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Biomedical subjects

L Giuffrè

Publications and source records attributed to L Giuffrè.

At least 19 recordsLinked to original sources
PubMed1997

Monocyte adhesion to activated aortic endothelium: role of L-selectin and heparan sulfate proteoglycans.

This study examines the role of L-selectin in monocyte adhesion to arterial endothelium, a key pathogenic event of atherosclerosis. Using a nonstatic (rotation) adhesion assay, we observed that monocyte binding to bovine aortic endothelium at 4 degrees C increased four to nine times upon endothelium activation with tumor necrosis factor (TNF)-alpha. mAb-blocking experiments demonstrated that L-selectin mediates a major part (64 +/- 18%) of monocyte attachment. Videomicroscopy experiments performed under flow indicated that monocytes abruptly halted on 8-h TNF-alpha-activated aortic endothelium, approximately 80% of monocyte attachment being mediated by L-selectin. Flow cytometric studies with a L-selectin/IgM heavy chain chimeric protein showed calcium-dependent L-selectin binding to cytokine-activated and, unexpectedly, unactivated aortic cells. Soluble L-selectin binding was completely inhibited by anti-L-selectin mAb or by aortic cell exposure to trypsin. Experiments with cycloheximide, chlorate, or neuraminidase showed that protein synthesis and sulfate groups, but not sialic acid residues, were essential for L-selectin counterreceptor function. Moreover, heparin lyases partially inhibited soluble L-selectin binding to cytokine-activated aortic cells, whereas a stronger inhibition was seen with unstimulated endothelial cells, suggesting that cytokine activation could induce the expression of additional ligand(s) for L-selectin, distinct from heparan sulfate proteoglycans. Under flow, endothelial cell treatment with heparinase inhibited by approximately 80% monocyte attachment to TNF-alpha-activated aortic endothelium, indicating a major role for heparan sulfate proteoglycans in monocyte-endothelial interactions. Thus, L-selectin mediates monocyte attachment to activated aortic endothelium, and heparan sulfate proteoglycans serve as arterial ligands for monocyte L-selectin.

Animals↗
PubMed1996

P-selectin glycoprotein ligand 1 is a ligand for L-selectin on neutrophils, monocytes, and CD34+ hematopoietic progenitor cells.

Selectins play a critical role in initiating leukocyte binding to vascular endothelium. In addition, in vitro experiments have shown that neutrophils use L-selectin to roll on adherent neutrophils, suggesting that they express a nonvascular L-selectin ligand. Using a L-selectin/IgM heavy chain (mu) chimeric protein as an immunocytological probe, we show here that L-selectin can bind to neutrophils, monocytes, CD34+ hematopoietic progenitors, and HL-60 and KG-1 myeloid cells. The interaction between L-selectin and leukocytes was protease sensitive and calcium dependent, and abolished by cell treatment with neuraminidase, chlorate, or O-sialoglycoprotein endopeptidase. These results revealed common features between leukocyte L-selectin ligand and the mucin-like P-selectin glycoprotein ligand 1 (PSGL-1), which mediates neutrophil rolling on P- and E-selectin. The possibility that PSGL-1 could be a ligand for L-selectin was further supported by the ability of P-selectin/mu chimera to inhibit L-selectin/mu binding to leukocytes and by the complete inhibition of both selectin interactions with myeloid cells treated with mocarhagin, a cobra venom metalloproteinase that cleaves the amino terminus of PSGL-1 at Tyr-51. Finally, the abrogation of L- and P-selectin binding to myeloid cells treated with a polyclonal antibody, raised against a peptide corresponding to the amino acid residues 42-56 of PSGL-1, indicated that L- and P-selectin interact with a domain located at the amino-terminal end of PSGL-1. The ability of the anti-PSGL-1 mAb PL-1 to inhibit L- and P-selectin binding to KG-1 cells further supported that possibility. Thus, apart from being involved in neutrophil rolling on P- and E-selectin, PSGL-1 also plays a critical role in mediating neutrophil attachment to adherent neutrophils. Interaction between L-selectin and PSGL-1 may be of major importance for increasing leukocyte recruitment at inflammatory sites.

Antigens, CD34↗
PubMed1995

Ulnar ray defect in an infant with a 6q21;7q31.2 translocation: further evidence for the existence of a limb defect gene in 6q21.

Ectrodactyly is a developmental defect of the distal limbs characterized by marked clinical variability and genetic heterogeneity, also reflected in the observation of different chromosome abnormalities non randomly associated with longitudinal postaxial limb deficiencies. The one most frequently found in patients with split hand-split foot (SHSF) involves chromosome band 7q22. Recently, structural anomalies of chromosome 6q21 have been reported in 2 unrelated patients with SHSF, suggesting that this region may also contain genes responsible for limb development [Braverman et al., 1993. Am J Hum Genet, suppl 53: 410; Viljoen and Smart, 1993. Clin Dysmorph 2: 274-277]. We report on a third patient who had a de novo, apparently balanced t(6;7)(q21;q31.2) translocation and bilateral ulnar aplasia with postaxial oligodactyly. In spite of the different phenotypic effects observed in these 3 patients, we consider our case as further evidence that genes in 6q21 may play a role in distal limb development.

Chromosome Banding↗
PubMed1992

VATER/VACTERL association: clinical variability and expanding phenotype including laryngeal stenosis.

Vertebral abnormalities and anorectal and tracheoesophageal defects are the main manifestations in the VATER/VACTERL association. Radial defects vary from radial aplasia to thumb duplication. Heart and renal defects are reported with lower frequency. Additional malformations, such as the laryngeal stenosis described in the present patient, may expand the phenotype of the association. The wide spectrum of congenital abnormalities confirms the high clinical variability of VATER/VACTERL association which seems to be due to a disruption of blastogenesis.

Esophageal Atresia↗
PubMed1992

Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: prenatal diagnosis, clinical and pathological findings.

We present male monozygotic twins with thanatophoric dysplasia (TD) type I concordant for long bone abnormalities and discordant for cloverleaf skull. The twins were the product of the second pregnancy of unrelated parents, with advanced paternal age. Prenatal diagnosis and postmortem examination showed severe rhizomelic shortness of limbs, bowing of the long bones with "telephone-receiver" femora in both twins, and cloverleaf skull and hydrocephalus in one of them. It is now accepted that most of cases of TD, such as in the present report, represent an autosomal dominant mutation with a high new mutations rate.

Adult↗
PubMed1991

Kabuki make-up (Niikawa-Kuroki) syndrome: clinical and radiological observations in two Sicilian children.

The Authors describe two patients aged 5 and 8, a female and a male, affected by a condition of polymalformations known as Kabuki make-up or Niikawa-Kuroki syndrome, having a neonatal incidence of 1:32,000 in Japan. There are two hypothesis about the apparent rarity of the syndrome in the rest of the world, including the Asian Continent: the first is that it exists, but is infrequently recognized outside Japan and the second is that it is really more frequent in those parts of the world, where ethnic exchanges are uncommon, as it happens in Japan.

Abnormalities, Multiple↗
PubMed1991

[Role of diagnostic imaging in Rubinstein-Taybi syndrome. Personal experience with 8 cases].

Both etiology and pathogenesis of Rubinstein-Taybi syndrome (RTS) are still questionable, even though a genetic factor seems to be certain. A typical face, psychomotor delay, and thumb and halluces abnormalities (big, prevalently short, and often "spoon-like" toes) are the main characteristic patterns of RTS. Eight subjects (4 male and 3 female children aged 26 days-7 years, and a 31-year-old woman, mother of 1 of the affected children) with different signs of RTS were studied over the last 3 years. The results are here reported, with a special emphasis on malformations detected with conventional radiography (Rx), Computerized Tomography (CT), and ultrasound (US). Evaluated parameters were thumbs and halluces (Rx), bone age and skeleton (Rx), cranium (Rx) and encephalon (US, CT), cryptorchidism (US, CT), and urological (Rx, US) and cardiovascular (US) systems. A typical face and psychomotor delay were found in all cases, while thumb and halluces abnormalities were observed only in 6 cases. Among several clinical signs of RTS, we found: severe (less than 3rd centile) bone maturation delay in 4 cases; skull volume reduction (less than 50th centile) in 3 subjects and microcrania in 4; skeletal abnormalities in 7 cases (5 of them positive for bilateral coxofemoral abnormalities); urinary tract (4 cases) and cardiovascular (3 cases) malformations; and cryptorchidism in 3 of 4 males. A case was diagnosed during neonatal period (within the first month of life); it was a rare case associated with a variant form of Dandy-Walker anomaly; semiologic similarities were observed between mother and daughter patients. X-rays, US and CT rarely play an important role in the diagnosis of RTS, considering the several clinical signs, mainly the face, affecting the patients. However, diagnostic imaging techniques help diagnose hidden malformations and confirm and integrate clinical signs.

Adult↗
PubMed1990

gp33-38, an early human T cell activation antigen.

We describe an activation Ag Me14/D12 that appears early after T cell activation and is absent in resting T lymphocytes. Me14/D12 is a nondisulfide-linked heterodimeric structure containing two polypeptide chains of 33,000 and 38,000 Da. The expression of Me14/D12 on resting T lymphocytes can be induced by different activation stimuli such as the lectins PHA and Con A, the phorbol ester PMA, and anti-CD3 mAb. The induction of mRNA for Me14/D12 (gp33-38) in PHA-activated T lymphocytes precedes that of IL-2R gene transcripts by more than 20 h. Me14/D12 mRNA was detectable as early as 2 h after the onset of activation and mRNA for the IL-2R only after 24 h. The surface expression of Me14/D12 was detectable between 12 and 24 h after activation and was maximal between 24 and 48 h. Several T leukemia cell lines express the Me14/D12 Ag. On Me14/D12- cell lines, PMA and IFN-gamma induced surface expression of Me14/D12. Once Me14/D12 Ag were expressed on Jurkat cells after stimulation with either PMA or IFN-gamma, the binding of mAb Me14/D12 induced the production of significant amounts of IL-2 and of Ca2+ mobilization from internal stores. Comparative biochemical studies clearly demonstrate that Me14/D12 (gp33-38) is different from the CD69 molecular complex defined by mAb MLR3 and AIM.

Antibodies, Monoclonal↗
PubMed1990

Holoprosencephaly: examples of clinical variability and etiologic heterogeneity.

Clinical variability and causal heterogeneity of holoprosencephaly is discussed in relation to several newborn infants with cyclopia (cases 4,5,6), cebocephaly (cases 2,3), and premaxillary agenesis (case 1). In subjects with holoprosencephaly, the presence of multiple malformations is an indicator of concomitant chromosome aberrations, as in present case 1 (Down syndrome) and case 3 (trisomy 13). Cases 5 and 6 are two monozygotic twins with the same type of cyclopia and alobar holoprosencephaly recognized by prenatal ultrasonography. The diagnostic importance of ultrasonographic, cytogenetic, and pathological studies is pointed out in view of etiologic evaluation, genetic counseling, and prevention of holoprosencephaly.

Abnormalities, Multiple↗
PubMed1990

Growth charts of Down syndrome in Sicily: evaluation of 382 children 0-14 years of age.

We present the results of a study performed on a Sicilian population of children with Down syndrome (DS) 0-14 years of age, observed between 1977 and 1988. Data from the present report concern 382 subjects with nonmosaic 21 trisomy, including 239 males (62.6%) and 143 females (37.4%). We excluded all DS children observed in the same period with associated pathology (congenital heart defects, gastrointestinal malformations, malabsorption, hypothyroidism, and thalassemia). Overall, 1,464 measurements were performed of length or height, weight, and head circumference. Means and standard deviation (SD) were calculated for all of these parameters. Our data confirm a trend toward a progressive improvement of growth in children with DS, as shown in other recent reports. The purpose of this study was also to create a "normal growth pattern" useful to evaluate DS children and also to diagnose early pathologic conditions affecting growth, such as autoimmune diseases.

Adolescent↗
PubMed1989

Characterization of receptors for alpha-melanocyte-stimulating hormone on human melanoma cells.

Receptors for alpha-melanocyte-stimulating hormone (alpha-MSH) on human malignant melanoma cell lines were investigated with a specific binding assay and characterized with structural analogues of alpha-MSH and adrenocorticotropic hormone and by photoaffinity cross-linking of the hormone-receptor complex. Specific binding of high-performance liquid chromatography-purified, monoiodinated alpha-MSH in the presence of 1 mM 1,10-phenanthroline as protease inhibitor was highest after a 2-h incubation at 37 degrees C. The nonspecific binding was less than 20% and dissociation of the ligand-receptor complex was relatively slow. Ten out of 12 human cell lines showed specific binding sites for alpha-MSH with Kp values ranging from 0.195 to 2.87 nM and the sites/cell being approximately 400 to approximately 1600. Virtually identical results were obtained in an assay where the cells remained attached to the culture dishes during the entire experiment. The study of hormone analogues with the D10 cell line showed that oxidized alpha-MSH had an approximately 40-fold lower affinity than alpha-MSH whereas [Nle4,D-Phe7]-alpha-MSH displayed a threefold and the adrenocorticotropic hormone fragments (1-17) and (1-24) a 20- and 8-fold higher affinity. Cross-linking of the alpha-MSH-receptor complex of three cell lines using monoiodinated [Nle4,D-Phe7,Trp(2-nitro-4-azidophenylsulfenyl)9]-alpha-MSH as photoaffinity label revealed a major Mr 45,000 protein band on sodium dodecyl sulfate-polyacrylamide gels, analogous to the MSH receptor of mouse B16 melanoma cells.

Animals↗
PubMed1989

A novel interferon-gamma regulated human melanoma-associated antigen, gp33-38, defined by monoclonal antibody Me14-D12. II. Molecular cloning of a genomic probe.

The human Me14-D12 antigen is a cell surface glycoprotein regulated by interferon-gamma (IFN-gamma) on tumor cell lines of neuroectodermal origin. It consists of two non-convalently linked subunits with apparent mol. wt sizes of 33,000 and 38,000. Here we describe the molecular cloning of a genomic probe for the Me14-D12 gene using the gene transfer approach. Mouse Ltk- cells were stably cotransfected with human genomic DNA and the Herpes Simplex virus thymidine kinase (TK) gene. Primary and secondary transfectants expressing the Me14-D12 antigen were isolated after selection in HAT medium by repeated sorting on a fluorescence activated cell sorter (FACS). A recombinant phage harboring a 14.3 kb insert of human DNA was isolated from a genomic library made from a positive secondary transfectant cell line. A specific probe derived from the phage DNA insert allowed the identification of two mRNAs of 3.5 kb and 2.2 kb in primary and secondary L cell transfectants, as well as in human melanoma cell lines expressing the Me14-D12 antigen. The regulation of Me14-D12 antigen by INF-gamma was retained in the L cell transfectants and could be detected both at the level of protein and mRNA expression.

Antibodies, Monoclonal↗
PubMed1988

Cyclic AMP induces differentiation in vitro of human melanoma cells.

Treating human melanoma lines with dibutyryl adenosine 3':5'-cyclic monophosphate (dbc AMP) resulted in morphologic changes associated with the altered expression of cell surface antigens. After treatment, cells developed long cellular projections characteristic of mature melanocytes and showed the presence of an increased number of Stage II premelanosomes. In addition, induction of melanin synthesis, detected as brown perinuclear pigmentation, was observed. The AMP further drastically reduced the growth rate of the five melanoma cell lines that were tested. The influence of dbc AMP was completely reversible 3 days after the agent was removed from the culture medium. The antigenic phenotype of the melanoma lines was compared before and after dbc AMP treatment. This was done with four monoclonal antibodies directed against major histocompatibility complex (MHC) Class I and II antigens and 11 monoclonal antibodies defining eight different melanoma-associated antigenic systems. Treatment with dbc AMP reduced the expression of human leukocyte antigen (HLA)-ABC antigens and beta-2-microglobulin in five of five melanoma lines. In the two HLA-DR-positive cell lines dbc AMP reduced the expression of this antigen in one line and enhanced it in the other. No induction of HLA-DR or HLA-DC antigens was observed in the Class II negative cell lines. Furthermore, dbc-AMP modulated the expression of the majority of the melanoma antigenic systems tested. The expression of a 90-kilodalton (KD) antigen, which has been found to be upregulated by interferon-gamma, was markedly decreased in all the five cell lines. A similar decrease in the expression of the high molecular weight proteoglycan-associated antigen (220-240 KD) was observed. The reduced expression of Class I and II MHC antigens as well as the altered expression of the melanoma-associated antigens studied were shown to be reversible after dbc AMP was removed. Our results collectively show that the monoclonal antibody-defined melanoma-associated molecules are linked to differentiation. They could provide useful tools for monitoring the maturation of melanomas in vivo induced by chemical agents or natural components favoring differentiation.

Antigens, Neoplasm↗
PubMed1988

Antigen-independent activation of T cells mediated by a novel cell surface heterodimer (Tp135-145).

A new heterodimeric structure, Tp135-145, which can mediate interleukin 2 (IL2) production and Ca2+ mobilization by Jurkat cells is described. This structure was identified by a monoclonal antibody, MX24, on the surface of either T3/TcR+ or T3/TcR- human T cell lines as well as on B cell lines. Biochemical studies showed that antibody MX24 precipitated two polypeptide chains of 135 and 145 kDa, respectively, in lysates from 125I-labeled T cells. After reduction the 135-kDa polypeptide chain shifted to 140 kDa, whereas the molecular mass of the other polypeptide remained unchanged. The apparent molecular masses of the desialylated polypeptides differed by 5 kDa. No common peptide fragments between the two polypeptide chains were found after limited proteolysis by Staphylococcus aureus V8 protease. The expression of Tp135-145 was independent of the expression of the T3/TcR molecular complex. Incubation of Jurkat cells with anti-TcR or anti-T3 monoclonal antibody induced complete modulation only of the T3/TcR complex but not of Tp135-145. Conversely complete modulation of Tp135-145 was observed after incubation of these cells with MX24 antibody. Functional studies showed that anti-Tp135-145 antibody MX24 induced high levels of IL2 production in Jurkat cells. In addition, incubation of these cells with MX24 resulted in Ca2+ mobilization from internal stores. In peripheral blood, Tp135-145 was found to be expressed by 39%-76% of resting T cells in individual donors. Two-color flow microfluorimetry showed that the Tp135-145+ cells were equally distributed on the CD4+ and CD8+ subsets. Incubation of peripheral blood T cells with antibody MX24 resulted in IL2 production and cell proliferation. Taken together these results suggest that Tp135-145 is a novel surface molecule involved in antigen-independent pathway of T cell activation.

Antibodies, Monoclonal↗