Search PubMed⌕ Search

Biomedical subjects

P Galieni

Publications and source records attributed to P Galieni.

At least 19 recordsLinked to original sources
PubMed1998

Expression of the T-cell-specific tyrosine kinase Lck in normal B-1 cells and in chronic lymphocytic leukemia B cells.

Src family kinases play a key role in mitogenesis. The exquisitely tissue-specific distribution of different Src family members suggests that a fine tuning of their expression might be a key prerequisite for cell homeostasis. We tested B cells from patients affected by B-cell chronic lymphocytic leukemia (B-CLL) for expression of Src family kinases. The T-cell-specific tyrosine kinase Lck was found to be expressed at significant levels in CLL B-cells. This finding could be accounted for either by ectopic expression of Lck in B-CLL or by specific expression of this kinase in normal B-1 cells, which are believed to be the normal counterpart of CLL B cells. To answer this question B cells from different sources, characterized by a different size of the B-1 subpopulation, were tested for Lck expression. The results show that Lck expression is a feature of CD5(+), B-1 cells, suggesting a potential role for Lck in the self-renewal capacity of this B-cell subpopulation and supporting the notion that B-1 cells are the subset undergoing oncogenic transformation in B-CLL. Furthermore, we show that the CD5(-), B-2 subpopulation, while normally lacking Lck expression, acquires the capacity to express Lck ectopically upon transformation by EBV.

B-Lymphocyte Subsets↗
PubMed1998

5'-nucleotidase activity in lymphocytes from patients affected by B-cell chronic lymphocytic leukemia.

OBJECTIVES: The activity of membrane-bound ecto-5'-nucleotidase and soluble e-Ns and c-N-II 5'-nucleotidases was evaluated on lymphocytes from patients affected by B-cell chronic lymphocytic leukemia (B-CLL). A statistically significative decrease in ecto-5'-nucleotidase, e-Ns, and c-N-II activities was observed in peripheral blood lymphocytes and in B and T populations from affected individuals. DESIGN AND METHODS: For the assay of ecto-5'-nucleotidase, e-Ns, and c-N-II activity we used a radioactive procedure coupled to HPLC. Since the ecto-5'-nucleotidase is identified as CD73 antigen, we performed immunofluorescence analysis using a specific monoclonal antibody. We analyzed ecto-5'-nucleotidase mRNA by RT-PCR to ascertain the possibility of an alteration in the transcription of its gene. RESULTS: A decrease in ecto-5'-nucleotidase activity was correlated to reduction in ecto-5'-nucleotidase positive cells (CD73+) in leukemia patients. RT-PCR produced a fragment of the expected size and the specific mRNA was found expressed in both healthy subjects and leukemia patients. CONCLUSIONS: The decrease in ecto-5'-nucleotidase activity in patients with B-CLL is not due to loss of transcription of the specific mRNA. The presence of point mutations, splicing alteration, or posttranslational modifications must be investigated. If a defect at DNA or RNA level will be detected, the molecular analysis will be considered for diagnosis of B-cell chronic lymphocytic leukemia.

5'-Nucleotidase↗
PubMed1998

Behaviour of human lymphocytic isoenzymes of 5'-nucleotidase.

The behaviour of 5'-nucleotidase isoenzymes (ecto-5'-nucleotidase, e-Ns and c-N-II soluble 5'-nucleotidases) was studied in lymphocytes from patients with B-cell chronic lymphocytic leukemia. A strong reduction in ecto- and soluble activities was observed, although the pattern of the three 5'-nucleotidases did not always strictly overlap. A significant decrease (p<0.05) in ecto-5'-nucleotidase, e-Ns and c-N-II was found in B and T populations (B lymphocytes: 1.13, 0.88 and 1.26 nmol/h/10(6) cells versus 95.96, 9.64 and 13.73 nmol/h/10(6) cells in controls; T lymphocytes: 1.31, 0.23 and 0.06 nmol/h/10(6) cells versus 9.25, 1.31 and 2.10 nmol/h/10(6) cells in healthy subjects). The percentage of ecto-5'-nucleotidase-positive cells (CD73+) was reduced in leukemia patients, indicating a lower number of active molecules on the cell surface. The results of RT-PCR analysis showed that the ecto-5'-nucleotidase mRNA of leukemia patients was not defective.

5'-Nucleotidase↗
PubMed1998

All-trans retinoic acid (ATRA) in patients with chronic myeloid leukemia in the chronic phase.

Since in vitro observations indicated that all-trans retinoic acid (ATRA), especially in combination with IFNalpha, can exert significant suppressive effects on Ph+ cells, we investigated the effects and the pharmacokinetic profile of ATRA in a selected cohort of patients with Ph+ chronic myeloid leukemia (CML) in chronic phase. Eighteen patients were treated with ATRA at a dose of 80 mg/m2/day (p.o.), divided into two equal doses after meals, for 7 consecutive days every other week for a maximum of 12 courses (1 course = 1 week on and 1 week off). Pharmacokinetic profiles of ATRA were evaluated during intermittent therapy on days 1 and 7 of course 1; on day 1 of course 2; on day 1 of course 6. Out of the 18 patients treated with ATRA, 11 (61%) went off study before the sixth course of treatment because of progressive hyperleukocytosis (seven cases), or thrombocytosis (one case), or refusal (three cases). Seven (39%) patients completed the first six courses (12 weeks) of treatment with ATRA and two of them (11%) maintained a white blood cell (WBC) <10 x 10[9]/l which was induced by the pretreatment with hydroxyurea. One patient completed the 12th course of ATRA maintaining WBC <10 x 10(9)/l, platelets <500 x 10(9)/l and spleen not palpable. The treatment with ATRA was well tolerated and only one patient discontinued the therapy because of non-hematological side-effects. The area under the concentration-time curve (AUC) decreased significantly (P< 0.001) during the first week of therapy. By adopting an intermittent dosing regimen, 1 week on/ 1 week off (1 course), at the start of courses 2 and 6, we obtained the ATRA AUCs equivalent to the ones achieved on day 1 of course 1. In conclusion, our results showed that ATRA alone appeared to be unable to control the WBC expansion in the CML patients in chronic phase. Moreover, it did not induce any remarkable cytoreductive effects on the platelet count and on the hemoglobin level. The major interest of ATRA would be in combination with other therapies. If ATRA was given in combination with IFNalpha or other agents, dose reduction of these would not be planned. On the basis of the pharmacokinetic profile, ATRA should be administered intermittently rather than continuously.

Adult↗
PubMed1998

CD4+/CD45RA+ 'naive' T cells and immunological response to influenza virus vaccine in B-cell chronic lymphocytic leukaemia patients.

B-cell chronic lymphocytic leukaemia (B-CLL) is characterized by a high frequency of infections, including those of viral aetiology. Previous reports have demonstrated a specific immunologic response to influenza virus vaccine in B-CLL patients with normal IgG levels. In this study, we have evaluated different immunophenotypically defined B and T cell subsets in 18 B-CLL patients before immunization with killed-influenza-virus vaccine. A correlation between immunological response to vaccination and both absolute numbers of CD4+/CD45RA+ naive T cells and CD5- B cells was found. These data may suggest a supporting role of the CD4+/CD45RA+ T cell subset in the specific antibody response to vaccination with influenza virus vaccine in B-CLL patients.

Adult↗
PubMed1997

Uncoupling of T-cell antigen receptor and downstream protein tyrosine kinases in common variable immunodeficiency.

Patients with common variable immunodeficiency (CVID) are heterogeneous in the clinical manifestations of the disease and the underlying mechanisms leading to the immunodeficiency. Although the overt defect is an impairment in B-cell function, there is increasing evidence of primary T-cell dysfunctions in a proportion of patients with CVID. We have analyzed T-cells from six CVID patients for activation of both early and late events in response to TCR triggering. The data showed that T-cells from three of six CVID patients were defective in the capacity to initiate the TCR/CD3 signaling pathway by activating intracellular tyrosine kinases, associated with impaired proliferative responses to TCR/CD3 triggering. Since both surface expression of the TCR/CD3 complex and intracellular expression of key tyrosine kinases such as p56lek and ZAP-70 were normal in these patients, our data suggest a defect in the earliest step of TCR signal transduction.

Adult↗
PubMed1997

2-Chlorodeoxyadenosine in the treatment of relapsed/refractory chronic lymphoproliferative disorders.

2-Chlorodeoxyadenosine (2-CdA) is a purine analog with cytotoxic activity on both resting and cycling lymphocytes which has been used as salvage therapy in advanced/resistant chronic lymphoproliferative disorders. In our study 39 patients (19 B-CLL, 5 B-PLL, 9 low-grade B-NHL, 5 CTCL and 1 high-grade T-NHL) who relapsed or became resistant after 1-4 chemotherapy regimens were treated with 2-CdA 6 mg/m2 per day by 2 h infusion for 5 d every 28 d. The overall clinical response rate, including complete remission (CR) and partial remission (PR), was 66%. Two of 19 (10%) B-CLL patients achieved a CR lasting 9 months, while 11/19 B-CLL (58%) and 4/5 B-PLL (3 B-PLL/B-CLL and 1 B-PLL) (80%) achieved a PR. Interestingly, 5 of 6 patients who had been previously treated with fludarabine obtained a clinical response (2 CR and 3 PR). One of 9 (11%) low-grade B-NHL patients achieved a CR and relapsed after 26 months, and 5/9 (55%) achieved a PR. One of 5 (20%) CTCL achieved a CR lasting 32 months, while 2/5 (40%) achieved a PR. The overall mean duration of PR was 7.4 months and no differences were observed among different groups of patients. Toxicity was acceptable, as only a transient severe hematological impairment was observed in 20% of the patients while nonhematological toxicity was not documented. Two patients died because of bacterial pneumonia, 1 of meningitis due to Listeria and 9 from progression of the disease. In conclusion, treatment with 2-CdA in heavily pretreated patients with chronic lymphoproliferative disorders is well tolerated and obtains high response rates, even in patients relapsed after treatment with fludarabine.

Adult↗
PubMed1996

Reduction of antithrombin III, protein C, and protein S levels and activated protein C resistance in polycythemia vera and essential thrombocythemia patients with thrombosis.

Patients with polycythemia vera (PV) or essential thrombocythemia (ET) show a high frequency of thrombosis. The reduction of hematocrit after phlebotomy and normalization of platelet counts do not completely eliminate thrombotic risk. Some preliminary studies reported a reduction in the concentration of natural anticoagulants (NA) in this group of patients. For this reason we evaluated protein S (PS) total antigen, antithrombin III (AT III), and protein C (PC) activity in 81 patients with chronic myeloproliferative disorders (33 with PV and 48 with ET). Data were compared with those obtained in 70 healthy sex- and age-matched subjects. Fifty-seven percent of patients (46 out of 81) showed one or more thrombotic episodes at diagnosis or during follow-up. Interestingly, we found a NA deficit in 43.5% of patients with thrombosis versus only 5.7% in the group of patients without thrombosis. These results may suggest new interpretations about the pathogenesis of thrombosis in PV or ET patients.

Adult↗
PubMed1996

Clinical and radiological presentation of 95 orbital lymphoid tumors.

BACKGROUND: Although most orbital lymphoid tumors are characterized by a slow, painless onset and a mass that molds to orbital structures, different presentations may occur. Intensity on T2-weighted MRI is a possible means for differentiating lymphoid tumors (hyperintense) from pseudotumors (hypointense). In addition, it is generally assumed that 75% of orbital lymphomas are at stage I on presentation. METHODS: The clinical, CT, and MRI presentation of 95 primary and secondary orbital lymphoid tumors (63 non-Hodgkin lymphomas and 32 lymphoid hyperplasias) and their histological grade and staging were reviewed. Immunohistochemistry and PCR were used to determine clonality. RESULTS: No significant differences were found between non-Hodgkin lymphomas and lymphoid hyperplasias, except for the mean age of the patients (6.3 years older in non-Hodgkin lymphomas). In both groups the most common presentation was a mass with an indolent course; visual impairment was seen in 13%, conjunctival redness in 25%, pain in 12%, and acute orbital inflammation in 15% of the patients. In most cases, the CT showed one or more lobulated or rounded masses, molding to adjacent structures, or a wedge-shaped enlargement of the lacrimal gland. Intramuscular lymphomas were rare and always associated with extramuscular masses. On T2-weighted MRI, only 35% of lymphoid tumors were hyperintense. Only 49% of lymphomas were at stage I on presentation. CONCLUSION: An inflammatory presentation is not uncommon in orbital lymphoid tumors. Shape, molding and multiple masses can help radiological diagnosis, whereas MRI T2 intensity is unreliable. Accurate staging can disclose systemic disease in more than 50% of cases of non-Hodgkin lymphoma.

Adolescent↗
PubMed1995

Solitary plasmacytoma of bone and extramedullary plasmacytoma: two different entities?

BACKGROUND: The objective of this study was to evaluate the similarities between solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EP). PATIENTS AND METHODS: The clinical features, treatment and survival of 54 patients with localized plasmacytoma (LP) 1990 were carefully reviewed. Follow-up was expected to continue until June 1993. RESULTS: Thirty-two patients were classified as having SPB and 22 EP. Most of the patients were males. particularly those in the SPB group. Their median age at diagnosis was 54 years and no significant difference between the two groups was observed. SPB occurred most frequently in the vertebral column (42%) and EP in the upper respiratory tract (73%). Fifteen patients with SPB and 2 with EP had paraproteinemia at diagnosis, multiple myeloma (MM) became evident in 75% of the patients with persistent paraprotein after therapy, and in only 22% of those in whom it disappeared. Four patients in the SPB group had immunoparesis, and 3 developed MM. Disease progression toward MM was significantly different (p=0.003) in the two groups, while overall survival differences were not significant (p=0.07) unless unrelated causes were excluded (p=0.02). Adjuvant chemotherapy did not seem to limit diffusion of the disease. CONCLUSIONS: Although EP and SPB are both localized forms of plasma cell dyscrasias, SPB seems to have a greater tendency to progression MM. It appears, however, that the apparent stronger propensity of SPB to progress is actually due to the great number of cases that at diagnosis conceal an occult MM.

Adult↗
PubMed1995

Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma.

Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.

Adult↗
PubMed1994

Detection of soluble interleukin-2 receptor and interleukin-10 in the serum of patients with aggressive non-Hodgkin's lymphoma. Identification of a subset at high risk of treatment failure.

BACKGROUND: This study explores the ability of the combined detection of soluble IL-2 receptor (sIL-2r) and interleukin-10 (IL-10) to predict treatment failure in patients with aggressive non-Hodgkin's lymphoma (NHL) and to evaluate the modifications in cytokine measurements induced by the therapeutic administration of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Serum levels of sIL-2r and IL-10 were measured serially in 93 patients with newly diagnosed aggressive NHL treated with four courses of a multiagent chemotherapy regimen. GM-CSF was administered subcutaneously in 39 of these patients from day +5 to day +18 after each chemotherapy course. RESULTS: Pretreatment levels of sIL-2r were greatly elevated in patients with NHL compared with control subjects (P < 0.001), significantly correlating with the Ann Arbor stage (P < 0.001) and beta 2-microglobulin (beta 2-m) concentrations (r = 0.552, P = 0.004). IL-10 was detected in 37 patients at diagnosis, with no correlation with clinicohematologic parameters, and was not detected in the control sample (P < 0.001). Cytokine and receptor levels progressively declined to normal ranges in responding patients, whereas they remained elevated in nonresponders. During administration of GM-CSF, the authors observed an increase of sIL-2r, whereas lower elevations were recorded for IL-10. However, on completion of the induction treatment, cytokine/receptor levels were comparable in patients with the same type of response, whether or not they had received GM-CSF. In the five patients who were investigated at relapse, the levels of sIL-2r, beta 2-m, and lactic dehydrogenase were found to be elevated. IL-10 concentrations were high in three of these patients: two already had detectable levels at presentation, whereas one tested positive only on recurrence. No single parameter was associated with response to therapy, but the combination of elevated IL-10 and sIL-2r concentrations greater than 3000 U/ml resulted in a subset of eight patients who failed induction chemotherapy (P < 0.001). In addition, six of eight patients with high IL-10 and beta 2-m concentrations greater than 3.3 mg/l had an unfavorable outcome (P = 0.003). A multivariate regression model was used to identify sIL-2r (P = 0.004) and beta 2-m (P = 0.043) as the covariates that amplified the prognostic ability of IL-10. CONCLUSIONS: sIL-2r and IL-10 measurements provide valuable information for better management of patients with NHL as markers to monitor disease activity and as prognostic indicators.

Adolescent↗