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N Bayer

Publications and source records attributed to N Bayer.

15 recordsLinked to original sources
PubMed2006

Predictors of disease course and remission in systemic juvenile idiopathic arthritis: significance of early clinical and laboratory features.

OBJECTIVE: To determine whether the disease course in systemic juvenile idiopathic arthritis (JIA) can be characterized as monophasic, polycyclic, or persistent, and to determine whether early clinical and laboratory characteristics can be used to predict the disease course and time to remission. METHODS: Forty-five children with systemic JIA diagnosed between 1996 and 2000 were followed up with a standardized data collection protocol, including data on clinical and laboratory features (mean followup 4.9 years). Disease was considered inactive if the clinical and laboratory features were normal. Three definitions of remission were applied to classify disease course. Predictors of disease course were evaluated using multiple logistic regression. Predictors of time to remission were evaluated using Cox proportional hazards regression. RESULTS: When applying a definition of remission requiring inactive disease while not receiving any medications for a period of 3 months, 42.2%, 6.7%, and 51.1% of the patients were classified as having monophasic, polycyclic, and persistent disease, respectively. Fever and active arthritis at 3 months (R2 = 0.42, area under the receiver operating characteristics curve [AUC] = 0.76) and an erythrocyte sedimentation rate (ESR) >26 mm/hour and corticosteroid use at 6 months (R2 = 0.49, AUC = 0.92) were predictive of a nonmonophasic course. Absence of active arthritis, an ESR of <26 mm/hour, and no requirement for corticosteroid therapy at 3 and 6 months were predictors of an earlier time to remission. CONCLUSION: The disease course in systemic JIA can be characterized as monophasic, polycyclic, or persistent using a definition of remission requiring 3 months of inactive disease while not receiving any therapy. Features at 3 and 6 months are predictive of the disease course and time to remission.

Adolescent↗
PubMed2001

Elevated endosomal pH in HeLa cells overexpressing mutant dynamin can affect infection by pH-sensitive viruses.

Many viruses gain access to the cell via the endosomal route and require low endosomal pH for infectivity. The GTPase dynamin is essential for clathrin-dependent endocytosis, and in HeLa cells overexpressing the nonfunctional dynaminK44A mutant the formation of clathrin-coated vesicles is halted. HRV2, a human minor group rhinovirus, is internalized by members of the low-density lipoprotein receptor family in a clathrin-independent manner. The low endosomal pH then leads to conversion of the capsid to C-antigen, which is required for release (uncoating) and transfer of the viral RNA into the cytosol and de novo synthesis of infectious virus. We here demonstrate that overexpression of dynaminK44A reduces this antigenic conversion and results in diminished viral synthesis. In contrast, lysosomal degradation is unaffected. The kinetics of the formation of C-antigen in vitro and in vivo suggest that the pH in endosomes is elevated by about 0.4 units upon overexpression of dynaminK44A. As a consequence, HRV2 uncoating is diminished early after internalization but attains control levels upon prolonged internalization. Thus, overexpression of dynaminK44A, in addition to trafficking defects, results in an elevated endosomal pH and thereby affects virus infection and most likely endosomal sorting and processing.

Binding Sites↗
PubMed2000

Inhibition of clathrin-dependent endocytosis has multiple effects on human rhinovirus serotype 2 cell entry.

Minor group human rhinoviruses (exemplified by human rhinovirus serotype 2 (HRV2)) use members of the low density lipoprotein receptor family for cell entry; all these receptors possess clathrin-coated pit localization signals. Viral infection should thus be inhibited under conditions of impaired clathrin-mediated endocytosis. However, Madshus et al. reported an increase in the cytopathic effect of HRV2 infection in HEp-2 cells upon suppression of clathrin-dependent endocytosis by hypotonic shock and potassium depletion (Madshus, I. H., Sandvig, K., Olsnes, S., and van Deurs, B. (1987) J. Cell. Physiol. 131, 14-22.) To resolve this apparent contradiction, we investigated the binding, internalization, conformational changes, and productive uncoating of HRV2 in HeLa cells subjected to hypotonic shock and potassium depletion. This treatment led to an increase in HRV2 binding, with internalization being barely affected. The generation of C-antigenic particles requiring pH </=5.6 was strongly reduced due to an elevation of the pH in endosomal compartments. However, K(+) depletion only slightly affected de novo viral protein synthesis, suggesting that productivity of viral RNA in the cytoplasm is enhanced and thus compensates for the reduction in C-antigenic particles. The distinct steps in the entry pathway of HRV2 are thus differently influenced by potassium depletion. Viral internalization under conditions of inhibited clathrin-dependent endocytosis without the need to disturb the ionic milieu was confirmed in HeLa cells overexpressing the nonfunctional dynamin-1 mutant K44A. Unexpectedly, overexpression of dynamin-1 K44A resulted in elevated endosomal pH compared with overexpression of wild-type dynamin.

Cell Membrane↗
PubMed1999

Human rhinovirus HRV14 uncoats from early endosomes in the presence of bafilomycin.

Determination of infectious progeny virus and in vivo labelling with [(35)S]methionine followed by immunoprecipitation demonstrates that the major receptor group human rhinovirus HRV14 is able to infect HeLa cells in the presence of the V-ATPase inhibitor bafilomycin A1. However, host cell shut off is delayed and viral yield is decreased in the presence of the drug. Uncoating can thus take place under conditions that prevent endosomal acidification indicating that it is catalysed by the viral receptor alone. Since transport is arrested in early endosomes upon inhibition of vesicle acidification, the data also suggest that productive uncoating takes place from early endocytic compartments.

Anti-Bacterial Agents↗
PubMed1998

Effect of bafilomycin A1 and nocodazole on endocytic transport in HeLa cells: implications for viral uncoating and infection.

Bafilomycin A1 (baf), a specific inhibitor of vacuolar proton ATPases, is commonly employed to demonstrate the requirement of low endosomal pH for viral uncoating. However, in certain cell types baf also affects the transport of endocytosed material from early to late endocytic compartments. To characterize the endocytic route in HeLa cells that are frequently used to study early events in viral infection, we used 35S-labeled human rhinovirus serotype 2 (HRV2) together with various fluid-phase markers. These virions are taken up via receptor-mediated endocytosis and undergo a conformational change to C-antigenic particles at a pH of <5.6, resulting in release of the genomic RNA and ultimately in infection (E. Prchla, E. Kuechler, D. Blaas, and R. Fuchs, J. Virol. 68:3713-3723, 1994). As revealed by fluorescence microscopy and subcellular fractionation of microsomes by free-flow electrophoresis (FFE), baf arrests the transport of all markers in early endosomes. In contrast, the microtubule-disrupting agent nocodazole was found to inhibit transport by accumulating marker in endosomal carrier vesicles (ECV), a compartment intermediate between early and late endosomes. Accordingly, lysosomal degradation of HRV2 was suppressed, whereas its conformational change and infectivity remained unaffected by this drug. Analysis of the subcellular distribution of HRV2 and fluid-phase markers in the presence of nocodazole by FFE revealed no difference from the control incubation in the absence of nocodazole. ECV and late endosomes thus have identical electrophoretic mobilities, and intraluminal pHs of <5.6 and allow uncoating of HRV2. As bafilomycin not only dissipates the low endosomal pH but also blocks transport from early to late endosomes in HeLa cells, its inhibitory effect on viral infection could in part also be attributed to trapping of virus in early endosomes which might lack components essential for uncoating. Consequently, inhibition of viral uncoating by bafilomycin cannot be taken to indicate a low pH requirement only.

Anti-Bacterial Agents↗
PubMed1994

Magnetic resonance imaging of nerve root inflammation in the Guillain-Barré syndrome.

We report gadolinium-enhancing nerve root lesions in a 52-year-old man with typical Guillain-Barré syndrome (GBS). This enhancement correlates well with the perineurial inflammatory and demyelinating processes known to characterize GBS and other inflammatory neuropathies. MRI should enable further exploration of patterns of disease in GBS and, with further study, perhaps assist in evaluating therapy.

Cauda Equina↗
PubMed1986

Intravenous heparin for the prevention of stroke progression in acute partial stable stroke.

In a double-blind, placebo-controlled trial, 225 patients with acute partial stable thrombotic stroke were randomly assigned to receive continuous intravenous heparin therapy or placebo for 7 days for the prevention of stroke progression or death. No statistically significant difference between the two groups was found in degree of neurologic change; incidence of stroke progression after 7 days; or functional activity level of survivors at 7 days, 3 months and at 1 year after treatment. Compared with controls, a statistically significant greater number of patients in the group receiving heparin died in the year after the stroke. These deaths occurred 3 to 12 months after the initial stroke and probably were not related to treatment. Results of this study do not support the use of intravenous heparin to treat patients who have had acute partial stroke.

Aged↗
PubMed1985

High resolution CT of Meckel's cave.

High resolution CT of the parasellar region was carried out in 50 patients studied for suspected pituitary microadenoma, but who showed normal pituitary gland or microadenoma on CT. This control group of patients all showed an ellipsoid low-density area in the posterior parasellar region. Knowledge of the gross anatomy and correlation with metrizamide cisternography suggest that the low density region represents Meckel's cave, rather than just the trigeminal ganglion alone. Though there is considerable variation in the size of Meckel's cave in different patients as well as the two sides of the same patient, the rather constant ellipsoid configuration of the cave in normal subjects will aid in diagnosing small pathological lesions, thereby obviating more invasive cisternography via the transovale or lumbar route. Patients with "idiopathic" tic douloureux do not show a Meckel's cave significantly different from the control group.

Adult↗
PubMed1984

Metabolic hydroxylation of the thiophene ring: isolation of 5-hydroxy-tienilic acid as the major urinary metabolite of tienilic acid in man and rat.

The metabolism of tienilic acid, a drug containing a thiophene ring, was reinvestigated in man, rat and dog. The major urinary metabolite in man and rat was isolated and completely characterized by comparison with a synthetic compound. This metabolite derives from the hydroxylation of the thiophene ring of tienilic acid in position 5. Its isomers, 3- and 4-hydroxy-tienilic acids, were synthetized but could be detected neither in man nor in rat urine. Because of its particular behaviour toward electrophiles, 5-hydroxy-tienilic acid was found to react with diazomethane with the formation of a complex mixture of methylated products. This made difficult its measurement by a previously described GLC technique, after acidic extraction and methylation by diazomethane. A new very simple assay using HPLC and direct injection of urine is described in this paper. This assay led to a very precise and reproductible determination of tienilic acid and its hydroxylated metabolite in urine. Up to 50% of tienilic acid is excreted in man or rat urine as 5-hydroxy-tienilic acid whereas this metabolite does not appear in dog urine. These data describe the first example of metabolic hydroxylation of the thiophene ring.

Adult↗
PubMed1982

Increased plasma histamine levels in migraine patients.

Whole blood and plasma histamine levels, peripheral basophil and eosinophil counts and serum immunoglobulins have been measured in a group of eighteen patients with migraine in remission and in twelve of these patients during a headache attack. Plasma histamine levels were significantly elevated (P less than 0.0005) in patients with migraine both during headache attacks and symptom-free periods.

Adult↗
PubMedDate not supplied

Prognosis in stroke.

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Cerebrovascular Disorders↗