Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has recently been demonstrated that luminal exposure of airway segments in vitro to HOCl produces airway muscle hyperresponsiveness to substance P and a decrease in neutral endopeptidase (NEP) activity of tissue segment homogenates, suggesting that HOCl may decrease airway epithelial cell NEP activity. To confirm that this effect occurs in humans and to investigate possible subcellular mechanisms for it, we assessed HOCl exposure of the human airway epithelial cell line Calu-1. These cells, grown to confluency in Dulbecco's modified Eagle medium with 10% fetal bovine serum and penicillin-streptomycin, were exposed in situ for 5 min to 100 microM HOCl in a phosphate-buffered saline solution (PBS; pH 7.0 at 37 degrees C) or to PBS alone. Thereafter, cells were rinsed and assayed for NEP activity employing reverse-phase high-pressure liquid chromatography. This activity was characterized by the generation of phosphoramidon-inhibitable product (ANA) cleaved from the synthetic substrate succinyl-(ala)3-p-nitroaniline during a 30 min incubation at 37 degrees C. Cell viability was assessed by changes in LDH release, trypan blue exclusion, and cell volume. In some experiments, crude plasma membrane and soluble components of exposed cells were isolated and differential NEP activity was assayed. We found that a 5 min exposure to HOCl decreased whole cell NEP activity from 74.1 +/- 4.4 (mean +/- SE) to 54.3 +/- 6.0 pmoles of ANA/min/10(6) cells (p less than 0.05), while no parameter of cell viability was affected. NEP activity in the crude membrane fraction decreased 36.3 +/- 3.1% after exposure (p less than 0.01), whereas NEP activity in the soluble fraction increased 4.0 +/- 0.6%. Isolated membrane NEP exposed by itself was not affected. Subsequent experiments with reducing agents demonstrated that NEP activity of cell cultures pretreated with 100 mM of either beta-mercaptoethanol or dithiothrietol before HOCl exposure was not significantly different from control values. We conclude that whole cell HOCl exposure decreases Calu-1 plasma membrane NEP. This loss appears to occur by internalization of cell membrane NEP.
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PMID:HOCl exposure of a human airway epithelial cell line decreases its plasma membrane neutral endopeptidase. 166 4

We examined the expression of cell-surface interleukin-2 (IL-2) receptor (Tac antigen) on peripheral blood leukemic cells and measured soluble IL-2 receptor p55(alpha) chain (sIL-2R) levels in sera from chronic myelogenous leukemia (CML) patients with blastic crisis. Flow cytofluorometric analysis performed by dual immunofluorescence in three cases demonstrated coexpression of Tac antigen with myeloid (CD13, CD14, or CD33) or lymphoid (CD10) antigen on significant proportions of peripheral blood leukemic cells. Radiolabeled IL-2-binding assay demonstrated the specific IL-2 binding sites in three cases examined. The exogenous IL-2, however, failed to induce proliferative response. A myeloid cell line, Yut-K3, established from peripheral blood leukemic cells from a CML patient with blastic crisis, also expressed cell-surface Tac antigen and CD13 concurrently. SIL-2R assay showed that Yut-K3 released a detectable amount of sIL-2R in its culture supernatant. The serum sIL-2R levels were significantly elevated (range: 2,580 to 172,000 U/mL) in 12 CML patients with blastic crisis and were slightly elevated in ten patients in chronic phase (range: 250 to 820 U/mL) and in three in accelerated phase (range: 790 to 1,305 U/mL) compared with those in 24 normal controls (range: 70 to 695 U/mL, P less than .01). These results indicated that the leukemic cells from CML patients with blastic crisis expressed and released IL-2 receptor (Tac antigen). Longitudinal studies performed in three cases of CML with blastic crisis showed that the change of serum sIL-2R level was closely associated with that of the number of peripheral blood leukocytes and blasts, the percentage of blasts and serum LDH levels, also suggesting that the serum sIL-2R level is a useful clinical indicator of the leukemic cell burden in vivo.
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PMID:Elevated serum-soluble interleukin-2 receptor (Tac antigen) levels in chronic myelogenous leukemia patients with blastic crisis. 278 81

An 83-year-old male was admitted with a right pleural effusion and generalized lymphadenopathy. Serum LDH level was elevated to 801 IU/L, and the pathological diagnosis from inguinal lymph node needle biopsy was malignant lymphoma (ML) of diffuse, large cell, non-cleaved type, according to the working formulation. The surface phenotypes of the malignant cells from the pleural effusion were analyzed by a fluorescent-activated cell sorter with a panel of monoclonal antibodies (MAbs). The ML cells coexpressed antigens detected by MAbs CD10 (CALLA), CD19, CD20, CD22, CD24, CD38, Ia, c-neu and surface immunoglobulin G kappa. A high expression of NRAS p21 was also detected by cytoplasmic immunofluorescence technique. The patient died 19 days later despite a combination of chemotherapy and intensive supportive therapy. From these findings it seems that c-neu may be a prognostic indicator not only for breast cancers but also for lymphoproliferative disorders. Further accumulation of such cases is needed.
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PMID:[Aggressive diffuse lymphoma with malignant pleural effusion expressing c-erbB-2 (neu) oncogene products]. 810 89

A total of 119 children (1990-95) with acute lymphoblastic leukemia (ALL) B-lineage either CD10+ or CD10- were registered into a single non-randomized chemotherapy protocol. Only untreated patients with standard risk were included in the study. Their ages ranged from 1.8-10 years with a mean of 5.1 years. There were 82 (68%) children with early pre B-All, 35 (29%) with pre B-ALL and 2(1.6%) with transitional pre B-ALL (p < 0.00001). The patients were divided according to CD10 reactivity, either + (94 children) or -(25 patients). The event-free survival (EFS) at 60 months for the CD10+ children was of 78% (alive 73/94), while for the CD10- was 71% (alive 18/25) (p = 0.6) and 74% for both groups. The factors that influenced favorably the survival in the CD10+ group were the age between 3 to 5.99 years (p < 0.00001), sex (either male or female), leukocyte count between 10-24.9 x 10(9)/l (p < 0.00001), LDH under 300 U/I (p < 0.00001) and L1 bone marrow cytomorphology (p < 0.00001). In the CD10- patients, the EFS was favorably influenced by the female sex (p = 0.04), leukocyte count under 10 x 10(9)/l (p = 0.05) and LDH < 300 U/l (p = 0.02). CNS infiltration was documented in 4.2% (5/119). Mortality secondary to chemotherapy was seen in 7%. In conclusion, this is the first large series in Mexican children with B-lineage ALL published. Because of the relatively small number of patients in each group (pre B and transitional pre B), all the patients in the current series were treated alike. When the 119 patients were divided only on the basis of CD10 reactivity, the EFS for both groups (CD10+ and-) was similar; therefore, the reactivity to CD10 has no prognostic value in this type of ALL.
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PMID:B-lineage acute lymphoblastic leukemia of childhood. An institutional experience. 920 15

An 82-year-old man was admitted to our hospital in September 1996 due to dysphagia and cardiomegaly. Physical examination detected the fourth heart sound and a Levine III/VI systolic murmur in the cardiac apex. Surface lymph nodes were not palpable. LDH 662 IU/I was detected by laboratory examinations, and ultrasound cardiography showed grade 3 mitral regurgitation. Computed tomography revealed a huge mass in the posterior mediastinum, pressing the heart from the posterior direction. Thereafter, a left pleural effusion developed and aspiration was performed. Cytological examination of the fluid showed clusters of lymphoid cells with a positive immunophenotype for CD10, CD19 and HLA-DR. Chromosome analysis revealed complex abnormal karyotypes including t(8;14) (q24;32). A diagnosis of B cell lymphoma was made, and combination chemotherapy consisting of cyclophosphamide, THP-adriamycin, vincristine, and prednisolone was initiated. The patient's mass disappeared promptly, and his mitral reguration subsided. We reported this case because malignant lymphoma of the posterior mediastinum is rare, and because we are unaware of any previous reports of malignant lymphoma causing acute mitral regurgitation.
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PMID:[Acute mitral regurgitation caused by malignant lymphoma of the posterior mediastinum]. 978 80

We report on a series of 26 patients diagnosed with primary (de novo) plasma cell (PC) leukemia (PCL) in whom we analyzed the clinicobiologic characteristics of the disease together with the immunophenotype, DNA cell content, proliferative index, and numeric chromosomal aberrations of the neoplastic PC, and compared them with 664 multiple myeloma (MM) patients at diagnosis. The median age, sex ratio, and bone lesion extension were similar, but PCL cases displayed a higher prevalence of clinical stage III, extramedullary involvement, and Bence Jones cases, with fewer IgA cases than for MM patients. In addition, according to several prognostic indicators (beta2-microglobulin serum level, proportion of S-phase PCs, proteinuria, calcium serum level, lactate dehydrogenase [LDH] and renal function), the incidence of adverse prognostic factors was significantly higher in PCL versus MM. Immunophenotypic expression was similar for CD38, CD138, CD2, CD3, CD16, CD10, CD13, and CD15, but PCL differed from MM in the expression of CD56, CD9 HLA-DR, CD117, and CD20 antigens. Twenty-two PCL cases were diploid and one was hypodiploid, while most MM cases (57%) showed DNA hyperdiploidy. With the fluorescent in situ hydridization (FISH) technique, 12 of 13 PCL cases displayed the numeric aberrations, -13 (86%), +/-1 (57%), +18 (43%), and -X in women (25%), but they lacked several numeric aberrations usually found in MM such as +3, +6, +9, +11, and +15. PCL cases had a lower overall response to therapy than MM cases (38% v 63%, P =.01332). Among PCL patients, a trend for a worse response was observed in cases treated with melphalan and prednisone (MP) versus polychemotherapy. Overall survival was significantly worse in PCL versus MM patients (8 v 36 months, P <.0001), but it was significantly better in PCL patients treated with polychemotherapy versus MP (18 v 3 months, P =.0137). By contrast, MM patients did not show significant differences in overall survival according to the treatment used, MP or polychemotherapy. Ten variables seemed to predict survival in PCL patients, but only the beta2-microglobulin level and S-phase PCs retained an independent value in multivariate analysis. In summary, our study illustrates that PCs from PCL display singular phenotypic, DNA cell content, and cytogenetic characteristics that lead to a different disease evolution versus MM.
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PMID:Primary plasma cell leukemia: clinical, immunophenotypic, DNA ploidy, and cytogenetic characteristics. 1061 Jan 15

A minority of centroblastic and centroblastic/centrocytic cell lymphomas are accompanied by a prominent epithelioid cell response and were suggested to be a distinct variant of B-cell lymphoma of germinal center cell origin. To confirm the clinicopathologic significance of these mainly large B-cell lymphomas with an epithelioid cell response (LBCL-ER), we reviewed 50 patients with LBCL-ER and compared the results with those of 167 other diffuse large B-cell lymphomas (DLBCL) and 94 follicular lymphomas (FL) without epithelioid response. The patients with LBCL-ER showed a higher age distribution (median 71, P =.03), a female predominance (M:F = 18:32, P =.001) and less frequent involvement of extranodal sites >1 (P =.004) compared with those with DLBCL, and presented with a bulky mass of the affected lymph nodes in 54% of cases. They were also older (P =.0006) and more associated with the aggressive clinical factors such as serum LDH level and International Prognostic Index score than those with FL. Histologically, nine cases (18%) partially showed a follicular growth pattern, and the others (82%) were occupied by a diffuse growth pattern. The epithelioid cells were accumulated in large demarcated masses, partially imparting a lymphoepithelioid (Lennert) lymphoma-like appearance to some portions of the lesions in every case. Immunohistochemically, LBCR-ER was positive for CD20 in every case, CD10 in 43% of the cases, and BCL-2 in 56%. None of the tumor cells in the 40 cases tested expressed CD5 antigen. Immunostaining also often highlighted the remnants of the follicular dendritic cell network. The BCL-2 gene rearrangement was detected in only 19% of the cases examined. The survival curve of the cases of LBCL-ER was almost identical with that of DLBCL and was significantly inferior to that of FL. The centroblastic and centroblastic/centrocytic lymphoma with an epithelioid cell response may be regarded as the morphologic variant of DLBCL preferentially arising in the aged population and reflecting the disease progression of FL.
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PMID:Centroblastic and centroblastic/centrocytic lymphoma associated with a prominent epithelioid granulomatous response: a clinicopathologic study of 50 cases. 1211 13

A 43-year-old female was admitted with therapy-resistant pancreatitis and an abdominal tumor around the pancreatic head. Laboratory data revealed leukocytosis with a white blood cell count of 18200/microl, 25% atypical cells and an LDH of 13410 IU/l. The bone marrow was comprised of 78.4 percent lymphoblastoid cells which were positive for CD10, CD19 and CD20, and the cytogenetic study of which demonstrated the presence of t(8;14) (q24;q32) and t(14;18) (q32;q21) in the same clone. The patient was diagnosed as having Burkitt's lymphoma (BL) with t(8;14) and t(14;18). Although CODOX-M and IVAC therapy combined with rituximab achieved complete remission, she died of rapid progressive disease during whole brain irradiation before autologous peripheral blood stem cell transplantation. Even if the intensive chemotherapy with rituximab is given adequately, durable remission may not be achieved in BL with translocation of t(8;14) and t(14;18). A more effective therapy remains to be established for the treatment of this disease.
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PMID:[Early relapse of Burkitt's lymphoma with t(8;14) and t(14;18) after rituximab-combined CODOX-M and IVAC therapy]. 1751 25

Clinicopathological and immunophenotypical characteristics in 24 patients with diffuse large B-cell lymphoma (DLBCL) under 30 years of age in Osaka, Japan were examined, and the results compared to those of DLBCL patients aged over 40 years in Osaka and of young DLBCL patients in Western countries. The level of LDH and IPI score at initial diagnosis were significantly lower in young than older patients. The sex ratio (M:F) and age range (median) in the young and older groups were 1.18 and 11-30 (24.8) years and 1.59 and 42-87 (62.4) years, respectively. Extranodal presentation was higher in the young group (83.3% versus 60.0%, P < 0.05). Based on immunophenotyping with anti-CD10, bcl-6, and MUM1 antibodies, the cases were categorized as germinal center B-cell (GCB) (CD10+ or CD10-, bcl-6+, MUM1+) or non-GCB phenotype. The frequency of GCB type was significantly lower in the young group than older group (25% vs. 54%, P < 0.05), and much lower than that reported for young patients in Western countries. In situ hybridization revealed one of the young patients to be positive for Epstein-Barr virus (EBV). In the older group, none of 31 cases showed EBV positivity. Three year event-free and overall survival rates of young patients were better than those of the older patients, although not significantly different. DLBCL in the young in Japan is characterized by a much lower frequency of the GCB phenotype compared to that in Western countries.
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PMID:Diffuse large B-cell lymphoma in the young in Japan: a study by the Osaka Lymphoma Study Group. 1757 93

CD5-negative chronic B cell lymphoproliferative disorders in leukemic phase (B-CLPD) are heterogeneous and relatively uncommon pathologies that often lack a histopathological definition because of the absence of accessible pathological tissue. We describe the clinical features and evolution-related variables of 156 patients with CD5/CD10-negative B-CLPD (median age 66 years, range 25-86). The median follow-up was 51 months (range 6-216), and overall 3- and 5-year survival was respectively 87 and 76%; 50 patients needed therapy at diagnosis, 56 during follow-up, and 50 remained untreated until the last control. A combined clinical, histological, cytomorphological, immunophenotypical, and cytogenetic diagnostic approach allowed the complete classification of only a minority of patients as being affected by splenic marginal zone or lymphoplasmacytic lymphoma; the majority of cases remained unclassifiable. Multivariate analysis showed that the clinicohematological variables adversely related to overall survival were serum LDH levels and age, whereas high serum LDH levels, hemoglobin levels of <11 g/dl, and splenomegaly related to treatment-free time (in "wait and see" cases); only splenomegaly related to time to progression (in treated patients). In conclusion, our retrospective study describes the clinical features and variables related to evolution in a large group of patients with CD5/CD10-negative chronic B-cell lymphoid leukemias and underlines the fact that a probable lymphoplasmacytic or marginal zone normal cell origin can be supposed in such leukemic forms, but never surely demonstrated.
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PMID:A multicenter retrospective clinical study of CD5/CD10-negative chronic B cell leukemias. 1838 27


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