Biomedical subjects
Publications and source records attributed to P Fischer.
We demonstrated that right-left orientation (R/L-O) on a confronting subject is more impaired in patients with dementia of the Alzheimer type than in patients with multi-infarct dementia of comparable degree of dementia. The impairment in R/L-O is independent of aphasia and spatial disorientation.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The aim of the first part of this study was to select the optimal technique for the enumeration and identification of viable mould propagules in the indoor air of houses. A comparison was made between the results obtained with six commercially available air sampling devices in combination with four culture media. The optimal technique was defined as the technique with the best precision and the highest yield. The coefficients of variation were high (generally greater than 20%) for all combinations. Statistical analysis showed that the Slit sampler and the N6-Andersen sampler in combination with DG18 and MEA gave the best precision and the highest yield in terms of CFU/m3 and number of species isolated. In the second part of this study the presence of viable mould propagules in the indoor air of 46 houses in relation to the dampness of these houses was investigated, using the N6-Andersen sampler in combination with DG18. To assess the variability in time, the measurements were repeated after five weeks. Overall, between the two periods no difference was found between the average number of CFU/m3 in the investigated homes. However, the variation between homes was much smaller than the variation within homes. The mean number of CFU/m3 was somewhat higher in "damp" houses than in "dry" houses. However, this difference was not significant. Furthermore, there were no demonstrable differences in the presence of specific mould species in "damp" and "dry" houses.
Explore the source record for details and available documents.
To study the putative precursor proteins (PreA4(695), PreA4(751), and PreA4(770] of Alzheimer's disease A4 amyloid protein, polyclonal and monoclonal antibodies were raised against a recombinant bacterial PreA4(695) fusion protein. These antibodies were used to identify the precursors in different cell lines as well as in human brain homogenates and cerebrospinal fluid (CSF). The precursors are tyrosine-sulfated, O- and N-glycosylated membrane proteins and have half-lives of 20-30 min in cells. Cells express the polypeptides at their surface but also secrete C-terminal truncated proteins into the medium. These proteins are also found in CSF of both Alzheimer's disease patients and normal individuals. The proteins are derived from their cognate membrane-associated forms by proteolysis and have apparently lost the cytoplasmic and the transmembrane domains. Since the latter contributes to the A4 amyloid sequence, it seems possible that this proteolytic cleavage represents the first step in the formation of A4 amyloid deposits.
Intact dipeptidyl aminopeptidase IV (DAP IV) was solubilized by bromelain treatment from human kidney brush border plasma-membranes. Purification of DAP IV was performed by a 3-step method, applying lectin-affinity chromatography on WGA-Sepharose, gel filtration and anion-exchange chromatography. DAP IV from human kidney cortex showed a pH optimum of 8.7 and was totally inhibited by 1 mmol/l Zn2+. Isolated DAP IV revealed a relative molecular mass of 250 kDa as determined by the native-PAGE method and of 220 kDa by the gel filtration method. Analytical isoelectric focussing of DAP IV revealed an isoelectric point of pH 5.3. Ultrastructural analysis of isolated DAP IV fractions, using the negative staining technique, disclosed the presence of numerous globular particles with an average diameter of 5 nm which correspond to the structural substrate of the purified protein.
Explore the source record for details and available documents.
Pachycarpine (4), the optical antipode of the lupine alkaloid (-)-sparteine (1), has been prepared from (-)-lupanine; its metabolism was studied in rats. After isolation and chromatographic purification, streochemically homogeneous (+)-(4S)-hydroxysparteine (7) was identified as the major urinary metabolite by use of mass spectrometry and high-field NMR-spectroscopy.
The recent introduction of the PhastSystem, an automatic electrophoresis and staining system with precast gradient-gels, allows rapid and reproducible analysis of proteinuria in patients suffering from renal injury. A routine method for sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis (SDS-PAGE) and silver staining of unconcentrated urine specimens in the PhastSystem is described and compared to our conventional "macro"-method with self-cast SDS-polyacrylamide gradient gels. The method described for the PhastSystem using 0.3 microL sample volumes and an 8-25% polyacrylamide gradient gel leads to highly reproducible results within 1.5 h. Before electrophoresis urine specimens were neither concentrated nor dialyzed. Samples with a protein concentration exceeding 5 mg/mL had to be diluted 1:5 (v/v). Analysis and documentation of PhastGels appeared as easy as with our conventional SDS-PAGE. Protein bands could reliably be identified by Western blotting. Urine and serum proteins, separated in PhastGels, were electrophoretically transferred to nitrocellulose and detected with specific antibodies against human albumin, transferrin, alpha-1-antitrypsin and IgG. Comparison of several standard kits for molecular weight determination revealed considerable differences concerning the quality of protein separation patterns. Availability of precast gels and automatization of SDS-PAGE and staining allows easy standardization of urine SDS-PAGE among clinical routine laboratories.
After pretreatment of rats with reserpine and pargyline (to inhibit vesicular uptake and monoamine oxidase, respectively) and after inhibition of catechol-O-methyl transferase (by U-0521) and in calcium-free solution, the adrenergic neurones of isolated vasa deferentia and atria were loaded with 3H-noradrenaline. The spontaneous efflux of 3H-noradrenaline and 3H-dihydroxyphenylglycol was determined, as well as the steady-state effect of two concentrations of desipramine. On the basis of a mathematical model of the adrenergic nerve ending, fractional rates (FR = rate of flux divided by tissue tritium content) were calculated for unidirectional outward diffusion, for outward transport and for neuronal re-uptake (all for 3H-noradrenaline). Although the density of adrenergic innervation is lower in atria than in vasa deferentia, neuronal re-uptake amounted to about 90% of the spontaneous efflux of 3H-noradrenaline in both tissues. While the FR for unidirectional outward diffusion was virtually the same in both tissues, the FR for outward transport of 3H-noradrenaline was more than three times higher in atria than in vasa deferentia. There is, as yet, no explanation for this pronounced difference.
Two dibenzofuran degrading bacteria, Brevibacterium strain DPO 1361 and strain DPO 220, were found to utilize fluorene as sole source of carbon and energy. Cells which were grown on dibenzofuran, transformed fluorene into a number of products. For five of the seven metabolites isolated, the structure could be established unequivocally. Accumulation of one metabolite, 1,10-dihydroxy-1,10-dihydrofluoren-9-one, indicated the presence of a novel type of dioxygenase, attacking polynuclear aromatic systems in the unusual angular position. Debenzofuran degradation is proposed to likewise proceed via initial angular dioxygenation. One aryl oxygen ether bond, which normally is extremely stable, is thus transformed to a hemiacetal. After spontaneous cleavage and subsequent rearomatization by dehydration, 2,2',3-trihydroxybiphenyl [3-(2-hydroxyphenyl)-catechol] thus results as the immediate product of the first enzymatic reaction in the degradation sequence.
Cardiac aliasing is a physiological phenomenon generating respiratory sinus arrhythmia in a frequency range lower than that of respiration if the mean respiration rate exceeds half of the mean heart rate. This was found in 8 out of 39 healthy fullterm newborns, 5 out of 33 fullterm and 3 out of 63 preterm newborns during intensive care. Quantification of cardiorespirographic data is considerably impaired in those cases when the mean respiration rate markedly exceeds half of the mean heart rate (two out of the 39 healthy full term newborns).
In January 1987, an air pollution episode occurred in central and western Europe. Levels of SO2, NO2, black smoke, sulphates and other components were elevated, with 24 hour average concentrations of SO2 reaching a maximum of close to 300 micrograms/m3 in an area in the southeast of the Netherlands. Pulmonary function was measured in a group of children of 6-12 years old at the end of the episode, and also two and three and a half weeks after the episode. A baseline lung function value was obtained about three months before the episode. Pulmonary function growth between baseline and retest dates was estimated from a simple growth model which was validated using measured pulmonary function growth data from a longitudinal study. A decline of pulmonary function (FVC, FEV1 and PEF) from predicted baseline levels was observed, starting on the last day of the episode. Two weeks after the episode, FVC, FEV1, PEF and MMEF were all decreased, and three and a half weeks after the episode, there was still a deficit compared to predicted baseline levels for FVC and FEV1.
Thirty four out of 750 patients entered into the Medical Research Council's (MRC) 9th Acute Myeloid Leukaemia Trial had more than 1% basophils (range 1-27%) often with bizarre granulation and primitive forms, a rare finding in this disease. Both normal and abnormal karyotypes were present including abnormalities of 6p, 12p, and the Philadelphia chromosome. Basophilia was found in both "monolineage" and "multilineage" leukaemias and the commonest French-American-British (FAB) classification group was M2, followed by M4. Basophilia did not seem to be associated with a worse prognosis, although cases with abnormalities of 6p died of disease that was resistant to first line conventional chemotherapy.
Monoclonal antibodies (MAb) raised against plasma membranes isolated from human kidney and renal cancer (CA) were capable of reacting with epitopes of either proximal or distal tubular antigens, also found to be excreted in urine of patients under pathological conditions. CA disclosed a microheterogenous distribution of antigens carrying proximal and distal tubule epitopes respectively. Some hybridoma produced MAb which were able to recognize epitopes strongly associated with CA.
Explore the source record for details and available documents.