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A Gallo

Publications and source records attributed to A Gallo.

At least 55 records · Page 3Linked to original sources

The localization and activity of cAMP-dependent protein kinase affect cell cycle progression in thyroid cells.

cAMP signals are received and transmitted by multiple isoforms of cAMP-dependent protein kinases (PKAs), typically determined by their specific regulatory subunits. We describe changes in the cAMP signal transduction pathway during cell cycle progression in synchronized rat thyroid cells. Both PKA type II (PKAII) localization and nuclear cAMP signaling are significantly modified during G(0) and G(1)-S transitions. G(1) is characterized by PKA activation and amplified cAMP signal transduction. This is associated with a decrease in the concentration of RI and RII regulatory subunits and enhanced anchoring of PKAII to the Golgi-centrosome region. Just prior to S, the cAMP pathway is depressed. Up-regulation of the pathway by exogenous cAMP in G(1) inhibited the subsequent decay of the Cdk inhibitor p27 and delayed the onset of S phase. Forced translocation of endogenous PKAII to the cytosol down-regulated cAMP signaling, advancing the timing of p27 decay and inducing premature exit from G(1). These data indicate that membrane-bound PKA amplifies the transduction of cAMP signals in G(1) and that the length of G(1) is influenced by cAMP-PKA.

Animals↗

alpha5 integrin distribution and TGFbeta1 gene expression in supraglottic carcinoma: their role in neoplastic local invasion and metastasis.

BACKGROUND: Head and neck carcinomas are characterized by tumor-infiltrating lymphocytes (TIL) producing cytokines. Adhesion molecules, extracellular matrix proteins (ECMPs), and cytokines regulate cell-cell and cell-ECMPs interactions. We investigated the distribution of these proteins to contribute to better understanding of their role in local tumor invasion and metastasis. METHODS: Distribution of integrins, laminin, type IV collagen, tenascin, and fibronectin was immunohistochemically evaluated in 13 supraglottis carcinomas. Cytokines gene expression was assessed by reverse-transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Neoplastic cells were alpha2beta1, alpha3beta1, alpha4beta1, alpha5beta1 and alpha6beta1 positive. Normal and metaplastic epithelium was alpha5beta1 negative; the stroma of primary and metastatic tumors was tenascin and fibronectin positive. TGFbeta1 and IFNgamma gene expression was observed in the majority of tumors. CONCLUSIONS: Because TGFbeta1 is known to down-modulate immune processes and to increase alpha2beta1, alpha5beta1, and tenascin distribution, we propose that their expression in neoplastic cells of supraglottis carcinoma might represent an immune-related process able to help tumor growth and progression.

Antigens, CD↗

Interleukin-12 related cytokine gene expression at a tissue level in carcinomas of the larynx.

Head and neck squamous cell carcinomas are highly immunogenic tumors in which tumor-infiltrating lymphocytes (TIL) consist largely of CD4, Th1, and Th2 lymphocytes and a minor proportion of other immune effector cells, such as macrophages and B cells. Interleukin (IL)-12 release and antigen presentation from macrophages induce Thl and Th2 differentiation. Gene expression for IL-12, interferon (IFN)gamma, IL-4, and other cytokines was studied by reverse transcriptase-polymerase chain reaction in tissue sections from laryngeal carcinomas to evaluate the mechanisms of Th1 and Th2 lymphocyte differentiation. Local effects of cytokines were probed evaluating immunohistochemically the presence of inducible nitric oxide synthase positive tumor-infiltrating macrophages in 13 cases of laryngeal carcinomas. IL-12 gene expression was observed in five cases and that for IFNgamma in nine cases. These cytokines were coexpressed in four specimens. IL-4 and transforming growth factor-beta1 were detected in 5 and 11 cases, respectively. These findings show that IL-12, IFNgamma, IL-4, and IL-6 in laryngeal carcinomas have different patterns of gene expression, suggesting distinct pathways of Th1 and Th2 lymphocyte differentiation to indicate that their exogenous modulation might be utilized in adoptive immunotherapy.

Carcinoma, Squamous Cell↗

The properties of a tRNA-specific adenosine deaminase from Drosophila melanogaster support an evolutionary link between pre-mRNA editing and tRNA modification.

Pre-mRNA editing involving the conversion of adenosine to inosine is mediated by adenosine deaminases that act on RNA (ADAR1 and ADAR2). ADARs contain multiple double-stranded RNA(dsRNA)-binding domains in addition to an adenosine deaminase domain. An adenosine deaminase acting on tRNAs, scTad1p (also known as scADAT1), cloned from Saccharomyces cerevisiae has a deaminase domain related to the ADARs but lacks dsRNA-binding domains. We have identified a gene homologous to scADAT1 in the region of Drosophila melanogaster Adh chromosome II. Recombinant Drosophila ADAT1 (dADAT1) has been expressed in the yeast Pichia pastoris and purified. The enzyme has no activity on dsRNA substrates but is a tRNA deaminase with specificity for adenosine 37 of insect alanine tRNA. dADAT1 shows greater similarity to vertebrate ADARs than to yeast Tad1p, supporting the hypothesis of a common evolutionary origin for ADARs and ADATs. dAdat1 transcripts are maternally supplied in the egg. Zygotic expression is widespread initially and later concentrates in the central nervous system.

5' Untranslated Regions↗

Different patterns of postoperative bleeding following cytoreductive surgery for gynecological cancer.

PURPOSE OF INVESTIGATION: To study the possible causes of postoperative bleeding following maximal cytoreductive surgery for gynecological cancers. METHOD: We have retrospectively reviewed all our cases of postoperative bleeding following major abdominal and pelvic cytoreductive surgery within a 48-hour period. In the postoperative period, replacement therapy was ineffective in achieving hemodynamic stability. During re-operation, the entire abdominal cavity was evaluated for bleeding sites that were adequately ligated or electrocoagulated. RESULTS: Of 942 women undergoing major cytoreductive surgery 22 women (2.3%) were re-operated for postoperative bleeding after a mean of 14.2 hours. Bleeding was either localized from a vessel in 9 women (40.9%) or diffuse (capillary oozing) in 13 women (59.1). Operative deaths have been as high as 36.8%. CONCLUSION: Postoperative bleeding following cytoreductive surgery can be from a single group of vessels or a capillary oozing from the edges or denuded areas of excised peritoneum.

Female↗

Otorhinolaryngology emergency unit care: the experience of a large university hospital in Italy.

We recorded the symptoms and disposition of every patient who visited the otorhinolaryngology emergency department at our hospital in Rome, Italy, during 1996. During that time, our ENT specialists saw 21,548 patients. Only 311 of these patients (1.4%) required immediate hospitalization, while another 2,391 patients (11.1%) received treatment and were released. The other 18,846 patients (87.5%) did not have any pathology or condition that qualified as an actual emergency, and they were examined and released, often with a prescription or instructions for home care. These patients could have easily been treated by a family physician. The fact that emergency care in Italy is rendered free of charge (unlike ambulatory care, for which fees are charged) provides patients with a strong incentive to misuse the system. Such overutilization drives up the cost of health care and stretches the capacity of the medical staff. Steps need to be taken to redirect patients who misuse emergency services to seek medical care in ambulatory care centers.

Emergency Service, Hospital↗

Interleukin-12-related cytokine gene expression in carcinomas of the breast, lung, and larynx: a study at tissue level.

Tumor-infiltrating lymphocytes (TIL) consist of T helper 1 (Th1) and T helper 2 (Th2) cells producing interferon-gamma (IFN-gamma) and interleukin4 (IL-4), respectively. Interleukin-12 (IL-12) induces Th1 and Th2 differentiation. Therefore, IL-12, IFN-gamma, and IL-4 gene expression were evaluated by reverse transcriptase-polymerase chain reaction in carcinomas of the breast (n = 10), lung (n = 17), and larynx (n = 13) to investigate whether TIL activation is IL-12-related. IL-12 and IFN-gamma were codistributed in breast carcinomas, and IL-4 was demonstrated in three instances. IL-12 and IFN-gamma were detected in 15 and 13 lung carcinomas, respectively, and were codistributed in 11 cases; IL-4 was observed in 9 cases and was codistributed with IL-12 and IFN-gamma in 7 instances. IL-12 and IFN-gamma expression was observed in five and nine larynx carcinomas, respectively, and were codistributed in four cases; IL-4 was detected in five instances. These data indicate that breast, lung, and larynx carcinomas are characterized by different patterns of IL-12, IFN-gamma, and IL4 gene expression and suggest that Th1 activation may be induced, at least in part, by the neoplastic microenvironment.

Breast Neoplasms↗

Thyroid transcription factor 1 phosphorylation is not required for protein kinase A-dependent transcription of the thyroglobulin promoter.

Thyroid transcription factor 1 (TTF1) is a nuclear homeodomain protein that binds to and activates the promoters of several thyroid-specific genes, including that of the thyroglobulin gene (pTg). These genes are also positively regulated by thyroid-stimulating hormone/cyclic AMP (cAMP)/protein kinase A (PKA) signaling. We asked whether PKA directly activates TTF1. We show that cAMP/PKA activates pTg and a synthetic target promoter carrying TTF1 binding site repeats in several cell types. Activation depends on TTF1. Phosphopeptide mapping indicates that TTF1 is constitutively phosphorylated at multiple sites, and that cAMP stimulated phosphorylation of one site, serine 337, in vivo. However, alanine substitution at this residue or at all sites of phosphorylation did not reduce PKA activation of pTg. Thus, PKA stimulates TTF1 transcriptional activity in an indirect manner, perhaps by recruiting to or removing from the target promoter another regulatory factor(s).

Alanine↗

BRCA1 and BRCA2 genes: role in hereditary breast and ovarian cancer in Italy.

The heritable defects of BRCA1 and BRCA2 genes have been shown to predispose to breast and ovarian cancers. In a previous report, we analyzed 46 Italian families with breast and/or ovarian cancer for BRCA1 mutations. In the present study, those families and 11 others were screened for BRCA2 mutations; the newly enrolled families were also analyzed for the BRCA1 gene. The coding region and splice boundaries of BRCA2 and BRCA1 genes were assessed by the protein-truncation test and single-strand conformational polymorphism. A total of 20 different mutations were found in 21 families (37%). A total of 9 families (16%) showed mutations in the BRCA1 gene, including the one new mutation identified in this study (5382insC), and 12 families (21%) presented mutations in the BRCA2 gene. BRCA2-mutated families presented breast and ovarian cancers or breast cancers only, whereas most BRCA1-mutated families presented ovarian cancer alone or in association with breast cancer. All the BRCA2 mutations led to a truncated protein: 6 were frameshift mutations, 4 were non-sense mutations and 2 involved the intronic invariant region leading to splice variants. Therefore, in the Italian population, the cumulative proportion of BRCA1 and BRCA2 mutations was within the range observed in other studies (37%), with higher involvement of BRCA2 than of BRCA1. Many families in which no mutations were found presented a very high incidence of breast and/or ovarian cancer. Among the 36 BRCA1 and BRCA2 wild-type families, 24 presented at least 4 cancer cases, indicating the existence of other important predisposing genes.

Adult↗

Protein kinase C activity is acutely regulated by plasma glucose concentration in human monocytes in vivo.

Activation of protein kinase C (PKC) by hyperglycemia is implicated in the pathogenesis of long-term diabetic complications. Monocyte activation and transformation into macrophages is a key step in the atherosclerotic process. Therefore, in this study, we sought to determine 1) the effect of hyperglycemia on monocyte PKC activity and on the distribution of Ca2+-dependent and diacylglycerol-sensitive PKC isoforms; and 2) whether the effects on these parameters are determined by hyperglycemia per se, independent of the diabetic state. The studies were performed in 19 type 2 diabetic patients and 14 control subjects. Plasma glucose concentration was higher and insulin sensitivity lower (both P < 0.01) in diabetic patients than in control subjects. Monocytes from diabetic patients showed similar cytosol PKC activity to those from control subjects but higher membrane PKC activity (78+/-6 vs. 50+/-5 pmol x min(-1) x mg(-1) protein; P < 0.01). A direct correlation was observed between fasting plasma glucose and membrane PKC activity (r2 = 0.4008, P = 0.0001). In contrast, a reciprocal correlation was observed between membrane PKC activity and insulin sensitivity index (r2 = 0.28, P < 0.05). Using immunoblotting analysis, we found that membrane beta2, but not alpha, isoform of PKC was more abundant in monocytes from diabetic patients. In diabetic patients, when euglycemia was acutely induced, membrane PKC activity decreased by approximately 42% and beta2 isoform by approximately 15%. In two normal subjects in whom hyperglycemia was induced, membrane PKC increased from 63 and 57 to 92 and 128.6 pmol x min(-1) x mg(-1) protein, respectively. This increase was associated with an increase in the membrane isoform beta2; alpha isoform was unchanged. We conclude that 1) monocytes express the glucose-sensitive beta2 isoform of PKC; 2) the prevailing plasma glucose acutely regulates the activity of the membrane PKC and the content of membrane PKC beta2 isoform; and 3) this effect appears to be a direct effect of glucose per se, since the phenomenon was observed in normal control subjects when hyperglycemia was induced. Monocyte PKC activation may account for the accelerated atherosclerosis of patients with type 2 diabetes.

Blood Glucose↗

Treatment of vaginal intraepithelial neoplasia (VAIN) with the carbon dioxide laser.

The increasing incidence of VAIN especially in young women, the frequent relapses, and renewed interest in maintaining sexual function have prompted gynecologists to a conservative management of the disease. Over the last decades, surgery, 5-fluorouracil, chemosurgery, electrocautery and cryotherapy were used. Carbon dioxide laser ablation therapy of VAIN has been reported from various authors with different results. From June 1991 through December 1998, 39 patients affected by VAIN were treated with laser surgery (35 vaporizations and 4 excisions). To achieve complete elimination of all lesions, seven patients had two vaporizations and one patient three. One patient was submitted to six combined repeated treatments. Five patients were not evaluable and three presented persistence of VAIN. One patient died because of AIDS. The remaining 30 patients, treated with laser surgery, were lesion free: 7 patients were negative at 12-24 months, 10 at 24-36 months and 13 at 37-90 months. No important complications occurred. Sexual function was not compromised. Carbon dioxide laser is a safe and efficacious tool in the treatment of pre-neoplastic lesions of the vagina.

Adult↗

Low incidence of BRCA1 mutations among Italian families with breast and ovarian cancer.

Most familial breast or ovarian cancers are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. The cloning of these genes has opened a new era for the genetic counseling of women with a family history of breast or ovarian cancer. To estimate the incidence of detectable BRCA1 mutations and to define the eligibility criteria for genetic testing in the Italian population, a total of 53 patients belonging to 46 families clustering multiple cases of breast and/or ovarian cancer were investigated. Seven families presented with ovarian cancer only, 16 had both ovarian and breast cancers, and 23 were characterized by breast cancer only. Using a combination of protein truncation test (PTT) and single strand conformational polymorphism (SSCP) analysis followed, when necessary, by direct sequencing, we found 8 distinct mutations, 2 of these not reported before. Five frameshift and 2 nonsense mutations led to a truncated protein. One mutation was a missense substitution involving a cysteine in the zinc finger domain. One variant creating an ETS binding site in intron I was found but its role was not defined. The percentage of families carrying mutations was 17%. Among the families characterized by ovarian cancer only and by breast and ovarian cancer, the percentage of BRCA1 mutations was 57% and 12.5%, respectively. In contrast, the percentage of altered BRCA1 in families with only breast cancers was 9%. In the 46 Italian families studied, BRCA1 mutations were detected in fewer kindreds than those previously hypothesized based on linkage analysis, especially when these were characterized by breast cancers only. Our results indicate that families with a low number of cancer patients should be referred for BRCA1 genetic testing mainly when ovarian cancer is present.

Adult↗

Molecular cloning and chromosomal localization of the mouse Gpr37 gene encoding an orphan G-protein-coupled peptide receptor expressed in brain and testis.

We report the cloning of the mouse ortholog of the human GPR37 gene, which encodes an orphan G-protein-coupled receptor highly expressed in brain tissues and homologous to neuropeptide-specific receptors (D. Marazziti et al., 1997, Genomics 45: 68-77; Z. Zeng et al., 1997, Biochem. Biophys. Res. Commun. 233: 559-567). The genomic organization of the GPR37 gene is conserved in both mouse and human species with a single intron interrupting the receptor-coding sequence within the presumed third transmembrane domain. Comparative genetic mapping of the GPR37 gene showed that it maps to a conserved chromosomal segment on proximal mouse chromosome 6 and human chromosome 7q31. The mouse Gpr37 gene contains an open reading frame coding for a 600-amino-acid protein 83% identical to the human GPR37 gene product. The predicted mouse GPR37 protein contains seven putative hydrophobic transmembrane domains, as well as a long (249 amino acid residues), arginine- and proline-rich amino-terminal extracellular domain, which is also a distinctive feature of the human GPR37 receptor. Northern blot analysis of mouse tissues with Gpr37-specific probes revealed a main 3.8-kb mRNA and a much less abundant 8-kb mRNA, both expressed in the brain. A 3-kb mRNA is also expressed in the testis. Both the mouse and the human GPR37 genes may belong to a class of highly conserved mammalian genes encoding a novel type of G-protein-coupled receptor predominantly expressed in the brain.

Amino Acid Sequence↗

Expression of folate binding protein as a prognostic factor for response to platinum-containing chemotherapy and survival in human ovarian cancer.

Overexpression of the folate binding protein (FBP) is a common feature in epithelial ovarian cancer, but its prognostic significance is not clearly understood. We investigated whether FBP in epithelial ovarian cancer specimens is a predictor of response to chemotherapy and survival. Between 1990 and 1995, 99 patients with epithelial ovarian cancer underwent primary surgery and were treated with chemotherapeutic regimens including platinum derivatives. First-line chemotherapy was performed in 58 patients with residual disease and in 41 patients without residual disease after primary laparotomy. FBP expression level was determined in frozen specimens by cyto-fluorimetric assay using the MOv 18 monoclonal antibody (MAb). Association of FBP fluorescence index (FI) with clinical characteristics, response to chemotherapy, and survival was studied by univariate and multivariate analysis. In the 58 patients with residual disease after primary surgery, failure to respond to chemotherapy (complete or partial remission) was about 15-fold higher (95% confidence interval, 2.96-77.43) when tumors had FBP FI above the median value (FBP FI = 3.25). FBP FI was not a predictor of survival in the entire series of tumors (99 patients). However, in the subgroup of 58 patients with residual disease after primary surgery, survival analysis confirmed the disadvantage observed with respect to response to chemotherapy in patients expressing FBP FI above the median value (hazard ratio 2.01; 95% confidence interval 0.95-4.24). In conclusion, higher levels of FBP expression might be a predictor of chemotherapy response failure in ovarian cancer. In patients with residual disease after primary surgery, FBP FI could represent a valuable prognostic marker for survival.

Adult↗

Novel lectin-related proteins are major components in lima bean (Phaseolus lunatus L.) seeds.

The only component of the lectin-related protein family so far reported in Lima bean (Phaseolus lunatus L.) seeds is the minor seed lectin (LBL). In the morphotype Big Lima, we have isolated and characterised two abundant lectin-related seed proteins and the corresponding cDNA clones. The clones show 93.7% nucleotide identity and encode an arcelin-like (ARL) and an alpha-amylase inhibitor-like (AIL) protein. Not considering the signal peptides, ARL and AIL polypeptides contain 239 and 233 amino acids, respectively. Each polypeptide is present in the mature protein as two glycoforms. ARL subunits (43 and 46 kDa) make up oligomers of about 125 to 130 kDa whereas AIL subunits (40 and 42 kDa) oligomerise in dimers of about 88 to 100 kDa. cDNA clones encoding two isoforms of the less abundant Lima bean lectin were also isolated. In common bean (P. vulgaris) the lectin locus encodes the lectin and the lectin-related proteins alpha-amylase inhibitor and arcelin, all plant defence proteins. Our data indicate extensive evolution of the locus also in Lima bean.

Amino Acid Sequence↗

Supracricoid partial laryngectomies: oncologic and functional results.

BACKGROUND: The authors present their study on oncologic and functional results of supracricoid partial laryngectomies (SPL) performed on 149 patients between January 1984 and December 1995. METHODS: Cricohyoidopexy (CHP) was carried out on 98 patients and cricohyoidoepiglottopexy (CHEP) on 51 patients. The patients were divided into two groups. The first group included those operated on between January 1984 and December 1992 and who therefore had a minimum follow-up period of 3 years. The second group included those operated on after December 1992 and who therefore had a follow-up period of less than 3 years. The statistical evaluation of this second group was carried out using an actuarial method according to Kaplan-Meier. RESULTS: In the first group, survival rate (regarding disease-related deaths) was 94% (95/101), whereas in the second group, survival rate was 95%. There were 9 recurrences in the 149 patients (6.71%), B of which occurred after CHP (6 for tumor [T] and 2 for node [N]) and 1 (for T) after CHEP. Three of the 6 recurrences for T after CHP occurred in the hypopharynx, 2 in the peristomal area, and 1 in the arytenoid area. The only recurrence for T after CHEP occurred in the paraglottic area. Decannulation was carried out in 85.7% of CHP patients (84/98) and in 98% of CHEP patients (50/51). The nasogastric tube was kept in position for an average of 28 days (range, 15-90 days) in the CHP patients and 15 days (range, 9-90 days) in the CHEP patients. Swallowing was excellent; only a small number of patients (n = 21) were forced to assume a particular posture during meals. Phoniatric controls performed on 104 patients also showed adequate speech recovery. CONCLUSIONS: If the indications are applied scrupulously, CHEP is a valid alternative to partial laryngeal surgery and CHP is a possible alternative to total laryngectomy in the treatment of glottic and supraglottic tumors.

Adult↗

Cloning of GPR37, a gene located on chromosome 7 encoding a putative G-protein-coupled peptide receptor, from a human frontal brain EST library.

A cDNA sequence encoding a putative peptide-specific G-protein-coupled receptor (GPR37) was isolated from a set of human brain frontal lobe expressed sequence tags. The GPR37 cDNA predicts a single open reading frame coding for a 613-amino-acid protein with seven hydrophobic transmembrane domains. The GPR37 genomic sequence was mapped to chromosome 7q31, and it was isolated upon screening of a chromosome 7-specific genomic library. The GPR37 gene spans more than 25 kb and contains two exons and a single intron which interrupts the GPR37 cDNA within the sequence encoding the presumed third transmembrane domain. Northern blot analysis with GPR37 probes revealed a main 3.8-kb mRNA and a less abundant 8-kb mRNA, both expressed in human brain tissues, particularly in corpus callosum, medulla, putamen, and caudate nucleus. The lowest level of expression was detected in cerebellum. The 3.8-kb mRNA is also less abundantly expressed in liver and placenta. Although the ligand for the putative GPR37 receptor has not been identified, its deduced amino acid sequence shows a high degree of homology (approximately 40% in the transmembrane regions) with most mammalian peptide-specific G-protein-coupled receptors and particularly with the human endothelin-B, bombesin-BB1, and bombesin-BB2 receptors.

Adult↗