of immunoglobulin variable (V) gene segments is a feature of some B-cell neoplasms, possibly as a consequence of antigen selection. In Hodgkin's disease, the primary tissues, cell lines, and even single Reed-Sternberg cells can carry immunoglobulin gene rearrangements. Here, we examined the immunoglobulin heavy-chain genes of a well-characterized Hodgkin's-derived cell line, L428, and found a hypermutated VH32 gene involving a conventional V(N)D(N)J4-C gamma 4 rearrangement. VH32 is one of two rearranging members of the VH5 family that is also rearranged preferentially in some B-cell neoplasms and familial CLL. Unexpectedly, the closest known rearranged sequence match for the rearranged VH gene of L428 was found in the single Reed-Sternberg cells of lymphocyte-predominance Hodgkin's disease, and is a mutated VH251, the only other rearranging member of the VH5 family. Assuming random usage of the human VH pool, the chance of coincident VH5 family gene rearrangement in the two cases of Hodgkin's disease is only about 10(-3). Biased use of VH genes suggests a B-cell target that is either selected by antigen or vulnerable to transformation at an early antigen-independent, developmental stage. These findings raise the question whether similar processes operate in Hodgkin's disease.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20368068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid and transient lymphocytopenia after i.v. administration of high doses of human recombinant erythropoietin.","authors":"M Buemi,&nbsp;A Allegra,&nbsp;F Corica,&nbsp;G Cavallaro,&nbsp;C Aloisi,&nbsp;G Pettinato,&nbsp;N Frisina","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The effect of administration of human recombinant erythropoietin on leukocytic cells has been evaluated. In humans the administration of 20,000 U i.v. of rHuEPO caused a rapid and transitory leukopenia that seemed to be caused by a preferential reduction of lymphocytes (2715 +/- 513 mm3 t 0; 1898 +/- 506 t 60', p < 0.002). Pretreatment with imidazole-2-hydroxybenzoate, a drug capable of inhibiting the synthesis of prostaglandins, caused a less marked and later reduction of lymphocytes (2242 +/- 477 t 0; 1560 +/- 318 t 180 minutes, p < 0.001). A less marked and later lymphocytopenia was also shown in subjects affected by chronic renal insufficiency (2907 +/- 726 t 0; 1944 +/- 512 t 180 minutes, p < 0.005).</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20368066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin inhibits IL1 alpha and TNF-alpha induction of AP-1 and NF-kB DNA-binding activity in bone marrow stromal cells.","authors":"Y X Xu,&nbsp;K R Pindolia,&nbsp;N Janakiraman,&nbsp;R A Chapman,&nbsp;S C Gautam","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We have previously demonstrated that anti-inflammatory and antioxidant compound curcumin (diferuloyl-methane) inhibits the expression of monocyte chemoattractant protein-1 (MCP-1/JE) in bone marrow stromal cells by suppressing the transcriptional activity of the MCP-1/JE gene. Since both AP-1 (TRE) and NF-kB (kB) binding motifs are present in the promoter of MCP-1/JE gene, we examined the effect of curcumin on IL1 alpha- and TNF-alpha-induced activation of ubiquitous transcription factors AP-1 and NF-kB by electrophoretic mobility shift assay and Western blotting. IL1 alpha and TNF-alpha rapidly induced both AP-1 and NF-kB DNA binding activities in +/+(-)1.LDA11 stromal cells. However, treatment of these cells with curcumin blocked the activation of AP-1 and NF-kB by both cytokines. These data suggest that inhibition of MCP-1/JE transcription by curcumin involves blocking of AP-1 and NF-kB activation by IL1 alpha or TNF-alpha.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20368073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translocations of 11q13 in mantle cell lymphoma fail to disrupt the S mu bp-2 gene.","authors":"M L Gulley,&nbsp;Q Zhang,&nbsp;R D Gascoyne,&nbsp;B R DuPont,&nbsp;P M Banks,&nbsp;C G Cho,&nbsp;J M Huang,&nbsp;E A Montalvo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We recently cloned a gene whose protein product binds to the Epstein-Barr virus BZLF1 gene promoter. The same gene has been previously cloned by another group who named it S mu bp-2 because its protein product binds to the S mu motif of the immunoglobulin heavy chain gene where it is postulated to function in immunoglobulin class switching. In the current study, we confirm that the S mu bp-2 gene is located on chromosome 11q13, a locus known to be altered by translocation in 50-70% of mantle cell lymphomas. We used Southern blot analysis to determine whether the S mu bp-2 gene was structurally rearranged in any of 25 mantle cell lymphomas. We found no evidence of rearrangement in any of these lymphomas including 18 that were proven to contain t(11;14) by cytogenetic analysis. These data suggest that structural alteration of the S mu bp-2 gene is not an underlying mechanism of tumorigenesis in mantle cell lymphomas.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1997-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20367556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-4 upregulates IL-1-induced chemokine gene expression in bone marrow stromal cells by enhancing NF-kB activation.","authors":"K R Pindolia,&nbsp;C J Noth,&nbsp;Y X Xu,&nbsp;N Janakiraman,&nbsp;R A Chapman,&nbsp;S C Gautam","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Bone marrow stromal cells play a critical role in the proliferation and differentiation of hematopoietic stem and progenitor cells by secreting numerous hematopoietic growth factors and colony-stimulating factors (CSFs). We have previously reported that monocyte chemotactic protein-1 (MCP-1 or MCP-1/JE) and interferon-inducible protein 10 KD (IP-10) are both induced in murine bone marrow stromal cell line +/(+)-1.LDA11 upon stimulation with various inflammatory agents, including IL-1 alpha, IFN-gamma, TNF-alpha, or LPS. In addition, the expression of MCP-1/JE and IP-10 mRNA by these inducers is potentiated by IL-4 and TGF-beta 1. In the present study we have investigated the mechanism of IL-4-mediated upregulation of MCP-1/JE gene expression. Our results of nuclear run-on experiments show that IL-4 enhances the IL-1-induced transcription of MCP-1/JE gene. Because the transcription of genes is regulated by DNA binding nuclear factors and binding sites for transcription factors AP-1 and SP-1, and NF-kB in the enhancer region of MCP-1/JE have been demonstrated, we examined the effect of IL-4 on the levels of these factors in stromal cells stimulated with IL-1. Whereas AP-1 and SP-1 are constitutively expressed in stromal cells, NF-kB is detected only after stimulation with IL-1. Furthermore, while unable to induce the activation of NF-kB alone, IL-4 enhanced the activation of NF-kB by IL-1. Taken together, these data suggest that upregulation of NF-kB may be the mechanism by which IL-4 increases the transcription of MCP-1/JE gene resulting in overabundance of the chemokine mRNA.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19999671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired type 2A von Willebrand disease in chronic myelocytic leukemia.","authors":"H Mohri,&nbsp;J Tanabe,&nbsp;E Yamazaki,&nbsp;M Yoshida,&nbsp;H Harano,&nbsp;M Matsuzaki,&nbsp;S Motomura,&nbsp;T Okubo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Acquired von Willebrand disease (vWD) has been described in a few patients with chronic myelocytic leukemia (CML). We present here acquired type 2 vWD associated with CML and provide characterization of an inhibitor to von Willebrand factor (vWF) from this patient. His bleeding time was prolonged. Ristocetin-induced platelet agglutination was abolished whereas botrocetin-mediated aggregation was normal. Multimeric analysis of vWF from patient's plasma showed that larger sizes of multimers were reduced. His past and family histories were negative for bleeding tendency. These results suggested that acquired type 2 vWD was present during his clinical course. The inhibitor was purified by Staphylococcal protein A, suggesting an IgG antibody. Both binding of 125I-vWF to GPIb and platelet agglutination by ristocetin were inhibited by the patient IgG with the concentrations of competing substances necessary to inhibit specific binding by 50% (IC50s) of 260 micrograms/ml and 420 micrograms/ml, respectively. However, the IgG had no effect on these studies mediated by botrocetin. The IgG only reacted with intact vWF and a 39/34 kDa fragment of vWF. These results indicate that the recognition of GPIb binding site(s) on vWF by the IgG is a central pathogenesis of acquired type 2 vWD in this case.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19845411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatal thrombotic thrombocytopenic purpura (TTP) presenting concurrently with metastatic multiple endocrine neoplasia (MEN) type I.","authors":"P A Kouides,&nbsp;P D Phatak,&nbsp;S F Cramer","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A 44-year-old women was treated for hyperparathyroidism resulting from parathyroid hyperplasia. Several months later, following a flu-like episode, she developed fever, confusion, abdominal pain, and diffuse petechiae, with severe thrombocytopenia and hemolytic anemia. She died on the 11th day of hospitalization. At autopsy she had multiple endocrine neoplasia type I, with two islet cell tumors, adrenal adenoma, pituitary adenoma, and bronchial carcinoid with liver metastasis. Florid visceral microthrombi involved arterioles and capillaries of the heart, including the conduction system. Brain, kidney, pancreas, adrenal, and portal areas of the liver were also heavily involved, but thrombi were rare in the liver sinusoids and the lungs. PAS-positive subendothelial deposits were demonstrated. In spite of the disseminated malignancy, the morphologic and laboratory findings were inconsistent with disseminated intravascular coagulation (DIC), and supported the clinical diagnosis of TTP. To the best of our knowledge this is the first report association of TTP with MEN and raises the question of a genetic linkage and/or hormonal interaction.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19845414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence of human phagocytes results in characteristic reorganization and redistribution of distinct F-actin pools.","authors":"R G Watts","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The F-actin based microfilamentous cytoskeleton (MFC) provides mobility for phagocytic immune cells including polymorphonuclear leukocytes (PMNs) and macrophages (MOs). In PMNs in suspension, the MFC is organized into two distinct F-actin pools [Triton Insoluble F-actin-(TIF), which form the sub-membranous, 3D actin meshwork and Triton Soluble F-actin (TSF), which exists as short oligomers] in equilibrium with G-actin. The structure of F-actin pools in adherent cells is unknown despite the fact that phagocytes are adherent in tissues in vivo. In order to determine the structure of F-actin pools in adherent phagocytes, human PMNs were isolated and allowed to adhere to plastic for 1 hour at 37 degrees C. Adherent cells were collected, actin pools separated and quantified by SDS-PAGE and compared to nonadherent PMNs in suspension. Likewise, the nonadherent human myeloid cell line U937 was induced to MO morphology and adherence by exposure to TPA (10(-6) M x 3 days) and similarly evaluated. Adherence of PMNs to plastic resulted in 75 +/- 15% adherence (n = 3). TPA differentiation of U937 cells resulted in 81 +/- 15% adherence (n = 10). In both cells, adherence resulted in a statistically significant increase in TIF, a decrease in TSF, and little to no change in G-actin. Basal, nonadherent PMNs in suspension contain TIF 40 +/- 0%, TSF 20 +/- 4%, and G-actin 40 +/- 4%, n = 3, whereas adherent PMNs contain TIF 61 +/- 3%, TSF 5 +/- 5%, G-actin 34 +/- 1%, n = 3. Basal U937 contain TIF 41 +/- 9%, TSF 17 +/- 6%, and G-actin 42 +/- 13%, n = 7. Adherent MO-like U937 contain TIF 53 +/- 4%, TSF 9 +/- 5%, and G-actin 38 +/- 4%. The results show that phagocyte adherence leads to a characteristic reorganization of actin pool structure that is remarkably quantitatively similar to, yet mechanistically distinct from, reorganization by chemotactic factor activation in suspension. Adherence-induced TIF-actin growth results exclusively from conversion of TSF-actin to TIF-actin.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19999675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosis and classification of the acute leukemias: recent advances and controversial issues.","authors":"C G Taylor,&nbsp;R Stasi,&nbsp;C Bastianelli,&nbsp;A Venditti,&nbsp;G Del Poeta,&nbsp;S Amadori,&nbsp;J Sargent","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Although morphology and cytochemistry continue to be the mainstay of the diagnosis of acute leukemia (AL), new developments in immunophenotyping, cytogenetics, molecular biology, and in vitro assays have dramatically improved our understanding of this disease and enabled the identification of entities with distinct clinico-biologic features. Immunophenotyping is essential for diagnosing and subclassifying acute lymphoblastic leukemia (ALL) and is also very helpful in certain types of acute myeloid leukemias (AML), such as AML with minimal differentiation or acute megakaryoblastic leukemia. Cytogenetic findings are clinically relevant for diagnosis and prognosis. Nonrandom chromosomal abnormalities such as t(15;17)(q22;q12) or t(1;19)(q23;p13) have been so closely associated with distinct types of acute leukemias that their recognition can allow diagnosis independent of the other criteria. Molecular analysis is a powerful method in the assessment of the malignant potential, clonality, and classification of the ALs. It has become clear that in some leukemias a proportion of patients exhibit the biologically relevant molecular defect in the absence of a karyotypic equivalent. On the other hand apparently uniform chromosomal abnormalities such as the t(1;19), t(9;22), t(8;14), or t(15;17) may differ at the molecular level. In vitro assays can evaluate the growth pattern and cell-cycle kinetics of leukemic cells, as well as their sensitivity to therapeutic agents. All these data are relevant to the management of AL. Because the French-American-British (FAB) classification does not fully correlate with much of this new information, alternative classifications have been proposed. In this review we concentrate on recent diagnostic contributions resulting from advances in biotechnology and discuss some of the points that arouse controversy in the single classifications.</p>","PeriodicalId":79440,"journal":{"name":"Hematopathology and molecular hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19763934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}