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Biomedical subjects

D Canioni

Publications and source records attributed to D Canioni.

At least 19 recordsLinked to original sources
PubMed2006

Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936.

Polymerase chain reaction (PCR) assessment of clonal immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements is an important diagnostic tool in mature B-cell neoplasms. However, lack of standardized PCR protocols resulting in a high level of false negativity has hampered comparability of data in previous clonality studies. In order to address these problems, 22 European laboratories investigated the Ig/TCR rearrangement patterns as well as t(14;18) and t(11;14) translocations of 369 B-cell malignancies belonging to five WHO-defined entities using the standardized BIOMED-2 multiplex PCR tubes accompanied by international pathology panel review. B-cell clonality was detected by combined use of the IGH and IGK multiplex PCR assays in all 260 definitive cases of B-cell chronic lymphocytic leukemia (n=56), mantle cell lymphoma (n=54), marginal zone lymphoma (n=41) and follicular lymphoma (n=109). Two of 109 cases of diffuse large B-cell lymphoma showed no detectable clonal marker. The use of these techniques to assign cell lineage should be treated with caution as additional clonal TCR gene rearrangements were frequently detected in all disease categories. Our study indicates that the BIOMED-2 multiplex PCR assays provide a powerful strategy for clonality assessment in B-cell malignancies resulting in high Ig clonality detection rates particularly when IGH and IGK strategies are combined.

Chromosomes, Human, Pair 11↗
PubMed2006

Variable expression of Epstein-Barr virus-induced gene 3 during normal B-cell differentiation and among B-cell lymphomas.

Epstein-Barr virus (EBV)-induced gene 3 (EBI3) is expressed by tumour cells in several EBV-associated malignancies. EBI3 was recently found to associate with a novel peptide, p28, to form a new heterodimeric cytokine, called interleukin-27. In this study, we investigated EBI3 and p28 expression in normal human B lymphocytes and in non-EBV-associated B-cell lymphomas. Low levels of EBI3 were detected in purified tonsillar B cells and expression was upregulated upon anti-CD40 or anti-micro stimulation via NF-kappaB activation. In non-neoplastic tissues, EBI3 expression by lymphocytes was largely restricted to a subset of germinal centre (GC) B cells located at the margin of the light zone, in close contact with CD3+ T lymphocytes. Over 50% of EBI3+ GC B cells were engaged in cell proliferation as assessed by Ki67 expression, and 10-30% expressed MUM1, an early marker of plasma cell differentiation expressed by late centrocytes. Many EBI3+ GC B cells had downregulated bcl-6 expression, which further suggests that these cells correspond to late CD40-activated centrocytes. Immunohistochemical analysis of 64 B-cell lymphomas showed that the highest EBI3 levels were detected in follicular lymphomas and in diffuse large B-cell lymphomas of both GC B-cell-like or non-GC B-cell-like types. No or rare p28 expression was detected in normal or tumour B cells. This constitutive expression of EBI3 by neoplastic B cells may be involved in lymphomagenesis, and may be a useful marker for lymphoma diagnosis.

B-Lymphocytes↗
PubMed2005

Fecal tumor necrosis factor-alpha and calprotectin as differential diagnostic markers for severe diarrhea of small infants.

OBJECTIVE: The etiology of early-onset diarrhea of neonates and small infants that persists despite bowel rest is heterogeneous. Two different categories of disorders presenting with diarrhea in the first weeks of life can be distinguished: constitutive intestinal epithelial disorders (microvillus atrophy [MVA] or epithelial dysplasia [ED]) and immune-inflammatory disorders, (autoimmune enteropathy [AIE] or inflammatory colitis [IC]). We aimed to evaluate in a prospective manner the use of fecal inflammatory markers in the differential diagnosis of severe persistent diarrhea. MATERIAL AND PATIENTS: Twenty-five patients (17 males) were enrolled in this study (median age 8 months). Fourteen children had a constitutive enterocyte disorder (group 1: MVA = 8, ED = 6), and 11 patients had an immuno-inflammatory disease (group 2: AIE = 5, IC = 6). Stool samples were collected at the time of diagnosis and stored at -80 degrees until tumor necrosis factor (TNF)-alpha and calprotectin were measured by enzyme-linked immunoadsorbent assay. RESULTS: No significant differences in age at onset of diarrhea or in stool volumes were observed between both groups. In group 1, fecal TNF-alpha was undetectable/normal in 14 of 14 children, whereas group 2 showed dramatically elevated TNF-alpha levels (mean 3,104, range 237-18,078 pg/g) in 8 of 11 patients. Similarly, calprotectin levels were undetectable/normal in 14 of 14 patients in group 1 and highly raised in 11 of 11 patients in group 2 (median 1,145, range 375-3,095 mug/g), P < 0.01. Under therapy, these inflammatory parameters normalized. CONCLUSIONS: Determination of fecal inflammatory markers is a simple method helping to distinguish constitutive from immuno-inflammatory etiologies of severe persistent diarrhea. These data also suggest that constitutive enterocyte disorders are not accompanied by an inflammatory mucosal reaction.

Age of Onset↗
PubMed2005

Reversibility of pulmonary arterial hypertension in HIV/HHV8-associated Castleman's disease.

The present study describes a case of pulmonary arterial hypertension (PAH) associated with multicentric Castleman's disease in a patient infected with HIV type 1 and human herpes virus 8. Therapy included highly active antiretroviral therapy, warfarin, diuretics, continuous i.v. epoprostenol and 12-monthly pulses of cyclophosphamide. The patient's condition improved dramatically with complete reversibility of PAH, allowing weaning of continuous i.v. epoprostenol therapy. After 5 yrs, both Castleman's disease and PAH have not relapsed. This supports the hypothesis that control of inflammation and retroviral replication may be of interest in the context of PAH, complicating the course of an inflammatory condition associated with viral infection. In conclusion, further studies should help in characterising the best candidates for anti-inflammatory treatment in the setting of pulmonary arterial hypertension.

Adult↗
PubMed2002

Chronic intestinal graft-versus-host disease: clinical, histological and immunohistochemical analysis of 17 children.

Graft-versus-host disease (GVHD) can be acute or chronic. The pathogenesis of chronic GVHD is unclear. Chronic GVHD affects mainly skin, liver and digestive tract. Intestinal involvement is uncommon and histological features are poorly described. We report here the clinical, histological and immunohistochemical features of chronic GVHD with intestinal involvement. Intestinal biopsies from children with chronic GVHD (n=17) were compared to control children (n=21: 10 non-transplant cases, four non-GVHD transplant cases, seven acute GVHD). We evaluated clinical outcome, histological features and characterized immunohistochemically the immune cells involved locally. Chronic GVHD with intestinal involvement was usually multisystemic (88.2%) and preceded by acute GVHD in 88.2% of cases. The outcome was severe with complete recovery in only 58.8% of cases, and death related to chronic GVHD in 17.6% of cases. Histological features were characterized by (1) villous atrophy and (2) glandular lesions, mainly apoptotic with variable intensity and (3) lamina propria infiltrate with cytotoxic T lymphocytes (CD3+, CD8+, TiA1+, granzyme B-) which were significantly (P<0.001) increased compared to non-GVHD transplant and non-transplant controls. Therefore in chronic intestinal GVHD, the apoptotic process could be related to cytotoxic T lymphocytes.

Adolescent↗
PubMed2002

Angio-immunoblastic T cell lymphoma (AILD-TL) rich in large B cells and associated with Epstein-Barr virus infection. A different subtype of AILD-TL?

We studied eight patients with characteristic features of angio-immunoblastic T cell lymphoma (AILD-TL) associated with more than 25% of large B cells. Polymerase chain reaction (PCR) analysis showed a clonal rearrangement of the T cell receptor (TCR)-gamma chain gene in all cases. One additional case showed a clonal rearrangement of the TCR-beta chain gene by Southern blot hybridization. PCR analysis showed a clonal immunoglobulin rearrangement in three cases presenting with more than 50% of large B cells whereas the other cases had a germline configuration. In 6/8 cases, double-labeling immunohistochemistry and in situ hybridization demonstrated that Epstein-Barr virus (EBV) was mostly present in the large B cells but also detected in some T cells. We further evaluated the frequency of AILD-TL with more than 25% of large B cells in the 106 cases collected by the French GELA group and found an incidence of 18%. The outcome of these patients did not differ significantly from those with less than 25% of B cells. With this approach we confirm the heterogeneity of AILD-TL features and the possible association with a substantial numbers of CD20(+), EBV(+) large B cells. We propose to denominate these cases as 'AILD-TL rich in large B cells' and to consider them as a different entity which can be misdiagnosed as a reactive process or as T cell rich B cell lymphoma.

Aged↗
PubMed2001

Lymphoproliferative disorders in children with primary immunodeficiencies: immunological status may be more predictive of the outcome than other criteria.

AIMS: Lymphoproliferative disorders (LPDs) are a severe complication in primary immunodeficiency and post-transplant patients. In primary immunodeficiency patients, LPDs are not well-known and, thus, we tried to evaluate their distinctive features and to determine prognostic factors predictive of clinical outcome by comparison with LPDs in post-transplant children. METHODS AND RESULTS: Clinical records and histopathology of 18 LPDs occurring in primary immunodeficieny children were compared with those of 10 LPDs in post-transplant children, together with results of in-situ hybridization for the detection of Epstein-Barr virus (EBV)-RNA and molecular biological techniques. LPDs were frequently extranodal, EBV-associated, and were more commonly pleomorphic in primary immunodeficiency than in post-transplant patients. A low T-cell count and abnormal T-cell function indicated bad prognosis in both groups. Polymorphic LPDs (PLPDs) were most frequent (n = 19), whereas lymphomas were rare (n = 7), and pseudo-tumoral lymphoid hyperplasias (n = 2) were observed only in primary immunodeficiency. Comparative p53/bcl-2 staining revealed a p53 overexpression in lymphomas compared with PLPDs; CD20/CD79a showed a similar staining in lymphomas, whereas PLPD expressed mainly CD20. TCR and IgH rearrangements did not help in distinguishing PLPDs from lymphomas, but detection of IgH clonality by Southern blot indicated poor prognosis, whereas oligoclonality by Southern blot regardless of PCR clonality and especially a polyclonal profile by Southern blot and PCR indicated a relatively good prognosis. CONCLUSIONS: This study documents the pleomorphism of LPDs in primary immunodeficiency compared to post-transplant children, even if some LPDs are similar in both groups (PLPDs). No criteria are useful enough to ascertain the diagnosis of malignancy in this series. Some molecular biological criteria help to predict the clinical outcome which, nevertheless, seems to depend more on the degree of immunosuppression and on T-lymphocyte presence and function.

Adolescent↗
PubMed2001

Cytotoxic T cells in AIDS colonic cryptosporidiosis.

BACKGROUND/AIMS: It is not known how enteric cryptosporidiosis induces severe intestinal impairment despite minimal invasion by the parasite. The aim of this study was to analyse the histological features and locally implicated immune cells in colonic biopsies of AIDS related cryptosporidiosis. PATIENTS/METHODS: Colonic biopsies from patients with AIDS related cryptosporidiosis (n = 10, group I), patients with AIDS but without intestinal infection (n = 9, group II), and human seronegative controls (n = 9, group III) were studied. Using immunohistochemistry the infiltrating mononuclear cells were analysed in both the epithelium and lamina propria for the expression of CD3, CD8, TiA1, granzyme B, and CD68 and for glandular expression of human major histocompatibility complex DR antigen (HLA-DR). RESULTS: Severe histological changes, resulting in abundant crypt epithelial apoptosis and inflammatory infiltrate in the lamina propria, were seen in all biopsies from group I. A significant increase of CD8+, TiA1+, and granzyme B+ T cells in the lamina propria and HLA-DR glandular expression was noted in group I compared with groups II and III. However, the number of intraepithelial lymphocytes, lamina propria CD3+ T cells, and macrophages was not significantly increased in cryptosporidiosis specimens compared with controls. CONCLUSION: Epithelial apoptosis mediated by granzyme B+ cytotoxic host T cells might play a major role in the development of colonic lesions in AIDS related cryptosporidiosis.

AIDS-Related Opportunistic Infections↗
PubMed2001

Nasal natural killer lymphoma associated with Epstein-Barr virus in a patient infected with human immunodeficiency virus.

Nasal natural killer (NK) lymphoma associated with Epstein-Barr virus (EBV) is a rare lymphoma that has not yet been reported in patients with human immunodeficiency virus (HIV). This report describes the first case, to our knowledge, of nasal NK cell lymphoma in an HIV-positive patient. A 50-year-old African man presented with an obstructive nasopharyngeal tumor, leading to the diagnosis of HIV infection. Nasal biopsy specimens showed NK cell lymphoma, confirmed on nasal tissues by morphologic, immunohistochemical, and polymerase chain reaction studies using a denaturing gradient gel electrophoresis technique that showed no T-cell receptor gamma rearrangement. The EBV was detected by in situ hybridization. The patient received chemotherapy but died from infection. To our knowledge, this is the first reported case of nasal NK cell lymphoma associated with EBV in an HIV patient. Involvement of EBV in HIV non-B-cell lymphomas may represent a further manifestation of opportunistic EBV infection arising in these patients.

AIDS-Related Opportunistic Infections↗
PubMed2000

Expression of p16/INK4a in posttransplantation lymphoproliferative disorders.

It was recently demonstrated that classification of posttransplantation lymphoproliferative disorders (PT-LPDs) into morphological and molecular categories is clinically relevant. It was also reported that PT-LPD not associated with Epstein-Barr virus (EBV) had a more aggressive course than most lesions associated with EBV. Because the cyclin-dependent kinase inhibitor p16/INK4a has been reported to be frequently inactivated in high-grade lymphomas, we evaluated 17 PT-LPD to determine whether p16/INK4a expression could be correlated to morphology, EBV detection, and a Ki-67 labeling index. We demonstrated that tumors with no p16/INK4a expression (n = 8) had a predominantly monomorphic appearance, and most were EBV negative (respectively, 7/8 and 5/8), whereas lesions with p16/INK4a expression (n = 9) were mostly polymorphic PT-LPD (6/9) (P = 0.049) and associated with EBV (9/9) (P = 0.015). In particular, strong p16/INK4a expression was observed in atypical immunoblasts and Reed-Sternberg-like cells. Furthermore, the proliferation index was significantly higher in tumors lacking p16/INK4a expression than in other lesions (P = 0.0008). In conclusion, down-regulation of p16/INK4a was mostly observed in PT-LPD lesions known to follow more aggressive courses: monomorphic tumors and EBV-negative PT-neoplasms. Conversely, overexpression of p16/INK4a was associated with EBV-positive PT-LPD. While p16/INK4a might play a role in the proliferative rate of LP-LPD, further investigations are needed to assess the clinical relevance of p16/INK4a expression in predicting the evolution of tumors and to explain how EBV could favor p16/INK4a protein accumulation in lesions.

Adult↗
PubMed2000

Allogeneic fetal small bowel graft in pigs treated with cyclosporin A.

BACKGROUND: The functional integrity of transplanted fetal intestine was proven in rodents. The authors examined the morphology and development of intraperitoneally transplanted fetal intestine under cyclosporin A (CsA) monotherapy in a large mammal. METHODS: Allogeneic fetal intestinal grafts were transplanted intraperitoneally in pigs. The graft was wrapped in omentum. Thirteen recipients received grafts harvested at 60 days of gestation and 5 at 105 days of gestation. All recipients received 25 mg/kg/d CsA. CsA blood levels were measured at the end of the study. The development of the grafts was assessed by inspection and histology studying revascularization, maturation, and immune rejection. RESULTS: All grafts developed neovascularization. The intestinal wall in the 105-day-old group was thick enough to lead to complete mucosal destruction, whereas the 60-day-old group showed viable mucosa. All grafts induced an immune rejection. This immune response was correlated with the CsA blood level. The graft was destroyed within 15 days when CsA trough level was below 70 ng/mL, had a subacute rejection with villi atrophy when CsA trough level ranged from 70 to 150 ng/mL, and had a good appearance in spite of mild blunting of villi when CsA trough level was over 150 ng/mL. CONCLUSION: Allogeneic fetal intestinal transplantation from 60-day-old embryos in pig achieved successful graft.

Animals↗
PubMed1998

Severe aplastic anemia of neonatal onset: a single-center retrospective study of six children.

We report severe aplastic anemia of neonatal onset diagnosed in six girls between 1985 and 1995 in a single center. Initial blood cell counts (mean age 3.8 days old, 1 to 15 days) showed thrombocytopenia (six of six), anemia (four of six), and neutropenia (two of six). Neutrophil counts gradually decreased below 0.5 x 10(9)/L, and severe aplastic anemia occurred in three patients by 3 months of age and in all patients by 1 year of age. Lymphocyte number and functions were normal. In all children bone marrow biopsy showed hypocellularity for age and absence of fibrosis, blasts, lymphocytic infiltrates, and cytologic abnormalities. Blood and medullary cytogenetic studies were normal. A search for known constitutional, viral, or toxic causes was negative. Immunosuppressive therapy failed to restore hematopoiesis (three of six). Five children received a bone marrow transplantation at an average age of 9 months (range 2.7 to 29 months). One child is alive and well after a human leukocyte antigen-identical bone marrow transplantation, whereas the other four died. Both congenital onset and the high rate of familial involvement suggest that this condition may be inherited.

Anemia, Aplastic↗
PubMed1998

Quantitative RNA slot-blot analysis of CCND1/cyclin D1 expression in suspected mantle cell lymphoma.

Abnormal CCND1 expression is found in the majority of mantle cell lymphomas (MCL) and in a minority of other mature B cell malignancies. Its evaluation can therefore aid diagnostic classification, in conjunction with clinical, morphological, immunophenotypic and cytogenetic analysis. We describe a rapid slot-blot hybridization technique allowing quantitative assessment of CCND1 expression relative to beta-actin, with a sensitivity cut-off of approximately 10%. This allowed clear separation (P < 0.01) of CCND1 MCL (0.89 +/- 0.4; range 0.23-1.81; n = 25) from control samples (0.02 +/- 0.04; range 0-0.09; n = 22) on limited quantities of RNA (1-3.5 microg). Of nine samples in which a potential diagnosis of MCL lymphoma was based on morphological analysis of paraffin-embedded material, without adequate immunophenotype analysis, all were CCND1 negative and subsequent immunophenotype demonstrated features compatible with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (CD5+, CD23+, FMC7-) in all cases tested. This study demonstrates the feasibility of slot-blot CCND1 quantification and the importance of the availability of cryopreserved material.

Adult↗