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Biomedical subjects

A Carbone

Publications and source records attributed to A Carbone.

At least 307 records · Page 17Linked to original sources
PubMed1994

Molecular evaluation of clonal remission in hairy cell leukemia patients treated with 2-chlorodeoxyadenosine.

Several reports have documented complete and long-lasting remissions in hairy cell leukemia (HCL) patients after a single one-week course of 0.1 mg/kg/d of 2-Chlorodeoxyadenosine (2-CdA) administered by intravenous infusion. In these studies the evaluation of the clinical response was based on physical examination, blood cell counts, as well as cytochemical and immunological detection of residual leukemic cells. Since HCL is a chronic lymphoproliferative disorder characterized by the expansion of monoclonal B cells, analysis of the configuration of the immunoglobulin gene regions represents a valuable tool towards a more accurate monitoring of treatment response. We hereby describe the molecular assessment of the neoplastic clone in six HCL patients treated with 2-CdA; in five of them a disappearance of the rearranged bands could be documented in bone marrow cells aspirated between 2 and 21 months after a single course of continuous infusion 2-CdA. The last HCL case analyzed, revealed molecular persistence of the neoplastic clone. In all cases but one, the molecular evaluation was in agreement with the definition of clinical response based on conventional analysis. This study demonstrates that HCL patients treated with 2-CdA show a high incidence of molecularly-defined complete remissions, the likelihood of which is much greater than for patients treated with Interferon alpha.

Bone Marrow↗
PubMed1994

Expression of the IL2 receptor alpha, beta and gamma chains in hairy cell leukemia.

The expression of the interleukin 2 (IL2) receptor chains was investigated by immunofluorescence and mRNA analysis in typical and variant hairy cell leukemia (HCL) cases. While typical hairy cells express both the alpha and the beta chains, variant HCL express the IL2 receptor beta chain on the surface membrane but not the alpha chain. Both typical and variant HCL have mRNA transcript of the p64 molecule (gamma chain). In B-cell chronic lymphocytic leukemia (B-CLL), EBV-transformed lymphoblastoid cell lines and normal B lymphocytes the expression of the IL2 receptor alpha and beta chains is very weak or negative. Furthermore, in B-CLL the IL2 receptor gamma chain shows a weaker expression compared to HCL. Both classic and variant HCL cases appear capable of proliferating in the presence of exogenous IL2, though the proliferative response of variant HCL appears lower than that of typical cases. Since in variant HCL the IL2 receptor alpha chain could not be induced by different stimuli, it appears that the CD25 antigen may not be essential in the process of IL2-promoted growth, while p75 and p64 play a primary role in IL2 activation. Taken together, it is suggested that the expression of IL2 receptors is up- or down-regulated during the process of B-cell lineage activation and differentiation.

Leukemia, Hairy Cell↗
PubMed1994

AIDS-associated Kaposi's sarcoma and non-Hodgkin's lymphomas reporting in Italy: a linkage study.

To evaluate the completeness and accuracy in the reporting of AIDS-associated Kaposi's sarcoma (KS) and non-Hodgkin's lymphomas (NHL) in Italy, a linkage study of the notifications to the Italian AIDS Registry (RAIDS--the national compulsory AIDS surveillance system) and the clinical and pathological records of the Italian Cooperative Group on AIDS-related tumors (GICAT--a nationwide voluntary reporting system for HIV-infected individuals who develop cancer) was carried out. A total of 288 cases of KS and 258 cases of NHL fulfilling the AIDS definition criteria, histologically diagnosed by the GICAT centers between January 1987 and March 1992, were matched with the 16,860 AIDS cases reported to the RAIDS up to March 1993. The linkage procedure, based on name, gender, and date of birth, identified 276 cases of KS (96%) and 241 cases of NHL (93%) present in both files ("linked" cases). The diagnosis of KS did not appear among the clinical manifestations of AIDS in the RAIDS file in 67 out of the 276 linked KS (24%), either with coincident dates of KS diagnosis and of case notification (19 cases) or when the KS diagnosis followed by > or = 2 months the case notification to RAIDS (48 cases). Of the 241 linked NHL, 84 (33%) had no such neoplastic complications of AIDS listed in the RAIDS file, 23 with coincident dates of NHL diagnosis and of case notification and 61 with the NHL diagnosis made > or = 2 months after the notification. A noteworthy discrepancy in the classification of the three histologic subtypes of NHL emerged between the GICAT and the RAIDS. The degree of underreporting of AIDS-associated cancers that emerged from the present study suggests that augmentation with other sources of oncological information is important to better estimate the burden of AIDS-related tumors and to study the interaction between HIV infection and cancer.

Acquired Immunodeficiency Syndrome↗
PubMed1994

The polymerase chain reaction detects B cell clonalities in patients with Sjögren's syndrome and suspected malignant lymphoma.

OBJECTIVE: To investigate the usefulness of the polymerase chain reaction (PCR) to detect B cell clonal expansions in tissues where lymphoproliferative disease was suspected in the course of Sjögren's syndrome (SS). METHODS: Tissue samples from 7 patients with definite (5 cases) or probable (2 cases) SS were subjected to routine histopathologic studies, immunophenotyping, and genotypic analysis, including Southern blotting and PCR amplification of immunoglobulin heavy chain (IgH) variable-diversity-joining (VDJ) region gene rearrangements. RESULTS: Malignant lymphoma was detected in 3 cases, and myoepithelial sialadenitis in the remaining 4. B cell clonal expansion was detected in 7/7 cases by PCR, 5/7 by Southern blotting, and in no case of myoepithelial sialadenitis by kappa/lambda light chain immunophenotyping. CONCLUSION: PCR may represent a quick and powerful tool to detect B cell clonalities in SS. Such information may provide new insights into the pathogenesis of the disease and may improve the clinical approach to the patients.

Adult↗
PubMed1994

Sieve-like areas in mature cystic teratomas of the ovary. A histochemical and immunohistochemical study of 7 cases.

The authors describe histologic and immunohistologic features of seven cases of ovarian mature teratomas showing multiple cysts, optically empty, in their walls. These cysts have been detected in 7 out of 31 cases of ovarian teratomas observed from 1985 to 1991 (incidence rate 22%); they measured from less than 0.1 mm up to 5 mm in their largest size, and were lined by flattened cuboidal cell, histiocytes and multinucleate foreign body-type giant cells. Masson trichrome stain revealed a fibrous framework around them. Immunohistochemical stains provided evidence of both macrophagic and endothelial nature of the lining cells of the cysts because of their cytoplasmic positivity for KP1, KIM 6 and, though focally, for FVIII-related antigen. Ovarian teratomas exhibiting such aspects, defined as pneumatosis cystoides-like appearances or multicystic structures, have been previously described. These peculiar morphologic finding are reported in gynecological literature under the heading of sieve-like areas but, generally, little information about the mechanisms of their constitution is available. Etiopathogenic hypotheses are hereafter considered and discussed. The present findings suggest that these multicystic spaces may be the result of a granulomatous lipophagic reaction due to extravasated material (such as lipids or sebum) and/or of a dilatation of lymphatics vessels.

Female↗
PubMed1993

Myocardial expression of atrial natriuretic factor gene in early stages of hamster cardiomyopathy.

Ventricular cardiomyocytes represent the most important source of atrial natriuretic factor (ANF) in pathological conditions such as congestive heart failure (CHF). It has been suggested that in cardiomyopathic Syrian hamster ventricles the ANF gene can be reactivated during the hypertrophic stage occurring before heart failure. The present study was undertaken to investigate ANF gene expression during early stages of myocardial damage and its distribution throughout atrial and ventricular myocardium in UM-X7.1 cardiomyopathic Syrian hamsters (CMPH) before hypertrophy and cardiac failure occur. Atria, right and left ventricles, and interventricular septum of hearts of 20-23 days old (young) and 90-95 days old (adult) CMPH were studied. The absence of hypertrophy and cardiac failure was preliminarly ascertained by microscopic and hemodynamic evaluation. ANF-mRNA as well as tissue and plasma immunoreactive ANF were assayed. Moreover, ANF secretion pattern was evaluated by immunocytochemical techniques. Young and adult CMPH hearts were in the necrotic stage of myocardial disease, as demonstrated by histopathological evaluation and by decreased wet weights (mg/g body weight) of different heart regions. Hemodynamic assessment showed no significant changes of left ventricular end-diastolic pressure (LVEDP) and a decrease of the left ventricular peak systolic pressure (LVSP) and +dP/dt. Plasma immunoreactive ANF (IR-ANF) levels were higher in young (3-fold) and adult (6-fold) CMPH than in age-matched normal hamsters. A reduced IR-ANF concentration (per milligram protein) was observed in both young and adult cardiomyopathic atria in respect to healthy controls, whereas a higher IR-ANF concentration was present in ventricles. A 3-fold, 6-fold and 20-fold increase of IR-ANF concentration was found in right ventricular free-wall (RV), left ventricular free-wall (LV) and interventricular septum (IVS), respectively. Northern-blot analysis confirmed that IVS was the major site of ventricular ANF-mRNA transcription in both young and adult CMPH. ANF-mRNA was increased also in atria where a faster peptide secretion can be hypothesized to lower tissue IR-ANF concentration. ANF secretion in ventricular myocardium was achieved via constitutive pathway as demonstrated by immunocytochemistry. Different patterns of ANF gene reactivation occur in CMPH myocardium before intraventricular pressure increases and structural hypertrophic modifications are detectable. The extent of ANF gene reactivation in CMPH ventricles parallels the severity of necrotic damage. Moreover, ANF gene expression is heterogeneously distributed throughout the myocardium, suggesting that interventricular septum, the ontogenically youngest heart region, might preserve foetal characters which can be rapidly reactivated in pathological conditions.

Animals↗
PubMed1993

Differential expression of cell adhesion molecules in B-zone small lymphocytic lymphoma and other well-differentiated lymphocytic disorders.

BACKGROUND: Cell adhesion molecules (CAM) may determine the patterns of growth and dissemination of lymphoproliferative disorders. METHODS: The authors have studied, by flow cytometric and immunohistochemical examination, the expression of several CAM, mediating cell-cell and cell-microenvironment interactions, on B-zone small lymphocytic lymphoma (BZSLL) and other B-cell low-grade non-Hodgkin lymphomas (NHL), including intermediate lymphocytic/mantle zone lymphoma (ILL/MZL), small lymphocytic lymphoma (SLL), and chronic lymphocytic leukemia (CLL). RESULTS: Relevant differences in the "adhesion phenotype" of BZSLL compared with other low-grade NHL examined were evidenced. Cells from BZSLL displayed a higher rate of expression and/or a stronger intensity of LFA-1, LFA-3, ICAM-1, and BL-CAM and a lower density of H-CAM and LAM-1 homing receptors, as opposed to SLL or CLL. A lower intensity of H-CAM along with a stronger expression of LFA-1, LFA-3, ICAM-1, and BL-CAM were also detected by comparing BZSLL with ILL/MZL: Malignant cells from BZSLL expressed Leu-CAMb determinants in three cases. BZSLL cells lacked VLA-alpha 5-integrins as opposed to CLL lymphocytes and displayed a stronger reactivity with anti-VLA-alpha 4 antibodies with respect to ILL/MZL and CLL. beta 1-integrins were consistently detected on BZSLL lymphocytes as opposed to ILL/MZL: CONCLUSIONS: These data suggest that the adhesion phenotype of BZSLL, by favoring homotypic and heterotypic adhesive interactions of tumor cells, might account at least in part for the peculiar intranodal compartmentalization leading to a deceptively benign (reactive) histologic appearance, and for the smoldering clinical course of this lymphoma. The pattern of CAM expression detected by the authors on malignant lymphocytes also is suggestive for a cellular origin of BZSLL from a rare subset of interfollicular or external mantle B-lymphocytes.

Cell Adhesion Molecules↗
PubMed1993

Subtypes of Epstein-Barr virus in HIV-1-associated and HIV-1-unrelated Hodgkin's disease cases.

Epstein-Barr virus (EBV) type 2 is considered to be a much less potent transformer of lymphocytes than type 1. However, type-2 EBV may be involved in the pathogenesis of non-Hodgkin's lymphomas (NHLs) arising in immunocompromised patients, i.e., subjects with malaria or HIV-1 infection. To determine whether type-2 EBV may also play a role in Hodgkin's disease (HD) developing in immunocompromised patients, we characterized EBV subtypes in EBV-positive HD samples from 10 HIV-1-positive patients as well as from a control population of 24 HIV-1-negative patients. Type-2 EBV was detected in 5/10 HD samples from the HIV-1-positive group (1 case showed concomitant type-1 EBV positivity), but only in 1/20 HD samples from the HIV-1-negative group, indicating that, during HIV-1-induced immunodepression, type-2 EBV may be pathogenetically involved also in HD, as previously reported for HIV-associated NHLs.

Base Sequence↗
PubMed1993

Differential expression of cell adhesion molecules CD54/CD11a and CD58/CD2 by human melanoma cells and functional role in their interaction with cytotoxic cells.

Immunohistochemical staining with monoclonal antibodies showed a differential distribution of intercellular adhesion molecule 1 (ICAM-1/CD54) and lymphocyte function-associated antigen 3 (LFA-3/CD58) and their respective counterreceptors lymphocyte function-associated antigens 1 (LFA-1/CD11a) and 2 (LFA-2/CD2) on ten melanoma cell lines and in 46 surgically removed metastatic melanoma lesions. CD11a and CD2 were not detected on melanoma cells while CD54 and CD58 were coexpressed on the majority of the melanoma cell populations investigated. CD54 showed a higher degree of intra- and intertumor heterogeneity than CD58. gamma-Interferon and/or tumor necrosis factor alpha upregulated the expression of CD54 by melanoma cells, but neither modulated that of CD58 nor induced that of CD11a and CD2. Anti-CD54 and anti-CD58 monoclonal antibodies partially inhibited the lysis of melanoma cells by allogeneic natural killer cells, lymphokine-activated killer cells and, to a greater extent, by autologous tumor-infiltrating lymphocytes. Soluble CD54 (cCD54) purified from serum of patients with melanoma inhibited the lysis of melanoma cells F0-1 by natural killer cells in a dose-dependent fashion. These results suggest that membrane-bound CD54 and CD58 and cCD54 play a role in host-tumor interactions in patients with malignant melanoma and may account for the relationship between CD54 expression in primary lesions and the clinical course of disease.

Antigens, CD↗
PubMed1993

Phenotypic analysis of hairy cell leukemia: "variant" cases express the interleukin-2 receptor beta chain, but not the alpha chain (CD25).

Hairy cell leukemia (HCL) is a B-cell chronic lymphoproliferative disorder in which the pathologic cells show a strong expression of CD25 (interleukin-2 [IL-2] receptor alpha chain or p55). "Variant" cases of HCL, characterized by hyperleukocytosis, neoplastic elements with a prominent nucleolus and a higher nucleo/cytoplasmic ratio, and an easily obtained bone marrow aspirate, lack surface CD25 determinants. Limited information is available on the expression of the IL-2 receptor beta chain (p75) on normal and neoplastic B cells. In this study, we have assessed by immunofluorescence and mRNA analysis the presence of the IL-2 receptor alpha and beta chains on 12 cases of classic HCL, as well as on 3 variant cases. The results obtained show that, while the alpha chain of the IL-2 receptor is present only on classic HCL, the IL-2 receptor beta chain (p75) is expressed on both the classic and variant form. Unlike hairy cells, only 8 of the 15 B-cell chronic lymphocytic leukemia cases tested showed a weak expression of the p75 antigen on a small proportion of cells. Purified B lymphocytes from normal healthy controls, as well as Epstein-Barr virus-transformed lymphoblastoid cell lines, showed a weak staining for the p75 determinant, while being CD25-. The results of this study suggest that the expression of the alpha and beta chains of the IL-2 receptor appears to be upregulated or downregulated during the process of B-cell-lineage activation and differentiation.

Adult↗
PubMed1993

High incidence of monoclonal EBV episomes in Hodgkin's disease and anaplastic large-cell KI-1-positive lymphomas in HIV-1-positive patients.

A series of selected lymphoid malignancies (LMs) occurring in Italian HIV-1-infected (HIV+) patients, principally intravenous drug users, was investigated. In addition to small non-cleaved-cell (SNCC) and large-cell immunoblastic (LCI) non-Hodgkin's lymphomas (NHLs), a relatively high occurrence of anaplastic large-cell Ki-I-positive (ALC Ki-I+) lymphomas and Hodgkin's disease (HD) was observed, at variance with other reported series of HIV+ patients. Combined results of in situ hybridization and Southern-blot analyses, in conjunction with immunohistochemical detection of Epstein-Barr virus (EBV)-encoded latent membrane protein-I (LMP-I), showed an almost complete association of ALC Ki-I+ lymphomas and HD cases with EBV. The neoplastic cells of both these LMs also showed common immunophenotypic features such as frequent absence of B- and T-cell differentiation markers and expression of the Ki-I activation marker, while SNCC and LCI lymphomas were mainly of mature B-cell origin and Ki-I-. The concomitant high incidence of ALC Ki-I+ lymphomas and HD in a specific group of HIV+ patients, their almost complete association with EBV in clonal and episomal form and the great similarity in differentiation, activation and virological markers which they display suggest that these LMs are pathological variants of a continuous spectrum of HIV-I-associated disorders etiopathologically linked to EBV.

Antigens, CD↗
PubMed1993

Heterogeneous immunoglobulin gene rearrangement in a B-chronic lymphocytic leukemia progressing into non-Hodgkin lymphoma (Richter syndrome).

BACKGROUND: The relationship between chronic lymphocytic leukemia (CLL) and supervening non-Hodgkin lymphoma is debated, as is whether a particular genomic pattern is related to the emergence of the terminal lymphoma. To investigate these features, the molecular organization of the immunoglobulin (Ig) gene region in a case during both the B-CLL and Richter transformation phase was studied. METHODS: B-CLL and non-Hodgkin lymphoma cells were processed for Southern blot analysis of Ig heavy- and light-chain gene configuration. RESULTS: Molecular studies of B-CLL cells revealed the presence of a single Ig heavy-chain rearrangement with both kappa and lambda light-chain rearranged genes, which was consistent with the occurrence of multiple mutational events during the development of the B-CLL clone. Molecular analysis of the lymphoma DNA showed new Ig heavy- and kappa light-chain rearrangements in addition to the original ones related to the CLL phase, indicating that the lymphoma tissue consisted of two genotypically distinct populations of cells. CONCLUSIONS: On the basis of the overall molecular configuration, this heterogeneous pattern of Ig gene rearrangement was interpreted as an inherent genetic instability of the CLL clone, in which multiple mutational events allowed a selective pressure toward more aggressive subclones, resulting in the emergence of the terminal lymphoma.

Antigens, CD↗
PubMed1993

Co-expression of Epstein-Barr virus latent membrane protein and vimentin in "aggressive" histological subtypes of Hodgkin's disease.

The presence of Epstein-Barr virus (EBV) genome in Hodgkin's and Reed-Sternberg (HRS) cells, as detected using in situ hybridization (ISH) with biotinylated BamHI "V" probes, along with the expression of EBV-encoded latent membrane protein (LMP) and vimentin was examined in paraffin-embedded sections of 39 immunomorphologically characterized cases of Hodgkin's disease (HD). ISH demonstrated EBV in HRS cells in 15 of 39 cases, whereas LMP expression was detected in 11 of 39 cases, only in the presence of EBV genome detection. With the exception of 1 case, in which HRS cells expressed B-cell-associated antigens, the LMP-positive cases included specimens in which HRS cells were of non-B, non-T phenotype. LMP expression showed a stronger association with lymphocyte depletion (LD) (3/3) and mixed cellularity (MC) (6/11) than with lymphocyte predominance (0/5) or nodular sclerosis (2/20) subtypes. Vimentin expression on HRS cells was found in all the LMP-expressing cases and only in a fraction (13/28) of LMP-negative cases. This study supports the view that HD represents a heterogeneous group of diseases also in terms of EBV association, LMP expression being strongly related to the "aggressive" LD and MC histological subtypes. In light of the supposed interactions between vimentin and LMP, their co-expression on HRS cells, as detected in this study, provides further evidence for a significant role of EBV in the development of a proportion of HD cases.

Antigens, CD↗