Biomedical subjects
Publications and source records attributed to L Nilsson.
Three models for mRNA translation are discussed in the light of available experimental data. It is concluded that the elongation rates vary along a messenger, possibly as a result of a coupling between ribosome movement and mRNA secondary structure. Some promising areas of further experimentation are indicated.
Bacterial ATP levels in Escherichia coli cultures were determined by luciferin/luciferase assay. Rapid effects of gentamicin on ATP levels in the cultures were studied, and a dose-dependent accumulation of extracellular ATP was demonstrated. This phenomenon was used to develop a rapid bioassay of gentamicin in clinical serum specimens. The accuracy of the assay, expressed as coefficient of variation over the range 16 to 1 mug/ml, varied between 1.8 and 6.5%, compared to 2.3 to 4.7% for an agar disk diffusion assay. Serum gentamicin concentrations were determined by both methods in 122 serum specimens from 43 patients receiving gentamicin alone or in combination with other antibiotics, and the results were compared (r = 0.942). Determination of gentamicin based on luciferase assay of extracellular ATP in bacterial cultures requires only 10 mul of serum, allowing for capillary sampling, and results are available within 2 h.
In 28-day-old rats injected with PMSG, ovarian cyclic AMP and PGE and PGF increased 2 and 3-4 h respectively after the LH peak.
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Fifteen chronic alcoholics and 15 presenile patients were matched in pairs with regard to their mean hemisphere cerebral blood parameters-an index of brain metabolism. The distribution of the regional cerebral blood flow was similar in the two groups. The alcoholics performed significantly better in all psychometric tests than the presenile patients and more alcoholics than presenile patients were still employed and working. Nine presenile patients and one alcoholic showed symptoms indicating brain stem dysfunction. The measurements of the cerebral blood blow were made at rest while the psychometric testings and the evaluation of the social performance gave information about the brain at work. It is suggested that cerebral dysfunction in alcoholics to some extent can be partly overcome by brain activation procedures. In contrast, the defects of higher mental functions in presenile dementia cannot be compensated for.
Short time effects of ampicillin on viability and levels of intracellular ATP were studied in bacterial cultures and a close relationship between intracellular ATP levels and viability was demonstrated. The connection between the effects observed and MIC values is discussed. The possibility of using the phenomenon for rapid antibioitc susceptibility testing was studied in clinical isolates incubated for 2 hours followed by luciferase assay of intracellular ATP. A positive correlation was demonstrated between ampicillin-induced decreases in intracellular ATP and inhibitory zone diameters, as measured by the agar diffusion technique.
Monolayer of HeLa cells were examined for their ability to endocytose Salmonella typhimurium 395 MS (wild) and MR10 (chemotype RD). Monolayers treated with the glycolytic inhibitors iodoacetic acid (IAA) or N-ethylmaleimide (NEM) or the respiratory inhibitor sodium azide (NaN3) or cytochalasin B (CB) were incubated with S. typhimurium. The numbers of cell-associated (intracellular plus cell-membrane attached extracellular) and intracellular bacteria were determined by viable counts, together with the HeLa cell ATP levels. IAA and NEM at concentrations 10(-4)M and 10(-3)M decreased significantly the number of intracellular MR10 and the cellular ATP levels, but did not influence significantly the total number of cell-associated bacteria except for 10(-3)M IAA which slightly increased the association. On the other hand, NaN3 at concentrations 10(-4)M and 10(-3)M did not affect the number of associated or intracellular bacteria, or the cellular ATP levels. CB at concentrations of 5, 10 and 20 microgram/ml increased the number of associated bacteria, decreased the number of intracellular bacteria and caused a small decrease in cellular ATP levels. Thus, HeLa cells may internalize S. typhimurium by an energy-requiring, glycolysis-dependent process. CB had a dose-dependent inhibitory effect on the internalization without influencing significantly the HeLa cell ATP levels. This indicates that CB might affect the internalization process by some means other than decreasing the ATP content.
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A rapid semiautomated bioassay of gentamicin in serum based on the effect of gentamicin on intracellular adenosine triphosphate (ATP) levels in bacterial cultures is presented. The ATP assay was performed with the firefly luciferin/luciferase system and results were compared with an agar diffusion technique. The lower limit of detection was set at 1 microgram/ml. The accuracy of the ATP assay expressed as a recovery of gentamicin over the range 1--8 microgram/ml was 98--103% and S.D. varied between 11-15%. The reproducibility was approximately within the same limits. Other antibiotics tested did not interfere with the determination of gentamicin. 112 clinical serum specimens containing gentamicin alone (N = 55) or in combination with other antibiotics (N = 57) were assayed and results with the two methods compared (r = 0.94). Volumes required were 0.1 ml serum and results were available within 3 h.
Five cases of hydrosalpinx simplex were studied by light microscopy and scanning electron microscopy (SEM). Comparison was made with normal fallopian tube epithelia. By light microscopy numerous ciliated cells as well as nonciliated cells were found in both hydrosalpinx and normal tubal material. In hydrosalpinx material the epithelium was found to be compressed to one-sixth its usual height. The SEM survey of large areas of hydrosalpinx did not reveal any deciliation. In fact, the mucosa of the hydrosalpinx did not differ conspiciously from that of a healthy fallopian tube. However, some nonciliated cells with collapsed areas were revealed by SEM. The significance of the compressed areas is unknown.
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In order to study the problem of how fast and to what degree severe hypoxic brain tissue changes are reversed after reoxygenation, we challenged the viability of the brain by exposing experimental animals to anoxia of such a duration that cardiopulmonary resuscitation was just possible. The brain tissue concentrations of glucose, lactate, pyruvate and of ATP, ADP, AMP and phosphocreatine were determined. Two series of experiments were carried out. In the first, groups of rats deprived of oxygen for 1, 2, 4 and 6 min were studied in order to show brain tissue changes in the period of impending death as well as the changes coinciding with the onset of clinical death (blood pressure zero). In addition, one group maintained at a rectal temperature of 37 +/- 0.5 degrees C and ventilated for 60 min with an oxygen free gas mixture was included aimed at representing a state of irreversibility. In the second series, restitution after 6 min of no oxygen supply was studied 10 min, 1/2 h, 1 h, and 2 h after cardiopulmonary resuscitation. Attempts were also made to correlate biochemical changes to EEG status and to clinical recovery. The restitution study showed that oxidative phosphorylation of the brain tissue was rapidly resumed with normalization of the adenylate energy charge in all animals in which the pump function of the heart could be restored by our artificial means. However, there was a strikingly poor correlation between recovery of mitochondrial function and restitution of EEG or clinical recovery. Thus, it seems likely that a delayed functional restitution is not due to energy failure but to other biochemical changes or to biophysical alterations not revealed by the present type of study.
The influence of halothane (0.6 and 2%) upon cerebral (cortical) blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) was studied in artificially ventilated rats, using a modified technique of Kety & Schmidt (1948). The values obtained in halothane anaesthesia were compared to those recorded in nitrous oxide anaesthesia, or to those measured in unanesthetized animals given an analgesic drug (fentanyl citrate). Although it could be confirmed that halothane induces vasodilatation in the brain, there were relatively small differences in CBF between the groups. The results demonstrate that, in the rat, halothane depresses CMRo2 in a dose-dependent way. With 0.6% halothane, CMRo2 was reduced by 20-30% and, with 2% halothane, CMRo2 was reduced by about 50%. Thus, in the rat the effect of 2% halothane upon metabolic rate is comparable to that observed in barbiturate anaesthesia.
Macromolecules may adsorb firmly as a monolayer to plastic surfaces and still retain their property to react specifically with antibodies. In the present communication four different principles for visualization of such antigenantibody interactions on plastic surfaces are described. In addition, a diffusion-ingel method for quantitation of antibodies is presented. The described methods offer simple, sensitive and accurate means of assaying antigen-antibody reactions.
Studies on the streptococcal epidemiology of impetigo in children below 12 years of age in Addis Ababa indicated that most streptococci isolated belonged to the classic serological impetigo strains. Streptococcal type 9 seemed to be a new impetigo strain. Several cases of severe acute glomerulonephritis on impetigo basis were observed during the study.
Short-term effects of doxycycline on viability and levels of intracellular ATP in bacteria were studied. Inhibition of growth by doxycycline was reflected in a corresponding inhibition of the accumulation of intracellular ATP which was clearly demonstrable within 1-2 hours. The effects of doxycycline on intracellular ATP were dose-dependent and the use of ATP assays for quantitation of antibiotics in serum is discussed. In 45 clinical isolates exposed to doxycycline a positive correlation was found between antibiotic-induced inhibition of intracellular ATP levels and inhibitory zone diameters with the disc diffusion method, indicating possible clinical applications in rapid susceptibility testing.
The effect of amphotericin B combined with rifampicin or doxycycline on growth, oxygen consumption and ATP levels in cultures of Candida albicans, was studied. Alone, neither rifampicin nor doxycycline--even at high concentrations--affected the growth of the test organism. However, when combined with a concentration of amphotericin B which alone did not affect the growth of C. albicans, a pronounced fungistatic effect was obtained with therapeutically attainable concentrations of the drugs.
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