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Biomedical subjects

R M Brown

Publications and source records attributed to R M Brown.

17 recordsLinked to original sources

Nerve growth factor: effects on D-amphetamine-induced activity and brain monoamines.

Adult male rats were given 6-hydroxydopamine lesions of the nucleus accumbens, followed immediately by injections of saline or nerve growth factor (NGF; 125 B.U.) near the substantia nigra. Such lesions were previously reported to attenuate the locomotor response to D-amphetamine. NGF-treated rats showed an enhanced response to D-amphetamine (1.5 mg/kg) when tested 15 days postoperatively. Levels of dopamine and norepinephrine in the striatum and nucleus accumbens were equivalently depressed in the two lesion groups, indicating that the apparent recovery of the NGF-treated rats was probably not due to catecholaminergic neuronal regrowth. Intracerebral NGF administeration enhanced the response to D-amphetamine 15 days later in rats without lesions, and also appeared to result in increased turnover of brain norepinephrine and serotonin at 3, but not 15, days postadministration. NGF might increase dopamine turnover at 15 days, but the evidence obtained did not convincingly confirm or negate this possibility. The results in brain-damaged and intact rats, and also modify the apparent turnover of brain monoamines.

Animals

Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey.

Depletion of dopamine in a circumscribed area of association cortex in rhesus monkeys produces an impairment in spatial delayed alternation performance nearly as severe as that caused by surgical ablation of the same area. This behavioral deficit can be pharmacologically reversed with dopamine agonists such as L-dopa and apomorphine. These data provide direct evidence that dopamine plays an important role in a specific cortical function.

Animals

Regional distribution of monoamines in the cerebral cortex and subcortical structures of the rhesus monkey: concentrations and in vivo synthesis rates.

Endogenous monoamine concentrations and turnover rates vary markedly in different regions of neocortex as well as in various subcortical structures of young adult rhesus monkeys. Monoamine levels and synthesis rates in amygdala, hippocampus, neostriatum, thalamus and brain stem are generally similar to comparable measures previously reported in a variety of species. However, extending and confirming the results of an earlier study, cortical monoamines exhibit topographically specific patterns of distribution. Thus, dopamine concentration is highest in the prefrontal and temporal neocortex; it decreases along the fronto-occipital axis and only trace amounts are detectable in the visual cortex. The distribution of norepinephrine is similar to that of dopamine except that the highest concentrations of norepinephrine are found in somatosensory cortex instead of prefrontal cortex. The pattern of distribution of serotonin is more uniform. However, the distribution of its metabolite, 5-hydroxyindoleacetic acid, is complementary to that of dopamine: the concentration is lowest in prefrontal cortex and highest in posterior regions of the telencephalon. Synthesis of catecholamines as measured by DOPA accumulation in monkeys treated with an aromatic amino acid decarboxylase inhibitor, NSD 1015, generally parallels the distribution of the catecholamines while indoleamine synthesis, as measured by 5-HTP accumulation, is similar to the distribution of 5-hydroxyindoleacetic acid. It may be significant that synthesis rates for the catecholamines are especially high in various areas of association cortex.

Amygdala

Zinc nutritional status of young middle-income children and effects of consuming zinc-fortified breakfast cereals.

The effects of consuming zinc-fortified ready-to-eat breakfast cereals were determined in a double-blind controlled study. The 96 healthy young children who participated (mean age 58 months) consumed either zinc-fortified cereal, providing 25% United States Recommended Dietary Allowance per 1 ounce serving (test children) or nonzinc-fortified cereals (controls) for a 9-month period. The test children were calculated on average to receive an additional 2.57 mg of zinc per day from this fortification program. This increment increased their mean daily zinc intake to a level that approached the Recommended Dietary Allowance (10 mg) of the National Academy of Sciences for children less than 10 years of age. By the end of the period, the test children (combined sexes) had a mean increment of plasma zinc that was 6.5 micrograms/dl greater than that of the control children (P less than 0.02). The test girls had a greater increment (28.5 micrograms/g) in hair zinc content than controls girls (P less than 0.05). There were no significant differences in other biochemical parameters including plasma copper and serum cholesterol. No significant differences in food intake or growth velocity were associated with the consumption of the zinc-fortified cereal. Multiple sex and time related differences occurred in plasma, hair, urine, and parotid saliva zinc concentrations that were unrelated to the type of cereal consumed.

Child

Maintenance dose of penicillamine in rheumatoid arthritis: a comparison between a standard and a response-related flexible regimen.

There is much individual variation in the response of rheumatoid arthritis (RA) to penicillamine, some patients deriving benefit from very small doses. A dose of 750 mg daily is widely regarded as standard, and, while their RA commonly responds, many patients discontinue treatment because of adverse reactions to penicillamine. A more flexible prescribing policy might be more successful in the long term and was tested in 1 group of 20 patients, another receiving a 'standard' regimen, each beginning treatment at a low dose level. Of those who were given increases of dose only if response was poor 17 completed 1 year of treatment on an average maintenance dose of 308 mg daily, but only 11 of the other group on an average dose 613 mg daily. Proteinuria, which was found only in the latter group accounted for 6 withdrawals, all at doses of 625 mg daily or above. The reduction in rheumatoid activity appeared to be of about the same degree among the members of both groups who completed 12 months of treatment. Penicillamine should be given initially in a low dose and this should be raised only if there is lack of response after at least 4 weeks.

Adult

Interactive effects of cognitive involvement and response topography upon differential eyelid conditioning to conceptual discriminanda.

The purpose of the experiment was to determine some cognitive differences underlying the superior differential conditioning of voluntary-form (V) over conditioned-form (C) responders. Two cognitive activities were hypothesized to be jointly necessary for the superiority of Vs: first, an active development of reinforcement contingency awareness by the subject himself, and, second, an active use of acquired contingency knowledge in predicting UCS occurrences. The first variable was manipulated by asking half of the subjects to "figure out" the contingencies, while the other half were fully informed of them at the start. The second variable was assessed by requiring half of the subjects to engage in a button-pressing US prediction task on each trial. Conditioned discrimination indicated that, as predicted, both of these cognitive activities were required for good performance by Cs, supporting the hypothesis that Cs are normally deficient in these respects. An unpredicted deterioration in discrimination for Vs when both task manipulations were imposed suggested that competition between the Vs' spontaneous cognitive activities and the experimentally imposed ones developed in the high external demand situation.

Awareness

Cell wall structure and deposition in Glaucocystis.

Events leading to cell wall formation in the ellipsoidal unicellular alga Glaucocystis are described. The wall is deposited in three phases: (a) a thin nonfibrillar layer, (b) cellulosic microfibrils arranged in helically crossed polylamellate fashion, and (c) matrix substances. At poles of cells, microfibrils do not terminate but pass around three equilaterally arranged points, resulting in microfibril continuity between the twelve helically wound wall layers. These findings were demonstrated in walls of both mother cells and freeze-fractured growing cells, and models of the wall structure are presented. Cellular extension results in spreading apart, and in rupture, of microfibrils. On freeze-fractured plasma membranes, there were 35 nm X 550 nm structures associated with the ends of microfibrils. These are interpreted as representing microfibril-synthesizing centers (terminal complexes) in transit upon the membrane. These terminal complexes are localized in a zone, or zones. The plasma membrane is subtended by flattened sacs, termed shields, which become cross-linked to the plasma membrane after completion of wall deposition. During wall deposition, microtubules lie beneath the shields, and polarized filaments lie between shields and plasma membrane. The significance of these findings in relation to understanding the process of cellulose deposition is discussed, and comparisons are made with the alga Oocystis.

Cell Division

Cell wall biogenesis in Oocystis: experimental alteration of microfibril assembly and orientation.

Cell wall biogenesis in the unicellular green alga Oocystis apiculata has been studied. Under normal growth conditions, a cell wall with ordered microfibrils is synthesized. In each layer there are rows of parallel microfibrils. Layers are nearly perpendicular to each other. Terminal linear synthesizing complexes are located in the plasma membrane, and they are capable of bidirectional synthesis of cellulose microfibrils. Granule bands associated with the inner leaflet of the plasma membrane appear to control the orientation of newly synthesized microfibrils. Subcortical microtubules also are present during wall synthesis. Patterns of cell wall synthesis were studied after treatment with EDTA and EGTA as well as divalent cations (MgSO4, CaSO4, Cacl2). 0.1 M EDTA treatment for 15 min results in the disassociation of the terminal complexes from the ends of microfibrils. EDTA-treated cells followed by 15 min treatment with MgSO4 results in reaggregation of the linear complexes into a paired state, remote from the original ends to which they were associated. After 90 min treatment with MgSO4, normal synthesis resumes. EGTA and calcium salts do not affect the linear complexes or microfibril orientation. Treatments with colchicine and vinblastine sulphate do not depolymerize the microtubles, but the wall microfibril orientation is altered. With colchicine or vinblastine, the change in orientation from layer to layer is inhibited. The process is reversible upon removal of the drugs. Lumicolchicine has no effect upon microfibril orientation, but granule bands are disorganized. Treatment with coumarin, a known inhibitor of cellulose synthesis, causes the loss of visualization of subunits of the terminal complexes. The possibility of the existence of a membrane-associated colchicine-sensitive orientation protein for cellulose microfibrils is discussed. Transmembrane modulation of microfibril synthesis and orientation is presented.

Calcium

A freeze-etching and replication study of wall deposition in elongating plant cells.

The architecture of the expanding wall of mung bean hypocotyl (Phaseolus aureus) and collenchyma of celery (Apium graveolens) was examined using freeze-etching without any cryoprotectant, and surface-replication of frozen-ground and air-dried specimens. The polylamellated organization of the wall was seen. Freeze-etching clearly visualized, within one single fracture plans, the intermediate strata in which the microfibril orientation gradually changes between the main transverse and longitudinal directions. They corresponded to the bow-shaped arcs seen with surface replication and conventional microtomy. The organization of newly-formed microfibrils (periplasmic microfibrils) was seen by their imprints on the plasmalemma. When they were being deposited the microfibrils were loose and sinuous though tightly packed, rigid and parallel on the further layers. Therefore it seems that the fibrillogenesis and the spatial orientation of the microfibrils are two subsequent steps. The role of the periplasm in controlling the three-dimensional arrangement of the wall is emphasized.

Cell Membrane

Antigenic properties of the Golgi derived scales of Pleurochrysis scherffelii.

The cell wall of the marine alga Pleurochrysis scherffelii is composed of Golgi-derived scales with four distinct subcomponents: amorphous coating material, radial microfibrils, spiral coating substances and spiral microfibrils. The antigenic properties of the Pleurochrysis scales were studied. Antibodies were produced in rabbits to the amorphour to the amorphous coating material and to a heretofore undescribed peripheral subcompoent, known as the amorphoous rim modification substance. The antigenic subcomponents were detected by agglutination/precipitation, negative staining, and shadowing procedures. Scales of the Cricosphaera phase produced negative results when tested with Pleurochrysis scale antisera. A possible function of the amorphous rim modification substance in maintaining the integrity of spiral microfibrillar organization is introduced.

Animals

Visual and phonetic memory in preschool children: evidence for coding flexibility.

This study examined visual and verbal (phonetic) memory coding in 22 preschool children 4 to 5 yr. of age. A major goal was to determine whether these children would code visual items phonetically during input in a short-term memory task as older children and adults often appear to do. Items to be remembered were visually presented letters that varied in visual as well as phonetic similarity. Subjects labeled each letter during presentation, and serial recall was probed either visually or verbally. Recall scores were analyzed according to planned individual comparisons and a 4-factor analysis of variance: probe modality (visual, verbal) X visual similarity (low, high) X phonetic similarity (low, high) x serial position (1, 2, 3, 4). Data indicated (1) a significant detrimental effect of high phonetic similarity for subjects whose recall was probed verbally, (2) a significant facilitating effect of high visual similarity, and (3) significant interactions indicating differential effects of phonetic similarity and probe modality on the serial position curve. These findings suggest flexibility of coding in children of the age range tested.

Adult

Electron microscopy of the cotton fibre: new observations on cell wall formation.

The ultrastructure of the cotton fibres was examined after developing successful fixation methods. Fibre cells were fixed at different stages of development. In cells which were elongating and producing primary cell walls, the Golgi apparatus appeared to be directly involved in secretion and synthesis of primary wall components. In cells which were synthesizing thick secondary cell walls, evidence suggested a major role for the endoplasmic reticulum and plasma memebrane in the synthesis and secretion of secondary wall materials. The possibility of a shift from a Golgi apparatus pathway for primary wall synthesis to an endoplasmic reticulum pathway for secondary wall synthesis is discussed. Plasma membrane micro-invaginations are present only during secondary wall synthesis and may represent sites of cellulose assembly. A model for primary wall biogenesis via the Golgi apparatus is presented, and the potential of the cotton fibre as a model system for studying cellulose biogenesis in higher plants is discussed.

Cell Membrane

Functional and biochemical aspects of catecholamine metabolism in brain under hypoxia.

Animals exposed to 6% oxygen showed a partial inhibition of the rate of tyrosine hydroxylation and a blockade of the conditioned avoidance response. The behavioral disruption was suggested to result, at least in part, from a dopaminergic disturbance, since the behavior was restored by the administration of DOPA or apomorphine but not by 5-hydroxytryptophan. Biochemical data showed a selective retardation in brain dopamine (DA) disappearance after synthesis inhibition. Methoxytyramine formation was markedly retarded. Analysis of this effect indicated that the decreased DA turnover was related to the release of transmitter rather than to an effect on catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO). In addition, there was evidence for a partial inhibition of MAO activity by hypoxia as well as a decreased activity of dopamine-betahydroxylase. It was concluded that the disruption of behavior was related to decreased dopaminergic receptor activation and that decreased synthesis played at most a contributory role.

5-Hydroxytryptophan