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Biomedical subjects

R Masson

Publications and source records attributed to R Masson.

At least 19 recordsLinked to original sources

[Pediatric cases in preclinical emergency medicine: critical aspects in the range of missions covered by ground ambulance and air rescue services].

BACKGROUND: The aim of this study was to demonstrate differences in structure and severity of pediatric emergencies treated by aeromedical (air rescue) or ground ambulances services. Conclusions for the training of emergency physicians are discussed. PATIENTS AND METHODS: In a 3-year study period, a total of 9,274 pediatric emergencies covered by the ADAC air rescue service are compared to 4,344 pediatric patients of ground ambulance services in Saarland. RESULTS: In aeromedical services pediatric emergencies are more frequent (12.9% vs. 6.4%), trauma predominates (59.9% vs. 35.6%) and severe injuries or diseases occur more frequently (30.5% vs. 15.0%). In both groups pediatric emergency cases are concentrated into very few diagnostic groups: more than one third of the cases involving pre-school children is due to convulsions. Respiratory diseases and intoxication are the next most frequent causes and are more common in ground ambulance patients. Head trauma is the most common diagnosis in cases of pediatric trauma, followed by musculoskeletal and thoracoabdominal trauma. All types of severe trauma are more frequent in pediatric patients of the aeromedical services. CONCLUSIONS: Training of emergency physicians should include pediatric life support and specific information about frequent pediatric emergency situations. For emergency physicians in aeromedical services, an intensive training in pediatric trauma life support is also necessary.

Air Ambulances↗

High cancer cell death in syngeneic tumors developed in host mice deficient for the stromelysin-3 matrix metalloproteinase.

Matrix metalloproteinases (MMPs) are extracellular enzymes. Some of them are known to be involved in tumor development and/or progression. Several cellular functions have been proposed for MMPs during malignant processes. Notably, they may be involved in tissue-remodeling processes through their ability to digest matrix components or to participate in tumor neoangiogenesis and, subsequently, in cancer cell proliferation. One of these MMPs, stromelysin-3 (ST3/MMP11), although devoid of enzymatic activity against the matrix components, is associated with human tumor progression and poor patient clinical outcome. Using several in vivo experimental models, it has been demonstrated that ST3 expression by the fibroblastic cells surrounding malignant epithelial cells promotes tumorigenesis in a paracrine manner. The present study was devoted to the identification of the cellular function underlying this ST3-induced tumor promotion using a syngeneic tumorigenesis model in mice. Our results show that ST3 exhibits a new and unexpected role for a MMP, because ST3-increased tumorigenesis does not result from increased neoangiogenesis or cancer cell proliferation but from decreased cancer cell death through apoptosis and necrosis. Thus, during malignancy, the cellular function of ST3 is to favor cancer cell survival in the stromal environment.

Animals↗

pS2/TFF1 interacts directly with the VWFC cysteine-rich domains of mucins.

BACKGROUND & AIMS: Trefoil factors (TFFs) are secreted gastrointestinal proteins that have been shown to protect and promote healing of the gastrointestinal tract. Moreover, pS2/TFF1 is essential for normal differentiation of the gastric mucosa because deficient mice develop antropyloric adenomas. To date, it is unclear how TFFs mediate their functions. METHODS: Using the yeast 2-hybrid system, we attempted to identify murine TFF1 interacting proteins by screening a stomach and duodenum complementary DNA (cDNA) expression library. RESULTS: Four positive clones were isolated. Sequence and expression studies showed that they corresponded to the murine counterpart of human cDNA sequences encoding carboxy-terminal fragments of mMuc2 (489 residues) and mMuc5AC (427, 430, and 894 residues) mucin proteins. Mutagenesis experiments showed that TFF1 interacts with the 2 mucins through binding with their VWFC1 and VWFC2 (von Willebrand factor C) cysteine-rich domains. CONCLUSIONS: These results show that the gastrointestinal protective effect of TFF1, and presumably of the other TFFs, is caused at least partially by their participation, via mucin binding, in the correct organization of the mucous layer that protects the apical side of the mucosa from deleterious luminal agents.

Amino Acid Sequence↗

Identification and characterization of a novel gastric peptide hormone: the motilin-related peptide.

BACKGROUND & AIMS: This study looked for new proteins with expression restricted to the gastric epithelium that may provide insight to the differentiation and function of the gastric unit. METHODS: A novel complementary DNA was isolated and sequenced, and its expression was examined in mouse tissues at both messenger RNA and protein levels. Subcellular localization was studied using immunoelectron microscopy. The posttraductional processing of the protein was analyzed in vitro by protein microsequencing and in vivo by Western blotting. RESULTS: We identified a novel protein that is mainly expressed by the secretory granules of the stomach enteroendocrine cells. This protein has sequence similarity with prepromotilin, the precursor of the motilin hormone and the motilin-associated peptide. As for the prepromotilin, a posttraductional maturation leads to a secreted peptide that is further cleaved at a dibasic site and gives rise to the motilin-related peptide (MTLRP) and MTLRP-associated peptide. CONCLUSIONS: We have identified and characterized a novel gene encoding the preproMTLRP protein. MTLRP presents similarity to motilin and is specifically expressed by enteroendocrine cells of the stomach and therefore represents a novel hormone.

Animals↗

Expression of matrix metalloproteinases during murine chorioallantoic placenta maturation.

A large body of experimental evidence supports the participation of two groups of extracellular proteases, matrix metalloproteinases (MMPs), and plasminogen activators/plasmin, in tissue remodeling in physiological and pathological invasion. In the late mouse placenta, several tissue remodeling and cell invasion processes take place. Spongiotrophoblast migration into maternal decidua, as well as decidual extracellular matrix remodeling require the coordinated action of extracellular proteolytic enzymes. Via Northern and in situ hybridization, we have analyzed the spatio-temporal expression patterns of members of the MMP family (stromelysin-3, gelatinases A and B), as well as their inhibitors TIMP-1, -2 and -3 in late murine placenta (days 10.5 to 18.5 of gestation). Gelatinase activity in placental extracts was assessed by substrate zymography. Gelatinase A and stromelysin-3 were found to be prominently expressed in decidual tissue; shortly after midpregnancy, the decidual expression patterns of gelatinase A and stromelysin-3 became overlapping with each other, as well as with the expression domain of TIMP-2. On the other hand, gelatinase B transcripts were expressed only by trophoblast giant cells at day 10.5, and were downregulated at later stages. TIMP-1 and TIMP-3 transcripts were detected in decidual periphery at day 10.5, while later the expression was restricted to the endometrial stroma and spongiotrophoblasts, respectively. The areas of stromelysin-3 expression were the same (giant trophoblasts) or adjacent (decidua) to those where urokinase (uPA) transcripts were detected, suggesting a possible cooperation between these proteinases in placental remodeling. We generated mice doubly deficient for stromelysin-3 and uPA, and report here that these mice are viable and fertile. Furthermore, these animals do not manifest obvious placental abnormalities, thereby suggesting the existence of compensatory/redundant mechanisms involving other proteolytic enzymes. Our findings document the participation of MMPs and their inhibitors in the process of late murine placenta maturation, and warrant the characterization of other members of the MMP family, like membrane type-MMPs, in this process.

Allantoin↗

In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy.

Stromelysin-3 (ST3; Basset, P., J.P. Bellocq, C. Wolf, I. Stoll, P. Hutin, J.M. Limacher, O.L. Podhajcer, M.P. Chenard, M.C. Rio, P. Chambon. 1990. Nature. 348:699-704) is a matrix metalloproteinase (MMP) expressed in mesenchymal cells located close to epithelial cells, during physiological and pathological tissue remodeling processes. In human carcinomas, high ST3 levels are associated with a poor clinical outcome, suggesting that ST3 plays a role during malignant processes. In this study we report the ST3 gene inactivation by homologous recombination. Although ST3 null mice (ST3-/-) were fertile and did not exhibit obvious alterations in appearance and behavior, the lack of ST3 altered malignant processes. Thus, the suppression of ST3 results in a decreased 7, 12-dimethylbenzanthracene-induced tumorigenesis in ST3-/- mice. Moreover, ST3-/- fibroblasts have lost the capacity to promote implantation of MCF7 human malignant epithelial cells in nude mice (P < 0.008). Finally, we show that this ST3 paracrine function requires extracellular matrix (ECM)-associated growth factors. Altogether, these findings give evidence that ST3 promotes, in a paracrine manner, homing of malignant epithelial cells, a key process for both primary tumors and metastases. Therefore, ST3 represents an appropriate target for specific MMP inhibitor(s) in future therapeutical approaches directed against the stromal compartment of human carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗

Chromosomal assignment and expression pattern of the murine Lasp-1 gene.

The human Lasp-1 (LIM and SH3 protein) gene was previously identified by differential screening of a breast cancer-derived metastatic lymph node cDNA library. It was located on the q12-q21 region of human chromosome 17 and was shown to be amplified and overexpressed in 12% of breast tumors. Lasp-1 defines a new LIM-protein subfamily, as it associates a C-terminal Src homology 3 (SH3) domain to a N-terminal LIM motif. In this study, the isolation and characterization of the cDNA encoding the mouse Lasp-1 protein are described, and it is shown to be highly conserved with its human counterpart. In addition to the LIM and SH3 domains, both human and mouse Lasp-1 contain an actin-binding domain. The mouse gene was mapped by in situ hybridization to the 11C-11D region of chromosome 11. Northern blot analysis shows that this gene is expressed from 7.5 to 17.5 days post-coitum of mouse embryogenesis and in almost all adult tissues.

Adaptor Proteins, Signal Transducing↗

Tumor necrosis factor receptor associated factor 4 (TRAF4) expression pattern during mouse development.

This is the first in situ hybridization analysis of expression of a tumor necrosis factor (TNF) receptor associated factor (TRAF) during development. TRAF4 is observed throughout mouse embryogenesis, most notably during ontogenesis of the central (CNS) and peripheral (PNS) nervous system, and of nervous tissues of sensory organs. TRAF4 is preferentially expressed by post-mitotic undifferentiated neurons. Interestingly, TRAF4 remains expressed in the adult hippocampus and olfactory bulb, known to contain multipotential cells responsible for neoneurogenesis.

Amino Acid Sequence↗

[Extracellular proteases of stromal origin: contribution to tumor progression and therapeutic perspectives].

For a long time, extracellular proteinases were thought to be expressed by the cancerous cells and only able to cleave extracellular matrix components, in order to promote tumor cell invasion. Recent works have now demonstrated that these proteinases are currently synthesized by stromal fibroblastic cells and that some of them may exhibit additive function(s). These findings lead to a new therapeutical concept leading to target the activity of stromal proteinases, and most notably of the matrix metalloproteinases.

Endopeptidases↗

Gastric mucosa abnormalities and tumorigenesis in mice lacking the pS2 trefoil protein.

To determine the function of the pS2 trefoil protein, which is normally expressed in the gastric mucosa, the mouse pS2 (mpS2) gene was inactivated. The antral and pyloric gastric mucosa of mpS2-null mice was dysfunctional and exhibited severe hyperplasia and dysplasia. All homozygous mutant mice developed antropyloric adenoma, and 30 percent developed multifocal intraepithelial or intramucosal carcinomas. The small intestine was characterized by enlarged villi and an abnormal infiltrate of lymphoid cells. These results indicate that mpS2 is essential for normal differentiation of the antral and pyloric gastric mucosa and may function as a gastric-specific tumor suppressor gene.

Adenoma↗

Stromelysin-3 in the biology of the normal and neoplastic mammary gland.

Stromelysin-3 (ST3) is an extracellular proteinase predominantly expressed in fibroblasts. The particular structural features and in vitro functions of this molecule suggest it could be the first member of a new subgroup of the matrix metalloproteinase family. ST3 is transiently expressed during mammary gland post-weaning involution, embryonic implantation, various organogeneses, and during amphibian metamorphosis. Moreover, ST3 is expressed in a panel of human invasive carcinomas including breast, colon, and head and neck carcinomas. Almost all ST3-expressing tissues show intense extracellular matrix remodeling activities including the loss of basement membrane integrity. Thus, either directly, or indirectly in association with other proteinases, ST3 might be involved in tissue remodeling processes occurring in both physiological and pathological processes. In vitro and in vivo studies using malignant cells stably transfected in such a way as to modulate their ST3 expression levels indicate that ST3 modifies neither cell proliferation nor invasive properties, but rather favors tumor cell survival in host tissues. This hypothesis is consistent with clinical data showing that ST3 expression could be predictive of tumor progression leading to metastases.

Animals↗

Embolization of a dural arteriovenous fistula of the ventral cervical spinal canal in a nine-year-old boy.

A 9-year-old patient presented with an acute left hemiparesis secondary to an intradural hemorrhage of the cervical spinal cord. Angiography revealed a dural arteriovenous (AV) fistula with multiple venous aneurysms fed by a radicular branch of the right vertebral artery. This AV fistula did not contribute blood flow to the cervical segment of the spinal cord, which was tested by an intra-arterial injection of methohexital. Interruption of the fistula was possible by transluminal embolization with polyvinyl alcohol and silk. At a 6-month follow-up, the patient was neurologically intact, and angiography demonstrated no AV fistula. This case illustrates an unusual presentation of a dural AV fistula. Dural AV fistulas are rare in the cervical region and extremely unusual in patients less than 20 years of age. The lesion proved to be amenable to transluminal embolization alone, without the need for surgery, with a dramatic resolution of the neurological deficit.

Acute Disease↗

[Encephalic pseudotumoral toxoplasmosis in the course of blood diseases].

The authors report two cases, the first pathological and the second clinical of pseudo-tumoural cerebral toxoplasmosis, occurring during the course of blood diseases. They refer to the conditions of appearance of this rare complication, with only twenty cases recorded in the literature, during malignant blood diseases. They stress the primordial role of immunological deficiency related either to the underlying disease (especially Hodgkin's disease) or to immuno-suppressive therapy. The clinical picture, with little in the way of typical features, is thus that of a diffuse méningo-encéphalitis. Pseudo-tumoural forms are rare. The authors also stress the minimum conditions required for the validity of the dye test and the value of the diagnosis of cerebral toxoplasmosis. An association of sulphadiazine-purimethamine, active and effective, cured the second patient.

Brain↗

Pulmonary function: relation to aging, cigarette habit, and mortality.

The relation of pulmonary function to aging and cigarette habits has been examined cross sectionally and longitudinally in the Framingham cohort. On cross-sectional analysis, women were found to have lower forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV-1) values than men even after adjusting for height. Their FEV-1 percent was, on the other hand, higher than those of men. As the population aged over 10 years, their FVC and FEV-1 declined 9% to 27% depending upon age and sex. The FEV-1 percent, however, showed a decline only in the older age groups. In a cross-sectional analysis, cigarette smoking showed an inverse association to FVC and FEV-1 percent. Longitudinally, cigarette smokers showed a more rapid decline in FVC in 10 years than nonsmokers. On giving up smoking their FVC became more like that of the nonsmokers. A striking relation of FVC to mortality was noted in both sexes, which is not accounted for by associated cigarette habits.

Adult↗

[Study of neurological manifestations of chronic lymphatic leukemia (lymphosis). Role of associated globulin anomalies (apropos of 8 cases)].

The authors emphasize the relative frequency of neurological symptoms in lymphatic leukaemia. Clinically, these cause more or less diffuse encephalitic or multineuritic syndromes, generally a combination of the two. Their pathogenesis is usually connected with lymphoid tissue infiltration into either the meninges or the vascular sheaths of the central nervous system or the sheaths of the roots or of the peripheral nerves. The authors stress the possible function of immunoglobulin abnormalities of the C.S.F. indicative of the presence of the leukaemic process within the nervous system. This pathogenesis prompts the use of therapeutic methods directly attacking leukaemic infiltration of the nervous system (focal cobalt therapy, intrathecal chemotherapy) and the authors have found that these give favourable results.

Aged↗