Role of NMDA receptors in methamphetamine-induced changes in extrapyramidal and limbic neuropeptide systems.
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Animals↗
Biomedical subjects
L Bush
Publications and source records attributed to L Bush.
Effects of cocaine on extrapyramidal and limbic dynorphin systems.
The principal central nervous system effects of cocaine are a consequence of its ability to inhibit monoaminergic uptake systems. This agent influences dopamine-related behavior in a manner similar to other sympathomimetics, such as methamphetamine; however, the effect of these two agents on neurochemical dopaminergic parameters are distinct. Several peptidergic neurotransmitter systems, such as the dynorphin pathways, have been shown to be distal to and regulated by the postsynaptic activity of dopaminergic pathways; therefore, we evaluated the response of extrapyramidal and limbic dynorphin A1-17 (Dyn) systems to cocaine by measuring Dyn content in associated structures. Extrapyramidal and limbic dynorphin-like immunoreactivity (DLI) content markedly increased after cocaine treatment. This change appeared to be due primarily to the ability of cocaine to block dopamine re-uptake; consequently, the increase in DLI levels was either totally or partially blocked by coadministration of selective D1 (SCH 23390) and D2 (sulpiride) receptor blockers and multiple doses of the selective dopamine uptake blockers, amfonelic acid and GBR 12909, caused cocaine-like enhancement of extrapyramidal DLI content. Serotonin did not appear to play a major role in mediating the cocaine effects on Dyn systems as multiple doses of the selective serotonin uptake blocker, fluoxetine, did not alter extrapyramidal DLI levels, and depletion of serotonin by pretreatment with parachloroamphetamine did not significantly alter the increases in extrapyramidal Dyn content caused by cocaine administration. Because the behavioral effects of cocaine and methamphetamine are similar, the neurochemical response of Dyn systems to both of these agents is compared and discussed.
Animals↗
Conversion of domains into subunits in the processing of egg yolk biotin-binding protein I.
Biotin-binding protein I (BBP-I), a protein that differs in its heat stability at low concentrations from that of BBP-II, has been purified from the yolk of hen oocytes and compared to BBP-II. Rabbit antiserum to BBP-II cross-reacts with identity to BBP-I. The molecular mass of BBP-I under denaturing conditions is about 68 kDa, a value four times that of BBP-II. Limited trypsin proteolysis of BBP-I generates subunits of 18 kDa with intermediate forms of approximately 51 and 34 kDa. The NH2-terminal sequence of BBP-I is very similar to that of BBP-II but has little of the polymorphism that is presumed to be generated at several positions by the slightly different subunits of BBP-II. These results indicate an unusual processing pathway in which four tandemly repeated biotin-binding domains of BBP-I become the subunits of BBP-II after limited proteolysis.
Amino Acid Sequence↗
Response by the neurotensin systems of the basal ganglia to cocaine treatment.
Multiple administrations of high doses of cocaine had profound effects on the neurotensin (NT) systems of the basal ganglia. Approximately 200-300% increases in striatal content of neurotensin-like immunoreactivity (NTLI) were observed 1-8 h following five doses of 30 mg/kg per dose of cocaine. The effect subsided by 48 h after treatment. Significant changes in striatal NTLI levels were not observed after a single dose of this stimulant. The nigral NT systems appeared to be even more sensitive to cocaine administration. Compared to striatal changes, increases in nigral NTLI content were greater (as much as 455% of control), required lower cocaine doses (20 mg/kg per dose), lasted longer (still elevated to 200% of control after 48 h) and were significant following a single cocaine exposure. The response of the striatal NT systems to cocaine appeared to be mediated principally by dopamine D-1 receptors, while both D-1 and D-2 receptors contributed to the response by the nigral NT projections. Specific dopamine, but not serotonin, uptake blockers caused increases in striatal and nigral NTLI concentrations similar to that seen with cocaine treatments, suggesting that interference with the dopamine uptake carrier complex by cocaine was responsible for its actions on extrapyramidal NT systems.
Animals↗
Avidin traps biotin diffusing out of chicken egg yolk.
1. The unequal distribution of biotin and biotin-binding proteins between the yolk and albumen of freshly laid chicken eggs provides the potential for time-dependent redistribution of biotin that could affect egg quality, biotin availability, and hatchability. 2. Avidin-bound biotin was measured in albumen next to the shell and next to the yolk in eggs stored up to 23 days. 3. Biotin bound to biotin-binding proteins (BBP-I and BBP-II) was measured at the center and periphery of yolk from the same eggs. 4. After 11 days of storage, significant amounts of biotin from the yolk began to accumulate in the albumen adjacent to the yolk. 5. This transfer is attributed to a change in the vitelline membrane that permits diffusion of biotin, not BBP-I or BBP-II, out of the yolk. 6. The dynamics of this phenomenon suggest that in addition to its antimicrobial role, avidin may be involved in the utilization of biotin by the chick embryo.
Animals↗
Employers' attitudes to diabetes.
In order to examine the knowledge and attitude of employers to diabetes and diabetic employees, a questionnaire was sent to a random sample of approximately 2500 businesses and industries in eight different areas of the United Kingdom. Information was collected on the employment of people with diabetes, such as sickness absence, suitability of types of job for the diabetic person, the proportion of people with diabetes registered as disabled, and the provision of pension schemes. Only 1% of firms claimed that they would not consider a person with diabetes for employment within the firm. Nearly a third of employers did not know whether they employed anyone with diabetes. Over a quarter of the manufacturing industries reported some jobs that were unsuitable and 8% reported certain unfavourable job conditions for a diabetic employee such as shift work, working at heights, strenuous work, etc. A total of 7% of those firms with a diabetic employee reported that diabetic workers were more often absent from work due to sickness and 16% of firms employing a diabetic person did not allow paid time off for clinic visits. The attitude of the majority of employers seemed to indicate that diabetes in itself does not limit employment prospects since most people with diabetes have few problems arising from their condition and can make good employees in a range of occupations.
Absenteeism↗
Unemployment and diabetes.
Unemployment was examined in a random sample of diabetic clinic attenders and a group of non-diabetic control subjects aged 17-65 years, selected from eight different centres in Great Britain. Data on employment were obtained using a postal questionnaire and medical details were collected from diabetic clinic notes. Out of a 61% response rate, 22% of males and 12% of females with diabetes were unemployed compared with 8 and 5% of the control group (both p less than 0.001). A greater percentage of people with diabetes were economically inactive, that is retired, unable to work, ill or housewives compared with the control group (29 vs 14%, p less than 0.001). Young people with diabetes (16-25 years) had the highest rates of unemployment. A matched pairs analysis confirmed that diabetic men had higher unemployment rates than their controls (14 vs 7%, p less than 0.001). Comparisons were made between unemployment rates for the eight geographical areas and published unemployment statistics; unemployment rates were significantly higher for men with diabetes except at one centre. A stepwise multiple logistic regression analysis indicated that variables which were predictive of unemployment were similar to those expected for people without diabetes. Unemployment is apparently a problem for the person with diabetes, especially for the young.
Adolescent↗
Effects of amphetamine analogs on central nervous system neuropeptide systems.
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3,4-Methylenedioxyamphetamine↗
Purification and characterization of biotin-binding protein II from chicken oocytes.
BBP-II, the major biotin-binding protein from chicken oocytes, was purified 12,000-fold with a 22% yield. The purification procedure includes butan-1-ol extraction of yolk lipids, phosphocellulose chromatography of the water-soluble proteins, DEAE-cellulose chromatography at pH 7.4 and hydroxyapatite column chromatography. Final purification was obtained by using a second DEAE-cellulose column chromatography at pH 6.0. BBP-I activity separated from BBP-II activity during elution from the first DEAE-cellulose column. Purified BBP-II was homogeneous on both polyacrylamide-gel electrophoresis and SDS/polyacrylamide-gel electrophoresis under conditions that would detect a 1% impurity. The subunit Mr determined from SDS/polyacrylamide-gel electrophoresis was 18,200 (72,600 for tetramer), which compares favourably with an Mr value of 17,300 (69,100) calculated from the amino acid analysis. A single precipitin line formed when rabbit antiserum to the protein was directed against a crude chicken egg-yolk sample. BBP-II purified by this procedure lacked carbohydrate and phosphate, was stable indefinitely when frozen, and was quite stable at room temperature. The N-terminal amino acid sequence showed polymorphism at three positions in the first 23 residues and was about 45% identical with the N-terminal 22 residues of avidin. Antiserum to BBP-II cross-reacted with BBP-I and similar proteins in the yolk of eggs from various birds and alligator as judged by immunodiffusion and enzyme-linked immunosorbent assays. No cross-reaction was observed with chicken egg-white by either of these methods.
Amino Acid Sequence↗
Characterization of methamphetamine effects on the striatal-nigral dynorphin system.
Multiple high doses of methamphetamine (METH) induced 200-300% increases in the concentration of striatal and nigral dynorphin-like immunoreactivity (DLI). Increases in striatal and nigral DLI levels also were seen within 6 h following a single administration. The changes in the striatal-nigral dynorphin system had subsided 48 h after either acute or multiple treatments with METH. Selective lesioning of the nigral-striatal dopamine pathway blocked the effects; thus, the METH-induced changes appeared to be mediated by dopamine released from the nigral-striatal dopamine projection. Administration of the METH analog, 3,4-methylenedioxymethamphetamine, appeared to alter striatal and nigral DLI concentrations in a manner similar to that of METH.
3,4-Methylenedioxyamphetamine↗
Methamphetamine-induced changes in the striatal-nigral dynorphin system: role of D-1 and D-2 receptors.
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Animals↗
Conversion from chronic to acute coronary artery disease: speculation regarding mechanisms.
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Adult↗
Utilization of a human tumor cloning system to monitor for bone marrow involvement in children with non-hodgkin's lymphoma.
The objective of this study was to evaluate the sensitivity of two methods for determining bone marrow involvement with non-Hodgkin's lymphoma. These methods were histologic review of bone marrow aspirates, and clot sections versus in vitro growth of lymphoma colonies on soft agar. Forty-two bone marrow aspirates were studied from 14 children who were without bone marrow involvement at diagnosis. There were seven bone marrow aspirates (from five patients) that had histologic evidence of metastatic lymphoma. Six of these seven specimens formed colonies in vitro. Twenty-nine of 35 histologically negative specimens showed no lymphoma colony growth. However, six histologically negative specimens (from three patients) formed lymphoma colonies. Both the Fisher's exact test and the K statistic were significant, indicating not only an association between histology and in vitro culture results, but also a close agreement. In addition, growth of lymphoma colonies in vitro was associated statistically with both a short duration of complete remission and a short duration of survival.
Adolescent↗
Nitrendipine: effects on vascular responses and myocardial binding.
We have further defined the binding characteristics of [3H]nitrendipine to myocardial microsomal membranes of cats, dogs, rats, and rabbits and to canine coronary vasculature (1.5-3.0 mm OD), and we have studied nitrendipine's effect on contractile responses in isolated feline cardiac muscle and canine coronary arteries. [3H]nitrendipine binding is rapid, saturable, and reversible in all four species and in all of these tissues. Feline myocardium has a single binding site with a dissociation constant (KD) of 1.94 nM. Canine myocardium may have two classes of binding sites, with the high-affinity site having a KD of 0.17 nM. Nitrendipine depresses contractility in isolated feline cardiac muscle and canine coronary arteries in a dose-dependent manner [half-maximal dose (ED50) 0.20 microM in isolated feline cardiac muscle and 1.6-6.3 nM for potential dependent contractile responses in isolated canine coronary arteries] and severely blunts the contractile response to increases in extracellular calcium concentration in isolated feline papillary muscles. In contrast to verapamil and D 600, nitrendipine does not prevent the treppe phenomenon. In isolated feline cardiac muscle and large canine coronary arteries, the minimal nitrendipine concentration required for specific binding and for depression of contractile responses is similar. However, only in large canine coronary arteries is the ED50 for nifedipine's depression of contractility similar to the KD for [3H]nitrendipine binding in the respective tissue.
Animals↗
Iodine-123 phenylpentadecanoic acid: detection of acute myocardial infarction and injury in dogs using an iodinated fatty acid and single-photon emission tomography.
The ability of an iodinated fatty acid, iodine-123 phenylpentadecanoic acid (1-123 PPA), and single-photon emission computed tomography (SPECT) to detect myocardium injured by temporary or permanent coronary arterial occlusion was evaluated. In 5 control dogs, 11 dogs that underwent 90 to 120 minutes of fixed left anterior descending coronary artery (LAD) occlusion, and 8 dogs that underwent 90 minutes of temporary LAD occlusion and up to 90 minutes of reflow, 2 to 6 mCi of I-123 PPA were injected and the dogs were imaged with SPECT. Control dogs showed relatively uniform uptake and clearance of I-123 PPA in similar left ventricular (LV) regions. Dogs with permanent LAD occlusion were identified by computer algorithm as having regions of decreased I-123 PPA uptake in the infarct-related area and a reduced rate of I-123 PPA clearance (-9.4% in infarct sectors [washin], +3.7% in sectors adjacent to the area of infarction, and +15.4% in control LV sectors [p less than 0.01]). Dogs with temporary LAD occlusion and reperfusion had decreased clearance of I-123 PPA from the regions with infarction; I-123 PPA clearance was -5.2 +/- 16.4% in infarct sectors, 12.7 +/- 7.4% in periinfarct zones, and 30.4 +/- 12% in control LV regions. These data demonstrate that tomographic analysis of I-123 PPA uptake and clearance permits the relatively noninvasive detection of LV myocardium injured by permanent or temporary LAD occlusion and reperfusion.
Animals↗
Hydrogen peroxide contrast echocardiography.
Several agents are used as echocardiographic contrast agents, but their unreliability discourages routine clinical use. Studies from the early 1960s suggest that dilute hydrogen peroxide (H2O2) is a safe intravascular agent. Its use was evaluated in contrast echocardiography. To obtain dense opacification reliably, H2O2 (3%) was passed through a sterile 0.2 micron Millipore filter and diluted with heparinized saline solution to make a 0.1 to 0.2% solution. A drop of blood was withdrawn from an indwelling peripheral venous needle into a syringe containing 0.5 to 2.0 ml of the dilute H2O2 and the contents injected. Studies in dogs, normal adults and 36 patients with noncyanotic congenital and acquired cardiac disorders produced dense opacification with no complications. In vitro mixture of H2O2 (0.3%) with leukocyte-poor blood or plasma produced only a few microbubbles, while addition to whole blood or buffy coat produced many, suggesting a role for leukocyte peroxidase. H2O2 contrast echocardiography is simple, inexpensive, and reliably provides dense, sustained opacification. This study and previous studies suggest that intravenous injection of 0.2% H2O2 can be done safely. Great caution should be exercised in patients with severe pulmonary hypertension or large right-to-left shunts because little clinical experience with H2O2 is available.
Animals↗
Differences in myocardial alpha- and beta-adrenergic receptor numbers in different species.
In the present study, we tested the hypotheses that 1) different species have different myocardial adrenergic receptor numbers and 2) selected "slow-channel" calcium antagonists compete with alpha-adrenergic antagonists for binding to varying degrees in different species. The data obtained in the present study demonstrate that there is a markedly decreased number of alpha 1-adrenergic and increased number of beta-adrenergic receptors in canine compared with rabbit and rat myocardium. The differences in adrenergic receptor numbers exist without major differences in alpha 1-adrenergic receptor affinity in the species studied. There was no significant difference in left ventricular or plasma catecholamine content between the rat and dog. Selected slow-channel calcium antagonists compete for alpha 1-adrenergic receptor binding in rabbit, rat, and canine myocardium. However, only in rabbit myocardium does verapamil antagonize alpha 1-adrenergic receptor binding at moderate concentrations, whereas verapamil in canine and rat myocardium and 1) 600 in all three species antagonize alpha 1-adrenergic receptor binding only at relatively high concentrations. Nifedipine, a dihydropyridine-type slow-channel calcium antagonist, had no effect on prazosin binding to rat, rabbit, and dog myocardial membranes.
Animals↗