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Biomedical subjects

A Meier

Publications and source records attributed to A Meier.

At least 55 records · Page 3Linked to original sources
PubMed1996

Correlation of molecular resistance mechanisms and phenotypic resistance levels in streptomycin-resistant Mycobacterium tuberculosis.

Quantitative susceptibility testing of clinical isolates of streptomycin-resistant Mycobacterium tuberculosis demonstrated that there is a close correlation between the molecular resistance mechanism and the in vitro activity of streptomycin: mutations in rpsL were mainly associated with high-level resistance, mutations in rrs were associated with an intermediate level of resistance, and streptomycin-resistant isolates with wild-type rpsL and rrs exhibited a low-level resistance phenotype. Investigations of streptomycin-resistant isolates with wild-type rpsL and rrs revealed that (i) there is no cross-resistance to other drugs and (ii) a permeability barrier may contribute to resistance, because resistance was significantly lowered in the presence of a membrane-active agent.

Antibiotics, Antitubercular↗
PubMed1996

Genetic basis for clarithromycin resistance among isolates of Mycobacterium chelonae and Mycobacterium abscessus.

Resistance to clarithromycin among isolates of Mycobacterium chelonae and M. abscessus was observed in 18 of 800 (2.3%) patients tested between 1990 and 1995. Patients whose isolates were resistant had either disseminated disease or chronic lung disease, and the resistant isolates were recovered after clarithromycin monotherapy. Sequencing of the gene coding for the 23S rRNA peptidyltransferase region revealed a point mutation involving adenine at position 2058 (38%) or adenine at position 2059 (62%) in 20 of 20 relapse isolates from the first 13 patients identified. By pulsed-field gel electrophoresis or random amplified polymorphic DNA PCR, initial and relapse isolates were shown to have identical DNA patterns. M. chelonae and M. abscessus isolates were found to have only a single chromosomal copy of the rRNA operon, thus making them susceptible to single-step mutations. Thus, clarithromycin resistance in these species of rapidly growing mycobacteria relates to a point mutation in the gene coding for 23S rRNA and occurs in limited clinical situations, but was identified in almost 5% of isolates tested in 1995.

Blotting, Southern↗
PubMed1995

Stimulation of protein phosphatases as a mechanism of the muscarinic-receptor-mediated inhibition of cardiac L-type Ca2+ channels.

Acetylcholine decreases currents through cardiac L-type Ca2+ channels after stimulation with agents which elevate levels of cyclic adenosine monophosphate, such as isoproterenol, but there is still a controversy over the mechanisms of this muscarinic effect. We tested the hypothesis of whether, after isoproterenol stimulation, protein phosphatases are activated by acetylcholine. Whole-cell currents were recorded from guinea-pig ventricular myocytes. The effect of 10(-5) M acetylcholine on currents induced by 10(-8) M isoproterenol was studied in the absence or presence of protein phosphatase inhibitors. Three agents reduced the acetylcholine response: okadaic acid (3 or 9 x 10(-6) M) and cantharidin (3 x 10(-6) M) added to the pipette solution, and bath-applied fluoride (3 mM). In contrast, pipette application of other phosphatase inhibitors, namely the inhibitor PPI2 (1000 U/ml), ciclosporin (10(-5) M), or calyculin A (10(-6) M) did not significantly diminish the acetylcholine effect. Interestingly, there was no correlation between the effects of the compounds on basal Ca2+ current and their interference with the muscarinic response. An activation of type 2A phosphatases by acetylcholine would explain these findings. Indeed, okadaic acid is 3 orders of magnitude more potent in vitro in its inhibition of this isoform (purified from cardiac myocytes) than is calyculin A, while type-1 phosphatases are inhibited equally. The data support the attractive possibility that stimulation of protein phosphatases is part of the signal transduction cascade of Ca2+ channel inhibition by acetylcholine.

Acetylcholine↗
PubMed1995

[Narcotic gas burden of personnel in pediatric anesthesia].

METHODS: To assess the occupational exposure of the anaesthetist to anaesthetic gases, a total of 1 German and 25 Swiss hospitals were investigated. A Brüel & Kjaer Type 1302 multi-gas monitor was used to measure concentrations of nitrous oxide and halogenated anaesthetic agents in the anaesthetist's breathing zone. Measurements were performed during 114 general anaesthetic, 55 of which were in patients under 11 years of age. In these 55 patients, the influence of various factors on the exposure (time-weighted average concentrations) was estimated by comparing different data groups. The efficiency of the applied scavenging equipment was examined by surveying the exhalation valve with a leak detector (type TIF 5600, TIF Instruments, Miami). RESULTS: Sessions with patients under 11 years of age revealed much higher anaesthetic gas exposures compared to older patients. The concentrations of nitrous oxide were on average threefold (Fig. 1), those of the halogenated anaesthetics fivefold higher (Fig. 2) for the younger patients. In 11- to 16-year-old patients the exposure level was the same as in adult patients. The measurements showed a reduction of 85% in exposure if an efficient scavenging system (i.e., no waste gas discharge to room air through the exhalation valve) or lower fresh gas flow were used (Fig. 4); 42% of the inspected scavengers were inefficient, and reduced the exposure on average by only 30%. In operating theatres with a ventilation rate of at least ten air changes per h, the measured concentrations of anaesthetic gases in the inhalation zone of the anaesthetists were reduced more than 50% compared to poorly ventilated rooms (Figs. 4 and 5). The use of tracheal intubation or laryngeal mask airway (LMA) anaesthesia resulted in a reduction of 80% in exposure compared to standard face masks if efficient scavenging was used. The exposures during sessions with inefficiently scavenged Bain coaxial systems or unscavenged semi-open delivery systems of the Jackson-Rees type were tenfold higher than with scavenged rebreathing circuit systems (Fig. 6). During anaesthesia with IV or double-mask induction, the average levels of inhalation anaesthetics were reduced by about 80% compared to inhalational induction with standard masks (Fig. 7). The anaesthetist's working technique is a very important factor that strongly influences the concentrations. Poor work practices, like lifting off the face mask with anaesthetic gas flow turned on, increased the exposure of the anaesthetist and other operating room personnel drastically, even if the other conditions (scavenger and room ventilation) were good. DISCUSSION: The exposure levels of anaesthetic gases are generally higher during anaesthesia in children up to 10 years of age than in older patients. Nevertheless, the measurements showed that exposure during paediatric anaesthesia can be kept below the recommended limit (8-h TWA in Switzerland) of 100 ppm nitrous oxide and 5 ppm halothane or 10 ppm enflurane or isoflurane. Causes of high exposures were particularly high fresh gas flows often applied without scavenging or together with inefficient scavenging devices and the high part of mask anaesthesia and inhalation induction with a loosely held mask. To achieve an effective reduction of occupational exposure, well-adjusted and maintained scavenging systems and low-leakage work practices are of primary importance. As leakage can never be completely avoided, a ventilation rate of at least ten air changes per h should be maintained in operating rooms and rooms where anaesthesia is induced to keep down concentrations of waste anaesthetic gases. High exposure during mask anaesthesia and inhalation induction can be prevented by further measures. Using a LMA instead of a standard mask reduces the exposure to the same level as endotracheal intubation.

Adolescent↗
PubMed1995

rpsL+: a dominant selectable marker for gene replacement in mycobacteria.

Molecular genetic manipulations in mycobacteria would benefit from procedures which efficiently select for double-crossover events by homologous recombination. Here we describe a vector-host system for gene replacement in mycobacteria, the utility of which was investigated using functional inactivation of the pyrF gene in Mycobacterium smegmatis as a model. This system is based on the expression of the wild-type rpsL gene coding for ribosomal protein S12 in a streptomycin-resistant host. Owing to the absence of a mycobacterial origin the plasmids are unable to replicate autonomously in mycobacteria. The first selection for maintenance of cloned sequences is conferred by the kanamycin-resistance gene. The second simultaneous selection by streptomycin is against maintenance of cloned sequences which contain the gene encoding the streptomycin-sensitive allele of the rpsL gene. By placing the gene for positive selection and that used for negative selection within and outside the target gene of interest, respectively, gene replacement is obtained. A one-step double selection procedure provides a means to distinguish strictly between gene replacement by double crossover versus homologous recombination by single crossover events. The system should have considerable potential for genera or species where single-crossover events or even illegitimate recombination are the predominant recombination mechanisms. It should also be of wide use for the construction of mutants without a selectable phenotype.

Base Sequence↗
PubMed1994

The antimicrobial activity of essential oils and essential oil components towards oral bacteria.

A method for reproducibly determining minimal inhibitory concentrations and minimal bactericidal concentrations of plant extracts towards fastidiously and facultatively anaerobic oral bacteria, predicated upon measurements of optical densities in microtitre plate wells, was devised. The antimicrobial properties of some botanical oils were surveyed; of these, Australian tea tree oil, peppermint oil, and sage oil proved to be the most potent essential oils, whereas thymol and eugenol were potent essential oil components.

Actinomyces viscosus↗
PubMed1994

Genetic alterations in streptomycin-resistant Mycobacterium tuberculosis: mapping of mutations conferring resistance.

We report on the identification of mutations associated with streptomycin resistance in Mycobacterium tuberculosis. Two isolates (3656 and 3976) showed a wild-type ribosomal protein, S12, but exhibited a single point mutation at 16S rRNA position 491 (C-->T) or 512 (C-->T), respectively. Sequence analysis of a third isolate (2438) revealed a single base change at 16S rRNA position 904 (A-->G). This position is equivalent to invariant position 913 of the Escherichia coli 16S rRNA gene, an A-->G transition of which has been shown previously to impair streptomycin binding and streptomycin-induced misreading in vivo. Surprisingly, strain 2438 harbors an additional mutation in the ribosomal protein S12 (Lys-88-->Gln).

Base Sequence↗
PubMed1994

Identification of mutations in 23S rRNA gene of clarithromycin-resistant Mycobacterium intracellulare.

Clarithromycin is a potent macrolide that has been used for treating infections with nontuberculous mycobacteria. Pairs of susceptible and resistant Mycobacterium intracellulare strains were obtained from patients with chronic pulmonary M. intracellulare infections undergoing monotherapy with clarithromycin. Nucleotide sequence comparisons of the peptidyltransferase region in 23S rRNAs from parental and resistant strains revealed that in three of six resistant strains, for which the MIC was > 32 micrograms/ml, a single base was mutated (Escherichia coli equivalent, A-2058-->G, C, or U). As the modification of adenine 2058 by dimethylation is a frequent cause of macrolide resistance in a variety of different bacteria, we suggest that mutation of A-2058 confers acquired resistance to clarithromycin in M. intracellulare.

Base Sequence↗
PubMed1994

Zinc, a structural component of adenylate kinases from gram-positive bacteria.

The recent finding that Bacillus stearothermophilus adenylate kinase contains a zinc atom coordinated to four cysteines prompted us to investigate the metal-binding properties of the enzyme from various bacteria. We conclude that zinc was present only in adenylate kinase from gram-positive species and that this property is correlated with the presence of three or four Cys residues in the sequence Cys-X2-Cys-X16-Cys-X2-Cys/Asp, in which X stands for different amino acid residues.

Adenylate Kinase↗
PubMed1994

Lipoprotein(a) concentrations in cord and capillary blood from newborns and in serum from in-patient children, adolescents and adults.

Investigations have been made upon the distribution of lipoprotein(a) concentrations in cord and capillary blood from newborns and in serum from in-patient children and adults. Full-term neonates (n = 123), children aged 1 month to 16 years (n = 331) and adults aged between 17 and 88 years (n = 252) of age were included in the study. Lipoprotein(a) was determined using an immunoluminometric assay and a single lot of reagents. The assay had an effective measuring range of 1-800 mg/l. Lipoprotein(a) could be measured either in cord or capillary blood in the majority of cases. Problems arose in isolated cases, in each of which there was a large concentration difference in lipoprotein(a) between mother and child. The correlation data was: r = 0.897, n = 37, log (capillary blood) = 0.874 log (cord blood) + 0.165. The median lipoprotein(a) concentrations in cord and capillary blood were 13.9 and 10.2 mg/l respectively. Median lipoprotein(a) concentrations increased from birth up until the 6th decade (159 mg/l), decreasing to 95 mg/l during the 9th decade of life. In mature newborns, the median lipoprotein(a) concentrations correlated with gestational age. The distribution of lipoprotein(a) concentrations in serum is skewed throughout life, the ratio mean/median being 2.07 at birth, 2.71 in children and 2.72 in adults. The percentage of children with lipoprotein(a) concentrations above 250 mg/l was 23.0 (male) and 23.8 (female). The corresponding figures for adults was 38.2 for males and 28.2 for females respectively. In the group of newborns 27.7 percent had concentrations above 25 mg/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Anorexia nervosa in an elderly man.

Anorexia nervosa (AN) rarely develops after the age of 30 years, and rarely occurs in men. We report a case of chronic AN in a 72-year-old man, who reported a 20-year history of extreme low body weight, persistent fears of obesity, and feelings of being fat even at 93 lb. Also reported were episodes of self-induced vomiting, laxative abuse, and excessive exercising. Patient's scores on a battery of questionnaires were also consistent with a diagnosis of AN.

Aged↗
PubMed1993

Mycobacterium intermedium sp. nov.

Strains of a new type of slowly growing mycobacterium were repeatedly isolated from sputum from a patient with pulmonary disease. This photochromogenic organism grew at 22, 31, 37, and 41 degrees C, possessed catalase, acid phosphatase, esterase, beta-galactosidase, and arylsulfatase activities, and hydrolyzed Tween. It did not produce nicotinic acid or have nitrate reductase, acetamidase, benzamidase, isonicotinamidase, nicotinamidase, pyrazinamidase, succinidamidase, and acid phosphatase activities. Urease activity was variable. The organism is susceptible to ethambutol and resistant to isoniazid and streptomycin. A mycolic acid analysis revealed the presence of alpha-mycolates, alpha'-mycolates, and keto-mycolates. The results of comparative 16S rRNA sequencing placed this organism at an intermediate position between the rapidly and slowly growing mycobacteria. On the basis of the pattern of enzymatic activities and metabolic properties, the results of fatty acid analyses, and the unique 16S rRNA sequence, we propose that this organism represents a new species, for which we propose the name Mycobacterium intermedium. The type strain is strain 1669/91; a culture of this strain has been deposited in the Deutsche Sammlung von Mikroorganismen und Zellkulturen as strain DSM 44049.

Bacterial Typing Techniques↗
PubMed1993

Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot.

Multidrug-resistant strains of Mycobacterium tuberculosis have resulted in several recent outbreaks. Recognition of drug resistance is important both for treatment and to prevent further transmission. Here we use molecular biology techniques to study the basis of streptomycin resistance in single and multidrug-resistant M. tuberculosis. We demonstrate that streptomycin resistance is associated with mutations implicated in ribosomal resistance. The mutations found either lead to amino acid changes in ribosomal protein S12 or alter the primary structure of the 16S rRNA. The 16S rRNA region mutated perturbs a pseudoknot structure in a region which has been linked to ribosomal S12 protein.

Base Sequence↗
PubMed1993

Genotypic identification of mycobacteria by nucleic acid sequence determination: report of a 2-year experience in a clinical laboratory.

Clinical isolates of Mycobacterium spp. were identified by direct sequence determination of 16S rRNA gene fragments amplified by polymerase chain reaction. Identification was based on a hypervariable region within the 16S rRNA gene in which mycobacterial species are characterized by species-specific nucleotide sequences. A manually aligned data base including the signature sequences of 52 species of mycobacteria easily allowed rapid and correct identification. The results of this study demonstrate that polymerase chain reaction-mediated direct sequence determination can be used as a rapid and reliable method for the identification of mycobacteria in the clinical laboratory. In addition, the prompt recognition of previously undescribed species is now feasible.

Base Sequence↗
PubMed1993

Elimination of contaminating DNA within polymerase chain reaction reagents: implications for a general approach to detection of uncultured pathogens.

Analysis based on comparisons of 16S rRNA sequences provides a rapid and reliable approach to identifying human pathogens. By directing oligonucleotide primers at sequences conserved throughout the eubacterial kingdom, bacterial 16S ribosomal DNA sequences of virtually any member of the eubacterial kingdom can be amplified by polymerase chain reaction and subsequently analyzed by sequence determination. Indeed, automated systems for broad-range amplification, sequencing, and data analysis are now feasible and may form the basis of the next generation of automated microbial identification systems. However, identification of pathogens by this strategy is hampered by the frequent contamination of reagents used for the amplification reaction, in particular Taq polymerase, with exogenous bacterial DNA. Here, we describe detailed investigations on the use of 8-methoxypsoralen and long-wave UV light to eliminate contaminating DNA in polymerase chain reaction reagents. The clinical utility of the developed procedure was demonstrated in a case of paucibacillary osteomyelitis, for which no specific bacterial agent had been cultured.

Bacteria↗
PubMed1992

[Rehabilitation following falls of undetermined etiology: results of an intervention study].

In a population of 355 nursing-home patients 35 could be identified with "idiopathic senile gait disturbance" or falls. Out of these, twelve patients were motivated to participate in a trial to improve the gait. Six patients participated in an intensive daily physiotherapy-program for five weeks, six patients served as a control group. Five of the six patients in the intervention group improved the gait to a high degree. The gait analysis documented an abnormal posture due to a long use of walking aids, which was not influenced by the training. The study documents that very old nursing home patients can improve the mobility by intensive gait training if they can be motivated for such therapy.

Accidental Falls↗
PubMed1991

Potential photosensitizers for photodynamic therapy. III. Photophysical properties of a lipophilic chlorin and its zinc and tin chelates.

Photophysical properties of a lipophilic chlorin derivative and its zinc and tin chelates were investigated in chloroform. The quantum yields of the fluorescence phi F, of the S1----T1 intersystem crossing phi T and of singlet oxygen (1 delta g) formation phi delta, as well as the Stern-Volmer constants for the quenching of the S1 states by oxygen and the rate constants of quenching of O2(1 delta g) by the chlorins were measured. In comparison to the metal-free chlorin an increase of phi T and a decrease of phi F have been observed for the metal-containing derivatives, whereas the phi delta values remain constant.

Chelating Agents↗