γ Heavy Chain Disease in Man: cDNA Sequence Supports Partial Gene Deletion Model

Human gamma heavy chain disease (HCD) is characterized by the presence in serum of a short monoclonal Ig gamma chain unattached to light chains. Although most HCD proteins have internal deletions, in some the defect is NH2-terminal. The OMM gamma 3 HCD serum protein is of the latter type, having undergone an extensive NH2-terminal deletion with a sequence starting within the hinge. A cell line synthesizing the OMM protein has enabled us to study the biogenesis of the abnormal molecule. In vitro translation of isolated mRNA yields a protein containing a hydrophobic NH2-terminal leader sequence. In the intact cell, the precursor molecule is processed normally to yield a protein with an NH2-terminal sequence homologous to the beginning of the variable (V) region. The nucleotide sequence of cDNA prepared from the OMM mRNA encodes a 19-amino acid leader followed by the first 15 residues of the V region. An extensive internal deletion encompasses the remainder of the V and the entire CHl domain. Immediately following the short V region, there is information in the cDNA for the entire normal hinge. The primary synthetic product is thus an internally deleted molecule that undergoes postsynthetic degradation to yield the NH2-terminally deleted serum protein. The structure of the OMM mRNA suggests that the protein abnormality results from a partial gene deletion rather than defective splicing

Can ReGeneraTing Agents Improve Functional Recovery of Transected Peripheral Nerve through a Nerve Gap Bridged with an Artery Graft

Background The purpose of this study was to use artery grafts filled with CACIPLIQ20 and see if they promote nerve regeneration. Methods Sixty male Wistar rats were used. The rats were randomly divided into four experimental groups (n = 15): transected control group (negative control group [NCG]), sham-operated group (positive control group [SO]) artery graft group filled with saline (AG/NS), and CACIPLIQ20-treated group (AG/CACIPLIQ20). Fifteen rats were used as artery graft donors. In the SO group, the sciatic nerve was dissected from the surrounding tissues and left intact. In the NCG, AG/NS and AG/CACIPLIQ20) groups, a 10-mm gap was created in the left sciatic nerve. In the NCG group, the gap was not bridged with a graft. In the AG/NS group, the gap was bridged with a graft filled with saline. In the AG/CACIPLIQ20 group, the graft was filled with CACIPLIQ20. Walking track analysis was performed at 4, 8, 12, and 16 weeks after surgery. At 16 weeks postoperatively, the rats were sacrificed, nerve sections were harvested for histopathology analysis, and the weight ratio of the gastrocnemius muscle was measured. Results There was no significant difference in myelin sheath thickness between the AG/NS and AG/CACIPLIQ20 groups. Muscle weight in the AG/CACIPLIQ20 group was higher but not statistically significant (p = 0.168) compared with the AG/NS group. Also, AG/CACIPLIQ20 mean was better than AG/NS mean, although there was no statistically significant difference (p = 0.605). Conclusion There could be an indication that CACIPLIQ20 improves functional recovery of a transected peripheral nerve through a nerve gap bridged with an artery graft

RGTA® or ReGeneraTing Agents mimic heparan sulfate in regenerative medicine: from concept to curing patients

The importance of extracellular matrix (ECM) integrity in maintaining normal tissue function is highlighted by numerous pathologies and situations of acute and chronic injury associated with dysregulation or destruction of ECM components. Heparan sulfate (HS) is a key component of the ECM, where it fulfils important functions associated with tissue homeostasis. Its degradation following tissue injury disrupts this delicate equilibrium and may impair the wound healing process. ReGeneraTing Agents (RGTA®s) are polysaccharides specifically designed to replace degraded HS in injured tissues. The unique properties of RGTA® (resistance to degradation, binding and protection of ECM structural and signaling proteins, like HS) permit the reconstruction of the ECM, restoring both structural and biochemical functions to this essential substrate, and facilitating the processes of tissue repair and regeneration. Here, we review 25 years of research surrounding this HS mimic, supporting the mode of action, pre-clinical studies and therapeutic efficacy of RGTA® in the clinic, and discuss the potential of RGTA® in new branches of regenerative medicine

ASPECTS IMMUNOLOGIQUES DE L'EPITHELIUM CONJONCTIVAL DANS LES PATHOLOGIES DE LA SURFACE OCULAIRE

PARIS12-CRETEIL BU Multidisc. (940282102) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

ETUDE D'UN NOUVEAU RECEPTEUR AU FACTEUR DE CROISSANCE DES FIBROBLASTES FGF2 ET DE DEUX PROTEINES ASSOCIEES

LES FACTEURS DE CROISSANCE DES FIBROBLASTES SONT DES POLYPEPTIDES QUI JOUENT LE ROLE D'AGENTS MITOGENES, ANGIOGENES, NEUROTROPHIQUES ET CHEMOTACTIQUES VIS-A-VIS DE CERTAINES CELLULES. ILS INTERVIENNENT AU COURS DES PROCESSUS DE DEVELOPPEMENT EMBRYONNAIRE, DE CONTROLE DE L'HOMEOSTASIE TISSULAIRE, DE REGENERATION ET REPARATION TISSULAIRES ET DE PROLIFERATION TUMORALE. ILS AGISSENT PAR L'INTERMEDIAIRE DE RECEPTEURS DE HAUTE AFFINITE A ACTIVITE TYROSINE KINASE (FGFR) ET DE BASSE AFFINITE DE TYPE HEPARANE SULFATE PROTEOGLYCANE (HSPG). LE SUJET DE CETTE THESE PORTE SUR L'ETUDE D'UN NOUVEAU RECEPTEUR AU FGF2 APPELE P150. CE RECEPTEUR EST CO-PURIFIE, A PARTIR DE CERVEAUX DE BUFS, AVEC DEUX AUTRES PROTEINES NOMMEES P46 ET P79. LE CLONAGE ET LE SEQUENCAGE DE LEURS ADNC ONT PERMIS DE METTRE EN EVIDENCE DES IDENTITES DE SEQUENCE AVEC D'AUTRES MOLECULES. AINSI, LA P46 EST HOMOLOGUE A LA SOUS-UNITE D'UN COMPLEXE MULTIENZYMATIQUE MITOCHONDRIAL (MTP). LA P79 PRESENTE, QUANT A ELLE, UNE IDENTITE ELEVEE POUR LA SOUS UNITE DE CE MEME COMPLEXE (MTP) ET POUR LA GBP (GASTRIN-BINDING PROTEIN). ENFIN, LA P150 EST PRATIQUEMENT IDENTIQUE AU CFR (CYSTEINE-RICH FGF RECEPTOR), A LA MG160 (MEDIAN GOLGI MEMBRANE SIALOGLYCOPROTEIN), A L'ESL-1 (E-SELECTIN LIGAND-1) ET A LA LTCP (LATENT TGF COMPLEXED PROTEIN). L'ETUDE DE L'EXPRESSION DE CES TROIS PROTEINES ET DE LEURS MESSAGERS A ETE REALISEE A LA FOIS AU COURS DU DEVELOPPEMENT EMBRYONNAIRE ET CHEZ L'ADULTE. ELLES SONT COEXPRIMEES AVEC LE FGF2 CHEZ L'EMBRYON DE SOURIS ET DANS LE CERVEAU CHEZ LE RAT ADULTE. PAR AILLEURS, DU FAIT DE LA CAPACITE DE FIXATION DU FGF2 SUR LA P79 ET LA P150, IL EST RAISONNABLE DE PENSER QUE CES TROIS PROTEINES POURRAIENT JOUER UN ROLE A L'EGARD DE CE FACTEUR DE CROISSANCE. L'UNE DES HYPOTHESES AVANCEES CONCERNANT LA P150, EST QU'ELLE SERAIT IMPLIQUEE DANS LA REGULATION DU TRANSPORT DU FGF2. EN CE QUI CONCERNE LA P46 ET LA P79, ELLES POURRAIENT INTERVENIR EN FORMANT UN COMPLEXE AVEC LA P150 ET CE FACTEUR.PARIS12-CRETEIL BU Multidisc. (940282102) / SudocSudocFranceF

Angiogenin and endothelial cells

International audienceAntiogenin is a potent blood vessel-inducing polypeptide that has a unique ribonucleolytic activity. Initially identified from tumor cells conditioned medium through its ability to induce neovascularization in the chick embryo chorioallantoic membrane assay, angiogenin has also been purified from normal plasma which suggested that it might be involved in endothelium homeostasis. Angiogenin is highly homologous to pancreatic ribonuclease A with 68% amino acid sequence homology and conserved essential active site residues [3]. However, angiogenin is inactive in standard ribonuclease assays but has a ribonucleolytic specificity toward ribosomal and transfer RNAs. This enzymic activity might be relevant to the process of angiogenesis since a functional active site seems necessary for the expression of its angiogenic property; however, it appears not to be sufficien

Case Reports for Topical Treatment of Corneal Ulcers with a New Matrix Therapy Agent or RGTA® in Dogs

Superficial corneal ulcers that fail to heal within a normal time period and are refractory to conventional therapy in dogs are common in veterinary practice. Different etiologies can lead to this result, including spontaneous chronic corneal epithelial defects (SCCEDs) and ulcerative keratitis associated with bullous keratopathy. Thus, there is an urgent need to find new therapeutic approaches such as matrix therapy replacement. To determine the efficacy of a new ophthalmic treatment (Clerapliq®) for SCCEDs and ulcerative keratitis associated with bullous keratopathy, a total of 11 dogs referred to the clinic because of nonhealing erosive ulcers after a classic primary treatment were enrolled to get this new treatment. Dogs underwent ophthalmic exams and 7 dogs (10 eyes) were diagnosed with superficial ulceration and 4 dogs (5 eyes) with bullous keratopathy due to endothelial dystrophy/degeneration. They received eye drops of Clerapliq® every 3 days until recovery. The results showed that the corneas with recurrences of the ulcers were resolved predominantly by using Clerapliq® every 3 days in 83.3% of the cases during a period of treatment ranging between 6 to 35 days. Therefore, this new approach using matrix therapy regenerating technology in treating superficial ulcers and bullous keratopathy in dogs can be successfully considered as an adjunctive therapy

In vivo and in vitro studies of angiogenin--a potent angiogenic factor

International audienceAngiogenin is a potent blood-vessel-inducing polypeptide with a molecular weight of 14,000 that has a unique ribonucleolytic activity. First isolated from the conditioned medium of tumour cells, angiogenin has since been purified from normal plasma, which suggested that its propensity to induce neovascularization should be strictly controlled. Modulation of that activity might involve interaction of angiogenin with cell-surface receptors and extracellular matrix of endothelial cells, tight-binding inhibition of both its ribonucleolytic activity and cell binding property by ribonuclease inhibitor, as well as the overall influence of divalent copper, a modulator of angiogenesis