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Biomedical subjects

M Morra

Publications and source records attributed to M Morra.

At least 37 records · Page 2Linked to original sources
PubMed2001

CD150 is a member of a family of genes that encode glycoproteins on the surface of hematopoietic cells.

Human CD150 (SLAM) is a glycoprotein expressed on the surface of T, B, natural killer, and dendritic cells. The extracellular domain of CD150 is the receptor for measles virus and CD150 acts as a co-activator on T and B cells. We characterized the mouse and human CD150 genes, each of which comprises seven exons spanning approximately 32 kb. Mouse CD150 mRNA was detected in T cells and in most thymocyte subsets, except CD4-8- cells. Surprisingly, the CD4-8- thymocytes of CD3gammadeltanull mice, but not of Ragnull or severe combined immunodeficiency mice, expressed CD150. Whereas high levels of CD150 were found in Th1 cells, only small amounts were detectable in Th2 cells. CD150 expression was up-regulated upon in vitro activation of mouse T cells by anti-CD3. The complete mouse CD150 gene is highly homologous to its human orthologue in terms of nucleotide sequences and intron/exon organization. The human genomic sequences indicate that all isoforms detected so far have arisen from alternative splicing events. As judged by fluorescence in situ hybridization, mouse CD150 mapped to Chromosome (Chr) 1, band 1H2.2-2.3, and human CD150 was found on Chr 1q22. Human and mouse CD150 share sequence homologies with six other genes, five of which - CD84, CD229 (Ly-9), CD244 (2B4), CD48, and 19A - are localized in a 250-kb segment in close proximity to the human gene. Their location and their sequence similarities strongly suggest that the CD150 family of cell surface receptors arose via successive duplications of a common ancestral gene.

Amino Acid Sequence↗
PubMed2001

Temporal profile of serum anti-inflammatory and pro-inflammatory interleukins in acute ischemic stroke patients.

The presence of an inflammatory response in the pathophysiology of acute brain ischemia is relatively well established, but less is known about the anti-inflammatory mechanisms. The aim of the present study was to evaluate part of the immune response in acute stroke patients and to analyze a possible correlation with other hematological parameters, clinical outcome, size of infarct and subtypes of strokes. We prospectively studied 42 stroke patients, without signs of infections or inflammatory diseases, at days 0, 1, 3, 7 and 14, and 39 healthy control subjects. We measured serum levels of the anti-inflammatory cytokine interleukin-10 (IL-10) and the pro-inflammatory cytokine interleukin-6 (IL-6) by ELISA method. We observed a highly inverse correlation between these two molecules in control subjects (r=-0.78, p=0.0000001), and this correlation was lost in stroke patients. Patients had significantly lowered IL-10 serum levels soon after the acute event (p=0.00005), with a slight increase at the seventh day. On the other hand, patients had increased IL-6 serum levels compared with controls after day one until day 14 (p<0.04), with a maximum increase at day 3. Interleukin-6 correlated with clinical outcome whereas interleukin-10 did not. Low levels of interleukin-10 indicate that the antiinflammatory response is down-regulated in acute stroke patients. The pro-inflammatory response begins 24 hours after the onset of acute cerebral ischemia, as indicated by the increased serum levels of interleukin-6. The physiological balance between these two molecules is altered in acute stroke patients.

Acute Disease↗
PubMed2001

Pilot-testing a cancer education curriculum for grades K-6.

Risk behaviors established during childhood including tobacco use, sunning, and eating habits contribute to most adult cancers. This project pilot-tested a developmentally appropriate cancer prevention curriculum for grades K-6, using a treatment group only design with pretesting and posttesting using a standardized, semistructured interview and involving 67 students (77% of eligible students) attending mixed grade classes. A seven-unit curriculum based on cognitive development, social cognitive, and social influence theories was taught by classroom teachers. Students showed a significant (p < .0001) gain in conceptual understanding for causality and prevention of cancer; the gain for causality of cancer was comparable to the baseline difference between kindergarten and the highest (5-6) grade. Significant gains in factual knowledge and decreases in misconceptions about casual contact also were documented. A developmentally based elementary school cancer prevention curriculum can enhance young children's conceptual understanding and factual knowledge of common contributors to adult cancers.

Child↗
PubMed2001

X-linked lymphoproliferative disease: a progressive immunodeficiency.

Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the last two years. The gene that is altered in the condition (SAP/SH2D1A) has been cloned and its protein crystal structure solved. At least two sets of target molecules for this small SH2 domain-containing protein have been identified: A family of hematopoietic cell surface receptors, i.e. the SLAM family, and a second molecule, which is a phosphorylated adapter. A SAP-like protein, EAT-2, has also been found to interact with this family of surface receptors. Several lines of evidence, including structural studies and analyses of missense mutations in XLP patients, support the notion that SAP/SH2D1A is a natural inhibitor of SH2-domain-dependent interactions with members of the SLAM family. However, details of its role in signaling mechanisms are yet to be unravelled. Further analyses of the SAP/SH2D1A gene in XLP patients have made it clear that the development of dys-gammaglobulinemia and B cell lymphoma can occur without evidence of prior EBV infection. Moreover, preliminary results of virus infections of a mouse in which the SAP/SH2D1A gene has been disrupted suggest that EBV infection is not per se critical for the development of XLP phenotypes. It appears therefore that the SAP/SH2D1A gene controls signaling via the SLAM family of surface receptors and thus may play a fundamental role in T cell and APC interactions during viral infections.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Force measurements on cell repellant and cell adhesive alginic acid coated surfaces.

The atomic force microscope (AFM) was used to acquire force versus distance curves between the cantilever tip and samples bearing a surface overlayer of covalently linked alginic acid. The alginic acid coating resists cell-adhesion in in vitro experiments involving a normal and a tumor cell line. However, the surface becomes cell adhesive when alginic acid coated samples are subjected to glow discharge treatment. Force curves show in both cases the typical features resulting from the interaction between the cantilever tip and a hydrophilic, compressible polymer overlayer, suggesting that in both cases a diffuse interface with water exists. Following some recent findings on oligoethyleneglycol-terminated self-assembled-monolayers, it is suggested that conformational and molecular aspects of hydrophilic surface layers, rather than steric repulsion effects, could play a significant role in the mechanism that controls resistance to bio-adhesion.

Journal Article↗
PubMed2000

The gene defective in X-linked lymphoproliferative disease controls T cell dependent immune surveillance against Epstein-Barr virus.

Our understanding of the X-linked lymphoproliferative syndrome (XLP) has advanced significantly in the past two years. The gene that is aberrant in the condition - SH2D1A/SAP, which encodes SAP (signaling lymphocytic activation molecule [SLAM]-associated protein) - was cloned, the crystal structure of its product was solved and insights into the signaling mechanisms of this small SH2-domain-containing protein via the cell surface receptors SLAM and 2B4 have been provided. SAP mutation, and not Epstein-Barr virus infection per se, may be critical for XLP.

Antigens, CD↗
PubMed2000

On the molecular basis of fouling resistance.

This paper presents a review of models used to describe the properties of fouling resistant surfaces, i.e. the relationship between molecular structure and resistance to adsorption/adhesion of biological moieties. In particular, the well established 'physical' school of thought, mostly based on ideas stemming from the Alexander--De Gennes theory of polymer interfaces, which appears especially suitable for the modeling of resistance to bio-adhesion in terms of entropic effects, is compared to approaches that call into play the role of interfacial forces based on hydrogen bonding and molecular conformations. It is underlined that the presently prevailing view based on 'steric' stabilization effects is based on models that do not take into account some of the most fundamental aspects of water-soluble polymers and that, within this approximation, repulsive forces resulting from the 'compression' of tethered layers is the only possible explanation. When effects typical of water, such as hydrogen bonding, are considered, different pictures arise, even if their quantification poses several analytical challenges and new theoretical problems.

Adsorption↗
PubMed2000

Evaluation of interfacial properties of hyaluronan coated poly(methylmethacrylate) intraocular lenses.

Polymethylmethacrylate intraocular lenses (IOLs) were surface-modified by the linking of a overlayer of hyaluronan. In vitro experiments show that the hydrophilic HA overlayer prevents fibroblasts adhesion and greatly reduces Staphyloccous epidermidis adhesion to the IOL surface. To gain insights into the interfacial properties of untreated and hyaluronan-coated PMMA IOLs, force-distance curves were obtained by atomic force microscopy, using standard and modified tips. These measurements allow clear appreciation of the marked difference between the mechanical and chemico-physical properties at the aqueous interface of the uncoated and hyaluronan-coated lenses.

Animals↗
PubMed1999

Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition.

SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TIpYXX(V/I).

Amino Acid Sequence↗
PubMed1999

Non-fouling properties of polysaccharide-coated surfaces.

Hyaluronic acid and alginic acid, examples of hydrophilic polysaccharides whose biological and technological properties are deeply related to strong interaction with water, have been coupled to substrate surfaces. These coatings can prevent mammalian cells adhesion and greatly reduce bacterial cells adhesion in vitro and in several in vivo applications. The anti-adhesive properties of these surfaces are discussed in terms of the surface fractional coverage by the polysaccharide, as evaluated by XPS analysis and water contact angle. The implications of chemical-molecular considerations to the properties of these coatings are discussed from an analytical and mechanistic point of view.

Alginates↗
PubMed1998

The X-linked lymphoproliferative-disease gene product SAP regulates signals induced through the co-receptor SLAM.

In addition to triggering the activation of B- or T-cell antigen receptors, the binding of a ligand to its receptor at the cell surface can sometimes determine the physiological outcome of interactions between antigen-presenting cells, T and B lymphocytes. The protein SLAM (also known as CDw150), which is present on the surface of B and T cells, forms such a receptor-ligand pair as it is a self-ligand. We now show that a T-cell-specific, SLAM-associated protein (SAP), which contains an SH2 domain and a short tall, acts as an inhibitor by blocking recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to a docking site in the SLAM cytoplasmic region. The gene encoding SAP maps to the same area of the X chromosome as the locus for X-linked lymphoproliferative disease (XLP) and we found mutations in the SAP gene in three XLP patients. Absence of the inhibitor SAP in XLP patients affects T/B-cell interactions induced by SLAM, leading to an inability to control B-cell proliferation caused by Epstein-Barr virus infections.

Amino Acid Sequence↗
PubMed1998

Characterization of a CD38-like 78-kilodalton soluble protein released from B cell lines derived from patients with X-linked agammaglobulinemia.

Studies on murine B lymphocytes showed that Bruton's tyrosine kinase mediates signal transduction induced via CD38, a nonlineage-restricted 45-kD ectoenzyme. This signaling is defective in B cells from X-linked immunodeficient mice affected with the analogue of human X-linked agammaglobulinemia (XLA). We performed a structural and functional analysis of CD38 in XLA and other immunodeficiencies, using EBV-immortalized B cells derived from such patients. Membrane CD38 was not significantly different from controls in structure, epitope density, enzymatic activity, and internalization upon binding of agonistic mAbs. Meanwhile, an increased release of soluble CD38 from XLA cells was observed: immunoprecipitation from XLA culture media yielded a protein of approximately 78 kD (p78), reacting also in Western blot and displaying both enzymatic activities and a peptide map similar to membrane CD38. Soluble forms and homotypic aggregations of CD38 were documented in different cell models and by crystallographic analysis of the Aplysia ADP-ribosyl cyclase, the ancestor of human CD38. p78 might represent the product of an altered turn-over of membrane CD38, a starting point for studying its association with Bruton's tyrosine kinase and its role in XLA and other B cell immunodeficiencies.

ADP-ribosyl Cyclase↗
PubMed1998

Human CD38 (ADP-ribosyl cyclase) is a counter-receptor of CD31, an Ig superfamily member.

Human CD38 is a cell surface molecule involved in the regulation of lymphocyte adhesion to endothelial cells. This suggests that HUVEC bear a ligand(s) for CD38 on the cell surface. By means of the mAb Moon-1, which specifically inhibits CD38-mediated cell adhesion, we have identified a trans-membrane 130-kDa molecule acting as a ligand for CD38. Here, we report that the molecule recognized by the Moon-1 mAb is CD31, a member of the Ig superfamily. This conclusion is based on 1) cross-inhibition assays between Moon-1 and reference anti-CD31 mAbs; 2) sequential immunoprecipitation experiments using Moon-1 and known anti-CD31 mAbs, and 3) reactivity of the Moon-1 mAb with CD31 transfectants. Further, CD31 and CD38 cognate interactions were found to modulate heterotypic adhesion as well as to implement cytoplasmic calcium fluxes identical to those obtained by means of agonistic anti-CD38 mAbs. Other effects tested included the synthesis of messages for a panel of cytokines, markedly increased upon receptor-ligand interactions. These results suggest that the interplay between CD38 and its ligand CD31 is an important step in the regulation of cell life and of the migration of leukocytes (and CD38+ cancer cells) through the endothelial cell wall.

ADP-ribosyl Cyclase↗
PubMed1998

CD38 is functionally dependent on the TCR/CD3 complex in human T cells.

One of the functions of surface CD38 is the induction of phosphorylation of discrete cytoplasmic substrates and mobilization of cytoplasmic calcium (Ca2+). The present work addresses the issue of whether the signaling mediated via CD38 operates through an independent pathway or, alternatively, is linked to the TCR/CD3 signaling machinery. We studied the signals elicited through CD38 by the specific agonistic IB4 monoclonal antibody (mAb) by monitoring the levels of cytoplasmic Ca2+ and the induced phenotypic and functional variations in T cell growth. IB4 mAb presented the unique ability to increase cytoplasmic Ca2+ levels, which correlated with the phosphorylation of the PLC-gamma1. These effects were blocked by phorbol 12-myristate 13-acetate (PMA) and were dependent on the presence of a functional TCR/CD3 surface complex, no effects being recorded on mutant Jurkat cells lacking part of the CD3 structures. CD38 signaling appeared to share with TCR/CD3 the ability to induce apoptotic cell death in Jurkat T cells, an event paralleled by specific up-regulation of the Fas molecule and inhibited by cyclosporin A. CD28, a costimulatory molecule, is synergized by increasing CD38-induced apoptotic cell death. The results indicate the existence of a strong functional interdependence between CD38 and TCR/CD3.

ADP-ribosyl Cyclase↗
PubMed1997

Reduced plaque accumulation on hydrocarbon thin film deposited on restorative acrylic polymers.

The deposition of a thin polymeric film from ethylene plasma was used to modify the surface properties of acrylic teeth, commonly used in the dental practice for crown and bridge restorations. The effects of the surface modification process on the surface composition, morphology, and energetics were evaluated by electron spectroscopy for chemical analysis, atomic force microscopy, and contact angle measurement respectively. Plaque accumulation on the plasma-coated and untreated material was evaluated in in vivo experiments, in which the same patient received conventional and plasma-coated restorations. The hydrocarbon-like surface of the plasma-coated restoration remained remarkably free from plaque, even in the absence of brushing. On the other hand, plaque accumulation was observed on the unmodified restoration. Results are discussed according to recent theories on bioadhesive phenomena.

Acrylates↗
PubMed1997

Organic surface chemistry on titanium surfaces via thin film deposition.

In order to develop a synthetic strategy for the fine tuning of the interfacial properties of titanium-based implants and implant parts, a thin polymeric film was deposited from ethylene plasma on the surfaces of Ti foils. The intended aim was to further modify the adherent, delamination-resistant organic coating using the techniques of surface modification of polymers to direct interfacial interactions at the metal foil-biological phase interface. In particular, air-plasma treatment and Ce(IV)-induced hydroxyethylmethacrylate grafting, two typical reactions of biomedical polymers surface chemistry, were used to improve cell adhesion or to impart cell resistance to the plasma-coated Ti. Results indicate that a plasma-deposited thin polymeric film effectively can act as a viable substrate for further surface chemical modifications and allow the application of a huge background of surface-modification polymers to metallic devices.

Animals↗
PubMed1997

Role of the human CD38 molecule in B cell activation and proliferation.

Human CD38 is a surface molecule which has been attributed the function of a signaling channel leading to cellular activation and proliferation, an ectoenzyme with multiple function as well as an inducer of Ca2+ mobilization from cytoplasmic stores. The effect mediated by CD38 have been studied in different cell populations: the results obtained in human B cells are apparently contradictory, with CD38 simultaneously leading to apoptosis in early B cells while increasing survival in cells derived from lymph node germinal center. Other effects recently reported concern a different potential in terms of signaling in early B cells and derived cell lines or in more detailed disease models of human leukemia, namely B chronic lymphocytic leukemia cells. To complete the picture of the effects mediated by CD38 in the B cell compartment, we have studied the signals elicited by ligation of the human molecule in mature B cells from circulating pool and also from spleen of normal individuals. The information obtained completes the picture of CD38 and mature B cells, where we also studied the contribution of relevant cytokines involved in maintenance and differentiation of these normal cells, namely IL-1 alpha, IL-2, IL-4 and IL-6. Our results indicate that human CD38 plays a key role as a co-receptor in mature B cells from normal individuals.

ADP-ribosyl Cyclase↗