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Biomedical subjects

G Peluso

Publications and source records attributed to G Peluso.

At least 37 records · Page 2Linked to original sources
PubMed1999

Defective growth in vitro of Duchenne Muscular Dystrophy myoblasts: the molecular and biochemical basis.

As the molecular basis of Duchenne Muscular Dystrophy (DMD) was being discovered, increasing focus was placed on the mechanisms of progressive failure of myoregeneration. In this study, we propose a pathogenesis model for DMD, where an autocrine growth factor release of TGF-beta1-from necrotic myofibers-could contribute to the increasing loss of muscle regeneration. In fact, we report evidence that DMD myoblasts reduce their proliferation rate, in time and later cultures; in connection with this, we observed TGF-beta1 increase in conditioned media of DMD myoblasts, able to control the myoblast growth by reducing fusion and differentiation of DMD satellite cells.

Cell Differentiation↗
PubMed1999

Pathogenesis of inclusion bodies in (CAG)n/Qn-expansion diseases with special reference to the role of tissue transglutaminase and to selective vulnerability.

At least eight neurodegenerative diseases, including Huntington disease, are caused by expansions in (CAG)n repeats in the affected gene and by an increase in the size of the corresponding polyglutamine domain in the expressed protein. A hallmark of several of these diseases is the presence of aberrant, proteinaceous aggregates in the nuclei and cytosol of affected neurons. Recent studies have shown that expanded polyglutamine (Qn) repeats are excellent glutaminyl-donor substrates of tissue transglutaminase, and that the substrate activity increases with increasing size of the polyglutamine domain. Tissue transglutaminase is present in the cytosol and nuclear fractions of brain tissue. Thus, the nuclear and cytosolic inclusions in Huntington disease may contain tissue transglutaminase-catalyzed covalent aggregates. The (CAG)n/Qn-expansion diseases are classic examples of selective vulnerability in the nervous system, in which certain cells/structures are particularly susceptible to toxic insults. Quantitative differences in the distribution of the brain transglutaminase(s) and its substrates, and in the activation mechanism of the brain transglutaminase(s), may explain in part selective vulnerability in a subset of neurons in (CAG)n-expansion diseases, and possibly in other neurodegenerative disease. If tissue transglutaminase is found to be essential for development of pathogenesis, then inhibitors of this enzyme may be of therapeutic benefit.

Animals↗
PubMed1999

Polyclonal antibodies against fusaproliferin.

Fusaproliferin (FP), a toxic metabolite of the world-wide maize pathogens Fusarium proliferatum and Fusarium subglutinans, was recently found to be a natural contaminant of maize. Its toxic activity on haematopoietic human cell lines and its teratogenic effects on chicken embryos has been recently proved. Therefore a sensitive, rapid, and inexpensive screening test to detect FP in agricultural commodities is necessary to protect human health. FP-hemiglutarate conjugated to modified bovine serum albumin was synthesized, characterized, and used as an antigen for raising polyclonal antibodies by immunizing rabbits. Indirect and competitive ELISA and immunoblotting analyses were performed to determine antibody specificity towards the mycotoxin. The determination of 10 micrograms of free FP/mL was achieved using antibodies purified by means of affinity chromatography on a FP-lysine-Sepharose column. This unsatisfactory detection limit is due to high background values; thus, this method is not competitive with traditional UV-HPLC methods.

Animals↗
PubMed1998

Possible role of alpha-1-microglobulin in mediating bacterial attachment to model surfaces.

Urine proteins in the molecular weight range of 9-137 kDa deposit to an equal extent from pooled human urine onto glass (12.7 +/- 1.9 micrograms/cm) and polystyrene (11.8 +/- 1.8 micrograms/cm). Selective desorption of the proteins was achieved by washing with water or water/isopropanol mixtures. Irrespective of the washing process, proteins of molecular weight greater than 90 kDa remained associated with both surfaces while water washings alone removed most low molecular weight material. A 29 kDa protein, alpha-1-microglobulin, was removed from glass by water washing but required a 30% (v/v) isopropanol wash to desorb from polystyrene, implying attachment via hydrophobic bonding. The adhesion to polystyrene surfaces of Pseudomonas aeruginosa B4, a clinical isolate from a urinary tract infection (UTI), was strongly associated with the presence of alpha-1-microglobulin, which may be acting as a mediator of bacterial adhesion.

Adsorption↗
PubMed1998

Tissue transglutaminase-catalyzed formation of high-molecular-weight aggregates in vitro is favored with long polyglutamine domains: a possible mechanism contributing to CAG-triplet diseases.

To investigate possible biochemical mechanisms underlying the "toxic gain of function" associated with polyglutamine expansions, the ability of guinea pig liver tissue transglutaminase to catalyze covalent attachments of various polyamines to polyglutamine peptides was examined. Of the polyamines tested, spermine is the most active substrate, followed by spermidine and putrescine. Formation of covalent cross links between polyglutamine peptides and polyamines yields high-M(r) aggregates--a process that is favored with longer polyglutamines. In the presence of tissue transglutaminase, purified glyceraldehyde-3-phosphate dehydrogenase (a key glycolytic enzyme that binds tightly to the polyglutamine domains of both huntingtin and dentatorubral-pallidoluysian atrophy proteins) is covalently attached to polyglutamine peptides in vitro, resulting in the formation of high-M(r) aggregates. In addition, endogenous glyceraldehyde-3-phosphate dehydrogenase of a Balb-c 3T3 fibroblast cell line overexpressing human tissue transglutaminase forms cross-links with a Q60 polypeptide added to the cell homogenate. Possibly, expansion of polyglutamine domains (thus far known to occur in the gene products associated with at least seven neurodegenerative diseases) leads to increased/aberrant tissue transglutaminase-catalyzed cross-linking reactions with both polyamines and susceptible proteins, such as glyceraldehyde-3-phosphate dehydrogenase. Formation of cross-linked heteropolymers may lead to deposition of high-M(r) protein aggregates, thereby contributing to cell death.

Animals↗
PubMed1998

Antisense oligonucleotides and myotonin gene expression in C2 mouse cells.

By describing the behavior of myotonin mRNA levels, from the quiescent to the differentiated state in C2 mouse myoblasts, we produced evidence bearing on the role of myotonin gene product in the control of cell growth and differentiation. To study the role of myotonin in myotonic dystrophy (DM) pathogenesis, we developed a suitable cellular model where myotonin gene expression was modulated by phosphorothioate antisense oligonucleotides in C2 cultured cells. Furthermore, an isoform of the gene product, similar to that described in humans and not yet described in the mouse, was found.

Animals↗
PubMed1998

Role of monocyte/macrophage population in immune response.

The central role of macrophages in host defence against infection and malignancy and processes such as atherosclerosis, makes macrophage biology a fascinating area for research in immunology and cell biology. The endocytic and phagocytic machinery of macrophages is particularly potent and their secretory potential is large and diverse. Studies of cell surface receptors and their role in antigen presentation, microbicidal and tumouricidal activity are actively researched and progress is now being made in defining receptors responsible for monocyte/macrophage cell adhesion within the immune system. This short-review highlights the recent advances in macrophage biology.

Endocytosis↗
PubMed1997

SV-IV, a major protein secreted from rat seminal vesicle epithelium, promotes lymphocyte cytotoxic activity against the lymphoblastoid Raji cell line in human peripheral blood mononuclear cells.

The treatment of human peripheral blood mononuclear cells (PBMC) with micromolar concentrations of SV-IV, a major protein secreted from the rat seminal vesicle epithelium, promotes in this cell population a marked cytotoxic activity against the Raji lymphoblastoid cell line. This activity is apparently due to cell-to-cell contact interactions. The expression of HLA DR on Raji cells has a modulatory effect on the SV-IV-induced cytotoxic activity. The experimental evidence strongly suggests that the cytotoxic effector cells are functionally activated NK cells.

Animals↗
PubMed1997

The differential effects of poly(2-hydroxyethyl methacrylate) and poly(2-hydroxyethyl methacrylate)/poly(caprolactone) polymers on cell proliferation and collagen synthesis by human lung fibroblasts.

Because of its chemical versatility and demonstrated biocompatibility, poly(2-hydroxyethyl methacrylate) (pHEMA) has been widely used as a polymer for biomedical applications. Since this hydrophilic material shows a poor interface with cells, blendings with other polymers were done to improve cytocompatibility. In our polymer, the presence of hydrophobic dominions on the material surface, due to the interpenetrating polymerization of pHEMA with poly(caprolactone) (PCL), seems to ameliorate the cytocompatibility in terms of cell adhesion and metabolism. For our experiments, we used IMR-90 human fibroblasts, as these cells strongly regulate DNA, RNA, and protein synthesis as anchorage-dependent variables. Cell attachment on a pHEMA/PCL interpenetrating polymer network was optimal, suggesting a strong adhesion between the cells and the polymer surface. Cell adhesion was weaker on pHEMA, as a significant fraction of the fibroblasts revealed a lack of spreading, with most cells remaining spherical. Moreover, only fibroblasts seeded on pHEMA significantly decreased mRNA synthesis; collagen production and cell shapes ranged from fully flat and proliferating, to minimally spread and nonproliferating. Finally, DNA synthesis, as a measure of cell proliferation, was markedly inhibited in cells cultured on pHEMA but not on pHEMA/PCL. In conclusion, our results suggest that control of cell growth and metabolism by biomedical polymers is based on physicochemical mechanism(s) in which the hydrophilicity/hydrophobicity ratio of the material surfaces may play an important role.

Base Sequence↗
PubMed1997

In experimental diabetes the decrease in the eye of lens carnitine levels is an early important and selective event.

Carnitine is present in the eye tissues of the rabbit and the highest concentration is found in the lens. In streptozotocin-diabetic rats, the carnitine loss of the lens is an initial and important event. At 8 days after the induction of diabetes, the carnitine content in the rat lens was reduced by 63% compared to control. The loss of lens carnitine continued at 15 and 45 days after the induction. Total carnitine level in the serum was diminished by 15 days, and the reduction in percentage term was much lower in comparison to the loss of lens carnitine. In the rabbit after alloxan-diabetes induction, there is an extensive loss of carnitine in the lens: -85% after 4 months. The carnitine levels in the other eye tissues seem substantially unaffected. The loss of lens carnitine was present even with an inconsistent hyperglycaemia. No difference was found in serum carnitine levels between controls and alloxan-treated rabbits. The role of carnitine in lens is still unclear, but its loss may be related to the appearance of cataract. A derivative of carnitine, acetylcarnitine, might prevent the processes involved in the formation of cataracts by a pharmacological action, as has been shown for aspirin.

Alloxan↗
PubMed1997

Adsorption of alpha-1-microglobulin from biological fluids onto polymer surfaces.

A recent study in our laboratory has identified the potential role of urine-derived alpha-1-microglobulin (alpha-1-m) in mediating Pseudomonas aeruginosa adhesion to polystyrene, while other workers have suggested a possible role of the protein in the immunological response. Due to the ubiquitous presence of alpha-1-m in body fluids, the adsorption of the protein from serum, cerebrospinal fluid, urine and used continuous ambulatory peritoneal dialysis fluid onto polystyrene was investigated. The treated surfaces were sequentially immersed in water and increasingly concentrated isopropanol-water solutions in order to selectively desorb bound proteins on the basis of their binding strength. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis of the wash supernatants showed different protein desorption profiles for each biological fluid, despite the qualitative similarity between the protein composition of the fluids, and highlighted the uptake of alpha-1-m from each fluid to the surface. In the case of urine, the analysis was extended to commercial polyurethane and silicone stents. The ease of desorption of urine-derived alpha-1-m could be correlated with surface hydrophobicity of the stent biomaterial.

Adsorption↗
PubMed1996

Synthesis and characterization of a new interpenetrated poly(2-hydroxyethylmethacrylate)-gelatin composite polymer.

Poly(2-hydroxyethylmethacrylate) [poly(HEMA)] is a widely used biomaterial which does not allow cell adhesion and growth on its surface, limiting its use in biomedical applications in which cell cohesion is detrimental. We have prepared a poly(HEMA)-gelatin composite hydrogel using a sequential interpenetrating polymer network technique. The properties of this material were compared with poly(HEMA) freeze-dried sponges in terms of morphology, mechanical properties and biocompatibility. Moreover, in vivo biocompatibility experiments highlighted the occurrence of cellular interactions on the surface of the poly(HEMA)-gelatin interpenetrating polymer network, which are usually absent when unmodified poly(HEMA) hydrogels are implanted in the same host organism. These tests also showed a progressive gelatin degradation from the surface to the bulk of the poly(HEMA)-gelatin specimens during short-term (7 d) implantation. Finally, in vitro tests confirmed an improved ability of this composite to scaffold for the cells.

3T3 Cells↗
PubMed1996

Modulation of cytokine production in activated human monocytes by somatostatin.

The immunosuppressor effects of the widely distributed neuropeptide somatostatin were examined on purified peripheral blood human monocytes. Somatostatin, at concentrations thought to be physiologic (10(-10)-10(-7) M), regulated monocyte/macrophage responses to (LPS) stimulation, as reflected by interleukin production. In particular, somatostatin had direct inhibitory effects on TNF-alpha, IL-1 beta, and IL-6 secretion by LPS-activated monocytes, while the decrease on IL-8 synthesis was modulated mainly by the action of somatostatin on TNF-alpha and IL-1 beta. In fact, the addition of these two inflammatory cytokines to the monocyte culture medium was able to induce IL-8 expression, as demonstrated by mRNA analysis, also in presence of the neuropeptide. Although somatostatin affected IL-8 production in an indirect way, it suppressed directly the chemotactic response of neutrophils to IL-8. Finally, somatostatin downregulation of monocyte activation was confirmed by the decrease of HLA-DR expression on cell plasma membranes (52% versus 33%). Our results confirm that somatostatin exerts preferential effects on the suppression of immunoreactions by modulating cytokine production and activity.

Cells, Cultured↗
PubMed1996

New polyoxypregnane ester derivatives from Leptadenia hastata.

Following the characterization of polyoxypregnane esters and esterified glycosides from the less polar extracts of Leptadenia hastata, 34 new congeners have been isolated from the more polar extracts. They possess sarcostin or deacetylmetaplexigenin as the aglycons and acetyl, benzoyl, cinnamoyl, nicotinoyl, and m-hydroxybenzoyl residues as the ester moieties linked at C-12 and/or C-20 of the aglycons. The oligosaccharide moiety linked to C-3 of the aglycons was made up of three to five 2,6-dideoxy-3-O-methylpyranoses, 6-deoxy-3-O-methylpyranoses, or glucose. Their structures have been elucidated on the basis of spectral evidence. Glycosides with more complex oligosaccharidic chains were tested for their antitumor activity on Raji cells.

Antineoplastic Agents, Phytogenic↗
PubMed1995

In vivo inhibition of cell-mediated and humoral immune responses to cellular antigens by SV-IV, a major protein secreted from the rat seminal vesicle epithelium.

Microgram amounts of protein SV-IV, a major secretory protein produced by adult rat seminal vesicle epithelium, markedly decrease the mouse humoral immune response to cellular xenogeneic or allogeneic antigens (sheep red blood cells (SRBC) or mouse epididymal spermatozoa). The significant reduction in the total number of splenocytes and their main cell subsets in SRBC-immunized mice, the dramatic decrease in the number of Ia+ splenic T cells and the marked inhibition of splenocyte ability to respond in vitro to polyclonal mitogen stimuli suggest that the macrophage accessory cells are the primary target of the SV-IV immunosuppressive activity in vivo. Moreover, the infection of SV-IV-treated mice with Salmonella typhimurium produced an increased mortality of the experimental animals associated with a marked decrease of the phagocytic and intracellular killing activities of their peritoneal macrophages.

Animals↗
PubMed1995

Studies on the inhibitory effects of caffeoylquinic acids on monocyte migration and superoxide ion production.

Three caffeoylquinic acids, isolated from the Peruvian plants Tessaria integrifolia and Mikania cordifolia that are used medicinally as anti-inflammatory agents, were tested for their activities on monocyte migration and superoxide anion production. 3,5-Di-O-caffeoylquinic and 4,5-di-O-caffeoylquinic acids exhibited an appreciable anti-inflammatory activity in vitro, while the tricaffeoyl derivative was inactive.

Amino Acid Sequence↗