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Biomedical subjects

J Maddock

Publications and source records attributed to J Maddock.

At least 19 recordsLinked to original sources
PubMed2001

Impact of skin cancer prevention on outdoor aquatics staff: the Pool Cool program in Hawaii and Massachusetts.

BACKGROUND: Aquatic staff, including lifeguards, are exposed to intense sunlight for many hours each day and are likely to be at a relatively high risk for developing skin cancer. However, no interventions have been specifically directed to staff at outdoor swimming pool sites. METHODS: We conducted a randomized controlled trial among aquatic staff at 28 outdoor pool sites in Hawaii and Massachusetts. Intervention pools received sun protection education and control pools received education on child injury prevention. Staff in both arms received orientation sessions and led instruction during swim lessons. Analysis of covariance was used to compare and test for changes in outcome variables (sun protection habits and sunburning rates of aquatic staff) and pool protection policies. Surveys were completed at the beginning and end of the summer. RESULTS: Surveys were completed by 220 aquatics staff at baseline; 194 surveys were completed at posttest. Compared with staff at control pools, sun protection policies (P < 0.04) and sunburning rates (P < 0.05) improved at sun protection pools from baseline to posttest. However, the difference in the mean score of all sun protection habits between the two study groups was nonsignificant. CONCLUSION: The Pool Cool sun protection intervention had significant effects on lifeguards' sunburn rates and pool sun safety policies but did not improve reported sun protection behaviors. More intensive strategies may be needed to influence aquatics workers who have already begun to adopt skin cancer prevention practices.

Adult↗
PubMed2000

Regulation of stalk elongation by phosphate in Caulobacter crescentus.

In Caulobacter crescentus, stalk biosynthesis is regulated by cell cycle cues and by extracellular phosphate concentration. Phosphate-starved cells undergo dramatic stalk elongation to produce stalks as much as 30 times as long as those of cells growing in phosphate-rich medium. To identify genes involved in the control of stalk elongation, transposon mutants were isolated that exhibited a long-stalk phenotype irrespective of extracellular phosphate concentration. The disrupted genes were identified as homologues of the high-affinity phosphate transport genes pstSCAB of Escherichia coli. In E. coli, pst mutants have a constitutively expressed phosphate (Pho) regulon. To determine if stalk elongation is regulated by the Pho regulon, the Caulobacter phoB gene that encodes the transcriptional activator of the Pho regulon was cloned and mutated. While phoB was not required for stalk synthesis or for the cell cycle timing of stalk synthesis initiation, it was required for stalk elongation in response to phosphate starvation. Both pstS and phoB mutants were deficient in phosphate transport. When a phoB mutant was grown with limiting phosphate concentrations, stalks only increased in length by an average of 1.4-fold compared to the average 9-fold increase in stalk length of wild-type cells grown in the same medium. Thus, the phenotypes of phoB and pst mutants were opposite. phoB mutants were unable to elongate stalks during phosphate starvation, whereas pst mutants made long stalks in both high- and low-phosphate media. Analysis of double pst phoB mutants indicated that the long-stalk phenotype of pst mutants was dependent on phoB. In addition, analysis of a pstS-lacZ transcriptional fusion showed that pstS transcription is dependent on phoB. These results suggest that the signal transduction pathway that stimulates stalk elongation in response to phosphate starvation is mediated by the Pst proteins and the response regulator PhoB.

Amino Acid Sequence↗
PubMed1998

The Chlamydomonas zygospore: mutant strains of Chlamydomonas monoica blocked in zygospore morphogenesis comprise 46 complementation groups.

Chlamydomonas monoica undergoes homothallic sexual reproduction in response to nitrogen starvation. Mating pairs are established in clonal culture via flagellar agglutination and fuse by way of activated mating structures to form the quadriflagellate zygote. The zygote further matures into a dormant diploid zygospore through a series of events that we collectively refer to as zygosporulation. Mutants that arrest development prior to the completion of zygosporulation have been obtained through the use of a variety of mutagens, including ultraviolet irradiation, 5-fluorodeoxyuridine, ethyl methanesulfonate, and methyl methanesulfonate. Complementation analysis indicates that the present mutant collection includes alleles affecting 46 distinct zygote-specific functions. The frequency with which alleles at previously defined loci have been recovered in the most recent mutant searches suggests that as many as 30 additional zygote-specific loci may still remain to be identified. Nevertheless, the present collection should provide a powerful base for ultrastructural, biochemical, and molecular analysis of zygospore morphogenesis and dormancy in Chlamydomonas.

Animals↗
PubMed1997

Identification of the fliI and fliJ components of the Caulobacter flagellar type III protein secretion system.

Caulobacter crescentus is motile by virtue of a polar flagellum assembled during the predivisional stage of the cell cycle. Three mutant strains in which flagellar assembly was blocked at an early stage were isolated. The mutations in these strains mapped to an operon of two genes, fliI and fliJ, both of which are necessary for motility. fliI encodes a 50-kDa polypeptide whose sequence is closely related to that of the Salmonella typhimurium FliI protein, an ATPase thought to energize the export of flagellar subunits across the cytoplasmic membrane through a type III protein secretion system. fliJ encodes a 16-kDa hydrophilic protein of unknown function. Epistasis experiments demonstrated that the fliIJ operon is located in class II of the C. crescentus flagellar regulatory hierarchy, suggesting that the gene products act at an early stage in flagellar assembly. The expression of fliIJ is induced midway through the cell cycle, coincident with other class II operons, but the FliI protein remains present throughout the cell cycle. Subcellular fractionation showed that FliI is present both in the cytoplasm and in association with the membrane. Mutational analysis of FliI showed that two highly conserved amino acid residues in a bipartite ATP binding motif are necessary for flagellar assembly.

Amino Acid Sequence↗
PubMed1997

Identification of an essential Caulobacter crescentus gene encoding a member of the Obg family of GTP-binding proteins.

We have identified an essential Caulobacter crescentus gene (cgtA) that encodes a member of a recently identified subfamily of GTPases (the Obg family) conserved from Bacteria to Archaea to humans. This evolutionary conservation between distantly related species suggests that this family of GTP-binding proteins possesses a fundamental, yet unknown, cellular role. In this report, we describe the isolation and sequence of the cgtA gene. The predicted CgtA protein displays striking similarity to the Obg family of small, monomeric GTP-binding proteins, both in the conserved guanine nucleotide-binding domains and throughout the N-terminal glycine-rich domain that is found in many members of the Obg family. Disruption of the cgtA gene was lethal, demonstrating that this gene is essential for cell growth. Immunoblot analysis revealed that CgtA protein levels remained constant throughout the C. crescentus cell cycle.

Alleles↗
PubMed1994

The control of spatial organization during cellular differentiation.

Caulobacter crescentus is a dimorphic bacterium that yields two distinct cell types with every cell division, a motile swarmer cell and a sessile stalked cell. Caulobacter, therefore, possesses a simple developmental program and is used as an model system to determine basic mechanisms of cellular morphogenesis. The generation of the asymmetric predivisional cell requires the temporal expression of many genes as well as the precise intracellular positioning of these gene products. Analysis of the biogenesis and positioning of cell type-specific genes and proteins has been instrumental in understanding the underlying principles as to how asymmetry in the predivisional cell is generated. This manuscript explores our current understanding of the mechanisms by which Caulobacter differentiation is achieved.

Bacterial Proteins↗
PubMed1993

Stereochemistry of ulapualides, a new family of tris-oxazole-containing macrolide ionophores from marine nudibranchs. A molecular mechanics study.

A molecular mechanics study of the marine metabolite ulapualide A, which is suggested to have ionophoric properties, has been carried out on various metal chelated complexes in order to predict the stereochemistry of the natural product. The results suggest a stereochemistry for ulapualide A which is closely similar to structurally related marine metabolites, whose stereochemistries have been established by X-ray crystallography and by partial synthesis.

Animals↗
PubMed1991

Simultaneous determination of clebopride and a major metabolite N-desbenzylclebopride in plasma by capillary gas chromatography-negative-ion chemical ionization mass spectrometry.

A procedure for the simultaneous assay of clebopride and its major metabolite N-desbenzylclebopride in plasma has been developed. The method utilizes capillary gas chromatography-negative-ion chemical ionization mass spectrometry with selected-ion monitoring of characteristic ions. Employing 2-ethoxy analogues as internal standards, the benzamides were extracted from basified plasma using dichloromethane. Subsequent reaction with heptafluorobutyric anhydride produced volatile mono- and diheptafluorobutyryl derivatives of clebopride and N-desbenzylclebopride, respectively. The methane negative-ion mass spectra of these derivatives exhibited intense high-mass ions ideal for specific quantitation of low levels in biological fluids. Using this procedure the recovery of the drug and metabolite from human plasma was found to be 84.4 +/- 1.5% (n = 3) and 77.4 +/- 4.7% (n = 3), respectively, at 0.5 ng/ml. Measurement of both compounds down to 0.10 ng/ml with a coefficient of variation of less than 10.5% is described. Plasma levels are reported in four volunteers up to 24 h following oral administration of 1 mg of clebopride malate salt.

Benzamides↗
PubMed1990

Plasma GABA-like activity in response to ethanol challenge in men at high risk for alcoholism.

Sons of alcoholic fathers (high risk, HR) and matched control men from families without alcoholism (low risk, LR) were administered, in a randomized double-blind fashion, either a placebo beverage or an isovolemic beverage containing ethanol (0.8 g/kg). Serial blood sampling for determination of plasma gamma-aminobutyric acid (GABA)-like activity, mood, and intoxication ratings were performed. The HR subjects were found to have significantly less plasma GABA-like activity than LR during the placebo condition. The alcoholic beverage condition washed out the differences in plasma GABA between groups. Significant interactions between risk group status and beverage conditions were found with respect to plasma GABA-like activity. Alcohol produced an increase in mean GABA-like activities among HR subjects, whereas a slight decline was noted among LR subjects. Plasma GABA-like activity also had a significant inverse correlation with self-reports of perceived tension in the placebo condition, and tension, confusion, and intoxication in response to the alcoholic drink. Since previous investigators have reported reduced plasma GABA levels in alcoholic individuals, reduced plasma GABA-like activity may be a biological marker for vulnerability to alcoholism or for heightened tension as a behavioral factor that predisposes to alcoholism.

Adult↗
PubMed1988

Determination of clebopride in plasma by capillary gas chromatography-negative-ion chemical ionization mass spectrometry.

A procedure for the analysis of clebopride in plasma using capillary gas chromatography-negative-ion chemical ionization mass spectrometry has been developed. Employing an ethoxy analogue as internal standard, the two compounds were extracted from basified plasma using dichloromethane. Subsequent reaction with heptafluorobutyryl imidazole produced volatile monoheptafluorobutyryl derivatives whose ammonia negative-ion mass spectra proved ideal for selected-ion monitoring. The recovery of clebopride from plasma at 0.536 nmol/l was found to be 85.5 +/- 0.9% (n = 3) whilst measurement down to 0.268 nmol/l was possible with a coefficient of variation of 7.9%. Plasma levels of the compound are reported in two volunteers following ingestion of 1 mg of clebopride as the malate salt.

Antiemetics↗
PubMed1986

Pharmacokinetics of isosorbide-5-nitrate in renal failure.

The pharmacokinetics of the antianginal drug isosorbide-5-nitrate (IS-5-N) was studied in 20 patients with varying degrees of chronic renal failure after repeated oral doses of standard 20 mg tablets t.d.s. Blood samples were taken in the steady state on the 2nd and 28th days, and the plasma level was assayed by HPLC. There was no statistically significant difference in Cssmax, t1/2 and AUCss0-8 between the 2nd and 28th days, nor was a difference found between patients with mild and severe renal failure.

Aged↗
PubMed1985

Improved method for the determination of N-acetylcysteine in human plasma by high-performance liquid chromatography.

An improved method for the determination of N-acetylcysteine by paired-ion reversed-phase high-performance liquid chromatography has been developed. Following incubation with dithiothreitol to release bound N-acetylcysteine, free N-acetylcysteine and the internal standard N-acetylpenicillamine were derivatised with 2,4-dinitro-1-fluorobenzene. The samples were then deproteinised by ultrafiltration. The dinitrophenyl derivatives were extracted from acidified ultrafiltrate into diethyl ether and purified by using a back-extraction step. They were then separated from naturally occurring plasma components and reagent impurities by high-performance liquid chromatography, utilising an Ultrasphere ODS (5 microns) reversed-phase column and detection at 360 nm.

Acetylcysteine↗
PubMed1984

[Treatment of morning migraine. Clinical and biokinetic correlation of programmed-release dihydroergotamine].

The authors have tested a new preparation of dihydroergotamine (microgranules in a capsule) by comparing the clinical results obtained in 30 patients suffering from morning migraine with the plasma levels of the active substance measured in 8 healthy subjects. The microgranules were administered in doses of 30 mg/24 hours and compared with a similar dose of a dihydroergotamine solution. The close correlation observed between sustained plasma levels and prolonged therapeutic effects indicates a truly programmed delivery of dihydroergotamine by the microgranule preparation.

Adolescent↗
PubMed1984

High-performance liquid chromatographic assay for N-acetylcysteine in plasma and urine.

A sensitive high-performance liquid chromatographic (HPLC) assay for N-acetylcysteine in human plasma and urine has been developed. The method employs a prechromatographic stage to produce the dinitrophenyl derivative of N-acetylcysteine, which is chromatographed on a 5-microns C18 bonded reverse-phase column using an external standard method. The derivatized N-acetylcysteine molecule has a retention time of congruent to 13 min at a flow rate of 1.0 mL/min for a mobile phase of methanol-aqueous 0.05 M citrate-0.001 M EDTA buffer pH 7.0 (30:70). In a multistep extraction procedure, which is slightly modified for the N-acetylcysteine assay in urine, the limits of sensitivity for the plasma and urine assays were found to be congruent to 60 ng/mL and congruent to 200 micrograms/mL, respectively. Preliminary data from pilot studies in human subjects are presented.

Acetylcysteine↗
PubMed1984

Determination of nitroglycerin and its dinitrate metabolites in human plasma by high-performance liquid chromatography with thermal energy analyzer detection.

A highly selective and sensitive high-performance liquid chromatographic assay employing a thermal energy analyzer as the detector for nitroglycerin and its dinitrate metabolites in human plasma has been developed. Prior to chromatography the method employs a simple one-stage extraction step. Nitroglycerin and its dinitrate metabolites are then chromatographed on a 10-micron nitrile bonded phase column using an internal-external standard method. The nitroglycerin and its 1,2,3-propanetriol-1,3- and -1,2-dinitrate metabolites (glyceryl-1,3- and -1,2-dinitrate) have a retention time of 8.5, 10.5, and 11.5 min, respectively at a flow rate of 2.0 mL/min for a mobile phase of 5% v/v acetone in n-hexane. The limits of sensitivity were 0.05 ng/mL for nitroglycerin and 0.25 ng/mL for the dinitrate metabolites. Linearity of response was observed over the 0.1-2.0-ng/mL range for nitroglycerin and 0.5-10.0-ng/mL range for the dinitrate metabolites. Blood level data from a pilot study with human volunteers in receipt of an oral form of nitroglycerin is presented.

Chemical Phenomena↗
PubMed1984

Dextromethorphan and codeine: comparison of plasma kinetics and antitussive effects.

Plasma kinetics of dextromethorphan (as dextrorphan ) and codeine were investigated after acute oral doses in 8 patients with pathological cough; after which the patients participated in an acute dose-response study of the antitussive effects of each drug administered as syrups. Maximum plasma codeine concentrations averaged 384 ng.ml-1 (s.d. +/- 78.3) occurring between 0.75 and 2h after ingestion of 60 mg codeine phosphate; in comparison mean peak plasma dextrorphan levels were 386 ng.ml-1 (s.d. +/- 107.2) and 388 ng.ml-1 (s.d. +/- 101.3) respectively, after administration of 60 mg dextromethorphan syrup and tablet formulations. Bioavailability of dextromethorphan tablets was comparable to syrup. No correlation emerged between instantaneous plasma concentrations of either dextrorphan or codeine and antitussive responses; however, peak antitussive effect was significantly related to log dose with both drugs. Antitussive effects of 30 mg codeine phosphate and 60 mg dextromethorphan hydrobromide did not differ significantly; both were superior to 30 mg dextromethorphan hydrobromide and placebo.

Administration, Oral↗