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Biomedical subjects

M C McKean

Publications and source records attributed to M C McKean.

12 recordsLinked to original sources
PubMed2005

Inhaled corticosteroids for non-specific chronic cough in children.

BACKGROUND: Cough in isolation of other clinical features is known as non-specific cough, which has been defined as non-productive cough in the absence of identifiable respiratory disease or any known aetiology. In children with non-specific cough the possibility of asthma being the underlying disorder is often raised (so called cough variant asthma). The proponents of cough variant asthma suggest a therapeutic trial of medications usually used to treat asthma. OBJECTIVES: To determine the efficacy of inhaled corticosteroids in non-specific cough in children over the age of two years. SEARCH STRATEGY: Searches were conducted on Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Searches were current as of March 2004. SELECTION CRITERIA: All randomised (randomised and quasi-randomised) controlled clinical trials in which an inhaled corticosteroid (beclomethasone (BDP), fluticasone (FP), triamcinalone (TAA) or any other corticosteroid) were given for cough in children over two years of age were included. Two review authors independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS: Data from trials was extracted by both review authors and entered into the Cochrane Collaboration software program RevMan Analyses 1.0.2. MAIN RESULTS: Two trials met the inclusion criteria (123 participants). One compared inhaled beclomethasone dipropionate (400 micrograms per day) with placebo and the other compared fluticasone propionate (2 mg per day for 3 days followed by 1 mg per day for 11 days) with placebo. Both studies used metered dose inhalers via a spacer. With the lower dose of inhaled corticosteroid there was no significant difference between the beclomethasone and placebo groups. With the higher dose there was a significant improvement in nocturnal cough frequency after two weeks in children presenting with persistent nocturnal cough. However, a significant but smaller improvement was also seen with placebo. AUTHORS' CONCLUSIONS: In one study beclomethasone dipropionate (400 micrograms per day) was no different from placebo in reducing the frequency of cough measured objectively or scored subjectively. There might be a small improvement with very high-dose inhaled corticosteroid but the clinical impact of this is unlikely to beneficial.

Adrenal Cortex Hormones↗
PubMed1998

Import rate of the E1beta subunit of human branched chain alpha-ketoacid dehydrogenase is a limiting factor in the amount of complex formed in the mitochondria.

Components of the mitochondrial branched chain alpha-ketoacid dehydrogenase multienzyme complex are all encoded by nuclear genes. The functional complex is formed with a known stoichiometric relationship of subunits, but how they enter the mitochondria and form the complex is not defined. Although cytosolic precursors for several of the proteins have been identified, the requirements for import and processing have not been described. Here we demonstrate the similar requirements for in vitro import and processing of the three catalytic subunits unique the this complex. Import was not affected by the amount of endogenous BCKD within the mitochondria. No cooperativity or competition among the subunits for import was found when subunits were used in combination. The relative rates of entry are E1alpha>E2>/=E1beta, making E1beta the limiting component supporting previously reported observations.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1996

Influence of subunit transcript and protein levels on formation of a mitochondrial multienzyme complex.

Constitutive expression of nuclear genes encoding mitochondrial proteins raises the question of whether these proteins are present in similar amounts in mitochondria of different tissues. We report that amounts of a single multienzyme complex can vary on a per mitochondrion basis depending on the number of mitochondria per cell. Human branched-chain alpha-keto acid dehydrogenase (BCKD) expression is used as a paradigm in these studies. Expression is compared and contrasted in HepG2 and DG75 cells in which mitochondrial content is twofold higher in the hepatocarcinoma line than in the lymphoblastoid line. Per cell, BCKD activity is equal in the two cells types, but BCKD protein concentration per mitochondrion is twofold higher in DG75 cells. Steady-state mRNA levels do not appear to be directly related to amounts of protein in the two cell lines. To test whether one subunit is limiting in formation of complex, overexpression of each BCKD subunit was elicited by plasmid transfection of the DG75 cells. Only overexpression of the beta-subunit of the decarboxylase component induced more BCKD activity without apparent increase in mRNA for the other endogenously expressed subunits. This implies that free BCKD subunits exist in a cell and can be recruited into an active complex when the limiting subunit becomes available.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1993

Thiamin-responsive maple syrup urine disease in a patient antigenically missing dihydrolipoamide acyltransferase.

Maple syrup urine disease results from inherited defects in human nuclear genes for branched chain alpha-ketoacid dehydrogenase, a mitochondrial multienzyme complex. Thiamin pyrophosphate is necessary for complex activity and a thiamin-responsive form of maple syrup urine disease is known. Here we demonstrate the use of [1-13C]leucine oxidation to [13C]O2 quantified in breath samples as a means of assessing whole body leucine oxidation. Analysis of cultured cells from this patient shows the antigenic lack of the E2 subunit, yet she gained branched chain alpha-ketoacid dehydrogenase activity in response to diet supplementation with pharmacologic doses of thiamin. These cultured cells were used to seek a molecular basis for the observed thiamin response. Despite normal thiamin transport in these cells, medium supplementation of up to 1000 thiamin/liter failed to increase complex activity or cause the antigenic appearance of the missing protein. This lack of response in cultured cells suggests that the observed whole body response to thiamin must be a tissue-specific effect in liver, muscle, or kidney. In addition, allele-specific detection of paternal and maternal mutations was used to genotype family members in this pedigree.

Acyltransferases↗
PubMed1992

Nucleotide sequence of the 5' end including the initiation codon of cDNA for the E1 alpha subunit of the human branched chain alpha-ketoacid dehydrogenase complex.

The 5' end including the start AUG codon has been defined for the human E1 alpha subunit of the branched chain alpha-ketoacid dehydrogenase complex by rapid amplification of cDNA ends. Considering conservative substitutions the amino acid sequence in the mitochondrial targeting sequence for the human clone is 73% identical to this sequence in rat and 84% identical to the bovine sequence. This peptide also shows similarity to the targeting sequence for the human beta subunit but not with targeting sequence for the other subunits of the complex.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1983

Subunit structure of electron transfer flavoprotein.

The electron transfer flavoprotein from pig liver mitochondria is a 57,000-dalton electron transferase which links several primary flavoprotein dehydrogenases with the mitochondrial electron transport system. The protein was previously reported to be a dimer of apparently identical subunits. There are conflicting estimates in the literature regarding the FAD content of the protein. The results presented here clearly show that the protein contains nonidentical subunits based on polyacrylamide gel electrophoresis in the presence of 8 M urea and sodium dodecyl sulfate. The molecular weights of the subunits are 31,000 and 27,000. Analysis of peptides generated by cleavage of the subunits with cyanogen bromide show that the subunits have different primary structures. This result and amino acid analyses of the protein and the purified subunits show that the heterogeneity cannot be due to proteolysis. Using an experimentally determined molar extinction coefficient for the protein-bound flavin, a minimum Mr = 55,000 was calculated, indicating that the protein contains 1 mol of FAD/mol of protein.

Amino Acids↗
PubMed1980

Properties of the general acyl-CoA dehydrogenase from pig liver.

The properties of the general acyl coenzyme A dehydrogenase from pig liver and the stable reduced dehydrogenase . product and oxidized dehydrogenase . acetoacetyl-CoA complexes of the dehydrogenase were investigated. The enzyme has a molecular weight of 178,000 to 183,000 determined by gel filtration chromatography and by gel electrophoresis at different acrylamide concentrations. The subunit molecular weight is 45,000 based on acrylamide gel electrophoresis in the presence of dodecyl sulfate which agrees with the minimum molecular weight calculated from the flavin:protein ratio and the amino acid analysis. The subunits are identical, or very similar, as judged by quantitative NH2-terminal analysis and mapping of tryptic peptides. Immunochemical analyses by the complement fixation technique show that the structure of the oxidized enzyme is different from the structure of enzyme . acyl-CoA complexes whether the flavin in these complexes is in the oxidized or reduced state. The amino acid analysis, isoelectric point, and a procedure for crystallizing the dehydrogenase are also reported.

Acyl-CoA Dehydrogenases↗