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Biomedical subjects

C M Brown

Publications and source records attributed to C M Brown.

At least 181 records · Page 10Linked to original sources

Lipoprotein lipase activity and chylomicron clearance in rats fed a high fat diet.

The relationships of tissue and plasma lipoprotein lipase (LPL) activities to tissue uptake and plasma clearance of 14C-labeled chylomicron-triglyceride (14C-CM-TG) were studied in female rats fed isoenergetic and isonitrogenous control (12% kJ from fat) or high fat diets (72% kJ from fat) for 8 wk. Animals fed the high-fat diet had higher levels of fasting plasma triglycerides and lower LPL activities in heart, renal adipose tissue and post-heparin plasma. Changes in LPL activities of skeletal muscles varied among muscles with higher values in the soleus and plantaris (32-61%) and no differences in the gastrocnemius. The lower LPL activity in renal adipose tissue was associated with lower uptake of fatty acids from 14C-CM-TG by adipose. Fatty-acid uptake from labeled TG was not associated with tissue LPL activity in other tissues. Clearance of 14C-CM-TG from plasma and the half-lives of 14C-CM-TG were similar in both dietary groups. These data indicate that tissue and plasma LPL activities are not a direct index of uptake of fatty acids by tissues or clearance of chylomicron triglycerides.

Animals↗

Activities of octopamine and synephrine stereoisomers on alpha-adrenoceptors.

1. The activities of the (-)- and (+)-forms of m- and p-octopamine and m- and p-synephrine on alpha 1-adrenoceptors from rat aorta and anococcygeus and alpha 2-adrenoceptors from rabbit saphenous vein were compared with those of noradrenaline (NA). 2. The rank order of potency of the (-)-forms on alpha 1-adrenoceptors from rat aorta and alpha 2-adrenoceptors was NA greater than m-octopamine = m-synephrine greater than p-octopamine = p-synephrine. The two m-compounds were 6 fold less active than NA on alpha 1-adrenoceptors from rat aorta and 150 fold less active on alpha 2-adrenoceptors. The two p- compounds were 1,000 fold less active than NA on both alpha 1-adrenoceptors from rat aorta and alpha 2-adrenoceptors. The rank order of potency of the (-)- forms on alpha 1-adrenoceptors from rat anococcygeus was NA = m-synephrine greater than m-octopamine greater than p-octopamine = p-synephrine. m-Octopamine was 4 fold less active than NA and (-)-m-synephrine. The two p- compounds were 30 fold less active than NA. 3. The rank order of potency of the (+)- forms was NA greater than m-octopamine greater than m-synephrine greater than p-octopamine greater than p-synephrine on both alpha 1- and alpha 2-adrenoceptors. The potency of each (+)- form was 1-2 orders of magnitude less than that of the (-) counterpart, the differences being greater for the stereoisomers of synephrine than for those of octopamine on both alpha 1- and alpha 2-adrenoceptors. 4. The yohimbine diastereoisomer antagonists, rauwolscine and corynanthine, were tested against (-)-NA and (-)-m-octopamine-induced contractions in both preparations. Based upon the known selectivities of these isomers for alpha-adrenoceptor subtypes, it is concluded that the rat aorta contains only alpha 1-adrenoceptors while the rabbit saphenous vein possesses predominantly alpha 2-adrenoceptors. 5. Ligand binding data for the octopamine and synephrine stereoisomers at alpha 1- and alpha 2-binding sites from rat cerebral cortex was also obtained. (-)-Forms were more active than (+)-forms. The rank order of affinity of the (-)-forms for both alpha 1- and alpha 2-binding sites was NA greater than m-octopamine = m-synephrine greater than p-synephrine greater than p-octopamine. The relative affinities of the members of the series against alpha 1-binding sites were very similar to their relative functional activities on rat aorta. However, the affinities of both m- and p-compounds relative to that of ( -)-NA were much greater at the x2-binding sites than were the relative activities in rabbit saphenous vein, possibly suggesting low intrinsic efficacy. Functional antagonist responses to NA by the (-)-octopamine and synephrines could not, however, be demonstrated on rat aorta or rabbit saphenous vein. 6. The activities of m-octopamine and m-synephrine were not significantly different from each other on either a,-adrenoceptors from rat aorta or x2-adrenoceptors; however, m-synephrine is more active than m-octopamine on a,-adrenoceptors from rat anococcygeus. Both m-octopamine and msynephrine can be considered to be naturally occurring x,-selective amines. However, if m- and poctopamine are co-released with NA in amounts proportional to their concentration, it is concluded that their activities on m,- and x2-adrenoceptors are too low to be physiologically significant.

2-Hydroxyphenethylamine↗

Sudden and unexpected death in horses and ponies: an analysis of 200 cases.

An analysis was made of the causes of death in horses and ponies over one year of age which died suddenly (Group 1) or were found dead but were considered normal when last seen (Group 2). There were 49 animals in Group 1. Thoroughbreds were overrepresented, but there were no ponies in this group. No cause of death was found in 30.6 per cent of cases and 16.3 per cent died from each of the following causes: haemorrhage in the respiratory system, central nervous system, and adverse drug reactions. Cardiovascular lesions were the cause of death in 14.4 per cent and the remaining 3.1 per cent had lesions of the gastrointestinal system. Racehorses mostly died suddenly from severe haemorrhage in various sites, particularly the thorax. In Group 2 there were 151 animals, and in 33.1 per cent no cause of death was determined. Gastrointestinal lesions were considered the cause of death in 39.2 per cent of cases and respiratory lesions killed 8.6 per cent. Lesions of both the central nervous system and cardiovascular system were considered the cause in 4.6 per cent of cases. The remaining 9.9 per cent of animals had miscellaneous lesions. Toxicological studies were performed in 46 of the total 200 cases, and only two had positive results; lead in one and nicotine in the other.

Age Factors↗

Iron toxicity in neonatal foals.

Newborn Shetland foals died of acute hepatic failure following oral administration of approximately 16 mg/kg body weight ferrous fumarate. Lesions in these foals were indistinguishable from lesions in foals given an oral digestive inoculant containing ferrous fumarate and were also similar to the syndrome characterised as 'toxic hepatopathy' in foals in the United States in 1983. We conclude that foals are susceptible to toxicity from low doses of iron compounds in the first few days of life. Vitamin E and selenium deficiency may contribute to this susceptibility.

Administration, Oral↗

Identification and procaryotic expression of the gene coding for the highly immunogenic 28-kilodalton structural phosphoprotein (pp28) of human cytomegalovirus.

Human cytomegalovirus contains a structural polypeptide that is 28 kilodaltons in apparent molecular size and is reactive in Western blot (immunoblot) analysis with the majority of human sera. The gene coding for this polypeptide was mapped on the genome of human cytomegalovirus strain AD169. A monoclonal antibody specific for the 28-kilodalton polypeptide was used to screen a cDNA library constructed from poly(A)+ RNA of human cytomegalovirus-infected cells in the procaryotic expression vector lambda gt11. Hybridization of cDNA with cosmid and plasmid clones mapped the gene to the HindIII R fragment. The gene was transcribed into a late 1.3-kilobase RNA. The nucleotide sequence of the coding region was determined. Parts of the 28-kilodalton polypeptide were expressed in Escherichia coli as hybrid proteins fused to beta-galactosidase. In Western blots these proteins were recognized by human sera. Antibodies raised against the hybrid proteins reacted specifically with the viral antigen in immunoprecipitations and Western blots. In vitro phosphorylation of HCMV virions and immunoprecipitation showed that the 28-kilodalton polypeptide was phosphorylated.

Amino Acid Sequence↗

Purification of human autoantibodies from cross-linked antigen immunosorbents.

A method is described whereby autoantibodies to the Sjögren's syndrome antigen La (SS-B) can be purified from re-usable immunosorbent columns constructed from covalently linked human autoantibodies to which the antigen is cross-linked. Previous attempts to link the antigen directly to CNBr-Sepharose beads resulted in loss of biological activity and thus each purification of antibody required fresh batches of antigen. The present technique is a significant improvement since the cross-linked immunosorbents prepared from a single batch of antigen can be re-used several times over a 6 month period. Furthermore F(ab')2 fragments of anti-La antibodies can be purified from pepsin-digested serum samples. These antibodies react in ELISA, Western blot and immunofluorescence in an identical way to serum and murine monoclonal anti-La antibodies and show no reaction with the Ro antigen. However, being of human origin the affinity-purified anti-La antibodies have the advantages of bearing the same idiotypes and reacting with the same antigenic epitopes as naturally occurring serum autoantibodies.

Autoantibodies↗

Paternity testing 3: exclusion probabilities.

Blood typing with several blood systems is used in many countries to determine paternity or nonpaternity with respect to an alleged father. Various probabilities are usually presented, in particular: the conditional probability of excluding a random man as father given a particular mother-child phenotype combination, and the expected (unconditional) exclusion probability for all mother-child combinations can be calculated for a given blood system. Because these probabilities are of general interest in paternity studies, explicit formulae for the unconditional probabilities have been derived for some of the systems. Algorithms suitable for a microcomputer are given here for finding the exclusion probabilities for any system. These algorithms avoid the need for developing new formulae whenever a new system is introduced or a current system is extended through the addition of further alleles.

Algorithms↗

Antihypertensive 1-acyl-4-[2-(1,4-benzodioxan-2-yl)-2-hydroxyethylamino]pip eridines.

Several 1-acyl-4-[2-(1,4-benzodioxan-2-yl)-2-hydroxy-ethylamino]piperidine s were prepared and a number of the compounds showed antihypertensive activity in the spontaneously hypertensive rat (SHR). This activity was specific for the (2S, 2R) enantiomers. General pharmacological evaluation and ligand binding data on selected compounds indicated a moderate degree of alpha 1- and beta-antagonistic activity. The alpha 1 antagonism was probably not of sufficient magnitude to explain the blood pressure lowering activity in the SHR.

Animals↗

Serum immunoreactive gastrin activity in horses: basal and postprandial values.

Using commercially available diagnostic reagents, serum immunoreactive gastrin activity was measured in five normal horses that were starved of food and water for 24 hours. Blood samples were taken every 15 minutes for two hours. The horses were then fed a pelleted diet for 15 minutes and samples were taken every 15 minutes for a further two hours. Three further samples were taken at hourly intervals. The total sampling period was seven hours. Basal immunoreactive gastrin activity was lower than that reported in other mammals, ranging from a mean of 7.0 pg/ml to 13.8 pg/ml. At 30, 60 and 75 minutes after feeding, mean gastrin immunoreactivity was significantly elevated at 17.4, 19.8 and 18.2 pg/ml respectively. A late significant elevation occurred also five hours after feeding reading 19.4 pg/ml. This low activity may reflect a lower concentration of serum gastrin in the horse than in other mammals, or the methods used in the study may have failed to detect equine serum gastrins.

Animals↗

A longitudinal study of nose growth from ages 6 to 18.

The purpose of this study was to investigate nose maturation by cephalometric sagittal surface area methodology longitudinally in males and females. Both males and females exhibited a statistically significant continuum of nose growth from ages 6 to 18. Growth ceased in both sexes at age 18. Correlation coefficients indicated that males' noses tended to be either large or small in all dimensions from ages 6 to 18. The same was not true for females. A major finding of possible clinical importance was that maturity is reached at age 12 in girls with 84% of adult area, and in boys at age 15 with 87% of adult size.

Adolescent↗

The induction of equine laminitis with an aqueous extract of the heartwood of black walnut (Juglans nigra).

An aqueous extract of the heartwood of black walnut (Juglans nigra) was given via stomach tube to 10 horses. Eight developed Obel grade 3 or 4 laminitis within 12 hr. Limb edema and mild sedation were the only other clinical signs observed. One horse was euthanized due to severe signs. The other 7 recovered within 6 days. Gas chromatography/mass spectrometry of aqueous extracts of heartwood, bark and nuts of black walnut identified juglone in the bark and nuts, but not in the heartwood. It was concluded that the aqueous extract of heartwood is laminogenic to horses, but the active ingredient is not juglone.

Animals↗

Antihypertensive aminotetralins related to labetalol and medroxalol.

A series of compounds was prepared in which the 1-methyl-3-phenylpropylamino moieties of the antihypertensive agents labetalol and medroxalol were replaced by 2-aminotetralins. Compounds containing a 6-methoxy and 6,7-methylenedioxy group in the aminotetralin were at least as active as labetalol in lowering the blood pressure of the spontaneously hypertensive rat (SHR). As determined by ligand binding, these compounds were comparable to labetalol as alpha 1-antagonists but were substantially weaker beta 1-antagonists.

Animals↗

Characterisation of sodium-dependent uptake of 5-hydroxytryptamine into guinea-pig brain.

The uptake of 5-hydroxytryptamine (5-HT) was studied using isolated nerve endings (synaptosomes) prepared from the corpus striatum of the guinea pig. Analysis of temperature-dependent uptake revealed that two processes were involved, a sodium-dependent and sodium-independent mechanism. Kinetic studies indicated that the affinity of 5-HT (Ku) and the transport capacity (Vu) of the uptake process were dependent upon the external concentration of sodium. The transport capacity increased linearly with increasing concentrations of sodium up to 140 mmol/l, whereas the affinity for 5-HT was enhanced at concentrations of sodium up to 100 mmol/l, but reduced at 130 mmol/l sodium. The findings of this study suggest that uptake of 5-HT occurs as a result of a mobile carrier transport system which, depending upon the external concentration of sodium proceeds by a single or double displacement mechanism.

Animals↗

Muramyl dipeptide protects decomplemented mice from surgically-induced infection.

Muramyl dipeptide (MDP) is a natural product of bacterial cell-wall breakdown, which can now be produced synthetically; it is the smallest component of the mycobacterial cell wall capable of reproducing the adjuvant activities of Freund's complete adjuvant. We tested the well-documented, protective effect of MDP to increase survival in a murine model simulating surgically-induced bacteremia. The protocol involved the bacterial innoculation of control and decomplemented mice in the presence and the absence of pretreatment with MDP. Bacteremia in both the control and decomplemented groups pretreated with MDP was decreased statistically at 24 h (P less than 0.01) as compared to controls. Likewise, survival was increased significantly at 24 h (P less than 0.05), 48 h (P less than 0.001), and 72 h (P less than 0.001) using the same group comparisons. We conclude, therefore, that MDP maintains its protective effect in the absence of complement, supporting the view that the mechanism of action of MDP is complement independent.

Acetylmuramyl-Alanyl-Isoglutamine↗

Increase of serum gamma-glutamyltransferase in neonatal Standardbred foals.

Serial blood samples were obtained from 16 Standardbred foals from time of birth to postpartum day 28. Sera were obtained and analyzed for gamma-glutamyltransferase (GGT), aspartate transaminase, and immunoglobulin (Ig) G. Presuckle colostrum from the respective mares of these foals was analyzed for GGT activity. Mean serum aspartate transaminase activities were significantly increased above presuckle values by postpartum hour 48 (P less than 0.01) and increased gradually over the first 14 days. Mean serum IgG concentrations were significantly greater than presuckle values by 5 hours after foals first suckled (P less than 0.01) and remained significantly increased during the 28-day sampling period. Serum GGT activity did not differ significantly over the period sampled. The SD were large, since there was a large degree of interindividual variation. Serum GGT activity in the foals was significantly increased over that in the mares throughout the period of the study. The profile of serum GGT activity over time in each foal did not show a pattern of change. There was no postsuckle increase in serum GGT activity nor a correlation between serum GGT activities and IgG concentrations at 24 hours after foals first suckled. Evidence was not obtained to support a colostric source of GGT involved in the increase of serum GGT activity in foals. Serum GGT activity seems to be increased in foals due to endogenous sources.

Analysis of Variance↗

Retropharyngeal infections in five horses.

Five horses with retropharyngeal (RP) infections had clinical signs of dysphagia and/or dyspnea. Diagnosis was confirmed, using pharyngeal endoscopy and lateral radiography of the pharynx. One horse responded to surgical drainage of a RP abscess and was sound at light work. One horse responded to medical management after the site of infection was surgically explored. Two horses recovered after medical management; the RP abscess of 1 of these 2 horses ruptured spontaneously into the pharynx and the other horse became racing sound. The fifth horse remained dysphagic and had left laryngeal hemiplegia after medical treatment.

Abscess↗

Deficiency of the contact phase of intrinsic coagulation in a horse.

A 16-year-old gelding was examined because of weight loss, inappetence, and intermittent fever of 2 months' duration. Preliminary laboratory findings revealed anemia, hypoproteinemia, thrombocytopenia, and prolongation of the activated partial thromboplastin time. A deficiency or inhibition of coagulation factor XI, factor XII, or high molecular weight kininogen was diagnosed. This defect was not associated with a bleeding diathesis, but should be considered as a cause of prolongation of the activated partial thromboplastin time.

Animals↗