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Biomedical subjects

J Peetermans

Publications and source records attributed to J Peetermans.

At least 19 recordsLinked to original sources

T wave alternans as a predictor of recurrent ventricular tachyarrhythmias in ICD recipients: prospective comparison with conventional risk markers.

INTRODUCTION: The current standard for arrhythmic risk stratification is electrophysiologic (EP) testing, which, due to its invasive nature, is limited to patients already known to be at high risk. A number of noninvasive tests, such as determination of left ventricular ejection fraction (LVEF) or heart rate variability, have been evaluated as additional risk stratifiers. Microvolt T wave alternans (TWA) is a promising new risk marker. Prospective evaluation of noninvasive risk markers in low- or moderate-risk populations requires studies involving very large numbers of patients, and in such studies, documentation of the occurrence of ventricular tachyarrhythmias is difficult. In the present study, we identified a high-risk population, recipients of an implantable cardioverter defibrillator (ICD), and prospectively compared microvolt TWA with invasive EP testing and other risk markers with respect to their ability to predict recurrence of ventricular tachyarrhythmias as documented by ICD electrograms. METHODS AND RESULTS: Ninety-five patients with a history of ventricular tachyarrhythmias undergoing implantation of an ICD underwent EP testing, assessment of TWA, as well as determination of LVEF, baroreflex sensitivity, signal-averaged ECG, analysis of 24-hour Holter monitoring, and QT dispersion from the 12-lead surface ECG. The endpoint of the study was first appropriate ICD therapy for electrogram-documented ventricular fibrillation or tachycardia during follow-up. Kaplan-Meier survival analysis revealed that TWA (P < 0.006) and LVEF (P < 0.04) were the only significant univariate risk stratifiers. EP testing was not statistically significant (P < 0.2). Multivariate Cox regression analysis revealed that TWA was the only statistically significant independent risk factor. CONCLUSIONS: Measurement of microvolt TWA compared favorably with both invasive EP testing and other currently used noninvasive risk assessment methods in predicting recurrence of ventricular tachyarrhythmias in ICD recipients. This study suggests that TWA might also be a powerful tool for risk stratification in low- or moderate-risk patients, and needs to be prospectively evaluated in such populations.

Adult↗

Characterization of a phosphoprotein whose mRNA is regulated by the mitogenic pathways in dog thyroid cells.

We have isolated cDNA clones encoding the dog and human forms of a novel protein whose function is still unknown. Sequence analysis indicates that dog clone c5fw protein contains 343 amino acid residues. several potential phosphorylation sites. and two of the 12 conserved subdomains (VIII and IX) that fold into a common catalytic core structure of the large family of protein kinases. Human clone c5fw shares 95% amino acid identity with its dog counterpart. We have also isolated another human-related clone c5fw sharing 70% amino acid identity with the dog sequence. We transiently expressed c-myc epitope-tagged clone c5fw protein in COS-7 cells and infected thyrocytes in primary culture with a recombinant adenovirus containing clone c5fw cDNA (adenovirus c5fw). In both experiments, a 46-kDa protein was detected and subsequently more extensively characterized. By two-dimensional gel electrophoresis and V8 protease digestion, we showed that this overexpressed protein is phosphorylated on different sites. Moreover, cells stimulated with thyrotropin or epidermal growth factor, thyrotropin and fetal calf serum increased the level of clone c5fw protein produced after infection by adenovirus containing clone c5fw. The disappearance of this 46-kDa protein after 1 h of puromycin treatment indicates that it is a labile protein. Immunofluorescence and subcellular fractionation analysis have revealed that c-myc-tagged clone c5fw was insoluble and localized mainly in the cytoplasm, in the form of granules.

Adenoviridae↗

Factors affecting the stability of viral vaccines.

The stability of viral vaccines is determined by the rate of loss of "integrity" of the viral antigen during storage. For live vaccines, such as measles, mumps, rubella, canine distemper, stability is equivalent to the preservation of the infectious titres. For inactivated and subunit vaccines, the preservation of the antigenic structure and the correct steric presentation of the relevant epitopes are the parameters which determine their stability. In general, the following factors may have a negative effect on stability: temperature, pH outside the physiological limits, organic solvents, repeated freezing and thawing, some antiseptics and inactivating agents, and light. However their negative effect is in most cases specific for the individual viruses. Approaches to stabilisation of most vaccines are based on the elimination or neutralisation of the negative factors. Practical examples for the most relevant existing vaccines are described.

Antigens, Viral↗

Cacogeusia in amyloidosis associated with plasma cell dyscrasia.

Cacogeusia, being the patients' main complaint, is reported as a new symptom of amyloidosis, probably caused by a peripheral sensory neuropathy. A case is presented of a patient with weight loss, dysphagia, macroglossia and taste disturbances, due to amyloidosis associated with a plasma cell dyscrasia. The importance of oral manifestations in amyloidosis is discussed.

Aged↗

Production, quality control and characterization of an inactivated hepatitis A vaccine.

The isolation and adaptation of hepatitis A virus to cell culture opened the way to the development of vaccines. Based on experience with inactivated poliovaccines, a similar approach was chosen for the development of an inactivated hepatitis A vaccine. Strain HM175, adapted to MRC-5 human diploid cells, was used as the virus strain. Vaccine production starts with growth and multiplication of the seed virus in MRC-5 cells. The harvests are clarified, purified and concentrated. Inactivation by formaldehyde is carried out on a pool of purified harvests. Close control of all process parameters results in consistent production of completely inactivated and highly immunogenic vaccine lots. Quality control testing is based on the general requirements for biologicals of WHO and National Control Authorities. Tests have been developed and validated to show the purity of the cell substrate used for each production cycle, the quality of the virus harvest, the adequacy of the purification and inactivation processes, and the conformity to stringent specifications for purity, safety and potency of the final bulk vaccine filled in final containers. The vaccine is characterized by adequate identity tests, by its reaction with polyclonal and monoclonal antibodies, by its immunogenicity in laboratory animals and by the detailed study of the immune response in primates and human volunteers. The final result of the development of adequate production and testing methods, confirmed by extensive characterization studies, is the availability of a consistent, safe and potent hepatitis A vaccine.

Cell Line↗

Tympano-ossicular allografts following J. Marquet: the evaluation of a school.

The experience with 1.645 transplantation procedures by ENT surgeons, trained in tympano-ossicular allograft technique following J. Marquet, is reported. The grafts originated from different tissue banks. The anatomical and functional results one year postoperatively were analysed. There appeared to be no statistical differences between tissue banks, nor between surgeons. Contrary to the anatomical results, functional differences existed between allograft tympanoplasties and some types of allograft tympano-ossiculoplasties. It was concluded that the routine use of allograft tympano-ossiculoplasty offers a major tool in otological surgery and that it is the method of choice by the ENT surgeons trained by the School of J. Marquet.

Belgium↗

Viscoelasticity of F-actin and F-actin/gelsolin complexes.

Actin is the major protein of eukaryote peripheral cytoplasm where its mechanical effects could determine cell shape and motility. The mechanical properties of purified F-actin, whether it is a viscoelastic fluid or an elastic solid, have been a subject of controversy. Mainstream polymer theory predicts that filaments as long as those found in purified F-actin are so interpenetrated as to appear immobile in measurements over a reasonable time with available instrumentation and that the fluidity of F-actin could only be manifest if the filaments were shortened. We show that the static and dynamic elastic moduli below a critical degree of shear strain are much higher than previously reported, consistent with extreme interpenetration, but that higher strain or treatment with very low concentrations of the F-actin severing protein gelsolin greatly diminish the moduli and cause F-actin to exhibit rheologic behavior expected for independent semidilute rods, and defined by the dimensions of the filaments, including shear rate independent viscosity below a critical shear rate. The findings show that shortening of actin filaments sufficiently to permit reasonable measurements brings out their viscoelastic fluid properties. Since gelsolin shortens F-actin, it is likely that the effect of high strain is also to fragment a population of long actin filaments. We confirmed recent findings that the viscosity of F-actin is inversely proportional to the shear rate, consistent with an indeterminate fluid, but found that gelsolin abolishes this unusual shear rate dependence, indicating that it results from filament disruption during the viscosity measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

Structure and mobility of actin filaments as measured by quasielastic light scattering, viscometry, and electron microscopy.

Actin filaments of different lengths were prepared by polymerizing actin in the presence of various concentrations of gelsolin, a protein which accelerates actin polymerization by stabilizing nuclei from which filaments grow and which binds to their fast growing ends. The lengths of the actin filaments following polymerization were measured by electron microscopy and showed that the number-average filament length agreed with the predicted length if each gelsolin molecule acted as a seed for the growth of an actin filament. The distribution of lengths was independent of the actin:gelsolin ratio and was similar to that of actin filaments polymerized in the absence of gelsolin (Lw/Ln = 1.8). The mobility of these filaments in solution was studied by quasielastic light scattering and by viscometry. The translational diffusion constant determined by quasielastic light scattering was in agreement with the infinite dilution values calculated from the dimensions and the distribution of lengths determined by electron microscopy for relatively short filament lengths. Under conditions where overlap of the rotational domains of the filaments would be expected to occur, the measured diffusion rates deviated from their predicted dilute solution values and the solution viscosity increased abruptly. The dependence of the diffusion constant and the solution viscosity on the length of the actin filaments can be explained in terms of a theory that describes the restraints on diffusion of independent rigid rods in semi-dilute solution. The results suggest that the rheology of actin filaments can be accounted for by steric restraints. The length of cytoplasmic actin filaments in some cell types is such that these steric constraints are significant and could produce large changes in physical properties with small changes in filament length.

Actins↗

Light-scattering study of depolymerization kinetics of sickle hemoglobin polymers inside single erythrocytes.

The time course of intracellular depolymerization of hemoglobin S aggregates is directly observed by using microscope laser light-scattering spectroscopy in single sickle erythrocytes upon slow reoxygenation. From the correlation functions of the light intensity scattered from a single cell, we determine the average diffusion coefficient as well as the fraction of hemoglobin aggregates that have intracellular mobility. The oxygen saturation of the hemoglobin of the same cell is measured by single-cell absorption spectrophotometry. Combining the results obtained with these techniques and information on the cellular morphology, we propose a model for the depolymerization process of hemoglobin inside single erythrocytes as they transform from the fully sickled to the normal biconcave shape upon reoxygenation.

Anemia, Sickle Cell↗

Effect of simultaneous administration of live measles vaccine on the "take rate" of live mumps vaccine.

During the course of clinical studies to develop a new bivalent measles-mumps vaccine, it was established that simultaneous administration of live measles and mumps vaccines at doses contained in the monovalent vaccines resulted in a reduced seroconversion rate against mumps but not against measles. This one-way interference was resolved by increasing the dose of the mumps component in the bivalent measles-mumps and the trivalent measles-mumps-rubella vaccines above that in the monovalent mumps vaccine. On the other hand, it was not necessary to adjust the doses of the measles and rubella components in the combined vaccines. This observation requires that not only the titres of vaccine viruses must be carefully adjusted in combined live mumps vaccines but also that the heat-stability of each component in such vaccines be carefully determined to ensure that interference is not a problem during the complete shelf-life of the product. The relative doses at release of combined mumps vaccines using the Urabe Am 9 strain and the heat-stability characteristics of these products will be presented and discussed.

Antibodies, Viral↗

Microscope laser light scattering spectroscopy of single biological cells.

A microscope laser light scattering setup was developed, allowing us to do intensity autocorrelation spectroscopy on the light scattered from a volume as small as (2 micron)3. This non-invasive technique makes cytoplasmic studies possible inside single live biological cells. The effect of osmotic swelling and shrinking on the diffusion coefficient of hemoglobin inside intact red blood cells is shown as an illustrative example of the applicability and sensitivity of this new experimental method.

Erythrocyte Membrane↗

Production and quality control of the Oka-strain live varicella vaccine.

The Smith Kline-RIT live attenuated Oka-strain varicella vaccine (Varilrix) is manufactured following the seed lot principle, with each vaccine lot derived from the same working seed. Production of the vaccine basically consists in the multiplication of the working seed under standardized, well-defined conditions guaranteeing consistency of the vaccine lots. Quality control tests, determining the vaccine's purity, safety, potency, and efficacy, are carried out at each defined stage of the production process.

Chickenpox Vaccine↗

Direct observation of delta-crystallin accumulation by laser light-scattering spectroscopy in the chicken embryo lens.

By using the technique of laser light-scattering spectroscopy, direct observation has been made on the intracellular accumulation of a crystallin protein within the cells of chicken embryo lens during the process of development. Appearance of delta-crystallin has been detected as early as day 4, and its concentration reaches a plateau at day 19. The measurements constitute a noninvasive determination of accumulation of protein molecules that specifically characterize the process of cell differentiation.

Animals↗