Biomedical subjects

M Forsman

Publications and source records attributed to M Forsman.

49 records · Page 3Linked to original sources

PubMed1990

Molecular analysis of beta-lactamases from four species of Streptomyces: comparison of amino acid sequences with those of other beta-lactamases.

Genes encoding extracellular beta-lactamases of Streptomyces badius, Streptomyces cacaoi, Streptomyces fradiae and Streptomyces lavendulae were cloned and mapped in Streptomyces lividans. DNA sequence analysis of the beta-lactamase genes revealed a high overall G + C content, ranging from 71 to 75 mol%, with a G + C content of 95 mol% at the third position of the codons for all four genes. The primary structure of the beta-lactamases including their signal peptides was deduced. The four beta-lactamases exhibited homology to each other and to class A beta-lactamases from other bacterial genera. We suggest that Streptomyces beta-lactamases are representatives of a superfamily of genes, from which class A beta-lactamases of Gram-negative bacteria may have evolved.

Amino Acid Sequence↗

PubMed1990

Partial reversal of the cerebral effects of isoflurane in the dog by theophylline.

The cerebral effects of adding theophylline to 1.4% isoflurane anaesthesia were studied in five dogs by a sagittal sinus outflow technique with direct measurement of the cerebral blood flow (CBF) and calculation of the cerebral metabolic rate for oxygen (CMRo2). Three 3 mg.kg-1 doses of theophylline were given with intervals of 10 min. Five min after the second and third dose, when the mean theophylline plasma concentration was 41 and 65 mumols.1(-1), respectively, CMRo2 had increased significantly with a mean value varying between 15% and 13%, and the EEG had changed from a sleep pattern to a more awake pattern in the four dogs with evaluable recordings. There were no significant changes in CBF or mean arterial blood pressure (MABP). It is concluded that the adenosine receptor antagonist theophylline in this study partially reversed the cerebral effects of isoflurane.

Anesthesia, Inhalation↗

PubMed1990

Identification of Francisella species and discrimination of type A and type B strains of F. tularensis by 16S rRNA analysis.

Tularemia is a zoonotic disease, occurring throughout the Northern Hemisphere. The causative agent, the bacterium Francisella tularensis, is represented by two main types. Type A is found in North America, whereas type B is mainly found in Asia and Europe and to a minor extent in North America. No routine technique for rapid diagnosis of tularemia has been generally applied. We have partially sequenced 16S rRNAs of two F. tularensis strains, as well as the closely related Francisella novicida. Of 550 nucleotides analyzed, only one difference in 16S rRNA primary sequence was found. This 16S rRNA analysis enabled the construction of oligonucleotides to be used as genus- and type-specific probes. Such probes were utilized for the establishment of a method for rapid and selective detection of the organism. This method allowed identification of Francisella spp. at the level of genus and also discrimination of type A and type B strains of F. tularensis. The analysis also permitted the detection of F. tularensis in spleen tissue from mice infected with the bacterium. The results presented will enable studies on the epizootiology and epidemiology of Francisella spp.

Animals↗

PubMed1990

Effect of dexmedetomidine, a selective and potent alpha 2-agonist, on cerebral blood flow and oxygen consumption during halothane anesthesia in dogs.

The effect of the alpha 2-agonist dexmedetomidine on the cerebral blood flow (CBF) and the metabolic rate for oxygen was studied by a sagittal sinus outflow technique in dogs during halothane anesthesia. Dexmedetomidine was given in a dose (10 micrograms/kg) reported to reduce the anesthetic requirement of halothane by 90%. During 0.9% halothane anesthesia dexmedetomidine caused a significant reduction in CBF without influencing the metabolic rate for oxygen. Reducing the halothane concentration to 0.1% caused no further change in CBF, but increased the metabolic rate for oxygen 19%. The cerebral vasoconstrictive effect, combined with the 90% reduction in MAC for halothane, indicates that dexmedetomidine might be a useful adjunct to inhalation anesthetics during neurosurgery in situations where an increase in CBF should be avoided.

Adrenergic alpha-Agonists↗

PubMed1989

Transcriptional induction of Streptomyces cacaoi beta-lactamase by a beta-lactam compound.

The soil bacterium Streptomyces cacaoi produces an extracellular beta-lactamase. The beta-lactamase expression could be induced by the beta-lactam compound 6-amino penicillinoic acid (6-APA). In liquid cultures, a 50-fold increase in beta-lactamase expression was observed within the first three hours after addition of 6-APA. Using the cloned beta-lactamase gene as a probe, it was shown that this increase was mediated at the level of transcriptional initiation. The start point of the induced beta-lactamase transcript was determined, and the nucleotide sequence of the promoter region was analysed. No noticeable homology was found to control regions of inducible beta-lactamase genes of other bacteria. A striking feature was the presence of six direct repeats (ten base pairs each) upstream of the promoter region. Thus, an example of an inducible regulatory gene system in this Gram-positive microorganism is presented. Also, the primary structure of the beta-lactamase was deduced, showing a high degree of homology with class A beta-lactamases.

Amino Acid Sequence↗

PubMed1989

The effects of prolonged isoflurane anaesthesia on cerebral blood flow and metabolism in the dog.

To determine whether cerebral blood flow (CBF) changed with time under isoflurane anaesthesia, as has been reported for halothane, CBF and cerebral metabolic rate for oxygen (CMRO2) were studied in five dogs under prolonged isoflurane anaesthesia. CBF was measured with a modified sagittal sinus technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Maintaining this experimental dog model with 1% isoflurane in oxygen and nitrogen for 3 h in five dogs and for 4 h in three dogs did not cause any significant changes in CMRO2 or CBF. Cerebral metabolite levels were consistent with earlier reports from short-time studies and the EEG recordings showed a continuous sleep pattern with no pathological changes. It is concluded that there is no change in CBF or CMRO2 in our modified sagittal outflow model during 3-4 h of 1% isoflurane anaesthesia.

Anesthesia, Inhalation↗

PubMed1989

Effects of nimodipine on cerebral blood flow and cerebrospinal fluid pressure after cardiac arrest: correlation with neurologic outcome.

Fifty-one patients were included in a blind randomized study to evaluate whether the Ca-blocker nimodipine could influence cerebral blood flow (CBF) or cerebrospinal fluid pressure (CSFP) during the cerebral hypoperfusion period that follows resuscitation from cardiac arrest and to determine whether changes in CBF correlate with neurologic outcome. CBF measured 1 to 4 hours after arrest with the use of 133Xe intravenous was significantly greater with nimodipine than with placebo (27 +/- 3 versus 13 +/- 1 ml.100 g-1.min-1 at 3 hours), but with no significant difference at 24 hours. There was no clinical evidence of seriously increased CSFP in any patient in either group the first 48 hours. Mean arterial pressure was significantly lower (86 +/- 4 versus 101 +/- 4 mm Hg at 3 hours), and antiarrhythmic drugs were used significantly less frequently in the nimodipine group than in the placebo group. Twelve patients in each group eventually regained consciousness. There was no significant difference in neurologic status between the two groups at any point, and no positive correlation between CBF in the hypoperfusion period and neurologic outcome.

Aged↗

PubMed1988

Beta-lactamase genes of Streptomyces badius, Streptomyces cacaoi and Streptomyces fradiae: cloning and expression in Streptomyces lividans.

Genes encoding extracellular beta-lactamases (EC 3.5.2.6) of Gram-positive Streptomyces badius, Streptomyces cacaoi and Streptomyces fradiae have been cloned into Streptomyces lividans. The beta-lactamase gene of S. badius was initially isolated on a 7 kb BamHI fragment and further located on a 1300 bp DNA segment. An 11 kb BamHI fragment was isolated encompassing the S. cacaoi beta-lactamase gene, which was subcloned to a 1250 bp DNA fragment. The beta-lactamase gene of S. fradiae was cloned on an 8 kb BamHI fragment and mapped to a 4 kb DNA segment. Each of the three BamHI fragments encompassing the beta-lactamase genes hybridized to a BamHI fragment of the corresponding size in chromosomal DNA from the respective strain used for cloning. The activities of the three beta-lactamases were predominantly found to be extracellular in the S. lividans recombinants. The S. badius and S. cacaoi beta-lactamases exhibited a 10-100-times lower activity in S. lividans, whereas the S. fradiae beta-lactamase showed an approximately 10-fold higher activity in the cloned state, compared with the activities found in the original strains.

Biological Transport↗

PubMed1988

Superoxide dismutase and catalase failed to improve neurologic outcome after complete cerebral ischemia in the dog.

Superoxide dismutase (SOD) and catalase, natural scavengers of free oxygen radicals, or saline were administered as a continuous systemic infusion to 12 dogs, in a blind randomized fashion, starting 10 min prior to a 10-min episode of complete cerebral ischemia, and continued thereafter for 60 min. Reversible complete cerebral ischemia was achieved by simultaneously occluding the ascending aorta and venae cavae. There were no significant differences in physiological variables (arterial blood gases, hemoglobin, mean arterial blood pressure, heart rate, and temperature) between the two groups, either pre-ischemia or post-ischemia. There was no significant difference in neurologic outcome when evaluated at 48 h post-ischemia. It has previously been reported that the same dose of SOD and catalase as used in the current study could reduce infarct size by 50% when given systemically before reperfusion following coronary ischemia in dogs. The lack of a measurable effect on neurologic outcome in our cerebral ischemic model might be because of the failure of the free oxygen radical scavengers to reach the ischemic cells in sufficient amounts, or because free oxygen radicals do not contribute to brain injury following complete cerebral ischemia.

Animals↗

PubMed1988

Partial reversal of the cerebral effects of isoflurane in the dog by the benzodiazepine antagonist flumazenil.

Six dogs initially anaesthetized with isoflurane-N2O-O2 for surgery with cannulation of the sinus sagittalis for direct measurement of cerebral blood flow (CBF) and maintained with 1% isoflurane-N2-O2 anaesthesia, were given two 2-mg doses of the benzodiazepine antagonist flumazenil with an interval of 10 min. This was accompanied by a significant increase in the cerebral metabolic rate for oxygen (CMRO2) 10 min after the first 2-mg dose, and 5, 10 and 15 min after the second 2-mg dose, the increase varying in mean value from 9% to 14%. EEG was recorded in five of the six dogs and administration of flumazenil converted the EEG from a sleep pattern to an awake pattern in two of them. There were no significant changes in the CBF or mean arterial blood pressure (MABP) values. In the brain biopsies taken at the end of the study there were no significant changes in the adenylate energy charge (EC) and the lactate/pyruvate ratio (L/P) when compared to five other dogs not given flumazenil. It is concluded that flumazenil in this study demonstrated a partial antagonism of the cerebral effects of isoflurane.

Animals↗

PubMed1987

Chromogenic identification of promoters in Streptomyces lividans by using an ampC beta-lactamase promoter-probe vector.

A promoter-probe system, based on the ampC beta-lactamase gene of Escherichia coli, has been developed for the isolation and characterization of transcriptional signals in the gram-positive bacterium Streptomyces lividans. The promoter-probe vector, denoted pJAS14, has the SLP1.2 replicon with a copy number of four-five plasmids per cell. It contains a unique BamHI site just in front of the ampC ribosome-binding site, and upstream of this BamHI site a transcriptional terminator signal that prevents readthrough transcription from plasmid-borne promoters has been inserted. Using pJAS14, we have shot-gun cloned chromosomal DNA from S. lividans and S. lavendulae into the BamHI site, and isolated a number of promoter containing DNA fragments by the use of the chromogenic cephalosporin nitrocefin. On plates, we identified promoters of varying strengths and also with differences in nutritional and temporal expression. Using liquid cultures of S. lividans, it has been demonstrated that one promoter, denoted P1 (SEP8), as well as the ampC gene of E. coli, show activity corresponding to the vegetative growth of the cells. The P1 (SEP8) promoter was shown to be expressed also in E. coli, and it initiates RNA synthesis at exactly the same nucleotides in both S. lividans and E. coli. The promoter shows good homology to the E. coli promoter consensus sequence in both the -35 and -10 regions. Thus, this promoter is a representative of the SEP (Streptomyces E. coli-type promoter) class of promoters recently described (Jaurin and Cohen 1985). This indicates that an S. lividans RNA polymerase recognizes the same sequence determinants and chooses the point of initiation of RNA synthesis in the same way as the corresponding E. coli enzyme.

Base Sequence↗

PubMed1987

Effect of chronic bupivacaine infusion on seizure threshold to bupivacaine.

Thirty rats were pretreated with a continuous infusion of bupivacaine or placebo. On the fourth day the acute seizure threshold to bupivacaine was determined for both groups. The seizure dose, blood and brain concentration of bupivacaine showed no difference between the groups. The tachyphylaxis seen clinically when bupivacaine is used for a regional nerve blockade does not seem to evolve for the CNS-effects.

Animals↗

PubMed1986

The effects of nimodipine on cerebral blood flow and metabolism.

Nimodipine, a calcium entry blocker, was administered in increasing doses of 0.1-3.0 micrograms kg-1 min-1 to six dogs after they had recovered consciousness from a surgical preparation that was conducted under general anesthesia and while they were under the influence of total spinal anesthesia. CBF was measured with a sagittal sinus outflow technique and CMRO2 was calculated as the product of CBF and the arteriovenous O2 difference. Nimodipine did not influence either CBF or CMRO2. There was a decrease in the cortical pyruvate level at the end of the study, but no significant change in phosphocreatine, ATP, lactate, or energy charge when compared with six control dogs. It has previously been reported that nimodipine increases the CBF in global ischemia with a potentially beneficial effect on the neurological outcome. With no effect on normal CBF or metabolism, this suggests that nimodipine may be useful in a variety of ischemic situations without fear of either a steal phenomenon or untoward effects on intracranial pressure.

Animals↗