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Biomedical subjects

C Warner

Publications and source records attributed to C Warner.

At least 37 records · Page 2Linked to original sources
PubMed1992

Localization of receptor sites for insect-selective toxins on sodium channels by site-directed antibodies.

Site-directed antibodies corresponding to conserved putative extracellular segments of sodium channels, coupled with binding studies of radiolabeled insect-selective scorpion neurotoxins, were employed to clarify the relationship between the toxins' receptor sites and the insect sodium channel. (1) The depressant insect toxin LqhIT2 was shown to possess two noninteracting binding sites in locust neuronal membranes: a high-affinity (KD1 = 0.9 +/- 0.6 nM) and low-capacity (Bmax1 = 0.1 +/- 0.07 pmol/mg) binding site as well as a low-affinity (KD2 = 185 +/- 13 nM) and high-capacity (Bmax2 = 10.0 +/- 0.6 pmol/mg) binding site. (2) The high-affinity site serves as a target for binding competition by the excitatory insect toxin AaIT. (3) The binding of LqhIT2 was significantly inhibited in a dose-dependent manner by each of four site-directed antibodies. The binding inhibition resulted from reduction in the number of binding sites. (4) The antibody-mediated inhibition of [125I]AaIT binding differs from that of LqhIT2: three out of the four antibodies which inhibited LqhIT2 binding only partially affected AaIT binding. Two antibodies, one corresponding to extracellular and one to intracellular segments of the channel, did not affect the binding of either toxin. These data suggest that the receptors to the depressant and excitatory insect toxins (a) comprise an integral part of the insect sodium channel, (b) are formed by segments of external loops in domains I, III, and IV of the sodium channel, and (c) are localized in close proximity but are not identical in spite of the competitive interaction between these toxins.

Animals↗
PubMed1992

Biochemical properties and subcellular distribution of an N-type calcium channel alpha 1 subunit.

A site-directed anti-peptide antibody, CNB-1, that recognizes the alpha 1 subunit of rat brain class B calcium channels (rbB) immunoprecipitated 43% of the N-type calcium channels labeled by [125I]omega-conotoxin. CNB-1 recognized proteins of 240 and 210 kd, suggesting the presence of two size forms of this alpha 1 subunit. Calcium channels recognized by CNB-1 were localized predominantly in dendrites; both dendritic shafts and punctate synaptic structures upon the dendrites were labeled. The large terminals of the mossy fibers of the dentate gyrus granule neurons were heavily labeled, suggesting that the punctate labeling pattern represents calcium channels in nerve terminals. The pattern of immunostaining was cell specific. The cell bodies of some pyramidal cells in layers II, III, and V of the dorsal cortex, Purkinje cells, and scattered cell bodies elsewhere in the brain were also labeled at a low level. The results define complementary distributions of N- and L-type calcium channels in dendrites, nerve terminals, and cell bodies of most central neurons and support distinct functional roles in calcium-dependent electrical activity, intracellular calcium regulation, and neurotransmitter release for these two channel types.

Amino Acid Sequence↗
PubMed1992

Analysis of complement C4 loci in Caucasoids and Japanese with idiopathic membranous nephropathy.

Deletion of the HLA class III complement gene, C4A, has been linked with susceptibility to a number of autoimmune diseases. In this study, we show a strong positive association between C4A gene deletion and development of idiopathic membranous nephropathy (IMN) in European Caucasoids [patients, 17/27 (63%); healthy controls, 13/65 (20%); RR 6.8; P = 0.003]. To clarify whether C4A deletion is an independent risk factor for IMN or is increased secondarily to the Caucasoid HLA A1, B8, DR3 extended haplotype, we examined the frequency of C4A deletion in Japanese patients, in whom the disease is associated with another HLA haplotype (DR2-DQw1). Analysis of 31 Japanese patients and 46 healthy controls showed that C4A deletion was present in only one patient (3%) and one control (2%). In addition, examination of the C4B locus in Japanese patients showed that there was no significant increase in the estimated frequency of C4B deletion in patients against controls (31 vs. 27%) and no difference in the frequency of the C4B long gene (73 vs. 87%) or C4B short gene (77 vs. 78%). We conclude that although C4A deletion confers significant risk of IMN in Caucasoids, there is no significant association between C4 polymorphism, as detected here, and risk of IMN in Japanese. This suggests that either C4A deletion is irrelevant to the pathogenesis of IMN or that more than one genetic mechanism is involved.

Asian People↗
PubMed1991

Characterization of the two size forms of the alpha 1 subunit of skeletal muscle L-type calcium channels.

The molecular properties of two size forms of the alpha 1 subunit of purified skeletal muscle calcium channels were analyzed. The minor, full-length, form, alpha 1(212), was found to have an apparent molecular mass of 214 kDa by Ferguson plot analysis, while the major, truncated, form, now designated alpha 1(190), had an apparent molecular mass of 193 kDa. Antibody mapping of the C-terminal region of alpha 1(190) with 10 anti-peptide antibodies placed the C terminus between residues 1685 and 1699. Three consensus sites for cAMP-dependent protein phosphorylation are present in the C-terminal region of alpha 1(212) but not in alpha 1(190), and they may be important for the regulation of the ion conductance activity of the calcium channel.

Amino Acid Sequence↗
PubMed1990

Subunits of purified calcium channels. Alpha 2 and delta are encoded by the same gene.

Polyacrylamide gel electrophoresis of purified rabbit skeletal muscle L-type calcium channel before and after reduction of disulfide bonds confirmed that 27- and 24-kDa forms of the delta subunit are disulfide-linked to the 143-kDa alpha 2 subunit. The amino acid sequences of three peptides obtained by tryptic digestion of the delta subunits corresponded to amino acid sequences predicted from the 3' region of the mRNA encoding alpha 2. One of these peptides had the same sequence as the N terminus of the 24- and 27-kDa forms of the delta subunit and corresponded to residues 935-946 of the predicted alpha 2 primary sequence. Anti-peptide antibodies directed to regions on the N-terminal side of this site recognized the 143-kDa alpha 2 subunit in immunoblots of purified calcium channels under reducing conditions, whereas an antipeptide antibody directed toward a sequence on the C-terminal side of this site recognized 24- and 27-kDa forms of the delta subunit. A similar result was obtained after immunoblotting using purified transverse tubules or crude microsomal membrane preparations indicating that alpha 2 and delta occur as distinct disulfide-linked polypeptides in skeletal muscle membranes. Thus, the delta subunits are encoded by the same gene as the alpha 2 subunit and are integral components of the skeletal muscle calcium channel.

Amino Acid Sequence↗
PubMed1990

Influence of single and multiple doses of oral ranitidine on the gastric transit of an indigestible capsule in humans.

The effect of single and multiple doses of ranitidine on the gastric residence time of an indigestible pH-sensitive radiotelemetric device, the Heidelberg capsule, was evaluated in 12 healthy men (mean age, 29 +/- 8 years) in a placebo-controlled, randomized, crossover study. Each subject received 150 mg ranitidine or placebo orally 2 hours before administration of the Heidelberg capsule. A 500 kcal standardized breakfast was served 1/2 hour before the capsule was administered. Gastric pH was monitored at 15-minute intervals, until pyloric passage (pH increase greater than or equal to 3 U) of the Heidelberg capsule was observed. Blood samples (n = 12) were collected 0 to 8 hours after administration of drug or placebo. The subjects continued to receive ranitidine or placebo b.i.d. for 7 days and returned on day 8 for a similar evaluation. After a 1-week washout period, the subjects received the alternative treatment. The mean (+/- SD) gastric residence time of the Heidelberg capsule was significantly decreased after both single and multiple doses of ranitidine compared to placebo (3.1 +/- 0.9 versus 3.8 +/- 1.1 hours, p less than 0.02; and 2.9 +/- 0.74 versus 3.9 +/- 0.9 hours, p less than 0.005, n = 9). Gastric residence time was not determined in three subjects who showed unusually slow gastrointestinal motility after both placebo and ranitidine. Mean AUC(0-8 hr) and AUC(0-infinity) were significantly increased, whereas Cmax, tmax, and t1/2 remained unchanged after 7 days of ranitidine b.i.d. treatment. No ranitidine double-peak profile or linear pharmacokinetic-pharmacodynamic relationship was identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Restriction fragment length polymorphism analysis of major histocompatibility complex class II genes from inbred chicken lines.

High molecular weight DNA was extracted from sperm from chickens of 14 inbred lines. The DNA was digested with each of four restriction enzymes (Pvu II, Hind III, Bgl II, and Bam HI), electrophoresed for 18 or 45 h, blotted onto nitrocellulose, and hybridized to a chicken major histocompatibility complex (MHC, B complex) class II beta-chain probe (beta 2-exon specific). Restriction fragment length polymorphisms (RFLPs) were found with each of the restriction enzymes used. Birds with the same B haplotype always showed the same RFLP pattern; however, some birds of different B haplotypes also shared the same RFLP pattern. To test for the Mendelian inheritance of the RFLP patterns, the F2 progeny of an informative cross were analysed. The RFLP patterns corresponded with the serologically determined B haplotypes of the F2 birds, thereby showing the Mendelian inheritance of the polymorphic bands.

Animals↗
PubMed1988

Skin preparation in the surgical patient.

A historical review of skin antisepsis is given. Current practices, rationales for skin antisepsis as a segment of total wound care, and bacteriological factors are discussed. The results of a telephone survey of current practices of 16 medical centers around the country are presented. Discussion and conclusions relative to survey results and skin care agents are given. Characteristics of an ideal skin preparation yet to be obtained and some common myths relating to this subject are discussed.

Antisepsis↗
PubMed1986

The effect of ranitidine and cimetidine on imipramine disposition.

The pharmacokinetic characteristics of imipramine were studied after a single, oral, 100 mg dose was taken by 12 healthy male subjects following 3 days of pretreatment with placebo, cimetidine (300 mg every 6 h), and ranitidine (150 mg every 12 h) in a randomized, double blind, crossover trial. After each imipramine dose plasma samples were collected for 72 h and assayed for imipramine, desipramine, 2-hydroxyimipramine and 2-hydroxydesipramine by HPLC. Cimetidine preadministration statistically prolonged imipramine t 1/2 compared to ranitidine (22.7 vs. 13.0 h) or placebo (10.8 h). Mean imipramine area under the curve (AUC) following cimetidine pretreatment was more than double that following placebo (2.633 vs. 0.966 micrograms X h X ml-1) or ranitidine (1.14 micrograms X h X ml-1) pretreatment. Imipramine apparent oral clearance was reduced in all 12 subjects after cimetidine. Compared to ranitidine or placebo, cimetidine pretreatment was associated with an increased imipramine/desipramine AUC ratio, suggesting cimetidine-induced impairment of demethylation of imipramine. Ranitidine was not observed to alter imipramine pharmacokinetics.

Administration, Oral↗
PubMed1986

Can acute cholecystitis produce obstructive jaundice in the absence of choledocholithiasis?

A case is presented of acute cholecystitis that produced extensive ascending, intrahepatic acute cholangitis (sufficient to produce obstructive jaundice of significant degree) without evidence of choledocholithiasis or ductal dilatation.Questions are raised concerning the present accepted clinical classification of both cholangitis and obstructive jaundice.

Acute Disease↗
PubMed1980

Repair of radiation-induced DNA damage in nondividing populations of human diploid fibroblasts.

The occurrence of DNA repair in UV- (254 nm) and X-irradiated normal human diploid fibroblasts maintained in a quiescent, nondividing state using low serum (0.5%) medium was ascertained. Techniques that detect different steps of the excision repair process were used so that the extent of completion of repair at single sites could be determined. These included measuring the disappearance of pyrimidine dimers by chromatography, detecting repair synthesis by density-gradient and autoradiographic methods and detecting the rejoining of repaired regions and repair of x-ray-induced single-strand DNA breaks using alkaline sucrose gradients. Results show that dimer excision occurs and the subsequent steps of repair synthesis and ligation are completed. About 50% of the dimers formed by exposure to 20 J/m2 is excised in the initial 24-h post-UV period. DNA repair (unscheduled DNA synthesis) can be detected through a 5-d post-UV period. The fraction of damaged sites eventually repaired is not known. X-ray-induced single-strand DNA breaks are repaired rapidly.

Cell Line↗
PubMed1979

A direct role of dopamine in the rat subthalamic nucleus and an adjacent intrapeduncular area.

The subthalamic nucleus, a clinically important component of the extrapyramidal motor system, and a lateral area extending into the peduncle contain catecholamine terminals and dopamine receptors coupled to adenylate cyclase. In addition, dopamine agonists administered in vivo enhance glucose utilization in the region. Thus, neuronal function in this region is directly affected by dopamine and dopaminergic drugs.

Adenylyl Cyclases↗