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G Pizzolo

Publications and source records attributed to G Pizzolo.

At least 37 records · Page 2Linked to original sources
PubMed1999

Lymphocyte membrane antigen expression and intracellular cytokine patterns in an asymptomatic patient with persistently high serum levels of IgE.

BACKGROUND: Patients completely asymptomatic with extremely high levels of IgE have rarely been reported. One such case, in which the immunophenotype pattern of lymphocyte subsets and their cytokine profile were investigated, is described here. OBJECTIVE: To assess whether the cytokine production was consistent with a T helper 2-type immune response, as suggested by theories regarding the functional polarization of helper and cytotoxic T cells in hyper-IgE conditions. METHODS: An asymptomatic 79-year-old man presented with persistent high levels of serum IgE and sporadic hypereosinophilia without any evidence of an underlying pathologic condition. We investigated the immunophenotype of circulating lymphocytes, the expression/release of CD30 (a member of the tumor necrosis factor receptor family preferentially associated with T helper 2-type immune responses) and the intracellular patterns of interferon-gamma (IFN-gamma), Interleukin-2 (IL-2), IL-4, IL-5, and IL-10 production by T cell subsets, as evaluated by single-cell flow-cytometric analysis. RESULTS: The majority of lymphocytes displayed the membrane immunophenotype of NK cells. Both CD4+ and CD8+ T cells were reduced and expressed the "memory" (CD4+/CD45RO+) and the "naive" (CD8+/CD45RA+) phenotypes, respectively. Among CD4+ T cells, CD30 expression was increased in the resting condition and was further inducible following stimulation with mitogenic anti-CD3. Interleukin-4, IL-2, and IL-10 production by CD4+ T cells was increased, whereas IFN-gamma was reduced as compared with normals. CONCLUSIONS: The data suggest that a polarization of CD4+ T cells towards a T helper 0/2-type cytokine pattern occurred in this patient in spite of CD4+ cell reduction and NK cell expansion.

Aged↗
PubMed1999

Progressive polarization towards a T helper/cytotoxic type-1 cytokine pattern during age-dependent maturation of the immune response inversely correlates with CD30 cell expression and serum concentration.

In order to investigate the T cell cytokine profile during age-dependent maturation of the immune response, we evaluated the cytokine expression of CD4+ and CD8+ circulating cells by flow cytometric single-cell analysis after non-specific stimulation in vitro in different age groups of normal individuals, from cord blood to adulthood. Moreover, we correlated these lymphocyte cytokine patterns with the expression/release of CD30, a member of the tumour necrosis factor (TNF) receptor superfamily, which has been suggested to be related to the T helper/cytotoxic (Th(c))2-type immune responses, in order to verify this association in vivo, in non-pathological conditions. The results showed a progressive increase of circulating Th(c)1-type, interferon-gamma (IFN-gamma)- and/or IL-2-producing T cells along with ageing and, conversely, a stable number, although higher than in cord blood samples, of CD4+/IL-4+ T cells in the post-natal groups. In addition, serum levels of soluble CD30 (sCD30) and numbers of circulating CD4+/CD30+ and CD8+/CD30+ T cells were significantly higher in children aged < 5 years in comparison with those found either in cord blood or in blood from both older children and adults. These data support the concept of a progressive polarization of the Th(c) cell cytokine profile towards the Th(c)1 pattern during age-dependent maturation of the immune response. Moreover, the peak of CD30 expression/release in early infancy before the Th(c)1 shifting occurs, although not associated with a significant increase of circulating IL-4+ T cells, raises the question of the possible relationship in vivo between CD30 and Th(c)2-type immune responses.

Adolescent↗
PubMed1999

Invasive aspergillosis in neutropenic patients: rapid neutrophil recovery is a risk factor for severe pulmonary complications.

BACKGROUND: In invasive aspergillosis, the duration of neutropenia is an accepted risk factor, and recovery from neutropenia is generally associated with a favourable outcome. However, the rapidity of granulocyte recovery may rarely be associated with adverse sequelae. The purpose of this study was to define the relationship between neutrophil (polymorphonuclear, PMN) recovery after chemotherapy-induced bone marrow aplasia and the occurrence of severe pulmonary complications (haemoptysis, pneumothorax and death) in patients with haematological malignancies who developed invasive fungal pneumonias. METHODS: Twenty consecutive patients were retrospectively studied; eight of them had developed pulmonary events between 5 and 11 days after neutrophil recovery that followed deep neutropenia (PMN < 100 microL-1). RESULTS: Five patients had haemoptysis (one of these also had pneumothorax) and three had pneumothorax. According to the multiplicative logistic model, the odds of occurrence of a pulmonary event increased significantly with increasing PMN count on the fifth day (P < 0.001). Five of the eight patients who had pulmonary complications died. Also, the risk of death was larger in the presence of rapid neutrophil recovery, although the difference was not statistically significant (P = 0.111). Analysis of clinical and laboratory data showed that the risk of pulmonary complications significantly increased when the neutrophil concentration was > 4500 microL-1 on day 5 after deep granulocyte neutropenia (PMN < 100 microL-1). There was no correlation between pulmonary complications, dosage of amphotericin B and deaths. CONCLUSION: The occurrence of life-threatening complications in patients with invasive fungal pneumonia is closely related to rapid PMN recovery.

Adolescent↗
PubMed1999

Peripheral T lymphocyte cytokine profile (IFNgamma, IL-2, IL-4) and CD30 expression/release during measles infection.

BACKGROUND AND OBJECTIVE: Measles virus infection (MVI) has been reported to be characterized by an imbalanced Th(1/2)-type cytokine profile. CD30 has been proposed as a receptor preferentially associated with the Th(0/2)-type cytokine pattern. The aim of this study was therefore to define the peripheral T lymphocyte cytokine profile and to test which CD30 expression pattern it was associated with in MVI. DESIGN AND METHODS: The design of the study was a prospective evaluation with comparative analysis. The serum levels of the soluble form of CD30 (sCD30) were determined at diagnosis and at weekly intervals up to 4 weeks, using an ELISA, in 23 males (median age 19), who developed MVI while serving in the Italian army and who were admitted to the Infectious Disease Unit of the Military Hospital in Padua. In 10 of the patients at diagnosis we studied the lymphoid immunophenotype and, after non-specific ex vivo stimulation, the expression of IFNgamma, IL-2 and IL-4 by peripheral T cells using flow cytometry single cell analysis. In 3 patients such evaluations were also performed 7 weeks later. RESULTS: At diagnosis, we found (i) reduction of IFNgamma+/CD4+ T cells (p=0.048 vs controls) in the absence of substantial variation of IL-2+ and IL-4+ T cells (p=ns vs controls); (ii) expansion of CD30+/ CD4+ and CD30+/CD8+ T cell subsets (p<0.01 vs controls); (iii) high sCD30 values (median 61 U/mL; p<0.001 vs controls); (iiii) a context of lymphopenia (0. 728+/-0.292 lymph x10(9)/L). sCD30 remained elevated up to 4 weeks from MVI onset [median values 53, 49, 50, 34 U/mL after 1, 2, 3 and 4 weeks, respectively (p=ns between different time points)]. In 3 patients tested 7 weeks after diagnosis, we still observed decreased IFNgamma production by CD4+ and CD8+ T cells (p=0.05 and <0.01, respectively vs controls) and reduction of CD4+ and CD8+/IL-2+ T cells (p<0.01). INTERPRETATION AND CONCLUSIONS: MVI was characterized by featuresof inadequate Th/Tc(1) activation associated with increased circulating CD30+ T cells and elevated sCD30 levels, supporting a correlation between Th/Tc status and CD30 expression/release pattern in vivo.

Adult↗
PubMed1999

CD138/syndecan-1: a useful immunohistochemical marker of normal and neoplastic plasma cells on routine trephine bone marrow biopsies.

Detection of abnormal numbers and/or distribution of bone marrow (BM) plasma cells (PCs) on trephine biopsies can be important in the differential diagnosis of multiple myeloma (MM) and other PC disorders. A variety of immunohistochemical markers can potentially improve the specificity and sensitivity of PC detection on routine histological sections obtained from trephine BM biopsies, but most of them are not completely satisfactory. In this study, we investigated whether the antibody CD138/B-B4, which is an optimal marker for PC detection on BM aspirates by flow cytometry, can be used successfully for the identification of PCs also on formalin-fixed, decalcified biopsies. A series of samples including normal BM [12], MM [65], monoclonal gammopathies of undetermined significance [44], and B-cell lymphoma of various types [94], including B-cell precursor lymphoblastic leukemia [9], lymphoplasmacytoid [17], immunoblastic [14], lymphocytic/CLL [23], hairy cell leukemia [4], large B-cell [8], mantle-cell [3], marginal zone [6] and follicular [10] lymphomas, have been investigated for CD138 expression using a sensitive immunohistochemical technique. Within the BM microenvironment, CD138 was characterized by excellent sensitivity and specificity. Virtually all normal and neoplastic PCs expressed clear-cut membrane CD138 immunostaining, whereas all other cell types did not. All cases of MM, including plasmablastic and leukemic cases, showed strong immunoreactivity. Conversely, all B-cell lymphomas, including all cases characterized by secretive features, lymphoplasmacytoid, and immunoblastic lymphomas, were completely negative. These results demonstrate that CD138 is a highly sensitive and specific marker that is useful for the rapid and precise localization of normal and neoplastic PCs on routine BM sections. In addition, because of its clear-cut cell membrane localization, CD138 can be used successfully in double-marker immunostaining reactions to evaluate precisely nuclear prognostic markers such as Ki67 and p53 in MMs.

Biomarkers, Tumor↗
PubMed1998

Serum level of the soluble form of the CD30 molecule identifies patients with Hodgkin's disease at high risk of unfavorable outcome.

Preliminary reports suggested a prognostic significance for serum levels of soluble CD30 (sCD30) in patients with Hodgkin's disease (HD). In this study, we investigated the prognostic impact of sCD30 concentration at diagnosis in relation to the other recognized prognostic parameters in 303 patients with HD observed in three different institutions between 1984 and 1996. sCD30 levels were correlated with stage, presence of B symptoms, and tumor burden. High sCD30 levels entailed a higher risk of poor outcome, and the event-free survival (EFS) probability at 5 years for patients with sCD30 levels >/=100 and less than 100 U/mL was 59.9% (95% confidence interval [CI], 40.6% to 65.9%) and 87.5% (95% CI, 81.5% to 91.6%), respectively (P < .001). On the basis of the results of univariate analysis of 14 pretreatment characteristics, we included five prognostic factors (high sCD30 serum level, stage III-IV, B symptoms, low hemoglobin level, and age >/=50 years) into a multivariate model. High sCD30 and advanced stage were independently associated with an unfavorable prognosis. Their combined evaluation identified patients at high risk (stages III and IV and sCD30 >/=100 U/mL: EFS, 46.9%) and low risk (stages I and II with sCD30 <100 U/mL: EFS, 88. 7%) of treatment failure (P < .001). We conclude that the combined evaluation of sCD30 serum level and stage at presentation identifies patients with HD at high risk of an unfavorable outcome.

Adolescent↗
PubMed1998

Estimated 6-year event-free survival of 55% in 60 consecutive adult acute lymphoblastic leukemia patients treated with an intensive phase II protocol based on high induction dose of daunorubicin.

On the basis of a previous experience suggesting that daunorubicin dose in induction was an independent prognostic factor in adult ALL, we designed a chemotherapeutic regimen (ALLVR589) characterized by high doses of daunorubicin (270 mg/m2) in induction and by high-dose Ara-C in post-remission. The protocol was otherwise conventional: induction and post-remission therapy were followed by chemo-radio prophylaxis of the central nervous system (CNS) and periodical reinductions over a 3-year maintenance period. Sixty consecutive patients (male 42, female 18, median age 34 years, range 14-71; B-lineage, 35; T-lineage, 25; Ph' and bcr/abl positive, 7) recruited between 1989 and 1996, were evaluated for treatment outcome. Complete remissions were 56 (93%), one patient had refractory disease, early deaths were five (8%); 19/56 (34%) patients relapsed, five of whom were Ph'+. Median time to relapse was 11 months (range 3-47); 68% of relapses occurred within 12 months from CR. No CNS relapses were observed. After a median follow-up of 44 months (1-100), 33/60 (55%) patients remain event-free; 23/60 (38%) are off-therapy in continuous CR (median follow-up from diagnosis: 63 months; range 38-100). These results suggest that increasing DNM dosage in induction is one of the possible approaches to improve the outcome of adult ALL by decreasing the relapse occurrence.

Adolescent↗
PubMed1998

Serum levels of p55 and p75 soluble TNF receptors in adult acute leukaemia at diagnosis: correlation with clinical and biological features and outcome.

The tumour necrosis factor (TNF)/TNF-receptor (TNFR) complex plays a role in the growth of leukaemic cells. We retrospectively investigated the relationship between pretreatment serum concentration of soluble TNFR (p55- and p75-sTNFRs) and outcome in adult acute myeloid (AML 82 cases) and lymphoid (ALL 44 cases) leukaemia. Both sTNFRs were significantly higher in AML (p55-sTNFR 4.53 +/- 3.7, median 3.75; p75-sTNFR 6.51 +/- 5.25 ng/ml, median 4.72) and ALL sera (3.31 +/- 1.5, median 2.95; 5.30 +/- 2.3 ng/ml, median 4.56, respectively) than in controls (1.89 +/- 0.5, median 1.98; 2.22 +/- 0.8 ng/ml, median 2.37) (P < 0.01 for both sTNFRs). Fresh leukaemic cells expressed p55- and p75-sTNFRs, which were modulated and released into the supernatant (SN) following short-term in vitro culture, suggesting that in vivo sTNFRs were also leukaemia-derived. Whereas no correlation was observed between sTNFRs and outcome in ALL, in AML higher p55-sTNFR levels (> 3.75 ng/ml) were associated with shorter disease-free survival (DFS) (P = 0.006) and overall survival (OS) (P = 0.0004). At multivariate analysis p55-sTNFR was the most significant predictor of DFS (P = 0.006) and OS (P < 0.001). Our data suggest that the prognostic significance of p55-sTNFR in AML could be related to relevant biological features of AML blasts.

Adolescent↗
PubMed1998

Differential expression of cyclin-dependent kinase 6 in cortical thymocytes and T-cell lymphoblastic lymphoma/leukemia.

Cyclin-dependent kinase-6 (CDK6) is the earliest inducible member of the CDK family in human T lymphocytes, involved in growth factor stimulation and cell cycle progression. CDK6 is one of the targets of p16 and p15, CDK inhibitors encoded by MTS1 and MTS2, two tumor suppressor genes that are frequently deleted in T-cell leukemia. In this study we have investigated CDK6 expression in normal and neoplastic lymphoid tissues using immunohistochemistry and flow cytometry. In normal (six samples) and hyperplastic (four samples) thymuses, strong CDK6 expression was observed in a discrete proportion of cortical thymocytes (10 to 15%), mainly located in the peripheral (subcapsular) zone of the cortex. All tested cases of T-cell lymphoblastic lymphoma/leukemia (T-LBL/ALL) showed strong CDK6 expression in the majority (up to 100%) of neoplastic lymphoid cells. Western blot analysis confirmed the expected CDK6 protein size (40 kd). According to Southern blot analysis, CDK6 overexpression in neoplastic T lymphoblasts was not due to gene amplification. In all other lymphomas investigated (28 peripheral T-cell non-Hodgkin's lympohomas (T-NHLs), 7 CD30+ anaplastic NHLs, 22 high-grade B-NHLs, 15 low-grade B-NHLs, 25 B-cell precursor ALLs), CDK6 was not expressed or expressed at low levels, with the only exception of three nasal angiocentric T-NHLs, all exhibiting CDK6 immunoreactivity comparable to that observed in T-LBL/ALL. These data provide evidence that CDK6 is abnormally expressed in T-LBL/ALL and may be involved in the pathogenesis of this malignancy. In addition, the quantitative difference of CDK6 expression between neoplastic and non-neoplastic cortical thymocytes can be potentially useful in the differential diagnosis of thymic neoplasms on histological and cytological specimens.

Blotting, Southern↗
PubMed1998

Differential expression of p57kip2, a maternally imprinted cdk inhibitor, in normal human placenta and gestational trophoblastic disease.

Evidence has recently been provided to support a role for genomic imprinting in the regulation of embryonic implantation and development and placental growth, as well as in the pathogenesis of proliferative trophoblastic diseases. The cyclin-dependent kinase inhibitor p57KIP2 has recently been recognized as a maternally imprinted gene. We investigated p57KIP2 expression in first-trimester normal placentas from interrupted pregnancy, spontaneous abortions, and different types of proliferative trophoblastic diseases using single- and double-marker immunohistochemical techniques. In normal placenta, nuclear p57KIP2 expression was observed at high frequency (up to 100%) in extravillous trophoblast, cytotrophoblast, and implantation-site interstitial trophoblast, but was absent in syncytiotrophoblast. p57KIP2 was also expressed in the stromal cells of maternal decidua, which was one of the few adult tissues retaining p57KIP2 expression (most other adult tissues investigated were negative). p57KIP2 expression was either absent or low in all cases of diploid/tetraploid complete moles (20 cases) and in three cases of gestational choriocarcinoma. On the other hand, all spontaneous abortions (12 cases) and triploid partial moles (19 cases) showed p57KIP2 levels comparable to those observed in normal placenta. These findings are in line with the hypothesis that deregulation of genomic imprinting, particularly the loss of cell-cycle inhibitors such as p57KIP2, is involved in the abnormal development of androgenetic trophoblastic proliferations. In addition, this simple immunohistochemical analysis could provide a useful diagnostic marker in difficult cases.

Choriocarcinoma↗
PubMed1998

Regulation of the proliferative potential of cord blood long-term culture-initiating cells (LTC-IC) by different stromal cell lines: implications for LTC-IC measurement.

BACKGROUND AND OBJECTIVE: Long-term culture-initiating cells (LTC-IC) are the best available approximation to an in vitro assay of stem cells in humans although they still represent a heterogeneous population in terms of proliferative capacity and sensitivity to different growth factors. Human umbilical cord blood (CB) is rich in hemopoietic progenitor cells, as measured by clonogenic assays and contains stem cells capable of reconstituting the marrow after ablation in clinical transplantation. We evaluated the influence of culture conditions on the in vitro behavior of LTC-IC from CB. DESIGN AND METHODS: LTC-IC were evaluated in long-term cultures, comparing two types of murine stromal cell lines: M2-10B4 and M2-10B4 transfected with cDNAs for human G-CSF and IL-3. RESULTS: Two and five fold higher numbers of terminally differentiated cells were produced during nine weeks of culture of CB mononuclear or CD34+ cells respectively, in cultures containing a M2-10B4 IL-3 G-CSF cell line compared to cultures containing the parental cell line. Likewise, a higher number of colony-forming cells (CFC) were detected in the supernatant of cultures with the transfected cell line. In contrast, the number of CFC generated within the stromal layer, after 5 or 9 weeks of culture, was significantly higher in cultures on M2-10B4 cells than those on M2-10B4 IL-3 G-CSF. INTERPRETATION AND CONCLUSIONS: Our results show that the proliferative capacity of CB LTC-IC can be strongly influenced by culture conditions and that the frequency of LTC-IC estimated using these cell lines as stromal support is not identical.

Cell Communication↗
PubMed1997

Interleukin-15 triggers the proliferation and cytotoxicity of granular lymphocytes in patients with lymphoproliferative disease of granular lymphocytes.

The recently cloned cytokine interleukin-15 (IL-15) shares several functional activities with IL-2 in different cell systems. Although IL-15 does not show sequence homology with IL-2, it uses components of the IL-2 receptor (IL-2R) for binding and signal transduction, namely, p75 (beta) and the p64 (gamma) chains of IL-2R. To evaluate whether IL-15 is involved in the activation of granular lymphocytes (GL) in patients with lymphoproliferative disease of granular lymphocytes (LDGL), we evaluated the ability of IL-15 to stimulate GL proliferation, cytotoxic function, and the role of IL-2R beta and gamma molecules on relevant cells. Our results show that IL-15 stimulates cell proliferation and cytotoxic activity of GL in LDGL patients. Reverse-transcriptase polymerase chain reaction (RT-PCR) and phenotypic analyses using the anti-IL-2R gamma-chain-specific TUGh4 monoclonal antibody (MoAb) indicate that both CD3+ and CD3- GL express the p64 IL-2R, a result previously unknown. IL-15 activity was inhibited by antibodies against p75 and p64 IL-2R chains, while no inhibitory effects are detectable with anti-p55 IL-2R antibody. The association of anti-p75 and anti-p64 IL-2R MoAbs resulted in a nearly complete (95%) inhibition of IL-15-induced GL proliferation. Using RT-PCR analysis, we demonstrated that highly purified CD3+ and CD3- GL did not express mRNA for IL-15 or IL-2. By contrast, a clear-cut IL-15 mRNA signal was detected by RT-PCR in patients' peripheral blood mononuclear cells, with monocytes likely accounting for the source of IL-15 in LDGL patients. However, even in concentrated supernatants from enriched monocyte populations, we could not demonstrate the presence of IL-15 protein. Using anti-IL-15 specific MoAbs, a membrane-bound form of this cytokine was demonstrated both on CD3+ and CD3- LDGL cells. By RT-PCR analysis, purified GL from these patients were found to express the message for IL-15 receptor alpha chain. Taken together, these results indicate that both CD3+ and CD3- GL are stimulated by IL-15 and that this cytokine mediates its activity through the beta and gamma chains of the IL-2R, providing further suggestions for the interpretation of the mechanisms that lead to cell expansion in patients with LDGL.

Adult↗
PubMed1997

High serum level of soluble CD30 in acute primary HIV-1 infection.

CD30 has been suggested to play a role in HIV infection. In this study the serum concentration of soluble CD30 (sCD30) was determined by an ELISA essay on samples collected from patients with acute primary HIV-1 infection during the acute phase (n = 17) and after seroconversion (n = 13). sCD30 during acute infection was consistently elevated (137.58 +/- 120.33 versus 6.4 +/- 5.4 U/ml (mean +/- s.d.) in normal controls, P<0.0001) and decreased after seroconversion (49.1 +/- 66.17 U/ml; P = 0.0018 compared with acute infection). This trend mirrored the disappearance of detectable levels of HIV antigen in the blood, resulting in a direct correlation between sCD30 and HIVAg values (P = 0.002). These data suggest that the high levels of sCD30 observed during the peak concentration of HIVAg in acute primary HIV infection might reflect the high rate of viral replication.

Acute Disease↗
PubMed1997

Soluble molecules as biological markers in Hodgkin's disease.

Hodgkin's disease (HD) is characterised by a complex architectural and functional derangement of involved tissues. The interactions between neoplastic cells and the heterogeneous microenvironment lead to the expression and release of different cellular messengers [cytokines, soluble (s) forms of cytokine receptors and other membrane-associated molecules] which can be detected in the circulation and evaluated as biological markers. We and others investigated several of these molecules looking for their possible role as diagnostic or prognostic parameters in patients with HD. We update here the results of serum determination of sIL-2Ralpha, sCD8, sICAM-1, sTNFRs, and sCD30 in a large series of cases from our institution. We found that their levels are generally increased at presentation and during the active phase of the disease. They correlate with stage and clinical aggressiveness and have some prognostic implication. However, we were unable to demonstrate a prognostic usefulness for their detection, with the exception for sCD30 which was found to directly correlate with disease spread and burden at presentation and, most importantly, to have an independent prognostic significance. The prognostic significance of sCD30 might derive from a crucial involvement of this molecule in the pathophysiology of HD.

Adult↗
PubMed1997

In vivo CD30 expression in human diseases with predominant activation of Th2-like T cells.

CD30 is a member of the tumor necrosis factor (TNF) receptor family, originally described as a marker for Hodgkin and Reed-Sternberg cells in Hodgkin's disease, which has been found to be preferentially expressed by T cells producing Th2-type cytokines. The presence of CD30 expression was assessed by both immunohistochemistry and reverse transcriptase-polymerase chain reaction in the target organs of patients with Th1- or Th2-dominated disorders. CD30 expression was found in neither the gut of patients with Crohn's disease nor in the gastric antrum of Helicobacter pylori-infected patients, where there was high interferon-gamma (IFN-gamma) expression. In contrast, high CD30 expression in the apparent absence of IFN-gamma expression was observed in the skin of patients with systemic sclerosis or chronic graft versus host disease (GVHD), which can be considered Th2-dominated disorders. Moreover, high levels of soluble CD30 were found in the serum of both systemic sclerosis and GVHD patients but not in the serum of patients suffering from multiple sclerosis, a Th1-dominated disorder. Thus, CD30 expression appears to be preferentially associated with Th2-type responses not only in vitro but also in vivo.

Crohn Disease↗
PubMed1997

Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis.

The pattern of cytokine production of skin-infiltrating T cells from patients with progressive systemic sclerosis was investigated. Most CD4+ T-cell clones generated from skin biopsy specimens showed a type 2 helper (Th2) cytokine profile (production of interleukin-4, but no interferon (IFN)-gamma). High interleukin-4 but little or no IFN-gamma mRNA expression was found by in situ hybridization in skin perivascular mononuclear cell infiltrates. The immunohistochemical analysis revealed CD30 expression by high numbers of CD4+ T cells in the same specimens. Finally, the great majority of patients with diffuse disease had elevated levels of soluble CD30 in their sera. These data suggest the existence in patients with progressive systemic sclerosis of a predominant activation of Th2-like T cells, which may account for the major alterations (endothelial cell injury, fibrosis, and autoantibody production) occurring in this disease.

Adult↗
PubMed1996

p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function.

p21WAF1 (wild-type p53-activated fragment 1) is involved in the control of mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases (Cdk). Because the product of WAF1 gene is a potent downstream effector of the p53 tumor-suppressor gene function, its pattern of cellular expression might correlate with nuclear accumulation of p53-encoded protein and/or p53 gene mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21WAF1 proteins in tissue involved by non-Hodgkin's lymphomas (NHLs;253 cases) of various histologic types. In a proportion of them (80 cases), we also investigated the possible presence of p53 gene mutations using single-strand conformation polymorphism analysis and direct DNA sequencing. The absence of both p21WAF1 and p53 proteins was observed in 147 of 217 cases (67.7%) among CD30-NHL and in only 8 of 36 (22.2%) CD30+cases, which were mostly anaplastic large-cell lymphomas. A consistent number (> 10%) of p21WAF1-expressing cells was shown in 48 of 253 (18.9%) NHL cases, with a higher incidence in CD30+cases (25/36 [69.4%]), which mostly (21/36) coexpressed p53. These latter cases were characterized by a germline configuration of the p53 gene. In 50 of 253 NHL samples (19.7%), 47 of which (21.6%) belong to the CD30-group, neoplastic cells were p53+/p21-. In all of these cases, the p53+cells accounted for more than 50% of neoplastic cells, up to 100%. Point mutations of p53 gene were solely observed in all investigated cases with this latter phenotype. Our findings strongly suggest that the combined immunohistochemical evaluation of p53 and p21WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitorage and prognostication of individual cases.

Biomarkers↗