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P Bono

Publications and source records attributed to P Bono.

At least 19 recordsLinked to original sources

Distinct ligand binding properties of Mac-2-binding protein and mouse cyclophilin [correction of mousephilin] C-associated protein.

Human Mac-2-binding protein (Mac-2-BP) is a secreted glycoprotein that is widely expressed. It binds to the human macrophage-associated lectin Mac-2 and has been suggested to have a role in host defence. Mouse cyclophilin C-associated protein (mCyCAP) is also a secreted glycoprotein that binds with high affinity to cyclophilin C in the absence of the immunosuppressive drug cyclosporin A. The two proteins share a similar domain structure and considerable sequence identity, including a highly conserved scavenger receptor cysteine-rich domain, and both of them exert their function within the immune system. To elucidate whether these molecules are also functional homologues, we compared their ligand binding properties using cell lines which express Mac-2-BP or mCyCAP as well as transfected cell lines stably expressing mCyCAP or a mutant version lacking the scavenger domain. These experiments show that Mac-2-BP is unable to bind to either human or mouse cyclophilin C and thatmCyCAP cannot bind to Mac-2. The scavenger domain is not required for the interaction between mCyCAP and cyclophilin C. We conclude that these proteins may be part of a larger family of proteins of immunological importance in which closer functional homologues might exists.

Animals↗

Layilin, a novel integral membrane protein, is a hyaluronan receptor.

The actin cytoskeleton plays a significant role in changes of cell shape and motility, and interactions between the actin filaments and the cell membrane are crucial for a variety of cellular processes. Several adaptor proteins, including talin, maintain the cytoskeleton-membrane linkage by binding to integral membrane proteins and to the cytoskeleton. Layilin, a recently characterized transmembrane protein with homology to C-type lectins, is a membrane-binding site for talin in peripheral ruffles of spreading cells. To facilitate studies of layilin's function, we have generated a layilin-Fc fusion protein comprising the extracellular part of layilin joined to human immunoglobulin G heavy chain and used this chimera to identify layilin ligands. Here, we demonstrate that layilin-Fc fusion protein binds to hyaluronan immobilized to Sepharose. Microtiter plate-binding assays, coprecipitation experiments, and staining of sections predigested with different glycosaminoglycan-degrading enzymes and cell adhesion assays all revealed that layilin binds specifically to hyaluronan but not to other tested glycosaminoglycans. Layilin's ability to bind hyaluronan, a ubiquitous extracellular matrix component, reveals an interesting parallel between layilin and CD44, because both can bind to cytoskeleton-membrane linker proteins through their cytoplasmic domains and to hyaluronan through their extracellular domains. This parallelism suggests a role for layilin in cell adhesion and motility.

3T3 Cells↗

Expression of alpha4-integrins on human neutrophils.

alpha4 Integrins are important adhesion molecules mediating binding of lymphocytes, monocytes, and eosinophils to multiple cellular and extracellular ligands. Mature neutrophils have been recently suggested to express alpha4-integrins as well. We studied whether human neutrophils can synthesize alpha4-integrins upon activation in vitro or in vivo. Two anti-alpha4 mAbs, but not multiple subclass-matched non-binding controls, reacted with granulocytes in an inducer and time-dependent manner. Nevertheless, staining with Ig subclass-specific second-stage reagents surprisingly revealed that commercial anti-alpha4 mAbs contain two distinct Igs, the alpha4-specific IgG1 and an IgG2a of an unknown specificity. We showed that in vitro inductions used by us and others only induce the binding of nonspecific IgG2a from the commercial HP2/1 to activated neutrophils. By reverse-transcriptase polymerase chain reaction, alpha4 mRNA was not detectable in purified neutrophils. Our results show that alpha4 integrin protein and mRNA are absent from normal and stimulated human neutrophils.

Antigens, CD↗

[Erectile dysfunction: a missed opportunity?].

The increasing of andrological valuation for erectile dysfunction (ED), happened in the last ten years, and induced chemical industries and sanitary system to supply correct answers from cultural, diagnostic and therapeutic views. All these events allowed the people to approach easily to uro-andrological valuations. This situation is perhaps a unique way to involve a great number of men in a wide uro-andrological screeening, that is useful, with a total patient and couple involvement, not only for a ED causes research, but also for incidental pathology screening (neoplastic or dismethabolic). Even if more expensive than a simplified diagnostic ED protocol (95% of the patients accept it, if there is a good counseling), this way of diagnostic valuation permit to hit the targets and to add permanently andrology to scientific specialty, as the science that studies the sexuality behaviour of the man and all its pathology.

Adult↗

Mouse vascular adhesion protein 1 is a sialoglycoprotein with enzymatic activity and is induced in diabetic insulitis.

The continuous recirculation of lymphocytes requires an adequate expression and function of the molecules mediating the cellular interactions between endothelium and lymphocytes. Human vascular adhesion protein 1 (hVAP-1) is an endothelial cell adhesion molecule that mediates the binding of lymphocytes to venules in peripheral lymph nodes as well as at sites of inflammation. Recently the mouse homologue of hVAP-1 has been cloned. It is a previously unknown molecule with a significant sequence identity to copper-containing amine oxidases. Besides the sequence, very little is known about the expression, structure, and function of mouse VAP-1 (mVAP-1). In this study we demonstrate that mVAP-1 is prominently expressed in endothelial and smooth muscle (but not in other types of muscle cells), as well as in adipocytes. mVAP-1 is a 220-kd homodimeric sialoglycoprotein that displays cell-type-specific differences in glycosylation. The expression of mVAP-1 is induced on inflammation in the vessels of the endocrine pancreas during the development of insulitis, and the up-regulation correlates with the extent of the lymphocytic infiltrate. In general, different mouse strains displayed very similar VAP-1 expression, but the small differences seen in liver and gut suggest that immunostimulation may modulate VAP-1 synthesis in extrapancreatic organs as well. Finally, we show that mVAP-1 has a monoamine oxidase activity against naturally occurring substrates, implying a role in the development of vasculopathies. These data show that mVAP-1 and hVAP-1 are very similar molecules that nevertheless have certain marked differences in expression, biochemical structure, and substrate specificity. Thus mVAP-1 is a novel inflammation-inducible mouse molecule that has a dual adhesive and enzymatic function.

Amine Oxidase (Copper-Containing)↗

Isolation, structural characterization, and chromosomal mapping of the mouse vascular adhesion protein-1 gene and promoter.

Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule which mediates lymphocyte binding to endothelial cells. The cloning of a mouse VAP-1 (mVAP-1) cDNA revealed that mVAP-1 is a novel 110/220 kDa transmembrane molecule with significant identity to copper-containing amine oxidases. In this work the nucleotide sequence and primary structure of the mVAP-1 gene was determined and the promoter region was structurally characterized. The isolated approximately 14.4-kb mVAP-1 gene consists of 4 exons and 3 introns. Primer extension analysis and 5' rapid amplification of cDNA ends revealed multiple transcription initiation sites in different tissues suggesting that the mVAP-1 transcription is differently regulated in different tissues. Analysis of the sequence immediately upstream of the detected transcription initiation sites showed no canonical TATA or CCAAT elements, but putative regulatory elements were found close to the detected transcription start sites. The cloning of the mVAP-1 gene reveals the first insight into the genomic organization of murine amine oxidases and will, by targeted disruption of the gene, allow us to understand better the importance of VAP-1 in leukocyte trafficking and monoamine oxidase activity for the function of the immune system.

Amine Oxidase (Copper-Containing)↗

Cloning of vascular adhesion protein 1 reveals a novel multifunctional adhesion molecule.

Vascular adhesion protein 1 (VAP-1) is a human endothelial sialoglycoprotein whose cell surface expression is induced under inflammatory conditions. It has been shown previously to participate in lymphocyte recirculation by mediating the binding of lymphocytes to peripheral lymph node vascular endothelial cells in an L-selectin-independent fashion. We report here that the VAP-1 cDNA encodes a type II transmembrane protein of 84.6 kD with a single transmembrane domain located at the NH2-terminal end of the molecule and six potential N-glycosylation sites in the extracellular domain. In vivo, the protein exists predominantly as a homodimer of 170-180 kD. Ax endothelial cells transfected with a VAP-1 cDNA express VAP-1 on their cell surface and bind lymphocytes, and the binding can be partially inhibited with anti-VAP-1 mAbs. VAP-1 has no similarity to any currently known adhesion molecules, but has significant identity to the copper-containing amine oxidase family and has a monoamine oxidase activity. We propose that VAP-1 is a novel type of adhesion molecule with dual function. With the appropriate glycosylation and in the correct inflammatory setting, its expression on the lumenal endothelial cell surface allows it to mediate lymphocyte adhesion and to function as an adhesion receptor involved in lymphocyte recirculation. Its primary function in other locations where it is expressed, such as smooth muscle, may depend on its inherent monoamine oxidase activity.

Amine Oxidase (Copper-Containing)↗

Cloning and characterization of mouse vascular adhesion protein-1 reveals a novel molecule with enzymatic activity.

Human vascular adhesion protein-1 (VAP-1) is a sialylated endothelial cell adhesion molecule mediating the initial L-selectin-independent interactions between lymphocytes and endothelial cells in man. In this work we cloned and characterized mouse VAP-1 (mVAP-1) and produced an anti-mVAP-1 mAb against a recombinant mVAP-1 fusion protein. The isolated cDNA encodes a novel 84.5-kDa mouse molecule. The anti-mVAP-1 mAb stained high endothelial venules in peripheral lymph nodes, and smooth muscle cells and lamina propria vessels in gut. During immunoblotting, this anti-mVAP-1 mAb recognized a 110/220-kDa Ag, suggesting that mVAP-1 is a dimer. Since mVAP-1 has significant sequence identity to members of a family of enzymes called the copper-containing amine oxidases, we showed that mVAP-1 possesses monoamine oxidase activity. Thus, mVAP-1 is the first mouse membrane-bound amine oxidase identified at the molecular level. Based on the 83% identity between the isolated cDNA and human VAP-1 cDNA, the expression pattern, the molecular mass, and the enzyme activity against monoamines, the cloned molecule represents a mouse homologue of human VAP-1. Cloning of mVAP-1 provides a valuable tool for in vivo studies of the significance of VAP-1 for lymphocyte-endothelial cell interactions and of the possible relationship between leukocyte adhesion and amine oxidase activity.

Amine Oxidase (Copper-Containing)↗

TeleInViVo: a collaborative volume visualization application.

Converging technologies in the areas of networks, volume visualization algorithms, and computer performance have made possible the development of a new tool for collaboration, which extends the reach of health professionals, and other consumers of volumetric data around the world. TeleInViVo(tm) is a three-dimensional (3D) collaborative volume visualization tool for medical applications. It extends the capabilities of InViVo(tm), a fast volume visualization tool developed at the Fraunhofer IGD, Darmstadt, Germany [1-3], with efficient and intuitive network collaboration features for remote consultation and new modes of interaction. The software runs on both UNIX and Windows NT platforms. TeleInViVo provides a high degree of interactivity for the medical professional when interacting with the patient data, facilitates explanation and communication between field personnel and medical experts located far from the field, and permits viewing of the data in a multitude of ways designed to support rapid and accurate diagnosis. Current efforts involve architectural enhancements to support multiuser, distributed telemedical scenarios. The application includes the following features: Volume and subvolume data transmission at user specified resolution, Synchronization cues, Integration of Immersion Probe(tm), a 6 degree-of-freedom input device, for ergonomic 3D data exploration, Tools for measuring distances, Tools for planning instrument path, Arbitrary cutting planes in real time, Interactive segmentation tools, Virtual video recorder and playback (cine loops), 3D stereo mode. TeleInViVo is an essential part of the MUSTPAC-1 portable 3D ultrasound system developed by Battelle Pacific Northwest Labs, Richland, WA.

Computer Communication Networks↗

Analysis of the neurofibromatosis type 2 gene in different human tumors of neuroectodermal origin.

The autosomal dominant syndrome neurofibromatosis type 2 (NF2) is characterized by the development of bilateral vestibular schwannomas, meningiomas, ependymomas and gliomas. The NF2 gene, recently isolated from chromosome 22, is mutated in both sporadic and NF2 tumors such as schwannomas, meningiomas and ependymomas. Mutations of the gene have been described not only in the neoplasms usually associated with NF2, but also in 30% of the melanomas and 41 % of the mesotheliomas analyzed. In particular, the finding of mutations in melanomas supports the hypothesis that the NF2 gene is involved in the genesis of several tumor types that arise from the embryonic neural crest. In this study we examined, by single-strand conformational polymorphism (SSCP) analysis, 41 tumors of the central nervous system (11 schwannomas and 30 gliomas), 19 melanomas and 15 Merkel cell carcinoma specimens for mutations in the coding sequence of the NF2 gene. We found three inactivating mutations of the NF2 gene in schwannomas. No alterations of the gene were detected by SSCP analysis of the other tumors. These results confirm the role of NF2 in pathogenesis of schwannomas, but do not define its significance in the genesis of the other neuroectodermal tumors studied.

Central Nervous System Neoplasms↗

CD73 is involved in lymphocyte binding to the endothelium: characterization of lymphocyte-vascular adhesion protein 2 identifies it as CD73.

We have recently described a monoclonal antibody (mAb) 4G4 recognizing a 70-kD molecule constitutively expressed on human endothelial cells and on subpopulations of lymphocytes. We showed that this molecule, which we named lymphocyte-vascular adhesion protein 2 (L-VAP-2), mediates lymphocyte adhesion to cultured endothelial cells. Protein sequencing of tryptic peptides from immunoaffinity-purified L-VAP-2 revealed sequence identity between L-VAP-2 and CD73 (ecto-5'-nucleotidase, E.C.3.1.3.5), and COS cells transfected with a CD73 cDNA were positively stained with the mAb 4G4, which recognizes L-VAP-2. mAb 4G4 was also able to partially inhibit the ecto-5'-nucleotidase activity of peripheral blood lymphocytes. Moreover, cross-precipitation studies performed with mAb 4G4 and a CD73 workshop mAb 1E9 showed that these two antibodies recognize the same molecule. Since the tissue distribution and biochemical characteristics of the two molecules are also similar, we conclude that L-VAP-2 and CD73 are the same glycoprotein. Adhesion experiments showed significantly increased binding of freshly isolated lymphocytes to COS cells transfected with a CD73 cDNA, as compared to mock-transfected COS cells, and binding of lymphocytes to CD73-expressing COS cells was inhibited by the presence of mAb 4G4 in the adhesion assay. CD73 is a glycosyl phosphatidylinositol-linked molecule previously shown to have a cosignalling role in T lymphocyte proliferation. Our data suggest that it also has a function in mediating lymphocyte adhesion to the endothelium.

5'-Nucleotidase↗

[Urinary diversion using a Maizels catheter (K.I.S.S.S.) in pyeloplasty].

The increasing interest and progress showed by the surgical treatment of the ureteropelvic junction obstruction, have evidenced some problems that have not completely solved. Problem in which there is division in opinion concerns the role of splinting with or without nephrostomy in pyeloplasty. A strong impulse for proximal urinary diversion after pyeloplasty derived from data provided by Caine and Hermann (1), who have demonstrated in cineradiographic studies that the normal ureteral peristalsis did not return for about 3 weeks after anastomosis. The authors, who use systematically urinary diversion in pyeloplasty, emphasize the usefulness of the Kidney Internal Stent Splint Set (K.I.S.S.S.). This device developed by Max Maizels, From Children's Memorial Hospital Chicago USA, is employed after pyeloplasty, when kidney drainage is mandatory for the success of the procedure. The set contains: sof-flex stent, 55 cm. long: closed segment 25 cm. long, with 12 cm. malleable tapered positioning stylet; "cut-out" segment 30 cm. long. Silicone retention disc with pull-tie; Luer-lock adapter; 10 Fr. polyvinylchloride connecting tube 30 cm long. Introduction with the malleable stylet is the same as a nephrostomy interoperatively placed. The closed portion of the stent is sutured with adsorbable suture to the renal capsule and is performed as a nephrostomy drainage catheter. The "cut-out" portion is advanced interoperatively into the ureter. The K.I.S.S.S. explains essentially a twofold function: first to defend the neo-anastomosis, secondly like a nephrostomy drainage.

Anastomosis, Surgical↗

[The anterior approach after Chute, Baron and Olsson in renal pathology: the authors' own experience].

The authors describe their experience of 79 operations using the Chevron anterior transperitoneal approach in the treatment of 71 renal tumors and 8 cases of renal trauma. This approach respects the physiology of the respiratory system, has a low morbidity and mortality, in the post-operative period the need for anesthesia is moderate and hospitalization is shorter. The authors underscore the following advantages of the Chute-Baron-Olsson technique: it is easy to perform and can be easily extended, dehiscence and laparoceles are uncommon (only 2 of 79 patients). Furthermore, the Chevron partial or total approach in tumors and renal trauma permits exposure of an excellent inframesocolic and supramesocolic field and perfect control of the important elements of the renal vasculature.

Adult↗

[Ectopic adrenal cortex tissue in the spermatic cord: clinico-surgical implications].

Ectopic corticoadrenal tissue is not a very uncommon finding during orchiopexy in children. The causes can be found in the period of organ development and gonadal migration (spermatic cord). From 1986 to 1990, we have performed 88 orchiopexy procedures in the Urology Service of "San Antonio Abad de Gallarate" Hospital. Only one case (1.13%) of juxta-funicular corticoadrenal ectopia has been observed. The aim of the present study is to determine the correct surgical approach to this incidental finding during surgery of the inguinal canal in pediatric patients.

Adrenal Cortex↗

[Vertebral osteochondroma and trauma: a possible etiopathogenic correlation].

Three cases of vertebral osteochondroma are shown. The tumor was localized in the dorsal tract in two cases and in the lumbo-sacral junction in the other one. We found in all the cases, as a common anamnestic point, a clinical history of trauma. The etiopathological hypotheses are discussed and the hypothesis of a possible correlation between trauma and metaplastic osteochondromatosis is presented.

Adult↗

A mouse molecular mimic of human vascular adhesion protein-1.

Human vascular adhesion protein-1 (VAP-1) is an endothelial sialoglycoprotein which exists in forms of Mr 90000 and 170000 and mediates lymphocyte binding to vessels under shear. VAP-1 is functionally defined by an inhibitory mouse mAb 1B2. A large-scale immunoaffinity purification of VAP-1 from human tonsil lysates was performed to determine the protein sequence for VAP-1 cDNA cloning. A dominant protein of molecular weight 90000 was obtained which yielded an N-terminal sequence of 20 amino acids which bore no significant identity to any protein sequence in the data banks. A mouse mAb (5B11) against a synthetic peptide from this sequence was raised and found to stain tissues in an identical manner to mAb 1B2, to inhibit lymphocyte adhesion to endothelial cells and to recognize VAP-1. Later, the N-terminal sequence obtained from the 1B2 immunoprecipitations was found to be identical to a mouse cyclophilin C associated protein (mCyCAP) subsequently published by others. We show here by several criteria at the protein and DNA level that VAP-1 is distinct from mCyCAP. Moreover, we elucidate the mechanism which results in binding of mCyCAP to mAb 1B2 during antibody synthesis in hybridoma cells and the sequelae of co-precipitation of mCyCAP during the immunoaffinity chromatography. Binding of mCyCAP to a mouse mAb has not been described before and suggests a new function for this molecule in immunoglobulin synthesis and/or secretion. Moreover, these data indicate that the N-terminal peptide of mCyCAP is a molecular mimic of a functionally important epitope of VAP-1.

Amine Oxidase (Copper-Containing)↗