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V Poirier

Publications and source records attributed to V Poirier.

36 records · Page 2Linked to original sources

Expression of the N-myc oncogene in Wilms' tumour and related tissues.

Tissue samples and cell cultures from Wilms' tumour matched histologically normal kidney samples and EBV transformed B cells from the same patients, were analysed to detect changes in the structure and expression of the N-myc oncogene. The levels of expression of HLA class I and hypoxanthine guanine phosphoribosyl transferase were also measured in the various RNA preparations. Related tissue samples, from sources including congenital mesoblastic nephroma, paediatric neuroblastoma and a number of foetal tissues were also tested. Northern blot analysis indicated that the levels of N-myc were higher in Wilms' tumour tissues (with no parallel increase in gene copy number) compared to all other sources of material including foetal kidney. Particularly high levels of expression were observed in a number of the Wilms' tumours, several of which produced metastases. In situ hybridization, using [35S]-labelled RNA probes, confirmed that the high levels of N-myc RNA were present in the blastemal elements in the Wilms' tumour. All the tissue cultures, and tissue samples from other sources, except foetal brain and neuroblastoma, contained uniformly low levels of N-myc RNA.

Child↗

NAD and the synthesis of (ADP-ribose)n in a human cell strain (46BR) hypersensitive to the lethal effects of 3-aminobenzamide.

The cell strain 46BR, derived from an immunodeficient individual, is hypersensitive to the lethal effects of DNA-damaging agents, and of 3-aminobenzamide (3AB), the latter being an inhibitor of the enzyme ADP-ribosyltransferase (ADPRT). This hypersensitivity is not found with the noninhibitory analogue, 3-aminobenzoate. The NAD content of 46BR cells is similar to that of fibroblasts from normal human donors, as is the decrease in NAD content following treatment with dimethylsulphate. Both the activity of ADP-ribosyltransferase and its inhibition by 3AB in permeabilized cells are similar in 46BR and in normal cell strains. High concentrations of 3AB interfere with purine metabolism in cultured cells. Again this effect is similar in 46BR and normal cells. Thus there is no apparent anomaly either in the activity of ADPRT or in the gross effects of 3AB in 46BR. The sensitivity to 3AB may be caused by a defect in a specific acceptor for the ADP-ribose synthesized by ADPRT, or in some as yet undiscovered action of the inhibitor.

Adenosine Diphosphate Ribose↗

An appraisal of blood trauma and blood-prosthetic interface during left ventricular bypass in the calf and humans.

Mechanical circulatory support was accomplished in 20 calves (mean, 140 days) and in 5 patients following operation for acquired heart disease (range, 1 hour to 8 days) employing a pneumatically actuated xenograft-valved assist pump interposed between the left ventricular apex and aorta. Following pump implantation in calves, hematocrit and platelets decreased transiently and returned to normal within 14 days. Plasma hemoglobin and erythrocyte mechanical fragility values were elevated for 48 hours. Platelet survival was slightly reduced, but erythrocyte survival values were similar to controls. In patients who received assist pumps, plasma hemoglobin and erythrocyte mechanical fragility were transiently elevated, but rapidly decreased to normal. Thrombocytopenia occurred only in the presence of bleeding and renal failure requiring hemodialysis. Pump flow of the left ventricular assist device was maintained above 2.0 L/min/m2 despite serious arrhythmias. Postmortem examination revealed no evidence of thromboemboli in the clinical patients although anticoagulant agents were not administered.

Adult↗

Advances in electrical assist devices.

Marked improvements were realized in the development of electrically driven left ventricular assist systems. A volume reduction of 46%, a system weight reduction of 63%, and a factor of 2 improvement in overall efficiency (29%) were realized. The system, operating at a pressure of 120 mm Hg with a flow rate of approximately 7 L, requires only 7.5 W of input power. In addition, a unique brushless commutator was designed to replace standard brushes, thus increasing system life. A new polyurethane was synthesized for utilization in the TMS. This material has demonstrated high flex life in addition to being biocompatible. Further improvements in system weight and size, as well as efficiency, will be realized when flat plate pumps are mated to electric drivers.

Animals↗

Selection of materials for ventricular assist pump development and fabrication.

A study was undertaken to select 2 of the most promising bladder materials from a list of 8 carefully chosen polymers. The polymers chosen for testing included a wide spectrum of urethanes, as well as a polyester resin and a millable polyolefin rubber. The following materials were studied: Adiprene LW-500, Avcothane 51, Biomer, Hexsyn, Hytrel 4055, Mobay 240313, Pellethane 2103-80 AE, and Tecoflex HR. The selection process was based on a test matrix which was divided into segmented steps, each a logical sequel from its predecessor, and each of increasing technical complexity. Hydrolytic stability, flexure endurance, fabricability, tissue compatibility, hemocompatibility and chronic tissue compatibility were evaluated, forming the basis for the acceptance/rejection criteria. As a result of this search, 2 biomaterials were identified as most suitable for use in conventionally flocked bladders; Biomer and Tecoflex HR. Both Biomer and Tecoflex HR bladders have demonstrated impressive results in circulatory analog loop endurance tests, with Tecoflex bladders surpassing 50 million flexes to date, and Biomer bladders (the longest running bladders) exceeding 150 million flexes. Tests are continuing.

Alkenes↗

Relief of congenital obstruction to left ventricular outflow with a ventricular-arotic prosthesis.

Hypoplasia of the aortic valve annulus and ascending aorta is a rare form of congenital aortic stenosis, with a poor prognosis. Replacement of the aortic valve and ascending aorta with a suitable prosthesis is feasible, but the hypoplastic valve annulus must also be enlarged if an adult-sized aortic valve is to be placed in the subcornary position. In an effort to develop a new method of surgical treatment for this congenital abnormality, we fabricated a prosthesis which can be interposed between the left ventricular apex and descending thoracic aorta. This prosthesis is coupled to a 25 mm. Dacron graft and xenograft valve and is lined with flocked Dacron fibrils to encourage formation of a stable biologic lining and prevent thrombus buildup. The prosthesis was implanted in a 22 year old male patient of the Children's Hospital Medical Center without difficulty. Postoperative cardiac catheterization idicated that all of the contrast material was ejected from the left ventricle through the prosthesis. The patient was discharged from the hospital taking sodium warfarin and remains entirely asymptomatic.

Adult↗

A new method for temporary left ventricular bypass. Preclinical appraisal.

Surgical patients who cannot be weaned from cardiopulmonary bypass during operation or who develop balloon-dependent left ventricular failure postoperatively are now considered unsavable. However, in those with potentially reversible ventricular dysfunction, recovery might be possible if an improved means of temporary circulatory support were available. Towards this end, a pneumatically actuated, left ventricular assist pump was developed and evaluated in 20 consecutive calf experiments. The device, containing a flexible polyurethane pumping chamber, was positioned on the chest wall and connected to the left ventricular apex and descending thoracic aorta by two Dacron valved conduits (xenograft valves). All animals survived a 14 to 30 day pumping interval, and 7 underwent successful removal of the device by division of the Dacron conduits below skin level. As a prelude to human investigation, pumps were implanted during a series of routine autopsies through midline sternotomy incison. The device was positioned on the right anterolateral chest wall, with two valved conduits traversing the mediastinum to connect the pump to the left ventricular apex and ascending aorta.

Animals↗

Chromosomal aberrations induced by ethylene oxide in a human amniotic cell line in vitro.

Ethylene oxide was found to be a potent inducer of chromatid-type aberrations in a human amniotic cell line. This induction was dose-dependent. At doses corresponding to about 9% survival, the number of chromatid exchanges was increased about 20 times, and the number of induced breaks increased 50 times, above that observed in the controls.

Amnion↗

Molecular and cellular biology of Wilms' tumour.

Wilms' tumour is an embryonal kidney tumour which exists in an hereditary and sporadic form. Apart from its obvious importance as a model for renal development and differentiation, the tumour has recently been exploited as an example of the action of tumour suppressor genes (or anti-oncogenes). The latter genes are characterised by a somatic loss of genetic information in tumour development, specifically from the short arm of human chromosome 11 in Wilms' tumour. To further study the developmental aspects of the tumour we have established in vitro cell cultures from tumour tissues, which, unlike the majority of Wilms' tumour cell lines, have been genotyped according to their chromosome 11 gene status and their antigen expression patterns, compared to the original normal kidney and tumour tissues. The cell cultures exist both as primary and secondary cultures, and their limited life span in culture has been extended by transfection of SV40 large T antigen. The mechanism of tumour suppression by the Wilms' locus has been explored by producing cell hybrids between the immortalised kidney cells, and an "indicator cell" (HeLa), whose chromosome 11 genotypes have been monitored in vivo and in vitro by restriction fragment length polymorphisms. Non-random patterns of inheritance of the mutant allele have also been investigated, both in tumour tissue and in syndromes, like the Beckwith-Wiedemann Syndrome, which pre-dispose to development of Wilms' tumour (and other embryonal tumours). It is also apparent that allele-specific methylation occurs in Wilms' tumour tissues, probably resulting in changes of gene expression patterns. Significant elevation of transcription of the N-myc oncogene was detected in the blastemal cells of the most malignant Wilms' tumours, whereas a marked decrease in the expression of HLA class I, at both RNA and protein levels was observed in the same cells. Wilm's tumour provides a clear illustration of the requirement for a combination of dominantly and recessively acting genes, in order to produce a malignant embryonal tumour.

Antigens, Neoplasm↗

Carcinomatous encephalitis (miliary metastases): lack of contrast enhancement.

Carcinomatous encephalitis is a rare form of brain metastasis in which there is diffuse miliary spread of punctate tumor nodules in a perivascular distribution. In this case, these tiny tumor nodules were seen throughout the cortical and basal gangliar gray matter only on T2-weighted images. Contrast-enhanced CT and T1-weighted MR images did not demonstrate these tumor nodules.

Brain↗