Biomedical subjects
G Scala
Publications and source records attributed to G Scala.
Regulation of NF-kappa B through the nuclear processing of p105 (NF-kappa B1) in Epstein-Barr virus-immortalized B cell lines.
Transcription factors of the NF-kappa B/Rel family are retained in the cytoplasm as inactive complexes through association with I kappa B inhibitory proteins. Several NF-kappa B activators induce the proteolysis of I kappa B proteins, which results in the nuclear translocation and DNA binding of NF-kappa B complexes. Here, we report a novel mechanism of NF-kappa B regulation mediated by p105 (NF-kappa B1) precursor of p50 directly at the nuclear level. In Epstein-Barr virus-immortalized B cells, p105 was found in the nucleus, where it was complexed with p65. In concomitance with NF-kappa B activation, mitomycin C induced the processing of p105 to p50 in the nucleus, while it did not affect the steady-state protein levels of I kappa B alpha and p105 in the cytoplasm. Differently, phorbol 12-myristate 13-acetate induced a significant proteolysis of both I kappa B alpha and p105 in the cytoplasm, while it did not affect the protein level of p105 in the nucleus. These results suggest that in Epstein-Barr virus-positive B cell lines the nuclear processing of p105 can contribute to NF-kappa B activation in response to specific signaling molecules, such as DNA-damaging agents.
House-dust mite ingestion can induce allergic intestinal syndrome.
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[Morphofunctional study of the lingual papillae in cattle (Bos taurus)].
The morpho-functional and topographical features of the lingual papillae situated on the dorsal surface of the bovine tongue, were studied utilizing LM and SEM techniques. In the bovine species, the functional differentiation of the lingual papillae in their gustatory and mechanical modes, seems to be related to the position of the papillae rather than to their morphological features. The gustatory function predominates over the mechanical one on the caudal tract of the tongue body (lateral to the lingual torus and associated with circumvallate papillae). The gustatory function also involves the conical papillae situated on the caudal tract of the tongue body. This gustatory function is aided by additional anatomical structures: 1. The grooves situated on the rostro-lateral side of the conical papillae; 2. The microcraters located on the top of the fungiform papillae; and 3. The furrows of the circumvallatae papillae vallum. The contact between saliva soluble food particles and taste buds is aided and made more efficient by these structures. Furthermore, a large variety of conical papillae were observed, whereas no filiform papillae were noted.
Morphostructural characteristics of the vallate papillae in Bos taurus.
The Morpho-structural characteristics of the vallate papillae of the bovine tongue were studied utilizing LM, SEM and TEM techniques. In the bovine, the vallate papillae are numerous and different in size. They have a prominent vallum papillae which surrounds a deep sulcus papillae. The sulcus has many elongated taste buds on its inner wall. Nervous fibers enter the taste bud and sometimes have rosary shaped axons. The gustative sensitivity of these animals may be instrumental, in their choice of food and avoidance of noxious plants.
DNA damaging agents increase the stability of interleukin-1 alpha, interleukin-1 beta, and interleukin-6 transcripts and the production of the relative proteins.
In this study, we addressed the question of whether carcinogens affected the expression of interleukin-1 alpha (IL1 alpha), interleukin-1 beta (IL1 beta), and interleukin-6 (IL6) genes and the production of the relative proteins. Primary cultures of human monocytes were exposed to the alkylating agents mitomycin C (Mit C), methylmethane sulfonate (MMS), and ethylmethane sulfonate (EMS) and tested for the production of IL1 alpha, IL1 beta, and IL6 proteins, as well as for the expression of IL1 alpha, IL1 beta, and IL6 transcripts. The production of IL1 beta and IL6 was significantly augmented by all the three chemicals after 24-48 h of treatment. IL1 alpha was also increased by Mit C and MMS. By Northern blotting analysis, the increased expression of IL1 alpha, IL1 beta, and IL6 genes was shown to occur at 30 min of Mit C and MMS treatment and to decline after 8 h. Similarly, EMS up-regulated the expression of IL1 beta and IL6 genes. The mutagen-mediated increase in interleukin transcripts did not require de novo protein synthesis, and it was due to the enhanced half-life of IL1 alpha, IL1 beta, and IL6 mRNAs rather than to the increased rate of gene transcription. These results suggest that carcinogens, in addition to causing DNA mutations and rearrangements, may also affect cell growth and differentiation by enhancing the expression of cytokine genes.
The expression of the interleukin 6 gene is induced by the human immunodeficiency virus 1 TAT protein.
Human immunodeficiency virus 1 (HIV1) infection is associated with severe psoriasis, B cell lymphoma, and Kaposi's sarcoma. A deregulated production of interleukin 6 (IL-6) has been implicated in the pathogenesis of these diseases. The molecular mechanisms underlying the abnormal IL-6 secretion of HIV1-infected cells may include transactivation of the IL-6 gene by HIV1. To test this hypothesis, we used the pIL6Pr-chloramphenicol acetyltransferase (CAT) plasmid, an IL-6 promoter-CAT construct, as a target of the transactivating function of the HIV1 TAT protein. By cotransfecting the pIL6Pr-CAT and the tat-expressing pSVT8 plasmid in MC3 B-lymphoblastoid or in HeLa epithelial cells, we observed that TAT transactivates the human IL-6 promoter. These results were confirmed when pIL6Pr-CAT was transfected in MC3 or HeLa cells that constitutively expressed the tat gene in a sense (pSVT8 cells) or antisense (pSVT10 cells) orientation. 5' deletion plasmids of pIL6Pr-CAT, in which regions at -658, -287, and -172 were inserted 5' to the cat gene, were transiently transfected in pSVT10 and pSVT8 cells and showed that TAT-induced activation of the IL-6 promoter required a minimal region located between -287 and -54 bp. Moreover, experiments with plasmids carrying the -658, -287, and -172 bp regions of the IL-6 promoter inserted downstream to a TAR-deleted HIV1-LTR identified the sequence of -172 to -54 as the minimal region of the IL-6 promoter required for TAT to transactivate the TAR-deleted HIV1-LTR. By DNA-protein binding experiments, tat-transfected cells expressed a consistent increase in kappa B and nuclear factor (NF)-IL-6 binding activity. Accordingly, the pDRCAT and IL-1REK9CAT, carrying tandem repeats of NF-kappa B or NF-IL6 binding motifs, respectively, were activated in TAT-expressing cells. The biological relevance of the TAT-induced IL-6 secretion was addressed by generating 7TD1 cells, an IL-6-dependent mouse cell line, stably expressing the tat gene. These tat-positive cells expressed the endogenous IL-6 gene, secreted high amounts of murine IL-6, and grew efficiently in the absence of exogenous IL-6. Moreover, the tat-positive 7TD1 cells sustained the growth of parental 7TD1 cells and showed a dramatic increase in their tumorigenic potency. These results suggest that TAT protein may play a role in the pathogenesis of some HIV1-associated diseases by modulating the expression of host cellular genes.
Farm workers' occupational allergy to Tetranychus urticae: clinical and immunologic aspects.
A group of 46 farm workers (32 men), affected by a recurrent "occupational disease of undetermined origin", underwent an immunologic investigation with a Tetranychus urticae (TU) whole-body extract (TU-WBE) prepared in our laboratory. The patients suffered from seasonal attacks of rhinitis, during the summer and autumn periods, when working in open fields (30 subjects) or in greenhouse flower cultivation (16 subjects). In most patients, rhinitis was associated with bronchial asthma (16 subjects), urticaria (14 subjects), or both (three subjects). Allergic alveolitis or other common allergic diseases had been excluded, and a diagnosis of "occupational disease of undetermined origin" had been made before by other medical centers. Ten healthy farm workers and 10 atopic townsmen were chosen as control groups. An in vivo and in vitro diagnostic trial by skin prick testing (SPT) and serum specific IgE dosage with TU-WBE were done in all subjects. Thirty-six patients (78%) were found to be positive to both SPT and the IgE enzyme allergosorbent test (EAST), with a good correlation between IgE serum levels and cutaneous wheal size. Control groups did not show any reaction. The IgE-EAST homologous inhibition test was positive. The IgE-EAST cross-inhibition test excluded cross-reactivity between TU and Dermatophagoides pteronyssinus. The TU-exposure test was positive for the 36 patients with TU-WBE-specific IgE. Three patients who were negative for TU-WBE-specific IgE reacted to the TU-exposure test; in these patients, the scratch-chamber test (Finn chamber) with eggs and droppings from TU was positive.(ABSTRACT TRUNCATED AT 250 WORDS)
[The microvascularization of the choroid plexus of the lateral ventricles in the goat (Capra hircus)].
The goat choroid plexus angioarchitecture of the lateral ventricles was studied under the SEM using the method of "microvascular corrosion casts". The whole plexus is semilunar shaped and directed in an antero-posterior, latero-median fashion. In the plexus the lateral extremity is larger than the median one. All the components of the vascular bed (arteries, veins and capillaries) of the choroid plexus have interesting morpho-structural features. In particular, the capillaries are more developed than the other components and they are variously located on both sides of the plexus. The capillary network has a various organization in different zones of each side of the plexus.
Interleukin-induced tumor immunogenicity.
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The human immunodeficiency virus type 1 long terminal repeat is activated by monofunctional and bifunctional DNA alkylating agents in human lymphocytes.
The activation of the human immunodeficiency virus, type 1 (HIV-1) by the DNA alkylating agents ethyl methanesulfonate, methyl methanesulfonate, and mitomycin C was observed in human B lymphocytes transiently transfected with plasmids in which the HIV-1 long terminal repeat (LTR) directed the expression of the bacterial chloramphenicol acetyltransferase gene. Deletion of the two NF-kappa B-binding sites of LTR abolished the HIV-1 activation induced by the three mutagens, while deletion of the three Sp1-binding sites slightly reduced it. Electrophoretic mobility shift assays revealed an increased binding to the kappa B sites of HIV-1 LTR in the nuclear extracts of human B lymphocytes upon mutagen treatment, while binding to Sp1 sites was unaffected. The TAR region was also involved in the mutagen-mediated activation of HIV-1 LTR inasmuch as a small deletion in the TAR sequence (nucleotides +34 to +37) greatly decreased the induction of HIV-1 expression. Moreover, an enhanced binding activity to the TAR DNA sequence (nucleotides +24 to +47) was observed in nuclear extracts of mutagen-treated lymphocytes. Thus, both the enhancer and the 5'-untranslated region of HIV-1 functionally cooperate in the mutagen-mediated induction of HIV-1 expression.
[The innervation of the syrinx of the duck (Anas platyrhynchos)].
The innervation of the Syrinx was studied in 15 female Peking Ducks of 10 to 12 months old by using L.M. and E.M. In this organ a nervous plexiform net is present located in the connective below the epithelium along the membrana tympaniformis medialis. This net-work is made of the nervous trunks which repeatedly anastomise among themselves and display during their course acapsulate ganglions. However, no specialized contact device were encountered at the periphery.
[Morphostructural study of the lingual papillae in the buffalo (Bubalus bubalus)].
The morphostructural characteristics of lingual papillae in 30 adult buffaloes were studied by SEM. In this species, dorsal lingual surface papillae shows different shape so that their classification is complicated. Topography and morphology of conical and vallate papillae presents significant aspects. Particularly, the conical papillae have a different morphological organization when they are localized over the side of the tongue apex or over dorso-lateral tract of the tongue body. The functional aspects are discussed.
Epstein-Barr virus nuclear antigen 2 transactivates the long terminal repeat of human immunodeficiency virus type 1.
Human immunodeficiency virus type 1 (HIV-1)-infected subjects show a high incidence of Epstein-Barr virus (EBV) infection. This suggests that EBV may function as a cofactor that affects HIV-1 activation and may play a major role in the progression of AIDS. To test this hypothesis, we generated two EBV-negative human B-cell lines that stably express the EBNA2 gene of EBV. These EBNA2-positive cell lines were transiently transfected with plasmids that carry either the wild type or deletion mutants of the HIV-1 long terminal repeat (LTR) fused to the chloramphenicol acetyltransferase (CAT) gene. There was a consistently higher HIV-1 LTR activation in EBNA2-expressing cells than in control cells, which suggested that EBNA2 proteins could activate the HIV-1 promoter, possibly by inducing nuclear factors binding to HIV-1 cis-regulatory sequences. To test this possibility, we used CAT-based plasmids carrying deletions of the NF-kappa B (pNFA-CAT), Sp1 (pSpA-CAT), or TAR (pTAR-CAT) region of the HIV-1 LTR and retardation assays in which nuclear proteins from EBNA2-expressing cells were challenged with oligonucleotides encompassing the NF-kappa B or Sp1 region of the HIV-1 LTR. We found that both the NF-kappa B and the Sp1 sites of the HIV-1 LTR are necessary for EBNA2 transactivation and that increased expression resulted from the induction of NF-kappa B-like factors. Moreover, experiments with the TAR-deleted pTAR-CAT and with the tat-expressing pAR-TAT plasmids indicated that endogenous Tat-like proteins could participate in EBNA2-mediated activation of the HIV-1 LTR and that EBNA2 proteins can synergize with the viral tat transactivator. Transfection experiments with plasmids expressing the EBNA1, EBNA3, and EBNALP genes did not cause a significant HIV-1 LTR activation. Thus, it appears that among the latent EBV genes tested, EBNA2 was the only EBV gene active on the HIV-1 LTR. The transactivation function of EBNA2 was also observed in the HeLa epithelial cell line, which suggests that EBV and HIV-1 infection of non-B cells may result in HIV-1 promoter activation. Therefore, a specific gene product of EBV, EBNA2, can transactivate HIV-1 and possibly contribute to the clinical progression of AIDS.
Hemodialysis related induction of interleukin-6 production by peripheral blood mononuclear cells.
Interleukin-6 (IL-6) has a complex spectrum of biological activities, for example, growth and differentiation of B cells and synthesis of acute-phase proteins by the liver. To evaluate the role of this cytokine in the inflammatory response induced by blood interaction with hemodialysis membranes, we have investigated the IL-6 synthesis and release in supernatant of 24-hour cultured peripheral blood mononuclear cells (PBMC) isolated from: (a) 10 hemodialyzed patients, (b) seven patients with advanced chronic renal failure (GFR less than or equal to 10 ml/min), and (c) eight healthy control subjects. In the same groups of subjects we evaluated the relationship between IL-6 synthesis and release and beta-2-microglobulin (beta 2m) production. Before and after dialytic treatment hemodialysis patient blood samples were drawn using the following criteria: (1) after two months of dialysis with cuprophan membranes, (2) after one and two months of dialysis with polymethylmethacrylate (PMMA) membranes, and finally, (3) after one further month of dialysis with cuprophan membranes. IL-6 was determined after 72 hours of incubation of PBMC supernatant serial dilutions with IL-6-dependent hybridoma cell line, 7TD1. Compared to IL-6 synthesis in control subjects (6.0 +/- 5.6 U/3 x 10(6) PBMC/24 hr), hemodialyzed patients, when treated with cuprophan membranes, showed significantly higher value of IL-6 production both before (23 +/- 13 U/3 x 10(6) PBMC/24 hr) and after (26.2 +/- 11.3 U/3 x 10(6) PBMC/24 hr) the dialytic session.(ABSTRACT TRUNCATED AT 250 WORDS)
Spontaneous and mutagen-mediated amplification of a neo gene integrated at different genomic sites in rat 2 fibroblasts.
A promoterless neo gene was stably transfected in rodent fibroblasts to act as a reporter gene for rearrangements resulting in its expression at the different genomic integration sites. Nine clones were isolated which had integrated a varying copy number of neo at one or more genomic sites but still displayed a Neo- phenotype (G418-sensitive). These clones were analyzed for their ability to become Neo+ (G418-resistant) either spontaneously or after mutagen treatment. They were all able to generate G418-resistant subclones spontaneously at frequencies ranging from 2 x 10(-8) to 6 x 10(-5). The acquired G418-resistance was always associated with amplification and enhanced transcription of neo. No correlation was observed between the frequency of occurrence of G418-resistance and the number of copies or integration sites of neo. When treated with the mutagens mitomycin C or methylmethane sulfonate, only one clone, RH15, produced G418-resistant subclones in a dose-related fashion. In this mutagen-inducible clone, DNA lesions of a different nature (monoadducts or cross-links) were equally efficient in the induction of G418-resistance. Amplification and enhanced transcription of the neo gene were observed in both the spontaneous and mutagen-induced G418-resistant subclones of RH15 cell line. These findings indicate that the exogenous neo gene integrated at different genomic sites was acting as a reporter gene for amplification. Interestingly, while all nine integration sites were observed to amplify spontaneously, only one could be induced to amplify by mutagens. This suggests that different genomic regions display differing susceptibilities to mutagen-mediated amplification. This may be important in view of the major role played by mutagen-mediated gene amplification in carcinogenesis.
[The epidemiology of adverse reactions to nonsteroidal anti-inflammatory drugs. Nimesulide is tolerated by patients with adverse reactions to NSAIDs and modulates in man the skin response to histamine and codeine].
We evaluated the tolerance to NIM in patients with adverse reactions to NSAIDs, expressed by urticaria-angioedema, bronchial asthma or erythema polymorphous on 92 patients among which 32 atopics affected by asthma, rhinitis or contact dermatitis. Challenge test has been performed with increasing amounts of NIM per os every 2 hrs to a maximum of 100 mg/dose. The last dosage was repeated every 12 hrs for 4 times more. No reactions were observed in 86 patients (93.4%). Moreover we evaluated the efficacy of NIM in modulating pomphoid cutaneous reaction to histamine (HIS) and codeine (COD). Three subjects were prick tested with HIS and COD solutions at different concentrations (0.1 to 10 mg/ml), before and after a 5 days therapy with NIM at different dosages/kg/die. At NIM dosages of 3.7 and 2.7 mg/kg/die we observed a strong reduction of pomphoid activity of both HIS and COD. No clear effects were detected at 2.2 mg/kg/die dosage. We assume a dose-related in vivo inhibitory effect of NIM on cutaneous mast cells releasability or a direct anti-histaminic effect. We point out the possible therapeutic role of NIM in the treatment of allergic flogosis at steroid and cromon's side.
Induction of tumorigenicity and plasmacytoid differentiation in EBV-B cells by expression of exogenous interleukin-6 or IL-6 receptor genes.
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