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Biomedical subjects

S Sommer

Publications and source records attributed to S Sommer.

At least 91 records · Page 5Linked to original sources
PubMed1997

Investigation of the mechanism of action of 2% fusidic acid lotion in the treatment of acne vulgaris.

We describe the results of a single-centre, double-blind, vehicle-controlled, parallel group study on the quantitative effects of 2% fusidic acid lotion (Fucidin lotion) in facial acne vulgaris. The trial was completed by 52 patients aged 15-25 years with mild to moderate acne who had been randomized to either Fucidin Lotion (n = 25) or its base (n = 27). Primary outcome measures included colony counts of Propionibacterium acnes and micrococcaceae and measurements of skin surface lipid free fatty acids and sebum excretion rate. Clinical assessment was based on the acne grade, count of inflamed and non-inflamed lesions and evidence of a primary irritant dermatitis. There was a variable but gradual reduction in lesion counts with the maximum improvement at 12 weeks for inflamed lesions, where the reduction was 19.9% for fusidic acid and 24.7% for the placebo. The non-inflamed lesions decreased by 10.8% in the fusidic acid group and increased by 15.9% in the placebo group; this difference was not statistically significant. Although the fusidic acid reduced the micrococcaceae count by 1 log cycle, inferring adequate compliance, there was no reduction in the counts of P. acnes, surface free fatty acids or sebum excretion rate. This study has failed to explain the mechanism of action of topical fusidic acid.

Acne Vulgaris↗
PubMed1996

Characterization of a mutant RecA protein that facilitates homologous genetic recombination but not recombinational DNA repair: RecA423.

A recA mutant (recA423; Arg169-->His), with properties that should help clarify the relationship between the biochemical properties of RecA protein and its two major functions, homologous genetic recombination and recombinational DNA repair, has been isolated. The mutant has been characterized in vivo and the purified RecA423 protein has been studied in vitro. The recA423 cells are nearly as proficient in conjugational recombination, transductional recombination, and recombination of lambda red- gam- phage as wild-type cells. At the same time, the mutant cells are deficient for intra-chromosomal recombination and nearly as sensitive to UV irradiation as a recA deletion strain. The cells are proficient in SOS induction, and results indicate the defect involves the capacity of RecA protein to participate directly in recombinational DNA repair. In vitro, the RecA423 protein binds to single-stranded DNA slowly, with an associated decline in the ATP hydrolytic activity. The RecA423 protein promoted a limited DNA strand exchange reaction when the DNA substrates were homologous, but no bypass of a short heterologous insert in the duplex DNA substrate was observed. These results indicate that poor binding to DNA and low ATP hydrolysis activity can selectively compromise certain functions of RecA protein. The RecA423 protein can promote recombination between homologous DNAs during Hfr crosses, indicating that the biochemical requirements for such genetic exchanges are minimal. However, the deficiencies in recombinational DNA repair suggest that the biochemical requirements for this function are more exacting.

Adenosine Triphosphatases↗
PubMed1996

Genetic engineering of plant secondary metabolism. Accumulation of 4-hydroxybenzoate glucosides as a result of the expression of the bacterial ubiC gene in tobacco.

The ubiC gene of Escherichia coli encodes chorismate pyruvatelyase, an enzyme that converts chorismate into 4-hydroxybenzoate (4HB) and is not normally present in plants. The ubiC gene was expressed in Nicotiana tabacum L. plants under control of a constitutive plant promoter. The gene product was targeted into the plastid by fusing it to the sequence for the chloroplast transit peptide of the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase. Transgenic plants showed high chorismate pyruvate-lyase activity and accumulated 4HB as beta-glucosides, with the glucose attached to either the hydroxy or the carboxyl function of 4HB. The total content of 4HB glucosides was approximately 0.52% of dry weight, which exceeded the content of untransformed plants by at least a factor of 1000. Feeding experiments with [1,7-13C2]shikimic acid unequivocally proved that the 4HB that was formed in the transgenic plants was not derived from the conventional phenylpropanoid pathway but from the newly introduced chorismate pyruvate-lyase reaction.

Amino Acid Sequence↗
PubMed1995

[Automated determination of total nitrogen in milk by the Dumas method].

A nitrogen analyser based on the Dumas method (LECO FP-428) and equipped with a liquid injector has been tested. The intensive steam production during injection may result in poor nitrogen recoveries for volatile nitrogen compounds such as ethylene diamine. However, recoveries could be improved by slow injection and by filling the combustion tube with Cer(IV)-oxide. For the analysis of milk the instrument was calibrated with NaN3 solutions because their response was found to be less sensitive to burning conditions. Dumas-N and Kjeldahl-N of milk showed good correlation (r = 0.998). However, with the Dumas method about 6.7% (+ 0.035% N) higher nitrogen values were obtained. With a standard deviation of repeatability S(r) = 0.002% N (CVr = 0.33) and a between day reproducibility SD = 0.006% N (CVD = 1.1%) the precision of the Dumas method was similar to that reported for the Kjeldahl method. In order to avoid systematic errors the use of standard milk samples for calibration is recommended. It is concluded that modern instruments using the Dumas method allow precise measurements of nitrogen in milk with a high sample throughout.

Animals↗
PubMed1994

[Macrocytic anemia in the last trimester of pregnancy due to dietary insufficiency--initially interpreted as the HELLP syndrome].

A case of severe macrocytic anaemia caused by cobalamin and folic acid deficiency in a 32 year-old gemellipregnant woman in gestational week 32 +2 is described. Her symptoms and the laboratory data were initially interpreted as HELLP-syndrome (haemolysis, elevated liver enzymes and low platelet count), and caesarean section was performed. None of the persons involved in her earlier prophylactic controls suspected anaemia, and no specific dietary advice were given. If she had received dietary advice early in the pregnancy, anaemia could have been avoided. This emphasizes the need for dietary advice early in pregnancy.

Adult↗
PubMed1994

Search for mutations in the beta 1 GABAA receptor subunit gene in patients with schizophrenia.

As alterations in GABAergic neurotransmission have been indirectly implicated in the pathogenetics of schizophrenia, GABAA receptor subunit genes are plausible candidate genes for the illness. We undertook a search for sequence variations in the coding region of beta 1 subunit gene by designing intron-based primers to amplify its 9 exons. Using single strand conformation polymorphism (SSCP) analysis, we found an exon 9 variant present in 3 of 86 unrelated schizophrenic cases derived from families having at least 2 first-degree relatives with schizophrenia. Direct sequencing of the SSCP variant revealed a C-->G nucleotide transversion at codon 396 predicting a histidine to glutamine substitution in the beta 1 peptide. The predicted amino acid substitution occurs at a highly conserved site, 9 residues from a cAMP-dependent serine phosphorylation consensus sequence. All known GABAA beta 1 subunit genes including human, bovine, and rat, code for histidine at position 396. Although the variant cosegregated with disease in a family with 2 affected sibs, it was only transmitted to 2 of 3 affected sibs in a multiplex family. The variant was not found in an additional sample comprising 155 unrelated schizophrenics and the sequence variant was present at a low frequency (approximately 1.1%) in control groups. Although these results indicate that the sequence variant is likely to be a natural polymorphism, it is possible that the variant may be a predisposing allele in rare instances. It is also possible that the variant may change the function or regulation of the GABAA receptor complex and it may be of pharmacogenetic relevance.

Adolescent↗
PubMed1994

Mutability of Salmonella tester strains TA1538 (hisD3052) and TA1535 (hisG46) containing the UmuD' and UmuC proteins of Escherichia coli.

We have studied the mutability of Salmonella typhimurium tester strains carrying plasmids in which either the umuDC or the umuD'C operon of Escherichia coli have been cloned. Reversion of the hisD3052 frameshift mutation by benzo[a]pyrene (B[a]P), aflatoxin B1 (AFB1) and 1-nitropyrene (1-NP), was very efficiently promoted by UmuD' (the activated form of UmuD) and UmuC proteins. In contrast, UmuD'C proteins promoted a moderate reversion of the missense hisG46 allele by B[a]P, and were not effective in mediating this reversion by AFB1. The Salmonella tester strain carrying the hisD3052 allele and containing the E. coli UmuD'C proteins has a sensitivity toward frameshift mutagens similar to that of the MucAB containing strain TA98, and may be useful for obtaining a high level of mutants generated by the SOS mutagenic mechanism in the absence of MucAB proteins.

Aflatoxin B1↗
PubMed1993

Homologous recombination-dependent initiation of DNA replication from DNA damage-inducible origins in Escherichia coli.

Escherichia coli cells induced for the SOS response express inducible stable DNA replication (iSDR) as an SOS function. Initiation of iSDR is independent of transcription, translation and DnaA protein, which are essential for initiation of DNA replication from oriC. We found that a recA mutant that is defective in recombination but proficient in SOS induction could not elicit iSDR. In contrast, iSDR was enhanced by recD and recJ mutations that inactivate the exonuclease V activity of the RecBCD enzyme and the RecJ exonuclease activity, respectively. A mutation in the ruvC gene that blocks the resolution of recombination intermediates (i.e. Holliday structures) also enhanced iSDR. Furthermore, inhibition of branch migration by recG or ruvAB mutations dramatically increased the iSDR activity. recBC mutants are defective in iSDR induction but the defect was suppressed by a mutation in the sbcA gene. The major product of minichromosomes replicated by iSDR was covalently closed circular monomers. We propose that recombination intermediates (i.e. D-loop structures) created by the action of RecA recombinase and RecBC(D) helicase play a central role in initiation of iSDR.

Bacterial Proteins↗
PubMed1993

Induction of only one SOS operon, umuDC, is required for SOS mutagenesis in Escherichia coli.

The actions of UmuDC and RecA proteins, respectively in SOS mutagenesis are studied here with the following experimental strategy. We used lexAl (Ind-) bacteria to maintain all SOS proteins at their basal concentrations and then selectively increased the concentration of either UmuDC or RecA protein. For this purpose, we isolated operator-constitutive mutations oc in the umuDC and umuD'C operons and also used the oc98-recA mutation. The oc1-umuDC mutation prevents LexA repressor from binding to the operator and improves the Pribnow box consensus sequence. As a result, 5000 UmuD and 500 UmuC molecules per cell were produced in lexAl bacteria. This concentration is sufficient to restore SOS mutagenesis. The level of RecA protein present in the repressed state promoted full UmuD cleavage. Overproduction of RecA alone did not promote SOS mutagenesis. Increasing the level of RecA in the presence of high concentrations of UmuDC proteins has no further effect on SOS mutagenesis. We conclude that, after DNA damage, umuDC is the only SOS operon that must be induced in Escherichia coli to promote SOS mutagenesis.

Bacterial Proteins↗
PubMed1993

The effects of midazolam on the EEG during sedation of critically ill patients.

Patients who require mechanical ventilation are often sedated with midazolam. As clinical signs of sedation are often confusing or nonexistent, and there are few adverse side effects when large doses are infused over a period of days, substantial drug accumulation can result in these critically ill patients, despite the short half-life of midazolam. An objective monitor of sedation would help maintain sedation at a constant level despite changing pharmacokinetic values in patients. We undertook this study to describe the electroencephalographic changes which occur with intravenous midazolam in critically ill patients, and to determine if a relationship exists between these changes and the depth of sedation as measured using a clinical scoring method. A series of 31 critically ill patients who required intravenous midazolam during mechanical ventilation were studied. Four different levels of sedation were defined ranging from execution of verbal commands to no response to suctioning through the tracheal tube or sternal rub. Electroencephalographic recordings were obtained in patients on a daily basis and a concurrent sedation level was determined. High frequency electroencephalogram activity decreased as sedation level increased. This was reflected in decreases in the spectral edge (17.61 to 10.56 Hz (p = 0.0024)), the median frequency (4.27 to 2.56 Hz (p = 0.0278)), and the logarithm of the absolute power in the beta 1 (p = 0.0012), and beta 2 (p < 0.0001) bands. An incidental finding of asymmetry in power between right and left frontal electrodes was observed, with right-sided power being 9-18% greater (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The appearance of the UmuD'C protein complex in Escherichia coli switches repair from homologous recombination to SOS mutagenesis.

The process of SOS mutagenesis in Escherichia coli requires (i) the replisome enzymes, (ii) RecA protein, and (iii) the formation of the UmuD'C protein complex which appears to help the replisome to resume DNA synthesis across a lesion. We found that the UmuD'C complex is an antagonist of RecA-mediated recombination. Homologous recombination in an Hfr x F- cross decreased as a function of the UmuD'C cell concentration; this effect was challenged by increasing RecA concentration. Recombination of a u.v.-damaged F-lac with the lac gene of an F- recipient was reduced by increasing the UmuD'C concentration while lac mutagenesis increased, showing an inverse relationship between recombination and SOS mutagenesis. We explain our data with the following model. The kinetics of appearance of the UmuD'C complex after DNA damage is slow, reaching a maximum after an hour. Within that period, excision and recombinational repair have had time to occur. When the UmuD'C concentration relative to the number of residual RecA filaments, not resolved by recombinational repair, becomes high enough, UmuD'C proteins provide a processive factor for the replisome to help replication bypass and repel the standing RecA filament. Thus, at a high enough concentration, the UmuD'C complex will switch repair from recombination to SOS mutagenesis.

Bacterial Proteins↗
PubMed1993

Pharmacokinetics of glycerol administered orally in healthy volunteers.

Of the three standard osmotherapeutics glycerol, mannitol and sorbitol, glycerol (CAS 56-81-5) alone can be applied orally. As only limited pharmacokinetic data after oral administration are available, studies were performed in 10 healthy subjects (2 female, 8 male, body weight 58-90 kg, age 23-47 years). After 12 h of fasting the subjects drank a single dose of 1.2 g/kg glycerol (Glycerol 85% DAB 9, flavoured with lemon juice). For the first 90 min venous blood was sampled every 15 min, for the following 6.5 h every 30 min. Glycerol serum concentrations were determined by an enzymatic procedure. Intestinal absorption was rapid. Maximum glycerol serum levels ranging from 1285-2238 mg/l (median = 1770 mg/l) were observed 1-2 h after ingestion. On the assumption of full intestinal absorption total body clearance was 0.18-0.26 l/h.kg, and the apparent volume of distribution 0.18-0.34 l/kg. The terminal elimination half-life ranged from 0.61-1.18 h. The concentration-time curves were not adequately described by linear pharmacokinetic models. In all subjects glycerol serum concentrations were high enough to induce increases of serum osmolality of at least 10 mosmol/kg. No signs of haemolysis or haemodilution were observed.

Administration, Oral↗
PubMed1992

Preventive care in general practice.

Preventive care is an integral component of general practice teaching in all Australian medical schools. While curriculum time and teaching methods vary, the overriding emphasis remains on integrating both epidemiological and behavioural science approaches into the primary care setting. Preventive aspects are stressed during attachments with general practitioners. Use of appropriate theoretical frameworks and models allows the role of the general practitioner in disease prevention to be formalized. Undergraduate teaching is further reinforced by programs within the Family Medicine Programme at a vocational training level, and the Royal Australian College of General Practitioners at a continuing medical education level.

Australia↗