Biomedical subjects

C R Brown

Publications and source records attributed to C R Brown.

At least 127 records · Page 7Linked to original sources

PubMed1990

Effects of food restriction on stretch induced muscle hypertrophy in chickens of various ages.

1. The patagialis muscle of three groups of different aged chickens was subjected to passive stretch by placing an inflexible sleeve over the left wing, and the right wing served as the control. 2. Food was removed from the animals 2 days prior to applying passive stretch. After 6 days of passive stretch on young 7-week-old animals, the stretched muscle was 200% larger than the control. 3. During the restriction, control muscle lost 69% of its weight and the stretched muscle maintained its original weight. 4. Changes in muscle DNA and hydroxyproline content were similar to changes in muscle weight but hydroxyproline content lagged changes in muscle weight. 5. Restricted 10-month-old chickens responded to passive stretch with an absolute increase in muscle mass which was accompanied by increases in protein, DNA and hydroxyproline content. 6. Muscle from the 28-month-old chickens did not respond to either 11 days of restriction or passive stretch. 7. The results of the present study indicate that as the chicken grows older, the ability of the muscle to respond to stimuli, stretch and/or starvation, is reduced.

Aging↗

PubMed1990

Dose-dependency of caffeine metabolism with repeated dosing.

Some recent epidemiologic studies have reported a nonlinear dose-response in the relationship between coffee consumption and health risks, such that the risks increase disproportionately to the increase in dose. Assuming caffeine contributes to the adverse health effects of coffee, a possible explanation for the nonlinear dose-response relationship is dose-dependent metabolism of caffeine. We examined the hypothesis that under chronic dosing conditions the metabolism of caffeine is dose-dependent. Nine healthy subjects were given, in randomized 5-day treatment blocks, placebo, 4.2 (low) and 12 (high) mg/kg/day caffeine in decaffeinated coffee, in six divided doses spaced throughout the day. On the third day of each dosing period, 25 mg of stable-isotope labeled caffeine (2-13C, 1,3-15N2) was given intravenously. Clearance of labeled caffeine fell from 0.118 (placebo treatment) to 0.069 (low dose; p less than 0.005) and to 0.54 (high dose; p less than 0.001) L/hr/kg. The formation and metabolite clearances of paraxanthine, the major primary metabolite of caffeine, also decreased comparing the low and high doses (p less than 0.05). We conclude that caffeine metabolism is dose-dependent, resulting in nonlinear accumulation of methylxanthines in the body. Dose-dependent metabolism of caffeine may explain in part why people who drink large amounts of coffee are at greater risk for cardiovascular disease.

Adult↗

PubMed1990

Changes in the composition of the hamster zona pellucida after fertilization in vivo but not in vitro.

Hamster zonae pellucidae were obtained from follicular oocytes, superovulated eggs, and eggs fertilized in vivo or in vitro. Zonae were labelled with N-succinimidyl-3(4-hydroxy,5-[125I]iodophenyl)propionate, and compared on single- and two-dimensional SDS-PAGE. Single-dimensional electrophoresis showed considerable differences between zona categories in the amount of label that they incorporated; follicular zonae incorporated the least label and zonae from eggs fertilized in vivo the most. On two-dimensional electrophoresis, polypeptides from 3 of the 4 zona categories migrated into 4 major groups: two of these groups each with Mr 150,000-250,000 were within the Mr range of ZP1, and two others, at Mr 90,000 and 55,000, appeared to be analogous to ZP2 and ZP3, respectively. The fourth zona category (zonae from eggs fertilized in vivo) showed a changed polypeptide profile as well as incorporating the most label; one of the polypeptides, Mr 150,000-250,000, was undetectable, but a train of Mr 70,000-90,000 polypeptides and a discrete polypeptide at Mr 20,000 were new. Since this changed profile did not occur in zonae from superovulated eggs, or in zonae from eggs fertilized in vitro, a synergism between oviductal factors and factors from the spermatozoon or egg, or both, towards the zona in vivo is indicated.

Animals↗

PubMed1990

Comparison of intravenous ketorolac tromethamine and morphine sulfate in the treatment of postoperative pain.

This study compared the efficacy and safety of ketorolac tromethamine and morphine sulfate in alleviating moderate or severe pain immediately after major surgery. One hundred twenty-two patients were randomly assigned to receive single intravenous injections of ketorolac 10 mg, ketorolac 30 mg, morphine 2 mg, or morphine 4 mg; patients could receive a second dose 15 minutes thereafter, upon request, and most received both available doses. Analgesic efficacy was measured by interviewing patients and assessing pain intensity and pain relief for 6 hours after the first medication administration. The two drugs showed a similar onset of action, peaking 1 hour after administration. When placed in order of descending efficacy, the mean scores for most efficacy measures fell into the following sequence: ketorolac 30 mg, ketorolac 10 mg, morphine 4 mg, and morphine 2 mg. There were no statistically significant differences among the two ketorolac doses and the high dose of morphine, but all three of these treatments were significantly superior to the low morphine dose. One patient who took morphine 4 mg withdrew because of drowsiness; other common adverse events reported included nausea, vomiting, somnolence, and dyspepsia. There were no statistically significant differences in the frequency of adverse events among the treatment groups. Intravenous ketorolac is effective for the treatment of postoperative pain.

Adolescent↗

PubMed1990

Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major surgery.

A multicenter, randomized, double-blind, parallel study in 542 patients with moderate or severe postoperative pain compared the analgesic efficacy and safety of intramuscular ketorolac 30 mg (324 patients), morphine 6 mg (110 patients), and morphine 12 mg (108 patients) administered as needed as often as every 2 hours for a maximum of 20 doses or 5 days. The efficacy of ketorolac 30 mg was comparable to that of morphine 12 mg on every efficacy measure (average pain intensity, average pain relief, mean overall medication rating, and percentage of patients withdrawing because of inadequate relief). Ketorolac was statistically superior to morphine 6 mg for average pain intensity and mean overall rating. Ketorolac-treated patients had fewer adverse events than those who received either morphine dose.

Adolescent↗

PubMed1990

Intramuscular ketorolac and morphine in the treatment of moderate to severe pain after major surgery.

A multicenter, randomized, open, parallel study in 227 patients with moderate or severe postoperative pain compared the analgesic efficacy and safety of multiple intramuscular injections of ketorolac 30 mg (184 patients) and morphine 10 mg (43 patients) administered as needed as often as every 2 hours for a maximum of 40 doses or 10 days. Supplemental standard analgesics, usually opiates, were permitted if additional pain medication was required. When used with supplemental analgesics (averaging less than 1 dose/day), ketorolac afforded equal or superior efficacy to morphine used with other supplemental analgesics. Given alone or with supplemental analgesics, ketorolac was better tolerated than morphine, as reflected by rate of terminations due to adverse events and frequency of common complaints. Intramuscular ketorolac thus provides an important additional approach to management of pain.

Adolescent↗

PubMed1990

Analgesic efficacy and safety of single-dose oral and intramuscular ketorolac tromethamine for postoperative pain.

The efficacy and safety of the analgesic drug ketorolac tromethamine in the treatment of moderate to very severe postoperative pain was assessed in five dose-ranging studies with single-dose, double-blind, randomized, parallel-group designs. The drug was administered orally (2.5-200 mg, 352 patients in three trials) and intramuscularly (5-90 mg, 395 patients in two trials), and compared with placebo and reference drugs. Patients subjectively evaluated pain intensity and relief using verbal categoric and visual analog scales; efficacy values included pain intensity difference (PID), summed PID, and total pain relief. Oral ketorolac 10, 12.5, 100, and 200 mg were each statistically significantly superior to placebo in all efficacy measurements, and 10 mg was equivalent to intramuscular morphine 10 mg. Intramuscular ketorolac 90 mg was superior to and 10 and 30 mg were similar to intramuscular morphine 12 mg, and all of these ketorolac doses were superior to intramuscular morphine 6 mg. Intramuscular ketorolac 10 and 30 mg were superior to intramuscular meperidine 50 and 100 mg. Ketorolac was well tolerated, with rates of adverse events generally lower than those of the opiate comparators. Ketorolac doses of 2.5 and 5 mg were less effective than higher doses; 10 mg or more resulted in faster onset of action and greater peak efficacy; 90 mg or more gave more prolonged analgesic effects.

Administration, Oral↗

PubMed1989

Genetic regulation of early survival and cyst number after peroral Toxoplasma gondii infection of A x B/B x A recombinant inbred and B10 congenic mice.

Genetics of two traits, survival and brain cyst number after peroral Toxoplasma gondii infection, were studied by using recombinant inbred strains of mice derived from resistant A/J (A) and susceptible C57BL/6J (B) progenitors, F1 progeny of crosses between A/J and C57BL/6J mice, and congenic mice (B10 background). Analysis of strain distribution pattern of survival of A x B/B x A recombinant mice indicated that survival is regulated by a minimum of five genes. One of these genes appears to be linked to the H-2 complex and another is related to an as yet unmapped gene controlling resistance to Ectromelia virus. Associations of defined traits with resistance or susceptibility to Toxoplasma cyst formation were also analyzed. Cyst number is regulated by a locus on chromosome 17 within 0 to 4 centimorgans of the H-2 complex (p = 0.001). Mice with the H-2a haplotype are resistant and those with the H-2b haplotype are susceptible. This analysis also indicated that the Bcg locus on chromosome 1 may effect cyst number (map distance = 12 centimorgans, p = 0.05). Resistance to cyst formation is a dominant trait. To analyze relative roles of H-2 and Bcg loci on cyst numbers, C57BL10 (B10)-derived congenic strains of mice with known H-2 and Bcg type were studied. These studies indicated that the H-2 complex locus has the primary effect on cyst number.

Administration, Oral↗

PubMed1989

Caffeine and cigarette smoking: behavioral, cardiovascular, and metabolic interactions.

Coffee drinking and cigarette smoking are strongly correlated behaviors which have been suggested to act synergistically to produce adverse health consequences, particularly coronary heart disease (CHD). We studied in smokers the influence of four days of multiple daily doses of coffee containing different doses or no caffeine on cigarette smoking behavior, nicotine intake from smoking, heart rate and blood pressure, circadian serum glucose, and urinary catecholamine excretion. We observed a tendency toward greater cigarette consumption during caffeine consumption, and a tendency toward higher plasma nicotine levels during low-dose caffeine compared with the no-caffeine condition; however, these effects were small. No caffeine effects on any other of the above parameters were observed. Previously published research has usually studied effects of single doses of caffeine, which does not account for development of tolerance to effects of caffeine. If caffeine does contribute to CHD risk, it is not likely to be related to caffeine effects on smoking behavior, nicotine intake, blood pressure, heart rate, glucose tolerance, or catecholamine release. Adverse effects of long-term caffeine consumption on lipids cannot be excluded.

Adult↗

PubMed1989

Characterization of proteins secreted by sheep oviduct epithelial cells and their function in embryonic development.

The role in early development of proteins secreted by oviduct epithelial cells has been investigated. Secreted proteins devoid of serum contamination have been produced by the surgical removal and immediate incubation of oviduct cells in [35S]methionine-containing medium. After electrophoretic separation, secreted polypeptides could be divided into those that were secreted uniformly throughout the oestrous cycle and a second class that showed a cyclical pattern of secretion. The first class of proteins represented a small proportion of total output whilst the predominant second class was composed mainly of polypeptides of Mr 92 and 46 x 10(3), respectively. Both of these polypeptide species, referred to as sheep oviduct proteins 92 and 46 (SOP 92, SOP 46), are detected only during the first 4 to 5 days after oestrus when the embryos are located in the oviduct. Oviduct cells collected at oestrus and maintained thereafter in culture secrete the same pattern of proteins and follow the same time course as their counterparts in vivo. The interaction between the oviduct proteins and the developing embryo was studied firstly by determining whether any of the secreted proteins bound to the zona pellucida. The results of iodination studies showed that two polypeptides of Mr 92 and 46 x 10(3), respectively, were bound to the zona pellucida of eggs removed from the oviduct but were absent from eggs that had not had contact with the oviduct epithelium. That these newly acquired proteins represent SOP 92 and 46 is suggested by their electrophoretic mobility and their ability to bind to the zona of follicular eggs when added in vitro and by the fact that they both disappear from the zonae of embryos after exit from the oviduct. The collection of unlabelled secreted proteins enabled us to produce a monoclonal antibody, which was used in the second series of experiments on oviduct-embryo interactions. The results confirmed that SOP 92 binds to the zona pellucida and moreover showed that this protein crosses the zona and becomes associated with the individual blastomeres of the developing embryo. These findings provide evidence that the mammalian oviduct probably plays a direct role in supporting embryonic development through specific polypeptides produced by its epithelium.

Animals↗

PubMed1988

Changes in rate and pattern of caffeine metabolism after cigarette abstinence.

Caffeine metabolism is known to be accelerated in cigarette smokers, but the effects of smoking on the kinetics and pattern of metabolism in a daily consumption pattern have not been described. We investigated the effects of tobacco abstinence on the rate and pattern of caffeine metabolism in nine habitual smokers who consumed six cups of coffee per day, each cup containing 2 mg/kg caffeine. Abstinence from smoking for 4 days resulted in a 46% increase in the 24-hour AUC. Thus, significant, although probably not complete, normalization of the enzyme-inducing effects of cigarette smoking can be seen after 4 days abstinence. During abstinence, 24-hour urine ratios of dimethylxanthines to caffeine and mono-dimethylxanthines to dimethylxanthines were reduced, suggesting that cigarette smoking accelerates both demethylation steps. Other metabolic pathways were unaffected.

Adult↗

PubMed1987

Identification and characterization of the 2D6 and Mr 23,000 antigens on the plasma membrane of rat spermatozoa.

Previous investigations [Jones, Brown, von Glos & Gaunt (1985) Exp. Cell Res. 156, 31-44] have demonstrated the appearance of a new antigenic determinant (recognized by monoclonal antibody 2D6) on the plasma membrane of rat spermatozoa during post-testicular maturation in the epididymis. Identification of the 2D6 antigen on Western blots from one-dimensional SDS/polyacrylamide gels revealed that it co-migrated with a membrane protein (designated Mr 23,000 antigen) present on testicular and immature germ cells, suggesting that one antigen might be a modified version of the other. In the present work, however, we demonstrate that, although they have similar Mr and are present in soluble and membrane-bound forms, the 2D6 and Mr 23,000 antigens are biochemically and immunologically distinct molecules. The properties of the antigens are described and compared. The Mr 23,000 antigen is present on both testicular and cauda epididymidal spermatozoa, has a pI of 6.1, contains no detectable carbohydrate, is not tissue-specific and is degraded by V8 protease. By contrast, the 2D6 antigen is glycosylated, has a broad pI from 4.5 to 6.1, is tissue- and species-specific and is resistant to digestion with V8 protease. Its role in sperm-egg recognition is discussed.

Animals↗

PubMed1987

Identification of a zona-binding protein from boar spermatozoa as proacrosin.

The initial stages of fertilization in vertebrates and invertebrates are thought to involve complementary recognition molecules on spermatozoa and eggs. In a previous work (C. R. Brown and R. Jones, 1987, Development) we described one such putative molecule (a protein of approximate molecular weight 53 kDa) in detergent extracts of boar spermatozoa that has affinity for glycoproteins from the zona pellucida of pig eggs. This molecule has now been identified as proacrosin, the zymogen form of the acrosomal protease acrosin, on the basis of its electrophoretic behavior, the ability of zona glycoproteins to recognize and bind to proacrosin on Western blots, and the cross-reactivity of specific antisera to the 53-kDa molecule and proacrosin. A role is proposed for this enzyme in binding the sperm head to the zona pellucida during the initial stages of sperm-egg interaction.

Acrosin↗

PubMed1987

Effects of passive stretch on growth and regression of muscle from chickens of various ages.

A non-invasive procedure was used to determine the effect of animal age on the growth response of muscle to passive stretch. Stretch increased patagialis muscle weight 61% in 6-week-old chicks and 34% in 10-month-old chicks, 28-month-old animals had an 18% loss of muscle mass during passive stretch. Removal of the stretch stimulus was followed by a rapid return of patagialis weight to control values in 6-week and 10-month animals, while muscle size of 28-month-old animals had not returned to control levels by 22 days, following removal of the stretch. The stretch-induced changes in muscle wet weight could, in part, be attributed to changes in muscle protein. Total muscle DNA content increased during rapid growth in 6-week- and 10-month-old chickens, and returned to control levels during muscle regression. Muscle hydroxyproline content increased in parallel with increases in muscle mass but did not return to control levels during muscle regression in 6-week-old animals. Results of the present study indicate that there was an effect of animal age on stretch-induced hypertrophy and regression of the patagialis muscle.

Age Factors↗

PubMed1987

A comparison of the adhesion, coaggregation and cell-surface hydrophobicity properties of fibrillar and fimbriate strains of Streptococcus salivarius.

Fibrillar and fimbriate strains of Streptococcus salivarius were compared for their ability to adhere to buccal epithelial cells and saliva-coated hydroxyapatite beads, and for their ability to coaggregate with Veillonella strains. The fibrillar Lancefield group K strains adhered statistically significantly better to both buccal epithelial cells and saliva-coated hydroxyapatite beads than the fimbriate strains, which lacked the Lancefield group K antigen. After 1 h the fibrillar strains coaggregated statistically significantly better than the fimbriate strains with V. parvula strain V1, but after 24 h, coaggregation both of fibrillar and of fimbriate strains reached approximately 90%. Freshly isolated Veillonella strains all coaggregated with the S. salivarius strains, but the percentage coaggregation varied considerably after 1 h depending on the Veillonella strain. Coaggregation was independent of the presence of Ca2+. S. salivarius strain HB-V5, a mutant of strain HB that had lost the Veillonella-binding protein, coaggregated weakly with V. parvula strain V1, but coaggregated very well with other wild-type veillonellae, suggesting the presence of an alternative mechanism for Veillonella-binding for strain HB. Fibrillar strains were, therefore, more adhesive to oral surfaces and coaggregated with veillonellae after 1 h better than the fimbriate S. salivarius strains. Both fibrillar and fimbriate strains were highly hydrophobic in the hexadecane-buffer partition assay.

Bacterial Adhesion↗

PubMed1987

Binding of zona pellucida proteins to a boar sperm polypeptide of Mr 53,000 and identification of zona moieties involved.

Experiments have been carried out to identify proteins on boar spermatozoa that bind to components of the zona pellucida. Polypeptides in sodium deoxycholate extracts of boar spermatozoa and in whole seminal plasma have been separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, transferred onto nitrocellulose sheet by electroblotting and probed with 125I-labelled heat-solubilized zona pellucida from pig oocytes or ovulated eggs. Zona proteins bound avidly and consistently to a polypeptide of Mr 53,000 on blots of capacitated and noncapacitated sperm and weakly to polypeptides of Mr 67,000, 38,000 and 18,000. On blots of seminal plasma the 125I-labelled probes bound to two polypeptides of Mr 65,000 and 19-24,000. Identification of the zona proteins that were binding to the aforementioned proteins on blots showed that all the major zona pellucida glycoproteins were involved, including those acquired from oviduct secretions. Binding of 125I-ovulated zona pellucida to the polypeptide of Mr 53,000 also occurred in extracts of testicular and epididymal boar spermatozoa. The results are discussed in relation to sperm-egg recognition in the pig.

Animals↗

PubMed1986

The morphological and molecular susceptibility of sheep and mouse zona pellucida to acrosin.

The effect of acrosin on the gross morphology and macromolecular constituents of the mouse and sheep zona pellucida has been examined by light microscopy and SDS-PAGE following labelling of the zona with 125I. Ram and boar acrosin had similar effects on the sheep zona in that while there was no discernible alteration in the gross morphology of the investment it was proteolysed to the same limited extent by both enzymes; during 1 h major polypeptides of Mr 180,000 (present on the zona pellucida of eggs but absent from that of oocytes) and 80,000 were hydrolysed, giving rise to polypeptides of Mr 68,000, 54,000 and 46,000, of which the last accumulated and represented the lowest molecular weight hydrolysis product. By contrast, the mouse zona pellucida was completely dissolved from the egg by ram acrosin and the investment's macromolecules were extensively hydrolysed.

Acrosin↗

PubMed1986

Changes in composition of the porcine zona pellucida during development of the oocyte to the 2- to 4-cell embryo.

Our objective was to identify any changes that occur in the composition of the porcine zona pellucida during development of the 2- to 4-cell embryo from the oocyte. Oocytes, unfertilized eggs and single and 2- to 4-cell embryos have been recovered surgically and their zonae pellucidae 125I-labelled and analysed individually by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The zonae from ovulated eggs possessed two major glycoproteins Mr250 000 and 90 000 which were absent from follicular oocytes but present in the fluid from the oestrus, but not luteal, oviduct. The glycoproteins remained on the zona pellucida of 2- to 4-cell embryos whose analysis showed the presence of additional polypeptides of Mr 150 000, 57 000, 50 000 and 25 000. It is concluded (i) that shortly after ovulation, and in spite of the presence around the egg of cumulus oophorus and corona radiata cells, significant amounts of oviducal glycoproteins are able to bind firmly to the zona pellucida, and (ii) that after contact with spermatozoa there is evidence of a limited hydrolysis of the structure by the sperm protease acrosin.

Animals↗