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1.
Actas Dermosifiliogr ; 2024 Jun 07.
Article in English, Spanish | MEDLINE | ID: mdl-38852841

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seems to have a more favorable prognosis.

2.
J Chem Phys ; 157(5): 054303, 2022 Aug 07.
Article in English | MEDLINE | ID: mdl-35933193

ABSTRACT

A semiclassical model describing the charge transfer collisions of C60 fullerene with different slow ions has been developed to analyze available observations. These data reveal multiple Breit-Wigner-like peaks in the cross sections, with subsequent peaks of reactive cross sections decreasing in magnitude. Calculations of charge transfer probabilities, quasi-resonant cross sections, and cross sections for reactive collisions have been performed using semiempirical interaction potentials between fullerenes and ion projectiles. All computations have been carried out with realistic wave functions for C60's valence electrons derived from the simplified jellium model. The quality of these electron wave functions has been successfully verified by comparing theoretical calculations and experimental data on the small angle cross sections of resonant C60+C60 + collisions. Using the semiempirical potentials to describe resonant scattering phenomena in C60 collisions with ions and Landau-Zener charge transfer theory, we calculated theoretical cross sections for various C60 charge transfer and fragmentation reactions which agree with experiments.

3.
Br J Dermatol ; 179(2): 486-490, 2018 08.
Article in English | MEDLINE | ID: mdl-28865079

ABSTRACT

Congenital erythropoietic porphyria is a rare autosomal recessive disease caused by a deficiency of uroporphyrinogen III synthase, owing to mutations in UROS in chromosome 10. Occasionally, patients show a mild, late-onset disease, without germline UROS mutations, associated with haematological malignancies. We report a 65-year-old patient with photosensitivity, overexcretion of porphyrins and thrombocytopenia. Bone marrow analysis gave a diagnosis of myelodysplastic syndrome (MDS) with the presence of a derivative chromosome 3, possibly due to an inversion including 3q21 and 3q26 break points. After allogeneic stem-cell transplantation, complete remission of MDS and uroporphyria was achieved. To our knowledge, this is the first reported case of acquired erythropoietic uroporphyria associated with MDS, with chromosome 3 alterations.


Subject(s)
Chromosomes, Human, Pair 3/genetics , Late Onset Disorders/diagnosis , Myelodysplastic Syndromes/diagnosis , Porphyria, Erythropoietic/diagnosis , Aged , Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Blood Transfusion , Bone Marrow/pathology , Bone Marrow Transplantation , Chromosome Inversion , Humans , Late Onset Disorders/etiology , Late Onset Disorders/pathology , Late Onset Disorders/therapy , Male , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/therapy , Porphyria, Erythropoietic/etiology , Porphyria, Erythropoietic/pathology , Porphyria, Erythropoietic/therapy , Porphyrins/blood , Porphyrins/urine , Skin/pathology , Treatment Outcome
4.
Leukemia ; 32(3): 645-653, 2018 03.
Article in English | MEDLINE | ID: mdl-28924241

ABSTRACT

Genome studies of chronic lymphocytic leukemia (CLL) have revealed the remarkable subclonal heterogeneity of the tumors, but the clinical implications of this phenomenon are not well known. We assessed the mutational status of 28 CLL driver genes by deep-targeted next-generation sequencing and copy number alterations (CNA) in 406 previously untreated patients and 48 sequential samples. We detected small subclonal mutations (0.6-25% of cells) in nearly all genes (26/28), and they were the sole alteration in 22% of the mutated cases. CNA tended to be acquired early in the evolution of the disease and remained stable, whereas the mutational heterogeneity increased in a subset of tumors. The prognostic impact of different genes was related to the size of the mutated clone. Combining mutations and CNA, we observed that the accumulation of driver alterations (mutational complexity) gradually shortened the time to first treatment independently of the clonal architecture, IGHV status and Binet stage. Conversely, the overall survival was associated with the increasing subclonal diversity of the tumors but it was related to the age of patients, IGHV and TP53 status of the tumors. In conclusion, our study reveals that both the mutational complexity and subclonal diversity influence the evolution of CLL.


Subject(s)
Biomarkers, Tumor , Clonal Evolution/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation/genetics , Adult , Aged , Aged, 80 and over , DNA Copy Number Variations , Disease Progression , Female , Follow-Up Studies , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Signal Transduction , Young Adult
5.
Leukemia ; 29(3): 598-605, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25151957

ABSTRACT

Prospective identification of patients with chronic lymphocytic leukemia (CLL) destined to progress would greatly facilitate their clinical management. Recently, whole-genome DNA methylation analyses identified three clinicobiologic CLL subgroups with an epigenetic signature related to different normal B-cell counterparts. Here, we developed a clinically applicable method to identify these subgroups and to study their clinical relevance. Using a support vector machine approach, we built a prediction model using five epigenetic biomarkers that was able to classify CLL patients accurately into the three subgroups, namely naive B-cell-like, intermediate and memory B-cell-like CLL. DNA methylation was quantified by highly reproducible bisulfite pyrosequencing assays in two independent CLL series. In the initial series (n=211), the three subgroups showed differential levels of IGHV (immunoglobulin heavy-chain locus) mutation (P<0.001) and VH usage (P<0.03), as well as different clinical features and outcome in terms of time to first treatment (TTT) and overall survival (P<0.001). A multivariate Cox model showed that epigenetic classification was the strongest predictor of TTT (P<0.001) along with Binet stage (P<0.001). These findings were corroborated in a validation series (n=97). In this study, we developed a simple and robust method using epigenetic biomarkers to categorize CLLs into three subgroups with different clinicobiologic features and outcome.


Subject(s)
B-Lymphocytes/metabolism , Biomarkers, Tumor/genetics , Epigenesis, Genetic , Immunoglobulin Heavy Chains/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Transcriptome , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , B-Lymphocytes/classification , B-Lymphocytes/pathology , DNA Methylation , Disease Progression , Female , High-Throughput Nucleotide Sequencing , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/classification , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Male , Middle Aged , Proportional Hazards Models , Support Vector Machine , Survival Analysis , Time-to-Treatment , Treatment Outcome
6.
Leukemia ; 27(9): 1826-31, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23594705

ABSTRACT

Refractory anaemia with ring sideroblasts (RARS) and marked thrombocytosis (RARS-T) is a provisional entity in the World Health Organisation 2008 classification and has previously been shown to have a high proportion of JAK2(V617F) (Janus Kinase 2) and SF3B1 (Splicing Factor 3B subunit 1) mutations. The purpose of the present study was to analyse the frequency of SF3B1 mutations in a large cohort of 111 patients with RARS-T and 33 patients with RARS and to explore the prognostic impact of SF3B1 mutational status on RARS-T. The frequency of SF3B1 mutations in RARS-T (96/111, 86.5%) and RARS (28/33, 84.8%) was similar. In RARS-T, median survival was better in SF3B1-mutated patients than in SF3B1-non-mutated patients (6.9 and 3.3 years, respectively, P=0.003). RARS can be differentiated from RARS-T by the frequency of JAK2(V617F) (0% vs 48.6%). In RARS-T patients, SF3B1 (P=0.021) and JAK2 mutations (P=0.016) were independent factors for a better prognosis. Altogether, our results confirm that RARS-T is an independent entity that should be recognised by the next World Health Organisation classification. The assessment of SF3B1 mutations is of prognostic interest in RARS-T patients. Younger age, JAK2(V617F) and SF3B1 mutations are the main predicting factors for survival in RARS-T.


Subject(s)
Anemia, Refractory/genetics , Anemia, Refractory/mortality , Janus Kinase 2/genetics , Mutation , Phosphoproteins/genetics , Ribonucleoprotein, U2 Small Nuclear/genetics , Adult , Age Factors , Aged , Aged, 80 and over , Anemia, Refractory/complications , Anemia, Refractory/diagnosis , Anemia, Sideroblastic/complications , Chromosome Mapping , Female , Humans , Karyotype , Male , Middle Aged , Mutation Rate , Prognosis , RNA Splicing Factors , Thrombocytosis/complications , Young Adult
7.
Leukemia ; 27(5): 1100-6, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23295735

ABSTRACT

NOTCH1 has been found recurrently mutated in a subset of patients with chronic lymphocytic leukemia (CLL). To analyze biological features and clinical impact of NOTCH1 mutations in CLL, we sequenced this gene in 565 patients. NOTCH1 mutations, found in 63 patients (11%), were associated with unmutated IGHV, high expression of CD38 and ZAP-70, trisomy 12, advanced stage and elevated lactate dehydrogenase. Sequential analysis in 200 patients demonstrated acquisition of mutation in one case (0.5%) and disappearance after treatment in two. Binet A and B patients with NOTCH1-mutated had a shorter time to treatment. NOTCH1-mutated patients were more frequently refractory to therapy and showed shorter progression-free and overall survival after complete remission. Overall survival was shorter in NOTCH1-mutated patients, although not independently from IGHV. NOTCH1 mutation increased the risk of transformation to diffuse large B-cell lymphoma independently from IGHV, with this being validated in resampling tests of replicability. In summary, NOTCH1 mutational status, that was rarely acquired during the course of the disease, identify a genetic subgroup with high risk of transformation and poor outcome. This recently identified genetic subgroup of CLL patients deserves prospective studies to define their best management.


Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Mutation , Receptor, Notch1/genetics , Cell Transformation, Neoplastic , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Middle Aged , Risk
8.
Leukemia ; 27(3): 595-603, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23022987

ABSTRACT

Acute myeloid leukemia (AML) with t(8;16)(p11;p13) (t(8;16) AML) has unique clinico-biological characteristics, but its microRNA pattern is unknown. We analyzed 670 microRNAs in seven patients with t(8;16) AML and 113 with other AML subtypes. Hierarchical cluster analysis showed that all t(8;16) AML patients grouped in an independent cluster. Supervised analysis revealed a distinctive signature of 94-microRNAs, most of which were downregulated, including miR-21 and cluster miR-17-92. The mRNA expression analysis of two known transcription factors of these microRNAs (STAT3 and c-Myc, respectively) showed significant downregulation of STAT3 (P=0.04). A bioinformatic analysis showed that 29 of the downregulated microRNAs might be regulated by methylation; we treated a t(8;16) AML sample with 5-aza-2'-deoxycytidine (5-AZA-dC) and trichostatin A and found that 27 microRNAs were re-expressed after treatment. However, there was no difference in methylation status between t(8;16) and other AML subtypes, either overall or in the microRNA promoter. Cross-correlation of mRNA and microRNA expression identified RET as a potential target of several microRNAs. A Renilla-luciferase assay and flow cytometry after transfection with pre-microRNAs confirmed that RET is regulated by miR-218, miR-128, miR-27b, miR-15a and miR-195. In conclusion, t(8;16) AML harbors a specific microRNA signature that is partially epigenetically regulated and targets RET proto-oncogene.


Subject(s)
CREB-Binding Protein/genetics , Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 8/genetics , Histone Acetyltransferases/genetics , Leukemia, Myeloid, Acute/genetics , MicroRNAs/genetics , Proto-Oncogene Proteins c-ret/genetics , Translocation, Genetic/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Azacitidine/analogs & derivatives , Biomarkers, Tumor/genetics , Cluster Analysis , DNA Methylation , DNA, Neoplasm/genetics , Decitabine , Female , Flow Cytometry , Gene Expression Profiling , Gene Expression Regulation, Leukemic , Gene Rearrangement , Humans , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Oncogene Proteins, Fusion/genetics , Polymerase Chain Reaction , Prognosis , Proto-Oncogene Mas , Tumor Cells, Cultured , Young Adult
9.
Ann Oncol ; 19(1): 135-41, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17962207

ABSTRACT

BACKGROUND: Extranodal involvement, including central nervous system (CNS), is a frequent event in patients with mantle cell lymphoma (MCL). However, the incidence, risk factors, and impact on outcome remain controversial. PATIENTS AND METHODS: Main clinical, biological, and evolutive features of 82 patients (60 males/22 females; median age: 61 years) diagnosed with MCL (blastoid, 26%) in a single institution were analyzed for risk of CNS involvement and prognosis. RESULTS: Most patients had advanced stage and intermediate or high-risk International Prognostic Index (IPI). Eleven patients eventually developed CNS involvement with an actuarial 5-year risk of 26% (95% confidence interval 10% to 42%). In one asymptomatic patient, cerebrospinal fluid infiltration was detected at staging maneuvers (1/62; 1.6%). The remaining 10 patients developed neurological symptoms during the course of the disease (median time from diagnosis, 25 months). Initial variables predicting CNS involvement were blastoid histology, high proliferative index measured by Ki-67 staining, high lactate dehydrogenase (LDH) and intermediate- or high-risk IPI. Histological subtype and serum LDH maintained significance in multivariate analysis. Treatment of CNS infiltration consisted of intrathecal chemotherapy (two cases), and intrathecal chemotherapy plus systemic treatment (seven cases). Median survival after CNS involvement was 4.8 months, patients with this complication having shorter survival than those with no CNS disease. CONCLUSION: This study confirms the high incidence of CNS involvement in MCL patients. Treatments aimed at preventing this complication are warranted.


Subject(s)
Central Nervous System/pathology , Lymphoma, Mantle-Cell/pathology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cerebrospinal Fluid/cytology , Chlorambucil/administration & dosage , Cyclophosphamide/administration & dosage , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Female , Humans , Injections, Spinal , Lymphocytosis/drug therapy , Lymphocytosis/etiology , Lymphoma, Mantle-Cell/cerebrospinal fluid , Lymphoma, Mantle-Cell/drug therapy , Male , Methotrexate/administration & dosage , Middle Aged , Prednisolone/administration & dosage , Prognosis , Risk , Severity of Illness Index , Vincristine/administration & dosage
10.
Ann Hematol ; 83(1): 67-70, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14574461

ABSTRACT

Severe retroperitoneal hemorrhage represents an infrequent and serious complication of bone marrow biopsy. A 53-year-old man, diagnosed with polycythemia vera 12 years earlier, was submitted to a bone marrow biopsy due to the appearance of anemia with clinical and hematological features suggesting myelofibrotic transformation, a diagnosis that was confirmed by the marrow study. At 2 h of a right anterior iliac bone marrow trephine biopsy, the patient suddenly developed severe pain in the area of the biopsy, with antialgic flexion of the right leg. Computed tomographic (CT) scan of the abdomen showed a 5 x 9.5 cm hematoma in the right iliac and psoas muscles. The patient was initially managed with analgesics and transfusional support, but the pain persisted and a continuous fall in the hematocrit was observed in the following days. Angiographic examination of the right external iliac artery showed contrast extravasation arising from the circumflex iliac branch, which was embolized using polivinyl alcohol particles and one coil. Following such procedure, the patient recovered uneventfully and was discharged in good condition a few days later. This case illustrates the effectiveness of an endovascular approach in providing a fast and minimally invasive treatment for this life-threatening complication of bone marrow trephine biopsy.


Subject(s)
Biopsy/adverse effects , Bone Marrow/pathology , Embolization, Therapeutic , Hemoperitoneum/therapy , Polycythemia/complications , Postoperative Hemorrhage/therapy , Primary Myelofibrosis/complications , Adult , Angiography , Hemoperitoneum/diagnostic imaging , Hemoperitoneum/etiology , Humans , Iliac Artery , Male , Polycythemia/diagnosis , Polycythemia/etiology , Postoperative Hemorrhage/etiology , Retroperitoneal Space , Tomography, X-Ray Computed
11.
Br J Haematol ; 123(4): 631-6, 2003 Nov.
Article in English | MEDLINE | ID: mdl-14616966

ABSTRACT

Patients with smoldering multiple myeloma (SMM) meet the diagnostic criteria of multiple myeloma (MM) but are asymptomatic. Between January 1978 and July 2001, 53 patients (median age 63 years) were diagnosed with SMM. The median serum M-protein and proportion of bone marrow plasma cells were 36 g/l and 27% respectively. Two subsets of SMM were identified: (i) evolving SMM (n = 22), characterized by a progressive increase in serum M-protein, a previously recognized monoclonal gammopathy of undetermined significance (MGUS) and a significant higher proportion of IgA type and (ii) non-evolving SMM (n = 26) with stable M-protein that abruptly increases when symptomatic MM develops. Thirty-four patients developed symptomatic MM. The median time to progression in the overall series was 3.2 years and the only feature associated with a shorter time to progression was the evolving versus non-evolving type (1.3 vs. 3.9 years respectively, P = 0.007). The pattern of progression consisted of anaemia, lytic bone lesions or both, without renal failure, hypercalcaemia or extramedullary plasmacytomas. Fifty-seven per cent of patients that required chemotherapy showed no or minimal response. The median survival from diagnosis and from progression was 8.2 and 3.5 years respectively.


Subject(s)
Multiple Myeloma/diagnosis , Myeloma Proteins/analysis , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Examination , Disease Progression , Female , Humans , Male , Middle Aged , Multiple Myeloma/drug therapy , Multiple Myeloma/mortality , Plasma Cells/pathology , Prognosis , Survival Rate , Treatment Outcome
12.
Semin Oncol ; 30(2): 178-81, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12720132

ABSTRACT

Monoclonal gammopathy of undetermined significance (MGUS) is a frequent disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), or primary amyloidosis (AL). Although one fourth of these individuals will develop a malignant disease, there are no well-established predictors of outcome, particularly in the IgM type MGUS. Among 434 patients diagnosed with MGUS from 1970 to 2001 with a minimum follow-up of 1 year, 52 (27 men and 25 women; median age, 67 years) of IgM type were identified. After a median follow-up of 5 years, five patients (9.6%) have developed WM. The risk of transformation was 13.3% (95% confidence interval [CI], 0 to 27) and 27.7% (95% CI, 0.3 to 55.1) at 10 and 20 years, respectively. The variables significantly associated with transformation were the proportion of bone marrow plasma cells (BMPC) and the percentage of bone marrow lymphocytes (BML). No significant differences in the risk of transformation were found between IgM MGUS and the remaining MGUS types. Thus, in IgM MGUS the rate of transformation was similar to the risk observed in other MGUS types, the percentage of BMPC and BML being the features significantly associated with evolution into WM.


Subject(s)
Immunoglobulin M/immunology , Paraproteinemias/physiopathology , Waldenstrom Macroglobulinemia/etiology , Aged , Cell Transformation, Neoplastic , Female , Humans , Male , Middle Aged , Paraproteinemias/immunology , Paraproteinemias/pathology , Prognosis , Risk Factors
13.
Phys Rev Lett ; 89(13): 135501, 2002 Sep 23.
Article in English | MEDLINE | ID: mdl-12225033

ABSTRACT

The restoration of the spatial structure of heterogeneous media, such as composites, porous materials, microemulsions, ceramics, or polymer blends from two-point correlation functions, is a problem of relevance to several areas of science. In this contribution we revisit the question of the uniqueness of the restoration problem. We present numerical evidence that periodic, piecewise uniform structures with smooth boundaries are completely specified by their two-point correlation functions, up to a translation and, in some cases, inversion. We discuss the physical relevance of the results.

14.
Leukemia ; 16(8): 1454-9, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12145685

ABSTRACT

The association of hairy cell leukemia (HCL) with other neoplasms, mainly non-Hodgkin's lymphomas, is well known. However, the simultaneous diagnosis of HCL and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, with only few cases of such an association having been reported. We describe three patients with a well-characterized HCL in whom a CLL/SLL population was detected. Of note, these cases represent a significant proportion (11.5%; 95% CI: 0% to 24%) of the total number of HCL cases diagnosed in our institution during the same period of time. All three patients were treated with deoxycoformycin. They achieved a complete response of the HCL, whereas the CLL/SLL population persisted in all cases. The immunoglobulin gene rearrangement analysis, in two informative cases, suggested that the HCL and CLL/SLL populations arose from different B cell clones. This study indicates that the association of HCL and CLL/SLL might be much more frequent than previously recognized. Therefore, a large panel of monoclonal antibodies, including those necessary to detect CLL/SLL, should be employed when studying patients with HCL.


Subject(s)
Leukemia, Hairy Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Neoplasms, Multiple Primary/diagnosis , Antimetabolites, Antineoplastic/therapeutic use , B-Lymphocytes/pathology , Cell Lineage , Cladribine/therapeutic use , Combined Modality Therapy , Comorbidity , Gene Rearrangement, B-Lymphocyte , Genes, Immunoglobulin , Hematopoietic Stem Cell Transplantation , Humans , Immunophenotyping , Leukemia, Hairy Cell/drug therapy , Leukemia, Hairy Cell/epidemiology , Leukemia, Hairy Cell/therapy , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Male , Mass Screening , Middle Aged , Neoplasms, Multiple Primary/drug therapy , Neoplasms, Multiple Primary/epidemiology , Neoplasms, Multiple Primary/therapy , Neoplastic Stem Cells/pathology , Pentostatin/therapeutic use , Prospective Studies , Remission Induction , Salvage Therapy , Transplantation, Autologous
15.
Leukemia ; 16(6): 1028-34, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12040434

ABSTRACT

To investigate the role of the cell cycle regulators p21(Waf1), p27(Kip1), retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnormalities. p21(Waf1)immunohistochemical expression was negative in 12 of 15 CLL (80%), whereas it was moderate or strong in three of seven RS (43%). p21(Waf1) gene was in germline configuration in all the tumors analyzed. Four immunohistochemical patterns of p53 and p21(Waf1) expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27(Kip1) gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21(Waf1) expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL.


Subject(s)
Cell Cycle Proteins/metabolism , Leukemia, Lymphocytic, Chronic, B-Cell/metabolism , Lymphoma, Large B-Cell, Diffuse/metabolism , Adult , Aged , Cell Cycle , Cyclin D1/metabolism , Cyclin-Dependent Kinase Inhibitor p21 , Cyclin-Dependent Kinase Inhibitor p27 , Cyclins/metabolism , Female , Genes, p53 , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/diagnosis , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/genetics , Male , Middle Aged , Mutation , Retinoblastoma Protein/metabolism , Tumor Suppressor Proteins/metabolism
17.
Phys Rev E Stat Nonlin Soft Matter Phys ; 63(6 Pt 2): 066701, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11415252

ABSTRACT

A highly efficient algorithm for the reconstruction of microstructures of heterogeneous media from spatial correlation functions is presented. Since many experimental techniques yield two-point correlation functions, the restoration of heterogeneous structures, such as composites, porous materials, microemulsions, ceramics, or polymer blends, is an inverse problem of fundamental importance. Similar to previously proposed algorithms, the new method relies on Monte Carlo optimization, representing the microstructure on a discrete grid. An efficient way to update the correlation functions after local changes to the structure is introduced. In addition, the rate of convergence is substantially enhanced by selective Monte Carlo moves at interfaces. Speedups over prior methods of more than two orders of magnitude are thus achieved. Moreover, an improved minimization protocol leads to additional gains. The algorithm is ideally suited for implementation on parallel computers. The increase in efficiency brings new classes of problems within the realm of the tractable, notably those involving several different structural length scales and/or components.

18.
J Acquir Immune Defic Syndr ; 26(2): 185-90, 2001 Feb 01.
Article in English | MEDLINE | ID: mdl-11242188

ABSTRACT

Because HTLV-I, HTLV-2, and HIV share identical modes of transmission, simultaneous or subsequent infections with these retroviruses are to be expected. The population of Santos, the largest port in Latin America, includes large numbers of female commercial sex workers and intravenous drug users, presumably having been exposed to retroviral infection. To evaluate the seroprevalence of HTLV infection and their associated risk factors, a cross-sectional survey was carried out in 499 HIV-infected individuals from Santos, Brazil. HTLV testing consisted of enzyme immunoassays for serologic screening and confirmatory Western blot testing. Overall HTLV-I and HTLV-2 seroprevalences were 6.0% (95% confidence interval [CI], 3.9-8.1) and 7.4% (95% CI, 5.1-9.7), respectively. Multivariate logistic regression for statistical analysis revealed HTLV-I infection to be independently associated with: intravenous drug use (IDU) (odds ratio [OR]. 2.99; 95% CI, 1.09-8.20), seropositivity to hepatitis C virus (HCV) (OR, 3.03; 95% CI, 1.02-9.01) and < 3 years of education (OR, 4.73; 95% CI, 1.56-14.41). HTLV-2 infection was associated with: IDU (OR, 3.22; 95% CI, 1.33-7.84), HCV seropositivity (OR, 5.40; 95% CI, 1.86-15.66) and nonwhite race (OR, 3.32; 95% CI, 1.58-7.00). Results indicate that HIV-infected individuals living in Santos are at similarly high risk of being exposed to HTLV-1 and HTLV-2. IDU constitutes the main risk factor for HTLV acquisition in this population, and there is no significant risk associated with sexual practice.


Subject(s)
HIV Infections/complications , HTLV-I Infections/complications , HTLV-II Infections/complications , Human T-lymphotropic virus 1 , Human T-lymphotropic virus 2 , Adolescent , Adult , Antibodies, Viral/blood , Brazil/epidemiology , Cross-Sectional Studies , Female , HIV Infections/blood , HIV Infections/epidemiology , HTLV-I Infections/epidemiology , HTLV-II Infections/epidemiology , Hepatitis C/complications , Hepatitis C/epidemiology , Hepatitis C Antibodies/blood , Humans , Male , Odds Ratio , Regression Analysis , Risk Factors , Seroepidemiologic Studies , Socioeconomic Factors , Substance Abuse, Intravenous/complications
19.
Am J Clin Pathol ; 115(1): 127-35, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11190798

ABSTRACT

We attempted to differentiate monoclonal gammopathies of unknown significance (MGUS) and multiple myeloma (MM) on morphologic grounds and to determine interobserver reproducibility of the differentiation. Cytologists blindly evaluated bone marrow smears from 154 patients with bone marrow plasmacytosis for the proportion of plasma cells with predefined cellular atypias. The single morphologic characteristic that most strongly differentiated MM from MGUS was the presence of nucleoli. The percentage of plasma cells, cytoplasmic contour irregularities, and anisocytosis also predicted a diagnosis of myeloma in multivariate analysis. Six cytologists independently evaluated 68 consecutive cases to determine sensitivity and specificity of these cytomorphologic features. The interobserver coefficient of variation for the plasma cell count was 33%. On consideration of the diagnosis, 36 of 41 MGUS cases and all 24 cases of myeloma were classified correctly. The use of a predesigned score system did not present such a bias, although it did not improve overall efficiency. The plasma cell count is the most predictive characteristic of myeloma from a cytologic viewpoint, but the interobserver variability is high. Interobserver variability is also high in the assessment of morphologic atypia, and atypical traits are not uncommon in plasma cells in MGUS.


Subject(s)
Multiple Myeloma/pathology , Paraproteinemias/pathology , Blood Cell Count , Diagnosis, Differential , Diagnostic Errors , Humans , Pilot Projects , Plasma Cells/pathology , Reproducibility of Results
20.
Eur J Clin Nutr ; 55(12): 1076-83, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11781674

ABSTRACT

OBJECTIVE: To determine and compare the glycaemic index (GI) values of a range of Vietnamese foods in two racial groups. DESIGN AND SUBJECTS: Twelve healthy subjects (six Asian and six Caucasian) consumed 50 g carbohydrate portions of a reference food (glucose sugar) and nine Vietnamese foods (three rices, three noodle products and three sweet foods) in random order after an overnight fast. The reference food was tested on two separate occasions, and the Vietnamese foods were each tested once. Capillary blood samples were taken at time 0 (fasting), 15, 30, 45, 60, 90 and 120 min from the start of each meal. Samples were analysed for plasma glucose and the incremental areas under the plasma glucose curves (AUC) were used to calculate the GI values of the test foods, using glucose as the reference food (ie GI value of glucose=100). The mean GI value of each food was calculated for the entire group of subjects (n=12) and for both racial groups (n=6). RESULTS: The three rices had surprisingly high GI values (86-109), whereas the noodle products had relatively low GI values (39-61). The sugar-rich foods produced intermediate GI values (54-79). The GI values for the nine foods calculated separately for the two racial groups were not significantly different from each other (P=0.26). CONCLUSIONS: The GI values derived from Caucasian subjects are likely to be applicable to Asian populations. Varieties of imported rice from Thailand were found to have high GI values. Alternative low-GI staples, such as rice noodles, may be preferable for Asian/Vietnamese people with diabetes. SPONSORSHIP: This study was funded by the University of Sydney.


Subject(s)
Asian People , Blood Glucose/analysis , Diabetes Mellitus, Type 2/prevention & control , Dietary Carbohydrates/metabolism , White People , Animals , Area Under Curve , Australia , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Fabaceae/metabolism , Food Analysis , Fruit/metabolism , Glucose Tolerance Test , Humans , Milk/metabolism , Oryza/metabolism , Vietnam/ethnology
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