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Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 181 records · Page 10Linked to original sources
PubMed2000

Active control of coupled structural/acoustic intensities in a fluid-loaded elastic plate

In this paper, active control of structural intensity and radiated acoustic power in a coupled structure-fluid system is explored. The response of an infinite fluid-loaded plate and the resultant acoustic pressure field are calculated using a hybrid analytic/numerical approach. Two control strategies are examined: (1) the minimization of the total input power, and (2) the minimization of a weighted sum of structural intensity and the radiated acoustic power. Below coincidence, the vibration response of the plate is dominated by nondecaying waves, thus it can be reduced very efficiently by the active control strategies of minimizing the total input power or minimizing the structural intensity. Below coincidence, the acoustic radiation is caused by fast decaying structural waves thus, and active control strategies that aim to minimize the structural intensity have little impact on the radiated pressure field. Furthermore, the control strategy for minimizing the radiated acoustic power does not perform satisfactorily below coincidence since the controllers cannot be coupled to the fast decaying waves. Above coincidence, a slowly decaying structural wave dominates both the plate response and the acoustic radiation, and thus the structural intensity and the radiated acoustic power can be reduced significantly by each of the two control strategies.

Journal Article↗
PubMed2000

Mycobacterium heckeshornense sp. nov., A new pathogenic slowly growing Mycobacterium sp. Causing cavitary lung disease in an immunocompetent patient.

A pathogenic scotochromogenic Mycobacterium xenopi-like organism was isolated from the lung of an immunocompetent young woman. This pathogen caused severe bilateral cavitary lung disease, making two surgical interventions necessary after years of chronic disease. This case prompted us to characterize this mycobacterium by a polyphasic taxonomic approach. The isolate contained chemotaxonomic markers which were typical for the genus Mycobacterium, i.e., the meso isomer of 2,6-diaminopimelic acid, arabinose, and galactose as diagnostic whole-cell sugars, MK-9(H(2)) as the principal isoprenoid quinone, a mycolic acid pattern of alpha-mycolates, ketomycolates, and wax ester mycolates, unbranched saturated and unsaturated fatty acids plus a significant amount of tuberculostearic acid, and small amounts of a C(20:0) secondary alcohol. On the basis of its unique 16S rRNA and 16S-23S spacer gene sequences, we propose that the isolate should be assigned to a new species, Mycobacterium heckeshornense. This novel species is phylogenetically closely related to M. xenopi. The type strain of M. heckeshornense is strain S369 (DSM 44428(T)). The GenBank accession number of the 16S rRNA gene of M. heckeshornense is AF174290.

Adult↗
PubMed2000

Novel diagnostic algorithm for identification of mycobacteria using genus-specific amplification of the 16S-23S rRNA gene spacer and restriction endonucleases.

A novel genus-specific PCR for mycobacteria with simple identification to the species level by restriction fragment length polymorphism (RFLP) was established using the 16S-23S ribosomal RNA gene (rDNA) spacer as a target. Panspecificity of primers was demonstrated on the genus level by testing 811 bacterial strains (122 species in 37 genera from 286 reference strains and 525 clinical isolates). All mycobacterial isolates (678 strains among 48 defined species and 5 indeterminate taxons) were amplified by the new primers. Among nonmycobacterial isolates, only Gordonia terrae was amplified. The RFLP scheme devised involves estimation of variable PCR product sizes together with HaeIII and CfoI restriction analysis. It yielded 58 HaeIII patterns, of which 49 (84%) were unique on the species level. Hence, HaeIII digestion together with CfoI results was sufficient for correct identification of 39 of 54 mycobacterial taxons and one of three or four of seven RFLP genotypes found in Mycobacterium intracellulare and Mycobacterium kansasii, respectively. Following a clearly laid out diagnostic algorithm, the remaining unidentified organisms fell into five clusters of closely related species (i.e., the Mycobacterium avium complex or Mycobacterium chelonae-Mycobacterium abscessus) that were successfully separated using additional enzymes (TaqI, MspI, DdeI, or AvaII). Thus, next to slowly growing mycobacteria, all rapidly growing species studied, including M. abscessus, M. chelonae, Mycobacterium farcinogenes, Mycobacterium fortuitum, Mycobacterium peregrinum, and Mycobacterium senegalense (with a very high 16S rDNA sequence similarity) were correctly identified. A high intraspecies sequence stability and the good discriminative power of patterns indicate that this method is very suitable for rapid and cost-effective identification of a wide variety of mycobacterial species without the need for sequencing. Phylogenetically, spacer sequence data stand in good agreement with 16S rDNA sequencing results, as was shown by including strains with unsettled taxonomy. Since this approach recognized significant subspecific genotypes while identification of a broad spectrum of mycobacteria rested on identification of one specific RFLP pattern within a species, this method can be used by both reference (or research) and routine laboratories.

Algorithms↗
PubMed2000

Comparison of Escherichia coli O157:H7 antigen detection in stool and broth cultures to that in sorbitol-MacConkey agar stool cultures.

We evaluated the Meridian IC-STAT direct fecal and broth culture antigen detection methods with samples from children infected with Escherichia coli O157:H7 and correlated the antigen detection results with the culture results. Stools of 16 children who had recently had stool cultures positive for this pathogen (population A) and 102 children with diarrhea of unknown cause (population B) were tested with the IC-STAT device (direct testing). Fecal broth cultures were also tested with this device (broth testing). The results were correlated to a standard of the combined yield from direct culture of stools on sorbitol-MacConkey (SMAC) agar and culture of broth on SMAC agar. Eleven (69%) of the population A stool specimens yielded E. coli O157:H7 when plated directly on SMAC agar. Two more specimens yielded this pathogen when the broth culture was similarly plated. Of these 13 stool specimens, 8 and 13 were positive by direct and broth testing (respective sensitivities, 62 and 100%). Compared to the sensitivity of a simultaneously performed SMAC agar culture, the sensitivity of direct testing was 73%. Three (3%) of the population B stool specimens contained E. coli O157:H7 on SMAC agar culture; one and three of these stool specimens were positive by direct and broth testing, respectively. The direct and broth IC-STAT tests were 100% specific with samples from children from population B. Direct IC-STAT testing of stools is rapid, easily performed, and specific but is insufficiently sensitive to exclude the possibility of infection with E. coli O157:H7. Performing the IC-STAT test with a broth culture increases its sensitivity. However, attempts to recover E. coli O157:H7 by culture should not be abandoned but, rather, should be increased when the IC-STAT test result is positive.

Antigens, Bacterial↗
PubMed2000

Short course acid suppressive treatment for patients with functional dyspepsia: results depend on Helicobacter pylori status. The Frosch Study Group.

BACKGROUND AND AIMS: Treatment of functional dyspepsia with acid inhibitors is controversial and it is not known if the presence of Helicobacter pylori infection influences the response. METHODS: After a complete diagnostic workup, 792 patients with functional dyspepsia unresponsive to one week of low dose antacid treatment were randomised to two weeks of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, or omeprazole 20 mg daily. Individual dyspeptic and other abdominal symptoms were evaluated before and after treatment according to H pylori status. RESULTS: The proportions of patients considered to be in remission (intention to treat) at the end of treatment with placebo, ranitidine 150 mg, omeprazole 10 mg, and omeprazole 20 mg were, respectively, 42%, 50%, 48%, and 59% in the H pylori positive group and 66%, 73%, 64%, and 71% in the H pylori negative group. In H pylori positive patients, the therapeutic gain over placebo was significant for omeprazole 20 mg (17.6%, 95% confidence intervals (CI) 4.2-31.0; p<0.014 using the Bonferroni-adjusted p level of 0.017) but not for omeprazole 10 mg (6.8%, 95% CI -6.7-20.4) or ranitidine 150 mg (8.9%, 95% CI -4.2-21. 9). There was no significant therapeutic gain from active treatment over placebo in H pylori negative patients. Complete disappearance of symptoms and improvement in quality of life also occurred most frequently with omeprazole 20 mg and was significant in both H pylori positive and H pylori negative groups. The six month relapse rate of symptoms requiring treatment was low (<20%) in all groups. CONCLUSIONS: Omeprazole 20 mg per day had a small but significant favourable effect on outcome in H pylori positive patients. The differential response in these patients may be explained by an enhanced antisecretory response in the presence of H pylori. The effect of weaker acid inhibition was unsatisfactory.

Adolescent↗
PubMed2000

Biosynthesis of vitamin b2 (riboflavin).

The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. The imidazole ring of GTP is hydrolytically opened, yielding a 4, 5-diaminopyrimidine which is converted to 5-amino-6-ribitylamino-2, 4(1H,3H)-pyrimidinedione by a sequence of deamination, side chain reduction and dephosphorylation. Condensation of 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione with 3, 4-dihydroxy-2-butanone 4-phosphate obtained from ribulose 5-phosphate affords 6,7-dimethyl-8-ribityllumazine. Dismutation of the lumazine derivative yields riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, which is recycled in the biosynthetic pathway. The structure of the biosynthetic enzyme, 6,7-dimethyl-8-ribityllumazine synthase, has been studied in considerable detail.

Bacillus subtilis↗
PubMed2000

Effects of methylphenidate on functional MRI blood-oxygen-level-dependent contrast.

OBJECTIVE: The authors' goal was to determine potential hemodynamic consequences of methylphenidate on functional magnetic resonance imaging (MRI) blood-oxygen-level-dependent (BOLD) contrast. METHOD: BOLD and perfusion changes were recorded from the motor cortex of six healthy subjects while they performed flexion-extension movements of the right index finger (finger tapping) at varying rates before and after oral methylphenidate administration. RESULTS: Functional MRI signals increased monotonically with faster movement rates. Subjects' heart rates increased modestly after methylphenidate administration, but no changes in finger tapping performance or functional MRI signals were observed. CONCLUSIONS: Methylphenidate does not alter BOLD neural-hemodynamic coupling. Consequently, functional MRI can be used to map neural systems that subserve cognitive operations (e.g., attention and executive processes) in subjects taking methylphenidate.

Adult↗
PubMed2000

PCR-derived ssDNA probes for fluorescent in situ hybridization to HIV-1 RNA.

We developed a simple and rapid technique to synthesize single-stranded DNA (ssDNA) probes for fluorescent in situ hybridization (ISH) to human immunodeficiency virus 1 (HIV-1) RNA. The target HIV-1 regions were amplified by the polymerase chain reaction (PCR) and were simultaneously labeled with dUTP. This product served as template for an optimized asymmetric PCR (one-primer PCR) that incorporated digoxigenin (dig)-labeled dUTP. The input DNA was subsequently digested by uracil DNA glycosylase, leaving intact, single-stranded, digoxigenin-labeled DNA probe. A cocktail of ssDNA probes representing 55% of the HIV-1 genome was hybridized to HIV-1-infected 8E5 T-cells and uninfected H9 T-cells. For comparison, parallel hybridizations were done with a plasmid-derived RNA probe mix covering 85% of the genome and a PCR-derived RNA probe mix covering 63% of the genome. All three probe types produced bright signals, but the best signal-to-noise ratios and the highest sensitivities were obtained with the ssDNA probe. In addition, the ssDNA probe syntheses generated large amounts of probe (0.5 to 1 microg ssDNA probe per synthesis) and were easier to perform than the RNA probe syntheses. These results suggest that ssDNA probes may be preferable to RNA probes for fluorescent ISH. (J Histochem Cytochem 48:285-293, 2000)

Cell Line↗
PubMed2000

The lack of binding ability of staphylococcal protein A and streptococcal protein G to egg yolk immunoglobulins of different fowl species (short communication).

The binding ability of staphylococcal protein A (SpA) and streptococcal protein G (SpG) to egg yolk antibodies of four fowl species (turkey, duck, moskovy duck and goose) was studied and compared with the binding ability to three serum antibodies from chicken, horse and cattle. SpA and SpG were not able to bind to any of the avian immunoglobulins.

Animals↗
PubMed2000

RAPD variation among and within small and large populations of the rare clonal plant Ranunculus reptans (Ranunculaceae).

In the pre-alpine region of Europe numbers and sizes of populations of the clonal lake shore plant Ranunculus reptans have declined because of the regulation of lake water levels. We investigated genetic variation among and within 17 populations of different size (cover 1-10 000 m) in R. reptans with RAPD (random amplified polymorphic DNA) profiles. We sampled 127 rosettes in 14 populations at Lake Constance and three populations at or near Lake Como. There was significant genetic variation between plants from the two lake regions (5.9%, analysis of molecular variance [AMOVA], P < 0.001), among populations within lake regions (20.4%, P < 0.001), and within populations (73.7%, P < 0.001). Under the assumptions of Wright's island model the variation among populations corresponds to a gene flow of N(e)m = 0.70. Within the 14 Lake Constance populations we detected significant genetic variation among subpopulations separated by only a few metres (4.0% of the within-population variation; P < 0.05). Molecular variance was 24% smaller in small populations covering <100 m area than in larger ones (P < 0.03), indicating that samples from large populations were genetically more variable than samples representing comparable areas of smaller populations. We conclude that gene flow among populations is very limited and that genetic drift has caused reduced genetic variability of smaller populations. Conservation of genetic variability in R. reptans requires persistence of large and also of small populations (because of population differentiation), and it could be enhanced by increasing the size of small populations (to counter genetic drift).

Journal Article↗
PubMed2000

Costs of plasticity in foraging characteristics of the clonal plant Ranunculus reptans.

In clonal plants, evolution of plastic foraging by increased lengths of leaves and internodes under unfavourable conditions may be constrained by costs and limits of plasticity. We studied costs and limits of plasticity in foraging characteristics in 102 genotypes of the stoloniferous herb Ranunculus reptans. We grew three replicates of each genotype with and three without competition by the naturally co-occuring grass Agrostis stolonifera. We used regression and correlation analyses to investigate potential costs of plasticity in lengths of leaves and stolon internodes, developmental instability costs of these traits, and a developmental range limit of these traits. We used randomization procedures to control for spurious correlations between parameters calculated from the same data. Under competition the number of rosettes, rooted rosettes, and flowers was 58%, 40%, and 61% lower, respectively, than in the absence of competition. Under competition lengths of leaves and stolon internodes were 14% and 6% smaller, respectively, than in the absence of competition. We detected significant costs of plasticity in stolon internode length in the presence of competition when fitness was measured in terms of the number of rosettes and the number of flowers (selection gradients against plasticity were 0.250 and 0.214, respectively). Within-environment variation (SD) in both foraging traits was not positively correlated with the corresponding plasticity, which indicates that there were no developmental instability costs. More plastic genotypes did not have less extreme trait values than less plastic genotypes for both foraging traits, which indicates that there was no developmental range limit. We conclude that in R. reptans costs of plasticity more strongly constrain evolution of foraging in the horizontal plane (i.e., stolon internode length) than in the vertical plane (i.e., leaf length).

Adaptation, Physiological↗
PubMed1999

Gemcitabine--a novel immunosuppressive agent--prevents rejection in a rat cardiac transplantation model.

BACKGROUND: 2',2' -difluorodeoxycytidine (dFdC, gemcitabine) is a pyrimidine antimetabolite with antineoplastic activity against a wide range of solid tumors. The immunosuppressive activities of this compound have not been described to date. METHODS: The in vitro effects on activated T lymphocytes were studied with a lymphocyte colony-forming assay in a microagar culture system. Heart transplantations were performed in the fully allogeneic Lewis/ Brown Norway combination. dFdC was administered once daily at various dosages from the time of surgery until day 50. RESULTS: Phytohemagglutinin-induced lymphocyte proliferation was inhibited 50% by dFdC at a concentration of 3.25+/-0.9 nmol/L. Allografts of untreated animals survived for 7.5 (7-8) days and those with 25, 50, and 75 microg/kg body weight dFdC for 7.3 (7-8), 9.3 (8-10), and 16.3 (10-38) days, respectively. Treatment with 100 or 125 microg/kg body weight of dFdC, however, prolonged allograft survival until day 152.8 (129-178). Dose-dependent leukopenia was the main toxicity. CONCLUSIONS: DFdC is a new immunosuppressive agent that can successfully prevent cardiac rejection in a rat transplantation model.

Animals↗
PubMed1999

The period of latency before a muscle receptor generates an action potential as a response to a muscle stretch.

Six primary (Ia) and seven secondary (II) muscle spindle afferents and eight Golgi tendon organ afferents (Ib) from the tibial anterior muscle of the cat, recorded at the dorsal roots, were subjected to a sinusoidal stretch of the host muscle, the frequency of which increased linearly from 2 to 80 Hz over four different lengths of time. Both the amplitude of the sinusoidal stretch and the prestretch of the muscle were varied. The phase of the action potentials was determined. The phase of the action potential, driven 1:1, increased linearly with frequency. From the gradient of the phase of this action potential the muscle-muscle receptor latency was determined, i.e., the period of latency between the stretch of the muscle and the occurrence of the action potential at the muscle nerve where it enters the muscle. The muscle-muscle receptor latency had values lying between 3 and 8 ms: it was dependent on the experimental parameters and became shorter as the conduction velocity of the afferent fiber increased. In three experiments the muscle latency was determined, i.e., the period of latency before the stretch was transferred from the tendon of the muscle to the proximal third of the muscle belly. The muscle was stretched sinusoidally under the same varying parameters as given above. The length changes occurring in the proximal third of the muscle were measured with a piezo element. The muscle latency was determined from the slope of the phase of the zero points of the sinusoidal piezo length changes; the phase increases linearly with frequency. The muscle latency had values lying between 6 and 15 ms: it was dependent on the experimental parameters. The muscle spindle latency, i.e., the period of latency between the stretch of the polar parts of the intrafusal muscle fibers and the recording of the action potentials from the spindle nerve near the spindle capsule, was determined from 5 Ia fibers and 1 II fiber of isolated muscle spindles. The isolated muscle spindle was stretched under the same varying parameters as given above. The muscle spindle latency was determined from the slope of the phase of the phase-locked action potential. The muscle spindle latency as measured by our method proved to be 0 ms. The latencies of the three elements and their dependence on the experimental parameters are discussed in the light of the transfer properties of the muscle and the muscle receptors.

Action Potentials↗
PubMed1999

Temperature effects on the discharge frequency of primary and secondary endings of isolated cat muscle spindles recorded under a ramp-and-hold stretch.

The effects of changes in temperature on primary and secondary endings of isolated cat muscle spindles were investigated under ramp-and-hold stretches and different degrees of pre-stretch. Temperature-induced alterations of the discharge frequency were compared over a temperature range of 25-35 degrees C. Both primary and secondary endings responded to warming with increasing discharge frequencies when the spindle was pre-stretched by 5-10% of its in situ length. The following differences between the temperature effects on primary and secondary endings were observed: (1) The temperature coefficients (Q(10)) obtained from the discharge frequencies during the dynamic and static phase of a stretch were similar for endings of the same type, but they were larger in primary endings (range of Q(10): 2.3-3.3; mean: 2.9) than in secondary endings (range of Q(10): 1.6-2.2; mean: 2.0); (2) With primary endings, but not with secondary endings, the temperature sensitivity (imp s(-1) degrees C(-1)) was larger during the dynamic phase than during the static phase of a stretch; (3) In primary endings, the fast and slow adaptive components occurring in the discharge frequency during the static phase of a stretch clearly increased with warming while in secondary endings, the slow decay was less affected, and the fast decay showed no change; (4) In relaxed spindles, the excitatory effect of warming was overlaid by a strong inhibitory effect as soon as the temperature exceeded about 30 degrees C, resulting in an abrupt cessation of the background activity in most secondary endings, but not usually in primary endings. In general, warming induced an enhanced stretch sensitivity in both types of ending, and additionally an inhibitory effect that is obvious only in secondary endings of relaxed spindles. The different effects of temperature on the discharge frequency of primary and secondary afferents are assumed to be caused by different properties of their sensory membranes.

Adaptation, Physiological↗
PubMed1999

Investigation of solid-phase peptide synthesis by the near-infrared multispectral imaging technique: a detection method for combinatorial chemistry.

A near-infrared (NIR) multispectral imaging spectrometer was used to monitor solid-phase peptide synthesis. This imaging spectrometer has fast scanning ability and high sensitivity because it is based on an acousto-optic tunable filter and a NIR InGaAs focal plane array camera. This NIR imaging instrument possesses all the advantages of conventional NIR spectrometers; namely, it can be used for noninvasive monitoring of the reactions and identification of the products during the solid-phase peptide synthesis of glycine, alanine, and valine mediated by aminomethylstyrene resin beads. The reaction was determined by monitoring either the decrease of the band at 1529 nm, which is due to the amine group on the beads, or the increase of the amide band generated at 1483 nm. The amine band at 1529 nm was also used to determine the presence of the Fmoc protecting groups and the efficiency of its removal. More importantly, this NIR imaging spectrometer has additional features that conventional NIR spectrometers cannot offer; namely, its ability to measure spectra at different positions within a sample. This feature was utilized for the first demonstration in which reactions of three different solid-phase peptide syntheses (in a three-compartment cell) were simultaneously monitored. As expected, the kinetics obtained for three reactions are similar to those obtained when the each of the reactions was individually determined. In this study, data recorded by 16 x 16 pixels were used to calculate a spectrum for each sample. However, a relatively good spectrum can be obtained by using data recorded by a single pixel. Since the NIR camera used in this camera is equipped with 240 x 320 pixels, this NIR mutispectral imaging technique is not limited to the three-compartment cell used in this study but rather can be used as the detection method for the solid-phase peptide synthesis in combinatorial chemistry.

Chemistry, Organic↗
PubMed1999

Histidine 179 mutants of GTP cyclohydrolase I catalyze the formation of 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone triphosphate.

GTP cyclohydrolase I catalyzes the conversion of GTP to dihydroneopterin triphosphate. The replacement of histidine 179 by other amino acids affords mutant enzymes that do not catalyze the formation of dihydroneopterin triphosphate. However, some of these mutant proteins catalyze the conversion of GTP to 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone 5'-triphosphate as shown by multinuclear NMR analysis. The equilibrium constant for the reversible conversion of GTP to the ring-opened derivative is approximately 0.1. The wild-type enzyme converts the formylamino pyrimidine derivative to dihydroneopterin triphosphate; the rate is similar to that observed with GTP as substrate. The data support the conclusion that the formylamino pyrimidine derivative is an intermediate in the overall reaction catalyzed by GTP cyclohydrolase I.

Catalytic Domain↗
PubMed1999

Neisseria meningitidis serogroup B outer membrane vesicle vaccine in adults with occupational risk for meningococcal disease.

Vaccination provides a safe and effective means of reducing the risk of laboratory-acquired infection due to some Neisseria meningitidis serogroups. However, there is currently no serogroup B meningococcal vaccine licensed for use in the US. We used an investigational N. meningitidis serogroup B outer membrane vesicle (B:15:P1.7,16) vaccine produced by the National Institute of Public Health (NIPH) in Norway to immunize 20 researchers with occupational risk for disease. Three doses of vaccine were administered via intramuscular injection at 8-week intervals. The vaccine produced moderate or severe pain with 19 (33%) of the 58 doses administered. Reactions were similar following first, second and third doses. The number and severity of reactions peaked at 24 h postvaccination and then gradually waned. Of 16 vaccinees with results available from all blood draws, 12 (75%) showed a fourfold or greater rise in serum bactericidal activity (SBA) against the vaccine type-strain following two doses of vaccine, and 15 (94%) responded after three doses. Geometric mean titers increased by more than sixfold following two doses of vaccine when compared with prevaccination levels, and by more than 11-fold following a third dose. There was no significant difference between SBA measured using the vaccinee's own complement versus a donor complement source. The NIPH vaccine elicited an excellent bactericidal response against the vaccine type-strain in researchers with an occupational risk for disease. It may be useful for other laboratory personnel who routinely work with meningococcal strains containing similar outer membrane antigens. These findings reconfirm that the NIPH vaccine is immunogenic in adults and support the validity of using properly screened human donor complement in serum bactericidal assays against serogroup B meningococci.

Adult↗