PubMed Health⌕ Search

Biomedical subjects

T Faraggiana

Publications and source records attributed to T Faraggiana.

At least 19 recordsLinked to original sources
PubMed2006

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↗
PubMed2005

Dysregulated apoptosis in primary varicose veins.

OBJECTIVE: Programmed cell death plays a critical role in various physiological processes. To investigate its possible pathogenic role in primary varicose veins we studied histological changes in surgical specimens from human varicose veins. In varicose and healthy veins, we also determined the number of cells in apoptosis, and investigated mediators regulating the intrinsic apoptotic mitochondrial pathway (Bax and caspase 9). METHODS: A total 23 varicose veins were obtained from 18 patients undergoing lower-extremity varicose vein surgery for primary varicose disorders. We used nine healthy veins obtained from nine patients undergoing distal arterial bypass grafting surgery as controls. The venous segment analysed was the distal part of the greater saphenous vein. Specimens for histological examination were stained with hematoxylin and eosin, trichromic and Victoria blue. Cell apoptoses and mediators of the mitochondrial pathway were detected in the media by immunohistochemistry using antibodies to peroxidase in situ apoptosis, Bax and caspase 9. Results were expressed as indexes for the three antibodies tested. The Mann-Whitney test was used to compare the results obtained in the two groups. RESULTS: Varicose vein specimens exhibited a more disorganised architecture than healthy veins and showed an increased number of collagen fibres and a decrease in the density and size of elastic fibres. All anti-apoptotic antibodies tested detected significantly fewer immunoreactive cells in tissue sections from the media of varicose veins than of healthy veins (peroxidase in situ, varicose veins (VV) median 2.4% (inter-quartile range 1.6-3.9) versus control (C) 14% (IQR 8.8-19); Bax, VV 1.4% (IQR 0.36-2.4) versus C 11% (IQR 7.6-15); and caspase 9, VV 1.7% (IQR 0.06-3.4) versus C 10% (IQR 9.1-12), P=0.0001 (Mann-Whitney test). CONCLUSION: Apoptosis is down regulated in the medial layer of varicose veins. This dysregulation of the cellular mechanism that maintains normal tissue integrity is mediated through the intrinsic apoptotic pathway and may be among the causes of primary varicose veins.

Adult↗
PubMed2001

Collagen VII expression in glomerular sclerosis.

Glomerular sclerosis is the final stage of a variety of kidney diseases and matrix molecules not normally expressed in the extracellular matrix are synthesized and accumulate during the sclerotic process. Collagen type VII is the major component of the anchoring fibrils at the dermal-epidermal junction, but it is usually not present in normal glomeruli. The aim of this study was to investigate whether this type of fibrillary collagen, different from types I and III, is expressed in chronically diseased glomerular extracellular matrix. The presence and distribution of collagen VII have been examined in 50 renal biopsies by indirect immunofluorescence staining, standard electron microscopy, and immuno-electron microscopy. In selected cases, collagen VII mRNA expression was also measured by RT-PCR on isolated glomeruli. Cases included focal segmental glomerulosclerosis, minimal change disease, membranous glomerulonephritis, IgA nephropathy, SLE nephritis, diabetic glomerulosclerosis, ischaemic renal disease, extracapillary glomerulonephritis, and end-stage renal disease. Collagen VII protein and mRNA expression was absent or present in trace amounts in normal kidneys or in disorders with only a mild increase of mesangial matrix, without scarring of the tuft. Maximal expression was evident in the presence of adhesions between the glomerular tuft and Bowman's capsule or fibrous crescents. The results showed that collagen VII is actively synthesized and laid down in areas of glomerular and/or tubular scarring, irrespective of the underlying disease, confirming the de novo expression of fibrillary collagens in diseased renal extracellular matrix. The appearance of an anchoring collagen may be a response to support mechanical stress and it takes part in the process of cell proliferation and tissue repair.

Case-Control Studies↗
PubMed2001

Melanoma cells stimulate osteoclastogenesis, c-Src expression and osteoblast cytokines.

Malignant melanomas metastasise to the bone and enhance osteoclast bone resorption. We demonstrated that a 48-h-B16 melanoma cell conditioned media (B16CM) induced osteoclastogenesis in mouse bone marrow cultures, without the requirement of B16 cell-bone marrow cell co-culture. B16 cells transcriptionally expressed detectable levels of TGFbeta1, IL-6, M-CSF, GM-CSF and TNFalpha mRNAs, albeit to a lower extent compared with levels in osteoblasts, and failed to express PTHrP, OPGL, OPG and IL-1beta. Interestingly, B16CM greatly upregulated IL-1beta, IL-6 and GM-CSF, and modestly enhanced TNFalpha and OPGL mRNA expression in osteoblasts, suggesting a potential indirect stimulation of osteoclastogenesis via the osteogenic lineage. B16CM barely upregulated c-Fos, but strongly and time-dependently enhanced c-Src expression in the total bone marrow cultures during osteoclast differentiation. Moreover, c-Src expression was enhanced in differentiated and purified osteoclast preparations to higher levels than in stromal cells. In conclusion, melanoma induces osteoclast generation with a paracrine mechanism independent of cell-cell contact, specifically upregulating c-Src in osteoclasts and cytokine expression in osteoblasts.

Animals↗
PubMed2001

Correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi.

BACKGROUND: The validity of clinical and histologic criteria in identifying dysplastic nevi is controversial. Recognition of the dysplastic nevus as a distinct clinicopathologic entity requires demonstration of significant agreement between clinical atypia and histologic dysplasia. OBJECTIVE: We attempted to determine the correlation between clinical atypia and histologic dysplasia in acquired melanocytic nevi and to evaluate the sensitivity and specificity of clinical criteria for dysplastic nevi when compared with histopathologic features. METHODS: A total of 940 acquired melanocytic nevi 3 mm in diameter or larger were selected by initially choosing clinically unequivocal dysplastic and nondysplastic nevi and then, from these, histologically unequivocal dysplastic and nondysplastic lesions. The level of concordance between clinical atypia and histologic dysplasia was estimated by kappa statistics. RESULTS: Nevi were classified as clinically dysplastic (n = 499) or nondysplastic (n = 441). On the basis of histologic features, 739 were classified as dysplastic and 201 as nondysplastic. Agreement between clinical atypia and histologic dysplasia was found in 432 nevi, that is, a sensitivity of 58.4% (3-5 mm = 27.2%, >5 mm = 69.8%). Agreement between clinical and histologic criteria on the absence of dysplasia was found in 134 nevi, a specificity of 66.6% (3-5 mm = 92.4%, >5 mm = 47.9%). The kappa value was 0.17 (3-5 mm = 0.14, >5 mm = 0.10). CONCLUSION: The limited sensitivity and specificity together with the negligible kappa value indicate a poor agreement between clinical and histologic diagnoses of dysplastic nevus. The dysplastic nevus cannot be considered a distinct clinicopathologic entity because histologic dysplasia is found in a range of nevi that may or may not show clinical atypia.

Adult↗
PubMed2001

Distribution of alpha-chains of type IV collagen in glomerular basement membranes with ultrastructural alterations suggestive of Alport syndrome.

BACKGROUND: In Alport syndrome (AS) impaired production and/or assembly of col IV alpha-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV alpha-chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS. METHODS: GBM distribution of col IV alpha1-, alpha3-, and alpha5-chain was investigated by immunohistochemistry in 32 patients (21 males and 11 females, mean age at biopsy of 11.5 years) with ultrastructural findings suggestive of AS. Ten patients had a proven COL4A5 mutation. Based on the severity of ultrastructural findings, the biopsies were grouped in three (I-III) electron microscopy (EM) classes. Significant EM changes of GBM (thinning, thickening, splitting, basket weaving of the lamina densa) were singularly evaluated using a semiquantitative scale (0-3). RESULTS: Col IV alpha1-chain was demonstrated in GBM of all patients. Three patterns of staining for col IValpha3- and alpha5-chains were observed: positive, negative, and alpha3(IV)-positive/alpha5(IV)-negative. By chi(2)-test, EM class III lesions and complete loss of alpha3(IV)- and alpha5(IV)-antigen were significantly more frequent (P<0.05 and P<0.01) in male patients, but no significant relation was observed between EM classes and immunohistochemical patterns. GBM alterations did not correlate with staining for alpha5(IV)-chain. Intensity of alpha3(IV)-chain staining, however, had a negative correlation (P<0.05) with the severity of GBM basket weaving. CONCLUSIONS: Our results suggest that the alpha3(IV)-chain-containing col IV-network plays a fundamental role in structural and, possibly, functional organization of GBM. Absence of alpha3(IV)-chain in GBM could indicate a more severe renal disease in AS.

Adolescent↗
PubMed2000

Decreased c-Src expression enhances osteoblast differentiation and bone formation.

c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry showed that bone formation was increased in Src null compared with wild-type mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization were increased in primary calvarial cells and in SV40-immortalized osteoblasts from Src(-/-) relative to Src(+/+) mice. Src-antisense oligodeoxynucleotides (AS-src) reduced Src levels by approximately 60% and caused a similar increase in ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction in cell proliferation was observed in primary and immortalized Src(-/-) osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative reverse transcriptase-PCR revealed upregulation of ALP, Osf2/Cbfa1 transcription factor, PTH/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin remained unchanged. Based on these results, we conclude that the reduction of Src expression not only inhibits bone resorption, but also stimulates osteoblast differentiation and bone formation, suggesting that the osteogenic cells may contribute to the development of the osteopetrotic phenotype in Src-deficient mice.

Alkaline Phosphatase↗
PubMed2000

The ERK-1/2 signaling pathway is involved in the stimulation of branching morphogenesis of fetal mouse submandibular glands by EGF.

We have previously reported that epidermal growth factor (EGF) stimulates branching morphogenesis of the fetal mouse submandibular gland (SMG) (M. Kashimata and E. W. Gresik, 1997, Dev. Dyn. 208, 149-161) and that the EGF receptor (EGFR) is localized principally, if not exclusively, on the epithelial components of the fetal SMG (E. W. Gresik, M. Kashimata, Y. Kadoya, R. Mathews, N. Minami, and S. Yamashina, 1997, J. Histochem. Cytochem. 45, 1651-1657). The EGFR is a receptor tyrosine kinase, and after binding of its ligand, it triggers several intracellular signaling cascades, among them the one activating the mitogen-activated protein kinases (MAPK) ERK-1/2. Here we investigated whether EGF utilizes the ERK-1/2 signaling cascade to stimulate branching morphogenesis in the fetal mouse SMG. SMG rudiments were collected as matched pairs at E14, E16, and E18 (E0 = day of vaginal plug); placed into wells of defined medium (BGJb); and exposed to EGF for 5 or 30 min or to medium alone (controls). By Western blotting we found that EGF induced the appearance of multiple bands of phosphotyrosine-containing proteins, including bands at 170 kDa and 44 kDa/42 kDa, presumably corresponding to the phosphorylated forms of EGFR and ERK-1/2, respectively. Other blots showed the specific appearance of the phosphorylated EGFR and of phospho-ERK-1/2 in response to EGF. Immunohistochemical staining for phosphotyrosine increased at the plasma membrane after EGF stimulation for 5 or 30 min. Diffuse cytoplasmic staining for MEK-1/2 (the MAPK kinase that activates ERK-1/2) increased near the cell membrane after EGF stimulation. Phospho-ERK-1/2 was localized in the nuclei of a few epithelial cells after EGF for 5 min, but in the nuclei of many cells after EGF for 30 min. PD98059, an inhibitor of phosphorylation and activation of MEK-1/2, by itself inhibited branching morphogenesis and, furthermore, decreased the stimulatory effect of EGF on branching. Western blots confirmed that this inhibitor blocked phosphorylation of ERK-1/2 in fetal SMGs exposed to EGF. These results show that components of the ERK-1/2 signaling cascade are present in epithelial cells of the fetal SMG, that they are activated by EGF, and that inhibition of this cascade perturbs branching morphogenesis. However, EGF did not cause phosphorylation of two other MAPKs, SAPK/JNK or p38MAPK, in fetal SMGs. These results imply that the ERK-1/2 signaling is responsible, at least in part, for the stimulatory effect of EGF on branching morphogenesis of the fetal mouse SMG.

Animals↗
PubMed2000

Cephotaxime-associated allergic interstitial nephritis and MPO-ANCA positive vasculitis.

We report a case of reversible acute renal failure after cefotaxime treatment in a patient affected by non-Hodgkin lymphoma. Renal biopsy showed necrotizing vasculitis associated with eosinophil-rich interstitial inflammatory infiltrates and patchy infiltrates of CD20+ lymphoid cells. High serum p-ANCA titers were also detected. Drug withdrawal was closely related with recovery of renal function and disappearance of ANCA. Acute renal failure therefore represented a consequence of ANCA-mediated renal vasculitis and acute interstitial nephritis related to cefotaxime treatment.

Aged↗
PubMed1999

Delayed onset of systemic lupus erythematosus in patients with "full-house" nephropathy.

Three patients are described who presented with a glomerulopathy suggestive of lupus nephritis in the absence of other clinical and biological evidence of systemic lupus erythematosus (SLE). Renal biopsies showed a "full-house" immunofluorescence pattern and two patients also had cytoplasmic tubuloreticular inclusions by electron microscopy. All these patients developed antinuclear and anti-double-stranded DNA antibodies 3, 5, and 10 years after their original presentation. Subsequently, 1 patient also developed clinical symptoms of lupus. Reviewing all renal biopsies performed in our department, we found 14 additional patients who presented with a "full-house" immunofluorescence glomerulonephritis in the absence of other features of SLE. After a mean follow-up of 5.8 years, these patients have not developed serological or clinical evidence of SLE. We conclude that a "full-house" glomerulopathy in children may be the first symptom of SLE, especially when cytoplasmic tubuloreticular inclusions are detected. The appearance of other clinical and biological symptoms may be delayed by several years.

Adolescent↗
PubMed1999

Spatial arrangement of subepithelial deposits in lupus and nonlupus membranous nephropathy.

Subepithelial deposits are a common feature of idiopathic membranous glomerulonephritis (MGN) and lupus membranous glomerulopathy (LMGN). We investigated the spatial arrangement of immunoglobulin G (IgG) and C3c fraction of complement (C3c) in the immune deposits of MGN and LMGN with confocal laser scanning microscopy to correlate specific patterns of IgG-C3 interactions with different diseases. Ten patients with MGN and 8 patients with LMGN (World Health Organization class VB) were selected. A determination of the spatial arrangement of the two fluorochromes and the glomerular area occupied by each fluorochrome was performed for each case. Our results showed MGN specimens have an orderly distribution of IgG and C3c, with each deposit showing an outer ring of sole IgG. IgG was always more abundant than C3c (1,619 +/- 271 v 790 +/- 105 micrometer(2), P = 0.002). In LMGN, IgG and C3c were haphazardly arranged, with deposits made of C3c only and an outer ring of IgG only rarely present. Also, the relative amounts of the two antigens were variable, and two groups could be identified (group 1: IgG, 5,515 +/- 1,179 micrometer(2) v C3c, 4,810 +/- 1,174 micrometer(2); P = 0.02; group 2: IgG, 3,358 +/- 658 micrometer(2) v C3c, 4,047 +/- 740 micrometer(2); P = 0.03). Our data show that diffuse IgG capping of the subepithelial immune deposits is diagnostic of MGN. The absence of an orderly three-dimensional arrangement in LMGN deposits (ie, outer ring of IgG) is likely to render active complement components more readily available to inflammatory activities.

Adult↗
PubMed1999

Progressive increase in telomerase activity from benign melanocytic conditions to malignant melanoma.

The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR) in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction-based assay (TRAP). High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastases = 54.5, lymph node metastases = 56.5). Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9). Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.

Humans↗
PubMed1999

Melanocytic nevi of palms and soles: a histological study according to the plane of section.

Melanocytic nevi of palms and soles (MNPS) cause diagnostic problems to dermatopathologists because they share histologic features with malignant melanoma (MM). Early MNPS frequently display a striate appearance, suggesting that, in this subset of nevi, both melanocytes and melanin might have a particular distribution in relation to dermatoglyphics. To verify this hypothesis, we undertook a histological study on 78 junctional MNPS sampled along a plane either perpendicular or parallel to dermatoglyphics. Histologic examination revealed symmetry in 56% of the lesions, circumscription in 60%, intraepidermal scatter of melanocytes in 79%, and melanin columns in 61%. Interestingly, comparison between histologic features of nevi sampled perpendicularly and those of nevi cut parallely to dematoglyphics showed that features of benignity, namely symmetry, circumscription and melanin columns, were significantly more frequent in lesions dissected along a perpendicular plane. Moreover, in 70% of perpendicular samples, intraepidermal scatter of melanocytes and melanin columns were strictly concentrated in furrows. Therefore, to avoid diagnostic pitfalls in the differentiation between junctional MNPS and MM, we strongly suggest to dissect MNPS along a plane perpendicular to skin markings. We hypothesize that mechanical stress can be responsible for concentration of intraepidermal scatter of melanocytes and melanin columns in skin furrows.

Adolescent↗
PubMed1999

Clonality of cutaneous B-cell infiltrates determined by microdissection and immunoglobulin gene rearrangement.

Diagnosis of primary cutaneous B-cell lymphoma (PCBCL) is supported by the demonstration of a monoclonal B-cell population. Immunoglobulin heavy chain (IgH) gene-rearrangement analysis by polymerase chain reaction (PCR) is a reliable technique to detect B-cell monoclonality in paraffin-embedded tissue, but the presence of numerous reactive B lymphocytes in PCBCL may complicate the interpretation of clonality test results. To test this hypothesis, IgH gene-rearrangement analysis by PCR was performed on paraffin-embedded whole tissue sections of 19 cutaneous B-cell infiltrates diagnosed either as consistent with PCBCL (10 specimens) or unclassified lymphoid infiltrates (ULI) (9 specimens). In specimens that did not show monoclonal bands by IgH gene-rearrangement on DNA extracted from whole tissue sections, clonality assays were repeated on microdissected B-cell subpopulations suspicious for neoplastic cells. In the analysis of whole tissue sections, 4 (40%) of 10 specimens consistent with PCBCL showed one or two monoclonal bands, whereas 9 of 9 ULI specimens showed either a ladder or a smear. Clonality analysis of microdissected B-cell subpopulations showed 3 additional PCBCL specimens (total, 7 of 10) and 1 ULI specimen (total, 1 of 9) with unequivocal and reproducible monoclonal bands. Addition of microdissection increases the sensitivity of PCR-based B-cell clonality assay in PCBCL compared with analysis performed on the whole section (70% versus 40% monoclonal cases) and allows the recognition of a dominant clone in ULI specimens, possibly representing early PCBCL.

B-Lymphocyte Subsets↗
PubMed1998

Expression of TGF-beta receptors type I and II in human glomerulonephritis.

BACKGROUND: Transforming growth factor-beta (TGF-beta) is a multipotent cytokine involved in the turnover of the extracellular matrix. Signal transduction of TGF-beta is regulated via at least five different surface receptors; most of the effects, however, are mediated through the interaction of receptors type I and II (RI and RII). We investigated the glomerular expression of TGF-beta and its receptors RI and RII in human glomerulonephritis. METHODS: Indirect immunofluorescence using monoclonal and polyclonal antibodies against TGF-beta isoforms (1,2,3 and 2,3), TGF beta-RI and TGF beta-RII has been carried out on 30 consecutive renal biopsies (5 FSGS, 11 IgAN, 4 MCGN, 6 SLE, 2 RPGN) and on normal kidney tissue. RESULTS: Glomerular immunoreactivity for TGF-beta isoforms correlated with the severity of proliferative lesions: immunofluorescent signal was absent or trace-like in normal kidneys, FSGS, and IgAN with mild mesangial cellularity, and was highest in IgAN with severe mesangial proliferation, MPGN, RPGN, and SLE. Glomerular positivity for TGF-beta-RI and -RII was detectable in SLE and RPGN; a low signal was present also in MPGN. Other types of glomerulonephritis, including focal extracapillary proliferations, and glomeruli of normal kidneys were always negative. CONCLUSIONS: Our data show that TGF-beta expression is a good indicator of the severity of proliferative glomerular lesions in most, if not all cases and that RI-RII expression occurs at levels detectable with indirect immunofluorescence in limited number of glomerulonephritides, mostly associated with systemic diseases. A complex interaction between TGF-beta and its ligand may represent a critical factor conditioning the tissue response to immunological injury.

Fluorescent Antibody Technique, Indirect↗