Biomedical subjects

S Guerin

Publications and source records attributed to S Guerin.

16 recordsLinked to original sources

PubMed2006

Hydrogen peroxide as an irrigation solution in arthroplasty - a potential contributing factor to the development of aseptic loosening.

The reason for revision of primary total hip arthroplasty is quoted as aseptic loosening in 60.6% of cases between 1979 and 2003 in the Swedish National Hip Arthroplasty Registry. Much research effort has been directed toward enhancing the bone-cement interface of total joint arthroplasties, in an attempt to reduce this complication. Haemostatic agents have been popularized as effective means of retarding the development of potentially harmful debris interposition adjacent to, and blood lamination patterns within, the methylmethacrylate. Such agents include hydrogen peroxide (H(2)O(2)), local freezing saline, saline at room temperature and adrenaline solution. One main concern with the use of hydrogen peroxide is whether it affects the material properties of bone cement such that in the long term it contributes to aseptic loosening. This would have enormous clinical consequences. Preliminary studies indicate that porosity increases and that the tensile strength and yield stresses are reduced by up to a factor of 10 by contaminating samples with increasing concentrations of hydrogen peroxide. We postulate that the current use of hydrogen peroxide as an irrigation solution in arthroplasty contributes to the development of aseptic loosening.

Adhesiveness↗

PubMed2001

Changes in intragastric meal distribution are better predictors of gastric emptying rate in conscious pigs than are meal viscosity or dietary fibre concentration.

The effect of dietary fibre on the gastric emptying rate of solids is controversial. Similarly, the mechanisms by which it modulates food intake are partially unknown. Gastric emptying and proximal v. distal stomach filling were evaluated in triplicate on four conscious pigs using scintigraphic imaging. Each animal received in an isoenergetic manner a concentrate low-fibre diet enriched in starch (S) and two high-fibre diets based on sugar beet pulp (BP) or wheat bran (WB). All meals had the same viscosity before ingestion (100.0-100.5 Pa.s). Viscosity of the gastric contents was measured in four additional animals fitted with a gastric cannula. The gastric emptying rate of BP diet was significantly slower than S and WB diets (t1/2 78.4 (sem 5.68), 62.8 (sem 10.01) and 111.6 (sem 10.82) min for S, WB and BP diets respectively, P<0.05). For BP diet only, rate of distal stomach filling was steady during the first 120 min after the meal whereas that of S and WB diets decreased in an exponential manner. Numerous backflow episodes from the distal into the proximal stomach were observed for BP diet that generated the larger intragastric viscosity (0.26 (sem 0.03), 0.3 (sem 0.02) and 0.52 (sem 0.002) Pa.s for S, WB and BP respectively). In conclusion, viscosity of the meal or the percentage total fibre, unlike viscosity of the gastric contents, are poor predictors for emptying. The reduced emptying rate observed with BP is associated with major changes in intragastric distribution of the meal absent with WB and S diets.

Animal Feed↗

PubMed1999

Cleavage and relocation of the tyrosine kinase P59FYN during Fas-mediated apoptosis in T lymphocytes.

Ligation of Fas with its natural ligand or with anti-Fas antibodies induces an apoptotic program in Fas sensitive cells. We report here the identification of the tyrosine kinase p59Fyn as a substrate for CPP32-like proteinases and more particularly caspase 3 during Fas-mediated apoptosis in Jurkat T cells. Inhibition of CPP32-like proteinases by Ac-Asp-Glu-Val-Asp-aldehyde but not by Ac-Tyr-Val-Ala-Asp-aldehyde prevents CPP32, PARP and p59Fyn cleavage indicating that CPP32 or CPP32-like proteinases are responsible for the cleavage of p59Fyn. Cleavage occurs in the N-terminal domain of p59Fyn between Asp19 and Gly20 and is accompanied by relocation of an active p57Fyn kinase to cytoplasm of Fas-stimulated Jurkat cells as judged by both biochemical and confocal microscopy experiments. Thus, p59Fyn relocation and activity may play an important role during Fas-mediated cell death in human T lymphocytes.

Apoptosis↗

PubMed1998

Synergistic effects of colony-stimulating factor 1 and leukemia inhibitory factor in inducing early myeloid cell differentiation.

Cells of the M1D+ murine myeloid leukemic cell line differentiate into macrophages in response to either leukemia inhibitory factor (LIF) or interleukin 6. Previously, it was shown that LIF treatment of M1D+ cells leads to an increased expression of colony-stimulating factor (CSF) receptor mRNA encoded by c-fms. CSF-1, a macrophage growth factor, induces the survival, growth, and differentiation of mononuclear phagocytes but has not been implicated in the regulation of early myeloid cell differentiation. Here we show that low-dose LIF treatment of M1D+ cells results in CSF-1 secretion and CSF-1 receptor up-regulation. CSF-1, when applied alone, induces some M1D+ adherence and the up-regulation of lysozyme M, a macrophage-specific marker. Finally, we show that when applied together, LIF and CSF-1 act synergistically to induce macrophage morphology, phagocytosis, and the expression of the macrophage-specific markers CD11b/Mac-1 alpha chain, lysozyme M, FcgammaRII, and JE/MCP.1. These results indicate that instead of being part of exclusive pathways, as thought until this work, LIF and CSF-1 can function synergistically to further stimulate the early stages of myeloid differentiation.

Animals↗

PubMed1997

CD10 (endopeptidase 24.11) is a thymic peptide-degrading enzyme possibly involved in the regulation of thymocyte functions.

Human immature thymocytes express significant levels of the CD10 (endopeptidase 24.11) cell surface antigen. We report here that IOB5, an anti-CD10 mAb, as well as the phorbol ester PMA down-regulate CD10 activity at the surface of human thymocytes. The kinetics of CD10 modulation were drastically different for both effectors, indicating different regulatory mechanisms. We also demonstrated that intact human thymocytes hydrolyze thymopentin and that CD10 significantly participates in this process. Finally, we found that thymopentin and to a lesser extent phosphoramidon, a specific endopeptidase 24.11 inhibitor, induced up-regulation of CD4 and CD8 molecules at the thymocyte cell surface. In view of these results, we suggest that down-regulation of endopeptidase 24.11 at the thymocyte cell surface might reduce its activity toward thymic factors possibly involved in the regulation of thymocyte functions.

Antibodies, Monoclonal↗

PubMed1997

Endopeptidase 24.11 (CD10/NEP) is required for phorbol ester-induced growth arrest in Jurkat T cells.

Jurkat T cells express a functional endopeptidase 24.11 that is involved in the regulation of T cell activation. We have analyzed the effect of ectopic CD10 expression in mutant Jurkat cell clones that fail to express CD10 and, unlike wild-type cells, are resistant to the growth-inhibitory effects of the protein kinase C activator, PMA. No differences in the expression of the mRNA encoding the alpha, beta, gamma, delta, epsilon, and zeta isoforms of PKC were found in parental vs. PMA-resistant Jurkat cells, ruling out the possibility that the defect could be accounted for by an altered expression of one of these isoforms. Phorbol ester-induced growth arrest was not due to apoptosis since PMA failed to trigger DNA fragmentation in parental and mutant Jurkat T cells. CD10 mRNA expression and activity were abrogated in four independent PMA-resistant Jurkat T cell clones compared to parental cells, whereas the activities of several other peptidases were unaffected. Transfection of one mutant clone with a functional endopeptidase 24.11 restored in a significant manner PMA-induced growth arrest in all the clones selected and tested, whereas transfection of an inactive form of endopeptidase 24.11 had no effect, demonstrating that the enzymatic activity of CD10 is critical in the mediation of the PMA growth arrest. The data presented here demonstrate that a functional CD10 is required for PMA-induced growth arrest in Jurkat cells and provide further evidence for a role of endopeptidase 24.11 in the regulation of tumor cell proliferation.

Apoptosis↗

PubMed1997

Diabetes during pregnancy does not alter whole body bone mineral content in infants.

A previous study using single photon absorptiometry has reported low bone mineral density of the radius in infants of diabetic mothers. The aim of this study was to assess by dual x-ray absorptiometry the whole body bone mineral content (WbBMC) and the body composition of 40 infants of diabetic mothers at birth (mean gestational age +/- SD, 37.5 +/- 1.3 weeks; mean birth weight +/- SD, 3815 +/- 641 g). WbBMC was not correlated with gestational age, but was well correlated with birth weight (r = 0.73; P = 0.0001) and also with fat mass (r = 0.87; P = 0.0001) and lean mass (r = 0.42; P = 0.008). The z-scores +/- SD adjusted for weight for WbBMC and fat mass were significantly increased (1.3 +/- 0.9 and 2.6 +/- 1.3, respectively (P < 0.0001), but were not significantly influenced either by in utero growth or by the type of the diabetes mellitus of the mother. Bone mineralization and fat mass studied by whole body dual x-ray absorptiometry are increased at birth in these infants compared with reference curves.

Absorptiometry, Photon↗

PubMed1996

Thrombin and trypsin-induced Ca(2+) mobilization in human T cell lines through interaction with different protease-activated receptors.

This study was conducted to determine whether serine proteinases may induce [Ca(2+)]i mobilization in different hematopoietic cell lines and to analyze their mechanisms of action. We show that in addition to thrombin and thrombin receptor agonist peptide (TRP, SFLLRN), trypsin induced [Ca(2+)]i mobilization in a highly thrombin-sensitive Jurkat T cell clone. Thrombin, TRP, and trypsin were found to induce [Ca(2+)]i release in three different Jurkat T cell clones differing in the level of T cell receptor expression. Similar results were obtained with a prothymocytic leukemic cell line, HPB.ALL, although these cells were much more responsive to trypsin than to thrombin and TRP. Other cell types such as THP1, a myelomonocytic cell line, or CEM, a CD4(+) positive leukemic cell line, were unresponsive to thrombin, TRP, and trypsin. The effect of trypsin was mimicked by SLIGRL, a peptide corresponding to the cleaved amino-terminal sequence of the recently characterized murine trypsin-activated receptor (PAR2). At suboptimal concentrations, the effects of SFLLRN and SLIGRL were additive, whereas saturating doses of peptides did not further increase [Ca(2+)]i mobilization in Jurkat T cells, indicating that both peptides were able to mobilize the same pool of calcium. Northern blot analysis of mRNAs from different leukemic cell lines indicated a remarkable correlation between PAR2 expression in different cell lines and SLIGRL or trypsin responses in the same cells. The expression of the "trypsin receptor" was also confirmed by polymerase chain reaction analysis. Moreover, a 24 h treatment of Jurkat cells by an anti-CD3 monoclonal antibody, a condition known to down-regulate thrombin receptor expression, induced loss of thrombin and TRP responses but only partially affected trypsin stimulation of [Ca(2+)]i release. Finally, after a first stimulation with either thrombin or trypsin, Jurkat cells were still able to respond to trypsin or thrombin, respectively, demonstrating that thrombin and trypsin essentially activated their own receptors. Our data provided evidence that 1) the human T leukemic cell line Jurkat and other T cell lines express at least two different functional protease-activated receptors, the thrombin receptor and a highly sensitive trypsin receptor, likely the human counterpart of the murine PAR2, and 2) at variance with the commonly accepted model, trypsin exerts most of its effect in T leukemic cell lines by thrombin receptor-independent mechanisms.

Animals↗

PubMed1994

High levels of functional endopeptidase 24.11 (CD10) activity on human thymocytes: preferential expression on immature subsets.

Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes.

CD3 Complex↗

PubMed1989

Secondary trisomy or mosaic "tetrasomy" 8p.

We report on two patients with mosaic tetrasomy of 8p[46,XY/47,XY,+i(8p)], a previously unreported cytogenetic anomaly. The first patient had a low percentage of tetrasomic (secondary trisomic) cells in lymphocytes and fibroblasts, an only mildly abnormal phenotype, and a rather benign clinical course. The second patient had a considerably larger percentage of tetrasomic cells in lymphocytes and fibroblasts, and had more severe congenital anomalies that led to his death at 8 months. A characteristic phenotype +i(8p) is suggested but not yet established. The manifestations of these two patients resemble those of mosaic trisomy 8 and mosaic trisomy 8p, with rib and vertebral abnormalities, absent corpus callosum, and enlarged cerebral ventricles.

Abnormalities, Multiple↗

PubMed1986

Cloning and characterization of chromosomally encoded cephalosporinase gene of Enterobacter cloacae.

The cephalosporinase gene, cpa, which codes for an inducible class I chromosomal beta-lactamase in Enterobacter cloacae was cloned on a fragment of 6.05 kilobase pairs inserted into plasmid pACYC184 and transferred into Escherichia coli HB101 recipient cells. The constructed hybrid plasmid, designated pGGQ101, carried a genomic fragment which retained its parental inducibility characteristics, although its expression level in transformed E. coli cells fell to 40-65% of its initial level in E. cloacae. The localization of the cpa gene on pGGQ101 plasmid was determined by Bal31 exonuclease deletion mapping and further confirmed by subcloning HindIII-AvaI restriction fragment on pMB9 plasmid vector. Labeling with [35S]methionine of pGGQ101 specified proteins in a minicell system showed that six or seven proteins are encoded by the insert. Two proteins with apparent molecular mass of 42 000 and 39 500 daltons, respectively, most probably represent the premature and mature cephalosporinase forms.

Bacterial Proteins↗

PubMed1985

Expression of class I genes in the major histocompatibility complex: identification of eight distinct mRNAs in DBA/2 mouse liver.

The mouse H-2 multigene family includes the genes coding for the major transplantation antigens and for genes located in the Qa-TIa region. We have studied a collection of class I cDNA clones made from liver mRNA of DBA/2 mice (H-2d haplotype) and found that at least six distinct class I genes are transcribed, including three genes of the Qa-TIa region. Two of these six genes each yield two distinct mRNAs, resulting from alternate splicing. Altogether, liver cells may express at least eight distinct class I polypeptides, of which three might be secreted, while one may be a new presumptive nonpolymorphic surface antigen.

Amino Acid Sequence↗

PubMed1982

Pancreatic and gastrointestinal hormones in chronic pancreatitis.

Pancreatic and gut hormones have been measured in 39 patients with chronic pancreatitis, 16 of whom had severe pancreatic insufficiency. Patients with pancreatic insufficiency had significantly diminished fasting levels and postprandial rises of pancreatic polypeptide which were less than 20% of normal. Patients with chronic pancreatitis, with or without exocrine insufficiency, had two- to threefold higher plasma levels of motilin and enteroglucagon than controls. Plasma levels of insulin, pancreatic glucagon, gastric inhibitory polypeptide and gastrin were similar to normal in these patients. The pattern of response of these hormones to a test breakfast differs markedly from those seen in other gut disease states and may reflect pathophysiological mechanisms.

Adult↗

PubMed1981

Gut hormone responses in the irritable bowel syndrome.

Fasting and postprandial levels of gastrin, insulin, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, enteroglucagon and neurotensin were measured in 42 patients with irritable bowel syndrome (IBS). No overall major abnormalities of secretion of any of these peptides were found, although minor differences from normal of pancreatic polypeptide and neurotensin were observed. It is doubtful whether abnormalities of gut hormone secretion play an important role in the pathophysiology of IBS.

Adult↗

PubMed1978

Gut-hormone profile in coeliac disease.

Patients with coeliac disease have a highly significant reduction in the release of secretin and gastric inhibitory polypeptide from the upper small intestine, but a greatly increased release of enteroglucagon, and also of neurotensin, from the lower part of the small intestine. The release of gastrin and pancreatic polypeptide, from the antrum and pancreas respectively, is, however, normal. Thus the pattern of hormone release reflects the location of the mucosal lesion. The gut-hormone profile may also help to characterise other gastrointestinal diseases.

Adolescent↗

PubMedDate not supplied

Heterogeneity in ampR-ampC gene interaction in Enterobacter cloacae.

The ampR gene and its regulation of AmpC beta-lactamase synthesis were investigated for Enterobacter cloacae 1194E, a wild-type strain producing a group A (pI 8.7) enzyme. Expression of the cloned E. cloacae 1194E ampR-ampC region was examined initially in Escherichia coli HB101. However, transformants showed only constitutive beta-lactamase expression. For study of enzyme expression in a more closely related host, the cloned E. cloacae 1194E ampR-ampC region was transformed into E. cloacae 55, a wild-type strain producing a group B (pI 7.8) enzyme. Results indicated a functional E. cloacae 1194E ampR gene that could not be transcomplemented by E. cloacae 55. A comparative analysis of ampR nucleotide and amino acid-sequence data from E. cloacae 1194E and E. cloacae MHN1 revealed related but divergent genes. Thermal induction studies of AmpC beta-lactamase also indicated a difference between E. cloacae 1194E and E. cloacae 55 in ampR-ampC interaction. Thus, it appears that, in at least some strains of Enterobacter, significant intraspecies divergence of ampR has occurred. This heterogeneity in ampR would not have been detected with beta-lactamase expression studies conducted exclusively in E. coli.

Amino Acid Sequence↗