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Biomedical subjects

S Travali

Publications and source records attributed to S Travali.

At least 37 records · Page 2Linked to original sources
PubMed2000

CD44 standard form (CD44H) expression and distribution in dysfunctional human temporomandibular joint discs.

The expression pattern of the cell adhesion molecule CD44 standard form (CD44H) in dysfunctional human temporomandibular joint (TMJ) discs was studied immunohistochemically and compared with normal disc pattern in order to evaluate the expression of this adhesion molecule and correlate it to histopathological changes. Immunohistochemistry with anti-CD44H antibodies was performed on paraffin sections of pathological and normal discs. In normal TMJ discs, a moderate immunolabelling with anti-CD44H antibodies was detectable in fibroblastlike cells, in the few fibrochondrocytes and in chondrocytelike cells. In dysfunctional discs, the staining pattern and intensity varied according to the histopathological findings of the specimens. The TMJ discs showing abnormal collagen arrangement or fragmentation of collagen fibres presented overall the same immunolabelling pattern of normal discs. In the discs showing areas of fibrocartilaginous metaplasia, CD44H expression was upregulated in fibrochondrocytes and fibroblastlike cells, especially around the chondroid tissue. Overall, these results suggest that CD44H mediates the binding of some ECM proteins in TMJ disc cells. The up-regulation of CD44H observed in some dysfunctional TMJ discs seems to indicate a prevention of apoptosis in fibroblastlike cells and an important role in phenotypical change of fibrochondrocytes into chondroblastlike cells, enabling the aggregation of chondroid tissue pericellular matrix components.

Adult↗
PubMed1999

Blocking signaling through the Gp130 receptor chain by interleukin-6 and oncostatin M inhibits PC-3 cell growth and sensitizes the tumor cells to etoposide and cisplatin-mediated cytotoxicity.

BACKGROUND: The mechanisms of drug resistance associated with advanced, hormone-independent prostate carcinoma are poorly understood. The human prostate carcinoma PC-3 cell line, derived from a metastatic tumor and lacking androgen receptors, represents a useful model to investigate drug resistance. METHODS: The effects of oncostatin M (OM), antiinterleukin-6 (IL-6) treatment, or interference with the gp130-mediated signaling on etoposide- or cisplatin-mediated cytotoxicity were investigated. RESULTS: Both endogenous and exogenous IL-6 and exogenous OM up-regulated cell growth and enhanced resistance of PC-3 tumor cells to both etoposide and cisplatin. The influence of IL-6 is controlled by treating PC-3 tumor cells with anti-IL-6 neutralizing antibody and, more efficiently, by a mutated IL-6, Sant7. Sant7 has a high affinity binding to the IL-6 receptor-alpha (IL-6Ralpha) subunit, but does not bind to the signaling subunit gp130; therefore, it behaves as a receptor antagonist. Both IL-6- and OM-mediated effects are inhibited by the treatment of PC-3 with an antisense oligodeoxynucleotide against gp130, the protein kinase inhibitor genistein (GNS), or the monoterpene perillic acid (PA), a posttranslational inhibitor of p21ras isoprenylation. CONCLUSIONS: These results demonstrate the protective roles in drug sensitivity of IL-6 and OM through signaling of the common chain gp130 and, most likely, a downstream ras-dependent pathway in PC-3 tumor cells. These findings suggest the potential clinical application of anticytokine therapy or interference with gp130 signaling in the treatment of drug resistant prostate carcinoma.

Antigens, CD↗
PubMed1999

Rapid screening of the LDL receptor point mutation FH-Genoa/Palermo. Mutation in brief no. 238. Online.

The LDL-receptor gene point mutation FH-Genoa/Palermo is the most frequent mutation responsible for Familial Hypercholesterolemia in Sicily. The mutation does not introduce or abolish any useful restriction site. We establish a GeneComb-based strategy to identify this mutation in a population of Sicilian unrelated clinically diagnosed FH probands. The method was very sensitive and specific; 12 out of 90 (13.3%) unrelated FH probands were found to carry the FH-Genoa/Palermo mutation. According to these results, the FH-Genoa/Palermo is the more frequent LDL-receptor gene mutation among the Sicilian FH patients. Moreover FH-Genoa/Palermo is the mutation cluster to date more represented in Southern Italy.

Genetic Testing↗
PubMed1999

Lipoprotein(a) levels in relation to albumin concentration in childhood nephrotic syndrome.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a lipoprotein consisting of a low-density lipoprotein (LDL) particle linked to a polymorphic glycoprotein, apoprotein(a) [apo(a)]. Prior studies have reported high Lp(a) levels in the nephrotic syndrome, but it is still controversial whether this is due to the degree of hypoalbuminemia or proteinuria. METHODS: To investigate a model of nephrotic syndrome in the absence of renal failure, we studied a group of 84 children in different clinical stages of the disease for a period of five years. We evaluated the direct relationships between lipoproteins, including Lp(a), and/or plasma albumin and proteinuria. RESULTS: Lp(a) levels were significantly higher in the subjects with the active disease compared with patients in remission, and were also significantly different when subjects were ranked by albumin quartiles. Multiple regression analysis revealed that Lp(a) levels were inversely correlated with apo(a) isoform size and plasma albumin levels but not with the proteinuria/creatinine clearance ratio. Among subjects in complete remission, Lp(a) levels were different in patients with albumin levels below or above the fifth percentile. After the improvement of the clinical stage of the disease, the Delta% variation of albumin levels was related to the Delta% of apoB and LDL cholesterol (LDL-C), but not with the Delta% variation of Lp(a), whereas the Delta% variation of LDL-C was, in turn, related to the Delta% of Lp(a) levels. CONCLUSIONS: These results suggest that in the childhood nephrotic syndrome, the increased Lp(a) levels are mainly related to hypoalbuminemia, probably through a mechanism involving apoB overproduction, which leads to an increased number of LDL particles to be converted into Lp(a).

Apolipoproteins B↗
PubMed1999

Alteration in alpha 2 integrin immunocytochemical expression on cultured human gingival fibroblasts following nicotine exposure.

BACKGROUND: Clinical epidemiologic studies carried out in smokers versus non smokers support the concept that tobacco-related factor may affect the periodontal tissues and wound healing. METHODS: In this study, the role of nicotine on the integrin alpha 2 chain immunocytochemical expression, in human gingival fibroblasts (HGF) was investigated in vitro. The kinetic induction of this type of integrin on HGF in response to increasing percentage of nicotine was been characterized. A human gingival fibroblast strain, derived from a healthy individual with non-inflamed gingiva, was used in this study. The cells were then grown on acetylated microscope slides and fixed with cold ethanol, samples were then incubated for 16 to 19 hrs at 4 degrees C to anti-human alpha 2 integrin chain monoclonal antibody. RESULTS: In control cultures and in HGF treated with 0.025 microM nicotine the initial higher expression of alpha 2 chain decreased (grade 1 in both culture) while in HGF treated with 0.075 microM increased (grade 3). After 48 hours HGF exposed to 0.075 microM nicotine, increased further their expression of alpha 2 chain. CONCLUSIONS: The results obtained demonstrate a dose-time dependent nicotine influence on immunocytochemical expression of alpha 2 integrin chain. These data suggest that nicotine may promote a collagene breakdown via an increase of alpha 2 integrin chain expression.

Cells, Cultured↗
PubMed1998

Cloning and expression of the programmed cell death regulator Bad in the rat brain.

The Bcl-2 family of proteins consists of both antagonists (e.g. Bcl-2) and agonists (e.g. Bax) that regulate apoptosis and compete through dimerization. In the present study we cloned the cDNA encoding the rat brain BAD, a distant member of the Bcl-2 family that was shown to promote cell death. The cloned cDNA encoded a protein of 205 amino acids, containing three putative Bcl-2 homology domains (BH1, BH2 and BH3) and no C-terminal signal-anchor sequence. The predicted amino acid sequence was identical to the Bad-cDNA recently cloned from the rat ovary with the exception of a stretch of six amino acids, thus indicating the existence of two Bad alternative splice variants or a sequence artifact in the rat ovary Bad-cDNA. Immunohistochemical analysis in the rat brain revealed the exclusive expression of Bad in the epithelial cells of the choroid plexus, a result which is consistent with a very specialized function of Bad in the brain.

Amino Acid Sequence↗
PubMed1997

Myofibroblasts of palmar fibromatosis co-express transforming growth factor-alpha and epidermal growth factor receptor.

Several studies have shown that different growth factors are involved in the pathogenesis of palmar fibromatosis. The aim of the present study was to investigate whether transforming growth factor alpha (TGF-alpha) and its cellular receptor, epidermal growth factor receptor (EGF-R), are expressed in palmar fibromatosis. Nodules from 20 patients with palmar fibromatosis and control normal palmar fascias were studied by the reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. RT-PCR followed by Southern blotting demonstrated that palmar fibromatosis nodules contained high levels of TGF-alpha and EGF-R messenger RNA (mRNA) transcripts, while normal fascias showed only low levels. Depending on the degree of cellularity and fibrosis, the three following histological phases were recognized in palmar fibromatosis nodules: proliferative, involutional, and residual. Immunohistochemistry, using alpha-smooth muscle actin as a cellular marker for myofibroblasts, revealed that TGF-alpha and EGF-R are co-expressed by myofibroblasts in the highly cellular areas of both proliferative and involutional phases, while they are absent or only focally detectable in the fibroblasts of normal fascia and in hypocellular and fibrotic areas of both involutional and residual phases. The restricted co-expression of TGF-alpha and EGF-R to myofibroblasts, the proliferating cellular component of nodules, suggests that an autocrine and/or juxtacrine growth stimulation by TGF-alpha via the EGF-R may be involved in the pathogenesis of palmar fibromatosis.

Actins↗
PubMed1997

Liver is not the unique site of synthesis of beta 2-glycoprotein I (apolipoprotein H): evidence for an intestinal localization.

Apolipoprotein H is a protein of about 50 kilodaltons, structurally related to the regulators of the complement activation family. Its physiological function is poorly understood but it has been implicated in lipid metabolism and coagulative pathways. The major site of synthesis is thought to be the liver. Several reports indicate that apolipoprotein H is the antigen of the antiphospholipid antibodies and also behaves as an acute-phase reactant. Moreover, 40% of plasma apolipoprotein H is associated with very low-density lipoprotein, high-density lipoprotein, and postprandial chylomicrons. In this study we investigated other sites of synthesis by reverse transcription/polymerase chain reaction and we found apolipoprotein H mRNA expression in intestinal cell lines and tissues. Immunohistochemistry was performed on various fresh and paraffin-embedded tissues and apolipoprotein H was immunolocalized in the cytoplasm of hepatocytes and epithelial cells from colon and jejunum. This study indicates that apolipoprotein H is expressed at both mRNA and protein levels in enterocytes.

Apolipoproteins↗
PubMed1997

Immunohistochemical expression and distribution of alpha2beta1, alpha6beta1, alpha5beta1 integrins and their extracellular ligands, type IV collagen, laminin and fibronectin in palmar fibromatosis.

Palmar fibromatosis is characterized by changes in the expression of extracellular matrix (ECM) proteins and re-organization of the interactions between cellular and extracellular compartments. We compared the expression and distribution of alpha2beta1, alpha6beta1, alpha5beta1 integrins and their corresponding extracellular ligands, type IV collagen, laminin and fibronectin in palmar fibromatosis nodules from 24 patients. Depending on the degree of cellularity and fibrosis, three different histologic phases were identified: proliferative, involutional, and residual. Immunohistochemistry revealed that only stromal cells of the highly cellular areas of both proliferative and involutional phases were myofibroblasts, as demonstrated by their cytoplasmic positivity for alpha-smooth-muscle actin. The ECM, surrounding these cells, was strongly and diffusely positive to type IV collagen, laminin and fibronectin, whereas no immunoreactivity was found in the ECM of the fibrotic and hypocellular areas of both involutional and residual phases. Immunostaining for alpha2beta1, alpha6beta1 and alpha5beta1 integrins revealed that alpha5beta1 integrin was expressed and restricted to the myofibroblast-rich cellular areas, whereas no expression was detected for alpha2beta1 and alpha6beta1 integrins. By examining serial sections, a co-localization of alpha5beta1 integrin and fibronectin was observed in the myofibroblast-rich cellular areas, indicating that, in palmar fibromatosis, a co-ordinate expression between cellular and extracellular ligand is detected only for the alpha5beta1 integrin/fibronectin complex. These findings suggest that the alpha5beta1 integrin/fibronectin complex may be involved in regulating the interactions between myofibroblasts and ECM in palmar fibromatosis.

Actins↗
PubMed1996

Characterization of vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptors in human benign hyperplastic prostate.

Vasoactive intestinal peptide (VIP) is an important member of the group of neuropeptides that appears to be involved in the regulation of prostatic growth and function. Here we studied VIP receptors in membranes from human benign hyperplastic prostate. Accordingly to observations in rat prostatic membranes, [125I]VIP binding to human prostatic membranes suggested two classes of binding sites with high Kd = 0.22 nM) and low (Kd = 37.7 nM) affinities. VIP bound in human and rat membrane preparations to a common VIP/pituitary adenylate cyclase-activating peptide (PACAP) receptor, as VIP, PACAP-27, and PACAP-38 were equipotent for competition of [125I]VIP binding. A PACAP-preferring receptor appears to be expressed in human prostate, since [125I]PACAP binding was displaced with more potency by PACAP than by VIP, and a messenger RNA corresponding to type I PACAP receptor was found. Cross-linking experiments suggested a VIP receptor of about 71 kDa in human and 52 kDa in rat prostates. The binding of [125I]VIP to membranes and the labeling of the bands observed after electrophoresis were competitively inhibited by GTP, suggesting the coupling of VIP receptors to a G protein. Moreover, after solubilization and cross-linking, we observed a 120-kDa band that corresponded to the VIP receptor-alpha s association. VIP stimulated adenylyl cyclase activity in a dose-dependent manner, but the potency and/or the efficacy of VIP were lower in all human preparations studied than in rat prostatic membranes. In conclusion, this study clearly demonstrates the expression of VIP/PACAP common receptors associated with alpha s protein in human prostate and suggests that these neuropeptides could play an important and complex role in the physiology and pathophysiology of this human gland.

Adenylyl Cyclases↗
PubMed1996

Pituitary adenylate cyclase activating polypeptide prevents apoptosis in cultured cerebellar granule neurons.

The two forms of pituitary adenylate cyclase-activating polypeptide, PACAP27 and PACAP38, are two neuropeptide hormones related to the vasoactive intestinal peptide/secretin/ glucagon family of peptides. PACAP receptors that are positively coupled to adenylyl cyclase and phospholipase C have been identified in cultured cerebellar granule cells. Using the reverse transcription-polymerase chain reaction methodology, we demonstrated the expression of the PACAP-R and PACAP-R-hop mRNAs in cultured granule cells. When grown in the absence of serum or in low K+ concentrations, these neurons underwent apoptosis, a naturally occurring process characterized by cell shrinkage and internucleosomal DNA cleavage. We used these models of programmed cell death to study the relationship between PACAP receptor activation and neuronal apoptosis. Treatment with PACAP27 and PACAP38 reduced the development of apoptosis in a dose-dependent manner. The neuroprotective activity of PACAP was mimicked by high concentrations of vasoactive intestinal peptide or forskolin but not by carbamylcholine. Thus, we suggest that the activation of type I PACAP receptors may contribute to the survival of cerebellar granule neurons.

Animals↗
PubMed1995

p53-independent induction of WAF1/CIP1 in human leukemia cells is correlated with growth arrest accompanying monocyte/macrophage differentiation.

The p53 tumor suppressor gene plays a role in controlling a G1 phase checkpoint. The WAF1/CIP1 gene with encodes p21WAF1/CIP1 protein, an inhibitor of cyclin-dependent kinases, is a downstream mediator of p53 function. We examined expression of the WAF1/CIP1 gene and its relationship to growth arrest and differentiation in p53-null human leukemic cell lines. We show that p53-independent induction of WAF1/CIP1 occurs in human leukemia cells treated with 12-O-tetradecanoylphorbol-13-acetate, okadaic acid, or IFN-gamma but not with retinoic acid, vitamin D3, or DMSO. Furthermore, WAF1/CIP1 induction correlates with growth arrest associated with monocyte-macrophage differentiation. The present studies support the idea that WAF1/CIP1 gene expression can be regulated through multiple mechanisms, suggesting that strategies may be designed to restore the G1 checkpoint controls in p53-null cells by targeting these p53-independent mechanisms of WAF1/CIP1 induction.

Blotting, Northern↗
PubMed1995

Differentiation induces pituitary adenylate cyclase-activating polypeptide receptor expression in PC-12 cells.

The two forms of pituitary adenylate cyclase-activating polypeptide (PACAP), PACAP27 and PACAP38, are neuropeptide hormones related to the vasoactive intestinal peptide/secretin/glucagon family of peptides. PACAP receptors that are positively coupled to adenylyl cyclase and phospholipase C have been recently identified. We have investigated the expression of PACAP-Rs in undifferentiated and differentiated PC-12 cells. PACAP27 and PACAP38 failed to significantly increase cAMP or [3H]inositol monophosphate levels in undifferentiated PC-12 cells treated with vehicle, insulin-like growth factor I, or epidermal growth factor but greatly elevated levels after differentiation with nerve growth factor (NGF) or basic fibroblast growth factor. PACAP responsiveness increased significantly after 24 hr of NGF treatment, reaching a maximum within 4 days. At this time of differentiation, the effect of PACAP was dose dependent between 1 nM and 0.1 microM, whereas vasoactive intestinal peptide, at the maximal dose of 10 microM, slightly increased cAMP formation and failed to affect [3H]inositol monophosphate content. Radioreceptor assays, performed with 125I-PACAP27, revealed the induction of high affinity type I PACAP receptors in differentiated PC-12 cells. Using reverse transcription-polymerase chain reaction methodology, we showed the absence of type I PACAP receptor mRNAs in undifferentiated PC-12 cells and the expression of PACAP-R-hop mRNA after NGF or basic fibroblast growth factor treatment. The increased PACAP responsiveness induced by these growth factors in PC-12 cells may therefore result from the expression of the PACAP-R-hop isoform, positively coupled to both adenylyl cyclase and phospholipase C.

Animals↗
PubMed1994

Constitutive expression of B-myb can bypass p53-induced Waf1/Cip1-mediated G1 arrest.

Overexpression of wild-type p53 protein has been shown to induce arrest in the G1 stage of the cell cycle and to transactivate expression of the gene that encodes the 21-kDa Waf1/Cip1 protein, a potent inhibitor of cyclin-dependent kinase activity. p53-dependent G1 arrest is accompanied by decreased expression of the B-myb gene, a relative of the c-myb cellular oncogene. In this study we show that B-myb expression is required for cells to progress from G1 into S phase and that high levels of ectopic B-myb expression uncoupled from cell cycle regulation rescues cells from p53-induced G1 arrest even in the presence of Waf1/Cip1 transactivation and inhibition of cyclin E/Cdk2 kinase activity. Cotransfection experiments with p53 expression plasmids and expression plasmids encoding in-frame deletion mutations in B-myb coding sequences indicate that the DNA-binding domain of the B-Myb protein is required for this activity. These results provide evidence of a bypass of p53-induced Waf1/Cip1-mediated cell cycle regulatory pathways by a member of the myb oncogene family.

Base Sequence↗
PubMed1992

The Jun family members, c-Jun and JunD, transactivate the human c-myb promoter via an Ap1-like element.

The c-myb protooncogene, which is preferentially expressed in hematopoietic cells at the G1/S boundary of the cell cycle, encodes a transcriptional activator that functions via DNA binding. The regulatory mechanisms governing this specific pattern of expression are not fully understood, although human c-myb expression appears to be positively autoregulated via myb-binding sites in the 5'-flanking region of the c-myb gene (Nicolaides, N. C., Gualdi, R., Casadevall, C., Manzella, L., and Calabretta, B. (1991) Mol. Cell. Biol. 11, 6166-6176). To determine the contribution of other transcription regulators such as JUN family members in the control of c-myb expression, transient expression assays were carried out which revealed a 6- to a 15-fold enhancement by c-Jun and JunD, but not JunB, in chloramphenicol acetyltransferase reporter gene expression driven by different segments of the human c-myb 5'-flanking region. An Ap1-like element located at nucleotide -149 from the c-myb initiation site appears to be required for this transactivation upon binding to a nuclear protein complex containing c-Jun and JunD, since site-directed mutations of this Ap1-like element abolished c-Jun and JunD binding and transactivation. Exposure of phytohemagglutinin-stimulated peripheral blood mononuclear cells to c-jun and junD antisense oligodeoxynucleotides resulted in a 46 and 43% inhibition of T-lymphocyte proliferation that was accompanied by a decrease in c-myb mRNA levels as compared with sense-treated cultures. Because T-lymphocytes induced to proliferate express c-jun and junD before c-myb, these data suggest a mechanism whereby c-Jun and JunD contribute to the transcriptional activation of c-myb that, in turn, is maintained at the G1/S transition and during S phase by positive autoregulation.

Base Sequence↗
PubMed1991

The protooncogene c-myb increases the expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor messenger RNAs by a transcriptional mechanism.

The protooncogene c-myb is the cellular equivalent of the viral transforming oncogene v-myb. When human c-myb is constitutively expressed in Balb/c3T3 cells it abrogates their absolute requirement for insulin-like growth factor 1 (IGF-1). We show now, in two different cell lines, that the constitutive expression of the protooncogene c-myb causes an increase in both IGF-1 and IGF = 1 receptor mRNA levels. This increase in mRNA levels is due, at least in part, to an increase in the rate of transcription since, by run-on assay, cells carrying the human c-myb cDNA show a 3-fold increase in transcriptional rates in comparison to the control parent cell lines. The increased expression of IGF-1 receptor mRNA also results in an increased number of IGF-1 binding sites per cell. Although some oncogenes have been described that are homologous to growth factors, or growth factor receptors, c-myb seems to represent a novel way of oncogene action inasmuch as it increases the expression of both a growth factor receptor and its ligand, thus establishing a quasi-autocrine mechanism which modifies the growth factor requirements of the cell and its growth regulation.

3T3 Cells↗