Safety and effectiveness of endovascular embolization or stent-graft reconstruction for treatment of acute carotid blowout syndrome in patients with head and neck cancer: Case series and systematic review of observational studies.

BACKGROUND: Indications for treatment and outcomes after endovascular management of carotid blowout syndrome for patients with head and neck cancer are not well defined. We investigated the safety and effectiveness of endovascular embolization and stent-graft reconstruction. METHODS: A literature review was performed for studies published between 2001 and 2015 with relevance to treatment outcomes. Our institutional database was examined to identify patients treated with endovascular techniques. RESULTS: A total of 266 patients were included. Rates of procedural stroke were higher after embolization of internal carotid artery (ICA)/common carotid artery (CCA) compared to stent graft (embolization 10.3%; stent graft 2.5%; P < .02). Stent graft of ICA/CCA was associated with higher rates of recurrent bleeding (embolization 9.1%; stent graft 31.9%; P < .01). CONCLUSION: Both embolization and stent grafts are safe therapeutic options for acute carotid blowout syndrome. Embolization for ICA/CCA carotid blowout syndrome was associated with higher risks of procedural stroke and lower recurrent bleeding compared to stent grafts.

A knock-in mouse model of congenital erythropoietic porphyria.

Congenital erythropoietic porphyria (CEP) is a recessive autosomal disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosynthetic pathway. The severity of the disease, the lack of specific treatment except for allogeneic bone marrow transplantation, and the knowledge of the molecular lesions are strong arguments for gene therapy. An animal model of CEP has been designed to evaluate the feasibility of retroviral gene transfer in hematopoietic stem cells. We have previously demonstrated that the knockout of the Uros gene is lethal in mice (Uros(del) model). This work describes the achievement of a knock-in model, which reproduces a mutation of the UROS gene responsible for a severe UROS deficiency in humans (P248Q missense mutant). Homozygous mice display erythrodontia, moderate photosensitivity, hepatosplenomegaly, and hemolytic anemia. Uroporphyrin (99% type I isomer) accumulates in urine. Total porphyrins are increased in erythrocytes and feces, while Uros enzymatic activity is below 1% of the normal level in the different tissues analyzed. These pathological findings closely mimic the CEP disease in humans and demonstrate that the Uros(mut248) mouse represents a suitable model of the human disease for pathophysiological, pharmaceutical, and therapeutic purposes.

Differential expression of the nm23 genes in the developing human trophoblast.

NDP kinases are the non-specific enzymes which catalyse the synthesis of the NTPs through a transfer reaction using ATP as phosphoryl donor. In addition to their enzymatic activity, they display other not yet explained functions related to cell growth, differentiation and apoptosis, embryonic development, tumour progression and metastasis. In this study, the expression patterns of the three highly related NDP kinases A, B and C isoforms were investigated in the developing human trophoblast. Both NDP kinase A and B were found to be primarily present in the villous and extravillous cytotrophoblasts, while NDP kinase C was found almost exclusively in the syncytiotrophoblast layer. This suggests that NDP kinase A and B could be a marker for the mononuclear stage of differentiation of villous trophoblasts, while NDP kinase C could be a marker of the syncytiotrophoblast layer.

Knockout mice as model systems for studying nm23/NDP kinase gene functions. Application to the nm23-M1 gene.

Mice carrying a homozygous germ-line mutation in the nm23-M1 gene that eliminates its protein expression and drives expression of beta-galactosidase by nm23-M1 promoter have been generated. nm23-M1 gene inactivation is not teratogenic and the pups can grow to adult age without apparent health problems. However, they undergo a growth retardation and knocked out females cannot feed their pups. Both effects are background dependent. Beta-galactosidase mapping of nm23-M1 promoter activation during embryogenesis shows that the nm23-M1 gene is principally expressed in epithelial layer of tissues which require inductive epithelial-mesenchymal interactions for their formation. In conclusion, invalidated mice could be interesting models to analyze the role of nm23-M1 on signal transduction pathway regulation, or cancer induction and proliferation.

Characterization of the nm23-M2, nm23-M3 and nm23-M4 mouse genes: comparison with their human orthologs.

The nm23 gene family is thought to be involved in physiopathological processes such as growth, differentiation and cancer promotion, progression or metastasis. We report here the mouse nm23-M3 and nm23-M4 complementary DNA sequences and the genomic cloning, characterization and tissue expression pattern of the nm23-M2, nm23-M3 and nm23-M4 genes, in comparison with their human and rat orthologs and with the human nm23-H1 and mouse nm23-M1 genes. The organization and structure of the members of this gene family are remarkably similar in human and rodents. Accordingly, the striking similarities between the human and mouse nm23 genes enable the use of mouse transgenic and knock-out models for studying the role of nucleoside diphosphate kinase isoforms in human physiopathology.

Galanin and galanin receptor expression in neuroblastic tumours: correlation with their differentiation status.

Neuroblastoma and its benign differentiated counterpart, ganglioneuroma, are paediatric neuroblastic tumours arising in the sympathetic nervous system. Their broad spectrum of clinical virulence is mainly related to heterogeneous biologic background and tumour differentiation. Neuroblastic tumours synthesize various neuropeptides acting as neuromodulators. Previous studies suggested that galanin plays a role in sympathetic tissue where it could be involved in differentiation and development. We investigated the expression and distribution of galanin and its three known receptors (Gal-R1, Gal-R2, Gal-R3) in 19 samples of neuroblastic tumours tissue by immunohistochemistry, in situ hybridization and fluorescent-ligand binding. This study provides clear evidence for galanin and galanin receptor expression in human neuroblastic tumours. The messengers coding for galanin, Gal-R1 and -R3 were highly expressed in neuroblastoma and their amount dramatically decreased in ganglioneuroma. In contrast, Gal-R2 levels remained unchanged. Double labelling studies showed that galanin was mainly co-expressed with its receptors whatever the differentiation stage. In neuroblastic tumours, galanin might promote cell-survival or counteract neuronal differentiation through the different signalling pathways mediated by galanin receptors. Finally, our results suggest that galanin influences neuroblastoma growth and development as an autocrine/paracrine modulator. These findings suggest potential critical implications for galanin in neuroblastic tumours development.

Reversion of hepatobiliary alterations By bone marrow transplantation in a murine model of erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is characterized clinically by cutaneous photosensitivity and biochemically by the accumulation of excessive amounts of protoporphyrin in erythrocytes, plasma, feces, and other tissues, such as the liver. The condition is inherited as an autosomal dominant or recessive trait, with a deficiency of ferrochelatase activity. A major concern in EPP patients is the development of cholestasis with accumulation of protoporphyrin in hepatobiliary structures and progressive cellular damage, which can rapidly lead to fatal hepatic failure. The availability of a mouse model for the disease, the Fech(m1Pas)/Fech(m1Pas) mutant mouse, allowed us to test a cellular therapy protocol to correct the porphyric phenotype. When Fech/Fech mice received bone marrow cells from normal animals, the accumulation of protoporphyrin in red blood cells and plasma was reduced 10-fold but still remained 2.5 times above normal levels. Interestingly, in very young animals, bone marrow transplantation can prevent hepatobiliary complications as well as hepatocyte alterations and partially reverse protoporphyrin accumulation in the liver. Bone marrow transplantation may be an option for EPP patients who are at risk of developing hepatic complications.

Organization and expression of mouse nm23-M1 gene. Comparison with nm23-M2 expression.

Nm23 is a gene family encoding different isoforms of the nucleotide diphosphate kinase (NDPK), an enzyme involved in the synthesis of nucleoside triphosphates. In the present study, the organization and expression of the nm23-M1 gene encoding the mouse NDPKA isoform are described. This gene is about 10kb long and composed of five exons. The organization and the exon-intron boundaries are strictly conserved as compared to the human and rat related genes. The gene promoter region did not exhibit any consensus TATA box, SP1 binding element or Inr sequence. By contrast, TCF-1/LEF-1 binding elements and Pit-1 consensus sequence were present. Northern blotting and in situ hybridization methods were carried out in adult and 18.5 days post-coitum (dpc) mouse embryo, respectively. They showed tissue-specific expression of nm23-M1 transcripts, despite housekeeping gene promoter features. The strongest signals were detected in the nervous system, sensory organs and embryonic thymus. In contrast nm23-M2 mRNA was shown to be more widely expressed.The relationship between nm23-M1 gene tissue-specific expression and the putative binding element of the promoter region is discussed.

Cloning of a second nm23-M1 cDNA: expression in the central nervous system of adult mouse and comparison with nm23-M2 mRNA distribution.

Nm23 has been identified as a gene family encoding different isoforms of the nucleoside diphosphate kinase. This protein is a key enzyme in the control of cellular concentrations of nucleoside triphosphates. Moreover, it has been shown to play important roles in various cellular functions such as differentiation and metastasis. In the present study, a second cDNA for nucleoside diphosphate kinase A (Nm23-M1) was isolated from a cDNA library of mouse embryonic stem cells. This clone encodes the same putative 152 aminoacids long protein as an already published cDNA but is longer in both its 5' and 3' untranslated regions. Tissue and cellular distribution of nm23-M1 mRNA was investigated by using Northern blot analysis and in situ hybridization. Nm23-M1 transcripts were found to be widely distributed throughout the mouse central nervous system with prominent expression in several restricted areas. No differences were noticed between the distribution of long and short transcripts. Furthermore, a similar pattern of expression was described in the central nervous system for nm23-M2 mRNA, encoding a second isoform of the nucleoside diphosphate kinase. However, the transcript of this isoform displayed a wider distribution and was expressed in all organs analysed by northern blotting. The possible involvement of nm23-M1 in differentiation of mouse nervous system is further discussed.

Human interleukin for DA cells or leukemia inhibitory factor is released by Vero cells in human embryo coculture.

In the light of the newly discovered implications of human interleukin for DA cells and leukemia inhibitory factor in embryology, we searched for the presence of this soluble cytokine in the supernatant of Vero cell coculture systems. Using a bioassay as well as a specific ELISA, we demonstrated that Vero cells are able to release large quantities of human interleukin for DA cells and leukemia inhibitory factor in the embryo-growing medium of such cocultures.

Adenylate energy charge: a possible trophic index for management of oyster intensive aquaculture.

1. O. edulis and C. gigas both exhibit a seasonal variation in AEC with minimum values in summer. Two factors, food and temperature, were examined to explain these low summer values. 2. The AEC level varied with food level but a seasonal pattern was still observed. Two age groups of oysters were tested, giving a similar response. 3. The effect of temperature on the seasonal variations in AEC was confirmed by a significant correlation between AEC and temperature. This relationship allows us to calculate an AEC standard that only retains the trophic information. 4. Different trophic levels were identified in Marennes-Oléron Bay with AEC standard but growth rate was not related to them. So, AEC may inform on the carrying capacity of a given area but does not predict growth performances which will depend on other parameters.

Breast cancer-associated pS2 protein: synthesis and secretion by normal stomach mucosa.

The human pS2 gene is specifically expressed under estrogen transcriptional control in a subclass of estrogen receptor-containing human breast cancer cells. The pS2 gene encodes an 84-amino acid protein that is secreted after signal peptide cleavage. The distribution of pS2 protein in normal human tissues was studied with antibodies to pS2; pS2 was specifically expressed and secreted by mucosa cells of the normal stomach antrum and body of both female and male individuals. Moreover, no estrogen receptor could be detected in these cells, indicating that pS2 gene expression is estrogen-independent in the stomach. The function of the pS2 protein in the gastrointestinal tract is unknown. However, the pS2 protein is similar in sequence to a porcine pancreatic protein that has been shown to inhibit gastrointestinal motility and gastric secretion.

Evidence of androgen and estrogen receptors in the preen gland of male ducks.

Androgen receptors have been found in duck preen glands by using dextran-coated charcoal adsorption. They bound DHT with high affinity (KD = 0.2 nM), limited capacity (45 fmoles/mgP) and good specificity. They sedimented at 8 S in a sucrose gradient and were destroyed by pronase digestion and heating. An estrogen receptor having different binding specificity was also demonstrated. On the basis of a marked annual cycle of gonadal activity in ducks, this system appears appropriate for studying the regulation of sex steroid hormone receptors.