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Biomedical subjects

C Landry

Publications and source records attributed to C Landry.

33 records · Page 2Linked to original sources

Mutations of the beta2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides.

Mutations have been identified in the beta2-microglobulin gene of tumor cells of two metastatic melanoma patients who received immunizations with MAGE peptides. One mutation abolishes the start codon whereas the other introduces a premature stop codon. The second beta2-microglobulin allele of both tumors appears to be lost on the basis of sequence data and loss of microsatellite heterozygosity. The lack of beta2-microglobulin gene product results in the absence of HLA class I antigens on the surface of the tumor cells. This may explain why the tumors of both patients progressed despite the immunization treatment and shows the necessity of analyzing in depth the antigen presentation capability of the tumor cells for the interpretation of clinical trials involving anti-tumor vaccination.

Antigens, Neoplasm↗

[Morphometric characteristics of the scoliotic spine].

GOAL: Results from a morphometric investigation performed on a rare complete scoliotic specimen are presented. The aim of the study is to describe the vertebral body wedging. MATERIALS: The specimen used in the study presented a thoracic curve of 150 degrees Cobb angle with the apex at T8. The measures were made using 3D-computer graphics models. The wedging in the frontal and sagittal planes as well as the 3D wedging were measured. The height variation of the vertebral bodies was also measured. RESULTS: The wedging measures show that it increases progressively with the vertebral level to reach a maximum of 27 degrees at the apex. Perdriolle has found a linear relation between the vertebral body wedging and the Cobb angle. The relation predicts a wedging of 24 degrees for 150 degrees of Cobb angle. An inflection point was identified on the vertebral end plate on the convex side. These inflection points were described by Perdriolle as being on the concave side of the vertebra. CONCLUSION: Our measures follow the relation between the Cobb angle and the wedging of the vertebral body, even for very large Cobb angles. Furthermore, inflection points on the vertebral body were identified on the convex side as opposed to the concave side in the literature. This leads us to believe that the vertebral body wedging progressively affects the vertebral endplates.

Adult↗

HNF-6 is expressed in endoderm derivatives and nervous system of the mouse embryo and participates to the cross-regulatory network of liver-enriched transcription factors.

Hepatocyte nuclear factor-6 (HNF-6) is a liver-enriched transcription factor that contains a single cut domain and a novel type of homeodomain. Here we have studied the developmental expression pattern of HNF-6 in the mouse. In situ hybridization experiments showed that HNF-6 mRNA is detected in the liver at embryonic day (E) 9, at the onset of liver differentiation. HNF-6 mRNA disappeared transiently from the liver between E12.5 and E15. In transfection experiments HNF-6 stimulated the expression of HNF-4 and of HNF-3 beta, two transcription factors known to be involved in liver development and differentiation. HNF-6 was detected in the pancreas from E10.5 onward, where it was restricted to the exocrine cells. HNF-6 was also detected in the developing nervous system. Both the brain and the spinal cord started to express HNF-6 at E9-9.5 in postmitotic neuroblasts. Later on, HNF-6 was restricted to brain nuclei, to the retina, to the ventral horn of the spinal cord, and to dorsal root ganglia. Our observations that HNF-6 contributes to the control of the expression of transcription factors and is expressed at early stages of liver, pancreas, and neuronal differentiation suggest that HNF-6 regulates several developmental programs.

Animals↗

[Computer graphic analysis of the three dimensional deformities of scoliotic vertebrae].

GOAL: A computer graphics method that permits the reconstruction, visualization and measure of the vertebral deformities of the scoliotic spine is presented. MATERIALS: Medical imaging techniques utilizing computerized tomography is at the foundation of the reconstruction technique. The studied morphometric parameters are: 1) vertebral body wedging, 2) transverse and spinous process orientation and dimensions and 3) bilateral variation of pedicular dimensions. RESULTS: The reconstructed specimen showed the usefulness of this technique for visualizing and measuring vertebral deformities. Preliminary results seem to be in agreement with the literature concerning the deformities of scoliotic vertebrae. CONCLUSION: This tool will be useful in morphometric investigations for the evaluation of the deformations of scoliotic vertebrae.

Computer Graphics↗

Could oral erythromycin optimize high energy continuous enteral nutrition?

BACKGROUND: Intravenous erythromycin has previously been reported to stimulate gastric emptying, to inhibit gastric acid secretion and to stimulate pancreatic secretion during continuous gastric infusion of a liquid diet in healthy volunteers. AIM: The aim of this study was to evaluate the effects of oral erythromycin (160 mg/h) on gastrointestinal function under these conditions in seven healthy subjects. METHOD: This randomized double-blind cross-over study measured the gastric emptying rate of nutrients, gastric acid secretion, gastric pH, jejunal flow rate as well as biliopancreatic secretion and duodeno-caecal transit time during a 19.9 kJ/min continuous infusion of a nutrient solution (4.18 kJ/mL) in the antrum over a 6-h period by a perfusion method. RESULTS: The nutrition was well tolerated except by one subject with placebo perfusion. During the 6-period, total gastric volume and gastric volume of nutrient decreased during erythromycin administration by 22 +/- 8 and 22 +/- 6%, respectively. Gastric acid secretion was not modified by erythromycin. Lipase and bile salt outputs were significantly higher with erythromycin. The duodeno-caecal transit time was not statistically different with drug and placebo (169 +/- 15 and 146 +/- 19 min, respectively). CONCLUSION: During continuous gastric infusion of a liquid diet, the effect of oral erythromycin on gastric emptying could be useful to optimize cyclic enteral nutrition or to enhance the tolerance of enteral nutrition.

Administration, Oral↗

Managed care fundamentals: implications for health care organizations and health care professionals.

Managed care is changing our health care delivery system as radically as the computer chip has changed telecommunications. Health care professionals and organizations that do not understand managed care's implications will not be prepared for the future. For example, one implication of managed care is payment capitation, which is the transfer of financial risk from the insurer to the provider. As a result, health care providers, including occupational therapy professionals, need to be better managers of scarce resources by recognizing the cost implications among various alternative procedures while still delivering quality care. Under managed care with capitation, occupational therapists will need to learn to provide services within the parameters of a fixed budget, requiring reengineering of the therapies and processes of care and a considerable reduction in the procedures and modalities for any given treatment or therapy. As a result, patients will be required to do more for themselves, and occupational therapists will have to become better patient educators and motivators. Additionally, managed care will require changes in professional curriculums, emphasis through continuing education, and assimilation of better cost information to practitioners to facilitate decision making. Implications of managed care other than payment capitation are assigning to enrollees a gatekeeper who is responsible for limiting access to costly specialty services, practicing utilization review to audit usage patterns and provide constructive recommendations to reduce costs and improve service quality, and forming networks and associations among medical providers for developing economies of scale and providing an integrated continuum of health care services to enrollees.

Capitation Fee↗

Conditionally immortalized oligodendrocyte cell lines migrate to different brain regions and elaborate 'myelin-like' membranes after transplantation into neonatal shiverer mouse brains.

Five immortalized oligodendrocyte cell lines, representing a spectrum of different stages of oligodendrocyte maturation, were transplanted into neonatal shiverer mouse brains and examined for their ability to survive, multiply, and migrate in vivo. Each of the cell lines migrated to different regions of the brain with remarkable consistency when injected into the mouse forebrain, suggesting that the cells might be responding to different environmental cues present in the neonatal mouse brain. These results are consistent with the fact that cells at different stages in the oligodendrocyte lineage probably possess different sets of surface molecules and receptors. Significant differences were also observed in the survival and proliferation of the lines examined, even when the lines tested had quite similar in vitro phenotypes. Interestingly, the cell line with the most mature in vitro phenotype, N20.1, appeared to elaborate membranous processes when transplanted into the brain, reminiscent of oligodendrocytes ensheathing axonal segments. The experiments suggest that these immortalized cells could be useful models to study the cellular and molecular mechanisms involved in the development, maturation and possibly formation of myelin by oligodendrocytes in the mammalian brain.

Animals↗

Effects of erythromycin on gastric emptying, duodeno-caecal transit time, gastric and biliopancreatic secretion during continuous gastric infusion of a liquid diet in healthy volunteers.

OBJECTIVE: Erythromycin, a macrolide antibiotic, has been reported to increase gastric emptying. The aim of this study was to evaluate the effects of intravenous erythromycin (150 mg/h) on gastric emptying, small intestinal transit time, gastric and biliopancreatic secretions during gastric infusion of a liquid diet in healthy volunteers. DESIGN: A randomized double-blind crossover study (erythromycin versus placebo). METHODS: Gastric emptying rates of nutrients, gastric acid secretion, gastric pH, jejunal flow rates, as well as biliopancreatic secretions and duodeno-caecal transit time, were evaluated during a continuous infusion at 4.5 kcal/min of a nutrient solution (1 kcal/ml) in the antrum, over a 6 h period, by a perfusion method. RESULTS: During the 6 h period, total gastric volume and gastric acid secretion decreased during erythromycin administration of 37 and 22%, respectively (area under the curves). Lipase outputs were significantly higher with erythromycin than placebo. Bile salt output was not significantly different between erythromycin and placebo. Duodeno-caecal transit time increased significantly during erythromycin infusion compared with placebo (191 +/- 12 versus 159 +/- 17 min; P < 0.05). CONCLUSION: During continuous gastric infusion of a liquid diet, intravenous erythromycin has a powerful effect on gastrointestinal function. The motor and secretory effects may enhance the tolerance and the efficiency of enteral nutrition in humans.

Adult↗

Comparative analysis of neutral endopeptidase (NEP) and villin gene expression during mouse embryogenesis and enterocyte maturation.

Neutral endopeptidase (Endopeptidase 24.11; NEP; neprilysin), an integral membrane protein, and villin, a major microvillar cytoskeletal actin-binding protein, are both typically associated with brush border epithelia. In this study, cRNA probes were hybridized in situ to investigate the expression of NEP and villin genes in embryo and adult mouse enterocytes. During development, villin mRNAs were easily detected in the immature digestive tract well before establishment of the brush border. In 17-day-old embryos, a transient elevation of villin mRNA occurred just prior to a dramatic increase in microvilli length and density. NEP only appeared by day 17 as the embryonic gut began to become functional. It therefore appears that the onset of transcription of specialized cytoskeletal proteins from the brush border preceded that of intrinsic membrane-bound enzyme from microvilli. In the adult intestinal fold, both mRNAs were expressed along the whole length of the villus with maximal expression at its base. In contrast, both proteins were uniformly expressed along the whole crypt-villus axis. Quantitative analysis revealed an asymmetric intracellular distribution of both mRNAs that were differentially polarized in the apical cytoplasm of enterocytes.

Age Factors↗

Characterization of neutral endopeptidase 24.11 in dog glomeruli.

Neutral endopeptidase (NEP; also known as neprilysin and enkephalinase; EC 3.4.24.11) is a cell-surface metallopeptidase that is present in many mammalian tissues. It is particularly abundant on the brush-border membranes of the kidney proximal tubule. In this paper, the presence of NEP in purified glomeruli from dog kidney was assessed by measuring phosphoramidon- and thiorphan-sensitive [D-Ala2,Leu5]enkephalin-degrading activity. Using this assay, the Km and kcat. of the glomerular enzyme were found to be identical to those of the tubular enzyme. By Western blotting the apparent M(r) of the glomerular enzyme was found to be 104,000, compared with 94,000 for the tubular enzyme. This might be due to a different glycosylation pattern, since endoglycosidase F treatment of NEP obtained from both tissues yielded deglycosylated enzymes with similar electrophoretic mobilities. The glomerular enzyme also appears to be membrane-bound, since it was retained in the detergent-rich phase after phase separation with Triton X-114. Autoradiography experiments performed with RB104, a new highly selective and potent NEP inhibitor, showed that NEP was expressed in both glomeruli and proximal tubules. The presence in glomeruli of NEP and some other brush-border peptidases (dipeptidyl-dipeptidase IV, aminopeptidase N and angiotensin I-converting enzyme) suggests that cell-surface peptidases might play an important role as regulators of plasma-derived peptides in this part of the nephron.

Animals↗

Differential expression of neuropeptide gene mRNA within the LUQ cells of Aplysia californica.

Two neuropeptide precursor cDNAs (LUQ-1 and L5-67) have been recently isolated from the Left Upper Quadrant (LUQ) neurons of the abdominal ganglion of Aplysia californica (Shyamala, Fisher, and Scheller, 1986; Wickham and DesGroseillers, 1991). Using in situ hybridization techniques as well as dot blot and polymerase chain reaction (PCR) assays, we have studied the expression of these genes in the central nervous system (CNS) of Aplysia californica. The LUQ-1 gene was found to be expressed in neuron L5 in the abdominal ganglion, whereas the expression of the L5-67 gene was observed in the other four LUQ cells (L2-4 and L6). When in situ hybridization was performed on paraffin sections of the abdominal ganglion, clusters of smaller cells located in the left hemiganglion, were also found to express either the LUQ-1 or the L5-67 gene, never both. In many sections, the mRNAs coding for the two neuropeptides were found not only in cell bodies but also in the axon of individual LUQ neurons and even as far as the pericardial nerve. The presence of neuropeptide mRNA in axons, pericardial nerve, and kidney has been confirmed by polymerase chain reaction. A specific, although diffuse hybridization in the left upper quadrant also suggests that mRNA is present in the neuritic field. Taken together these results indicate that neuron L5 is the only giant neuron expressing the LUQ-1 gene and might therefore have a physiological function different from the other four LUQ cells. Neuropeptide mRNAs were also found in the axon and/or the neuritic field of giant neurons and could play important roles related to cell signalling in axons and nerve termini.

Animals↗

Cell-specific expression of high levels of human S100 beta in transgenic mouse brain is dependent on gene dosage.

The beta-subunit of S100 protein (S100 beta) is highly conserved in the mammalian brain. The gene coding for human S100 beta has been mapped to chromosome 21. In order to study the consequences of overexpression of the S100 beta gene, transgenic mice were generated by microinjection of a 17.3 kilobase human genomic fragment containing the three exons and the transcription control elements of the human S100 beta gene. Mice from four transgenic lines carried approximately 10-100 transgene copies. Northern blotting demonstrated a tissue-specific and gene dose-dependent expression of human S100 beta mRNA in mouse brain. Increased expression of S100 beta mRNA was correlated with an increased production of S100 beta protein. Examination of brain sections by in situ hybridization and immunocytochemistry indicated that S100 beta was localized globally to astrocytes, as well as to discrete neurons in the mesencephalic and motor trigeminal, facial, and lemniscus nuclei in both normal and transgenic mice. In peripheral tissues, human S100 beta was expressed at 10-50-fold lower levels than in brain. The strict gene dosage dependence and cell specificity of transgene expression suggest the presence of a locus control region (LCR) in the human S100 beta gene. The mice tolerated 10-100-fold higher than normal levels of S100 beta gene expression in brain without any gross physical or behavioral abnormalities. The high-level expression and cell specificity of the S100 beta promoter/LCR suggest that it may provide a valuable tool to direct the expression of other transgenic products to specific cell types in the CNS.

Animals↗

Reduction in S100 protein beta subunit mRNA in C6 rat glioma cells following treatment with anti-microtubular drugs.

S100 protein is a calcium-binding protein found in vertebrate nervous tissue. Synthesis of S100 protein in the rat glioma cell line, C6, is inhibited by the addition of anti-microtubular drugs. We have cloned a cDNA for the beta subunit of S100 protein from rat brain in a lambda gt 11 expression vector and used this cDNA to measure the amounts of S100 beta subunit mRNA in C6 cells after treatment with anti-microtubular drugs. Levels of alpha-tubulin and beta-actin mRNAs were also measured. All measurements were performed using RNA-RNA hybridization techniques at high stringency with rat mRNA-specific probes. After 24 h of treatment, the S100 beta subunit mRNA was reduced to levels of 25% by colchicine and 32% by vinblastine when compared to untreated controls. In contrast, the levels of tubulin and actin mRNAs were only slightly changed by these treatments. These studies demonstrate that disruption of the microtubular cytoskeleton causes a specific reduction in the level of S100 protein mRNA in C6 cells.

Amino Acid Sequence↗