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Biomedical subjects

P A Brown

Publications and source records attributed to P A Brown.

14 recordsLinked to original sources

Synaptosomal uptake of hypothalamic monoamines and recovery of pituitary-adrenal activity following medial forebrain bundle lesions in rats.

The normal diurnal variation in plasma corticosterone (COR) was abolished and the response to ether stress was enhanced at 3 days following the production of medial forebrain bundle (MFB) lesions in male rats. However, by 7 days following surgery, basal plasma COR levels and the response to ether stress appeared normal. These alterations and subsequent recovery of pituitary-adrenal activity were accompanied by decreasing hypothalamic synaptosomal uptake of serotonin (5HT) and increasing synaptosomal uptake of dopamine (DA), evident at 3 and continuing at 7 days following the lesion. Uptake of norepinephrine (NE) was not affected at 3 days but showed a reduction at 7 days following surgery. The results suggest that disruption of ascending 5HT and NE fibers to the hypothalamus can alter pituitary-adrenal activity but that normal activity recovers by 7 days following the lesion. The correlation between recovery of pituitary-adrenal activity and increases in the normal uptake of hypothalamic DA suggest that DA may interact with 5HT and NE systems in the normal control of adrenocorticotrophin (ACTH) release.

Animals

A specific pattern of connections from the sensorimotor region of the cerebral cortex to the thalamus in the rat.

In the course of an investigation of the thalamic connections of the frontoparietal cortex in the albino rat, lesions were placed in the parietal cortex of adult rats, and the resulting terminal degeneration was observed in the ventrobasal complex, using the Fink-Heimer silver impregnation technique. Lesions made in the primary somatosensory forelimb region of the cortex result in a narrow band of terminal degeneration which extends dorsoventrally throughout the rostrocaudal two-thirds of the ventrobasal complex. This portion of the ventrobasal complex coincides with the electrophysiological representation of the thalamic primary somatosensory forelimb area, and corresponds closely to the medial portion of the lateral part of the ventrobasal complex as described by Smith, as well as to the medial portion of the posterolateral ventral nucleus according to Matano et al. These results serve to confirm the close correlation determined electrophysiologically between the topographical organization of the somatosensory forelimb areas of both the parietal cortex and the ventrobasal complex of the rat thalamus.

Animals

Effects of intraperitoneal nitroprusside on peritoneal clearances in man with variations of dose, frequency of administration and dwell times.

Clinical studies with intraperitoneal nitroprusside were designed to examine drug effects on peritoneal clearances as a function of dose, frequency of administration and dwell times. Increases in clearances and protein losses were seen with 1 mg of nitroprusside per liter of dialysis solution, with progressively greater effects up to maximum doses of 4.5 mg/1. Maximum effects were seen at the high dose after 3 or more consecutive exchanges. Clearance effects promptly returned toward control during postdrug exchanges and, in some studies, even during alternate exchanges. Proportional effects on solute clearances appeared independent of dwell time, supporting previous studies suggesting area permeability alterations. Series of 12 or more consecutive exchanges showed little change in blood pressure. Increases in serum thiocyanate were not detected after multiple exchanges. Dialysate cell counts showed no evidence of chemical irritation.

Biological Transport

Aspirin- and indomethacin-induced ulcers and their antagonism by antihistamines.

Gastric ulceration produced by aspirin and indomethacin was compared in acutely stressed and non-stressed rats. We found a synergism between these anti-inflammatory agents and acute stress in the production of gastric ulcers. Even at relatively high doses, neither agent caused appreciable gastric damage in non-stressed rats, whereas moderate doses of both agents produced massive ulceration in stressed rats. The synergism appears unrelated to the effect of these agents on the pituitary-adrenal response. The size and regional distribution of ulcers produced by aspirin and indomethacin in stressed rats were comparable. However, the dose--response curves of the two drugs were markedly dissimilar. Furthermore, the ulceration produced by indomethacin was attenuated by both H1 and H2 histamine receptor antagonists, whereas ulceration produced by aspirin was attenuated only by an H2 antagonist. The results suggest that the ulcerogenic mechanism of indomethacin may differ from that of aspirin and add to the growing evidence on the importance of endogenous histamine in various forms of gastric ulceration.

Animals

Cerebellar decussation of fibres from the nucleus reticularis tegmenti pontis in the brain of the albino rat.

The existence of a cerebellar decussation of fibres from the medial portion of each nucleus reticularis tegmenti pontis (Rtp) of the albino rat is indicated. Definite cell loss in the medial aspect of the most rostral third of Rtp is detectable after cerebellar hemisection involving parts or the entire depth of sublobule VIb. Cell loss in the medial aspect of the caudal half of Rtp is evident as a consequence of experimental lesions which damage both sublobules IIb and III.

Animals

Isolation of bacteriophage-like particles from uninduced Clostridium tetani cultures.

The isolation of hexagonal-headed, tailless, bacteriophage-like particles from uninduced cultures of Clostridium tetani is described. Clear, round, 1--3 mm diameter plaques were noted on Clostrisel agar plates, which were overlaid with soft agar inoculated with 7--14 day broth cultures. Particles were detected by transmission electron microscopy from broth cultures seeded with scrapings from the plaques. Both electron dense and electron lucent heads were noted. An electron dense head was observed attached to the surface of a dividing bacterium.

Bacteriophages

Guinea-pig milk-protein synthesis. Isolation and characterization of messenger ribonucleic acids from lactating mammary gland and identification of caseins and pre-alpha-lactalbumin as translation products in heterologous cell-free systems.

1. The major milk proteins synthesized by the lactating mammary gland of the guinea pig were identified and designated as caseins A, B and C and alpha-lactalbumin, with estimated mol.wts. of 28000, 25500, 20500 and 14500 respectively. 2. Antisera to the total casein fraction and to alpha-lactalbumin were prepared from rabbits. The milk proteins were also iodinated with either 131I or 125I. 3. A poly(A)-rich RNA fraction was isolated from lactating guinea-pig mammary glands. Isolation was by affinity chromatography on oligo(dT)-cellulose. 4. Examination of this RNA fraction by electrophoresis on polyacrylamide gels containing formamide indicated three major species 1, 2 and 3, with estimated wol.wts. of 5.4 X 10(5) and 3.3 X 10(5), and the apparent absence of rRNA species. 5. The poly(A)-rich RNA stimulated protein synthesis in heterologous cell-free systems based on wheat germ, Krebs II ascites-tumour cells, and the latter supplemented with an initiation factor-3 fraction from rabbit reticulocyte ribosomes. 6. Between 80 and 90% of the protein synthesis directed by the mRNA was for milk proteins. 7. Analysis of the proteins immunoprecipitated by the alpha-lactalbumin antiserum showed in the wheat-germ system that the product was a protein with a molecular weight greater than that of alpha-lactalbumin, whereas in the ascites-tumour-cell systems both this protein and alpha-lactalbumin were found. When the larger protein was treated with CNBr and the resulting peptides were examined, it was shown that the extra peptide was at the N-terminus. This and other evidence is adduced for the initial translation product of alpha-lactalbumin being a precursor with an addition of about ten amino acids at the N-terminus. 8. Similar analysis of the casein immlnospecific proteins produced under the direction of mRNA indicated that the products had a molecular weight that was apparently a littel smaller than that of the caseins synthesized in vivo. This was not consistent with higher-molecular weight casein precursors. 9. Possible explanations for the results obtained are discussed, especially in terms of the physiological significance of the pre-alpha-lactalbumin as a secretory protein.

Animals