Biomedical subjects

E Schmidt

Publications and source records attributed to E Schmidt.

At least 55 records · Page 3Linked to original sources

PubMed2001

A multi media load model for the Baltic Sea.

The background of this work is the international decision process with regard to the selection of chemicals to be assessed with priority. In order to stress the precautionary principle, mass flows were analysed rather than concentrations, threshold values, etc., as preferred by the chemical legislation (which still excludes the marine area). Lindane, hexachlorobenzene (HCB), trichloroacetic acid and its sodium salt, medium-chained chlorinated paraffins and tributyltin (TBT) were selected due to their great relevance for the marine area. Trichloroacetic acid is an interesting model compound on account of its accidental formation by degradation of volatile chlorinated hydrocarbons and during chlorination processes. In addition, a hypothetical compound was modelled, representing a highly water-soluble substance with low vapour pressure. The balancing area is the Baltic Sea and its catchment area. In order to model the substance flows, the 'Input/Output-load model' has been developed. The model quantifies the shift and the distribution of a yearly load of the substance investigated from the terrestrial-limnic into the marine compartment (Baltic Sea). Water-soluble substances, which are usually considered to be of no concern, may enter the sea in great amounts and, if not degradable, remain there. It turned out to be necessary to take into account remobilisation, unintended formation and point as well as line-sources.

Baltic States↗

PubMed2001

Species diversity of nematode communities in the digestive tract of domestic ruminants: multivariate versus univariate estimations.

The evaluation of species diversity can be performed using species richness (number of species), diversity (number and relative proportions of species) or evenness (equitability of the proportion of each species). A large number of indices related to diversity or evenness is available but their mathematical properties remain unexplained, and hence their use is somewhat unreliable. We intended to present an array of well defined methods, based on discriminant analysis, to evaluate diversity in helminth communities of ruminants. The database used concerned seven cattle farms and seven sheep farms located in temperate areas, from which at least three necropsies were undertaken in autumn. The hosts were chosen because they had experienced nearly a complete grazing period and no anthelmintic treatment was performed for a minimum of 2 months before the necropsies were undertaken, so that the helminth communities could be considered as representative of each farm at one specific moment. We used discriminant analyses to evaluate diversity, based either on proportions of species, or on proportions of species arranged in decreasing order, or on a set of six indices of diversity selected from the most commonly used. We showed that actual proportions were the most efficient in cattle but not in lambs, and that discriminant analyses based on six indices of diversity or based on actual proportions of species ranked in decreasing order yielded very similar results in both host communities. We rejected the use of one single index for evaluating diversity in all cases and proposed the following procedure: actual proportions of species provide information on interactions between species and, when there is limited or no interaction, a combination of diversity indices or single indices could be used for estimating diversity. When interactions between species have to be taken into account, the best information will be obtained either from species proportions arranged in decreasing order or a combination of biodiversity indices.

Animal Husbandry↗

PubMed2001

[Knee joint prosthesis implantation after fractures of the head of the tibia. Intermediate term results of a cohort analysis].

A significant number of patients with operated tibial plateau fractures develop osteoarthritis and require total knee arthroplasty. In cases of primary osteoarthritis the results are generally good. However, it is not known whether patients with post-traumatic osteoarthritis obtain comparably favorable results. In a retrospective study we analyzed 72 patients who had undergone a self-aligning (SAL) total knee arthroplasty. Ten patients received arthroplasty due to sequelae of a tibial head fracture (group I). The median time to follow-up in this group was 30 months. Clinical and radiological evaluation was based on the Knee Society Clinical Rating System. The score comprises pain, range of motion, stability, and function. We defined the axis and possible loosening by radiological examination. For comparative descriptive statistics, a cohort of patients was chosen who had received an arthroplasty because of primary gonarthrosis (group II, 76 arthroplasties in 62 patients). The median time to follow-up in this group was 46.5 months. Three patients in group I underwent revision surgery, four patients displayed severe functional deficits and pain, and one patient had a varus deformity with good clinical function. This corresponded to an early complication rate of 27% and a late complication rate of 36%; a relevant instability or loosening of the components did not occur in this group. In group II the incidence of early complications was 10%. The patients in group I reached a mean value of 153 points using the rating system vs 167 points in group II. Analyzing the clinical parameters of the score, we found that patients in group I experienced significantly more pain, thereby affecting functions of daily living, such as walking and climbing stairs. Because of the small number of patients in group I, conclusions can only be drawn to a limited extent. However, we saw that these patients displayed a higher incidence of complications and performed less well. This has to be taken into consideration and discussed prior to surgery.

Activities of Daily Living↗

PubMed2001

Cicatricial pemphigoid: IgA and IgG autoantibodies target epitopes on both intra- and extracellular domains of bullous pemphigoid antigen 180.

BACKGROUND: Cicatricial pemphigoid (CP) is an autoimmune subepidermal blistering disease where autoantibodies target various components of the dermal-epidermal junction, including the bullous pemphigoid antigen 180 (BP180). OBJECTIVE: We determined the exact specificity of circulating IgG and IgA autoantibodies to BP180 in a large number of CP patients. METHODS: Twenty-six consecutive CP sera were analysed by Western blotting using a panel of cell-derived and recombinant proteins covering the entire BP180 molecule. RESULTS: Circulating autoantibodies were detected in all CP sera. Seven sera reacting with laminin-5 were excluded from further analyses; the remaining 19 sera recognized BP180, including six sera (32%) that showed only IgA reactivity to this protein. With the combined use of the soluble BP180 ectodomain (LAD-1) and recombinant BP180 NC16A, 16 of these 19 CP sera (84%) targeted BP180. IgG reactivity was preferentially found against NC16A, whereas IgA antibodies predominantly recognized LAD-1. Thirty-two per cent of the BP180-reative sera revealed reactivity with the intracellular domain of this protein. CONCLUSIONS: Our findings demonstrate that autoantibodies in CP target epitopes on both extra- and intracellular domains of BP180 and highlight the importance of testing for both IgG and IgA reactivity in these patients' sera.

Aged↗

PubMed2001

The IL-8 release from cultured human keratinocytes, mediated by antibodies to bullous pemphigoid autoantigen 180, is inhibited by dapsone.

Bullous pemphigoid (BP) is a subepidermal blistering disease associated with autoantibodies to the hemidesmosomal 180 kD BP autoantigen (BP180). However, the binding of autoantibodies to BP180 alone is not sufficient for blister formation in this disease and the infiltration of neutrophils into the skin is required. Dapsone and nicotinamide inhibit neutrophil chemotaxis and are used effectively in treating BP. IL-8 is a known chemoattractant for neutrophils and has been implicated in the inflammatory process of both human and experimental murine BP. We have recently shown that antibodies to BP180 mediate a dose and time-dependent release of IL-6 and IL-8 from cultured normal human epidermal keratinocytes (NHEK). In the present study, we addressed the question whether dapsone or nicotinamide influence this cytokine release. We demonstrate that dapsone, but not nicotinamide, in its pharmacological range, inhibits the IL-8, but not the IL-6 release from NHEK, induced by anti-BP180 IgG, in a dose-dependent fashion as detected by ELISA. IL-8 mRNA levels, as determined by RT-PCR, were the same in cells treated with BP IgG alone compared to cells treated with BP IgG plus dapsone. This observation suggests that dapsone inhibits the BP IgG-induced IL-8 release from cultured NHEK by mechanisms at the post-transcriptional level. Our findings contribute to the understanding how dapsone leads to a reduced influx of neutrophils into BP lesions and, finally, to the cessation of blister formation in this disease.

Animals↗

PubMed2001

Leading through rough times. An interview with Novell's Eric Schmidt. Interview by Bronwyn Fryer.

Few large companies have soared as high, sunk as low, and struggled as long as the 18-year-old networking software maker Novell. For years, the company dominated the market for local area networks, but by 1997, it had faltered due to misguided acquisitions, product missteps, and large unsold inventories. That's when Eric Schmidt arrived from Sun Microsystems to take over as Novell's third CEO. He turned the company around with a deft combination of cost reductions, divestitures, and new product rollouts, and by 1998, it was back in the black. Unfortunately, the good times didn't last, and like most technology companies, Novell is once again struggling with a slowdown in demand. But Schmidt is optimistic about returning Novell to good health, and his strategies suggest ways for other organizations to handle themselves during downturns. He counsels against being overly cautious during such times. It may be necessary to eliminate excess inventory, cut costs, and reduce the size of the staff and the management team in order to stabilize a company. Working to retain those employees whom he calls the "smart people" and keeping them motivated will have long-term payoffs. Further, Schmidt says it is necessary to acknowledge and overcome a "culture of fear," the deadening environment of cynicism in which employees suppress thoughts and feelings because they're worried about layoffs. His additional advice: keep new products coming out to sustain the interest of customers and the press, pay attention to your cash position, stay focused on your desired outcomes, and take heart from other industry leaders.

Administrative Personnel↗

PubMed2000

[Dipyridamole test in the early detection of cerebrovascular disorders?].

The diagnosis of transient ischaemic attack (TIA) is mainly based on the clinical symptoms presented by the patient. Professionals in nuclear medicine have made a successful attempt to detect TIA by single photon emission tomography (SPECT) imaging. Improved sensitivity of the examination using stress test (e.g. acetazolamide) is well known in the literature. The dipyridamole stress test combined with SPECT imaging was regularly performed in patients (n = 100) with ischaemic heart disease. After injecting dipyridamole intravenously it found various forms of transient neurological deficits in 23% of the patients with considerably higher incidence reported previously in the literature (1.22/10,000). The so called "TIA positive" patients were examined further using the combination of dipyridamole stress test and brain SPECT imaging. The aim of this study was to analyse the relationship between transient neurological symptoms provoked by DPD test and the change in regional cerebral blood flow indicated by brain SPECT imaging. It is emphasized, that perfusion abnormalities revealed by brain SPECT were topographically consistent with the neurological deficits. In this article the attention was drawn to advantages of this test which may be suitable to provoke TIA safely. Combined with brain SPECT it may have an important role in the neurologic diagnostic procedures and in the prevention of stroke.

Cerebrovascular Circulation↗

PubMed2000

Enhanced quantum correlations in bound higher-order solitons

Quantum effects in N-bound solitons can be drastically enhanced compared to the fundamental soliton. In particular, the spectral photon-number correlations are much stronger. The formation of spectral domains of almost perfect positive and negative correlations is predicted. Criteria that are based on the Cauchy-Schwarz inequality are used for studying nonclassical correlations. Interferences between different soliton components of the N-bound solution being responsible for the strong changes in the coherent amplitude may also be a mechanism for the strong correlations. The results offer novel possibilities of producing light with highly nonclassical properties.

Journal Article↗

PubMed2000

Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans.

Expansion of polyglutamine repeats in several unrelated proteins causes neurodegenerative diseases with distinct but related pathologies. To provide a model system for investigating common pathogenic features, we have examined the behavior of polyglutamine expansions expressed in Caenorhabditis elegans. The expression of polyglutamine repeats as green fluorescent protein (GFP)-fusion proteins in body wall muscle cells causes discrete cytoplasmic aggregates that appear early in embryogenesis and correlates with a delay in larval to adult development. The heat shock response is activated idiosyncratically in individual cells in a polyglutamine length-dependent fashion. The toxic effect of polyglutamine expression and the formation of aggregates can be reversed by coexpression of the yeast chaperone Hsp104. The altered homeostasis associated with polyglutamine aggregates causes both the sequestration of an otherwise soluble protein with shorter arrays of glutamine repeats and the relocalization of a nuclear glutamine-rich protein. These observations of induced aggregation and relocalization have implications for disorders involving protein aggregation.

Animals↗

PubMed2000

Serum levels of autoantibodies to BP180 correlate with disease activity in patients with bullous pemphigoid.

OBJECTIVE: To investigate the possible correlation of levels of circulating anti-BP180 autoantibodies with disease activity in bullous pemphigoid (BP). DESIGN: Diagnostic study. SETTING: Regional referral center at a university dermatology department. PATIENTS: Fifteen patients with typical clinical, histologic, and immunofluorescence findings of BP who had not received prior systemic treatment. INTERVENTIONS: Initially, 6 consecutive patients with BP were treated with oral doxycycline and niacinamide. Subsequently, 9 consecutive patients with BP received a combination of oral dapsone and prednisolone. MAIN OUTCOME MEASURES: Disease activity, serum levels of autoantibodies to BP180, and titers of antibasement membrane zone autoantibodies were assayed before initiation of treatment and 4 and 8 weeks later. Reactivity to BP180 was analyzed by enzyme-linked immunosorbent assay using a recombinant form of BP180 NC16A. Titers of anti-basement membrane zone autoantibodies were assayed by indirect immunofluorescence on 1-mol/L sodium chloride-split human skin. RESULTS: In both treatment groups, disease activity correlated with serum levels of autoantibodies to BP180 NC16A (P = .004 [dapsone-prednisolone] and .007 [doxycycline-niacinamide]). No correlation was seen between disease activity and indirect immunofluorescence reactivity (P = .18 and .16, respectively). In patients receiving dapsone plus prednisolone, the dose of corticosteroids necessary to suppress new blister formation correlated with anti-BP180 reactivity (P = .002). CONCLUSIONS: In contrast to indirect immunofluorescence reactivity that reflects reactivity to both BP 180 and BP230, serum levels of autoantibodies to BP180 correlate with disease activity in BP. Assaying reactivity to BP180 should be a helpful guide for the therapeutic management of patients with this disease. Our results underline the pathogenic relevance of autoantibodies to human BP180.

Aged↗

PubMed2000

Effects of hydrogen peroxide scavenger Catalase on villous microcirculation in the rat small intestine in a model of inflammatory bowel disease.

This study was conducted to quantify the effect of systemic Catalase, a hydrogen peroxide scavenger, on villous microcirculation in the inflamed small intestine of the rat. Intestinal inflammation was induced with s.c. application of Indomethacin. Intravital fluorescence microscopy and FITC-labeled erythrocytes were used to quantify erythrocyte velocity and arteriolar diameter in the main arteriole of the villi in the terminal ileum following i.v. application of Catalase in the inflamed intestine, and the blood flow was calculated. Control groups were formed for Ringer's lactate, Catalase and Indomethacin, respectively. We found that villous blood flow was significantly increased in the in the inflamed intestine. Application of Catalase led to a significant decrease in villous perfusion, but had no effect in the control group. The increase in villous blood flow was accompanied by changes in the diameter of the main arteriole. This effect on arteriolar diameter was reversed by i.v. Catalase. Our results provide evidence that systemic application of Indomethacin leads to vasodilatation of the main arteriole of the villus in the rat ileum and hyperemia in the mucosa. Hyperemia and the vascular diameter of the main arteriole were significantly reduced by H(2)O(2)-scavenger Catalase, suggesting that endogenous H(2)O(2) may be one of the mediators of hyperemia in the mucosa in this animal model of intestinal inflammation.

Animals↗

PubMed2000

[Pemphigus. Loss of desmosomal cell-cell contact].

Pemphigus diseases comprise a group of autoimmune disorders which are characterized by intraepidermal blisters and autoantibodies to components of desmosomes. Desmosomes mediate adhesion between neighbouring keratinocytes. A common feature of pemphigus diseases are intercellular deposits of IgG or, less frequently, of IgA within the epidermis. The group of pemphigus diseases includes pemphigus vulgaris, pemphigus foliaceus, pemphigus vegetans, pemphigus herpetiformis, pemphigus erythematosus, paraneoplastic pemphigus, drug-induced pemphigus, and IgA pemphigus. Using molecular tools, some of the autoantigens in these diseases have been characterized. In pemphigus vulgaris, autoantibodies are directed to desmoglein 3 and in pemphigus foliaceus to desmoglein 1. Target antigens in IgA pemphigus are desmocollin 1 and desmoglein 3. In paraneoplastic pemphigus, autoantibodies react with a complex of various proteins, including desmoplakin 1 and 2, BP230, envoplakin, periplakin, plectin, desmoglein 3, and a yet uncharacterized 170 kD protein. This review summarizes new insights into the immunopathogenesis and diagnosis of pemphigus diseases.

Animals↗

PubMed2000

[New aspects on the pathogenesis of bullous pemphigoid].

Bullous pemphigoid (BP) is a subepidermal blistering autoimmune disease of the elderly. Autoantibodies are directed against two hemidesmosomal proteins, designated BP180 and BP230. While BP230 localizes intracellularly and associates with the hemidesmosomal plaque, BP180 is a transmembrane glycoprotein with an extracellular domain consisting of approximately 1000 amino acids. The non-collagenous (NC) 16A domain, that encompasses 76 amino acids and localizes directly adjacent to the transmembrane region, has been identified as an immunodominant region of the BP180 ectodomain. In the majority of BP sera, circulating antibodies to BP180 NC16A are detected; their serum levels correlate with disease activity. Neonatal mice that are injected with rabbit anti-murine BP180 antibodies develop a BP-like subepidermal blistering disease demonstrating the biological importance of antibodies to BP180. The pathogenically relevant site on murine BP180 corresponds to a stretch of the NC16A domain on human BP180. In contrast to pemphigus, in BP, autoantibodies alone are not sufficient to induce blisters. In addition, complement activation, the infiltration of inflammatory cells and the release of proteases and various inflammatory mediators, including cytokines, are essential for lesion formation. In this review, we give an up-date on the pathogenesis of BP.

Animals↗

PubMed2000

Different effects of nabilone and cannabidiol on binocular depth inversion in Man.

The physiological and pathophysiological roles of the central nervous endogenous cannabinoid system are not completely understood, but still represent a challenge in basic neurobiological, cognitive, and psychiatric research. The system has been implicated in the pathogenesis of schizophrenia. Binocular depth inversion, an illusion of visual perception, provides a model of impaired perception during psychotic states. Using this model the effects of nabilone, a psychoactive synthetic 9-trans-ketocannabinoid, and of cannabidiol, the main natural component of herbal cannabis, and a combined application of both substances on binocular depth inversion and behavioural states were investigated in nine healthy male volunteers. The time course of the effects of both substances on binocular depth inversion was analysed after oral administration using three different groups of natural stimuli. A significant impairment of binocular depth perception was found when nabilone was administered, but combined application with cannabidiol revealed somewhat reduced effects on binocular depth inversion. The influence of psychoactive cannabinoids on this perceptual model and the role of the endogenous cannabinoid system in visual information processing are discussed.

Adult↗

PubMed2000

[Management of severe head injuries during the first 24 hours, in the emergency department, in neurosurgery].

In France, the role of the neurosurgeon in the emergency department depends on local health care policies and geographical constraints. Some departments include a neurosurgical team with a dedicated operating room. In others, a neurosurgeon can be reached by phone, possibly with an image transfer. Whatever the case, it should be possible to remove on site and without delay an intracranial haematoma, which is most often an extradural injury. The management of a haematoma of the posterior fossa or a bleeding dural venous sinus would be difficult for a surgeon not qualified in neurosurgery. The optimal situation is the presence of a neurosurgeon in the medical team admitting patients with a severe head or spine trauma, for assessment of the neurological status, or interpretation of radiological explorations, insertion of an intracranial pressure monitoring device. Besides the extradural haematoma, other injuries such as an acute subdural haematoma, a haematoma associated with a contusion, an acute hydrocephalus, a depressed fracture of the skull, or a craniocerebral wound, also require an emergency decompressive procedure.

Brain Injuries↗

PubMed2000

In vivo assessment of villous microcirculation in the rat small intestine in indomethacin-induced inflammation: role of mast-cell stabilizer Ketotifen.

Indomethacin induces an inflammatory reaction in the small intestine in several rat strains. This animal model is widely used to study the implications of intestinal inflammation. Macroscopically, there is evidence that Indomethacin induces a hyperaemic inflammatory reaction in the mucosa, and in our previous studies, we found a significant increase in villous perfusion in the acutely inflamed small intestine. Mast-cell activation was found to take part in inflammatory reactions in several organ systems in various species. However, no data are available about the effect of mast-cell degranulation on the perfusion of the mucosa in Indomethacin-induced intestinal inflammation. Therefore, we used the mast-cell stabilizer Ketotifen to identify if mast-cell activation may contribute to changes in the perfusion of single villi in the rat ileum. We found that Ketotifen significantly reduced the Indomethacin induced increased blood flow in the main arteriole 60 min after i.v. application, indicating that mast-cell degranulation effects microcirculatory disturbances in the mucosa in Indomethacin-induced intestinal inflammation.

Animals↗

PubMed2000

Isolation and characterization of HsfA3, a new heat stress transcription factor of Lycopersicon peruvianum.

Stress-induced transcription of heat shock proteins (Hsps) in eukaryotes is mediated by a conserved class of transcription factors called heat stress transcription factors (Hsfs). Here we report the isolation and functional characterization of HsfA3, a new member of the Hsf family. HsfA3 was cloned from a tomato heat stress cDNA library by yeast two-hybrid screening, using HsfA1 as a bait. HsfA3 is a single-copy gene with all the conserved sequence elements characteristic of a heat stress transcription factor. The constitutively expressed HsfA3 is mainly found in the cytoplasm under control conditions and in the nucleus under heat stress conditions. Functionally, HsfA3 behaves similarly to the already known members of tomato Hsf family. It is able to substitute yeast Hsf for viability functions and is a strong activator of Hsf-dependent reporter constructs both in tobacco protoplasts and yeast. Finally, similar to the AHA motifs in HsfA1 and HsfA2, the activator function depends on four short peptide motifs with a central tryptophan residue found in the C-terminal domain of HsfA3.

Amino Acid Sequence↗

PubMed2000

Autoantibodies to BP180 associated with bullous pemphigoid release interleukin-6 and interleukin-8 from cultured human keratinocytes.

Bullous pemphigoid is an inflammatory subepidermal blistering disease that is associated with auto- antibodies to the keratinocyte surface protein, BP180. In addition to the binding of autoantibodies, the infiltration of inflammatory cells is necessary for blister formation. Cytokines, including interleukin-6 and interleukin-8, have been implicated in the disease process of both human and experimental murine bullous pemphigoid. This study was aimed at testing the hypothesis that the binding of anti-BP180 antibodies to their target antigen triggers a signal transduction event that results in the secretion of these pro-inflammatory cytokines. Consistent with this hypothesis, treatment of cultured normal human epidermal keratinocytes with bullous pemphigoid IgG, but not control IgG, led to increased levels of interleukin-6 and interleukin-8, but not interleukin-1alpha, interleukin-1beta, tumor necrosis factor-alpha, interleukin-10, or monocyte chemoattractant protein-1, in the culture medium. This effect was concentration- and time-dependent and was abolished by depleting the bullous pemphigoid IgG of reactivity to two distinct epitopes on the BP180 NC16A domain. Upregulation of interleukin-6 and interleukin-8 was found at both protein and mRNA levels. In addition, bullous pemphigoid IgG did not induce the release of interleukin-6 and interleukin-8 from BP180-deficient keratinocytes obtained from a patient with generalized atrophic benign epidermolysis bullosa. These data indicate that bullous pemphigoid-associated autoantibodies to the human BP180 ectodomain trigger a signal transducing event that leads to expression and secretion of interleukin-6 and interleukin-8 from human keratinocytes.

Autoantibodies↗