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PubMed1985

Systemic response to local urate crystal induced inflammation in man: a possible model to study the acute phase response.

The production of a systemic inflammatory response to intradermal monosodium urate crystal injection is described. A transient, self-limiting local response is associated with a systemic response detectable by a rise in the white cell count and serum amyloid A protein. The white cell change parallels the evolution of the local response, whereas the serum amyloid A response lags behind the local lesion, peaking after the local lesion is resolving. Intradermal monosodium urate injection is proposed as a possible inflammatory stimulus to explore the acute phase protein response in different disease states.

Acute Disease↗

PubMed1993

Correlation of interleukin-2 and soluble interleukin-2 receptor with clinical activity of multiple sclerosis.

Concentrations of interleukin-2 (IL-2) and soluble IL-2 receptor (sIL-2R) in serum and CSF samples were measured in 63 patients with multiple sclerosis (MS) to evaluate their usefulness as markers of disease activity. CSF concentrations of IL-2 and sIL-2R were significantly higher in MS relapse compared with MS patients in remission or with control subjects. These concentrations correlated with the clinical score by which disease severity was assessed, with the number of relapses per year, and with the total disease duration. Furthermore, there was evidence of intrathecal release of IL-2 and sIL-2R in clinically active MS. The results extend the notion that an activated cellular immune state parallels the evolution of the pathological process in MS and suggest that measurement of IL-2 and sIL-2R concentrations may provide an objective marker of disease activity in patients with MS.

Adult↗

PubMed2004

Intravascular stents in the last and the next 10 years.

The first balloon-expandable coronary stent was approved "for the prevention of restenosis" in 1994, the same year that the Journal of Endovascular Therapy was inaugurated. Since then, the development of the stent has paralleled the evolution of endovascular intervention as a new specialty. Innovators have pushed to explore new and varied stent applications outside the coronary arteries. Carotid stenting, transjugular intrahepatic portocaval shunts, and covered stents are a few of these new applications that have now become commonplace. Dozens of stent designs and several new materials have been tested to solve the problem of in-stent restenosis, but it is the drug-eluting stent (DES) that has emerged as the most promising, at least in the coronary arteries. However, the benefits of DES technology are not likely to be effective in the more pervasive forms of in-stent restenosis, such as encountered in the femoropopliteal segment. In the future, technologies aimed at stimulating rather than inhibiting tissue response to an implant may be part of the next wave of developments, as we take aim against the poor and/or slow tissue incorporation that manifests as leaks and dislodgement. In the superficial femoral artery, for example, mechanical stresses that cause fractures and dislocations may be addressed by using a very flexible endovascular device with a tissue-friendly inner surface that promotes rapid stent endothelialization to counter the biological effects of motion and microtrauma. The rapidly developing fields of nanotechnology, microelectronics, and advanced materials technology will enable the surface engineer to design molecular-specific surfaces for a new generation of vascular devices. Interactive implantable or injectable microdevices aimed at providing specific information upon demand from an external source will revolutionize disease prevention, as emphasis shifts toward monitoring cardiovascular risk exposure. There is no doubt that during the next 10 years, we will witness impressive technological progress in the field of cardiovascular implantable devices.

Femoral Artery↗

PubMed1981

Antibody-induced degradation of acetylcholine receptor in myasthenia gravis: clinical correlates and pathogenetic significance.

Sera of myasthenic patients containing anti-AChR antibodies increase the rate of degradation of mammalian AChR. This phenomenon, antigenic modulation (AMd), was tested on AChR of rat myotubes in serum from 48 myasthenic patients. Sixty-six percent of the sera increased AChR degradation. AMd activity was higher in more severely affected patients, paralleled clinical evolution in individual patients, and was related to AChR-antibody titer. Steroid treatment and thymectomy did not affect AMd activity. Patients who had a thymoma always had greater AMd activity.

Adolescent↗

PubMed2004

Expression systems for the production of recombinant pharmaceuticals.

The new generation of biological products are largely the result of genetic engineering. The qualitative and quantitative demand for recombinant proteins is steadily increasing. Molecular biologists are constantly challenged by the need to improve and optimise the existing expression systems, and also develop novel approaches to face the demands of producing the complex proteins of tomorrow. This continuous evolution is paralleled by growing concerns about the safety of these novel pharmaceuticals, with health authorities setting high standards for certification. One of the strategies used by researchers in this field involves sourcing new genetic elements for incorporation into expression systems by systematically analysing the rich natural diversity of microorganisms and plant-based expression systems. There are, in addition, numerous tools for modifying microorganisms and for re-engineering existing biological pathways or processes to meet the needs of the pharmaceutical industry. The aim of this review is to present the conventional and alternative expression systems, focusing on prokaryotic expression systems and briefly exploring other complementary recombinant protein production systems and their unique features.

Animals↗

PubMed2004

Harvey W. Cushing and cerebrovascular surgery: Part I, Aneurysms.

The development of surgical techniques for the treatment of intracranial aneurysms has paralleled the evolution of the specialty of neurological surgery. During the Cushing era, intracranial aneurysms were considered inoperable and only ligation of the carotid artery was performed. Cushing understood the limitations of this approach and advised the need for a more thorough understanding of aneurysm pathology before further consideration could be given to the surgical treatment of cerebral aneurysms. Despite his focus on brain tumors, Cushing's contributions to the discipline of neurovascular surgery are of great importance. With the assistance of Sir Charles Symonds, Cushing described the syndrome of subarachnoid hemorrhage. He considered inserting muscle strips into cerebral aneurysms to promote aneurysm sac thrombosis and designed the "silver clip," which was modified by McKenzie and later used by Dandy to clip the first intracranial aneurysm. Cushing was the first surgeon to wrap aneurysms in muscle fragments to prevent recurrent hemorrhage. He established the foundation on which pioneers such as Norman Dott and Walter Dandy launched the modern era of neurovascular surgery.

Adult↗

PubMed1991

Neurobiorheology. A new branch of biorheology. Historical background and current ideas.

The application of principles of biorheology, hemorheology and perihemorheology on problems of the nervous system in health and disease was suggested by Alfred L. Copley (1982, 1987). Late in 1988 Copley and Sourander considered neurobiorheology to be an appropriate term for a new branch of biorheology bridging the gap between biorheology and neurobiology. Neurobiorheology can be defined as a research field concerned with deformation behaviour of matter including flow and transportation in context with the structure and function of the nervous system at macroscopic, cellular, subcellular and molecular levels. It may be considered a basic life science with important clinical applications. Its "raison d'être" should be to apply various ways of thinking, calculations and techniques used in biorheology to treat and if possible to solve neurobiological problems. Many regionally different chemical, structural and functional properties characterize the developing and adult nervous system and those parts of the circulatory system ("vessel-blood organ") which penetrate the nervous system at all levels. Considering the close metabolic and functional relations between neurons and surrounding non-neuronal ectodermal cells, neuroglial and Schwann cells deriving from common precursor cells in the wall of the neural tube and neural crest respectively, the term neuroectodermal organ appears suitable. The almost parallel ontogenetic evolution of vessel-blood organ and neuroectodermal organ and their interaction during the entire individual life cycle constitutes a challenging stimulus for integrated research. The main purpose of this review is to give some examples of importance concerning still insufficiently elucidated neurobiological problems suitable for biorheological approaches. Particular attention will be paid to the microenvironment at central and peripheral levels of the neuroectodermal organ.

Animals↗

PubMedDate not supplied

Three years of "CASMS": the world's busiest medical simulation centre.

Medical simulation is a relatively new teaching modality suitable for medical education at all levels, although its long-term benefits have not yet been validated. Simulation allows the participant to practise diagnosis, medical management and behavioural approaches in the care of acutely ill patients in a controlled environment. Simulators have achieved widespread acceptance in the fields of anaesthesia, intensive care and emergency medicine. More recently, team training for pre-hospital and within-hospital multidisciplinary medical response teams has become popular. The increasing number and diversity of courses at "CASMS" parallels the evolution of simulation centres into regional clinical skills centres elsewhere. Such centres are likely to become a cost-effective means of achieving greater consistency in medical skill acquisition and may improve patient outcomes after medical crises.

Anesthesiology↗

PubMedDate not supplied

Neutralizing influenza antibodies, IgA and total protein in the nasopharyngeal secretions of subjects vaccinated by nasal route with the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology.

Intranasal administration of two doses of the inactivated influenza vaccine prepared in the "Stefan S. Nicolau" Institute of Virology was followed by rises in the level of neutralizing secretory influenza antibodies in 82% of the cases. The concomitant study of secretory antibody, IgA and total protein levels, as well as of the serum HAI influenza antibodies demonstrated that their evolution was parallel only in 23% of the vaccinees. The percentage of secretory antibody conversion was similar to the rate of protection conferred by the vaccine.

Administration, Intranasal↗

PubMed2002

[Contemporary university: a betrayed tradition?].

The current evolution of University is examined in parallel with the evolution of society. Society of uncertainty, crisis of the social actor, selective mechanisms of the elite, fundamental role of technical predominance and of economical processes are analyzed based on the "tradition" concept. The possibility of an authoritative comeback of the role of University is found in an active and articulated intervention of integration and cultural mediation, substantiating the bridge of tradition.

Cultural Characteristics↗

PubMed1992

Failla Memorial Lecture. From beans to genes--back to the future.

Developments in radiation biology have inevitably paralleled the evolution of systems and end points in the wider field of biology. I review the development of three areas that have interested me during the 35 years that I have been involved with radiation research. (1) The dose-rate effect. My first graduate student, Joel Bedford, and I demonstrated the dependence of mammalian cell killing on the dose rate at which gamma rays are delivered. These studies led to the recent development of pulsed low-dose-rate brachytherapy and the design of a new machine for clinical use. (2) Hypoxic radiosensitizers and bioreductive drugs. The hypothesis that the presence of foci of hypoxic cells in human tumors could limit their curability by gamma rays led to the development of nitromidazales that preferentially sensitize hypoxic cells. Our contributions included the observation that misonidazole was also cytotoxic to hypoxic cells, that sensitization was increased by prolonged preincubation, and that the mechanism involved depletion of thiols. More recently we have collaborated with Ged Adams and Bob Sutherland in the development of a new generation of hypoxic cell cytotoxins. In particular, we have been concerned with the assessment of oncogenicity in relation to drug structure. (3) Oncogenic transformation in vitro. The use of in vitro assays for oncogenic transformation has represented a major interest for this laboratory largely due to collaborations first with Carmia Borek, and more recently with Richard Miller and Tom Hei. We published the first dose-response curves for gamma rays, and more recently for a range of neutron energies and for charged particles of defined LET. Radiation-induced oncogenic transformation in C3H 10T1/2 cells has been shown to be due to a dominant acting transforming gene, which has been isolated and is in the process of being characterized and sequenced by Greg Freyer.

Animals↗

PubMedDate not supplied

Dynamics of the changes in the cerebral amounts of cyclic AMP and some prostaglandins during cobalt-60 gamma-radiation-induced brain edema.

The total amounts of cyclic AMP (cAMP), prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in cerebra have been measured in rats, at constant intervals, up to 18 days after whole body exposure to either a unique moderate dose (500 rads) or a unique lethal dose (750 rads) of cobalt-60 gamma-radiation. The experimental findings indicate that this radiation (i) results in an abrupt short-lasting increase in the amount of cerebral cAMP after a 500 rad-irradiation and a progressive long-lasting increase in its amount after a 750 rad-irradiation, and (ii) induces no change in the normally, existing correlation between cerebral PGE1 and cAMP, but affects deeply the normally existing correlation between cerebral PGF2alpha and cAMP. These biochemical alterations generally parallel the evolution of the radiation-induced brain edema.

Animals↗

PubMed1985

[Metabolic effects of exposure to air and the post-aeration response in the intertidal anthozoan Actinia equina L].

Metabolic adjustments occurring during air exposure have been studied in a population of Actinia equina submitted to long-lasting emersion periods. Oxygen consumption upon reimmersion seems to account for the discharge of an oxygen debt related to the accumulation of end-products derived from anaerobic pathways. Incorporation of radioactive labelled glucose into both submerged and air exposed animals has allowed identification of these final products. A correspondence between the length of exposure-time and the amount of oxygen debt is encountered, which parallels the evolution of the rate of radioactivity incorporation into amino acids. Increasing levels of amino acid synthesis from glucose in the exposed conditions appear as the main metabolic feature.

Adaptation, Physiological↗

PubMed1985

[Deficiency of NK activity evolving in a parallel manner with immune granulopenia].

The role of NK cells and their place in blood lines remain the subject of controversy. The authors report on a 42-year-old patient who exhibited a regressive auto-immune granulopenia following administration of anti-lymphocytic serum and also during immunosuppression by cyclophosphamide after a relapse. The NK activity level closely paralleled the evolution of the granulopenia. The possible relationships between these two phenomena are discussed, and the possible role of membrane antigens common to NK cells and myeloid lines.

Adult↗

PubMedDate not supplied

[Paraneoplasic acrokeratosis of Bazex (author's transl)].

Acrokeratosis of Bazex is a true paraneoplasic syndrome of evocative by its acromegalic and symetric topography of erythemato-keratosic lesions. It always reveals an aerodigestive epithelioma. Its diagnosis is very useful for early treatment of the epithelioma. Its diagnosis is very useful for early treatment of the epithelioma. Its evolution is parallel with primitive cancer and is the best criteria of watching.

Acromegaly↗

PubMed1981

Lung catecholamines and cyclic nucleotides during perinatal development in the rat. Possible relationships with biochemical and morphological differentiation.

In this study, we investigated in parallel the evolution of endogenous catecholamine and cyclic nucleotide levels in lung tissue in the course of normal fetal development of the rat from day 17 of gestation to day 10 postpartum; the findings were correlated with the successive stages of lung differentiation. These were assessed morphologically by electron microscopy, and biochemically by measuring the levels of the main lung tissue phospholipids and studying their fatty acid composition. Dopamine levels were low and always remained under 5 ng/g of wet tissue. Nevertheless, slight rises were observed between days 17 and 19 of gestation (1.8 and 2.78 ng/g, respectively) and between days 21 of gestation and birth (2.56 and 4.25 ng/g, respectively). These changes were significant (P less than 0.05). Norepinephrine (NE) levels first decreased by about 50% between days 17 and 19 of gestation (7.34 and 3.88 ng/g, respectively), (P less than 0.01) and then rose sharply about 4 times until birth (17.24 +/- 3.90 ng/g), and more slowly from then on. On day 10 postpartum, the mean NE level was 34.31 +/- 3.28 ng/g. The levels of the two cyclic nucleotides [cyclic adenosine 3':5'-monophosphate and cyclic guanosine 5'-monophosphate (cGMP)] were quite high on day 17 and remained so until day 19 (cAMP = 220 pmoles /g; cGMP = 20 pmoles/g). From day 19 until day 21, the levels of the two nucleotides decreased (cAMP = 140 pmoles/g; cGMP = 8 pmoles/g; P less than 0.05). During this period, the decrease in cGMP level was about twice that of cAMP. During the last day of gestation, the cAMP level was still decreasing, whereas cGMP was increasing. After birth, the levels of the two cyclic nucleotides rapidly increased to day 5. Between days 5 and 10 postpartum, no significant changes were observed in either cAMP or cGMP levels. The time course of the variations reported suggests that they are related to the maturation processes of lung assessed on the basis of morphological and biochemical criteria. On day 19 of gestation, when the first lamellar bodies appear, large changes occur in the evolution of NE and cyclic nucleotide levels, suggesting that these changes may be related to the onset of surfactant synthesis. On day 21 of gestation, the cAMP and cGMP ratio rises sharply; at the same time, the total phospholipid level is increased by 50%. At this stage, lamellar bodies are actively differentiating within type II pneumocytes and massively released into the fetal airways. The relationships between the variations of the studied biochemical parameters and the maturation processes of lung suggest that dopamine and NE could be involved in surfactant synthesis and release via their second messenger, the cyclic nucleotides. Further investigations are needed to elucidate the mechanisms regulating these changes.

Animals↗

PubMed1983

An ultrastructural analysis of endothelial change paralleling platelet aggregation in a light/dye model of microvascular insult.

Those microvascular endothelial events that parallel the evolution of platelet aggregation were evaluated in a well-controlled animal model. Cat pial microvessels were observed through a cranial window while local platelet aggregation was produced by intravenous injection of sodium fluorescein and simultaneous exposure of the pial vessels to light from a filtered mercury lamp that excited the fluorescein. The vessels were fixed in situ when the in vivo observations of a preselected vessel indicated early, intermediate, or advanced aggregation in that vessel. The preselected vessel was then harvested for ultrastructural study together with adjacent vessels from the illuminated field. These vessels and appropriate controls were compared in semiserial thin sections. The onset of platelet aggregation in both venules and arterioles was accompanied by focal endothelial lucency, vacuole formation, luminal membrane rupture, and swelling of the nuclear envelope. These changes were not found in control material. With intermediate aggregation these changes were more common, while with advanced aggregation these abnormalities occurred together with focal endothelial denudation. Thus, in this model denudation occurred only with advanced aggregation and was not a prerequisite for aggregation.

Animals↗

PubMedDate not supplied

[Microdissection study of the kidneys of reptiles living under different ecologic conditions].

Microdissectional studies on the kidneys of 24 reptilian species living in different habitats show that the relative length of the distal tubuli is higher in animals adapted to a limited water supply and to fresh-water basins, as compared to animals which have unlimited access to water. No regular changes in the length of proximal, intermediate and connective parts were observed. The increase in the length of the distal tubuli occurs simultaneously among different taxonomic groups of reptiles, indicating the existence of parallelism in evolution of their kidneys.

Adaptation, Physiological↗