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Biomedical subjects

L Persson

Publications and source records attributed to L Persson.

At least 127 records · Page 7Linked to original sources
PubMed1994

The Auger electron effect in radiation dosimetry.

The Auger electron effect is of importance in radiation protection related to work in radiobiology, radiophysics, and nuclear medicine. Radionuclides that emit Auger electrons are widely used in nuclear medicine (99mTc, 123I, and 201Tl) and in biomedical research (51Cr and 125I). They are also present in the environment (40K). Therefore, calculation of the absorbed dose and equivalent dose to tissues from these incorporated radionuclides is important for risk assessment. Depending on the subcellular distribution of the radionuclide, the biological effects caused by cell-incorporated Auger emitters can be as severe as those from high-linear energy transfer (LET) alpha particles. However, the recently adopted recommendations of the International Commission on Radiological Protection in Publication No. 60 do not provide guidance on calculating the equivalent dose for these radionuclides. A better understanding of the effects of Auger electrons is required to estimate the equivalent doses, and further research in this field is appropriate. There are good reasons to consider the Auger electron effect not only in medical radiation protection of patients but also in the context of annual limits of intake for workers and the public.

Animals↗
PubMed1994

HIV infection: social network, social support, and CD4 lymphocyte values in infected homosexual men in Malmö, Sweden.

STUDY OBJECTIVE: The aim was to determine if there is an association between social network and social support and the CD4 cell count in HIV infected homosexual men. DESIGN: The study was cross sectional. A structured questionnaire assessing psychosocial factors such as social network and social support was administered at interview. Information on CD4 cell counts and HIV symptoms were obtained from participants' medical records. SETTING: The study population consisted of all HIV seropositive homosexual and bisexual men who had not been diagnosed as having AIDS seen at the Department of Infectious Diseases, the only hospital clinic in the city of Malmö (230,000 inhabitants), Sweden that provides care for HIV infected patients. PARTICIPANTS: Altogether 47 (68%) of 69 men in the population agreed to be interviewed. MAIN RESULTS: A low CD4 cell count was found more frequently in men with low social participation scores (OR 3.3; 95% CI 1.0, 11), in those with a low adequacy of social participation (OR 3.8; 95% CI 1.1, 13), and in men with low material support scores (OR 3.9; 95% CI 1.1, 13). After adjustment for age and time of awareness of the HIV infection, the two former associations remained statistically significant. CONCLUSIONS: These results, if reproduced in a longitudinal study, might suggest that psychosocial factors can affect an individual's immune system.

Adult↗
PubMed1994

Effect of low level energy laser irradiation on gingival inflammation.

The effect of low level energy infra-red laser irradiation on gingival inflammation was studied. Gingivitis was induced in ten female dental students by refraining from all oral hygiene measures for 28 days. On days 21 and 24 the marginal gingiva, buccal to one of the lateral mandibular incisors, was exposed to 4 minutes of laser irradiation (total dose = 1J). Serving as a control site the gingiva of the contralateral incisors was exposed to ordinary light. There was no statistical difference between the laser exposed sites and the control sites related to either plaque formation or gingival bleeding. The gingivitis reaction was evaluated with the aid of a stereophotographic method by calculating changes in the number of gingival vessels. It was found that the number of vessels identified increased over time for both laser exposed and control sites. The difference between sites at day 28 was not statistically significant (t = 0.82, P > 0.05). These results suggest that low energy laser irradiation (LLLT) does not influence the inflammatory reaction of the gingiva.

Adult↗
PubMed1993

Development of resistance to hydroxyurea during treatment of human myelogenous leukemia K562 cells with alpha-difluoromethylornithine as a result of coamplification of genes for ornithine decarboxylase and ribonucleotide reductase R2 subunit.

alpha-Difluoromethylornithine (DFMO), an enzyme-activated irreversible inhibitor of ornithine decarboxylase (ODC), was used to select two very highly drug-resistant cell lines, designated K562-DFMOr and V79-DFMOr. Both DFMO-resistant cell lines exhibited elevated ODC expression due to gene amplification. Moreover, the K562-DFMOr cells, but not the V79-DFMOr cells, had an elevated level of ribonucleotide reductase subunit R2 (R2) mRNA and an increased R2 gene copy number. By analysis of their electron paramagnetic resonance spectra, an increased level of the R2 protein was observed in the K562-DFMOr cells as compared to the wild type K562 cells. This is the first description of a DFMO-induced mutant cell line exhibiting coamplification of the genes for ODC and R2, and overexpression of their products. There was no coamplification of the N-myc protooncogene, which is located close to the ODC and R2 genes on human chromosome 2. The alterations exhibited by the K562-DFMOr cell line were shown to be stable for many passages and to convey resistance not only to DFMO but also to hydroxyurea, an inhibitor of ribonucleotide reductase and thus DNA replication. In the absence of the selective pressure exerted by DFMO, the V79-DFMOr cell line produced revertants by loss of ODC gene amplification within three passages. Coamplification of linked genes may turn out to be an important mechanism in the development of cross-resistance and should be considered when designing therapeutic strategies.

Animals↗
PubMed1993

Feedback regulation of mammalian ornithine decarboxylase. Studies using a transient expression system.

Ornithine decarboxylase catalyzes the first step in the biosynthesis of polyamines in mammalian cells. The enzyme is subject to various control mechanisms to maintain adequate intracellular levels of polyamines. Polyamines exert a strong feedback control on ornithine decarboxylase. In a recent study [van Daalen Wetters, T., Macrae, M., Brabant, M., Sittler, A. & Coffino, P. (1989) Mol. Cell. Biol. 9, 5484-5490], it was concluded that feedback control of ornithine decarboxylase is mainly, if not exclusively, a posttranslational phenomenon. The existence of a fast-acting polyamine-stimulated component of ornithine decarboxylase degradation that acts on newly synthesized monomeric forms of the enzyme was postulated. In the present study we have used a transient expression system to test this hypothesis. The expression of ornithine decarboxylase in mock-transfected COS cells varied depending on the cellular supply of polyamines as has been found in other mammalian cells. Thus, supplementing the cells with exogenous spermidine resulted in a marked decrease in ornithine decarboxylase activity, whereas depletion of intracellular polyamines, using an ornithine decarboxylase inhibitor, gave a large increase in the cellular content of the enzyme. COS cells expressing an ornithine decarboxylase mRNA devoid of its 5' non-translated region did not exhibit any feedback control of the enzyme, neither in the presence of exogenous spermidine nor when the intracellular polyamine levels were depleted to the same extent as in the mock-transfected COS cells. The results strongly suggest that the feedback control of ornithine decarboxylase is not merely a posttranslational phenomenon.

Animals↗
PubMed1993

Diethylglyoxal bis(guanylhydrazone), a potent inhibitor of mammalian S-adenosylmethionine decarboxylase. Effects on cell proliferation and polyamine metabolism in L1210 leukemia cells.

The polyamines are cell constituents essential for growth and differentiation. S-Adenosylmethionine decarboxylase (AdoMetDC) catalyzes a key step in the polyamine biosynthetic pathway. Methylglyoxal bis(guanylhydrazone) (MGBG) is an anti-leukemic agent with a strong inhibitory effect against AdoMetDC. However, the lack of specificity limits the usefulness of MGBG. In the present report we have used an analog of MGBG, diethylglyoxal bis(guanylhydrazone) (DEGBG), with a much greater specificity and potency against AdoMetDC, to investigate the effects of AdoMetDC inhibition on cell proliferation and polyamine metabolism in mouse L1210 leukemia cells. DEGBG was shown to effectively inhibit AdoMetDC activity in exponentially growing L1210 cells. The inhibition of AdoMetDC was reflected in a marked decrease in the cellular concentrations of spermidine and spermine. The concentration of putrescine, on the other hand, was greatly increased. Treatment with DEGBG resulted in a compensatory increase in the synthesis of AdoMetDC demonstrating an efficient feedback control. Cells seeded in the presence of DEGBG ceased to grow after a lag period of 1-2 days, indicating that the cells contained an excess of polyamines which were sufficient for one or two cell cycles in the absence of polyamine synthesis. The present results indicate that analogs of MGBG, having a greater specificity against AdoMetDC, might be valuable for studies concerning polyamines and cell proliferation.

Adenosylmethionine Decarboxylase↗
PubMed1993

Polyamine-mediated regulation of S-adenosylmethionine decarboxylase expression in mammalian cells. Studies using 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine, a suicide inhibitor of the enzyme.

Cell proliferation is dependent on an adequate supply of the polyamines putrescine, spermidine and spermine. One of the key steps in the polyamine biosynthetic pathway is catalyzed by S-adenosylmethionine decarboxylase (AdoMetDC). In the present study we have used a newly synthesized enzyme-activated irreversible AdoMetDC inhibitor, 5'-([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine [(Z)-AbeAdo], to investigate the regulation of this enzyme. Treatment of mouse L1210 leukemia cells with (Z)-AbeAdo resulted in a total inhibition of their AdoMetDC activity followed by depletion of the spermidine and spermine content. The putrescine content, however, was dramatically increased after treatment with (Z)-AbeAdo. In spite of the cellular depletion of spermidine and spermine, only a minor inhibitory effect was obtained on cell growth, indicating that putrescine at a high concentration might partly replace spermidine and spermine in their growth-promoting functions. Cells grown in the presence of (Z)-AbeAdo exhibited an increased synthesis of AdoMetDC, which was counteracted by the addition of either spermidine or spermine. The change in AdoMetDC synthesis could not be fully explained by a change in the level of AdoMetDC mRNA, indicating also a translational control. Mammalian AdoMetDC is synthesized as a larger proenzyme, which is then cleaved into two subunits of different sizes. The conversion of the proenzyme into the subunits is a very rapid process, which is stimulated greatly by putrescine in vitro. However, the processing of the proenzyme in the (Z)-AbeAdo-treated L1210 cells was not affected by their very high putrescine content, indicating that the conversion might be saturated at low levels of putrescine, or that most of the putrescine in the (Z)-AbeAdo-treated L1210 cells might be bound to sites normally occupied by spermidine and spermine.

Adenosylmethionine Decarboxylase↗
PubMed1993

Ornithine decarboxylase-like immunoreactivity in rat spinal motoneurons and motoric nerves.

Ornithine decarboxylase (ODC) is the rate-limiting enzyme in the formation of the polyamines putrescine, spermidine and spermine. In the present study ornithine decarboxylase-like immunoreactivity (ODC-LI) was localized immunocytochemically in rat spinal motoneurons, motoric nerves and myoneural junctions in several muscles. In the spinal cord ODC-LI was expressed in most of the large multipolar neurons located in the ventral horn at cervical and lumbar levels. ODC-LI was localized in the cytoplasm, dendrites and axons of the labelled neurons. The nuclei of motoneurons were unlabelled; however, the nuclear membranes and the surrounding cytoplasm were strongly stained. ODC-immunoreactive (IR) axons could be traced through the white matter entering the ventral roots. The myelinated axons in the ventral roots and in the nerve bundles among the muscles were intensely stained with ODC antiserum. The myoneural junctions apposing individual muscle fibers showed ODC-LI with slightly less intensity. Some ODC-IR nerve fibers were seen in the muscle spindles. The present results show that motoneurons in adult rat spinal cored express ODC-LI and that OCD-LI is transported to motoric nerves and myoneural junctions. This suggests that polyamines can be synthesized both in the motoneuron somata and in their peripheral projections. Polyamines may thus regulate cellular functions in all parts of motoneurons. In addition, polyamines may be secreted from their distal projections and have tropic effects on Schwann cells and/or muscular tissue.

Animals↗
PubMed1993

Antileukemic effects of non-metabolizable derivatives of spermidine and spermine.

To determine whether non-metabolizable derivatives of spermidine and spermine exert anticancer effects, L1210 leukemic mice were treated with 5,8-dimethylspermidine and 5,8-dimethylspermine. Both derivatives cured 5% of the leukemic mice. The increase in median survival time, however, was slight. In combination with alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, only 5,8-dimethylspermine had a favorable effect. Treatment with DFMO is known to increase the uptake of extracellular polyamines and presumably their derivatives, by depleting the intracellular putrescine and spermidine content. However, treatment of L1210 leukemia cells in vitro with DFMO did not affect the uptake of the methyl-substituted polyamines added to the growth medium. 5,8-Dimethylspermidine and 5,8-dimethylspermine repressed the ornithine decarboxylase activity when added to cultures of L1210 leukemia cells. S-Adenosylmethionine decarboxylase activity was only repressed by 5,8-dimethylspermine. This finding may explain the potentiation by this derivative and not by 5,8-dimethylspermidine, of the antileukemic effect of DFMO.

Adenosylmethionine Decarboxylase↗
PubMed1993

Stabilization of S-adenosylmethionine decarboxylase by aminoguanidine.

Aminoguanidine, an inhibitor of copper-containing amine oxidases, is often used in cell culture studies to prevent the oxidation of added polyamines or their derivatives by the amine oxidase present in bovine serum. However, in the present study, we demonstrate that aminoguanidine, besides affecting the degradation of polyamines, may affect one of the important regulatory enzymes in the biosynthesis of polyamines, namely S-adenosylmethionine decarboxylase (AdoMetDC). Aminoguanidine was shown to induce a 2-3-fold increase in the AdoMetDC levels in L1210 cells. This increase was fully explained by a stabilization of the enzyme, probably caused by the binding of aminoguanidine to the active site of AdoMetDC.

Adenosylmethionine Decarboxylase↗
PubMed1993

Public reaction to radiation: fear, anxiety, or phobia?

Public fear reactions to ionizing radiation are discussed in a social psychological context. The common use of the terms fear, anxiety, panic, and phobia is related to their clinical meanings, and the authors stress the importance of caution when using certain psychiatric terms for interpreting public reactions to radiation. Differences related to existing knowledge and belief structures, trust, and preferences, create obstacles to effective communication; however, the study of such differences also offers explanations to different reactions and different viewpoints. More information and communication on radiation, clear behavioral guidelines in situations of increased radiation levels, and respect for citizens' concerns about radiation protection would counterbalance lay people's fears and feelings of vulnerability. Such measures may enhance familiarity with radiation, increase perceived personal control in anxiety-creating situations, and develop trust in authorities and their expertise.

Anxiety↗