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C Serra

Publications and source records attributed to C Serra.

At least 91 records · Page 5Linked to original sources
PubMed1995

Productive HIV-1 infection of human vascular endothelial cells requires cell proliferation and is stimulated by combined treatment with interleukin-1 beta plus tumor necrosis factor-alpha.

Vascular endothelial cells (EC) play a key role in viral tropism in vivo. Since conflicting reports have been published on the capability of HIV to infect EC in vitro, we analyzed some factors potentially capable of influencing the susceptibility of human umbilical vein endothelial cells (HUVEC) to HIV-1. Both primary cultures and differentiated immortalized HUVEC lines were used. HUVEC were negative for the expression of CD4, but weakly CD26- and galactosylceramide-positive. Although binding of HIV to EC was substantial, the virus was apparently incapable of replicating in nonproliferating cultures. In resting cultures, the content of cell-associated HIV disappeared 4-6 days after infection without production of p24 and infectious progency. In contrast, infection of proliferating EC cultures led to the transient release of p24 and infectious virus (10(2.5)-10(3.5) SFU/ml) peaking 2-6 days postinfection. Antibody neutralization of cytokines that may be produced by EC (IL1, IL6, IL8, TNF, IFN-beta) failed to modify virus adsorption and replication, whereas treatment with IL1-beta plus TNF-alpha stimulated both virus binding and virus release. As seen by gag polymerase chain reaction (PCR), the viral genome persisted up to 15 days in untreated EC cultures, but over 20 days in cultures exposed to IL1-beta plus TNF-alpha. This study shows that: (a) CD4-negative HUVEC are capable of binding substantial amounts of HIV-1; (b) binding is enhanced by proinflammatory cytokines; (c) the establishment of productive infection is favored by cell proliferation; and (d) exposure to IL1-beta plus TNF-alpha enhances virus replication.

CD4 Antigens↗
PubMed1995

Productive HIV-1 infection of normal human mammary epithelial cells.

OBJECTIVE AND DESIGN: To determine the susceptibility of mammary epithelial cells (MEC) to HIV-1 as breastfeeding is an established route of HIV transmission, although the origin of virus in breastmilk is unclear. METHODS: Primary epithelial cell cultures were derived from the mammary glands of healthy donors; immortalized MEC lines were also used. HIV infection was followed by detection of infectious particle production, p24 antigen and viral sequences. RESULTS: Seven out of 11 primary MEC cultures and two out of three MEC lines were productively infected by HIV-1. Virus replication significantly reduced cell proliferation, although cell viability was only slightly affected. Cytopathic changes were not observed. MEC cultures expressed low levels of surface CD4, galactosylceramide and CD26, but essentially no human leukocyte antigen (HLA)-DR. Infection of HIV-permissive MEC cells was associated with the upregulation of surface HLA-DR and CD26. In contrast, the expression of CD4, tissue-specific markers, adhesion molecules and growth-factor receptors was downregulated. To a lesser extent, similar effects were also observed in non-permissive cells. Hormones (triiodothyronine plus beta-estradiol and prolactin) enhanced HIV replication, possibly through the stimulation of cellular DNA synthesis. CONCLUSIONS: We concluded that HIV-1 replication in ductal/alveolar MEC may be, in part, responsible for the presence of HIV-1 in milk; that hormones may stimulate virus replication; and that infection reduces the growth of epithelial cells. Although in vitro HIV is produced by MEC to a lesser extent than lymphoid cells, MEC-derived HIV might have selective advantages for the infection of mucosal epithelial cells during breastfeeding.

Breast↗
PubMed1994

Mutual interactions between HIV-1 and cytokines in adherent cells during acute infection.

The production of cytokines by HIV-infected cells from adherent tissues as well as their effects on HIV replication in the same cells were investigated. CD4-transfected HeLa-T4-6c epithelial cells, CD4-positive normal lung fibroblasts and CD4-negative RD rhabdomyosarcoma cells were infected with HIV-1. All cultures were permissive for virus replication, which was completed within 48-72 h by Hela-T4-6c and RD cells and 2-3 weeks in normal fibroblasts. During the course of HIV replication, a series of cytokines (particularly IL-6 and TNF alpha) was produced and released in parallel to the peak of virus growth, in amounts varying with the cell system studied. Treatment of cultures with recombinant cytokines given at concentrations in the range of those induced by HIV-1 indicated that IL-6 and TNF alpha caused an increase of: i) CD4 expression, ii) HIV absorption to uninfected cells, and iii) release of infectious virions by infected cells. The fact that HIV-1 absorption and spread can be mediated by HIV-induced cytokines may be relevant in the pathogenesis of the in vivo disease, as it may constitute a possible self-enhancing model of HIV infection also in the solid tissues.

CD4 Antigens↗
PubMed1994

Infectious virus with reduced cytopathogenicity resulting from persistent infection of normal lung fibroblasts by HIV type 1 strains.

We asked whether HIV-1 had the capacity to establish a persistent infection of cultured human diploid fibroblasts. Human strains of normal diploid embryo lung fibroblasts were infected with HIV-1 of the HTLV-IIIB and HIV-1P1 strains. Infection was followed over time, to analyze HIV expression. Virus production (intra- and extracellular virus) was evaluated as follows: ability to form syncytia in the C8166 T cell line, production of p24 and other viral antigens (ELISA and indirect immunofluorescence), search for a gag sequence in cell DNA by the polymerase chain reaction followed by hybridization to an HIV-1-specific probe (SK19). Cell-free culture supernatant was used as a virus source to infect de novo fibroblasts and C8166 T cells. Infection of cultured fibroblasts with either the HTLV-IIIB or HIV-1P1 strain led regularly to the establishment of persistently infected cultures. Fibroblast cells were capable of continuous virus production for at least 10 months. The released virus was capable of reinfecting cultured fibroblasts and of producing cytopathic effects in the C8166 T cell line. However, when compared to wild-type strains, the infectious virus derived from fibroblasts showed a prolonged replication cycle and a decreased ability to form syncytia in the T cell line. Therefore, HIV-1 can establish a persistent and productive infection in normal lung fibroblasts. The data are consistent with the hypothesis that in vivo, at least in the lung, fibroblasts may represent a virus reservoir and that infection of these cells may lead to the production of attenuated variants of HIV.

Cell Line↗
PubMed1993

Alternative splicing of a previously unidentified CFTR exon introduces an in-frame stop codon 5' of the R region.

The cystic fibrosis transmembrane conductance regulator (CFTR) has been extensively characterized as the carrier of the basic defect in cystic fibrosis. CFTR is part of a growing family of proteins encoded by a single gene, the variant isoforms of which are generated by alternative splicing or RNA editing. We have analyzed the CFTR mRNA in the region of exons 10-11 in T84 cells and detected an alternatively spliced exon (10b) accounting for about 5% of the CFTR mRNA. The exon 10b found in both the human and mice genomes, introduces an in-frame stop codon. The resulting mRNA is translated into a truncated CFTR protein, identified in T84 cells by immunoprecipitation with the CFTR-specific monoclonal antibody MATG 1061. The insertion of a differentially spliced exon carrying an in-frame stop codon is a novel cellular mechanism for the production of a protein sharing common sequences with another, but having different properties and functions.

Amino Acid Sequence↗
PubMed1993

Skin-specific expression of a truncated E1a oncoprotein binding to p105-Rb leads to abnormal hair follicle maturation without increased epidermal proliferation.

In cultured cells, mutants of the Adenovirus E1a oncoprotein which bind to a reduced set of cellular proteins, including p105-Rb, p107, and p60-cyclin A, are transformation defective but can still interfere with exogenous growth inhibitory and differentiating signals, such as those triggered by TGF-beta. We have tested the ability of one such mutant, NTdl646, to interfere with keratinocyte growth and differentiation in vivo, in the skin of transgenic mice. Keratinocyte-specific expression of the transgene was achieved by using a keratin 5 promoter. Two independent lines of transgenic mice were obtained which expressed E1a specifically in their skin and exhibited an aberrant hair coat phenotype with striking regional variations. Affected hair shafts were short and crooked and hair follicles exhibited a dystrophic or absent inner root sheath. Interfollicular epidermis was normal, but its hyperplastic response to acute treatment with TPA (12-O-tetradecanoylphorbol-13-acetate) was significantly reduced. Primary keratinocytes derived from these animals were partially resistant to the effects of TPA and TGF-beta. The rate of spontaneous or chemically induced skin tumors in the transgenic mice was not increased. Thus, expression of a transgene which interferes with known negative growth regulatory proteins causes profound disturbances of keratinocyte maturation into a highly organized structure such as the hair follicle but does not lead to increased and/or neoplastic proliferation.

Adenoviridae↗
PubMed1993

'Idiopathic' jaundice in Sardinian full-term newborn infants: a multivariate study.

'Idiopathic' hyperbilirubinaemia in the first 4 days of life was studied in 431 unselected healthy full-term (gestational age > or = 37 weeks) singleton Sardinian infants with birthweight > or = 2500 g. All infants were free from malformations or any disease requiring treatment other than jaundice, they were ABO and Rh compatible with their mothers and were not G6PD deficient. The serum bilirubin level was > 11.9 mg/dl (204 mumol/l) and > 14.9 mg/dl (256 mumol/l) in 37.1% and 15.3% of the study subjects. The vast majority of the infants (94%) were breast fed; no difference in the incidence of jaundice was found between breast-fed and bottle-fed infants. A logistic regression analysis indicated that high alpha-fetoprotein concentrations in cord blood, history of neonatal jaundice in previous full-term siblings, delayed first meconium passage and weight loss were associated with jaundice, defined as a serum bilirubin level > 11.9 mg/dl. These results suggest that the high rate of neonatal hyperbilirubinaemia in Sardinia is mostly related to constitutional and possibly hereditary factors.

Breast Feeding↗
PubMed1992

Interferon-alpha/beta in virus-induced mouse mammary carcinogenesis: effects on the spontaneous process and on the progression of transplanted pre-neoplastic lesions.

Low levels of anti-viral activity, mainly interferon alpha/beta (IFN-alpha/beta), are regularly found in lymphoid tissues of BALB/c mice infected with the C3H strain of mammary tumor virus. At the time of tumor development, significant amounts of anti-viral activity were detected in homogenates of spleen and mammary tumors, but not in blood and normal mammary glands. This activity is pH2-resistant and neutralized by antibody to IFN/alpha-beta. The pathogenetic role of IFN in mammary carcinogenesis was investigated in 2 ways: (a) by treating virus-infected newborn mice with antibody to IFN-alpha/beta, and (b) by giving either the latter antibody or IFN-alpha/beta to virus-free animals transplanted with pre-neoplastic lesions. Mice were treated only for 2 months, starting either 1 week after birth or immediately after tumor transplant. In case (a), treatment with antibody to IFN-alpha/beta shortened the incubation period of mammary carcinomas and decreased the mean survival time. In case (b), anti-IFN antibody did not significantly affect the development of mammary tumors. However, exogenous IFN-alpha/beta markedly reduced both tumor incidence and mortality rate. These results indicate that endogenous IFN-alpha/beta plays a crucial role in the in vivo restriction of the early infectious phase of spontaneous carcinogenesis and that relatively high doses of IFN-alpha/beta may inhibit the progression of pre-neoplastic lesions.

Aging↗
PubMed1992

Regulation of surface-differentiation molecules by epidermal growth factor, transforming growth factor alpha, and hydrocortisone in human mammary epithelial cells transformed by an activated c-Ha-ras proto-oncogene.

Spontaneously immortalized human mammary epithelial cells MCF-10A were transfected with an activated c-Ha-ras oncogene. Transfected cells (MCF-10T) acquire a malignant phenotype, as already reported. Studies of 125I-2'-deoxyuridine incorporation in cultures given graded doses of hydrocortisone (HC), cholera toxin (CT), epidermal growth factor (EGF), and transforming growth factor alpha (TGF-alpha) showed that though MCF-10T had become almost independent on exogenous EGF and TGF-alpha, they continued to respond to the synergistic effect of HC and CT plus EGF. Both lines were phenotypically characterized with an immunoradiometric assay in live cells. Expression of MHC class-I molecules, human milk-fat-globule-I antigen, and EGF receptor was reduced in ras-transfected cells, although other differentiation markers were unchanged. Exogenous EGF down-regulated the expression of functional EGF-R, selectively in transformed cells. TGF-alpha failed to modulate EGF-R. In contrast, HC strongly stimulated the expression of EGF-R while depressing MHC class-I molecules. Thus, it appears that in vivo HC may co-operate with TGF-alpha and EGF in promoting the growth of transformed mammary cells. This hormone might also favor the escape from immune surveillance by reducing the expression of surface differentiation markers.

Antigens, Differentiation↗
PubMed1992

Treatment of malignant mesothelioma with epirubicin and ifosfamide: a phase II cooperative study.

From May 1988 to March 1990, 17 consecutive patients with histologically proven malignant mesothelioma were treated with epirubicin 75 mg/sqm i.v. on day 1 and ifosfamide 1.8 gr/sqm/day i.v. from day 1-5. Treatment was repeated every 3 weeks until progression. Fifty-three chemotherapy cycles were administered to the 17 patients treated (median, 3 cycles/patient). No complete responses, 1 partial response, 8 stable diseases and 8 progressions were noted. Toxocity was acceptable and no treatment-related deaths occurred. Actuarial median survival was 6 months. In this study, a combination of full doses of epirubicin and ifosfamide did not prove to be active in malignant mesothelioma.

Adult↗
PubMed1991

Epirubicin in the treatment of malignant mesothelioma: a phase II cooperative study. The North-Eastern Italian Oncology Group (GOCCNE)--Mesothelioma Committee.

From September 1986 to April 1988, all consecutive patients with histologically proven (pathologic review mandatory) malignant mesothelioma, measurable disease, age less than 75 years, Karnofsky performance status equal to or greater than 40, and no previous chemotherapy were treated with epirubicin at the dosage of 75 mg/m2 i.v. every 3 weeks. Of the 23 patients who entered the study, 2 were retrospectively found not to have malignant mesothelioma. In the 21 eligible patients (all evaluable), no complete remission, 1 partial remission, 11 stable diseases and 9 progressions were noted. Toxicity was very mild. Median survival was 7.5 months. At the dosage used, epirubicin proved to be of little value in the management of these patients. Whether higher doses are more effective, as has been noted in other tumors, remains to be ascertained.

Aged↗
PubMed1991

Serum levels of secretory IgA in ankylosing spondylitis.

An ELISA test was performed in order to measure the serum levels of secretory IgA (sIgA) in 51 patients with ankylosing spondylitis (AS) and 30 healthy controls. Raised values of sIgA were found in AS patients compared to controls. Patients with active disease, defined by clinical criteria, showed a significant elevation of serum sIgA compared to healthy controls (p = 0.03) or to patients with inactive disease (p = 0.02). A positive correlation between total serum IgA and sIgA was found (p = 0.001). Our findings further support the role of the mucosal stimulation in the pathogenesis of AS.

C-Reactive Protein↗