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P De Luca

Publications and source records attributed to P De Luca.

At least 37 records · Page 2Linked to original sources

A conserved TATA-less proximal promoter drives basal transcription from the urokinase-type plasminogen activator receptor gene.

The urokinase-type plasminogen activator receptor (uPAR) focuses at the cell surface the activation of pro-uPA and, hence, the formation of plasmin, thus enhancing directional extracellular proteolysis. To characterize the transcriptional regulatory mechanisms that control receptor expression, we have cloned an uPAR DNA segment containing upstream regulatory sequences from both the human and murine genomes. We report that a proximal promoter, contained within 180 bp from the major transcription start sites of the human uPAR gene, drives basal transcription. This region lacks TATA and CAAT boxes and contains relatively GC-rich proximal sequences. A subregion of this sequence, highly conserved between human and murine genes, contains most of the promoter activity and is specifically bound by HeLa nuclear proteins, one of which belongs to the SP1 class.

Animals↗

Differential transcriptional regulation of c-myc promoter through the same DNA binding sites targeted by Sp1-like proteins.

Sp1 and Sp3 are closely related members of a gene family encoding proteins with very similar structural features. The zinc finger DNA binding domains of Sp1 and Sp3 are highly conserved and they bind to GC and GT box with comparable affinities. To begin to delineate the specific roles of these two members of the Sp1-like gene family, here we have analysed the DNA binding specificity and their effects on activation of human c-myc promoter. We found that both proteins bind to the same sites of c-myc promoter, upstream to both the P1 and P2 initiation sites. Cotransfection experiments, in mammalian and insect cells, indicated that Sp1 trans-activate c-myc promoter, whereas Sp3 did not. In addition, enforced expression of Sp3 repressed Sp1-mediated activation of c-myc. Finally, we found that Sp1 and E2F-1/DP-1 cooperatively trans-activate c-myc promoter. In contrast enforced expression of Sp3 fails to repress E2F-1/DP-1-mediated activation.

Base Sequence↗

Different members of the Sp1 multigene family exert opposite transcriptional regulation of the long terminal repeat of HIV-1.

Recently, a family of transcription factors structurally related to Sp1 has been described; thus, more than one activator may bind to the GC boxes present in a number of viral and cellular promoters. We have compared the transactivation potentials of Sp1, Sp3 and Sp4 proteins on the human immunodeficiency virus type 1 (HIV-1) promoter. The long terminal repeat (LTR) of HIV-1 contains three binding sites for the transcription factor Sp1 (GC boxes) which are involved in both basal and Tat-mediated transcriptional activation. Moreover, a cooperative interaction between NF-kappa B and Sp1 is required for HIV enhancer activation. We now demonstrate that Sp4 is an activator, while the Sp3 protein represses basal expression of HIV promoter. Remarkably, we found that over-expression of the transcription factor Sp3 was able to suppress Tat-mediated transactivation. These inhibitory effects of Sp3 correlate with its DNA binding activity, suggesting that Sp3 inhibition involves competition with Sp1 for occupancy of the GC boxes. Next, we have analyzed the role of different Sp1-related proteins in the stimulation of HIV-1 promoter in response to mitogens. We found that the binding of NF-kappa B is not by itself sufficient to induce HIV gene expression. Instead, an interaction between NF-kappa B and the trans-acting domain (A domain) of Sp1 bound to an adjacent site must occur. We found that the cooperative interaction between NF-kappa B and Sp1 is highly specific, since neither Sp3 nor Sp4 is capable of cooperating with NF-kappa B.

Base Sequence↗

[Ovarian neoplasms and tumor markers].

This is an experience about the utility of CA125 in diagnosis, staging, prognosis, and therapeutic response of ovarian cancer. The patients were 21 (the ages range was 38-66). They had an epithelial cancer (10 serous, 3 mucinous, 2 endometrioid, 6 non specific). The quantitative test of CA125 was performed with purified monoclonal antibody OC125 pre and post antineoplastic treatment. The reduction of CA125 was in connection with the neoplastic regression. Perservering or increasing values were related to neoplastic stasis or to non-responsive neoplasia, respectively. Even if the method we used was specific its sensibility is lower in patients with smallest residue disease.

Adult↗

[Evaluation of the clinical efficacy of azithromycin in acute respiratory infections in children].

Azithromycin activity in vivo has been studied in a group of children with acute respiratory tract infections in order to test the efficacy and tolerability of this antibiotic. The study involved 135 children treated with a single daily 10 mg/kg dose of azithromycin for three consecutive days. Ten days after this treatment 100% of children with otitis media, tracheobronchitis, or rhinosinusitis and 95.9% of children with pharyngo-tonsillitis were cured. Recurrences were never observed. Azithromycin proved remarkably effective for treatment of acute respiratory infections and otitis media in children. Tolerability and therapeutic compliance were excellent.

Acute Disease↗

Purification and partial characterization of single-chain ribosome-inactivating proteins from the seeds of Phytolacca dioica L.

Three ribosome-inactivating proteins (RIPs) similar to those already known (Stirpe et al. (1992) Bio/Technology 10, 405-412) were purified from the seeds of Phytolacca dioica. These proteins, called Phytolacca dioica RIPs (PD-S1, PD-S2 and PD-S3 RIPs), are glycoproteins, with M(r) approx. 30,000, inhibit protein synthesis by a rabbit reticulocyte lysate and phenylalanine polymerization by isolated ribosomes, and depurinate rat liver rRNA in an apparently identical manner as the A-chain of ricin and other RIPs (Endo et al. (1987) J. Biol. Chem. 262, 5908-5912). Part of the purified rat liver ribosomes appeared resistant to the action of PD-S RIPs. The most abundant protein, PD-S2 RIP, gave a weak or nil cross-reaction with sera against various other RIPs, including a pokeweed antiviral protein from the roots of Phytolacca americana. PD-S2 RIP was linked to a monoclonal antibody (Ber-H2) against the CD30 human lymphocyte antigen and the resulting immunotoxin was selectively toxic to the CD30 + Hodgkin's lymphoma-derived L540 cell line.

Amino Acid Sequence↗

YAC-assisted cloning of transcribed sequences from the human chromosome 3p21 region.

The region surrounding the ZNF35 zinc finger protein gene on 3p21 is of particular interest, as this region of chromosome 3 is frequently involved in rearrangements and/or deletions associated with various human tumors including lung and renal carcinoma. We have analyzed yeast artificial chromosomes (YACs), identified by PCR screening, using oligonucleotides derived from the ZNF35 gene. PFGE and Southern blot/hybridization analysis revealed that the clones cover 750-kb including the ZNF35 gene. The use of specific somatic cell hybrids have allowed us to locate the YAC contig telomeric to the D3F15S2 locus, in a region which is frequently deleted in lung carcinomas. In addition, we have developed a novel cDNA hybridization protocol allowing the isolation of transcribed sequences present in the overlapping YAC clones. Using the cDNA hybridization selection, we have isolated and characterized one transcribed sequence (D3S1362E) from the 3p21 YAC contig and the corresponding cDNA has been isolated. DNA sequencing analysis indicated that the D3S1363E cDNA codes for a putative transcription factor. Northern blot analysis indicated that the D3S1362E sequence hybridized to multiple transcripts in skeletal muscle, and weakly hybridizing transcripts of similar sizes were detected in other tissues.

Amino Acid Sequence↗

Structural and functional organization of the HF.10 human zinc finger gene (ZNF35) located on chromosome 3p21-p22.

We report the structural and functional characterization of the HF.10 zinc finger gene (ZNF35) in normal human cells, as well as a processed pseudogene. The HF.10 gene spans about 13 kb and it is interrupted by three introns. All 11 zinc finger DNA-binding domains are contiguously encoded within the last 3' exon. The genomic region surrounding HF.10 exon 1 contains a CpG island and acts as a promoter in vitro. Using transient CAT assay in cotransfection experiments in cultured cells, we have determined that the HF.10 finger protein is a transcriptional transactivator. Restriction enzyme mapping and partial nucleotide sequencing of the HF.10 pseudogene indicated that it has arisen by retroposition of spliced HF.10 mRNA. In situ hybridization experiments revealed that both the functional locus and the pseudogene map to chromosome 3p21p22, a region that is frequently deleted in small cell lung and renal carcinomas. Hybridization of the HF.10 gene and the HF.10 pseudogene DNA probes to metaphases from a small cell lung carcinoma cell line with the 3p deletion revealed that both loci are part of the deleted chromosome region.

Amino Acid Sequence↗

[The importance of direct immunofluorescence in the diagnosis of oral lichen planus. A clinical study and proposal of new diagnostic criteria].

A series of 40 lesions of various kinds as lichen planus are examined using samples stained with trichromic test. HLA-DR expression with immunoperoxidase technique and direct immunofluorescence using the standard techniques. The aim of the study was to discover the usefulness for diagnosis of direct immunofluorescence, above all in histologically uncertain cases. The results suggest the view that direct immunofluorescence is essential for diagnosis of lichen planus, in all clinical aspects. The author concludes with description of clinical proceeding for differential diagnosis between white and erosive lesions of mouth.

Adult↗

Changes in the plasma levels of proteins C and S in young women on low-dose oestrogen oral contraceptives.

The physiological importance of proteins C and S as natural anticoagulants is demonstrated by the increased risk of thromboembolic disease among subjects with hereditary deficiency of both proteins. In the present study the effects were evaluated of low-dose oestrogen oral contraceptives (OC) on the plasma levels of immunological protein S, as free (PS-f), and in reversible complex with C4b-binding protein as well as functional protein C (PC) in a homogeneous group of 20 young healthy women. The participants were randomly given either gestodene (75 micrograms) or desogestrel (150 micrograms) in combination with ethinyl oestradiol (30 micrograms). Blood samples were taken prior to the initiation of the treatment and at the end of the sixth 21-day treatment cycle. The mean concentration of both free and bound PS fell significantly, the decrease still being within the reference range. Conversely, the plasma values for PC rose to a statistically significant extent. There were no significant differences between the two OCs. Hypothetically, the changes in PS-f (active fraction) might be conducive to a procoagulant state, which the increased PC may compensate. The reverse effect of two OCs on the activity of the protein C-protein S anticoagulant system might suggest a different regulation of their synthesis.

Adult↗