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Biomedical subjects

E Carlson

Publications and source records attributed to E Carlson.

At least 73 records · Page 4Linked to original sources
PubMed1993

Brain infarction is not reduced in SOD-1 transgenic mice after a permanent focal cerebral ischemia.

Using a mouse model with intraluminal blockade of the middle cerebral artery (MCA) which produced both cortical and striatal infarction, the effect that superoxide radicals have on cerebral infarction, local cerebral blood flow, and neurological deficits after 24 h of permanent focal cerebral ischemia in transgenic mice (Tg) overexpressing human CuZn-superoxide dismutase (SOD-1) was examined. There were no difference between SOD-1 Tg mice and non-Tg littermates observed in the infarct areas of brain slices, the infarct volume, the local cerebral blood flow, or the neurological deficits. These data suggest that pre-existing high levels of antioxidant enzyme failed to provide neuronal protection against permanent focal cerebral ischemia.

Animals↗
PubMed1993

Autoradiographic distribution of [3H]neurotensin receptors in the brains of superoxide dismutase transgenic mice.

Superoxide dismutase (SOD) plays an important role in the protection of cells against the deleterious effects of free radicals by dismutating the toxic superoxide anion radical. Although oxygen-based radicals have been implicated in the process of aging and in neurodegenerative disorders such as Parkinson's disease, the contribution of these free radicals to the pathology of these entities has yet to be clarified. It is also not certain that increased levels of free radical scavenging enzymes would attenuate the molecular and cellular processes that lead to these pathological states. In order to assess the contribution of increased SOD gene dosage to the pathogenesis of Down's syndrome, transgenic mice have been constructed that overexpress the human CuZnSOD. We are also using this model to evaluate the role of free radicals in age-associated changes in brain neurotransmitters and their receptors. In the present study, transgenic mice and their nontransgenic littermates, aged 6 weeks and 21 months, were used in an autoradiographic receptor study of the distribution of brain neurotensin receptors. At 6 weeks of age, there were no significant differences between the two groups of mice in most brain regions. In addition, [3H]NT binding sites showed parallel age-related decreases in the majority of the areas examined in both groups. However, significant age-related decreases in the septum, the diagonal band of Broca, and in some subdivisions of the caudate-putamen were observed only in SOD-Tg mice. In contrast, significant age-related decreases in the core area of the nucleus accumbens and the dorsal aspect of the dentate gyrus of the hippocampus were seen only in non-Tg mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

A survey of BSN curricula: research content.

The purpose in this study was to survey educators in National League for Nursing (NLN)-accredited programs regarding the goals in the research component. The 21-item survey instrument was sent to 200 randomly selected schools, of whom 165 (83%) responded. The responses fell into two classes: cognitive goals, i.e., critical thinking and theory/practice; and professional skills, i.e., research utilization and clinical judgment. While a number of variables were analyzed, no significant findings were observed.

Curriculum↗
PubMed1992

Nucleotide sequences and biologic properties of toxic shock syndrome toxin 1 from ovine- and bovine-associated Staphylococcus aureus.

Toxic shock syndrome toxin (TSST) 1 was purified from ovine (TSST-ovine) and bovine (TSST-bovine) mastitis-associated Staphylococcus aureus. These toxins were previously reported to have molecular weights identical to that of human TSST-1. However, TSST-ovine was reported as having an isoelectric point (pI) of 8.5, whereas TSST-bovine has the same pI (7.2) as TSST-1. Nucleotide sequence analysis revealed that TSST-bovine was identical to TSST-1 and that TSST-ovine had 14 nucleotide differences that changed 9 amino acid residues. Only 1 nucleotide difference, at position 514, was predicted to cause an amino acid charge difference, as glutamic acid at position 132 of TSST-1 was changed to lysine in TSST-ovine. Like TSST-1, TSST-ovine was mitogenic, but unlike TSST-1, it was not pyrogenic, was unable to enhance endotoxic shock, and was unable to induce TSS in a rabbit model. Also, TSST-ovine was less reactive to certain monoclonal antibodies raised against TSST-1.

Amino Acid Sequence↗
PubMed1992

Superoxide dismutase, catalase, and glutathione peroxidase activities in copper/zinc-superoxide dismutase transgenic mice.

Copper/zinc-superoxide dismutase (CuZn-SOD) transgenic mice overexpress the gene for human CuZn-SOD. To assess the effects of the overexpression of CuZn-SOD on the brain scavenging systems, we have measured the activities of manganese-SOD (Mn-SOD), catalase, and glutathione peroxidase (GSH-Px) in various regions of the mouse brain. In nontransgenic mice, cytosolic CuZn-SOD activity was highest in the caudate-putamen complex; this was followed by the brainstem and the hippocampus. The lowest activity was observed in the cerebellum. In transgenic mice, there were significant increases of cytosolic CuZn-SOD activity in all of these regions, with ratios varying from a twofold increase in the brainstem to 3.42-fold in the cerebellum in comparison with nontransgenic mice. Particulate Mn-SOD was similarly distributed in all brain regions, and its levels also were significantly increased in superoxide dismutase (SOD)-transgenic mice. In the brains of nontransgenic mice, cytosolic catalase activity was similar in all brain regions except the cortex, which showed less than 50% of the activity observed in the other regions. In transgenic mice, cytosolic catalase activity was significantly increased, with the cortex showing the greatest changes (133%) in comparison with nontransgenic mice. The smallest increases were observed in the hippocampus (34%). In contrast to what was observed for SOD and catalase, there were no significant changes in cytosolic GSH-Px activity in any of the brain regions examined. The present results indicate that, in addition to displaying marked increases in the levels of brain CuZn-SOD activity, SOD-transgenic mice also exhibit increases in other enzymes that scavenge oxygen-based radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Amitrole↗
PubMed1992

Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity.

Administration of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to mammals causes damage to the nigrostriatal dopaminergic pathway similar to that observed in Parkinson's disease. It has been suggested that the mechanism by which MPTP kills dopamine (DA) neurons involves an energy crisis due to the inhibition of mitochondrial complex I. In addition, superoxide radicals (O2-), generated subsequent to the blockade of mitochondrial complex I, may also be involved in MPTP-induced neurotoxicity. Superoxide dismutase (SOD) is a scavenger enzyme that protects cells from the hazard of O2- radicals. To evaluate further the role of O2- radical in MPTP-induced toxicity, we tested the effects of MPTP in transgenic mice with increased SOD activity. In nontransgenic littermates with normal SOD activity, MPTP injection causes a marked reduction in striatal levels of DA and its metabolites as well as in striatal and nigral 3H-DA uptake; these findings are consistent with a loss in dopaminergic neurons. In contrast, in transgenic mice with increased SOD activity, MPTP injection does not cause any significant changes either in levels of DA and metabolites or in 3H-DA uptake. We show that this lack of toxicity is not due to a lower delivery of MPTP to the brain following its intraperitoneal injection, to reduced brain biotransformation of MPTP to N-methyl-4-phenylpyridinium ion (MPP+), to diminished striatal mitochondrial monoamine oxidase B activity, to decreased synaptosomal uptake of MPP+, to lower potency of MPP+ to inhibit the complex I of the mitochondrial electron transport chain, or to faster brain elimination of MPP+. These results suggest that increased SOD activity is, most likely, the protective factor that confers resistance to transgenic mice against MPTP-induced neurotoxicity. Thus, this study provides further evidence that some of the deleterious effects of MPTP may be mediated by O2- radicals. The similarity between the MPTP model and Parkinson's disease further raises the possibility that oxy-radicals may play a significant role in the etiology of this neurodegenerative disorder.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase.

Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.

Animals↗
PubMed1991

Cold-induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn-superoxide dismutase.

It has been proposed that oxygen-derived radicals, superoxide in particular, are involved in the alteration of blood-brain barrier permeability and the pathogenesis of brain edema following trauma, ischemia, and reperfusion injury. Using transgenic mice that overexpress the human gene for copper-zinc-superoxide dismutase, we studied the role of superoxide radicals in the blood-brain permeability changes, edema development, and delayed infarction resulting from cold-trauma brain injury. At 2 hours after a 30-second cold injury, cerebral water and Evans blue contents were reduced, respectively, from 80 +/- 0.2% and 132.7 +/- 12.9 micrograms/gm of dry weight for nontransgenic mice to 78.5 +/- 0.3% and 87.1 +/- 9.9 micrograms/gm of dry weight for transgenic mice. Infarction, as measured by 2,3,5-triphenyltetrazolium chloride staining, was reduced by 52% in transgenic brains. These data indicate that an increased level of superoxide dismutase activity in the brain reduces the development of vasogenic brain edema and infarction. Superoxide radicals play an important role in the pathogenesis of these lesions in cold-traumatized brain.

Animals↗
PubMed1991

Quantitative autoradiographic distribution of [3H]-MPTP binding in the brains of superoxide dismutase transgenic mice.

Recently, we have shown that transgenic mice which exhibit increased superoxide dismutase (SOD) activity are resistant to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. Increased SOD activity has been related to impairment of cell membrane characteristics and enhanced lipid peroxidation. Thus it was thought that resistance to MPTP might possibly be attributable to alteration in the distribution of MPTP which is a highly lipophilic compound. This idea was stimulated by a previous suggestion that the resistance manifested by rats to MPTP might be due to a low level of [3H]-MPTP binding sites in brain regions which are critical to MPTP-induced toxicity. The comparison of the binding of [3H]-MPTP in the brain of SOD-transgenic mice and their nontransgenic littermates did not reveal any significant difference in either brain distribution or in concentrations of [3H]-MPTP binding between the two groups. Our data indicate that the observed lack of MPTP-induced toxicity of SOD-transgenic mice is not related to abnormal binding of the toxin in the brain of these transgenic animals which exhibit 2.07 to 3.48 higher SOD activity than their nontransgenic littermates. In addition, this study provides a normative description of the regional distribution of [3H]-MPTP binding in the brain of normal mice.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1991

Toxic shock syndrome toxin 1 enhances synthesis of endotoxin-induced tumor necrosis factor in mice.

Toxic shock syndrome toxin 1 (TSST-1) was tested for its ability to enhance the production of endotoxin-induced tumor necrosis factor (TNF) in C3H/HeN mice. The TNF level in serum was quantified by a sandwich enzyme-linked immunosorbent assay (ELISA). It was found that when mice were injected with 20 micrograms of TSST-1 12 h before exposure to 1 micrograms of endotoxin, the serum endotoxin-induced TNF was 20 times as high as that found in mice exposed to endotoxin alone. Although 20 micrograms of TSST-1 did induce a maximum level of near 1 ng of TNF per ml of serum 1.5 h after exposure, the TNF concentration was greatly diminished after 5 to 6 h and was no longer detectable after 12 h. Pretreatment of mice with 20 micrograms of TSST-1 or 1 micrograms of endotoxin did not influence TNF induction by TSST-1 12 h later. Also, pretreatment of mice with 1 micrograms of endotoxin did not enhance TNF induction by endotoxin 12 h later. Enhancement was achieved only when mice were exposed to TSST-1 more than 4 h and less than 24 h before injection of endotoxin. Despite the relatively high serum TNF levels (30 to 50 ng/ml), no mortality was observed in the mice treated with both TSST and endotoxin.

Animals↗
PubMed1990

Quantitative autoradiographic distribution of [3H]mazindol-labeled dopamine uptake sites in the brains of superoxide dismutase transgenic mice.

Superoxide dismutase (SOD) is an important enzyme which is involved in the dismutation of the toxic radical, superoxide anion. The activity of CuZnSOD is increased in patients who suffer from Down's Syndrome, Alzheimer's disease, and in Parkinson's disease. In order to evaluate the contribution of this enzyme to the neuropathology of these neurodegenerative diseases, transgenic mice have been constructed which express the human CuZnSOD gene. As a first step towards exploring these issues, we have carried out an autoradiographic binding study of the distribution of the catecholaminergic uptake blocker mazindol in the brain of these transgenic mice and of their littermates. Desmethylimipramine (DMI)-insensitive [3H]mazindol binding sites which correspond to dopamine uptake sites were located in the striatum, the nucleus accumbens, the olfactory tubercle and in the substantia nigra. Within the striatum, there was a lateromedial gradient, with higher concentration of dopamine uptake sites being found laterally. These findings suggest that subregions of the basal ganglia may be more susceptible to the deleterious effects of dopaminotoxic drugs which are taken up into the dopaminergic neurons via these uptake sites. Saturation experiments revealed no differences in the characteristics of [3H]mazindol binding sites between the two groups of mice. Thus, increased activity of SOD is not associated with diffuse changes in the molecular structures of receptors in mice brain.

Animals↗
PubMed1990

Tumor necrosis factor (TNF) is induced in mice by Candida albicans: role of TNF in fibrinogen increase.

One intraperitoneal dose of Candida albicans (10(8) CFU) caused a chronic (longer than 2 months), significant elevation of plasma fibrinogen levels (Clauss method) in mice of strain C3H/HeN. Even a small dose (10(6) CFU) resulted in a significant increase in fibrinogen level for 5 days following injection, whereas other blood parameters (leukocytes, erythrocytes, platelets, hematocrit, hemoglobin, blood urea nitrogen, aspartate aminotransferase, albumin, alkaline phosphatase, antithrombin III, glucose, calcium, and total protein) measured by standard methods were normal. Blood taken during this period was negative for C. albicans. The role of tumor necrosis factor (TNF) in C. albicans infections was investigated by measuring the fibrinogen response after the administration of C. albicans or recombinant mouse TNF-alpha. Both challenges resulted in an elevated fibrinogen level. When polyclonal antibodies to mouse TNF-alpha were given prior to challenge with C. albicans or mouse TNF-alpha, the fibrinogen increase was significantly inhibited. C. albicans injections were found to significantly elevate endogenous TNF levels in mice (enzyme-linked immunosorbent assay). It was concluded that C. albicans induces TNF in the mouse. Furthermore, these data give evidence which supports a relationship between TNF and the fibrinogen increase induced by C. albicans.

Animals↗
PubMed1990

[Effect of smear layer removal on bevelled and retrofilled teeth in vitro].

The "smear layer" is composed of debris that cover and insert into dentinal tubules. It is not really known if this form of debris may harbon viable bacterias or does form a barrier that enhances endodontic fillings by lining or plugging the tubules. The purpose of this study is to determine the role of the smear layer in leakage by using two groups of teeth in which the smear layer was removed of the root canals, in the first group and left into the roots in the second group. Some samples were beveled and all teeth were retrofilled after Root Canal Preparation, and then filled with India Ink. After examination of leakage under various conditions, it has been found a correlation between leakage and removal of smear layer.

Dental Cavity Preparation↗
PubMed1989

Monoadduct forming photochemical reagents for labeling nucleic acids for hybridization.

We describe the synthesis of three angelicin derivatives which can be used for labeling nucleic acids with biotin. These compounds were used to label nucleic acids in the presence of lysed cell constituents. The resulting labelled nucleic acids show hybridization to a genus specific probe for E. coli. The relative comparison of sensitivity indicates that a polyamine linker is better than a polyethylene oxide linker between the biotin and angelicin moieties.

Affinity Labels↗
PubMed1989

Rapid identification of microorganisms by nucleic acid hybridization after labeling the test sample.

A novel method for rapidly identifying microorganisms has been developed. This method employs a monoadduct-forming furocoumarin derivative, which can photochemically label nucleic acids. The labeled nucleic acid can, in turn, be hybridized simultaneously to a panel of immobilized probe DNAs arrayed as dots on a solid support such as nitrocellulose. This procedure offers several advantages over more conventional hybridization techniques in that sample nucleic acids can be photolabeled without substantial sample preparation and that identification can be achieved by a single, rapid hybridization reaction.

Bacterial Typing Techniques↗