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A L McCall

Publications and source records attributed to A L McCall.

At least 37 records · Page 2Linked to original sources
PubMed1994

Immunohistochemical localization of the neuron-specific glucose transporter (GLUT3) to neuropil in adult rat brain.

The precise histologic localization of GLUT3, a glucose transporter thought to be restricted to neurons, is unknown. Using a high-affinity, specific antiserum against rodent GLUT3 for immunocytochemistry, light microscopic staining concentrates heterogeneously in the neuropil in a region- and lamina-specific manner; intense staining characterizes areas with high rates of glucose utilization such as inferior colliculus and pyriform cortex. Neuropil localization with little perikaryal staining suggests that GLUT3 may provide the energy needed locally for synaptic transmission.

Animals↗
PubMed1993

An immunization method for generation of high affinity antisera against glucose transporters useful in immunohistochemistry.

Antipeptide antisera from unique amino acid sequences of proteins, predicted from their cDNA, are useful to study cellular distribution of these proteins, but such peptides often are poorly immunogenic. We describe a secondary immunization method with repeated intravenous administration of KLH-conjugated peptides to boost the immune response rapidly and transiently as high as 60-fold to peptides of low immunogenicity (glucose transporters, GLUT3 and GLUT4). Such antisera are suitable for immunocytochemistry with excellent anatomic detail. This method may be generally useful as it is reproducible and can yield progressive titer increases when repeated.

Amino Acid Sequence↗
PubMed1993

The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movement disorders.

BACKGROUND: Metoclopramide hydrochloride, a neuroleptic dopamine receptor antagonist used to treat gastric ailments, is reported to cause extrapyramidal movement disorders. The goals of this study were (1) to determine the prevalence and severity of tardive dyskinesia and acute extrapyramidal movement syndromes including akathisia, acute dystonia, and drug-induced parkinsonism in metoclopramide-treated patients and (2) to compare the prevalence and severity of tardive dyskinesia in metoclopramide-treated diabetics and nondiabetics. METHODS: From a list of metoclopramide-treated patients received from the Portland (Ore) Veterans Affairs Medical Center pharmacy, 53 patients met inclusion criteria and 51 (96%) agreed to participate. Controls consisted of a convenience sample drawn from the Portland Veterans Affairs Medical Center Outpatient Clinic who were matched to subjects on age (+/- 10 years), gender, and presence or absence of diabetes. Of 61 potential controls contacted, 51 (84%) agreed to participate. Metoclopramide-treated subjects and controls were seen by a rater who was "blind" to all diagnoses and treatments. The rater performed a standardized examination used to elicit signs and symptoms of tardive dyskinesia and acute extrapyramidal movement syndromes. RESULTS: The relative risk for tardive dyskinesia was 1.67 (95% confidence interval, 0.93 to 2.97), and the relative risk for drug-induced parkinsonism was 4.0 (95% confidence interval, 1.5 to 10.5). Metoclopramide-treated patients had significantly greater severity of tardive dyskinesia, drug-induced parkinsonism, and subjective akathisia than controls. Use of metoclopramide was associated with impairment in ambulation and increased use of benzodiazepines. Metoclopramide-treated diabetics had significantly greater severity of tardive dyskinesia than metoclopramide-treated nondiabetics. CONCLUSIONS: Metoclopramide use is associated with a significantly increased prevalence and severity of several extrapyramidal movement disorders.

Adult↗
PubMed1992

The impact of diabetes on the CNS.

The brain is not usually thought to be a target of chronic diabetes complications. Nonetheless, substantial evidence, summarized herein, suggests that diabetes causes brain damage. Clinical syndromes of diabetes-related brain abnormalities are discussed along with possible causes. Various physiological effects of diabetes are reviewed, and questions are raised about gaps in our knowledge. Appropriate directions for future research are suggested.

Brain↗
PubMed1990

Glucose is required to maintain ATP/ADP ratio of isolated bovine cerebral microvessels.

Isolated bovine cerebral microvessels (ICMV) were incubated with different metabolic fuels to determine the effect of each of them on microvessel energy state. With no fuel added to the medium, the ATP/ADP generally decreased from initial values of 1.5-3 down to 1-1.5 over 4 h; the ATP content also declined approximately 50%. In contrast, with glucose present, the ATP/ADP increased, and the ATP content was maintained. Pyruvate, beta-hydroxybutyrate, glutamate, and oleate were ineffective; oleate added together with carnitine gave some improvement but less than with glucose. Oxygen consumption by ICMV did not differ appreciably in fuel-free or glucose-containing medium. Addition of an inhibitor of fatty acid oxidation, 2-tetradecylglycidate, depressed the ATP/ADP. These results suggest that ICMV require glycolysis to maintain both their content of ATP and their ATP/ADP. They also suggest that endogenous lipid is an important fuel for isolated microvessels.

Adenosine Diphosphate↗
PubMed1988

Chronic exposure to high glucose decreases myo-inositol in cultured cerebral microvascular pericytes but not in endothelium.

It has been proposed that the development of diabetic complications may involve a depletion of cellular myo-inositol due to an increase in polyol (sorbitol) formation. We therefore initially examined the effect of diabetes on levels of these metabolites in isolated cerebral microvessels. Compared with microvessels from control rats, microvessels from diabetic animals showed no detectable alteration in myo-inositol levels and a small increase in sorbitol content. To assess whether myo-inositol depletion might occur in only certain microvascular cells, cultured bovine cerebral microvascular pericytes and endothelium were grown for 3 or 18-20 days at 1.1, 5.5, or 22.2 mmol/l glucose. Increased medium glucose concentration resulted in increased sorbitol content in both cell types after both periods of incubation (p less than 0.05). In contrast, a significant decrease in myo-inositol content (22%, p less than 0.01) was observed only in pericytes grown for 18-20 days in the high glucose medium. Neither the adenosine 5'-triphosphate content nor the adenosine 5'-triphosphate/adenosine 5'-diphosphate (ATP/ADP) ratio of the pericytes was affected by the medium glucose concentration, indicating that the decrease in myo-inositol was not caused by a deficiency in the cellular energy state affecting the active transport of myo-inositol. These data suggest that myo-inositol depletion occurs selectively in the pericyte, a cell type known to be the site of early morphological changes in diabetes. Furthermore, the depletion apparently requires prolonged exposure to high glucose and is not due to a change in energy state.

Adenosine Diphosphate↗
PubMed1988

Energy state of bovine cerebral microvessels: comparison of isolation methods.

Isolation procedures employed by various laboratories to obtain cerebral microvessels generally utilize meshes to sieve and collect the microvessels from homogenized brain. This is followed in some cases by further purification using density gradients of Percoll or sucrose, or albumin flotation. We have evaluated microvessels prepared by these methods in terms of ATP content and ATP/ADP ratio, which reflect the cellular energy state, and enrichment of the marker enzymes, alkaline phosphatase and gamma-glutamyltransferase. Albumin flotation generally increased the enrichment of marker enzymes; however, preparations using albumin flotation or a Percoll gradient exhibited considerable variability in ATP content and ATP/ADP ratio with the mean ATP/ADP ratio significantly lower than that observed in microvessels isolated by sieving through meshes. More uniformly high values for both ATP (approximately 1.6 nmole ATP/mg protein) and the ATP/ADP ratio (approximately 2.3) were obtained with meshes alone. Use of a sucrose gradient consistently resulted in preparations with a much lower ATP content and ATP/ADP ratio, compared with preparations obtained with the other methods. Values using the other methods were higher than those previously reported, yet were still lower than the ATP content of about 23 and ATP/ADP ratios of 18 and 7 we found in cultured microvascular endothelium and pericyte, respectively. These low values were not improved by supplying additional fuel to the microvessels during isolation, suggesting they were not the result of fuel deprivations during isolation. Despite the probable damage incurred during isolation, microvessel preparations are a useful in vitro model in which fuel metabolism appears to reflect the prior hormonal/nutritional state of donor animals. However, our data indicate the advisability of measurements of ATP content and ATP/ADP ratio for quality control of preparations used for metabolic studies, especially after Percoll density gradient or albumin flotation steps.

Adenosine Diphosphate↗
PubMed1988

Metabolic characterization of isolated cerebral microvessels: ATP and ADP concentrations.

Isolated cerebral microvessels (ICMV) have been increasingly used to study microvascular metabolism and function. Despite this, little systematic information exists about their metabolic viability and energy status. To evaluate this, we determined the ATP content and ATP/ADP ratios of ICMV with an ultrasensitive bioluminometric assay which had been adapted for small samples. In calf cerebral microvessels, freshly isolated by a homogenization and sieving procedure, ATP content averaged 1.5 +/- 0.8 nmole/mg protein (mean +/- SE for 45 observations on 18 preparations.) The ATP/ADP ratio for these vessels was 0.96 +/- 0.4. Similar values for ATP were obtained in several preparations of ICMV from dog and rat brain. Values varied considerably in different preparations, probably due to variable degrees of damage incurred during isolation. When microvessel ATP concentrations and ATP/ADP ratios were low, they were dramatically improved by brief incubation (2 hr at 37 degrees) in an enriched tissue culture medium (Dulbecco's modification of Eagle's minimal essential medium, DMEM), or perhaps somewhat less effectively in a buffered saline solution (Earle's-Hepes) containing glucose. Boiling or incubation of microvessels with Triton X-100 lowered ATP values to less than 0.01 nmole/mg protein. The ATP content of our preparations of isolated microvessels was considerably higher than values previously reported by others using similar methods, but still less than that of cultured bovine vascular endothelial cells, even after correction for a 20% difference in intracellular water space.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1988

Effects of hypoglycemia and diabetes on fuel metabolism by rat brain microvessels.

Glucose and beta-hydroxybutyrate metabolism were compared in isolated cerebral microvessels from chronically diabetic and hypoglycemic rats. As noted previously, glucose oxidation and conversion to lactate are diminished in rats with streptozotocin-induced diabetes. The decrease in glucose metabolism did not result from selective damage to diabetic vessels during isolation, since the ATP level and the ATP/ADP ratio were similar to those of nondiabetic rats, and O2 consumption was increased. In addition, cerebral microvessel oxidation of beta-hydroxybutyrate was enhanced by diabetes. By contrast, microvessels from rats made chronically hypoglycemic by insulinoma engrafting 30 days earlier had a more than twofold increase in glucose oxidation and conversion to lactate, whereas their oxidation of beta-hydroxybutyrate was diminished by 50%. Unlike the insulinoma rats, no consistent increase in glucose metabolism was observed in microvessels from rats made hypoglycemic either by acute insulin administration or by a 4-day infusion of insulin. These results indicate that diabetes, and under some circumstances chronic hypoglycemia, markedly alters fuel metabolism in the cerebral microvasculature.

3-Hydroxybutyric Acid↗
PubMed1987

Home blood glucose monitoring: keystone for modern diabetes care.

Home monitoring of capillary blood glucose concentrations has changed diabetes care, giving physicians and patients a way to adjust their therapy and achieve better diabetic control. The practical strategies and equipment for home diabetic monitoring are discussed, including the changing role of urine testing and how inexpensive machines may enhance the value of blood glucose monitoring.

Blood Glucose↗
PubMed1987

Distribution of glucose transporter messenger RNA transcripts in tissues of rat and man.

We used the complementary DNA for the human hepatoma Hep G2 glucose transporter to determine the distribution of glucose transporter messenger RNA (mRNA) in rat and human tissues. Under stringent hybridization conditions, a single 2.8-kilobase (kb) transcript is seen in all rat and human tissues examined. The mRNA is most abundant in brain, and is especially enriched in the brain microvascular fraction. The mRNA abundance in rat muscle and fat is 5% that in brain. Rat liver (both adult and fetal) and human liver have very little 2.8-kb mRNA, but it is abundant in cultured human fibroblasts and EB virus-transformed lymphoblasts. The same size mRNA is present in leg muscle of two type II diabetic patients. A very homologous glucose transporter mRNA is expressed in both insulin-sensitive and -insensitive tissues of rat and man. Hepatocytes, which have abundant glucose transport, may express a homologous but nonidentical glucose transporter.

Animals↗
PubMed1986

Chronic hypoglycemia increases brain glucose transport.

Glucose transport into the brain is depressed in chronically hyperglycemic (diabetic) rats. To determine whether hypoglycemia has the opposite effect, brain transport of hexoses and other substrates was examined in chronically and acutely hypoglycemic rats. We produced chronic hypoglycemia by implanting insulin-secreting tumors or insulin-releasing osmotic mini-pumps or by repeated injection of protamine zinc insulin (PZI) and acute hypoglycemia by intravascular injection of regular insulin. Blood-brain barrier (BBB) transport was measured using the brain uptake index (BUI) method. In the three models of chronic hypoglycemia, brain glucose extraction was increased compared with controls. The extraction of deoxyglucose and several other hexoses was also increased by chronic hypoglycemia. Acute hypoglycemia had no effect on brain transport. The transport of other substrates was either not affected or depressed, suggesting increased brain hexose transport is specific. Studies of freeze-blown brain in insulinoma-engrafted rats showed that brain glucose levels were depressed while creatine phosphate, ATP, and glucose 6-phosphate were maintained. Tumor removal led to a reversion of brain glucose transport to control rates but only after 5-25 days. These findings support the view that glucose transport across the BBB is modulated by chronic alterations in the ambient glucose concentration. They also may explain why some patients with chronic hypoglycemia tolerate low blood glucose concentrations.

Animals↗
PubMed1986

Home monitoring of diabetes mellitus--a quiet revolution.

Home monitoring of capillary blood glucose concentrations has changed diabetes care, giving physicians and patients a way to adjust their therapy and achieve better diabetic control. The practical strategies and equipment for home diabetic monitoring are discussed, including the changing role of urine testing and how inexpensive machines may enhance the value of blood glucose monitoring.

Blood Glucose↗
PubMed1984

Diabetes-induced alterations of glucose metabolism in rat cerebral microvessels.

The effect of diabetes on the metabolism of glucose and lactate was examined in isolated rat cerebral microvessels. In rats with diabetes induced with streptozotocin, glucose oxidation to CO2 by the microvessels was decreased by 54-83% and its conversion to lactate by 21-61%. Insulin therapy for several days or starvation for 48 h both lowered blood glucose levels in the diabetic rats and restored microvessel glucose metabolism to normal. Cerebral microvessels consist principally of the capillaries that constitute the blood-brain barrier. Direct assessment of the blood-brain barrier in vivo using the brain uptake index (BUI) technique revealed a close parallel to the findings in the microvessels. Thus, hexose transport was diminished in diabetic rats and restored to normal by both insulin therapy and starvation. The oxidation of [1-14C]lactate to CO2 like that of glucose was depressed in microvessels of diabetic rats. In contrast to glucose, however, the transport of lactate across the blood-brain barrier in vivo was not altered. These findings suggest that diabetes suppresses glucose metabolism in rat cerebral microvessels and downregulates glucose transport across the blood-brain barrier. They also suggest that both of these processes are regulated by chronic alterations in blood glucose concentration rather than by insulin per se.

Animals↗
PubMed1982

Blood-brain barrier transport of caffeine: dose-related restriction of adenine transport.

We studied the transport of 14C-caffeine across the blood-brain barrier (BBB) by measuring brain 14C:3H ratios five seconds after rats received the caffeine, with 3H2O, by intracarotid injection. Caffeine was found to enter the brain by both simple diffusion and saturable, carrier-mediated transport. This latter observation suggested to us that caffeine's transport might involve macromolecules that are structurally similar to caffeine. Hence, we examined caffeine's ability to inhibit the BBB transports of 14C-adenosine and 14C-adenine. Caffeine caused a dose-dependent inhibition of 14C-adenine transport but no clear change in that of 14C-adenosine. At very high blood levels (Ki = 9.8 mM), caffeine may restrict the availability of circulating purines to the brain. This effect may be important neonatally, when carrier-mediated adenine transport apparently is maximal.

Adenine↗
PubMed1982

Metabolic fuel and amino acid transport into the brain in experimental diabetes mellitus.

We used the Oldendorf brain uptake index method to study the blood-brain barrier transport of several metabolic substrates in diabetes. Glucose transport into the brain was decreased by 1/3 in rats with moderate diabetes induced by prior injection of streptozotocin (65 mg/kg of body weight). The transports of mannose and the poorly metabolized hexoses 2-deoxyglucose and 3-O-methylglucose were similarly reduced. Likewise, brain glucose transport was decreased in rats with alloxan-induced diabetes. These alterations in brain hexose influx appeared to be related to chronic (1-2 days) hyperglycemia rather than to insulin-lack per se. Thus, starvation of the diabetic rats for 48 hr restored both the plasma glucose concentration and brain hexose transport to normal. Conversely, the substitution of 10% sucrose for their drinking water both increased plasma glucose and decreased hexose transport in insulin-treated diabetic rats. The 45% decrease in maximal glucose transport rate observed and the uniformity of diminished hexose transport probably imply a decrease in the number of available high-affinity transport carriers at the blood-brain barrier. This defect was specific for hexoses in that the transports of neutral and basic amino acids and of beta-hydroxybutyrate were not similarly affected. These results suggest that chronic hyperglycemia decreases the number of hexose carrier molecules available at the blood-brain barrier. Such an adaptation could operate to decrease the net flux of glucose into the brain during sustained hyperglycemia. It also may explain the abnormal sensitivity to abrupt blood glucose lowering in patients with diabetes mellitus.

3-O-Methylglucose↗
PubMed1981

Non-saturable transport of [3H]oestradiol across the blood-brain barrier in female rats is reduced by neonatal serum.

Adult ovariectomized rats were decapitated 5 sec after intracarotid injection of a 200-microliter bolus containing [3H]oestradiol plus [14C]butanol, which served as a freely diffusible reference for transport across the blood-brain barrier. When buffered Ringer's solution (with 20% ethanol added to dissolve the oestradiol) was used as the injection vehicle, 83 +/- 6% (mean +/- s.e.m.) of the injected [3H]oestradiol (0.17 microM) reaching the brain microvasculature was extracted in one circulatory passage. Addition of unlabelled oestradiol (34 or 68 microM) to the injection bolus did not reduce this percentage of extraction. When 0.1% bovine serum albumin rather than ethanol was added to buffered Ringer's solution to ensure solubilization of [3H]oestradiol (0.043 microM), the percentage brain extraction was 82 +/- 6%, and again, addition of unlabelled oestradiol (300 microM) did not reduce this value significantly. This finding suggests that oestradiol diffuses into the rat brain passively and is not transported via saturable carrier molecules. When serum from and adult, ovariectomized, female rat was used as the injection medium, the brain extracted 56 +/- 4% of the injected [3H]oestradiol (0.17 microM), whereas only 13 +/- 1% was extracted from a pool of serum obtained from 9-day-old young rats of both sexes. Brain extraction of [3H]oestradiol (0.043 microM) was significantly lower when the injection vehicle used was serum collected from female rats killed on Days 0, 5 or 20 after birth than on Days 30 or 120. These in-vivo results suggest that neonatal rat serum contains a factor (presumably alpha-fetoprotein) that restricts oestradiol influx into the developing brain.

Animals↗