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Daniela Di Martino

Publications and source records attributed to Daniela Di Martino.

6 recordsLinked to original sources

V(H)3 and V(H)6 immunoglobulin M repertoire reconstitution after hematopoietic stem-cell transplantation in children.

BACKGROUND: Immune reconstitution after hematopoietic stem-cell transplantation (HSCT) occurs gradually. Thus, a variable period of immunodeficiency may be present, leading to immunomediated complications, such as graft-versus-host disease (GVHD) and opportunistic infections. METHODS: To better understand the kinetics of B-cell repertoire reconstitution in children, 49 pediatric patients were analyzed before and after transplantation by immunoglobulin (Ig) HCDR3 fingerprinting, which is a molecular technique that analyzes one of the hypervariable segments of the Ig heavy chain, which provides the amino acid residues that are essential to interact with antigens. RESULTS: In healthy donors, the CDR3 fingerprinting profile shows 16 to 20 bands, and each band corresponds to a particular length of CDR3. This situation is considered polyclonal. Patients analyzed just after transplantation show strong oligoclonality, because only a few CDR3 bands are detected within the first 3 to 6 months. CONCLUSIONS: The authors' data show a significant lag in diversification of the B-cell repertoire, which reaches the polyclonal situation of normal healthy donors approximately 6 months after HSCT. This period may vary depending on the type of transplant (autologous vs. allogeneic) and on the immunosuppressive therapy related to GVHD.

Adolescent↗

Molecular and cytogenetic characterization of a structural rearrangement of the Y chromosome in an azoospermic man.

OBJECTIVE: To better define an abnormal karyotype found in a male with primary infertility. DESIGN: Case report. SETTING: Molecular and cytogenetics unit in a university-affiliated hospital. PATIENT(S): A 41-year-old, azoospermic, but otherwise healthy male. INTERVENTION(S): Lymphocytic karyotype and genetic counseling. MAIN OUTCOME MEASURE(S): Metaphases were studied by standard G- and Q-banding, followed by fluorescence in situ hybridization (FISH) and polymerase chain reaction to analyze specific Y chromosome regions. RESULT(S): Chromosomal analysis and FISH allowed us to define the propositus's karyotype as 45,X/46,X,idic(Yp)/46,XY (71%, 26%, and 3% of analyzed metaphases, respectively). Molecular analysis of azoospermic factor (AZF) regions showed deletion of AZFb and AZFc. CONCLUSION(S): A 45,X/46,X,idic(Yp) mosaicism is associated with a very broad spectrum of phenotypes, including patients with Ullrich-Turner syndrome, patients with various degrees of genital ambiguity, or normal males. In the presence of a normal masculinization in otherwise healthy males azoospermia is a distinct feature that can be explained by partial deletion of AZF regions.

Adult↗

B-cell repertoire reconstitution after hematopoietic stem cell transplantation in children evaluated by immunoglobulin heavy chain third complementarity determining region fingerprinting.

Immunodeficiency after hematopoietic stem cell transplantation leads to a high risk of opportunistic infections. We evaluated B-lymphocyte reconstitution in 36 children by heavy chain third complementarity determining region (CDR3)-fingerprinting and immunophenotypic analysis. The time necessary to return to the normal immunoglobulin heavy chain-CDR3 polyclonal situation was basically related to the type of transplant and this process did not recapitulate fetal ontogenesis.

Adolescent↗

Circulating intercellular adhesion molecule-1 in chronic hepatitis C patients with normal or elevated aminotransferase before and after alpha-interferon treatment.

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during alpha-interferon (IFN) therapy. Immunohistochemical localization of ICAM-1 was also performed on liver tissue specimens of both groups. METHODS: Sixty subjects were divided into 3 groups: group A included 19 patients with CH-C and persistently normal aminotransferase; group B included 21 patients with CH-C and persistently elevated aminotransferase levels, and group C included 20 healthy subjects representing the control group. The first two groups were treated with recombinant alpha-IFN 2b at a dose of 6 MU 3 times a week for 3 months and followed up with 3 MU 3 times a week for another 3 months. RESULTS: Baseline values of serum ICAM-1 in groups A and B were significantly higher than those in group C (p < 0.0001). The median baseline value of sICAM-1 in group A (525.0 ng/ml) was lower than that of group B (561.0 ng/ml), but the difference was not statistically significant. Furthermore, there was a trend toward higher ICAM-1 values as histological severity increased (Mantel-Haenszel chi(2) 8.8, p < 0.003). Post-treatment sICAM-1 serum values showed a marked decrease in both groups, but only among responder patients, while ICAM-1 levels were unchanged in non-responders. Immunohistochemical localization showed no staining for ICAM-1 in normal liver specimens, while there was a quite similar staining for ICAM-1 in the two groups of patients, consistent with an inflammatory process. CONCLUSIONS: This study shows that circulating ICAM-1 levels in most patients with CH-C and persistently normal aminotransferase are higher than those in a control group and the fact that ICAM-1 molecules are also expressed on the hepatocyte membrane suggests that they could play an important role, in association with other molecules, in the intercellular adhesion processes during the induction and maintenance phases of the immune response. In both groups, only patients responding to alpha-IFN therapy showed a marked decrease in serum ICAM-1 below baseline values.

Adult↗

Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

Adolescent↗