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Biomedical subjects

J R Brown

Publications and source records attributed to J R Brown.

At least 127 records · Page 7Linked to original sources
PubMed1987

Pharmacological analysis of 125I-Bolton and Hunter labelled eledoisin binding sites in rat spinal cord by quantitative autoradiography.

Using the technique of quantitative autoradiography it has been possible to investigate and compare the pharmacological characteristics of 125I-Bolton-Hunter conjugated eledoisin (125I-BHE) binding sites in rat spinal cord with those in the rat cortex. 125I-BHE specific binding sites were discretely localised in the outer layers of the rat spinal cord. The rank order of affinity of unlabelled tachykinins in competing for 125I-BHE specific binding sites in rat spinal cord (NKB greater than ELE greater than NKA greater than SP) was identical to that found in the rat cortex suggesting the presence of 'NK-3 like' receptors in rat dorsal horn.

Animals↗
PubMed1987

Structure-activity studies on the C-terminal hexapeptide of substance P with modifications at the glutaminyl and methioninyl residues.

Analogues of [Orn6]-SP6-11 have been synthesized in which the SCH3 group of the Met11 side chain is replaced by other functional groups, such as (CH2)2NH2, COOH, CONH2, and COOR, which have basic, acid, or neutral character and which may act as either H-bonding donors or H-bonding acceptors. These analogues were tested in guinea pig ileum and rat colon muscularis mucosae, in vitro. Substitution of Lys, Gln, or Glu at position 11 caused a marked reduction in biological activity in both tissues. In contrast, the glutamate benzyl ester analogue had only slightly reduced activity in the guinea pig ileum and an increased (4.7 times) activity in the rat colon. It is concluded that charged groups in the side chain at position 11 of SP6-11 reduce the biological activity of SP hexapeptide.

Amino Acid Sequence↗
PubMed1987

Assessing assessment: the Goldman-Fristoe-Woodcock Auditory Skills Battery.

The purpose for this study was to determine the internal consistency (reliability) and the test-retest consistency (stability), and analyze the factor structures for the first ten tests of The Goldman-Fristoe-Woodcock Auditory Skills Battery (GFW Battery) in a population of normally hearing and regularly educated elementary children. The test battery was administered exactly as described in the test manuals to 100 children randomly selected from three public school districts. The results were that while the tests in the GFW Battery were typically reliable they were not stable. Additionally, the results indicated that factor structures suggested four distinct behaviors which conformed to auditory processing but which were significantly different than the factor structures reported for the GFW Battery. The first implication for clinicians is to retest children, after initial test administration, to ensure the stability of the initial test score. The second implication from this study is to question the validity of identifying each of the tests of the GFW Battery as unique and the validity for isolating the first 10 tests for planning and implementing auditory training.

Auditory Perception↗
PubMed1986

Effects of VIP and related peptides and Gila monster venom on genitourinary smooth muscle.

The pharmacological effects of peptide histidine isoleucine (PHI), glucagon and secretin were compared with vasoactive intestinal polypeptide (VIP) on rabbit urethra and anococcygeus muscle. VIP and PHI dose-dependently inhibited induced contractions of both smooth muscle preparations. Cross-tachyphylaxis between VIP and PHI was demonstrated in the urethra preparation, suggesting that their activity is mediated via a common receptor or second messenger. Glucagon and secretin were without effect on either preparation. Radioimmunoassays demonstrated substantial concentrations of VIP and PHI in both urethra and anococcygeus tissue extracts. These observations suggest that PHI is an additional candidate together with VIP to mediate relaxation of rabbit urethra and anococcygeus muscle. When compared with VIP, Gila monster venom was found to inhibit both smooth muscle preparations, producing concentration-response curves parallel to those produced by VIP.

Animals↗
PubMed1986

DNA sequence preferences for the anti-cancer drug mitoxanthrone and related anthraquinones revealed by DNase I footprinting.

The interaction has been studied of several anthraquinone-based intercalating drugs, including the anti-cancer agent mitoxantrone, with defined sites of DNA. A 160 base pair DNA sequence from tyrT was employed for footprinting with DNase I. The anthraquinones had aminoalkylamino substituents in various positions of the ring system. Inhibition of enzymatic cutting of the DNA was observed at various positions on the sequence, mostly around some of the pyrimidine-3',5'-purine sites. Enhancements to cutting were observed clustered around AT-rich regions. The compounds showed differences in detailed footprinting behaviour, which have been related to differences in their mode of interaction with DNA as found in earlier computer modelling studies.

Anthraquinones↗
PubMed1986

The effect of macromolecular conjugates of daunorubicin on nuclear ultrastructure in Trypanosoma brucei rhodesiense.

The effects of free and conjugated daunorubicin on T.b. rhodesiense in vitro are described. Free drug caused nucleolar lesions ranging from segregation to complete fragmentation. At equimolar concentrations a soluble bovine serum albumin conjugate with a stable succinyl linkage (D-BSAS) produced no ultrastructural lesions whereas a conjugate with a labile glutaraldehyde linkage (D-BSAG) and a conjugate linked to large agarose beads (D-ag) produced similar though less severe lesions than free drug. Polyisobutylcyanoacrylate nanoparticles caused trypanosomal lysis both with (D-PICA) and without adsorbed daunorubicin.

Animals↗
PubMed1986

Synthesis and biological activity of substance P C-terminal hexapeptide analogues: structure-activity studies.

A series of analogues of the C-terminal hexapeptide of substance P, modified at the glutaminyl residue, was synthesized and their relative activities as spasmogens were determined in the guinea pig ileum and rat colon muscularis mucosae preparations in vitro. In general, when compared to SP6-11, the loss of the carboxamide group has little effect on activity in the colon and reduces activity on the ileum. The exception to this is the Orn6 analogue which retains activity on both preparations and is proposed as a useful tool for structure-activity studies. It is concluded that the hydrogen-bonding potential of the position 6 substituent may be an important determinant of biological activity.

Animals↗
PubMed1986

An evaluation of the test for auditory comprehension of language.

The present study was designed to determine the internal consistency and test-retest consistency of the Test for Auditory Comprehension of Language (TACL) for a group of normally hearing and regularly educated children. Fifty-five children were randomly selected from three elementary schools and were administered the TACL exactly as described in the test's manual. From these 55 children, 30 were randomly selected and retested. The results indicated that the test was internally consistent but not consistent upon retesting.

Child↗
PubMed1986

An outbreak of gastroenteritis in an airmobile unit.

An infantry battalion as part of an Airmobile Brigade took part in a field exercise in Germany during mid summer 1984. During the exercise the battalion suffered from an outbreak of gastroenteritis which affected at least 64 men, some 10% of its total strength. The follow up investigation revealed that it was likely that the origin of the outbreak was uncontrolled drinking of polluted water from two streams. This paper seeks to underline the lesson that poor water discipline can have serious consequences for units in the field.

Disease Outbreaks↗
PubMed1986

A case of frostbite or "it takes more than two pairs of socks to keep your feet warm".

During February 1985 a squadron of an engineer regiment deployed into the field to exercise its men in basic infantry skills. One of these men was a 20 year old sapper. During the exercise he sustained frostbite injury to both feet, the right foot being more affected than the left. The background, clinical progress and preventive medicine implications are discussed.

Adult↗
PubMed1986

Test of auditory comprehension: a comparison of hearing-impaired and normal-hearing listeners.

Normal-hearing (NH) children (N:35) aged 9-11 yrs in regular classrooms were given all 10 subtests of the Test of Auditory Comprehension (TAC) (Trammel, 1976). Group means of raw scores, measures of dispersion, and of internal consistency, alpha, and of test-retest reliability, r, were computed and are presented here for the first time for NH Ss. These data were compared with TAC norms published for a group of 750 hearing-impaired (HI) children with moderate to severe sensorineural hearing loss. Group means for the NH Ss were substantially higher (p less than or equal to .05) on 9 of the 10 subtests than for the HI Ss, but the dispersion was always substantially greater. Furthermore, estimates of alpha and of r were greater on 8 of the 10 subtests for alpha and on 8 for r, the 8 tests not altogether overlapping. The implication is that different auditory processing information may be used by the two different populations, generally supporting the use in the clinic of only those tests specifically designed and demonstrated to be applicable for specific populations.

Auditory Perception↗
PubMed1985

Dissociation kinetics of DNA-anthracycline and DNA-anthraquinone complexes determined by stopped-flow spectrophotometry.

The first order rate constants for the dissociation of daunorubicin, doxorubicin, and 1-; 1,4-; 1,5-; and 1,8-; N,N-diethylaminoethylamino-substituted anthraquinones from calf thymus DNA were determined using stopped-flow spectrophotometry. Sodium dodecyl sulphate was used to disrupt the equilibrium. In all cases there was an increase in the rate constant with temperature. The dissociation rate constants at 20 degrees, 25 degrees and 37 degrees, were in the order 1-; much greater than 1,8-; greater than 1,4-; greater than daunorubicin and doxorubicin greater than 1,5-disubstituted anthraquinone. The 1,5-disubstituted anthraquinone (VII) thus shows the slowest rate of dissociation from DNA; the DNA complex dissociating more slowly than the DNA complexes of the anthracyclines, daunorubicin and doxorubicin. The result is consistent with the data from computer graphics modelling studies [39] which show that DNA-breathing (transient base pair unstacking) has to occur to allow the docking of the 1,5-disubstituted anthraquinone (VII) into the receptor site. Hence once the 1,5-disubstituted anthraquinone molecule has intercalated into DNA, DNA-breathing is required before dissociation can take place. This is not necessary with the other compounds (though the 1,4-disubstituted anthraquinone (V) can bind in this manner as well). So the very slow dissociation of the DNA/1,5-disubstituted anthraquinone complex relative to that of the DNA complexes of the other compounds examined here, supports the proposed mode of binding [39].

Anthraquinones↗
PubMed1985

Synthetic peptide substrates for mammalian pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase.

The specificities of pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase were probed using synthetic peptides corresponding to the sequence around phosphorylation sites 1 and 2 on pyruvate dehydrogenase [Tyr-His-Gly-His-Ser(P1)-Met-Ser-Asp-Pro-Gly-Val-Ser(P2)-Tyr-Arg]. The dephosphotetradecapeptide containing aspartic acid at position 8 was a better substrate for the kinase than was the tetradecapeptide containing asparagine at position 8. The apparent Km and V values for the two peptides were 0.43 and 6.1 mM and 2.7 and 2.4 nmol of 32P incorporated/min/mg, respectively. Methylation of the aspartic acid residue also increased the apparent Km of the tetradecapeptide about 14-fold. These results indicate that an acidic residue on the carboxyl-terminal side of phosphorylation site 1 is an important specificity determinant for the kinase. Phosphate was incorporated only into site 1 of the synthetic peptide by the kinase. The phosphatase exhibited an apparent Km of 0.28 mM and a V of 2.3 mumol of 32P released/min/mg for the phosphorylated tetradecapeptide containing aspartic acid. Methylation of the aspartic acid residue had no significant effect on dephosphorylation. The octapeptide and phosphooctapeptide produced by cleavage of the aspartyl-prolyl bond by formic acid were poorer substrates for the kinase and phosphatase than were the tetradecapeptide and phosphotetradecapeptide, respectively. Modification of the amino terminal by acetylation or lysine addition had only a slight effect on the kinase and phosphatase activities.

Amino Acid Sequence↗
PubMed1985

Comparative computer graphics and solution studies of the DNA interaction of substituted anthraquinones based on doxorubicin and mitoxantrone.

1-[[(Diethylamino)ethyl]amino]- and 1,4-, 1,5-, and 1,8-bis[[(diethylamino)ethyl]amino]anthraquinones are shown to intercalate into DNA. Computer graphics modelling of their intercalation into the self-complementary deoxydinucleoside d(CpG) showed differences in binding properties. While the 1-substituted compound can bind from either groove, the 1,8-disubstituted compound binds with both substituents in the major groove. In the low-energy state of the complex with the 1,5-disubstituted compound, this ligand "straddles" the site with a substituent in each groove--to do this, the compound must bind to a non-base-paired region, so inducing base pairing. The 1,4-compound binds from the major groove; "straddling" is also possible if full minimization of deoxydinucleoside geometry is performed. The differences in binding mode and interaction energies are reflected in the affinities of interaction (1,5- greater than 1,4- much greater than 1,8- greater than 1-); also the antiproliferative effects in vitro are in general agreement with this ranking.

Animals↗
PubMed1985

Iron stores in users of oral contraceptive agents.

A comparison of serum ferritin and other parameters of iron status was made between 46 women taking oral contraceptive agents (OCAs) for two or more years continuously and 71 women who never took OCAs. The mean serum ferritin level for the OCA users was 39.5 +/- 21.5 ng/ml and the control group mean level was 25.4 +/- 15.96 ng/ml, which is significantly different at p less than 0.001. Serum transferrin, serum iron, TIBC, MCH and MCHC levels were significantly greater for the OCA users group. Significantly lower RBC and hematocrit levels were found for OCA users while other parameters, hemoglobin, MCV and percent transferrin saturation, were not significantly different. No major differences in subject characteristics and dietary traits were evidenced, except a difference in reported menstrual cycle losses and a higher heme iron content in the diet of the OCA users.

Adolescent↗