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Biomedical subjects

D Donaldson

Publications and source records attributed to D Donaldson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Brain superoxide dismutase, catalase, and glutathione peroxidase activities in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a fatal paralytic disorder of unknown cause. Recent evidence implicated the role of free radicals in the death of motor neurons in this disease. To investigate this hypothesis further, we measured the activity of the main free radical scavenging enzymes copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, and glutathione peroxidase in postmortem brain samples from 9 patients with sporadic amyotrophic lateral sclerosis and from 9 control subjects. We examined samples from the precentral gyrus of the cerebral cortex, a region affected in amyotrophic lateral sclerosis, and from the cerebellar cortex, a region not affected. The two groups did not differ in age or postmortem delay. In the precentral gyrus from amyotrophic lateral sclerosis samples, glutathione peroxidase activity as measured by spectrophotometric assay (13.8 +/- 2.6 nmol/min/mg protein [mean +/- standard error of mean]) was reduced significantly compared to the activity in the precentral gyrus from control samples (22.7 +/- 0.5 nmol/min/mg protein). In contrast, glutathione peroxidase activity was not significantly altered in the cerebellar cortex from amyotrophic lateral sclerosis patients compared to controls. Copper/zinc superoxide dismutase, manganese superoxide dismutase (corrected or not corrected for citrate synthase), and catalase were not significantly altered in the precentral gyrus or cerebellar cortex in the patient samples. This study indicated that glutathione peroxidase activity is reduced in a brain region affected in amyotrophic lateral sclerosis, thus suggesting that free radicals may be implicated in the pathogenesis of the disease.

Amyotrophic Lateral Sclerosis↗
PubMed1996

Delayed hyperglycemia and intracellular acidosis during focal cerebral ischemia in cats.

The effects of hyperglycemia on permanent focal brain ischemia is controversial; its effects on the size of the infarct are variable according to experimental conditions. In this study, nuclear magnetic resonance (NMR) spectroscopy was used to assess brain pH and high-energy phosphate metabolites after focal middle cerebral artery (MCA) ischemia in hyperglycemic and normoglycemic cats. Sixteen adult cats underwent (MCA) occlusion under general anesthesia and nuclear magnetic resonance 31P spectroscopy to assess intracellular brain pH and energy metabolites throughout permanent ischemia. Animals were treated two hours after the onset of ischemia with either saline or glucose perfusions. Significant hyperglycemia (488 vs 105 mg/100 ml) was achieved in the experimental group. The response to hyperglycemia was dependent on the initial characteristics of the infants. A distinct pattern of phosphocreatine/inorganic phosphate recovery within 20 minutes of ischemia predicted a small infarct size. The addition of hyperglycemia did not affect acidosis, infarct size, or metabolite ratios in these animals. The lack of phosphocreatine/inorganic phosphate recovery within 20 minutes of ischemia was predictive of an eventual large infarct. In these animals, the delayed addition of hyperglycemia significantly lowered intracellular pH during the ischemic period (5.45 vs. 6.25, p = 0.25). These data support the theory that the response to hyperglycemia is very dependent on the initial metabolic state of the injured brain. This state can be predicted by early 31P spectroscopy data, which may, in turn, prove to be a useful marker for recoverable ischemic deficit in the cerebral region of interest.

Acid-Base Equilibrium↗
PubMed1996

Leximin population ethics.

This paper concerns the ethical issues that arise when policy decisions have to be taken that affect population size and characteristics. Such policies include social security systems, intertemporal resource allocation decisions, and policies designed to influence fertility rates. The authors provide characterizations of Leximin principles for social evaluation in an intertemporal framework, so that they can be used to compare social alternatives with different population sizes. "The main axioms used in our characterizations are Hammond Equity together with Independence of the Utilities of the Dead (a plausible intertemporal consistency requirement) for the Critical-Level Leximin principles, and Positional Leximin Consistency (an axiom that allows non-constant critical levels) for the Positional-Extension Leximin principle. The performance of these principles is compared in the pure population problem and we argue that the Critical-Level Leximin principles are ethically more attractive than Positional-Extension Leximin."

Demography↗
PubMed1996

Enhanced accumulation of free fatty acids in experimental focal cerebral ischemia.

Cerebral ischemia is well known to cause an increase in the level of free fatty acids (FFAs) in rodent species. Such FFA accumulations may signal regional lipid membrane damage and are postulated to participate in the pathogenesis of progressive infarction after cerebral ischemia. In this study we have examined the regional levels of FFAS in the cortices of cats after 8 h of middle cerebral artery occlusion. The levels of specific FFAs (palmitic, stearic, and oleic acids) were 1.5 and 2.0 times higher in the penumbral and dense ischemic regions, respectively, than those in the non-ischemic contralateral region. Although no significant differences were found between the penumbra and dense ischemic regions in the levels of arachidonic acid, the levels of docosahexaenoic acid in both of these regions were significantly higher than those in the contralateral region (P < 0.05). These results suggest that enhanced accumulation of FFAs are regionally distributed after focal ischemia and may contribute to neuronal damage after focal cerebral ischemia in non-rodent species.

Animals↗
PubMed1996

Effect of hyperglycemia on reperfusion-associated recovery of intracellular pH and high energy phosphates after transient cerebral ischemia in gerbils.

Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by the end of the reperfusion period (6.8 +/- 0.1 vs 7.04 +/- 0.1, p < 0.05). High-energy phosphates phosphocreatine-inorganic phosphate and phosphocreatine-adenosine triphosphate showed partial recovery in all groups throughout the reperfusion period; the recovery was not significantly altered by glucose status. Hyperglycemia worsened pH but not the recovery of high-energy phosphates in animals reperfused after 20 min of transient cerebral ischemia. This sustained acidosis may be a primary event in transient damage in hyperglycemic animals.

Adenosine Triphosphate↗
PubMed1996

Physical and sexual abuse and their relation to psychiatric disorder and suicidal behavior among adolescents who are psychiatrically hospitalized.

Adolescents who were psychiatrically hospitalized (N = 105) were classified as sexually abused, physically abused, both sexually and physically abused, or not abused, and studied to determine the prevalence of suicidal behavior and psychiatric disorders. Self-reports of hopelessness, depression, coping, and self-concept were also examined. No difference in suicidal behavior or psychiatric disorder, based on abuse history, was found, with one exception. Adolescents who were sexually abused, particularly those who experienced the most severe sexual abuse, used negative coping strategies more often than those not sexually abused. Findings suggest that symptomatology of adolescents who are psychiatrically hospitalized does not differ markedly based on history of abuse.

Adaptation, Psychological↗
PubMed1996

Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia.

This study examined the effect of AA-861, a specific 5-lipoxygenase inhibitor, on brain levels of leukotriene C4 (LTC4) and correlated any changes with changes in edema formation and cerebral blood flow (CBF) after transient ischemia in gerbils. Brain levels of LTC4 were observed to be increased at 1, 2, and 6 hours of reperfusion following 20 minutes of occlusion. At 2 hours of reperfusion, a pretreatment dose of 1000 mg/kg of AA-861 was required to inhibit more than 90% of the reperfusion-induced increases in brain LTC4. At this dose, inhibition of LTC4 production was observed at 2 and 6 hours of reperfusion. The specific gravity of both the cortex and subcortex was decreased at 6 hours of reperfusion after 20 minutes of occlusion. At 2 hours of reperfusion, no significant difference was observed in the specific gravity of the cortex and subcortex regions of gerbils pretreated with AA-861 or with vehicle, but at 6 hours of reperfusion significant positive differences were observed. Cerebral blood flow decreased to approximately 10% of preocclusion values during occlusion and returned to near-preocclusion values after 10 minutes of reperfusion. No significant differences were observed in regional CBF in the AA-861- and vehicle-pretreated gerbils during reperfusion. These findings indicate that LTC4 production after transient cerebral ischemia may be an important contributor to the development of cerebral edema and that CBF does not mediate the LTC4-involved development of edema.

Animals↗
PubMed1996

Interleukin-4 (IL-4) in combination with IL-11 or IL-6 reverses the inhibitory effect of IL-3 on early B lymphocyte development.

We have previously described a two-step methylcellulose culture system in which individual primitive progenitors from 5-fluorouracil (5-FU)-treated mice were shown to have both myeloid and B lymphoid differentiation capacity. Highly enriched Lin-Sca+FU2d BM cells were cultured in methylcellulose in the presence of Steel factor (SF), interleukin-7 (IL-7), and pokeweed mitogen stimulated spleen cell conditioned medium (PWM-SCM). Primary mixed myeloid colonies were replated after 8-11 days into secondary cultures containing SF and IL-7, which supported the generation of B220+sIgM- pre-B cell colonies. A number of growth factors, including IL-6, IL-11, granulocyte colony-stimulating factor (G-CSF), and IL-12 were shown to be capable of substituting for PWM-SCM to support the B lymphoid potential of primary colonies. B lymphoid potential was not supported, however, in SF + IL-3 or in SF + IL-3 plus any single growth factor (IL-1 to -12, granulocyte-macrophage colony-stimulating factor [GM-CSF], G-CSF, erythropoietin [Epo], leukemia inhibitory factor [LIF], tumor necrosis factor-alpha [TNF-alpha], transforming growth factor-beta [TGF-beta], gamma interferon [IFN-gamma], or insulin-like growth factor-1 [IGF-1]), but was supported in SF + IL-3 + 5% PWM-SCM. Experiments were designed to identify the factor or factors in PWM-SCM that reverse the inhibitory effects of IL-3 on B lymphoid potential. By substituting various cytokine combinations for PWM-SCM, we determined that combinations of IL-4 + IL-6 or IL-4 + IL-11, but not IL-4 alone, can substitute for PWM-SCM to reverse the inhibitory effect of IL-3 on B lymphoid potential. Neutralizing antibodies to IL-4 completely eliminated the activity in PWM-SCM, but antibodies to IL-6 only partially inhibited the activity. IL-11 was not detected in PWM-SCM, and the activity co-purified with IL-4, but not with IL-6. Thus, IL-4 plus IL-6, IL-11, or one or more unidentified growth factors in PWM-SCM can reverse the inhibitory effects of IL-3 on early B lymphocyte development in culture.

Animals↗
PubMed1995

The hazards of chronic exposure to nitrous oxide: an update.

This paper reviews the potential occupational hazards associated with chronic exposure to nitrous oxide. The evidence that chronic exposure to the gas produces problems related to reproduction in dental personnel is convincing. Recent evidence suggests that scavenging systems decrease the adverse effects which nitrous oxide has on fertility of dental surgery assistants. However, even in the presence of scavenging systems trace levels of the gas can exceed recommended minimum levels.

Air Pollution, Indoor↗
PubMed1995

Molecular analysis and breakpoint definition of a set of human chromosome 21 somatic cell hybrids.

Rodent-human somatic cell hybrids containing single human chromosomes or chromosome fragments are extremely valuable in physical mapping, marker analysis, and disease mapping. Chromosome 21 has been extensively studied in this fashion, and a single set of hybrids has been utilized in mapping the majority of chromosome 21 markers. The utility of a set of hybrids depends upon the definition of the human chromosome content. Recently, Chumakov and coworkers (1) utilized 198 chromosome 21 markers in the preliminary analysis of YACs spanning chromosome 21q. We have used these same markers to evaluate the STS content of a set of 27 chromosome 21 somatic cell hybrids, resulting in the description of the breakpoints at the molecular level, as well as the definition of 35 "bins. " The detailed molecular definition of chromosome 21 content of the hybrids, in combination with the further analysis of chromosome 21 YACs (2), has resulted in the most detailed picture of chromosome 21 to date.

Animals↗
PubMed1995

Effect of gestational age on levels of serum alkaline phosphatase isoenzymes in healthy pregnant women.

OBJECTIVES: To confirm that the bone isoenzyme of alkaline phosphatase (ALP) contributes significantly to the increased ALP in normal pregnancy, and to determine the gestational age at which the increase occurs. METHODS: Cross-sectional determinations of serum total, bone and placental ALP were carried out in 67 normal pregnant women. The results were compared with those of 18 normal age-matched non-pregnant controls using Student's t-test. RESULTS: At both 31-32 weeks and 38 weeks of gestation, serum activities of bone ALP were increased significantly (P < 0.05 and P < 0.001, respectively) when compared with controls. The percentage contribution of bone ALP to the total was higher at 31-32 weeks and lower at 38 weeks when compared with the contribution from placental ALP. CONCLUSION: Knowledge of time of elevation of serum bone ALP activity in normal pregnancy will be helpful in the interpretation of elevated serum total ALP activity during pregnancy.

Adult↗
PubMed1995

Dose-dependent lesions of the dopaminergic nigrostriatal pathway induced by intrastriatal injection of 6-hydroxydopamine.

Animal models with partial lesions of the dopaminergic nigrostriatal pathway may be useful for developing neuroprotective and neurotrophic therapies for Parkinson's disease. To develop such a model, different doses of 6-hydroxydopamine (0.0, 0.625, 1.25, 2.5 and 5.0 micrograms/microliters in 3.5 microliters of saline) were unilaterally injected into the striatum of rats. Animals that received 1.25 to 5.0 micrograms/microliters 6-hydroxydopamine displayed dose-dependent amphetamine and apomorphine-induced circling. 6-Hydroxydopamine also caused dose-dependent reductions in [3H]mazindol-labeled dopamine uptake sites in the lesioned striatum and ipsilateral substantia nigra pars compacta (up to 93% versus contralateral binding), with smaller losses in the nucleus accumbens, olfactory tubercle and ventral tegmental area. In the substantia nigra pars compacta and the ventral tegmental area, the number of Nissl-stained neurons decreases in parallel with the reduction in [3H]mazindol binding. The reduction in [3H]mazindol binding in the striatum and the nucleus accumbens, and the reduction in [3H]mazindol binding and in the number of Nissl-stained neurons in the substantia nigra pars compacta and the ventral tegmental area is stable for up to 12 weeks after the lesion. Macroscopically, forebrain coronal sections showed normal morphology, except for rats receiving 5.0 micrograms/microliters 6-hydroxydopamine in which striatal cross-sectional area was reduced, suggesting that this high dose non-specifically damages intrinsic striatal neurons. Nissl-stained sections revealed an area of neuronal loss and intense gliosis centered around the needle track, which increased in size with the dose of neurotoxin. Striatal [3H]sulpiride binding was increased by 2.5 micrograms/microliters and 5.0 micrograms/microliters 6-hydroxydopamine, suggesting up-regulation of dopamine D2 receptors. Striatal binding of [3H]CGS 21680-labeled adenosine A2a receptors, but not of [3H]SCH 23390-labeled dopamine D1 receptors, was reduced at the highest dose, suggesting preservation of the striatal intrinsic neurons with the lower doses. This study indicates that intrastriatal injection of different doses of 6-hydroxydopamine can be used to cause increasing amounts of dopamine denervation, which could model Parkinson's disease of varying degrees of severity. Injecting 3.5 microliters of 2.5 micrograms/microliters 6-hydroxydopamine appears to be particularly useful as a general model of early Parkinson's disease, since it induces a lesion characterized by robust drug-induced rotation, changes in binding consistent with approximately 70% dopamine denervation, approximately 19% dopamine D22 receptor up-regulation, negligible intrinsic striatal damage and stability for at least 12 weeks. This study outlines a technique for inducing partial lesions of the nigrostriatal dopamine pathway in rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1995

Intertemporal population ethics: critical-level utilitarian principles.

"This paper considers the problem of social evaluation in a model where population size, individual lifetime utilities, lengths of life, and birth dates vary across states. In an intertemporal framework, we investigate principles for social evaluation that allow history to matter to some extent. Using an axiom called independence of the utilities of the dead, we provide a characterization of critical-level generalized utilitarian rules. As a by-product of our analysis, we show that social discounting is ruled out in an intertemporal welfarist environment. A simple population-planning example is also discussed."

Ethics↗
PubMed1995

The effect of storage temperature on the resistance to failure of dental local anesthetic cartridges.

This in vitro investigation studied the effect of storing dental local anesthetic cartridges at room temperature and at 37 degrees C on the forces required for cartridge failure under strong injection pressures. Storage for three hours at the higher temperature resulted in a significant reduction in the forces required to produce failure of plastic cartridges (leakage of solution around the bung). The forces needed to cause failure of glass cartridges did not differ between the two temperatures.

Anesthesia, Dental↗
PubMed1995

A comparison of the effects of EMLA cream and topical 5% lidocaine on discomfort during gingival probing.

This investigation compared the use of a 5% eutectic mixture of local anesthetics (EMLA) cream to a "standard" intraoral topical anesthetic (5% lidocaine) as a means of anesthetizing the gingival sulcus in a double-blind, split-mouth study with human volunteers. A 5-min application of EMLA in a customized intraoral splint resulted in a significant increase in the depth of probing of the gingival sulcus without discomfort compared to a similar application of 5% lidocaine. Following application of EMLA, the pain-free probing depth measured at three sites in the upper premolar region increased by a mean total of 2.8 mm compared to an increase of 1.9 mm with lidocaine. This study suggests EMLA may be advantageous in providing periodontal anesthesia where manipulation of the gingiva is necessary.

Administration, Topical↗
PubMed1994

Synergistic interaction between interleukin-12 and steel factor in support of proliferation of murine lymphohematopoietic progenitors in culture.

We have investigated the effects of interleukin (IL)-12 (natural killer cell stimulatory factor/cytotoxic lymphocyte maturation factor) on the proliferation of murine myeloid and lymphohematopoietic progenitors in methylcellulose culture. In the presence of erythropoietin (Ep), IL-12 alone failed to support colony formation by mononuclear and enriched marrow cells of normal mice. Steel factor (SF) alone supported primarily formation of granulocyte/macrophage (GM) colony formation. However, the combination of the two cytokines yielded a significant number of multilineage colonies. When tested on marrow cells from 5-fluorouracil (5-FU)-treated mice, the combination of IL-12 and SF, but not the single factors, was effective in support of formation of various types of colonies. Approximately 25% of these colonies yielded pre-B-cell colonies when replated in secondary culture containing SF and IL-7, indicating that IL-12 can interact with SF in supporting the development of primitive lymphohematopoietic progenitors. These results demonstrate that IL-12, a cytokine believed to be involved in the development of cell-mediated immune responses, has a wider range of activity, including committed myeloid and multipotent lymphohematopoietic progenitors.

Animals↗