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A Pacchiarotti

Publications and source records attributed to A Pacchiarotti.

At least 19 recordsLinked to original sources

Expression of TCL1 and CD27 in primary cutaneous B-cell lymphomas.

AIMS: To investigate by immunohistochemical analysis the expression of the TCL1 oncogene product and of CD27 in 25 cases of primary cutaneous B-cell lymphomas (PCBCL) classified according to the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. In B-cell ontogenesis TCL1 is mainly expressed by 'naive' B lymphocytes and by a subset of germinal centre B cells, whereas CD27 is expressed by a subset of germinal centre B cells, 'memory' B lymphocytes and plasma cells, suggesting that their expression in physiological conditions is mutually exclusive. METHODS AND RESULTS: Overall, TCL1 was expressed in 5/25 cases (20%) and CD27 in 15/25 cases (60%). Furthermore, 7/25 cases (28%) were TCL1- and CD27- and 2/25 cases (8%) were TCL1+ and CD27+. In particular, primary cutaneous follicle-centre lymphomas (10 cases) showed a variable expression of both TCL1 and CD27, whereas primary cutaneous marginal-zone B-cell lymphomas (eight cases) showed, with the exception of a single case, a definite CD27+/TCL1- profile. CONCLUSIONS: These findings indicate: (i) the TCL1 oncogene product is uncommonly expressed in PCBCL (20% of cases, mainly of the follicle-centre subtype); (ii) in contrast, CD27 is often expressed in PCBCL (60% of cases), mainly of the marginal-zone subtype; (iii) the coexpression of TCL1 and CD27 may be seldom observed in PCBCL (8% of cases); (iv) PCBCL does not seem to show, in terms of either TCL1 or CD27 expression, significant differences compared with its systemic counterparts.

Biomarkers, Tumor↗

[Not Available].

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Journal Article↗

[Sentinel node biopsy for malignant melanoma. Technical details and clinical results on 390 patients].

BACKGROUND: The purpose of this paper is to present personal experience with sentinel node biopsy for the treatment of malignant melanoma. Technical details influencing the efficacy of the procedure are presented and the clinical, therapeutic and prognostic advantages of this technique discussed. METHODS: A total of 390 consecutive patients with primary skin melanoma (T2-3,N0,M0) underwent sentinel node biopsy between March 1996 and May 2001. All patients underwent previous excisional biopsy of the primary lesion and clinical and radiographic examination to exclude lymphatic or systemic macroscopic spreading of the disease. Preoperative lymphoscintigraphy (99mTc nanocoll) was routinely performed in the last 315 patients. Intraoperative detection of the sentinel nodes was performed by perilesional, intradermical, injection of blue dye associated with a g probe (Neoprobe(R) 2000) in the last 315 patients. Sentinel nodes, serially sectioned, were all Haematoxylin-Eosin and immunohistochemically stained. All patients positive for micro-metastasis underwent radical lymphadenectomy. Comparative analysis between the incidence of metastasis in sentinel and non-sentinel nodes, according to the clinical stage of the disease, was done. RESULTS: The overall detection rate of sentinel nodes was 97.4%. Relevant differences were found according to the site of dissection and the use of a g probe. The g-probe makes the procedure more effective, less invasive and less expensive. Timing and accuracy of the preoperative lymphoscintigraphy is a basic step of the procedure. The overall incidence of positive sentinel nodes was 14.7% with differences correlated with thickness of primary lesion (0.75-1.5 mm: 5,8%; 1.5-3 mm:18%; 3-4 mm: 24.6%). Metastasis in other non-sentinel nodes was found only with primary tumour thickness exceeding 2 mm. CONCLUSIONS: Sentinel node biopsy is a procedure requiring a multidisciplinary approach (surgery, nuclear medicine and pathology). A specific learning phase (>30 patients) is recommended to obtain reliable results.

Biopsy↗

[Immune tolerance in pregnancy. Maternal-fetal interactions].

The conceptus may be considered as a sort of semi-allogenic graft for the maternal organism, since it shares a half of genomic complement with the father. Nevertheless, its rejection does not take place physiologically during a pregnancy. The mechanisms resulting in the maternal immune tolerance versus the conceptus are not yet completely clarified. Such mechanisms are probably multiple and interacting with each other. In animal and in vitro studies provide evidence suggesting that the following factors are important in producing the maternal immune tolerance: the anatomical position of the fetus; the absence of expression of the class I and II Major Histocompatibility Complex (MHC) molecules in trophoblast tissues; the activity of blocking antibodies; a modification of the immune response; the fetal-placental production of immunosuppressive hormones and substances. Amongst pregnancy-related changes in the immune response, a reduced Natural Killer (NK) cell activity and an increased synthesis of Th2 cytokines (which inhibit the cell-mediated immunity) with an altered Th1/Th2 balance appear to be remarkably important. With regard to fetal-placental hormones, progesterone seems to exert an important immunosuppressive influence mediated by the protein named "Progesterone Induced Blocking Factor" (PIBF). Nevertheless, the real contribution of each of the above mentioned mechanisms still remains to be elucidated in humans.

Female↗

Pathogenetic and clinical implications of Bcl-6 and Bcl-2 gene configuration in nodal diffuse large B-cell lymphomas.

Bcl-6 (LAZ-3) and Bcl-2 gene rearrangements have been respectively reported in 20-35 per cent and 10-25 per cent of diffuse large B-cell lymphomas (DLBCLs). Although these genetic lesions have been associated with different clinical outcomes (i.e., more favourable in Bcl-6 rearranged cases and poorer in Bcl-2 rearranged cases), their prognostic significance is still controversial. In the present study, we have investigated by Southern blot analysis the Bcl-6 and Bcl-2 gene configuration in a series of 80 lymph nodes involved by well-characterized DLBCLs, histologically defined according to the REAL and the updated Kiel classifications. The molecular findings have been correlated with the clinical features at presentation and with response to therapy. The majority of cases (57/80 = 71.2 per cent) had a centroblastic morphology. Bcl-6 rearrangements were detected in 23/80 cases (28.8 per cent), and were similarly associated with centroblastic (18/57 = 31.6 per cent) or immunoblastic (3/11 = 27.3 per cent) histotypes. In contrast, Bcl-2 was found to be rearranged in only three cases of centroblastic lymphoma (3.8 per cent). No significant differences were found between Bcl-6 rearranged and germline cases, as far as the clinical features at presentation are concerned. Forty-one patients, in whom the lymph node biopsy was performed at diagnosis, could be evaluated for response to treatment and clinical outcome. Most of these cases (30/41 = 73.2 per cent) were nodal DLBCL, without extranodal site involvement. Analysis of the clinical outcome showed no statistically significant differences between Bcl-6 rearranged and Bcl-6 germline cases (actuarial overall survival 50 per cent vs. 48 per cent, event-free survival 45 per cent vs. 46 per cent, at 4 years). These findings confirm that Bcl-6 rearrangements are the most frequent genetic lesion in DLBCL. The incidence of Bcl-2 involvement in our series is significantly lower than the figures reported in other studies, mainly from North American countries, probably reflecting heterogeneous patient selection and/or epidemiological variability. Finally, our results suggest that no relevant clinical differences are observed between Bcl-6 rearranged and Bcl-6 germline cases, when nodal DLBCLs are considered.

Adolescent↗

Simultaneous occurrence of large B-cell non-Hodgkin lymphoma and myelodysplastic syndrome rapidly evolving into acute myeloblastic leukemia.

We describe a case of simultaneous occurrence of large B-cell non-Hodgkin lymphoma and myelodysplastic syndrome in the absence of previous chemotherapy or radiotherapy. After initiation of steroid treatment, the myeloid clone showed a rapid increase in both the bone marrow and peripheral blood with transformation into acute myeloid leukemia. The diagnosis were confirmed by immunophenotypic studies performed in the histologic sections of the lymph node, as well as in bone marrow and peripheral blast cells. This case may be indicative of potential down-regulation of a malignant myeloid clone induced by the malignant lymphoid clone.

Aged↗

Analysis of the BCL-6 gene configuration in diffuse B-cell non-Hodgkin's lymphomas and Hodgkin's disease.

BCL-6 is a novel proto-oncogene that codes for a zinc-finger protein sharing homologies with many transcription factors. It has recently been shown that BCL-6 is involved in chromosome band 3q27 aberrations in non-Hodgkin's lymphomas (NHLs) and BCL-6 rearrangements have been detected in 34-45 per cent of diffuse large cell lymphomas with B immunophenotype. We have studied the BCL-6 gene configuration by Southern blot analysis in 60 cases of B-cell NHL and in 17 cases of Hodgkin's disease (HD). BCL-6 was rearranged in 15/46 (32.6 per cent) diffuse B-large cell lymphomas, mainly with centroblastic morphology, and in 2/11 (18.2 per cent) follicular (centroblastic-centrocytic) lymphomas. Conversely, all cases of HD, including four cases of lymphocyte predominant, nodular type (nodular paragranuloma), had a germline configuration. These findings confirm that BCL-6 is rearranged in a significant percentage of diffuse B-large cell lymphomas, suggesting that this proto-oncogene might have a pathogenetic role in this subset of NHLs, but our preliminary analysis suggests that BCL-6 lesions are not involved in the pathogenesis of HD. However, further investigations using more sensitive techniques are required to confirm these findings.

Blotting, Southern↗

Peripheral neuroectodermal tumor of the chest (Askin tumor) as secondary neoplasm after Hodgkin's disease: a case report.

The authors present the case of a 20-year-old woman who developed a peripheral neuroectodermal neoplasm of the thoracopulmonary region (Askin tumor) 7 years after achieving complete remission of stage-IV Hodgkin's disease. The previous treatment had consisted of eight courses of alternating MOPP/ABVD combined with involved-field 20-Gy radiotherapy. The second neoplasm appeared in a nonirradiated area of the chest wall, with erosion of the ribs as shown by sonography and computed tomography. The histological pattern was in accordance with a generic diagnosis of a malignant small cell tumor; the immunostaining positivity of the neoplastic cells for the neuron-specific enolase allowed us to make the diagnosis of a tumor with a neuroectodermal origin. Partial resection of the neoplasm and four courses of chemotherapy including adriamycin, cisplatin, and ifosfamide induced a complete remission, confirmed by surgical restaging. She is alive and well 10 months after the completion of therapy. The clinical, radiological, and microscopic features of this tumor occurring as a secondary neoplasm after Hodgkin's disease are described.

Adult↗

Deoxycoformycin induces long-lasting remissions in hairy cell leukemia: clinical and biological results of two different regimens.

The use of alpha interferon (alpha IFN) and, more recently, of the purine analogues deoxycoformycin (dCF) and 2-chlorodeoxyadenosine (2-CdA) has dramatically improved the prognosis of patients affected by hairy cell leukemia (HCL). DCF has been shown to induce an higher and more durable response rate than IFN, with only moderate myelosuppression and relatively few side effects. In this paper, we report our experience with dCF in a series of 38 HCL patients who had progression of their disease after IFN therapy. Serum interleukin-1 beta (IL-1 beta), soluble interleukin-2 receptors (sIl-2R) and Tumor Necrosis Factor alpha (TNF alpha) levels were also evaluated before, both during and after treatment in order to monitor clinical response. Two schedules of treatment were employed: 23 patients were treated with the EORTC protocol and the following 15 with the NCI regimen. The overall response rate was 94.7%; no significant differences in response rates were observed between the two schedules. In respect to toxicity, we recorded nausea and in two cases a cutaneous rash. Four patients experienced localized herpes zoster and one had a fungal pneumonia. Median overall survival after therapy is 38.5 months, 55 percent of patients enrolled in the EORTC schedule and 77% of those who received the NCI program are currently in CCR at 3 years. Serum IL-1 beta and sIL-2R levels significantly decreased after treatment, while no significant changes in serum TNF alpha levels were observed. In our study, dCF was confirmed as an effective agent in HCL, inducing an high response rate with only moderate side effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

HLA typing in hairy cell leukemia.

In HCL patients some cases of familial occurrence of the disease were reported, without an association with a specific haplotype or HLA antigen. In a series of a non familial HCL patients an increase in DR11 frequency was reported. We performed HLA class I and class II antigens in a series of 38 consecutive HCL patients. An increased frequency of B17 (10/38-27%) and DR11 (22/38-57%) antigens compared with the normal Caucasian population was recorded. As clinical characteristics, no significant differences were recognized between DR11 positive and DR11 negative patients. In response to IFN treatment, a complete response (CR) was achieved in 20% of DR11 patients and in 46% of DR11 negative patients. In this study an increase frequency of B17 and DR11 antigens was found; furthermore DR11 positive patients seem to be less responsive to IFN treatment but a larger series of patients will have to be studied in the future in order to establish this observation with more certainty.

Adult↗

Multinucleated giant cells generation induced by interferon-gamma. Changes in the expression and distribution of the intercellular adhesion molecule-1 during macrophages fusion and multinucleated giant cell formation.

BACKGROUND: Multinucleated giant cells (MGC), interferon-gamma (IFN-gamma) production, and increased expression of adhesion molecules are features of granulomatous reactions. IFN-gamma induces the fusion of macrophages and the subsequent MGC generation in vitro. Moreover, IFN-gamma increases ICAM-1 expression on lymphoid cells and an important role for adhesion molecules in MGC generation has been proposed. EXPERIMENTAL DESIGN: The time course of the IFN-gamma-driven MGC generation was investigated in slide-chamber cultures of adherence-purified human monocytes. The fusion index, the monocytes clustering the total number of MGC were determined. The expression of intercellular cell adhesion molecule-1 (ICAM-1), LFA-1 and HLA-DR was investigated by immunohistochemistry. The effect of anti-ICAM-1, anti-LFA-1 and anti-HLA-DR monoclonal antibodies on IFN-gamma-induced MGC generation was also examined. RESULTS: IFN-gamma enhanced the generation of MGC in a dose- and time-dependent fashion. In all experiments, MGC formation was preceded by a sequence of changes in the morphology of cultured monocytes. Cell clustering occurred as early as 3 days after IFN-gamma stimulation and was followed by the adhesion of cells that eventually fused. Immunohistochemistry showed that ICAM-1 was increased by IFN-gamma and constantly polarized on a cell uropode. When monocytes clustered, ICAM-1 was localized on the membrane where the cell-to-cell contact occurred. In newly formed MGC, ICAM-1 stained in the center of the giant cell. The cellular distribution of LFA-1 on cultured monocytes was not modified by IFN-gamma. HLA-DR expectedly enhanced by IFN-gamma was mostly cytoplasmic and tended to disappear when MGC formed. Finally, anti-LFA-1 and anti-ICAM-1 monoclonal antibodies variably inhibited IFN-gamma-induced MGC generation. CONCLUSIONS: Taken together, these data add support to the concept that IFN-gamma is essential for MGC generation by promoting cell clustering and cell-to-cell adhesion. The present data also indicate that among the mechanisms by which IFN-gamma exert such a promoting effect, changes in the ICAM-1 expression and cellular distribution are included. The observation that ICAM-1 appears to be trapped in the cytoplasm of IFN-gamma-driven MGC and that HLA-DR tend to disappear from macrophages undergoing MGC formation, also suggest changes in the functional properties of these cells.

Cell Fusion↗

Lack of nocturnal serum thyrotropin surge after surgery.

The effects of surgery on TSH secretion, with particular regard to the nocturnal TSH surge, were evaluated in 10 consecutive patients followed for 6 days after surgery. Surgical trauma was associated in all patients with significant decreases in serum total and free T3 and a significant increase in serum rT3 levels, with no variations in serum total and free T4 concentrations. A marked increase in serum cortisol levels was observed, with higher values at night than in the morning. Serum cortisol levels and circadian rhythm normalized on the fifth day. Serum TSH values in the morning significantly decreased on the first day after surgery and returned to normal on the second day. Serum TSH values at night (2400-0200 h) were higher than in the morning preoperatively, but the nocturnal surge was abolished from days 1-5 after surgery and was restored only on the sixth day. Thus, surgery was associated with a prolonged loss of the nocturnal serum TSH surge. This effect on TSH secretion was more marked than predictable on the basis of serum TSH measurements in the morning alone. An inverse relationship was found between serum cortisol and serum TSH values at night, suggesting that the excessive endogenous cortisol secretion might play a role in the derangement of TSH secretion.

Adult↗

Nocturnal serum thyrotropin (TSH) surge and the TSH response to TSH-releasing hormone: dissociated behavior in untreated depressives.

TSH secretion, with particular regard to the nocturnal surge of the hormone, was evaluated in 15 women (age range, 35-66 yr; mean, 50 yr) with untreated major endogenous depression and 15 healthy women (age range, 32-67 yr; mean, 53 yr) using an ultrasensitive assay. Mean morning (0830 h) TSH values did not differ in the 2 groups (1.3 +/- 02 mU/L in depressives and 1.4 +/- 0.1 mU/L in controls), whereas mean nighttime (2400-0200 h) values were significantly reduced in depressives (1.5 +/- 0.3 vs. 3.1 +/- 0.3 mU/L; P less than 0.0005). At variance with the control group, morning and nighttime TSH values did not differ in the depressives. The nocturnal serum TSH surge was abolished in 14 of 15 depressed patients. The mean peak TSH value after TRH was slightly yet significantly lower in the depressives. Patients with subnormal (less than 0.4 mU/L) TSH values in the morning had a serum TSH increase after TRH less than 2 mU/L in 5 of 6 cases and a lack of the nocturnal TSH surge in 6 of 6. Among the 9 patients with normal TSH values in the morning, the nocturnal serum TSH surge was lost in 8 of 9, whereas the response to TRH was normal in all. The depressives, at variance with other reports, showed significantly lower values of total and free thyroid hormones. Mean serum sex hormone-binding globulin (SHBG) and ferritin were also significantly reduced. In conclusion, major endogenous depression is associated with a major impairment of TSH secretion, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal. In this regard, the loss of the nocturnal serum TSH rise would appear to be a more sensitive indicator of hypothalamus-pituitary-thyroid axis alterations in depressives than the TRH test, which is commonly used in the evaluation of these patients. The lack of the nocturnal TSH surge may be responsible for the reduced thyroid hormone secretion and supports the case for some degree of central hypothyroidism in endogenous depression.

Adult↗

Lack of nocturnal serum thyrotropin (TSH) surge in patients with chronic renal failure undergoing regular maintenance hemofiltration: a case of central hypothyroidism.

Thyrotropin (TSH) secretion was evaluated in a group of patients with chronic renal failure (CRF) undergoing regular maintenance hemofiltration and in normal controls. The study group included 68 patients (39 males and 29 females, age range 39-73 years, mean: 53 years). In all patients blood was drawn at 08:30-09:00 h; in 20 patients the nocturnal (24:00-02:00 h) serum TSH peak was also evaluated; 12 patients underwent stimulation test with synthetic TSH-releasing hormone (TRH). TSH was measured by an ultrasensitive immunoradiometric assay. CRF patients showed a significant decrease in serum total and free thyroxine and triiodothyronine concentrations, which in a substantial proportion of subjects were below the lower normal limit. Serum reverse triiodothyronine and thyroxine-binding globulin values did not differ in the two groups. Despite this trend of thyroid hormones to decrease, no patient had supranormal TSH values as in primary hypothyroidism. While the mean morning TSH concentrations of CRF patients did not differ from those of controls, the mean nocturnal values were significantly reduced in CRF (1.0 +/- 0.2 vs 3.2 +/- 0.4 mU/l, p less than 0.0005) and the nocturnal serum TSH surge was not observed in 18 of the 20 patients (90%) in whom it was evaluated. The mean serum TSH peak value after TSH-releasing hormone (TRH) administration was also reduced in CRF patients, and the TSH response to TRH was blunted in 3 out of 12 patients (25%). The results of this study demonstrate a major impairment of TSH secretion in CRF, which baseline TSH measurements in the morning and the evaluation of the TSH response to TRH may not reveal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Thyroxine uptake by human hepatoma cells from serum of patients submitted to long-term thyroxine suppressive therapy.

The significance of thyroxine (T4) uptake from serum in the assessment of thyroid status was evaluated, using human hepatoma (Hep G2) cells, in 30 euthyroid subjects, 6 hypothyroid and 19 hyperthyroid patients, and in 23 athyreotic cancer patients under T4 suppressive therapy. Cellular thyroxine (CT4) was determined according to Sarne and Refetoff, J. Clin. Endocrinol. Metab. 61: 1046, 1985. CT4 averaged 9.9 +/- 2.8 pg/well (mean +/- SD, range 5.7-15.3) in euthyroid subjects, 1.5 +/- 1.0 pg/well (range 0.05-4.2) in hypothyroid patients, 40.5 +/- 18.8 pg/well (range 18.3 +/- 104.7) in hyperthyroid patients, and 23.7 +/- 7.2 pg/well (range 14.2-40.2) in T4-treated patients. In eu-, hypo- and hyperthyroid patients, a significant correlation was observed between CT4 and free T4 index (FT4I), free T4 (FT4) or Sex Hormone Binding Globulin (SHBG) values. In T4-treated patients, CT4 values were correlated with FT4I values, but not with FT4 or SHBG levels. All T4-treated patients with elevated SHBG levels had elevated FT4, FT4I and CT4 values. In contrast, of the 16 T4-treated subjects with normal serum SHBG concentrations, all but one had normal FT3, 3 (19%) had elevated FT4, 10 (62%) elevated FT4I and 13 (81%) elevated CT4, but all (100%) had undetectable TSH levels. Thus, considering serum SHBG concentrations as a parameter of hepatic tissue response to thyroid hormone, CT4 values, at least in T4-treated patients, do not accurately reflect the liver responsiveness to thyroid hormone action.

Carcinoma, Hepatocellular↗