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91.
ALK Expression Defines a Distinct Group of T/Null Lymphomas (“ALK Lymphomas”) with a Wide Morphological Spectrum
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Brunangelo Falini Barbara Bigerna Marco Fizzotti Karen Pulford Stefano A. Pileri Georges Delsol Antonino Carbone Marco Paulli Umberto Magrini Fabio Menestrina Roberto Giardini Silvana Pilotti Alessandra Mezzelani Barbara Ugolini Monia Billi Alessandra Pucciarini Roberta Pacini Pier-Giuseppe Pelicci Leonardo Flenghi 《The American journal of pathology》1998,153(3):875-886
The t(2;5)(p23;q35) translocation associated with CD30-positive anaplastic large cell lymphoma results in the production of a NPM-ALK chimeric protein, consisting of the N-terminal portion of the NPM protein joined to the entire cytoplasmic domain of the neural receptor tyrosine kinase ALK. The ALK gene products were identified in paraffin sections by using a new anti-ALK (cytoplasmic portion) monoclonal antibody (ALKc) that tends to react more strongly than a previously described ALK1 antibody with the nuclei of ALK-expressing tumor cells after microwave heating in 1 mmol/L ethylenediaminetetraacetic acid buffer, pH 8.0. The ALKc monoclonal antibody reacted selectively with 60% of anaplastic large cell lymphoma cases (60 of 100), which occurred mainly in the first three decades of life and consistently displayed a T/null phenotype. This group of ALK-positive tumors showed a wide morphological spectrum including cases with features of anaplastic large cell lymphoma “common” type (75%), “lymphohistiocytic” (10%), “small cell” (8.3%), “giant cell” (3.3%), and “Hodgkin’s like” (3.3%). CD30-positive large anaplastic cells expressing the ALK protein both in the cytoplasm and nucleus represented the dominant tumor population in the common, Hodgkin’s-like and giant cell types, but they were present at a smaller percentage (often with a perivascular distribution) also in cases with lymphohistiocytic and small cell features. In this study, the ALKc antibody also allowed us to identify small neoplastic cells (usually CD30 negative) with nucleus-restricted ALK positivity that were, by definition, more evident in the small cell variant but were also found in cases with lymphohistiocytic, common, and “Hodgkin’s-like” features. These findings, which have not been previously emphasized, strongly suggest that the neoplastic lesion (the NPM-ALK gene) must be present both in the large anaplastic and small tumor cells, and that ALK-positive lymphomas lie on a spectrum, their position being defined by the ratio of small to large neoplastic cells. Notably, about 15% of all ALK-positive lymphomas (usually of the common or giant cell variant) showed a cytoplasm-restricted ALK positivity, which suggests that the ALK gene may have fused with a partner(s) other than NPM. From a diagnostic point of view, detection of the ALK protein was useful in distinguishing anaplastic large cell lymphoma cases of lymphohistiocytic and small cell variants from reactive conditions and other peripheral T-cell lymphoma subtypes, as well as for detecting a small number of tumor cells in lymphohemopoietic tissues. In conclusion, ALK positivity appears to define a clinicopathological entity with a T/null phenotype (“ALK lymphomas”), but one that shows a wider spectrum of morphological patterns than has been appreciated in the past. 相似文献
92.
A Cecile J W Janssens Yurii S Aulchenko Stefano Elefante Gerard J J M Borsboom Ewout W Steyerberg Cornelia M van Duijn 《Genetics in medicine》2006,8(7):395-400
PURPOSE: There is ongoing debate about whether testing low-risk genes at multiple loci will be useful in clinical care and public health. We investigated the usefulness of multiple genetic testing using simulated data. METHODS: Usefulness was evaluated by the area under the receiver-operating characteristic curve (AUC), which indicates the accuracy of genetic profiling in discriminating between future patients and nonpatients. The AUC was investigated in relation to the number of genes assumed to be involved, the risk allele frequency, the odds ratio of the risk genotypes, and to the proportion of variance explained by genetic factors as an approximation of the heritability of the disease. RESULTS: We demonstrated that a high (AUC > 0.80) to excellent discriminative accuracy (AUC > 0.95) can be obtained by simultaneously testing multiple susceptibility genes. A higher discriminative accuracy is obtained when genetic factors play a larger role in the disease, as indicated by the proportion of explained variance. The maximum discriminative accuracy of future genetic profiling can be estimated at present from the heritability and prevalence of disease. CONCLUSIONS: Genetic profiling may have the potential to identify individuals at higher risk of disease depending on the prevalence and heritability of the disease. 相似文献
93.
PG-M1: A New Monoclonal Antibody Directed against a Fixative-Resistant Epitope on the Macrophage-Restricted Form of the CD68 Molecule 总被引:9,自引:6,他引:9
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Brunangelo Falini Leonardo Flenghi Stefano Pileri Marcello Gambacorta Barbara Bigerna Horst Durkop Florian Eitelbach Juergen Thiele Roberta Pacini Antonio Cavaliere Massimo Martelli Nadia Cardarelli Elena Sabattini Simonetta Poggi Harald Stein 《The American journal of pathology》1993,142(5):1359-1372
A new anti-macrophage monoclonal antibody (PG-M1) was produced by immunizing BALB/c mice with fresh spleen cells from a patient with Gaucher's disease. PG-M1 reacts strongly with a fixative-resistant epitope of an intracytoplasmic molecule, selectively expressed by virtually all macrophages of the human body. Although attempts to immunoprecipitate the molecule recognized by PG-M1 have failed so far, the reactivity of the antibody with COS-1 and WOP cells transfected with a human complementary DNA clone encoding for the CD68 antigen suggests that PG-M1 is a new member of the CD68 cluster. However, unlike other CD68 antibodies (KP1, EBM11, etc.), which react with both macrophages and myeloid cells, PG-M1 detects a fixative-resistant epitope on the macrophage-restricted form of the CD68 antigen. In 957 routinely fixed, paraffin-embedded samples, PG-M1 showed a more restricted reactivity with elements of the monocyte/macrophage lineage than the previously described monoclonal antibodies MAC-387 (anti-calgranulins), KP1 (CD68) and Ki-M1P. Among hematological malignancies, PG-M1 only labels acute leukemias of M4 and M5 type and rare examples of malignant histiocytosis/true histiocytic sarcoma. In contrast, acute leukemias of the M1, M2, M3, M6, M7, and L1-L3 types, non-Hodgkin's lymphomas, and Hodgkin and Reed-Sternberg cells of Hodgkin's disease are consistently PG-M1-negative. In the daily diagnostic practice, PG-M1 seems to be particularly valuable for the diagnosis of myelomonocytic or monocytic leukemia and neoplasms of true histiocytic origin in routine paraffin sections. 相似文献
94.
Comparative Evaluation of Ligation-Mediated PCR and Spoligotyping as Screening Methods for Genotyping of Mycobacterium tuberculosis Strains 总被引:3,自引:0,他引:3
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Stefano Bonora M. Cristina Gutierrez Giovanni Di Perri Francesca Brunello Benedetta Allegranzi Marco Ligozzi Roberta Fontana Ercole Concia Veronique Vincent 《Journal of clinical microbiology》1999,37(10):3118-3123
Spoligotyping has been suggested as a screening test in multistep genotyping of Mycobacterium tuberculosis strains. Relying on restriction fragment length polymorphism (RFLP) analysis with IS6110 (IS6110 RFLP analysis) as a "gold standard," we performed a comparative evaluation of spoligotyping and ligation-mediated PCR (LMPCR), a recently described PCR-based typing method, as rapid screening tests for fingerprinting of 158 M. tuberculosis strains collected in Verona, Italy. LMPCR seemed to be comparable to spoligotyping in terms both of feasibility with rapidly extracted DNA and of generation of software-analyzable images. Moreover, LMPCR grouped considerably fewer strains than spoligotyping (38 versus 67%) and was found to reduce the cluster overestimation rate (26.3 versus 58%) and to give a better discriminatory index (0.992 versus 0.970) compared to spoligotyping. In our geographical region, where there was no evidence of clustered strains carrying fewer than six IS6110 copies, LMPCR was found to be more discriminatory than spoligotyping. We also evaluated two models of three-step typing strategies, involving the use of spoligotyping and LMPCR as screening methods and IS6110 RFLP analysis as a further supporting test. LMPCR proved to be a more effective first-step test than spoligotyping, significantly reducing the need for subtyping. LMPCR should be considered an alternative to spoligotyping as a rapid screening method for M. tuberculosis fingerprinting, particularly in areas with a low prevalence of M. tuberculosis strains carrying few copies of IS6110. 相似文献
95.
Ricci V Filocamo M Regis S Corsolini F Stroppiano M Di Duca M Gatti R 《American journal of medical genetics. Part A》2003,(1):84-87
Hunter syndrome (Mucopolysaccharidosis type II) is a rare X-linked recessive lysosomal storage disorder caused by the deficiency of the enzyme iduronate-2-sulfatase (IDS). To date, more than 200 different mutations have been reported in the IDS gene, located on Xq27.3-q28. Here, we report two new mutations (M488I and G489A) identified in hemizygosity in an Italian Hunter patient. Their "in vitro" expression by COS 7 cells was carried out in order to evaluate their functional consequence on enzyme activity as well as their possible cumulative effect on the malfunctioning of the protein. The results obtained enabled us to confirm the G489A mutation as causative. The M488I mutation, however, could not be unequivocally considered as causing disease because of its residual activity. Although a cumulative effect of the two mutations can be excluded "in vitro," we are cautious about drawing a conclusion with regard to the possible role that the two mutations could have played "in vivo" in modulating the phenotype of the patient. Finally, the knowledge of the molecular defect of the patient has enabled us to identify the carriers, providing reliable genetic counselling to the females of the family. 相似文献
96.
Lucia MB Rutella S Leone G Larocca LM Vella S Cauda R 《Journal of acquired immune deficiency syndromes (1999)》2002,30(4):369-378
P-glycoprotein (P-gp) transports a wide range of structurally unrelated drugs, such as HIV protease inhibitors (PIs) and cytotoxic compounds such as anthracyclines. Because modification of P-gp phenotype and function is an important underlying mechanism of drug interactions, the current study was conducted in order to evaluate whether highly active antiretroviral therapy (HAART), HIV plasma viral load (VL), or cancer chemotherapy may induce in vivo changes of P-gp phenotype in peripheral blood mononuclear cells (PBMCs) from HIV-infected treatment-naive and -experienced subjects at different stages of HIV infection and/or disease, including patients with HIV-associated Kaposi sarcoma (KS). Our results show that neither HAART nor HIV VL, nor the stage of HIV infection and/or disease, significantly alter P-gp expression on PBMCs. In particular, surface P-gp expression is expressed at low levels by T-cell subsets, B cells, and NK cells, whereas almost all monocytes are double positive and these results are not modified by HIV PI-containing regimens. By contrast, a significant phenotype modification is detected in PBMCs from AIDS/KS patients after challenge with the liposomal formulation of the anthracycline doxorubicin (L-DOX) with the higher expression reached 24 hours after the end of the drug infusion. In addition, accumulation of L-DOX is unaffected by P-gp-mediated drug efflux as documented by in vitro experiments, in sharp contrast to the kinetic of free DOX, based on HIV PI blockade experiments. Finally, P-gp expression was found in KS spindle cells from HIV-infected treatment-naive AIDS/KS patients. We conclude that P-gp phenotype in PBMCs and specific subsets is not altered by HAART and/or HIV, whereas a significant increase is induced by specific anticancer drugs such as L-DOX. Moreover, HIV PIs possess an inhibitory effect on P-gp function that may improve DOX sensitivity in KS spindle cells. 相似文献
97.
A. Antonini M. Di Stefano D. Minciacchi G. Tassinari 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1985,59(1):171-184
Summary Anatomical studies have shown an extensive network of homotopic and heterotopic interhemispheric connections in area 19 of the cat visual cortex (Segraves and Rosenquist 1982a; 1982b). We have investigated their functional organization by recording visual responses in area 19 of cats following a midsagittal section of the optic chiasm. This operation interrupts all crossed optic fibers coming both from the nasal and the temporal retinae; as a result, each hemisphere receives optic fibers only from the lateral hemiretina of the ipsilateral eye which conveys information from the contralateral visual field. Visual information transmitted to the same hemisphere from the contralateral retina and the ipsilateral visual field must be attributed to an indirect, interhemispheric pathway. We found that a rather high proportion of neurons (31.8%) in area 19 of seven split-chiasm cats responded to visual stimuli presented to the contralateral eye. 1 — All neurons receiving this interhemispheric activation were also driven by the ipsilateral eye via an intrahemispheric pathway. 2 — The property of binocularity was significantly related to the visuotopic map in that both receptive fields of each binocular neuron adjoined or were in the immediate vicinity of the vertical meridian. 3 — Due to the small size of receptive fields in area 19, the contribution of the interhemispheric pathway to the representation of the visual field is rather limited and it is certainly less extensive than that predicted by anatomical studies. The representation of the ipsilateral visual field in area 19 of intact cats, as assessed electrophy-siologically, was comparable to that found in split-chiasm cats. Recordings in areas 17–18 of split-chiasm cats showed that the visual field represented through the corpus callosum in these visual areas is certainly not less and probably more, extensive than that found in area 19. The results support the conclusion that the relation to the vertical meridian and the receptive field size can explain the organization of the interhemispheric connections in the visual areas studied so far. 相似文献
98.
M. Wittner A. Di Stefano B. Mandon N. Roinel C. de Rouffignac 《Pflügers Archiv : European journal of physiology》1991,419(2):212-214
The effect of antidiuretic hormone (ADH) on transepithelial Na+, Cl–, Ca2+ and Mg2+ net fluxes (JNa, JCl, JMg, JCa) was investigated in isolated perfused cortical thick ascending limb segments (cTAL) of the mouse nephron, using the microperfusion technique and the electron microprobe analysis to determine the ionic composition of the collected tubular fluid. Simultaneously, the transepithelial potential difference (PDte) and the transepithelial resistance (Rte) were recorded. Prior to the flux measurements cTAL segments were perfused for one hour. During this equilibration period PDte decreased significantly from +19.9±1.6 to +14.9±1.l mV and Rte increased from 30.6±3.5 cm2 to 38.8±2.4 cm2 (n=7), reflecting a decline in NaCl transport. After ADH was added to the bath solution at 10–10 mol.l–1, PDte increased from +14.4±1.1 to +18.0±1.5 mV, accompanied by a rise in JNa and JCl from 205±11 to 273±19 and from 216±12 to 283±21 pmol.min–1.mm–1 (n=7), respectively. JCa and JMg also increased from 0.81±0.07 to 1.50±0.12 and from 0.43±0.11 to 0.76±0.08 pmol.min–1.mm–1 (n=7), respectively. All these effects were fully reversible after withdrawal of the hormone. In conclusion our data indicate that ADH stimulates divalent cation transport and NaCl transport in the cortical thick ascending limb of Henle's loop of the mouse. 相似文献
99.
Montano SM Sanchez JL Laguna-Torres A Cuchi P Avila MM Weissenbacher M Serra M Viñoles J Russi JC Aguayo N Galeano AH Gianella A Andrade R Arredondo A Ramirez E Acosta ME Alava A Montoya O Guevara A Manrique H Sanchez JL Lama JR de la Hoz F Sanchez GI Ayala C Pacheco ME Carrion G Chauca G Perez JJ Negrete M Russell KL Bautista CT Olson JG Watts DM Birx DL Carr JK;South American HIV Molecular Surveillance Working Group 《Journal of acquired immune deficiency syndromes (1999)》2005,40(1):57-64
HIV cross-sectional studies were conducted among high-risk populations in 9 countries of South America. Enzyme-linked immunosorbent assay screening and Western blot confirmatory testing were performed, and env heteroduplex mobility assay genotyping and DNA sequencing were performed on a subset of HIV-positive subjects. HIV prevalences were highest among men who have sex with men (MSM; 2.0%-27.8%) and were found to be associated with multiple partners, noninjection drug use (non-IDU), and sexually transmitted infections (STIs). By comparison, much lower prevalences were noted among female commercial sex workers (FCSWs; 0%-6.3%) and were associated mainly with a prior IDU and STI history. Env subtype B predominated among MSM throughout the region (more than 90% of strains), whereas env subtype F predominated among FCSWs in Argentina and male commercial sex workers in Uruguay (more than 50% of strains). A renewed effort in controlling STIs, especially among MSM groups, could significantly lessen the impact of the HIV epidemic in South America. 相似文献
100.
Replacement of Candida albicans with C. dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole
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Martinez M López-Ribot JL Kirkpatrick WR Coco BJ Bachmann SP Patterson TF 《Journal of clinical microbiology》2002,40(9):3135-3139
Candida dubliniensis is an opportunistic yeast that has been increasingly implicated in oropharyngeal candidiasis (OPC) in human immunodeficiency virus (HIV)-infected patients but may be underreported due to its similarity with Candida albicans. Although most C. dubliniensis isolates are susceptible to fluconazole, the inducibility of azole resistance in vitro has been reported. Thus, the use of fluconazole prophylaxis in the treatment of these patients may have contributed to the increasing rates of isolation of C. dubliniensis. In this study, yeast strains were collected from the oral cavities of HIV-infected patients enrolled in a longitudinal study of OPC. Patients received fluconazole for the suppression or treatment of OPC, and isolates collected at both study entry and end of study were chosen for analysis. Samples were plated on CHROMagar Candida medium for initial isolation and further identified by Southern blot analysis with the species-specific probes Ca3 (for C. albicans) and Cd25 (for C. dubliniensis). Fluconazole MICs were determined by using NCCLS methods. At study entry, susceptible C. albicans isolates were recovered from oral samples in 42 patients who were followed longitudinally (1 to 36 months). C. albicans strains from 12 of these patients developed fluconazole resistance (fluconazole MIC, >/=64 micro g/ml). C. dubliniensis was not detected at end of study in any of these patients. Of the remaining 30 patients, eight (27%) demonstrated a replacement of C. albicans by C. dubliniensis when a comparison of isolates obtained at baseline and those from the last culture was done. For the 22 of these 30 patients in whom no switch in species was detected, the fluconazole MICs for initial and end-of-study C. albicans isolates ranged from 0.125 to 2.0 micro g/ml. For the eight patients in whom a switch to C. dubliniensis was detected, the fluconazole MICs for C. dubliniensis isolates at end of study ranged from 0.25 to 64 micro g/ml: the fluconazole MICs for isolates from six patients were 0.25 to 2.0 micro g/ml and those for the other two were 32 and 64 micro g/ml, respectively. In conclusion, a considerable number of patients initially infected with C. albicans strains that failed to develop fluconazole resistance demonstrated a switch to C. dubliniensis. C. dubliniensis in this setting may be underestimated due to lack of identification and may occur due to the impact of fluconazole on the ecology of oral yeast species. 相似文献