Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical and molecular genetic (bcl-2 gene) studies were performed on specimens from 24 patients with follicular small cleaved cell lymphoma (FSCCL), 24 patients with diffuse small cleaved cell lymphoma (DSCCL) and 4 patients with mantle zone lymphoma (MZL) to determine the cellular origin of the disease and whether or not DSCCL represents the diffuse counterpart of FSCCL. Two patients with FSCCL, 22 patients with DSCCL, and all of the patients with MZL had a phenotype of mantle zone (MZ) B-lymphocytes (SIgD+, Leu-1+, Leu-8+, positive alkaline phosphatase [ALPase+], and negative common acute lymphoblastic leukemia antigen [CALLA-]), and all the tested patients (2 patients with FSCCL, 13 patients with DSCCL, and 4 patients with MZL) had germlines of bcl-2 gene. Fourteen patients with FSCCL and 1 patient with DSCCL had a phenotype of follicular center cells (FCC) (CALLA+, SIgD-, Leu-1-, Leu-8- and negative ALPase), and 11 patients with FSCCL had bcl-2 gene rearrangements. These results indicate that FSCCL are almost always derived from FCC, whereas some FSCCL, most DSCCL, and all MZL are derived from MZ B-lymphocytes, and these lymphomas should be included in the same category as MZ B-lymphocyte-derived lymphomas. Histologically diagnosed DSCCL often may represent a diffuse counterpart of MZ B-lymphocyte-derived lymphoma. MZ B-lymphocyte-derived lymphomas histologically show a follicular (nodular), a follicular MZ, or a diffuse growth pattern and clinically show a high incidence of peripheral blood (PB) involvement or bone marrow (BM) involvement.
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PMID:Histogenesis of diffuse small cleaved cell lymphoma. An immunohistochemical and molecular genetic (bcl-2 gene) study with comparison to follicular small cleaved cell lymphoma and mantle zone lymphoma. 164 14

Recent evidence suggests that nodular lymphocyte predominance Hodgkin's disease (NLPHD) is a distinct entity that may be related to progressively transformed germinal centers, abnormal B-lymphoid hyperplasia, and low-grade B-cell lymphoma. bcl-2 is a marker for the translocation t(14;18)(q32;q21), which occurs in most follicular-derived B-cell lymphomas. Eleven cases of NLPHD and 19 cases of Hodgkin's disease of nodular sclerosis (NSHD) and mixed cellularity (MCHD) type were analyzed for immunoglobulin JH gene rearrangement. bcl-2 translocation was determined with Southern blot analysis and the polymerase chain reaction using biotin labeled probes to the major breakpoint region and the alkaline phosphatase reaction. All cases of NLPHD were negative for JH gene rearrangement and bcl-2 translocation. Cases of NSHD and MCHD were similarly negative for bcl-2, although three cases exhibited clonal JH gene rearrangements. These results confirm that a clonal B-cell population is not detected in NLPHD. Cases of NLPHD differ from most low-grade follicular B-cell lymphomas in that they lack bcl-2 gene rearrangement and t(14;18) translocation at the major breakpoint region.
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PMID:Absence of bcl-2 major breakpoint region and JH gene rearrangement in lymphocyte predominance Hodgkin's disease. Results of Southern blot analysis and polymerase chain reaction. 189 39

bcl-2 is a marker for the translocation t(14;18)(q32;q21) indicative of follicular B-cell lymphoma. We studied 115 cases of lymphoproliferative disease with the polymerase chain reaction for bcl-2 oncogene using biotin and radiolabeled probes to the major breakpoint and minor cluster regions. Twenty-three percent of B-cell lymphomas were positive for bcl-2. These included 12 of 20 cases of nodular follicular center cell lymphoma (nine small cleaved cell, one mixed small and large cell, and two large cell types). bcl-2 translocation was detected in only three of 45 cases of diffuse B-cell lymphoma, and cases of AIDS-related malignant lymphoma, monocytoid B-cell lymphoma, and mantle zone lymphoma were all negative. Nonneoplastic lymphoid proliferations were negative for bcl-2 including nine cases of abnormal follicular hyperplasia from patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. Cases of T-cell lymphoma and five cases of Hodgkin's disease were also negative. The polymerase chain reaction for bcl-2 is a rapid, sensitive technique in the evaluation of follicular B-cell proliferations, and the use of biotinylated probes and the alkaline phosphatase reaction eliminates the requirement for radioactive reagents.
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PMID:Polymerase chain reaction for bcl-2 in diagnostic lymph node biopsies. 226 90

We have investigated the precise distribution of human B-lymphocyte subpopulations (CD5+ B lymphocyte, Leu-8+ lymphocyte, immunoglobulin D (IgD)+ lymphocyte, alkaline phosphatase (ALPase)+ B lymphocyte and bcl-2 protein+ B lymphocyte) within the mantle zones (MZs) and phenotypic characterization of human CD5+ B lymphocytes using immunohistochemical techniques and flow cytometric analysis. IgD+ lymphocytes and ALPase B lymphocytes were confined to the inner layer and outer layer of the MZs of secondary follicles, respectively. CD5+ B lymphocytes and Leu-8+ B lymphocytes were mostly located in the inner layer of the MZs. Bcl-2 protein+ B lymphocytes were seen throughout the MZs. The precise distribution pattern of human B-lymphocyte subpopulations may help further understanding of the histogenesis and features of B-cell lymphomas, particularly mantle cell-derived lymphomas as well as the B-cell differentiation pathway. A minor population of CD5+ B lymphocytes expressed IgD. Almost all the CD5+ lymphocytes did not express ALPase. The data support the fact that CD5+ B lymphocytes are located more in the inner layer than in the outer layer of the MZs. Leu-8 and bcl-2 protein were detected in a large population of CD5+ B lymphocytes. In addition, Ki-67 antigen was not expressed on the CD5+ B lymphocytes. The data suggest that human CD5+ B lymphocytes may be long-living and resting (G0 and G1a stage) cells possessing the capability of continuously recirculating between blood and lymph nodes to participate in some immune responses. Moreover, Leu-8 and CD44 were detected in the majority of CD5+ B lymphocytes but intercellular adhesion molecule-1 (ICAM-1) and very late antigen-4 (VLA-4) were detected in the minority. The data may account for a high percentage of Leu-8 and CD44 expression and a low percentage of ICAM-1 and VLA-4 expression on B-chronic lymphocytic leukemia (B-CLL), which is considered to be a neoplastic counterpart of normal CD5+ B lymphocyte.
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PMID:Phenotypic characterization of human B-lymphocyte subpopulations, particularly human CD5+ B-lymphocyte subpopulation within the mantle zones of secondary follicles. 751 26

To clarify the histogenesis of B cell chronic lymphocytic leukemia (BCLL), clinicopathological and immunophenotypic studies were performed using a large panel of monoclonal antibodies on 12 cases with BCLL including three cases with prolymphocytic/chronic lymphocytic leukemia (CLL/PL). Immunophenotypically, CD19 and CD20 were positive for all cases of this series and CD5, CD21, CD22, CD23, CD25, CD38, Leu-8, KB-61, and bcl-2 protein were expressed in variable proportion from case to case. CD10, however, did not react. No alkaline phosphatase (ALP) positive cases were found. The phenotype of BCLL was similar to that of B cells of the mantle zone (MZ) of secondary follicle in the lymph node. It is therefore postulated that the neoplastic cells of BCLL in these cases might be derived from B cells of the MZ. Moreover, the cells possibly originated from the lymphocytes located in the inner layer of the MZ, since ALP+ B cells are usually observed in the outer layer of the MZ. The pseudofollicular (PF) pattern was observed in four biopsied lymph nodes among five cases tested, but no such a pattern in an aspiration clot of bone marrow. These four cases consisted of three cases with CLL and a case with CLL/PL. The immunohistochemical study showed that there were many proliferating cells showing Ki-67+ in the PF area of the lymph nodes. In these cases, leukemic cells might have developed from the PF area of the lymph node.
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PMID:Clinicopathological and immunophenotypic studies on 12 cases with B cell chronic lymphocytic leukemia. 783 79

There are conflicting data regarding the detection of t(14;18) in reactive lymphoid hyperplasia (RLH) by the polymerase chain reaction (PCR). Although most studies have not detected t(14;18), several groups have definitively shown that a very low number of cells with this translocation (one in 10(5) to 10(6)) are present in a significant proportion of follicular hyperplasias. Review of the methods from these series reveals that modifications of the PCR assay (ie, enhanced sensitivity steps such as seminesting, lengthy autoradiographic exposure times, multiple aliquot reactions of single samples, and/or high concentrations of template DNA) are probably necessary to detect t(14;18) in RLH. We evaluated a diverse set of 111 RLH (85 lymph nodes, 22 tonsils, and four other sites) from patients of different age groups (age range, 9 months to 80 years) to determine if a standard PCR assay would amplify t(14;18). Of these, 61 (55%) specimens had a prominent follicular hyperplastic component. Fifty-seven follicular lymphomas served as a control group. Polymerase chain reaction was performed as a single-run, two-primer-based assay for major breakpoint region bcl-2 translocations (5' major breakpoint region primer and 3' immunoglobulin heavy-chain gene-joining region consensus primer). Two different types of thermocyclers were employed. A metal block thermocycler was used with 35 cycles of amplification on 500 ng to 1 micrograms of genomic DNA, and a separate air thermocycler was used with 45 cycles of amplification on 50 ng of genomic DNA. Product detection was carried out through ethidium bromide staining and UV gel illumination, along with a digoxigenin-alkaline phosphatase-based, internal major breakpoint region oligonucleotide probe system. We found no amplified t(14;18) products in any RLH. In contrast, 36 (63%) of 57 follicular lymphomas showed t(14;18) (published range for detection of major breakpoint region translocations by PCR, 31% to 74%). Moreover, the assay's sensitivity, estimated through dilution studies, was to one in 10(4) to 10(5) cells. Although theoretically possible, our data suggest that there is practically no risk of amplifying a t(14;18) from RLH when utilizing a standard PCR assay.
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PMID:Standard polymerase chain reaction analysis does not detect t(14;18) in reactive lymphoid hyperplasia. 806 Feb 26

PCR product sizing on ethidium bromide-stained gels, coupled with Southern transfer and hybridization with nonisotopic probes, is an effective way of detecting t(14;18)(q32;q21). We evaluated an alternative ELISA-based test for detecting amplified t(14;18) products. Digoxigenin (DIG)-labeled dUTP is incorporated in a standard PCR method for amplification of bcl-2 major breakpoint region (mbr) rearrangements. The product is hybridized to a specific biotinylated DNA probe internal to the mbr primer, placed in streptavidin-coated wells of a microtiter plate, and detected with a alkaline phosphatase-conjugated anti-DIG antibody and enzyme substrate (pNpp). The colorimetric product is quantitated by an automated optical density (O.D.) reader. We evaluated 13 mbr-positive follicular lymphomas (FL), five mbr-negative B-cell neoplasms (BCN), 16 reactive lymphoid hyperplasias (RLH), 14 cases of Hodgkin's disease (HD), and normal peripheral blood samples from 20 healthy volunteers. All samples were evaluated in duplicate on separate plates. Positive [t(14;18)-containing cell line] and negative [cell line without t(14;18); master mix only] controls, and a standard curve were included with each run. Numerical O.D. readings from the specific hybridization assays revealed differences between FL and the other categories. All FL had an O.D. reading at > 2.0. The vast majority of RLH, HD, BCN, and normal peripheral blood samples showed O.D. readings well below 2.0. Specifically, 13/16 RLH and all HD, BCN, and normal peripheral blood samples had an O.D. of < or = 0.6 in all runs. The three outliers, which were all < 2.0, may represent the low level detection of t(14;18)-containing cells in RLH similar to previous reports. Moreover, all but four RLH had O.D. readings above the background negative controls, suggesting that rare t(14;18)-containing cells may have been present in these samples, as well. Dilution studies estimate that this assay is capable of detecting 1 t(14;18)-containing cell in approximately 10(5) cells, a greater level of sensitivity than can be obtained with gel visualization alone. We conclude that this semi-automated, potentially quantifiable ELISA-based system is a useful, objective and reproducible alternative hybridization procedure for verifying PCR product specificity in this setting.
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PMID:Semi-automated ELISA-based detection system for verifying the authenticity of amplified t(14;18)-containing products. 872 98

Cytokine-driven activation of hepatic stellate cells (HSC) in tissue injury and inflammation is a key pathogenetic event in liver fibrogenesis leading to an expanded pool of matrix producing myofibroblasts (MFB) which represent the transformed counterpart of HSC. We hypothesize that expansion of the pool of MFB might also be accomplished by modulation of apoptosis, which plays an opposite and complementary role to mitosis in the cellular homeostasis. We characterized the susceptibility of HSC in primary culture and of MFB in secondary culture to apoptosis induced by the soluble Fas ligand (sFasL) and related the effects to the expression levels of Fas (APO-1/CD95) and some major proapoptotic and contra-apoptotic protooncogenes. MFB showed a dose-dependent apoptotic reaction upon exposure to sFasL as evidenced by a strong increase of nucleosomal DNA fragments, loss of cellular DNA, positive TUNEL reaction, and annexin staining. The effect was found only if protein synthesis (cycloheximide) or RNA synthesis (actinomycin D) were arrested. HSC maintained for various times in primary culture were completely resistant to sFasL in combination with cycloheximide, but in late primary cultures (day 7 onward) an increasing susceptibility to sFasL-mediated apoptosis was developed. By semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis and alkaline phosphatase-anti-alkaline phosphatase staining Fas receptor was identified both in HSC and MFB at comparable expression levels. The expression of the contra-apoptotic protooncogenes bcl-2 and bcl-xl was found to be much stronger in early HSC than in late HSC and MFB as shown by ribonuclease protection assay. The expression of bcl-2 was additionally confirmed by semiquantitative RT-PCR and immunoblotting. Proapoptotic bax was found in comparable quantities at the RNA level in HSC and MFB but at the protein level MFB showed increased bax expression. It is concluded that transformation of HSC to MFB is paralleled by an increasing sensitivity to sFasL-mediated apoptosis, which might be related to a strong decrease of bcl-2 and bcl-xl expression, leading to a preponderance of proapoptotic gene expression in MFB. Modulation of apoptotic susceptibility of transforming HSC could be an important complementary pathway in the pathogenesis of fibrosis.
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PMID:Transformation-dependent susceptibility of rat hepatic stellate cells to apoptosis induced by soluble Fas ligand. 969 16

Bcl-2 expression has been studied extensively in a variety of human tumors. However, there are lack of clinical data in regard to its expression in germ cell testicular tumors (GCTTs). In this study we screened bcl-2 expression in 70 patient with GCTTs using the immunohistochemistry (IHC) and streptavidin biotin alkaline phosphatase method. Furthermore, we correlated this expression with metastatic behaviour and clinical stage. Overall, 41 (58%) carcinomas stained with anti-bcl-2 (DAKO-124) monoclonal antibody, By histologic type, these lesions included 11 (42.3%) of 26 seminomas (S) and 30 (68.18%) of 44 non seminomatous germ cell testicular tumors (NSGCT). The incidence of bcl-2 immunostaining was higher (P = 0.05, two-tailed, Fisher's test) in NSGCT than in seminomas. Bcl-2 expression was higher in tumors from metastatic patients than in tumors from metastatic-free patient (p = 0). There was a significant difference between the three stages of disease as to the expression of bcl-2 (chi 2 = 0). High level of bcl-2 was clearly dominant in tumors of advanced stages. The present finding revealed that bcl-2 expression occurs in GCTTs. Further, they suggested that bcl-2 is associated with a more progressed malignant phenotype in these tumors.
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PMID:[Bcl-2 expression in testicular cancer in relation to tumor progression]. 975 78

Breast cancer is associated frequently with skeletal metastases, which cause significant morbidity. The main mechanism is an increase in osteoclast-mediated bone resorption. We postulated that osteoblasts could be other essential target cells and previously showed that conditioned medium (CM) of breast cancer cells (BCCs) inhibits the proliferation of osteoblast-like cells. In this study, we investigated the effects of BCC-secreted products on osteoprogenitor cells using a clonal fetal human bone marrow stromal preosteoblastic cell line (FHSO-6) that expresses alkaline phosphatase (ALP) activity, type I collagen (COLI), and increased osteocalcin (OC) and osteopontin under treatment with dexamethasone (Dex), 1,25-dihydroxyvitamin D [1,25(OH)2D], or recombinant human bone morphogenetic protein 2 (rhBMP-2). Treatment with MCF-7 CM inhibited FHSO-6 cell survival in a dose-dependent and irreversible manner. Morphological investigation indicated that MCF-7 CM increased both apoptotic and necrotic cell number. MCF-7 CM increased caspases activity and a broad inhibitor of caspase activity (benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone [z-VAD-fmk]) partly reversed the CM-induced inhibition of FHSO-6 cell survival. Western blot analyses revealed an increased bax/bcl-2 ratio in MCF-7 CM-treated FHSO-6 cells. MCF-7 cells exhibit FasLigand as membrane-bound protein and as a soluble cytokine in the CM. Deprivation of MCF-7 CM from active FasLigand by saturation with a soluble Fas molecule suppressed the induction of FHSO-6 apoptosis, whereas fibroblast CM, which did not contain FasLigand, only weakly modified FHSO-6 cell survival because of increased cell necrosis. These data indicate that FasLigand secreted by BCCs induces apoptosis and necrosis of human preosteoblastic stromal cells through caspase cascade modulated by the bax and bcl-2 protein level. The induction of apoptosis in human bone marrow stromal cells by BCCs may contribute to the inappropriately low osteoblast reaction and bone formation during tumor-induced osteolysis in bone metastases.
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PMID:Breast cancer cells release factors that induced apoptosis in human bone marrow stromal cells. 1154 30


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