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Biomedical subjects

L L Brown

Publications and source records attributed to L L Brown.

At least 37 records · Page 2Linked to original sources
PubMed1995

Metabolic mapping of rat striatum: somatotopic organization of sensorimotor activity.

Diseases that affect the striatum produce movement disorders, for which rats have been a useful model. To determine the organization of functional, neural activity in the rat striatum related to motor activity, we used electrical stimulation of the motor cortex and [14C]deoxyglucose autoradiography. The stimulation produced movements of each of three body regions. Both the motor and somatosensory cortex were activated. Image analysis was used to objectively localize peak activation and to provide a map for further stereotaxic and localization studies. In the anterior striatum, in the dorsolateral sector, regions of peak activation were well separated for each body region: the hindlimb peak activation was dorsomedial, the forelimb ventrolateral and vibrissae medial. Also, the activation fields were larger in anterior than in posterior striatum. Furthermore, activation ipsilateral to movement was present and the peak localization was offset from peaks contralateral to movement. In addition, there were activation regions in lateral striatum where body region representations may overlap. This is the first demonstration of a global striatal somatotopy that separates the limbs and vibrissae in rats. The functional average revealed by the deoxyglucose autoradiography showed a predominant isotropic or rod-like representation of sensorimotor activity for the limbs in striatum during movement and confirms aspects of the anatomy known for the corticostriate system in primates: metabolism was 'patchy,' and extended throughout long anteroposterior domains in striatum. These extensive and patchy arrangements suggest integrative, combinational and/or associative networks.

Animals↗
PubMed1995

Ontogeny and topography of seizure regulation by the substantia nigra.

The substantia nigra pars reticulata (SNR) is a structure involved in the control of seizures, and its effects on seizures are age-dependent. GABAergic transmission in the SNR, mediated by GABAA receptors, influences seizure susceptibility. We have found that in the adult SNR there may be at least two segregated GABAA-sensitive SNR projection networks involved in regulating the SNR effects on seizures, perhaps reflecting the existence of an anticonvulsant and a proconvulsant network. The two networks with opposing effects on seizures originate from two topographically distinct regions. The anterior-medial region of the SNR is associated with anticonvulsant effects, whereas the posterior-dorsal region of the SNR is associated with proconvulsant effects. To explain ontogenic differences in the SNR effects on seizures, we hypothesize that the two functionally segregated networks which influence the expression of seizures may become segregated with maturation. The increased seizure susceptibility of rat pups may be due, in part, to delayed development of this anterior-medial SNR anticonvulsant network.

Age Factors↗
PubMed1994

Maturation and segregation of brain networks that modify seizures.

The mature brain is less susceptible to seizures than the immature brain. We demonstrate that in the mature substantia nigra (SN) there are two topographically discrete GABAA-sensitive regions which differ in the amount of mRNA expression of the GABAA receptor alpha 1 subunit. These two regions mediate separate anticonvulsant and proconvulsant effects and use divergent projection networks. By contrast, in the immature SN there is no special topography of mRNA expression of the alpha 1 subunit and only the proconvulsant network is present. The decreased seizure susceptibility of the mature brain may be related to postnatal segregation of GABAA-sensitive networks.

Animals↗
PubMed1992

Somatotopic organization in rat striatum: evidence for a combinational map.

2-Deoxy-D-[14C]glucose autoradiography was used in awake rats to map neural activity in the sensorimotor sector of striatum. Stimulation of hindlimb, trunk, or forelimb activated primary sensory cortex in a localized columnar pattern, indicating activation of somatosensory receptors and a discrete cortical functional unit. In sensorimotor striatum, an image analysis detection technique revealed regions of maximal activity, or features, that formed a patchy pattern of activation reminiscent of the known anatomic patterns of cortico-striate terminals. Ipsilateral as well as contralateral activation was observed. The activated areas revealed a body map in striatum that was organized in a manner consistent with cortical topography (dorsoventrally: hindlimb, trunk, forelimb) at most anteroposterior levels, similar to that found in other species. However, at other levels, a different organization (e.g., trunk, hindlimb, forelimb) was observed. Furthermore, the arrangements of body region and side were also unique at different anteroposterior levels. Thus, functional activity showed multiple, different juxtapositions of body elements--i.e., a combinational map. The data suggest that striatum may provide an anatomic substrate for different combinations of inputs necessary to select and integrate movement.

Animals↗
PubMed1991

Rapid measurement of leucine-specific activity in biological fluids by ion-exchange chromatography and post-column ninhydrin detection.

Commonly used methods for the measurement of leucine-specific activity use either high-performance liquid chromatography (HPLC) and pre-column derivatization or conventional ion-exchange chromatography. These are time-consuming, labor-intensive, relatively costly procedures, requiring high concentrations of radioactivity for accuracy. The present paper describes a method for the measurement of plasma leucine-specific activity using HPLC equipment, a large-bore ion-exchange column and post-column ninhydrin detection. With this method, determination of leucine concentration and leucine radioactivity was found to be linear (r2 greater than 0.999) over physiological ranges for both standards and deproteinized plasma. The intra- and inter-assay coefficients of variation for leucine concentrations were 1.4 and 2.7%, respectively. The intra- and inter-assay coefficients of variation for leucine-specific activities were 1.5 and 1.9%, respectively. The automated method is relatively fast (injection to injection time approximately 45 min), economical and capable of accurately assessing relatively small amounts of radioactivity.

Chromatography, High Pressure Liquid↗
PubMed1991

Interaction of exercise and insulin action in humans.

To assess the interaction of exercise and insulin action, healthy males were studied with saline infusion (n = 5) or with a hyperinsulinemic euglycemic clamp (0.5, 1.0, 2.0, or 15.0 mU.kg-1.min-1; n = 5 at each dose) during rest (40 min), moderate-intensity cycle exercise (100 min), and recovery (100 min). Metabolism was assessed using isotopic methods and indirect calorimetry. During rest, exercise, and recovery with saline infusion, plasma glucose was unchanged, total glucose utilization (Rd) was 2.4 +/- 0.4, 4.9 +/- 0.2, and 2.6 +/- 0.2 mg.kg-1.min-1, and carbohydrate (CHO) oxidation (OX) was 1.4 +/- 0.3, 10.6 +/- 1.1, and 0.5 +/- 0.2 mg.kg-1.min-1. The glucose infusion, insulin-dependent Rd, and CHO OX increased synergistically when exercise and insulin clamps were combined. Exercise decreased (P less than 0.05) the half-maximal doses (ED50) and increased the maximal responses (Vmax) for insulin-dependent Rd and CHO OX. Estimates of insulin-independent Rd were 1.3 +/- 0.7, 4.1 +/- 1.3, and 1.9 +/- 0.7 mg.kg-1.min-1 and insulin-independent CHO OX were 1.2 +/- 0.9, 10.4 +/- 1.3, and 0.6 +/- 0.3 mg.kg-1.min-1 during rest, exercise, and recovery. Estimates during exercise were greater than those at rest (P less than 0.05). The total suppression of free fatty acids (FFA) and fat OX by insulin were elevated by exercise (P less than 0.05). In summary, exercise and insulin interact synergistically in stimulating Rd and CHO OX.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Instability of orthophthalaldehyde reagent for amino acid analysis.

Determination of amino acids by reversed-phase chromatography of the adduct with orthophthalaldehyde and a thiol is rapid and sensitive. The major recognized adverse feature of this method is the instability of the reaction product, which requires precise control of reaction timing and chromatographic parameters for reliable quantitative application. We report another source of major variability: reagent instability. Deterioration of reagent was noted as low peak heights and peak broadening and was predictable if the premixed reagent was left at room temperature. Restoration of sharp chromatograms was accomplished by addition of mercaptoethanol or sodium metabisulfite. Reagent which was chromatographically inert contained minimal free thiol by direct assay. Free thiol disappearance was markedly slowed by addition of a chelating agent. Excess mercaptoethanol was deleterious. We conclude that reagent deterioration represents oxidation of the thiol, may be reversed by rereduction with minimal thiol or bisulfite, and may be minimized by inclusion of a metal chelator in the reagent.

Aldehydes↗
PubMed1989

The nucleus locus coeruleus modulates local cerebral glucose utilization during noise stress in rats.

Local cerebral glucose utilization (LCGU), estimated by the quantitative autoradiographic 2-deoxyglucose technique, was studied in rats with bilateral 6-hydroxydopamine lesions of the locus coeruleus (LC) and in vehicle-injected controls. Unanesthetized animals were studied during exposure to stressful levels of white noise (95 dB) or in relative silence (50 dB). Results indicated that noise caused greater and more widespread increases in LCGU in animals with LC lesions than in vehicle-injected controls. Lesions alone had little or no effect in animals not subjected to noise. Analyses of variance revealed significant treatment interaction effects (intact/lesion x silence/noise) for 37 of 109 regions measured. The pattern of results suggests that the LC acts during stress to limit unnecessary cerebral activity that might interfere with efficient sensory processing and/or the organization of appropriate behavioral responses. In this respect LC function may be similar to those actions of the peripheral sympathetic nervous system that suppress vegetative functions during stress to allow for the performance of coping responses.

Animals↗
PubMed1989

Intraperitoneal transplantation of microcarrier-attached enterocytes in rats.

The purpose of this study was to determine whether enterocyte transplantation could be used to correct a specific genetic metabolic defect. Bilirubin uridine diphosphoglucuronyl transferase (UDPGT) activity has been demonstrated in normal rat intestinal mucosa. We hypothesized that normal rat enterocyte transplantation may restore the ability of Gunn rats, which lack bilirubin UDPGT, to conjugate bilirubin. Small intestine was resected from normal Wistar rat donors. Enterocytes were harvested and suspended in Dulbecco's modified Eagle's medium with 10 percent fetal calf serum. Isolated enterocytes were attached to collagen-coated dextran microcarriers and transplanted into congeneic Gunn rat recipients. Recipient rats underwent bile duct cannulation after transplantation, and bile was analyzed for bilirubin glucuronides by high-pressure liquid chromatography. Fifty percent of the transplanted rats showed a significant increase in the concentration of bilirubin monoglucuronide and diglucuronide in their bile 4 and 7 days posttransplantation. Recipient rats had well vascularized microcarrier-enterocyte aggregates in the peritoneal cavity. Our method for intraperitoneal transplantation of isolated enterocytes in rats could potentially be used to correct specific enzymatic and metabolic defects.

Animals↗
PubMed1989

Central effects of beta-endorphins on glucose homeostasis in the conscious dog.

The effects of centrally administered beta-endorphins on glucose homeostasis in the conscious dog were studied. Intracerebroventricular administration of beta-endorphin (0.2 mg/h) caused a 70% increase in plasma glucose. The mechanism of the hyperglycemia was twofold: there was an early increase in glucose production and a late inhibition of glucose clearance. These changes are explained by marked increases in plasma epinephrine (30-fold) and norepinephrine (6-fold) that occurred during infusion of beta-endorphin. Central administration of beta-endorphin also resulted in increased levels of adrenocorticotropic hormone and cortisol. In addition there was an increase in plasma insulin but no increase in plasma glucagon. Intravenous administration of beta-endorphin did not alter glucose homeostasis. Intracerebroventricular administration of acetylated beta-endorphin did not perturb glucose kinetics or any of the hormones that changed during infusion of the unacetylated peptide. We conclude that beta-endorphin acts centrally to cause hyperglycemia by stimulating sympathetic outflow and the pituitary-adrenal axis. Acetylation of beta-endorphin abolishes the in vivo activity of the peptide.

Animals↗
PubMed1989

Amino acids augment insulin's suppression of whole body proteolysis.

Leucine (LEU) kinetics were assessed using a primed-continuous infusion of L-[1-14C]LEU in normal overnight-fasted male volunteers during a basal period and an experimental period where insulin (INS) was infused at either 0.6, 1.2, 2.5, 5.0, 10, or 20 mU.kg-1.min-1 with euglycemia maintained. Two protocols were used: 1) subjects were allowed to develop hypoaminoacidemia or 2) plasma essential amino acids (AA) were maintained near basal levels by frequently monitoring plasma LEU in conjunction with variable infusions of an AA solution (LEU infused = 0.41, 0.72, 0.93, 1.03, 1.31, and 1.35 mumol.kg-1.min-1 at escalating INS doses, respectively). Basal rates of LEU appearance (Ra), nonoxidative disappearance (NORd) and oxidative disappearance (OXRd) were similar in both protocols (means = 1.74, 1.40, and 0.36 mumol.kg-1.min-1, respectively). INS infusions without AA resulted in a progressive decrement in LEU Ra (14 to 45%), NORd (16-41%), and OXRd (3-56%) compared with basal values. The infusion of AA resulted in an additional reduction in endogenous Ra (P less than 0.01; approximately 100% suppression achieved at plasma INS greater than 1,000 microU/ml) and a blunting of NORd reduction (P less than 0.05) at each dose of INS. Observed differences in INS's suppression of LEU Ra between the two protocols suggests the existence of a component of whole body proteolysis that is highly dependent on circulating plasma AA. Therefore, hypoaminoacidemia associated with INS treatment would appear to blunt the responsiveness of INS's suppression of protein breakdown and in the presence of near basal plasma AA, proteolytic suppression by INS is enhanced.

Adult↗