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Biomedical subjects

L Persson

Publications and source records attributed to L Persson.

At least 199 records · Page 11Linked to original sources
PubMed1989

Neurologic and neuropathologic outcome after middle cerebral artery occlusion in rats.

Focal cerebral ischemia was produced in 45 rats by occlusion of the left middle cerebral artery. Groups of rats were investigated over a long period after occlusion, that is, from a few hours to 42 days after the production of focal ischemia. Light microscopy showed infarcts in the frontoparietal cortex and the lateral caudoputamen. The ischemic changes closely resembled those found in ischemic infarcts in humans and followed a similar pattern over time. Measurements of the sizes of the infarct, the ipsilateral (operated) hemisphere, and the contralateral hemisphere from camera lucida drawings revealed that the infarct size changed with time after occlusion. Rats killed during the first 7 days (acute phase) had the largest infarcts; in rats killed thereafter, the infarct size diminished. The size of the ipsilateral hemisphere also changed with time; during the first 7 days after occlusion this hemisphere was swollen and larger than the contralateral hemisphere. We suggest that these acute changes are caused by cerebral edema. After the first 7 days, enlargement of the ipsilateral hemisphere gave way to a significant reduction in the size of both the ipsilateral hemisphere and the infarct. We believe that the major reasons for this shift in size are resorption of fluid together with diminished production of edema and elimination of dead cells by macrophages. We suggest that the amount of tissue loss (i.e., the degree of atrophy and the remaining infarct "scar") found 21-42 days after occlusion (during the late phase) is a measure of the total amount of tissue that succumbed as a consequence of ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Regional cerebral blood flow and histopathologic changes after middle cerebral artery occlusion in rats.

Changes in regional cerebral blood flow were correlated with the distribution of histopathologic signs of brain injury in 35 rats after middle cerebral artery occlusion. Rats were allowed to survive for periods of up to 4 weeks after the operation, and we focused particular interest on the time course of blood flow changes from the initial ischemic events to the late stage of infarction. Regional blood flow was measured using [14C]iodoantipyrine and a quantitative autoradiographic technique. Blood flow in regions with histologic signs of infarction (i.e., the lateral caudoputamen and adjacent neocortex) was below 0.238 ml/g/min, corresponding to 15% of normal values for those regions. In perifocal regions without infarction such as the medial caudoputamen and globus pallidus, cerebral blood flow was also reduced, but it never declined below 20% of its normal value. The decrease in cerebral blood flow was most marked during the first hours after occlusion. Thereafter, cerebral blood flow values gradually normalized, and at 4 weeks there were no significant differences compared with the contralateral side. The border between cortical regions with hypoperfusion and normal cerebral blood flow was rather sharp in the coronal plane, but in the sagittal plane there was a more gradual transitional region. The region with hypoperfusion, observed in the sagittal plane, was most widespread in the acute stage, and normalization of flow occurred particularly from anterior and posterior cortical regions toward the ischemic focus. The possibility for penumbral conditions in the cortex thus exists, particularly in the anterior and posterior borders of the infarction, and remains for several hours after the initial insult.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage.

Cerebrospinal fluid (CSF) markers of brain damage are potentially capable of providing quantitative information about the extent of certain neurological injury. The presence of such markers in CSF after brain damage is transient and it is essential to understand their kinetics if they are to be used in clinical practice. In the present study, the CSF concentrations of two neurospecific proteins. S-100 protein and neuron-specific enolase (NSE), were determined in rats before and repeatedly after one of two types of experimental brain damage: traumatic cortical injury and focal cerebral ischemia induced by middle cerebral artery (MCA) occlusion. The two types of experimental brain damage resulted in significant differences in the kinetics of S-100 and NSE concentrations in CSF. Cortical contusion was followed by a rapid increase in both S-100 and NSE and a peak occurred in both after about 7 1/2 hours, at which time the values declined toward normal. A second, smaller peak was seen after about 1 1/2 days. The increase and decrease in S-100 and NSE levels in CSF was slower after MCA occlusion; a peak was seen after 2 to 4 days. Furthermore, S-100 was generally higher than NSE after trauma, whereas after MCA occlusion the NSE concentration was slightly higher than the S-100 value. These results support the use of CSF markers for estimation of the extent of brain damage in experimental models and forms a basis for the understanding of their kinetics, which is important for their use in clinical practice.

Animals↗
PubMed1989

The effects of brain edema on intracranial pressure in focal cerebral ischemia. An experimental study in a rat using magnetic resonance imaging.

Intracranial pressure (ICP) changes and the development of cerebral edema during the first 24 hours after middle cerebral artery (MCA) occlusion in a rat were studied. ICP was measured via a catheter implanted into cisterna magna and the dynamics of cerebral edema was observed using serial T2 magnetic resonance (MR) measurements. Two T2 components were separated, fast (30-120 ms) and slow (120-240 ms). The first IPC increase was noted within first 2 hours after MCA occlusion and thereafter ICP started to rise 6 hours after stroke. These findings correlated with the development of edema, especially with the increase in extracellular water seen in T2 images. The highest ICP and the largest edema was noted in rats with largest infarcts. An experiment forms a basis for further studies on ICP and edema in a rat model of focal cerebral ischemia.

Animals↗
PubMed1989

Magnetic resonance studies on the development of ischemic edema in an early period after occlusion of middle cerebral artery in a rat.

The development of ischemic edema after middle cerebral artery occlusion in a rat was studied using T1 and T2-weighted magnetic resonance imaging (MRI). Examinations were performed with Helmholtz coil and multiple echo sequences with TR 1,500 ms and TE 30-240 ms (8 echoes) were used. T2 prolongation was noted already 3 hours after experimental stroke and the values increased during the time of the study. T1-weighted images were much less sensitive for the detection of increased water content. This experiment forms a basis for MR studies on the formation and resolution of cerebral edema and can be useful for studies on efficacy of different medical measures against ischemic edema.

Animals↗
PubMed1988

Increased extracellular levels of ascorbate in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis.

Extracellular (EC) ascorbate concentrations were measured in microdialysates from the striatum bilaterally in rats subjected to unilateral middle cerebral artery occlusion (MCAO). The focal cerebral ischemia induced a dramatic increase in ascorbate on the ipsilateral (operated) side while the levels remained at the preocclusion level in the striatum of the contralateral (control) hemisphere. The possibility that ascorbate may aggravate ischemic neuronal damage by its proposed neuromodulatory properties and/or by its ability to induce lipid peroxidation is discussed.

Animals↗
PubMed1988

Feedback regulation of polyamine synthesis in Ehrlich ascites tumor cells. Analysis using nonmetabolizable derivatives of putrescine and spermine.

Ornithine decarboxylase (ODC) is subject to feedback regulation by the polyamines. Thus, addition of putrescine, spermidine or spermine to cells causes inhibition of ODC mRNA translation. Putrescine and spermine are readily converted into spermidine. Therefore, it is conceivable that the inhibition of ODC synthesis observed in putrescine- and spermine-supplemented cells is instead an effect of spermidine. To examine this possibility we have used two analogs of putrescine and spermine, namely 1,4-dimethylputrescine and 5,8-dimethylspermine, which cannot be converted into spermidine. Both analogs were found to inhibit the incorporation of [35S]methionine into ODC protein to approximately the same extent, suggesting that putrescine as well as spermine exert a negative feedback control of ODC mRNA translation in the cell. In addition to suppressing ODC synthesis, both analogs were found to increase the turnover rate of the enzyme. 5,8-Dimethylspermine caused a marked decrease in the activity of S-adenosylmethionine decarboxylase (AdoMetDC). This effect was not obtained with 1,4-dimethylputrescine, indicating that spermine, but not putrescine, exerts a negative control of AdoMetDC. Treatment with 1,4-dimethylputrescine caused extensive depletion of the cellular putrescine and spermidine content, but accumulation of spermine. 5,8-Dimethylspermine treatment, on the other hand, effectively depleted the spermine content and had less effect on the putrescine and spermidine content, at least initially. Nevertheless, the total polyamine content was more extensively reduced by treatment with 5,8-dimethylspermine than with 1,4-dimethylputrescine. Accordingly, only 5,8-dimethylspermine treatment exerted a significant inhibitory effect on Ehrlich ascites tumor cell growth.

Acetyltransferases↗
PubMed1988

Curative effect of DL-2-difluoromethylornithine on mice bearing mutant L1210 leukemia cells deficient in polyamine uptake.

The objective of the present investigation was to determine to what extent polyamine uptake from the host contributes to the ability of tumor cells in overcoming the antiproliferative effect of a polyamine synthesis inhibitor. A mutant L1210 leukemia cell line deficient in polyamine transport was isolated by selection for resistance to methylglyoxal bis(guanylhydrazone), an extremely cytotoxic agent which is taken up by the same transport system as the polyamines. C57BL/6 x DBA/2 F1 mice inoculated with mutant L1210 cells survived on the average 60 to 70% longer than mice inoculated with the parental cells. The therapeutic effect of a polyamine synthesis inhibitor, DL-2-difluoromethylornithine (3% in the drinking water), was much greater on mice bearing mutant L1210 cells (87% increase in median survival time; 13 of 40 mice cured) than on mice inoculated with parental cells (22% increase in median survival time). Similar results, although not as striking, were obtained using athymic nude mice, indicating that the therapeutic difference is not merely due to increased immunogenicity of the mutant cells.

Animals↗
PubMed1988

Regulation of ornithine decarboxylase mRNA translation by polyamines. Studies using a cell-free system and a cell line with an amplified ornithine decarboxylase gene.

The translational control of ornithine decarboxylase (ODCase) by polyamines has been studied using a cellular as well as a cell-free system. A mutant L1210 cell line, in which ODCase represents 4-5% of all soluble protein synthesized, was isolated by stepwise selection for resistance to the ODCase inhibitor 2-difluoromethylornithine (DFMO). The exceptionally high expression of ODCase in these cells was due to amplification of the ODCase gene. When the cells were grown in the absence of DFMO, dramatic increases in cellular putrescine and spermidine levels occurred. These increases were accompanied by a rapid decrease in ODCase synthesis. The change in ODCase synthesis was not associated with an alteration in the amount of ODCase mRNA, demonstrating a translational control in these cells. The effects of polyamines on ODCase mRNA translation were also studied in rabbit reticulocyte lysates using mRNA isolated from the DFMO-resistant cells. Low concentrations of spermidine stimulated synthesis of ODCase and that of total protein, when added to gel-filtered lysates. Notably, optimal stimulation of ODCase synthesis was achieved at a spermidine concentration lower than that required for an optimal rate of total protein synthesis. Higher concentrations of spermidine were inhibitory, and their effects of ODCase synthesis were stronger than on protein synthesis in general, resulting in a decrease in the fraction of protein synthesis accounted for by ODCase. The present results demonstrate that at least part of the feedback regulation of ODCase exerted by the polyamines is due to direct inhibition of ODCase mRNA translation.

Animals↗
PubMed1988

Polyamines, DNA methylation and cell differentiation.

The cellular concentration of AdoMet is normally very much higher than that of dcAdoMet, the aminopropyl group donor in polyamine synthesis. However, when cells are depleted of their putrescine and spermidine, i.e. the aminopropyl group acceptors, the dcAdoMet concentration increases dramatically, to a level that may greatly exceed that of AdoMet. Using a highly purified DNA methyltransferase and its preferred substrates, a defined hemimethylated duplex oligodeoxynucleotide or poly(dI-dC)-poly(dI-dC), we demonstrate that dcAdoMet is a poor methyl group donor, and that it starts to inhibit DNA methylation when its concentration exceeds that of AdoMet. At a dcAdoMet/AdoMet ratio of 5:1 there is very little methyl transfer. This study suggests that the antiproliferative and differentiative effects brought about by inhibitors of polyamine synthesis may be partly attributable to dcAdoMet-mediated inhibition of DNA methylation.

Cell Differentiation↗
PubMed1988

Comparison among five mutagenicity assays in workers producing polyurethane foams.

Thirty-two male individuals exposed to isocyanates and amines during the production of plastic foams and 20 male referents were studied by cytogenetic methods (chromosomal aberrations, sister chromatid exchanges and micronuclei in lymphocytes) and by urinary mutagenic assays (thioether concentrations and mutagenic activity with Salmonella TA98 and E. Coli WP2 uvrA). The occupational exposure was monitored by measurements of toluene diisocyanate and N-methylmorpholine in work-room air. The levels were below the current Swedish hygienic standards. Although all parameters, except the sister chromatid exchanges, showed increased mean values for the exposed group compared to the referents, only the urinary thioether concentrations differed significantly. The study was, however, non-conclusive with regard to a genetic effect of the occupational exposure as measured by the cytogenetic parameters. This may be due to the low exposure level. In the micronuclei frequencies there was a significant effect of age. Smoking significantly affected the SCE frequencies, the thioether concentrations and the mutagenic activities in the Salmonella assay. There were statistically significant correlations between the urine specimens collected during one working day and the following morning with regard to the mutagenic activities in the Salmonella and E. coli assays, and in the thioether concentrations as well. The association between the different cytogenetic and urinary mutagenic assays were weak but there were several statistically significant correlation coefficients, indicating that the variables may have a common metabolic background.

Adult↗
PubMed1988

Biological effects in a chemical factory with mutagenic exposure. III. Urinary mutagenicity and thioether excretion.

Eighty-five workers in a chemical plant, in which there was an increased frequency of B-lymphocyte tumours (myelomas and lymphomas) and lung cancer, did not excrete higher amounts of thioethers in urine than 48 control subjects. The chemically exposed workers had, however, a higher excretion of thioethers in urine during shift compared to an exposure-free period. The bacterial fluctuation test showed a statistically significantly increased mutagenic activity for E. coli Wp2 uvrA, but not for Salmonella TA98, in the urine of the exposed workers compared with the controls. However, no difference in excretion was found in the chemical workers between work and an exposure free-period. Further, no association of thioether or mutagen excretion with any specific chemical exposure (e.g. ethylene oxide and formaldehyde) in the plant could firmly be established.

Adult↗
PubMed1988

S-100 protein in cerebrospinal fluid of patients with subarachnoid haemorrhage: a potential marker of brain damage.

Concentrations of S-100 protein in cerebrospinal fluid (CSF) were measured by a recently developed radioimmunoassay (RIA) in 45 patients with subarachnoid haemorrhage (SAH), 44 with verified ruptured aneurysm. In each of 43 patients 2-15 serial CSF samples were analysed, and in the remainder 1 sample was examined. The concentrations of S-100 protein proved to be related to the brain damage caused by the SAH, indexed as outcome (Glasgow Outcome Scale). The S-100 concentrations were related to the severity of the haemorrhage and to the development of delayed ischaemic deterioration. Delayed ischaemic deterioration (vasospasm) was usually accompanied by an increase in CSF S-100 concentration after 4 days. Patients in whom no S-100 value exceeded 20 ng S-100 per ml during the course of the disease had a favourable outcome, whereas patients in whom one or several CSF samples contained more than 100 ng/ml became severely disabled or vegetative or died. The present study suggests that CSF S-100 analysis may be used as an objective and early measure of the degree of brain damage sustained by the SAH patient.

Adolescent↗
PubMed1988

Reversibility of detrusor hypertrophy and hyperplasia after removal of infravesical outflow obstruction in the rat.

The present investigation was performed in order to study the degree of reversibility of changes of the rat detrusor secondary to infravesical outflow obstruction for various periods of time. In a previous study it was shown that outflow obstruction induced both hypertrophy and hyperplasia of the smooth muscle cells. This was determined by means of morphometry and analyses of DNA and RNA. The results of the present investigation confirm the findings of previous studies that these changes to a considerable extent are reversible after removal of the outflow obstruction. This seems to be true both in animals obstructed for a short period of time (10 days) and in animals where the hypertrophy and hyperplasia processes have diminished (six weeks).

Animals↗
PubMed1988

Influence of cigarette smoking on vascular reaction during experimental gingivitis.

The influence of cigarette smoking on the vascular reaction during plaque induced gingivitis was studied in humans for 28 days. Sixteen healthy dental students, 8 smokers and 8 non-smokers, aged 19-42 yr, volunteered for the experiment. A numerical method was used for the evaluation of the vascular reaction. With the aid of stereophotographs changes in the number of gingival vessels were followed during the experiment. It was found that the number of vessels identified increased over time during the experiment in both smokers and non-smokers. However, in spite of the fact that the plaque accumulation rate was equal, the vascular reaction was less pronounced in smokers. At the end of the experiment after 28 days the intensity of the vascular reaction in smokers was only 50% of that observed in non-smokers. The difference was statistically significant at the P-level of 0.05. One week after termination of the experiment and reinstitution of oral hygiene the number of gingival vessels equaled the pre-experimental values in both groups. The results indicate that the vascular reaction associated with plaque induced gingivitis is suppressed in smokers.

Adult↗
PubMed1988

Neuron-specific enolase is a marker of cerebral ischemia and infarct size in rat cerebrospinal fluid.

Neuron-specific enolase concentrations were measured in samples of rat cerebrospinal fluid obtained repeatedly before and after occlusion of the middle cerebral artery. A method for reliable, repeated sampling of cisternal cerebrospinal fluid was developed for this purpose. Occlusion of the middle cerebral artery induced cerebral infarcts of slightly variable size with good correlation to raised neuron-specific enolase concentrations. Sham operation caused only superficial cortical damage at the site of surgery and was followed by an early, slight, and transient increase in neuron-specific enolase concentration. With our technique, the development of cerebral infarcts can be studied in individual rats under experimentally controlled conditions over an extended period of time. Analysis of neuron-specific enolase can be used in trials of drugs for mitigating the effect of ischemia. Information concerning the release of neuron-specific enolase from ischemic cerebral tissue to the cerebrospinal fluid is important because neuron-specific enolase in the cerebrospinal fluid can be determined in patients suffering from cerebrovascular insult.

Animals↗