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Biomedical subjects

L Persson

Publications and source records attributed to L Persson.

At least 109 records · Page 6Linked to original sources
PubMed1995

Cloning and expression of two ornithine decarboxylase forms from HMOA cells.

In HMOA cells [Mamont, Duchesne, Grove and Tardif (1978) Exp. Cell Res. 115, 387-393] the half-life of ornithine decarboxylase (ODC) is 8-14 h instead of 15 min as in the Hepatoma Tissue Culture parental cells, due to a single amino acid substitution [Miyazaki, Matsufuji, Murakami and Hayashi (1993) Eur. J. Biochem. 214, 837-844]. We demonstrate for the first time that HMOA cells possess two forms of ODC mRNA that are translated into two proteins differing greatly in turnover rates. We have cloned and transfected the cDNAs for the two ODC forms into COS-1 cells for a direct measurement of their turnover rate. The variant ODC form was much more stable than the wild-type protein, with a half-life of 14 h as compared with 2.5 h.

Animals↗
PubMed1995

Parabanic acid for monitoring of oxygen radical activity in the injured human brain.

The authors used intracerebral microdialysis to harvest allantoin and parabanic acid, potential markers of in vivo oxygen radical activity, from the frontal lobe cortex of three patients in the neurointensive care unit after serious aneurysmal subarachnoid haemorrhage. Clinical events involving severe secondary ischaemia, ultimately leading to structural damage, were associated with a dramatic elevation of the microdialysate level of parabanic acid, whereas allantoin showed less robust changes. In one patient with an uneventful clinical course and without signs of secondary ischaemia parabanic acid levels remained low. The results support the involvement of highly reactive oxygen radical species in human cerebral ischaemia. Parabanic acid appears to be an important marker of free radical reactions in vivo and may be used to monitor free radical activity and to evaluate pharmacological therapy with radical scavengers.

Aged↗
PubMed1995

Type 1 diabetes and the control of dexamethazone-induced apoptosis in mice maps to the same region on chromosome 6.

Quantitative trait loci mapping was used to identify the chromosomal location of genes that contribute to increase the resistance to apoptosis induced in immature CD4+8+ thymocytes. An F2 intercross of the nonobese diabetic (NOD) mouse (displaying an apoptosis-resistance phenotype) and the C57BL/6 mouse (displaying a nonresistance phenotype) was phenotypically analyzed and genotyped for 32 murine microsatellite polymorphisms. Maximum likelihood methods identified a region on the distal part of chromosome 6 that is linked to dexamethazone-induced apoptosis (lod score = 3.46) and accounts for 14% of the phenotypic variation. This chromosomal region contains the diabetes susceptibility locus Idd6, suggesting that the apoptosis-resistance phenotype constitutes a pathogenesis factor in IDDM of NOD mice.

Animals↗
PubMed1995

Regulation of mammalian ornithine decarboxylase. Studies on the induction of the enzyme by hypotonic stress.

One of the cellular responses to hypotonic stress is a marked induction of a key regulatory enzyme in the polyamine biosynthetic pathway, i.e. ornithine decarboxylase (ODC). This increase in ODC activity appears to be a physiological response since the elevated putrescine production seen after the hypotonic shock renders the cells less sensitive to the decrease in osmolarity. In the present study, we have investigated the mechanisms by which the hypotonicity may induce ODC activity. We provide support for a translational mechanism, closely related to the polyamine-mediated feedback regulation of ODC synthesis. In addition, we have examined whether the long G+C-rich 5' untranslated region of the ODC mRNA, which has been demonstrated to negatively affect the translatability of the message, is of any importance for the induction of ODC by hypotonic stress. Chinese hamster ovary (CHO) cells expressing ODC mRNA, with or without the 5' untranslated region, were isolated after transfecting ODC-deficient CHO cells with the appropriate constructs. Hypotonic treatment of the stable transfectants, however, revealed no major difference in ODC induction between the cells expressing a full-length ODC mRNA and those expressing an ODC mRNA deleted of its 5' untranslated region, demonstrating that this part of the message was not essential for the osmotic effects on ODC expression.

Animals↗
PubMed1995

Regulation of ornithine decarboxylase during cell growth. Changes in the stability and translatability of the mRNA, and in the turnover of the protein.

When Ehrlich ascites tumor cells were stimulated to grow, their ornithine decarboxylase (ODC) activity increased 20- to 30-fold. The increase in ODC mRNA content was one order of magnitude less during the corresponding period. Likewise, the subsequent changes in ODC activity failed to show proportionality to those of the ODC mRNA content. The changes in ODC activity were not attributable to changes in ODC turnover, even though the half-life of the enzyme decreased from 56 min during the period of increasing, to 36 min during the period of decreasing ODC activity. There was no evidence of an activation-inactivation-cycle for the enzyme. In view of these findings it appears that ODC mRNA alterations are amplified mainly at the translational level. The biphasic change in ODC mRNA content was partly attributable to a change in turnover of the message, as determined after inhibition of transcription with actinomycin D. Thus, the ODC mRNA half-life was estimated to decrease from 8.7 h during the period of increasing ODC activity to 4.0 h during the period of decreasing ODC activity. Despite the inhibition of transcription by actinomycin D, there was a marked superinduction of ODC activity. Our data demonstrate that the regulation of ODC expression is a complex phenomenon, involving controls at many levels.

Animals↗
PubMed1995

Regulation of mammalian S-adenosylmethionine decarboxylase as studied in a transient expression system.

Mammalian S-adenosylmethionine decarboxylase (AdoMetDC), which catalyzes a key step in the biosynthesis of polyamines, is regulated by a multitude of mechanisms. The polyamines exert a strong feedback control of the enzyme. In the present study we have used a transient expression system to study the regulation of mammalian AdoMetDC. COS cells were transfected with a SV 40-based expression vector containing a 5'- and 3'-truncated human AdoMetDC cDNA (pSDC:16). The cells were shown to contain high levels of AdoMetDC activity 2 days after expression. This was partly due to an increase in the synthesis of the enzyme. However a marked stabilization of the enzyme against degradation did also contribute to the high AdoMetDC activity seen in the COS cells after the transfection with pSDC:16. The high expression of AdoMetDC was reflected in a marked change in intracellular polyamine levels. The cells were almost depleted of their putrescine, and their spermidine content was decreased to about 35% of that found in the mock-transfected cells. The spermine content, on the other hand, was increased. This change in polyamine levels was most likely attributable to the pSDC:16-induced increase in decarboxylated S-adenosylmethinine, which favors the accumulation of spermine at the expenses of putrescine and spermidine. The effects on the expression of AdoMetDC of polyamine synthesis inhibitors varied dependent on whether the COS cells were transfected with control vector or pSDC:16, in spite of similar effects on cellular polyamine levels, indicating a difference in feedback regulation of 'native' and recombinant AdoMetDC. The construct used in the present study gave rise to an AdoMetDC mRNA without a 5' and devoid of most of the 3' untranslated regions. However, whether these parts of the mRNA are involved in the polyamine-mediated translational control of the enzyme remains to be confirmed.

Adenosylmethionine Decarboxylase↗
PubMed1995

Acute leukaemia and malignant lymphoma patients' experiences of disease, treatment and nursing care during the active treatment phase: an explorative study.

Five acute leukaemia or highly malignant lymphoma patients at a hospital in southern Sweden were interviewed about their daily living problems, their coping strategies and their opinions about the nursing care they received during the active phase of their treatment. In addition the EORTC QLQ-C30, the Global Life Quality and the Sense of Coherence scales were administered. The data were analysed from a hermeneutic phenomenological perspective and interpreted to indicate that the patients sensed a threat to their lives, loss of control, and having to live with uncertainty stemming from the disease and the treatment. They had problems with fatigue, diarrhoea, nausea and vomiting, loss of appetite, sore mouth and high temperature. However, they seemed to minimize the importance of these problems and instead focused on gaining control of the situation, developing their knowledge of the disease and relying on the support of their family. Contradictions appeared in their statements about the quality of care, the information given was said to be good but difficult to understand; although the quality of the nursing care was judged to be high it had to be asked for. That is, help was received on request. The patients' perspective of the family and the nurses should be studied in further research in order to fully understand the patients' coping strategies and how nursing care can support them.

Activities of Daily Living↗
PubMed1995

Impaired postural control in patients with cervico-brachial pain.

Dizziness and subjective balance disturbances are common complaints in cervical pain syndromes. We assessed balance function with posturography using vibration-induced and galvanically-induced body sway in consecutive patients (n = 116) with cervico-brachial pain syndrome of more than 3 months' duration. A total of 83% of the patients showed signs of cervical root compression on MRT scans. The incidence of complaints of vertigo was 50%. The patients manifested significantly poorer postural control than sex- and age-matched controls (n = 20). Disorders of the neck should be considered when assessing patients complaining of dizziness, vertigo and balance disturbances.

Afferent Pathways↗
PubMed1994

Effects of transient expression of spermidine/spermine N1-acetyltransferase in COS cells.

Mammalian spermidine/spermine N1-acetyltransferase (SSAT) was transiently expressed in COS cells. As compared to COS cells transfected with control vector alone, cells transfected with the expression vector containing SSAT cDNA contained lower concentrations of spermidine and spermine. The putrescine content, on the other hand, was markedly increased in the COS cells expressing large amounts of SSAT. These changes in polyamine content were most likely caused by an interconversion of spermine and spermidine into putrescine. The SSAT-induced changes in cellular polyamine content resulted in a compensatory increase in the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, i.e. the enzymes catalyzing the rate-limiting steps in polyamine biosynthesis. This is the first demonstration that a primary increase in SSAT activity will induce an interconversion-like change in the polyamine levels and the physiological role of SSAT is most likely to protect cells against too high concentrations of spermidine and spermine.

Acetyltransferases↗
PubMed1994

Characterization of a COS cell line deficient in polyamine transport.

In the present study, we describe the isolation and characterization of a COS cell line deficient in polyamine uptake that may provide an important tool for the molecular cloning of polyamine transporter(s). The cells were selected by isolation for resistance against the cytotoxic agent, methylglyoxal bis(guanylhydrazone) (MGBG), which is entering the cells using the same transport system as the polyamines. The isolated cell line was capable of growing in the presence of 100 microM MGBG, which totally inhibited the growth of the wild-type cells. The transport of putrescine and spermidine was markedly decreased in the COS-MGBGr cells. The decrease in putrescine transport was mainly a result of a 14-fold decrease in Vmax, whereas the reduced spermidine uptake was due to a 3-4-fold decrease in Vmax as well as 12-fold increase in Km, indicating the existence of at least two separate transport systems. No major difference in polyamine content was seen between the parental and the COS-MGBGr cells when grown without MGBG. In the presence of MGBG, both cell lines exhibited an increase in putrescine content. Treatment with MGBG also resulted in a decrease in spermidine and spermine contents in the wild-type cells. In the COS-MGBGr cells, on the other hand, there were no statistically significant effects on the spermidine and spermine contents by MGBG treatment. In the wild-type cells, depletion of polyamines, e.g., by treatment with the ornithine decarboxylase inhibitor 2-difluoromethylornithine (DFMO), stimulated the uptake of polyamines (3-7-fold), whereas in the COS-MGBGr cells the effect of DFMO treatment on polyamine transport was only minor. In contrast to the growth-medium of the wild-type cells, large amounts of polyamines accumulated in the medium of the COS-MGBGr cells, presumably indicating that COS cells normally excrete polyamines and then salvage them using the polyamine transport system.

Animals↗
PubMed1994

Clinical experiences from Sweden on the use of subcutaneously administered sumatriptan in migraine and cluster headache.

This article reviews, from the practitioner's point of view, more than 1 year of clinical experience of the use of subcutaneously administered sumatriptan succinate in the short-term treatment of migraine and cluster headache with regard to advantages and disadvantages of the drug. In accordance with the results of clinical trials, subcutaneous sumatriptan, also in the practitioner's hands, was found to relieve migraine headaches and all other symptoms associated with migraine in most patients and within a reasonable period. Adverse events, however, are common and were perceived by about 70% of the patients. The most common adverse events were pressure/stiffness in the neck and throat (32%), general tiredness (22%), pressure/tightness over the chest (21%), injection site reactions (16%), and tingling sensations in the head and arms (14%). Headache recurrence within 24 hours is a clinical problem not only for the patient but also for the prescribing physician. About every second (53%) migraineur using subcutaneous sumatriptan reports headache recurrence. Headache recurrence appears to be effectively treated by a second injection. Pending valid information about effects, adverse events, headache recurrence, and how to handle the autoinjector, the compliance and tolerability of subcutaneous sumatriptan appear to be most satisfactory among eligible patients with migraine.

Cardiovascular Diseases↗
PubMed1994

Neuropathological endpoints in experimental stroke pharmacotherapy: the importance of both early and late evaluation.

This study addresses the issue of endpoint selection in the evaluation of neuroprotective drugs in experimental focal ischaemia. Previous work with the permanent middle cerebral artery (MCA) occlusion model in the rat has demonstrated that the ischaemic lesion does not acquire its final appearance until at least 28 days after the ictus. Therefore, the effect of the NMDA receptor blocker MK-801 (dizocilpine maleate) was evaluated both early (3 days) and late (28 days) after MCA occlusion to determine if the previously reported protective effect of a single post-ischaemic dose of MK-801 found in acute experiments remained after 28 days. Mk-801 (0.5 mg/kg, i.v.) or isotonic saline was randomly given to rats 30 min after MCA occlusion. Infarct volume and volume of ipsilateral and contralateral hemispheres were estimated from camera lucida drawings of 8 defined coronal histological sections of the brain. As expected, a 40% (p < 0.05) reduction of infarct size was found in MK-801 treated rats after 3 days. In animals evaluated 28 days after MCA occlusion, no significant difference in infarct size, total tissue loss (infarct volume+ipsilateral hemisphere atrophy) or remaining non-infarcted tissue (contralateral hemisphere--total tissue loss) was seen between the MK-801 and placebo treated rats. The results suggest that the single dose treatment with MK-801 postponed the evolution of the infarct, which at 3 days after MCA occlusion is still in progress, possibly by ameliorating oedema formation. It remains to be shown if a multiple dose treatment with NMDA receptor antagonists improves the final neuropathological outcome after experimental stroke.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of tirilazad mesylate given after permanent middle cerebral artery occlusion in rat.

The effect of the antioxidant drug tirilazad mesylate (U-74006F) on histopathological and neurological outcome 3 days after permanent middle cerebral artery (MCA) occlusion was evaluated in rats. Several previous studies have demonstrated the efficacy of tirilazad in reducing infarct size when administered before and during MCA occlusion, whereas post-treatment may be less effective in permanent focal ischaemia. We sought to determine if a protective effect of tirilazad could be demonstrated when administered after the insult only. U-74006F (3 mg/kg, i.v.) or sterile vehicle, was randomly given to rats 10 minutes and 3 hours after permanent MCA occlusion produced by transcranial proximal electrocauterization. Infarct volume and hemisphere volumes were estimated blindly from histological sections of defined levels of the brain after 72 h of ischaemia. Neurological score was determined blindly 1, 2, and 3 days after insult. There was no significant difference in infarct volume, volume of non-infarcted tissue, or neurological score between the tirilazad and placebo-treated rats. In conclusion, our results support the conception that post-treatment with tirilazad mesylate is not efficacious in reducing infarct size in permanent focal ischaemia, while pre-treatment, as reported by other groups, appears to be effective in both permanent and temporary focal ischaemia models. In temporary focal ischaemia, the limited data available suggest that also post-treatment with tirilazad may prove to be neuroprotective.

Animals↗
PubMed1994

Platelet-derived growth factor (PDGF) in neoplastic and non-neoplastic cystic lesions of the central nervous system and in the cerebrospinal fluid.

The aim of this study was to determine the concentration of PDGF in vivo in neoplastic and non-neoplastic brain lesions. Fluid from cystic lesions and cerebrospinal fluid was tested in a radioreceptor assay that detects all described PDGF isoforms. High concentration of PDGF were found in cyst fluids from several astrocytomas, one metastatic melanoma, one metastatic lung adenocarcinoma and one intracerebral abscess. The PDGF concentrations were several times higher than the levels known to be required for maximal PDGF effects on cells in vitro. PDGF could also be detected in some non-neoplastic lesions, especially one intracerebral abscess. The finding of high amounts of PDGF in neoplastic lesions strongly supports the possibility that PDGF can be a mediator of tumour and stromal cell growth and motility in vivo. Comparison of PDGF and beta-thromboglobulin concentrations in the same fluids strongly indicates that the PDGF protein is locally produced rather than a result of platelet activation and derangement of the blood-brain barrier.

Astrocytoma↗