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Biomedical subjects

G M Anderson

Publications and source records attributed to G M Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Activators of protein kinase C decrease serotonin transport in human platelets.

Treatment of human platelets with activators of protein kinase C (PKC) for 5-20 min resulted in substantial reductions in the rate of platelet serotonin (5-HT) transport. The mean Vmax observed after 5 min treatment with 1 microM 4-beta-12-tetradecanoylphorbol 13-acetate (beta-TPA) was 66% (n = 16, P = 0.0001) of the control value. 5 min of treatment with 1 microM mezerein reduced uptake to 78% (n = 3, P = 0.01) of control. Both beta-TPA and mezerein had little effect on the Km of transport and had EC50 values of approx. 100 mM when a 20-min treatment period was used. The maximum effects of both were reached at approx. 20 min and could be blocked with staurospine. The beta-TPA effect was stereospecific, as alpha-TPA did not alter platelet 5-HT uptake. Although the PKC activators may have altered transmembrane ion-gradients for Na+ and Cl-, which are co-transported with 5-HT, minimizing ion-gradient changes had little effect on the observed reductions in transport. The PKC activators also had little or no effect on platelet 5-HT release or on the number (Bmax) of 5-HT transporters expressed at the platelet surface. The data indicate that PKC activation may down-regulate the activity of the 5-HT transporter in platelets. Apparently, most of this effect is mediated through mechanisms other than changes in ion-gradients, reductions in the number of available transporters, or increased 5-HT release. The apparent regulation of 5-HT transport by PKC may have important implications in platelet and neuronal functioning.

Alkaloids↗
PubMed1992

Platelet and whole blood serotonin content in depressed inpatients: correlations with acute and life-time psychopathology.

Platelet or whole blood serotonin content did not differ significantly in patients with major depression compared to healthy controls, but within the patient group, platelet serotonin levels correlated negatively with severity of depression (r = -0.49, p = 0.007). Levels were 39% lower in patients who had made a suicide attempt compared to nonattempter patients (47.2 +/- 27.3 versus 77.6 +/- 41.7 ng/10(8) platelets, p = 0.04). Conversely, comorbid borderline personality disorder (85.3 +/- 41.5 ng/10(8) platelets) was associated with 31% greater platelet serotonin content than nonborderline patients (58.9 +/- 31.1 ng/10(8) platelets) and 27% greater than healthy controls (62.4 +/- 19.8 ng/10(8) platelets). A pronounced seasonal variation in whole blood and platelet serotonin content was found in both patients and controls, largely due to lower levels in summer. Excluding cases tested in the summer abolished the statistically significant differences in patients with and without comorbid borderline personality disorder (BPD). Nevertheless, BPD attempters had lower serotonin levels than BPD nonattempters but higher serotonin levels than non-BPD attempters. Current hostility and a life-time history of aggression were positively correlated with platelet serotonin content (r = 0.44, p = 0.04 and r = 0.41, p = 0.06). This study provides evidence for an association between lower platelet serotonin content and depression and suicidal behavior, and association of higher platelet serotonin content and comorbid borderline personality disorder and behavior traits such as aggressivity.

Adult↗
PubMed1992

Effect of amygdala kindling on the in vivo release of GABA and 5-HT in the dorsal raphe nucleus in freely moving rats.

Our laboratory has previously reported a significant subsensitivity to iontophoretically applied GABA (gamma-aminobutyric acid) in dorsal raphe neurons of amygdala-kindled rats. This subsensitivity was selective for GABA and persisted at least 3 months after the last kindled seizure. In the present series of experiments, we explored mechanisms by which kindling could result in persistent GABA sensitivity changes, using in vivo microdialysis to quantitate neurotransmitter [including GABA and 5-hydroxytryptamine (5-HT)] release in the dorsal raphe nucleus of awake, unrestrained amygdala-kindled rats. Depolarization-induced release of GABA is markedly increased in the dorsal raphe nucleus in amygdala-kindled animals. This change in depolarization-induced GABA release appeared to be graded, dependent upon the stage to which the animal is kindled. Thus GABA release is increased in animals kindled to Stage 2 and even greater in animals kindled to Stage 5 seizures. The change in GABA release is also selective, since no consistent change in the release of other putative amino acid neurotransmitters or 5-HT was observed in these same animals. We hypothesize that this increase in depolarization-induced release of GABA in the amygdala-kindled animal underlies the development of subsensitivity to GABA in dorsal raphe neurons.

Amino Acids↗
PubMed1992

Differentiation of Neuro-2a neuroblastoma cells by an antibody to GM3 ganglioside.

A monoclonal antibody against GM3 ganglioside (GM3Ab) was found to trigger differentiation of Neuro-2a cells in culture. The differentiation of Neuro-2a cells by GM3Ab was accompanied by increased levels of intracellular serotonin and amino acid neurotransmitters viz. aspartate, glutamate, glutamine, glycine and taurine. Further study indicated that the increase in the serotonin level was not due to a higher rate of serotonin synthesis but rather to a higher rate of active transport of serotonin from the medium. Studies on the cell surface gangliosides revealed that unlike the proliferating cells, the GM3Ab-mediated differentiated cells contained higher gangliosides in addition to GM3 and GM2 gangliosides. Analysis of total cellular proteins indicated the appearance of a 25 kDa protein, pI 5.4, in the GM3Ab-treated cells--a small amount of this protein was observed in dibutyryl cAMP (Bt2cAMP)-treated cells, however, the protein was totally absent in the 5-bromo-2'-deoxyuridine (BrdU)-treated cells. Investigation of the mode of action of GM3Ab indicated that the cellular differentiation was due to increased cAMP accumulation resulting from an increase in the adenylate cyclase activity. Further studies with different agents affecting protein kinase C (PKC) activity and direct assay of PKC ruled out the possibility that GM3Ab mediated its effect via PKC. This GM3Ab-induced differentiation could be inhibited by protein kinase A (PKA) inhibitor, H8, but could not be inhibited by sphingosine, an inhibitor of PKC. Pertussis toxin could mimic the effect of GM3Ab, suggesting that GM3Ab caused the elevation in the adenylate cyclase activity by reducing the Gi-protein inhibition of the adenylate cyclase. The data suggests that GM3Ab, after interaction with cell surface GM3, elevated intracellular cAMP level by withdrawing the inhibitory effect of some undefined factor(s) present in culture medium which normally keeps adenylate cyclase activity low through activation of Gi-protein.

Amino Acids↗
PubMed1992

Coronary artery bypass grafting in Canada: What is its rate of use? Which rate is right?

We reviewed recent reports from administrative databases and clinical registries addressing the utilization of coronary artery bypass grafting (CABG) in Canada. The Canadian CABG rate per 100,000 people increased from 31.1 to 43.2 between 1981-82 and 1986-87. Between 1981 and 1986 the rate in the United States increased from 69.9 to 95.3 per 100,000, consistently about two times the Canadian rate. Provincial data have shown particular growth in utilization among elderly people. However, in the United States the 1985 CABG rate was twice as high as the aggregated age-specific rates for Ontario and Manitoba among people 65 to 74 years of age and four times higher among those 75 years or more. Limited registry data suggest that the Canadian CABG case mix is similar to the case mix in major US centres and that, utilization growth notwithstanding, the procedure is largely applied to patients who should, in theory, benefit (i.e., those with severe angina, impaired left ventricular function and left main-stem or triple-vessel disease). However, chart audits and registry evaluations using explicit criteria are needed to compare the use of CABG in Canada and the United States. In addition, Canadian data show moderate regional and municipal variations, the 1986-87 rates per 100,000 population in major census metropolitan areas varying from 19.5 to 46.9. Areas with consistently low rates raise particular concerns about impaired access to CABG. Reasons for variations should therefore be a research priority.

Adult↗
PubMed1992

Platelet dense granule release reaction monitored by high-performance liquid chromatography-fluorometric determination of endogenous serotonin.

The platelet dense granule release reaction was monitored by measuring the serotonin content of platelets collected by filtration following release. Sensitive HPLC-fluorometric analysis permitted release to be assessed using small (25-50 microliters) volumes of plasma and whole blood. Release could be examined for periods as short as 1 s due to the rapid stoppage effected by filtration. The half-life of thrombin-stimulated (1 U/ml) release was 2-3 s, the EC50 values observed for thrombin-stimulated release over a 60-s release period were 0.01-0.03 U/ml for diluted whole blood and plasma samples.

Blood Platelets↗
PubMed1992

Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder.

Rigorously designed clinical trials have demonstrated the efficacy and safety of fluoxetine in adults with major depressive disorder and obsessive-compulsive disorder (OCD) but not in patients below 18 years old. This report describes a randomized, double-blind, placebo-controlled, fixed-dose (20 mg qd) trial of fluoxetine in 14 children and adolescents with OCD, ages 8 to 15 years old; the study was 20 weeks long with crossover at 8 weeks. Obsessive-compulsive symptom severity was measured on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinician's Global Impression-Obsessive Compulsive Disorder scale (CGI-OCD). The CY-BOCS total score decreased 44% (N = 7, p = .003) after the initial 8 weeks of fluoxetine treatment, compared with a 27% decrease (N = 6, p = .13) after placebo. During the initial 8 weeks, the magnitude of improvement for the fluoxetine group significantly exceeded that for the placebo group as measured by the CGI-OCD (p = .01) but not by the CY-BOCS (p = .17). The most common drug side effects were generally well tolerated. The results suggest that fluoxetine is a generally safe and effective short-term treatment for children with OCD.

Adolescent↗
PubMed1991

Use of high-performance liquid chromatography for assay of glutamic acid decarboxylase. Its limitation in use for post-mortem brain.

Rat brain, obtained 10 min after death, contained high levels of endogenous gamma-aminobutyric acid (GABA) and glutamic acid. Incubation of this brain homogenate at 37 degrees C indicated decrease of GABA with time due to degradation by GABA-transaminase. Reported high-performance liquid chromatographic (HPLC) methods for glutamic acid decarboxylase (GAD) assay depend on the difference between the GABA content of the reaction mixture after and before the incubation period. None of the methods considered the degradation of GABA during incubation. Furthermore, during determination of the Michaelis constant (KM) for the reaction none of them considered the endogenous substrate. Here we have focused on these factors which seriously affect the maximum velocity (Vmax) and KM values during GAD assay by the HPLC technique. By a simple and rapid HPLC technique we have measured GAD activity in post-mortem rat brain after removing endogenous glutamic acid by charcoal treatment and using gabaquline to prevent GABA degradation during incubation period. By this method a Vmax value of 46 +/- 4 nmol/h/mg protein and a KM value of 7.5 +/- 0.6 mM were observed for GAD activity of crude brain homogenate. For a comparative study, we have carried out radiometric assay of GAD activity from the same sample and observed a Vmax of 48 +/- 6 nmol/h/mg protein and KM of 6.9 +/- 0.4 mM.

Animals↗
PubMed1991

Recent trends in acute care hospital utilization in Ontario for diseases of the circulatory system.

OBJECTIVE: To describe trends in the use of acute care hospital services for diseases of the circulatory system in Ontario. DESIGN: Observational study. DATA EXTRACTION: Information on diagnoses, procedures and demographic characteristics was obtained from routinely collected computerized abstracts of separations from all acute care hospitals in Ontario during 1979-80, 1983-84 and 1988-89. The data were combined with population estimates to calculate overall separation rates and rates specific for age, diagnosis and procedure. Resource intensity weights were used to estimate changes in resource use. MAIN RESULTS: The overall separation rate increased by 3% and the resource-intensity-weighted separation rate by 12% from 1979-80 to 1988-89. The overall medical separation rate increased by 2%, whereas the surgical rate increased by 12%. The surgical separation rate increased among patients 55 to 79 years of age but decreased in all the other adult age groups. The separation rates for coronary artery bypass surgery and cardiac valve surgery increased rapidly among patients 65 years of age or older. The medical separation rate decreased for patients of all ages except those less than 5 years and those 80 years or more. The medical separation rates decreased by less than 1% for diagnoses related to ischemic heart disease (IHD) and increased dramatically for coronary artery revascularization. CONCLUSIONS: The increasing elderly population has not resulted in large increases in acute care hospital utilization for diseases of the circulatory system. The impact of an aging population has been balanced by decreased utilization rates in the younger groups. The intensity of hospital care has risen primarily because of increases in surgical rates, especially in the elderly population. The large decrease in the rate of death from IHD over the past two decades has not been associated with similar decreases in acute care hospital utilization for this disorder.

Acute Disease↗
PubMed1991

Opinion leaders vs audit and feedback to implement practice guidelines. Delivery after previous cesarean section.

A randomized controlled trial with 76 physicians in 16 community hospitals evaluated audit and feedback and local opinion leader education as methods of encouraging compliance with a guideline for the management of women with a previous cesarean section. The guideline recommended clinical actions to increase trial of labor and vaginal birth rates. Charts for all 3552 cases in the study groups were audited. After 24 months the trial of labor and vaginal birth rates in the audit and feedback group were no different from those in the control group, but rates were 46% and 85% higher, respectively, among physicians educated by an opinion leader. Duration of hospital stay was lower in the opinion leader education group than in the other two groups. The overall cesarean section rate was reduced only in the opinion leader education group. There were no adverse clinical outcomes attributable to the interventions. The use of opinion leaders improved the quality of care.

Cesarean Section↗
PubMed1991

Reproducibility and temporal stability of ADP-induced platelet aggregation: comparison of the anticoagulants sodium citrate and D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone.

We compared the reproducibility and temporal stability of ADP-induced aggregation of platelet-rich plasma anticoagulated with citrate or with D-phenylalanyl-L-prolyl-L-arginyl-chloromethyl ketone (PPACK), a thrombin inhibitor. Citrate- or PPACK-platelet-rich plasma (PRP) was stored at room temperature in capped plastic tubes or in plastic syringes from which all air was expelled. At intervals over 1-5 hr after venipuncture, platelet aggregation was induced by 1-1.5 microM ADP. Initially, the aggregation of PPACK-PRP was nearly twice that of citrate-PRP. The response of PPACK-PRP stored in the syringe remained essentially constant over the interval of study, in contrast to the responses of the other samples which declined with time. The improved stability of the response obtained from samples anticoagulated with PPACK was due to the absence of citrate, since PRP containing both citrate and PPACK became less responsive over time in a manner similar to PRP which contained only citrate. Anticoagulation with PPACK rather than citrate results in a more reproducible and stable aggregation response and more closely reproduces the in vivo environment of the platelet.

Adenosine Diphosphate↗
PubMed1991

Signal-to-noise optimization of HPLC-fluorometric systems and their application to the analysis of indoles.

The signal-to-noise optimization of high performance liquid chromatographic (HPLC) flow-cell fluorometric systems is described and the possibilities for further improving limits of detection for indoles is discussed. Application of HPLC-fluorometry to analyses in rat cerebrospinal fluid (CSF), human lumbar CSF, and human blood is presented. Finally, the intriguing clinical finding of hyperserotonemia in autism is discussed.

Animals↗