Identification of novel Smad binding proteins.

The TGFbetas, a family of secreted polypeptide growth factors, are critical regulators of mammalian orofacial development. The importance of the TGFbetas in development of the orofacial region in mice is underscored by the resulting orofacial clefts in mice with targeted deletion of either TGFbeta2 or TGFbeta3 and most recently, a conditional knockout of the type II TGFbeta receptor (TbetaRII) gene. The TGFbetas signal via binding to specific cell surface receptors which, in turn, activates translocation of the nucleocytoplasmic Smad transcriptional regulators.

Molecular fingerprinting of TGFbeta-treated embryonic maxillary mesenchymal cells.

The transforming growth factor-beta (TGF(beta)) family represents a class of signaling molecules that plays a central role in normal embryonic development, specifically in development of the craniofacial region. Members of this family are vital to development of the secondary palate where they regulate maxillary and palate mesenchymal cell proliferation and extracellular matrix synthesis. The function of this growth factor family is particularly critical in that perturbation of either process results in a cleft of the palate.

Interaction of Smads with collagen types I, III, and V.

Ontogenesis of the mammalian orofacial region is controlled by numerous developmental signals, including those initiated by the transforming growth factors beta (TGFbetas). Targeted deletion of the genes encoding several of the TGFbetas in mice has been shown to result in clefts of the secondary palate. Members of the TGFbeta family of growth factors utilize intracellular Smads as signal transducers.

Intracellular dynamics of Smad-mediated TGFbeta signaling.

The transforming growth factor-beta (TGFbeta) family represents a class of signaling molecules that plays a central role in morphogenesis, growth, and cell differentiation during normal embryonic development. Members of this growth factor family are particularly vital to development of the mammalian secondary palate where they regulate palate mesenchymal cell proliferation and extracellular matrix synthesis. Such regulation is particularly critical since perturbation of either cellular process results in a cleft of the palate.

[Papillary microcarcinoma of the thyroid. Clinical implications and therapeutic strategy].

The Authors examine their experience about clinical implications and therapeutic strategies on Papillary MicroCarcinoma (PMC) of the thyroid gland. Clinical charts of 412 patients, who underwent thyroid surgery, were analyzed. The Authors stress "incidental diagnosis", benign associated lesions and frequency of population presentation; they conclude that the total thyroidectomy is the procedure of choice with oncology validity.

Identification of three novel Smad binding proteins involved in cell polarity.

A yeast two-hybrid screen was utilized to identify novel Smad 3 binding proteins expressed in developing mouse orofacial tissue. Three proteins (Erbin, Par-3, and Dishevelled) were identified that share several similar structural and functional characteristics. Each contains at least one PDZ domain and all have been demonstrated to play a role in the establishment and maintenance of cell polarity.

Expression of the retinoblastoma family of tumor suppressors during murine embryonic orofacial development.

Objective: To elucidate the role of the retinoblastoma (Rb) family of tumor suppressors and growth regulators in transforming growth factor beta (TGFbeta)-mediated embryonic palatal growth and morphogenesis.

Design: The spatio-temporal expression patterns of the RB1, RB2/p130, and p107 tumor suppressor genes, their gene products (pRb, p130 and p107) and phosphoforms were examined in the developing murine secondary palate utilizing reverse transcriptase polymerase chain reaction (RT-PCR) and immunoblot/immunolocalization analyses with phospho-specific antibodies.

Results: The RB1, RB2/p130, and p107 tumor suppressor genes and their gene products (pRb, p130, and p107) were differentially expressed in embryonic palatal tissue during the critical period of secondary palate development [gestational days (GD) 12-14].

Nuclear convergence of the TGFbeta and cAMP signal transduction pathways in murine embryonic palate mesenchymal cells.

Transforming growth factors beta (TGFbeta) and cyclic AMP (cAMP) both participate in growth and differentiation of the developing mammalian secondary palate and elicit similar biological responses. Cross-talk between these two signal transduction pathways in cells derived from the embryonic palate has been demonstrated previously. In the present study, we have examined nuclear convergence of these signalling pathways at the level of transcriptional complex formation.

BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling.

Background: The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC).

Patients And Methods: Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes.

Results: Three BRCA1/2 germline sequence variants were identified.

Increased susceptibility to retinoid-induced teratogenesis in TGF-beta2 knockout mice.

Transforming growth factor-beta (TGF-beta) and retinoic acid (RA) have been implicated in normal and abnormal embryonic development. The aim of this study was to investigate the effect of TGF-beta2 gene deletion on susceptibility to RA-induced teratogenesis in a mouse model. TGF-beta2 heterozygous or wild-type mice were mated and the dams dosed with a teratogenic dose of RA, or with control vehicle.

Phosphatase regulation of gene expression during development of the palate.

In mammalian cells, including those of the embryonic palate, the level of phosphorylation of cellular proteins at any given time reflects the activities of protein kinases and protein phosphatases. Both protein phosphatase-1 (PP-1) and PP-2A inhibit cAMP-mediated increases in transcription by dephosphorylating CREB at ser-133. Western blot analysis indicated that protein phosphatase 1 (PP-1) was expressed constitutively in palatal tissue during its development.

Chromosomal abnormalities and microsatellite instability in sporadic endometrial cancer.

Defective DNA mismatch repair and nonfunctional mechanisms controlling the proper progression of the cell cycle have been proposed as being responsible for the genomic instability and accumulation of karyotypic alterations in endometrial cancer (EC). To assess whether numerical chromosomal anomalies (aneuploidy) and microsatellite instability (MSI) might be representative of distinctive tumour behaviour, paraffin-embedded tissue samples from 86 patients with sporadic EC were evaluated by both fluorescence in situ hybridisation (FISH) and microsatellite analysis, using free nuclei and genomic DNAs (respectively). Approximately one-third of the tumours analysed (24/74; 32%) exhibited MSI, whereas 38/86 (44%) of the EC samples displayed aneuploidy.

Protein kinase C epsilon signaling complexes include metabolism- and transcription/translation-related proteins: complimentary separation techniques with LC/MS/MS.

The serine/threonine kinase protein kinase C epsilon (PKC epsilon) has been shown to be a critical component in the heart's resistance to cell death following ischemic insult. Recent studies have indicated that PKC epsilon forms multi-protein signaling complexes to accomplish signal transduction in cardiac protection. Using two-dimensional electrophoresis (2DE), combined with matrix-assisted laser desorption ionization mass spectrometry (MS), the initial analysis of these complexes identified signaling molecules, structural proteins, and stress-activated proteins.

Low fasting serum triglyceride and high free fatty acid levels in pulmonary fibrosis: a previously unreported finding.

Objective: The authors describe here the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in pulmonary fibrosis, a finding that has never been reported before.

Patients And Methods: TGs were measured in: (a) 44 patients (3 male and 41 female; mean age SEM: 63.06 +/- 4.

Primary hydatid cysts of psoas muscle.

Background: Hydatid cysts may occur in any area of the body, but they usually localize to the liver and the lungs. Primary localization in muscle is not common, accounting for 2-3% of all sites; even rarer is the development of multiple cysts.

Methods: The patient presented with a painless abdominal mass which gradually increased in size to a diameter of approximately 16 cm.

Microsatellite instability and mutation analysis of candidate genes in unselected sardinian patients with endometrial carcinoma.

Background: Microsatellite instability (MSI) is due mostly to a defective DNA mismatch repair (MMR). Inactivation of the two principal MMR genes, hMLH1 and hMSH2, and the PTEN tumor suppressor gene seems to be involved in endometrial tumorigenesis. In this study, Sardinian patients with endometrial carcinoma (EC) were analyzed to assess the prevalence of both the mutator phenotype (as defined by the presence of MSI and abnormal MMR gene expression at the somatic level) and the hMLH1, hMSH2, and PTEN germline mutations among patients with MSI positive EC.

[Microbial circulation and control in two Intensive Care Units].

A microbiological survey was carried out in two medical Intensive Care Units from January to June 2000. The patients, staff (hands and upper respiratory tract) and environment were monitored. The results obtained in both Care Units give cause for concern.

[Microbial environmental surveillance in a bone marrow transplant unit].

The aim of this study was to evaluate, after several years of application, in a bone marrow transplant (BMT) center of a Cagliari Hospital, the effectiveness of the disinfection protocol in minimizing the risk of environmentally transmitted infections. Microbial contamination of the air was evaluated every two months during normal activity using an SAS sampler. The contamination of surfaces was determined weekly, 2hrs after sanitation, using disposable surface contact plates.

Expression of the nuclear coactivators CBP and p300 in developing craniofacial tissue.

cAMP regulatory element-binding protein (CREB)-binding protein (CBP) and its functional homolog, the adenovirus E1A -associated 300-kDa protein (p300) are nuclear coactivators and histone acetyltransferases that integrate signals from disparate pathways by bridging specific transcription factors to the basal transcription apparatus. Their role in patterning and development was suggested by studies in mice in which CBP and p300 expression was disrupted and by the human Rubinstein-Taybi syndrome, which is associated with mutations of CBP. The cAMP signal transduction pathway plays a critical role during development of the palate.

[Levels of cytokines in mucosal biopsies of Crohn's colitis. Physiopatological observations].

Background: It is well known that mucosal concentrations of many pro and anti-inflammatory cytokines are elevated in diseased segments of colon in Crohn's colitis. The present study, showing preliminary results, aims to determine whether the IL-1beta, IL-6 and IL-8 levels are increased throughout the entire colon in patients with Crohn's colitis.

Methods: Five patients with active Crohn's colitis and five controls were studied by mucosal biopsies.

Painting with a molecular brush: genomic/proteomic interfacing to define the drug action profile of novel solid-tumor selective anticancer agents.

XK469 is an investigational anticancer agent that exhibits antiproliferative activity in tumor-bearing animal models. We examined the drug-action profile of this agent at the molecular level regarding alterations induced in gene expression and proteins in HCT-116 human colon adenocarcinoma cells. We used a unique cDNA microarray (GeneMap(TM) Cancerarray) comprising 1152 human tumor-related genes and 2-D gel electrophoresis, respectively, following a 24-hour exposure to a drug concentration that killed a two-log fraction of HCT-116 clonogenic cells.

Convergence of cAMP, TGF-beta and retinoic acid signaling pathways in cells of the embryonic palate.

We have previously described bi-directional cross-talk between the retinoic acid (RA) and transforming growth factor beta (TGF-beta) signal transduction pathways in primary cultures of murine embryonic palate mesenchymal (MEPM) cells. In this paper we identify interactions between the TGF-beta1, cyclic adenosine 3', 5'-monophosphate (cAMP) and RA signaling systems. TGF-beta1 and forskolin, an activator of the cAMP pathway, inhibited RA-induced expression of RAR-beta mRNA in MEPM cells, though only TGF-beta1 inhibited RA-induced RAR-beta protein expression.

[Clinical relevance of unusual metastases from colorectal neoplasms].

Background: The aim of the study was to evaluate the clinical relevance of isolated metastases (MII) in unusual sites (different from liver and lung), synchronous and metachronous, in patients operated on for colorectal carcinoma (CCR).

Methods: The study was performed on 655 patients who underwent surgery for CCR during the period 1985-2000. Work out for distance metastases was performed (both during preoperative evaluation and follow-up) with physical examination and other few exams (CEA, chest X-ray, abdominal US scan).