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Biomedical subjects

L Persson

Publications and source records attributed to L Persson.

At least 163 records · Page 9Linked to original sources
PubMed1991

Regulation of S-adenosylmethionine decarboxylase in L1210 leukemia cells. Studies using an irreversible inhibitor of the enzyme.

A potent irreversible inhibitor of S-adenosylmethionine (AdoMet) decarboxylase, S-(5'-adenosyl)-methylthio-2-aminooxyethane (AdoMeSaoe), was used to study the regulatory control of this key enzyme in the polyamine biosynthetic pathway. Treatment of L1210 cells with the inhibitor completely eradicated the growth-induced rise in AdoMet decarboxylase activity, resulting in a marked decrease in cellular content of spermidine and spermine. The putrescine content, on the other hand, was greatly elevated. Although no detectable AdoMet decarboxylase activity was found in the L1210 cells after treatment with AdoMeSaoe, the cells contained 50-fold higher amounts of AdoMet decarboxylase protein, compared to untreated cells during exponential growth. Part of this increase was shown to be due to elevated synthesis of the enzyme. This stimulation appeared to be related to the decrease in cellular spermidine and spermine content, since addition of either one of the polyamines counteracted the rise in AdoMet decarboxylase synthesis. The synthesis rate was determined by immunoprecipitation of labeled enzyme after a short pulse with [35S]methionine. In addition to a protein that co-migrated with pure rat AdoMet decarboxylase (Mr approximately 32,000), the antibody precipitated a somewhat larger labeled protein (Mr approximately 37,000) that most likely represents the proenzyme form. Treatment of the L1210 cells with AdoMetSaoe also gave rise to a marked stabilization of the decarboxylase which contributed to the increase in its cellular protein content. Addition of spermidine did not significantly affect this stabilization, whereas the addition of spermine reduced the half-life of the enzyme to almost that of the control cells.

Adenosylmethionine Decarboxylase↗
PubMed1991

Increases of neuron-specific enolase, S-100 protein, creatine kinase and creatine kinase BB isoenzyme in CSF following intraventricular catheter implantation.

In 15 patients without acute brain injury the concentrations of Neuron-specific Enolase (NSE), S-100 Protein (S-100), Creatine Kinase (CK), and Creatine Kinase BB isoenzyme (CK-BB) in ventricular cerebrospinal fluid (CSF) were measured immediately after lateral ventricle cannulation for diagnostic or treatment purposes. From patients who were treated with a shunt another CSF sample was obtained one week after shunt implantation by puncture of the antechamber of the valve. The CSF concentrations of NSE, S-100, CK and CK-BB after cannulation were found to be of the same order as found in patients with severe head injury, stroke or subarachnoid haemorrhage. One week after shunt implantation the concentrations of S-100, CK and CK-BB had returned to normal levels in almost all patients, while the NSE concentrations remained elevated. These findings indicate that the sampling procedure may result in contamination of CSF with NSE, S-100, CK and CK-BB and they should be taken into account in the prognostic evaluation of enzyme concentrations after brain injury.

Brain Damage, Chronic↗
PubMed1991

Neurosurgical intensive care improves outcome after severe head injury.

The present study compares the clinical outcome, as expressed by the Glasgow outcome scale, of two groups of severely head injured patients treated before (49 patients) and after (72 patients) the establishment of a neurosurgical intensive care (NIC) unit at the department of neurosurgery. Uppsala University Hospital. The number of "good recoveries" increased significantly after the establishment of the NIC. This was confirmed by univariate analysis (p less than 0.05) and by multivariate analysis using the logistic regression model to adjust for differences between the two groups of patients (p less than 0.05, p less than 0.005). The most striking improvement was found in patients with a Glasgow coma motor score (GCSM) greater than or equal to 4 on admission. In this subgroup of patients the "good recoveries" increased from 15% to 52%. The object of NIC is basically to prevent or minimize secondary brain damage, and it seems logical that the effect of such care is most obvious in GCS M greater than or equal to 4 patients in whom a good outcome can be anticipated if secondary damage can be prevented or minimized. In conclusion, the present study shows that improved clinical outcome after severe head injury can be achieved by organizing an NIC unit with a well trained staff capable of providing this care 24 hours a day using established methods of surveillance and treatment.

Adult↗
PubMed1991

Intracranial pressure changes following middle cerebral artery occlusion in rats.

Prolonged recording of intracranial pressure (ICP) was performed on rats subjected to middle cerebral artery (MCA) occlusion. ICP was repeatedly recorded before and after occlusion of the vessel via a narrow catheter placed in the cisterna magna. MCA occlusion was followed by an increase in ICP, and a pressure peak occurred after 12-24 h in all animals. Subsequently, essentially two patterns of ICP changes were observed. These seemed to be related to the severity of neurological deficits and extension of the infarct area. In the most severely affected animals, raised ICP was noted throughout the 1st week after MCA occlusion; in rats with reversible neurological deficits, ICP returned to normal values after the first peak at 12-24 h. The present investigation shows that prolonged ICP recording is feasible in MCA-occluded rats. The MCA occlusion model in rats is well characterized. Thus, ICP registration can be used in conjunction with other methods for evaluating treatment against increased ICP.

Animals↗
PubMed1991

Survey on immunization, diarrhoeal disease and mortality in Quang Ninh Province, Vietnam.

A survey on EPI, CDD, child morbidity, and mortality was conducted in 1988 in one province of northeastern Vietnam. Thirty out of 114 communes were randomly selected for the survey and the interviews were made by 60 students from the provincial nursing school, supervised by 10 teachers. It was found that 23 per cent of the children (n = 211) were fully vaccinated, while 54 per cent had partial coverage. Lack of information or ignorance were the main causes of vaccination failure. The adjusted yearly diarrhoeal rate was 1.6 per child under 5 years of age (n = 9.691). Infant mortality and under-five mortality rates were found to be 28 per thousand live births (95 per cent confidence interval: 21-35; n = 2.321) and 44 (36-52), respectively. High literacy among mothers, good breast-feeding practices, low mortality due to diarrhoea, malaria, and measles, and a well-functioning rural health care system were considered to be the main contributing factors to the low infant mortality. The results also point out the weaknesses in the existing reporting system and indicates the need for follow-up studies.

Cause of Death↗
PubMed1991

Posterior wiring without bony fusion in traumatic distractive flexion injuries of the mid to lower cervical spine. Long-term follow-up in 30 patients.

Thirty-four patients with traumatic distractive flexion injuries in the mid to lower cervical spine were treated with posterior wire stabilization without bony fusion from January 1981 through May 1987. Fifteen had cord involvement, and nine had root involvement. Ten were neurologically intact. Thirty patients were followed for a mean of 38 months. Two neurologically intact patients had root deficits postoperatively. One patient was reoperated because of redislocation due to a spinous process fracture. Mean loss of lordosis was 7.5 degrees. Eight patients had a wire break at follow-up, but no case of late instability was observed. Sixteen patients had signs of spontaneous anterior interbody fusion at follow-up, and 11 patients had signs of posterior fusion. Twenty-four patients complained of late--but in most cases--minor pain. These results indicate that simple posterior wiring without bony fusion is a reliable method to obtain good immediate stability in traumatic distractive flexion injuries of the mid to lower cervical spine. The wires provide sufficient stability during the time of soft tissue healing.

Adult↗
PubMed1991

Relation between tobacco use and urinary excretion of thromboxane A2 and prostacyclin metabolites in young men.

BACKGROUND: Cigarette smoking is a risk factor for cardiovascular disease. The present study addressed the effect of tobacco use on the formation of two eicosanoids, thromboxane A2 and prostacyclin, which have been implicated in both acute and chronic cardiovascular disorders. METHODS AND RESULTS: In 577 randomly sampled 18-19-year-old men, the urinary excretion of the 2,3-dinor metabolites of thromboxane A2 and prostacyclin (Tx-M and PGI-M, respectively) was analyzed and related to the subjects' self-reported use of tobacco. Sixty-five percent of the subjects used no tobacco, 7.5% were cigarette smokers, 22% used wet (oral) snuff, and the rest reported a mixed use of tobacco. The urinary excretion of Tx-M was higher (p less than 0.001) in cigarette smokers than in those not using tobacco (180 versus 128 pg/mg creatinine) and was correlated (r = 0.35, p less than 0.05) with the daily cigarette consumption. Snuff users had no increase in their urinary excretion of Tx-M, despite urinary cotinine levels comparable to those in the cigarette smokers (1,210 and 1,560 ng/ml, respectively). The excretion of PGI-M did not differ between non-tobacco users, cigarette smokers, and snuff users. CONCLUSIONS: We conclude that cigarette smoking, but not the use of snuff, facilitates the formation of thromboxane A2. We propose that such an increased formation reflects platelet activation in the absence of vascular injury and that it may be of significance for the subsequent development of cardiovascular disease.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Comparison of methods for the biomonitoring of nurses handling antitumor drugs.

Urinary mutagenicity, thioethers in urine, and sister chromatid exchanges and micronuclei in peripheral lymphocytes were determined for 60 nurses handling cytostatic drugs and 60 referents matched for sex, age, and smoking habits. Safety hoods were used by most of the nurses. The exposed nurses had more sister chromatid exchanges and higher urinary mutagenicity, as measured by Salmonella typhimurium TA 98, than the referents. There were no differences in the other tests. No dose-response relationship was established for any parameter. It was concluded that urinary mutagenicity with the Salmonella strain is the most sensitive test for monitoring nurses handling cytostatic drugs. Determining sister chromatid exchanges may also be a viable test, but it has the drawback of uncertainty as to whether the changes are attributable to present or past exposure. Only comparisons of rather large groups are useful, and a study design requiring matched referents would seem to be optimal.

Adult↗
PubMed1990

Superinduction of ornithine decarboxylase (ODC) by actinomycin D is due to stimulation of ODC mRNA translation.

Inhibition of transcription by treatment with actinomycin D caused superinduction of the ornithine decarboxylase (ODC) activity in Ehrlich ascites tumor cells. Experiments with cycloheximide ruled out the possibility that this superinduction was due to stabilization of ODC. Instead the ODC activity exhibited a more rapid turnover in the presence of actinomycin D (t1/2 = 56 min). The superinduction was found to coincide with an increased rate of ODC synthesis, as determined by measuring the incorporation of [35S )methionine into immunoreactive ODC protein. The steady-state level of ODC mRNA was unchanged, indicating an effect on the translational efficiency.

Animals↗
PubMed1990

Feedback regulation of ornithine decarboxylase expression. Studies using a polysomal run-off system.

The rate-controlling enzyme in polyamine synthesis, ornithine decarboxylase (ODC), is subject to feedback regulation by the polyamines at the level of translation. In the present study we used a cell-free translation system to further investigate the mechanism by which this regulation occurs. Lysates of ODC-overproducing cells were capable of synthesizing large amounts of ODC. The degree of initiation was poor in the lysates and the synthesis of ODC was mainly a result of continued elongation of peptide chains on pre-initiated ribosomes. By determining the amount of ODC produced in the lysate, we obtained an estimate of the number of ribosomes that were actively translating ODC mRNA at the moment of lysis. Using this polysomal run-off assay we demonstrated that the polyamine-mediated regulation of ODC synthesis occurs without any change in the number of ribosomes associated with the message. This finding indicates that the polyamines exert a coordinate effect on initiation and elongation.

Animals↗
PubMed1990

Neurometabolic monitoring of the ischaemic human brain using microdialysis.

Recent animal research has provided evidence that brain ischaemia is associated with a shift of energy related metabolites (lactate, adenosine, inosine, and hypoxanthine) and several transmitters from the intracellular to the extracellular fluid (ECF). These chemical changes of the ECF reflect the energy crisis of the ischaemic tissue. We have proposed that measurement of these metabolites in the ECF using microdialysis may be a useful technique for detection of secondary ischaemia in neurosurgical intensive care patients. As a first step in the evaluation of such a possible clinical application of microdialysis the aim of this study was to measure energy related metabolites and amino acid transmitters during cerebral ischaemia in man. Microdialysis probes were inserted in tumour-free cortical tissue in the frontal lobe in patients undergoing frontal lobe resection as a treatment for brain tumours. Dialysis samples were collected in 10 minutes fractions before and during frontal lobe resection, thus serving as a simulated ischaemia model. The resection procedure was associated with markedly elevated levels of the energy related metabolites as well as transmitter amino acids. The tissue surrounding the probes was examined histologically, and the degree of oedema was estimated from CT scans. In two of the patients the tissue hosting the probes was oedematous. These patients had markedly higher basal levels of lactate. The main conclusions were (1) that the results support the clinical potential of microdialysis, (2) that lactate may be a sensitive indicator of the metabolic disturbances associated with brain oedema, and (3) that frontal lobe resection may be a useful human brain ischaemia model.

Amino Acids↗
PubMed1990

The role of ornithine decarboxylase and polyamines in regeneration of the frog sciatic nerve.

The current study examined both in vivo and in vitro the effects of alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), on regeneration of sensory axons from a local crush of the adult frog sciatic nerve. If daily injections of DFMO started at the same time as crushing and continued throughout the regeneration period (7 days) the outgrowth in vivo of new sensory axons was reduced by about 30%. If DFMO injections started 2 days after crushing, the outgrowth distance did not differ from control values. The sensory axons of a cultured frog sciatic nerve with the attached spinal ganglia start to regenerate from a local crush applied 7 days after the start of the incubation. Five days after crushing the outgrowth distance was 4.5 mm. At the end of the culturing period (7 + 5 days) both the putrescine and spermidine concentrations in the ganglia had increased about 2.5 times, whereas the spermine concentration remained constant. The presence of 10 mM DFMO throughout the culturing period, 7 + 5 days, almost depleted putrescine and prevented the spermidine increase in the ganglia without affecting the regeneration distance. In the nerve putrescine was only reduced by 55% and the other polyamines were unaffected by DFMO. The results show that DFMO influences the early onset of regeneration in vivo. The in vitro results indicate that this is not due to a close mechanistic relationship between the perikaryonal ODC/polyamine system and nerve regeneration. The question of whether polyamines are of local importance for regeneration of the frog sciatic nerve cannot be answered by the present results.

Animals↗