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Biomedical subjects

B Morin

Publications and source records attributed to B Morin.

At least 19 recordsLinked to original sources

[Results of resection for ductal adenocarcinoma of the pancreatic head].

INTRODUCTION: Pancreaticoduodenectomy (PD) is the only curative treatment for adenocarcinoma of the pancreatic head but is associated with a significant early morbidity and a poor long term survival. Therefore, its value is still debated. The aim of this study was to evaluate early and distant results of PD for pancreatic adenocarcinoma, and to identify prognostic factors. SUMMARY: Seventy-nine patients who underwent PD with curative intent for adenocarcinoma of the pancreatic head from 1982 to 2002 were studied retrospectively. The following data were evaluated: operative mortality, long-term survival, prognostic factors (through univariate and multivariate analysis), and characteristics of 5-year survivors. RESULTS: Mortality rate was 1.3%. Survival at 1, 3 and 5 years was 46%, 26% and 11%. The median survival was 12 months. The prognostic factors were the T stage (T.N.M. classification) and radicality of resection. After multivariate analysis, radicality of resection was the only independent prognostic factor. Five patients survived for more than 5 years. They did not differ of the other patients but none had positive margin or venous invasion. CONCLUSIONS: These results (low mortality, significant distant survival including some long term survivors) suggest that PD for pancreatic adenocarcinoma must be indicated in most low-risk patients. PD remains the only curative treatment allowing prolonged survival.

Adenocarcinoma↗

[Late intestinal fistula following implantation of parietal abdominal prostheses].

STUDY AIM: The aim of this retrospective study was to describe an unusual complication of the nonabsorbable meshes used for repair of incisional hernia or inguinal hernia. PATIENTS AND METHODS: This study included eight observations of intestinal fistulas that occurred between 1 and 13 years after using Mersilène (Dacron) mesh for repair of an incisional hernia (7 cases) and an inguinal hernia (1 case). There were 6 men and 2 women (mean age: 58 years, range: 35-85 years) with an external intestinal fistula (n = 6) or an internal intestinal fistula (n = 2). All the patients required a reoperation for extraction of the mesh and treatment of the bowel injuries. RESULTS: There was one secondary death in a 85 years old woman in relation with a vascular complication after incomplete excision of the prosthesis. In five patients out of six, there was a recurrence of the incisional hernia. CONCLUSION: The intestinal fistulas associated with prosthetic repair of the abdominal wall are mostly observed with intraperitoneal mesh but this factor is not exclusive. Their frequency after repair of incisional or inguinal hernia with non absorbable mesh is estimated between 0.3 and 3.5%. The use of nonabsorbable mesh should be limited to the indications of strict necessity, without any septic context or emergency surgery. The contact of the mesh with the bowel should be formally avoided.

Adult↗

Heterodimerization between the glucocorticoid receptor and the unrelated DNA-binding protein, Xenopus glucocorticoid receptor accessory factor.

The adrenal steroid hormones, glucocorticoids, control many physiological responses to trauma, including elevated synthesis of fibrinogen, a major blood-clotting protein. Glucocorticoid regulation of the gamma-fibrinogen subunit gene in Xenopus laevis is mediated by a binding site for Xenopus glucocorticoid receptor accessory factor (XGRAF) and a contiguous glucocorticoid response element (GRE) half-site. Here, we characterize the protein:DNA complex formed by a cooperative interaction between XGRAF, GR, and the DNA. We demonstrate that the complex contains XGRAF by competition in a gel shift assay. The presence of GR is established by two criteria: 1) size dependence of the XGRAF:GR:DNA complex on the size of the GR component and 2) interference with complex formation by GR antibody. Cooperative binding of XGRAF and GR to the DNA was quantitated, showing that GR favors binding to XGRAF:DNA compared with free DNA by a factor of 30. The cooperative interaction between XGRAF and GR can occur on nicked DNA but is disrupted when 1 bp is inserted between the XGRAF binding site and half-GRE. Significantly, this loss of physical association in vitro correlates with loss of XGRAF amplification of GR activity in transiently transfected primary Xenopus hepatocytes. The simplest explanation for cooperativity between XGRAF and GR is formation of a DNA-bound heterodimer of these two proteins. This mechanism represents a new mode of transcriptional regulation in which GR and a nonreceptor protein form a heterodimer, with both partners contacting their specific DNA sites simultaneously.

Animals↗

The binding site for Xenopus glucocorticoid receptor accessory factor and a single adjacent half-GRE form an independent glucocorticoid response unit.

In Xenopus laevis, transcription of the gamma-fibrinogen subunit gene is activated by glucocorticoids. Hormone induction is regulated by three glucocorticoid response element (GRE) half-sites and an additional DNA sequence which binds a novel hepatocyte nuclear protein, Xenopus glucocorticoid receptor accessory factor (XGRAF). The XGRAF binding site (GAGTTAA) is located directly upstream of the most distal half-GRE. The proximity of the binding sites for XGRAF and the glucocorticoid receptor (GR) led to the hypothesis that these two sites form a glucocorticoid response unit (GRU). By transfecting DNA into primary hepatocytes, we showed that this GRU confers hormone responsiveness in the absence of other half-GREs. The XGRAF binding site enhances function of the half-GRE without itself responding to glucocorticoids. The GRU retains efficacy in other locations relative to the gamma-fibrinogen gene promoter, further increases transcription when present in multiple copies, and activates a heterologous promoter. Despite the contiguity of the XGRAF binding site and half-GRE, the two sites can be occupied simultaneously in vitro. The binding characteristics correlate with function since mutations that disrupt concurrent XGRAF and GR binding also impair transcription. This novel GRU represents a new regulatory mechanism that may be applicable to other glucocorticoid responsive genes that lack a full GRE.

5' Untranslated Regions↗

Adolescent cocaine and injection stress effects on the estrous cycle.

Chronic cocaine exposure during critical periods of development induces short- and long-term effects. During the pubertal period, the hypothalamic-pituitary-gonadal (HPG) axis undergoes many dynamic changes. The present study investigated whether chronic periadolescent cocaine alters reproductive maturity in the rat. Sixty female Long-Evans hooded rats were randomly assigned to one of three conditions (20 mg cocaine/kg/day, saline injected and uninjected), for dosing from postnatal day 21 (P21) through P60. Several indicators of reproductive maturation and functioning were assessed during and following treatment. Cocaine exposure had no effect on the onset of puberty or on the date of first ovulation. The number of proestrus-estrus transitions was significantly lower in cocaine-exposed females compared to uninjected females, but not compared to saline-injected controls. This reduction was observed during exposure to cocaine, as well as after the cessation of injections. During the dosing period, cocaine-exposed rats also exhibited a greater number of cycles that had no clear P-E transition than did UN subjects; this effect disappeared once injections stopped. These alterations suggest immediate, and possibly persisting, alterations in the control of ovulation after chronic cocaine exposure throughout adolescence. Interestingly, during the injection period, the saline-injected females had a significantly greater number of diestrus days compared to uninjected and cocaine-injected animals, as well as a lower proportion of regular 4- and 5-day cycles. These differences disappeared once injections stopped. These results suggest a stress-induced irregularity of the estrous cycle, possibly attenuated by cocaine and recoverable after exposure. The present findings indicate that the HPG axis is susceptible to short-term, and possibly to long-term, alterations induced by cocaine exposure throughout the adolescent period.

Aging↗

[Costal chondroma and chondrosarcoma].

The aim of this study was to report two cases of chondrosarcoma located on the chest wall, in order to emphasize the difficulty encountered by the pathologist to differentiate a chondrosarcoma from a chondroma and the importance, in our opinion, of performing a large resection with wide margins in all cases.

Adolescent↗

Histone H1- and other protein- and amino acid-hydroperoxides can give rise to free radicals which oxidize DNA.

Exposure of amino acids, peptides and proteins to radicals, in the presence of oxygen, gives high yields of hydroperoxides. These materials are readily decomposed by transition metal ions to give further radicals. We hypothesized that hydroperoxide formation on nuclear proteins, and subsequent decomposition of these hydroperoxides to radicals, might result in oxidative damage to associated DNA. We demonstrate here that exposure of histone H1 and model compounds to gamma-radiation in the presence of oxygen gives hydroperoxides in a dose-dependent manner. These hydroperoxides decompose to oxygen- and carbon-centred radicals (detected by electron paramagnetic resonance spectroscopy) on exposure to Cu(+) and other transition metal ions. These hydroperoxide-derived radicals react readily with pyrimidine DNA bases and nucleosides to give adduct species (i.e. protein-DNA base cross-links). Product analysis has demonstrated that radicals from histone H1-hydroperoxides, and other protein and amino acid hydroperoxides, can also oxidize both free 2'-deoxyguanosine and intact calf thymus DNA to give the mutagenic oxidized base 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-hydroxy-2'-deoxyguanosine, 8-oxodG). The yield of 7,8-dihydro-8-oxo-2'-deoxyguanosine is proportional to the initial protein-hydroperoxide concentration, and corresponds (for histone H1-hydroperoxide, 280 microM) to approx. 1. 4% conversion for free 2'-deoxyguanosine (200 microM), and 0.14% for 2'-deoxyguanosine in DNA (70 microgram/ml). Evidence has also been obtained with DNA for reaction at cytosine and thymine, but not adenine; the lack of damage to the latter may result from damage transfer to 2'-deoxyguanosine residues. These studies demonstrate that initial radical-induced damage to nuclear proteins can give rise to subsequent DNA damage; the latter includes both DNA-protein cross-links and formation of oxidized DNA bases.

8-Hydroxy-2'-Deoxyguanosine↗

[Treatment of diaphyseal femoral fractures in children: a clinical study].

UNLABELLED: Many therapeutic modalities have been reported for the management of femoral shaft fractures in children and young adolescents but there is no consensus on the preferable method. PURPOSE: To compare the malunion rate of femoral shaft fractures in children treated either by traction and spica cast or traction and functional brace. MATERIAL AND METHODS: Between 1982 and 1984 a prospective study was carried out in a tertiary pediatric university hospital on 43 patients (24 boys, 19 girls) with a closed femoral shaft fracture. The patient's age ranged from 5 to 13 years old. Open, pathologic, subtrochanteric and physeal fractures were excluded. Fifteen (15) patients were treated by a functional brace and 28 were treated by a spica cast. Clinical and radiological assessments of all patients were performed 5 years or more after the fracture by an independent observer. A malunion occurred if one of these criteria were met: an angulation > or = 10 degrees in the coronal plane, an angulation > or = 15 degrees in the sagittal plane, a malrotation > or = 15 degrees by opposition to the other leg, and a discrepancy > or = 10 mm between femur's length. RESULTS: A malunion was found in 17 patients, 6 in the functional brace and 11 in the spica cast group (p > 0.05). The leg length discrepancy was the most common type of malunion. The length of stay was not significantly different between both treatment groups. The functional brace was worn longer than the spica cast. CONCLUSION: There was no statistical difference between the malunion rate of children treated by traction-spica cast and traction-functional brace. The functional brace appears to be a good alternative for the treatment for femoral shaft fracture in children allowing an earlier ambulation than spica cast.

Adolescent↗

The protein oxidation product 3,4-dihydroxyphenylalanine (DOPA) mediates oxidative DNA damage.

A major product of hydroxy-radical addition to tyrosine is 3, 4-dihydroxyphenylalanine (DOPA) which has reducing properties. Protein-bound DOPA (PB-DOPA) has been shown to be a major component of the stable reducing species formed during protein oxidation under several conditions. The aim of the present work was to investigate whether DOPA, and especially PB-DOPA, can mediate oxidative damage to DNA. We chose to generate PB-DOPA using mushroom tyrosinase, which catalyses the hydroxylation of tyrosine residues in protein. This permitted us to study the reactions of PB-DOPA in the virtual absence of other protein-bound oxidation products. The formation of two oxidation products of DNA, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG) and 5-hydroxy-2'-deoxycytidine (5OHdC), were studied with a novel HPLC using gradient elution and an electrochemical detection method, which allowed the detection of both DNA modifications in a single experiment. We found that exposure of calf thymus DNA to DOPA or PB-DOPA resulted in the formation of 8oxodG and 5OHdC, with the former predominating. The formation of these DNA oxidation products by either DOPA or PB-DOPA depended on the presence of oxygen, and also on the presence and on the concentration of transition metal ions, with copper being more effective than iron. The yields of 8oxodG and 5OHdC increased with DOPA concentration in proteins. Thus PB-DOPA was able to promote further radical-generating events, which then transferred damage to other biomolecules such as DNA.

Basidiomycota↗

3-Hydroxylysine, a potential marker for studying radical-induced protein oxidation.

gamma-Irradiation of several amino acids (Val, Leu, Ile, Lys, Pro, and Glu) in the presence of O2 generates hydroperoxides. We have previously isolated and characterized valine and leucine hydroperoxides, and hydroxides, and have detected these products in both isolated systems [e.g., bovine serum albumin (BSA) and human low-density lipoprotein (LDL)] and diseased human tissues (atherosclerotic plaques and lens cataractous proteins). This work was aimed at investigating oxidized lysine as a sensitive marker for protein oxidation, as such residues are present on protein surfaces, and are therefore likely to be particularly susceptible to oxidation by radicals in bulk solution. HO* attack on lysine in the presence of oxygen, followed by NaBH4 reduction, is shown to give rise to (2S)-3-hydroxylysine [(2S)-2,6-diamino-3-hydroxyhexanoic acid], (2S)-4-hydroxylysine [(2S)-2,6-diamino-4-hydroxyhexanoic acid], (2S, 5R)-5-hydroxylysine [(2S,5R)-2,6-diamino-5-hydroxyhexanoic acid], and (2S,5S)-5-hydroxylysine [(2S,5S)-2,6-diamino-5-hydroxyhexanoic acid]. 5-Hydroxylysines are natural products formed by lysyl oxidase and are therefore not good markers of radical-mediated oxidation. The other hydroxylysines are however useful markers, with HPLC analysis of 9-fluorenylmethyl chloroformate (FMOC) derivatives providing a sensitive and accurate method for quantitative measurement. Hydroxylysines have been detected in the hydrolysates of peptides (Gly-Lys-Gly and Lys-Val-Ile-Leu-Phe) and proteins (BSA and histone H1) exposed to HO./O2, and subsequently treated with NaBH4. Quantification of the hydroxylysines yields, and comparison with hydroxyvalines and hydroxyleucines, supports the hypothesis that surface residues give higher yields of oxidized products than the hydrophobic leucines and valines, at least with globular proteins such as BSA. Hydroxylysines, and particularly 3-hydroxylysine, may therefore be sensitive and useful markers of radical-mediated protein oxidation in biological systems.

Amino Acids↗

Characterization of Nuclear Polyhedrosis Viruses from Three Subspecies of Lambdina fiscellaria

The eastern hemlock looper (EHL), Lambdina fiscellaria fiscellaria, the western hemlock looper (WHL), L. fiscellaria lugubrosa, and the western oak looper (WOL), L. fiscellaria somniaria, are closely related insects that are pests in Canadian forests. We have used restriction endonuclease (REN) and Southern blot analyses to characterize DNA of nuclear polyhedrosis viruses (NPVs) isolated from each of the three subspecies of L. fiscellaria. REN analysis of EHL-NPV, WHL-NPV, and WOL-NPV DNAs revealed that they have nonidentical REN-banding patterns. NPV DNA extracted from WOL larvae collected from Douglas fir trees had a different REN pattern than NPV DNA extracted from WOL larvae collected from Garry oak trees. Hybridization of radiolabeled EHL-NPV genomic DNA revealed that the EHL- and WHL-NPVs share considerable DNA sequence similarity, as radiolabeled EHL-NPV DNA hybridized strongly with all WHL-NPV DNA bands. The EHL-NPV polyhedrin gene hybridized strongly with WHL-NPV DNA, but the hybridization patterns of the two NPVs were different. Very weak hybridization was detected between the EHL-NPV polyhedrin gene and DNAs of the two WOL-NPVs. Nucleotide sequence analysis revealed that the polyhedrin genes of EHL-NPV and WHL-NPV differ in sequence by only eight nucleotide substitutions (five third position and three second position changes, resulting in four amino acid substitutions). Phlyogeneitc analysis using the polyhedrin genes of EHL-NPV and WHL-NPV indicate that these two viruses cluster with the Group II NPVs as described by Zanotto, Kessing, and Maruniak (1993, J. Invertebr. Pathol. 62, 147).

Journal Article↗

A nuclear polyhedrosis virus from the obliquebanded leafroller, Choristoneura rosaceana (Harris) (Lepidoptera:Tortricidae).

A nuclear polyhedrosis virus (CrMNPV) has been isolated from larvae of the obliquebanded leafroller Choristoneura rosaceana (Harris) collected near St. Quentin in northwest New Brunswick, Canada. Restriction endonuclease digestion-gel electrophoresis of this virus, using a number of different endonucleases and whole CrMNPV genome Southern hybridization, have shown it to be different but similar to the equivalent virus from the spruce budworm Choristoneura fumiferana (Clem.) (CfMNPV). The polyhedrin gene of CrMNPV has been isolated, cloned, and sequenced and shown to have a predicted amino acid sequence only two amino acids different from the CfMNPV polyhedrin. In bioassays against spruce budworm larvae, CrMNPV had little pathogenicity to that host.

Amino Acid Sequence↗

Insecticidal activity of a recombinant baculovirus containing an antisense c-myc fragment.

Attempts to develop baculovirus-based insecticides by insertion of genes encoding enzyme inhibitors, neuropeptides or toxins have met with some success. However, it is often difficult to ensure correct processing or secretion of the encoded peptides. Here we tested a simpler strategy by insertion of an antisense fragment of a host gene to block translation of a protein essential for larval growth and development. We selected the c-myc gene for two main reasons: (i) its protein is known to be well conserved in evolution and to have multiple essential functions during development; and (ii) c-myc family genes have yet to be characterized in insects, thus blockage of essential genes by anti-sense transcripts from a strong virus promoter could provide a sensitive test for the existence of myc-like gene products. An appropriate fragment of the human c-myc gene was inserted downstream from the polyhedrin promoter of Autographa californica nucleopolyhedrovirus and tested in bioassays on Spodoptera frugiperda larvae. Western blot analysis with a human c-myc antibody revealed an endogenous protein band which bound specifically to these antibodies. This band disappeared more rapidly from cells infected with the antisense c-myc recombinant virus than from those infected with c-myc-negative virus. Results of bioassays showed that the antisense construct stopped feeding as soon as the polyhedrin promoter-driven transcripts accumulated, followed shortly by death of the larvae. These results suggest that c-myc-like protein(s) exist in insects and that the antisense strategy is an effective approach to virus insecticide productions.

Animals↗

Management of fibular hemimelia: amputation or limb lengthening.

We reviewed retrospectively 22 patients (23 limb segments) with fibular hemimelia treated by amputation or limb lengthening to evaluate these methods of treatment. There were 12 boys and 10 girls, all with associated anomalies in the lower limbs. Twelve patients (13 limb segments) had early amputation and prosthetic fitting and ten had tibial lengthening using the Ilizarov technique. At the latest follow-up, the twelve patients who had amputation were functioning well and had few complications. The ten patients who had lengthening had suffered numerous complications, and all had needed either further corrective surgery or to wear braces or shoe-raises. Two of the ten lengthened limbs required late amputation for poor function or cosmesis. There were fewer hospital admissions, clinic visits, and periods of absence from school in the amputation group. Our findings suggest that amputation is a more effective method of management than limb-lengthening in severe fibular hemimelia. The Ilizarov method is an attractive alternative for selected patients, but its exact role is not yet established. One problem is that families often have unrealistic expectations of the surgical and prosthetic technology available and may refuse amputation when this has been recommended.

Amputation, Surgical↗

Learning through simulation: the next dimension in quality improvement.

Simulation modeling offers several distinct gains in learning opportunities beyond traditional quality improvement tools. A simulation model captures complex, multivariate system components and replicates system operation in compressed time. The visual aspect enables workers to "see" the effect of proposed changes and thus eliminates much of the fear of failure typically associated with change. Most important, simulation permits design of a total solution, addressing interactions of all system components.

Alabama↗

Effects of UV and visible radiation on DNA-final base damage.

Several mechanisms are likely to be involved in the solar radiation-mediated modifications of cellular DNA. Direct excitation of DNA bases by the UVB component (290-320 nm) of solar light gives rise, mostly through oxygen independent reactions, to the formation of dimeric pyrimidine lesions including cyclobutadipyrimidines, pyrimidine (6-4) pyrimidone photoproducts and related valence Dewar isomers. In addition, photoexcitation of cytosine and guanine may lead to the formation in relatively minor yields of 6-hydroxy-5,6-dihydrocytosine and 8-oxo-7,8-dihydroguanine, respectively. A second mechanism that requires the participation of endogenous photosensitizers together with oxygen is at the origin of most of the DNA damage generated by the UVA (320-400 nm) and visible light. Singlet oxygen, which arises from a type II mechanism, is likely to be mostly involved in the formation of 8-oxo-7,8-dihydroguanine that was observed within both isolated and cellular DNA. However, it may be expected that the latter oxidized purine lesion together with DNA strand breaks and pyrimidine base oxidation products are also generated with a lower efficiency through Fenton type reactions. A more definitive assessment of these mechanisms would require further studies aimed at the identification and quantification of the different DNA photolesions including both dimeric pyrimidine photoproducts and photooxidized lesions.

Animals↗

A common pathway for p10 and calyx proteins in progressive stages of polyhedron envelope assembly in AcMNPV-infected Spodoptera frugiperda larvae.

The assembly of the polyhedron envelope in baculovirus-infected cells has been the subject of several studies, yet it is still poorly understood. We have used immunogold-labelled antibodies to two baculovirus proteins, p10 and calyx (also referred to as polyhedron envelope protein or PEP), to follow envelope assembly in AcMNPV-infected tissues of Spodoptera frugiperda larvae. We show that, in wild type virus, both proteins colocalize in fibrillar structures and associated electron-dense spacers which progress to encircle the polyhedra, as well as in completed polyhedron envelopes. In cells infected with polyhedrin-negative (PH-) viruses, an unusual proliferation of these spacers was observed suggesting a deregulatory event in the envelope assembly process. Results of Northern and Western blot analysis revealed that synthesis of P10 and calyx mRNA and proteins in PH- AcMNPV is unaffected as compared to wild type virus. Taken together, the observed physical and compositional connection between fibrillar structures, spacers and polyhedron envelopes, as well as the abnormal appearance of the spacers in PH- mutants, provide further evidence in support of a cooperative role of these structures in the assembly of the polyhedron envelope.

Animals↗