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Biomedical subjects

S Berthier

Publications and source records attributed to S Berthier.

31 records · Page 2Linked to original sources

[Autoimmunity: a concept to be revisited?].

Autoimmunity is thought to be a defect in immunologic tolerance, resulting in the activation and expansion of self antigen-specific T and B lymphocyte clones and the production of circulating antibodies, and a myriad of cytokines and other inflammatory mediators. This hypothesis, which speculates on an aberrant response of the immune system to normal self antigens has exerced a powerful influence on clinical investigations and therapeutic researches. Although much information has accumulated, the mechanism of autoimmune disease remains poorly understood and little attention has been paid to the hypothesis that autoimmune diseases might be caused by a conventional immunological response against self antigens for which tolerance has never been established. Clinical practice would undoubtedly get a lot out of it, as well as new therapeutic measures.

Autoimmune Diseases↗

Proteolytic potential of human neutrophil membranes.

A synergistic role for proteases in the degradation of extracellular matrix proteins has been proposed. Plasma membrane was isolated from a neutrophil homogenate, on a sucrose gradient, and shown to activate gelatinolysis when purified 92 kDa gelatinase was added to the medium. This stimulatory activity was enhanced by the addition of phorbol 12-myristate 13-acetate (PMA), in a dose-dependent manner, and was partially sensitive to phenylmethylsulfonyl fluoride treatment. The effect was abolished by the addition of 1 M KCl or 0.05% Brij 35 extraction. Both elastase and urinary type plasminogen activator were shown to be involved in the process. Moreover, upon neutrophil stimulation by PMA, 92 kDa gelatinase, as elastase, became associated with the plasma membrane, as shown by a subcellular fractionation experiment. These in vitro observations suggest that human neutrophils may be able, in vivo, to recruit endogenous or exogenous proteinases to mediate proteolysis associated with diapedesis and chemotactism during the inflammation process.

Alkaline Phosphatase↗

A study of metalloproteinases in fifty joint fluid specimens.

OBJECTIVES: To study the activity and concentrations in joint fluid of gelatinases (A or matrix metalloproteinase (MMP)-2 and B or MMP-9), tissue inhibitor of metalloproteinases 1 (TIMP-1), and stromelysin-1 (MMP-3). METHODS: Synovial fluid specimens obtained as part of a diagnostic or therapeutic procedure were studied. Protein levels were determined, cells counted, crystals looked for and microbiological studies done. Gelatinolytic activity was determined quantitatively using computerized zymography. Proteins were identified by electrotransfer and immunorevelation. TIMP-1 and stromelysin-1 were assayed using an ELISA. Results were confronted with laboratory test and clinical findings. RESULTS: Of the 50 specimens studied, 25 were from joints with mechanical disorders and 25 from joints with inflammatory disorders. Activated MMP-2 was found in all the specimens, with no differences between the two groups. MMP-9 was found only in its inactive form. MMP-9, TIMP-1 and MMP-3 were found more often in inflammatory than in mechanical fluids and the levels of MMP-9 and TIMP-1 were correlated with neutrophil counts. In the 16 fluids from rheumatoid arthritis patients, levels of MMP-9 and TIMP-1 were closely correlated with serum C-reactive protein levels. CONCLUSIONS: MMP-9, TIMP-1, and MMP-3 levels show striking differences between inflammatory and mechanical joint fluids.

Adolescent↗

Further characterization of the gelatinase-containing particles of human neutrophils.

In addition to azurophil and specific granules, a third storage compartment is known to exist in the neutrophils. This compartment which consists of morphologically heterogeneous particles is characterized by a high specific activity in gelatinase. A gelatinase enriched fraction was prepared by subcellular fractionation of neutrophil homogenates using rate zonal centrifugation. This fraction was enriched in diamine oxidase. Among the proteins released from the neutrophils upon stimulation by formyl peptides, those belonging to the gelatinase enriched fraction were determined after removal of the proteins from specific and azurophil granules by selective immunoadsorption. Gelatinase was recovered together with tetranectin, beta 2-microglobulin and diamine oxidase in the same fraction. Differences in the kinetics of release of gelatinase and diamine oxidase versus vitamin B-12-binding protein suggest that the proteins belong to distinct subcellular structures.

Amine Oxidase (Copper-Containing)↗

[In vitro effects of the alkalinization of 0.25% bupivacaine and 2% lidocaine].

Recent clinical studies have suggested that alkalinization of local anaesthetic agents may shorten the onset time and lengthen their duration of action. In clinical practice, sodium bicarbonate 1.4 and 4.2% are often added to local anaesthetic agents to obtain these effects. We evaluated pH changes of 4 local anaesthetic solutions commonly used for obstetrical epidural anaesthesia, in order to develop titration curves with sodium bicarbonate 1.4 and 4.2%. Local anaesthetic agents tested included lidocaine 2% and bupivacaine 0.25% with and without epinephrine. Each one was divided in 10 mL aliquots, and supplemented with 25 micrograms of sufentanil (1 mL). The pH measurement were made with a pH-meter P 500 with a combined electrode (TBC 12/HS) in the standard solution and after incremental addition of 0.5 mL of 1.4 or 4.2% sodium bicarbonate. The percentage of the free form of local anaesthetic was calculated for each step, using the Henderson-Hasselbalch equation. Results showed that alkalinization is not beneficial with epinephrine free solutions. Increasing volumes of sodium bicarbonate, buffered the acidic effect of sodium bisulfite present in solutions containing epinephrine, and increased the percentage of the free form of local anaesthetic to the level of epinephrine free solutions. From this pH point upwards, the gain is poor and precipitates are generated. This study suggests that 1 mL of 4.2% sodium bicarbonate for 10 mL of local anaesthetic solution is the best theorical choice for alkalinization of a local anaesthetic associated with epinephrine.

Adult↗

Human neutrophil gelatinase is a collagenase type IV.

Secreted gelatinase from human neutrophils was purified as a 94 kDa polypeptide. Gelatinolytic and type IV collagenolytic activities of the purified protein were measured and compared. Immunoglobulins purified from antisera raised against gelatinase inhibited both the gelatinase and type IV collagenase activities. There was no cross-reaction in the inhibition with type I collagenase while the three metalloproteases were similarly inhibited by recombinant tissue inhibitor of metalloproteases. Purified gelatinase degraded denatured type I and native type IV collagens; there was no proteolysis of native type I collagen.

Collagenases↗

[Cerebral nocardiosis cured by repeated stereotaxic punctures and antibiotic therapy].

We report the case of a 58-year old man who had been on corticosteroid therapy for several months and presented with cerebral nocardiosis. Computerized tomography showed multiple brain abscesses. As the neurological status was getting worse, several stereotactic needle aspirations were performed, resulting in decompression of the brain and permitting bacteriological examination of the pus. Antibiotic therapy based on sensitivity tests was administered, and cure was obtained in the 4th month of treatment.

Anti-Bacterial Agents↗

The European space suit, a design for productivity and crew safety.

In order to fulfill the two major mission objectives, i.e. support planned and unplanned external servicing of the COLUMBUS FFL and support the HERMES vehicle for safety critical operations and emergencies, the European Space Suit System baseline configuration incorporates a number of design features, which shall enhance the productivity and the crew safety of EVA astronauts. The work in EVA is today--and will be for several years--a manual work. Consequently, to improve productivity, the first challenge is to design a suit enclosure which minimizes movement restrictions and crew fatigue. It is covered by the "ergonomic" aspect of the suit design. Furthermore, it is also necessary to help the EVA crewmember in his work, by giving him the right information at the right time. Many solutions exist in this field of Man-Machine Interface, from a very simple system, based on cuff check lists, up to advanced systems, including Head-Up Displays. The design concept for improved productivity encompasses following features: easy donning/doffing thru rear entry, suit ergonomy optimisation, display of operational information in alpha-numerical and graphical form, and voice processing for operations and safety critical information. Concerning crew safety the major design features are: a lower R-factor for emergency EVA operations thru increased suit pressure, zero prebreath conditions for normal operations, visual and voice processing of all safety critical functions, and an autonomous life support system to permit unrestricted operations around HERMES and the CFFL. The paper analyses crew safety and productivity criteria and describes how these features are being built into the design of the European Space Suit System.

Communication↗

[Purification of gelatinase secreted by human polynuclear neutrophils].

Gelatinase was purified from DFP treated human neutrophils which have been stimulated by the chemotactic peptide, N-formyl-methionyl-leucylphenylalanine. The secreted gelatinase was purified in two major steps: a gelatinase enriched fraction was recovered after a specific immunoadsorption of contaminant proteins from cytosol and immunoadsorption of proteins from specific or azurophilic granules; then gelatinase was isolated by affinity chromatography and FPLC gel filtration. Some kinetic properties of the Mr 94,000 purified enzyme were investigated.

Catalysis↗

Simulation by personal workstation for man-machine interface design.

This paper presents a simulation tool which has been developed for Man-Machine interface (MMI) design study, in the context of the European EVA Space Suit System development, under contract of ESA/ESTEC. The main new point is that this simulation is based on a personal workstation, and not on a heavy real-time computer, as in most simulation centres. It will be used in ESTEC to perform low cost simulations of the front part of a manned system, to improve and develop MMI with efficiency.

Computer Simulation↗

Acute dysautonomia secondary to autoimmune diseases: efficacy of intravenous immunoglobulin and correlation with a stimulation of plasma norepinephrine levels.

Acute dysautonomia is a disorder characterized by severe sympathetic and parasympathetic failure with relative preservation of motor and sensory function. The disease is considered to be idiopathic in most cases, but there is now a trend towards considering the disorder as an uncommon variant of Guillain Barré syndrome. We report two cases of acute dysautonomia which did not fulfill the criteria of the idiopathic form. The first case was associated with Sjögren's syndrome and the second with thyroiditis and antiganglioside antibodies which were correlated with the severity of the disease. Intravenous gammaglobulin (IVGG) was effective in both cases, as has been reported for the idiopathic form, and in one case the treatment was associated with an increase in the supine and standing plasma norepinephrine levels, thus substantiating the positive effects of IVGG on the orthostatic blood pressure and heart rate. We conclude that the spectrum of acute dysautonomia is superimposable on that of the inflammatory peripheric neuropathies and should include both the idiopathic form and dysautonomia with autoimmune associated disorders. IVGG are effective and seems to act by increasing plasma norepinephrine levels.

Acute Disease↗

[Focalized matrix proteolysis and inflammation].

The zinc metalloproteinases (MMPs or matrixins) are capable of damaging most of the constituents of the extra-cellular matrix and the basement membrane. The matrix proteolysis is the result of an imbalance both in the turnover of these constituants and in the ratio of the tissue inhibitors of metalloproteinases (TIMPs) versus metalloproteinases. After a brief description of the nature and structure of MMPs and TIMPs, this article reports on recent progress concerning the intra and extra-cellular activation mechanisms of proenzymes (proMMPs) which bring into play a series of proteolytic activations involving different proteinase families. Two points are stressed: 1) the main sites of focalized matrix proteolysis regulation, illustrated in the cellular interaction of inflammation, and 2) the wide phenotypic variety of MMPs and TIMPs.

Amino Acid Sequence↗