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Biomedical subjects

H Baum

Publications and source records attributed to H Baum.

At least 91 records · Page 5Linked to original sources

Haemosiderin-like properties of free-radical-modified ferritin.

Conjugated-Schiff's-base-type fluorescence was measured in iron-depleted samples and chloroform extracts of human spleen haemosiderin. Incubation of ferritin with liposomes and ascorbate led to the formation of compounds with similar fluorescence properties. Analysis of protein subunits by SDS/polyacrylamide-gel electrophoresis confirmed that ferritin was damaged in incubations with ascorbate. Since previous studies have shown that intact ferritin is resistant to proteolytic degradation, it is suggested that haemosiderin may be a product of oxidative reactions involving ferritin and lipid.

Electrophoresis, Polyacrylamide Gel↗

Demonstration of plasma-membrane adenosine diphosphatase activity in rat lung.

The adenosine diphosphatase (ADPase) activity of rat lung has been investigated. Subcellular fractionation of lung tissue homogenates by sucrose density gradient centrifugation has shown the ADPase activity to be associated with the plasma membrane. ADPase was solubilised from the membranes and fractionated by ammonium sulphate precipitation to separate a specific, low-Km ADPase from non-specific alkaline phosphatase activity. The solubilised ADPase has a Km of 50 microM at pH 7.5 and appears to be distinct from ATPase.

Adenosine Diphosphate↗

Formation of hydroxyl radicals in the presence of ferritin and haemosiderin. Is haemosiderin formation a biological protective mechanism?

Horse spleen and human spleen ferritins increase the formation of hydroxyl radicals (OH) at both pH 4.5 and pH 7.4 in reaction mixtures containing ascorbic acid and H2O2. The generation of OH is inhibited by the chelator desferrioxamine. Human spleen haemosiderin also accelerates OH generation in identical reaction mixtures, but is far less effective (on a unit iron basis) than ferritin under all reaction conditions. It is proposed that conversion of ferritin into haemosiderin in iron overload is biologically advantageous in that it decreases the ability of iron to promote oxygen-radical reactions.

Animals↗

Discrimination between M2 and M4 antimitochondrial antibodies in primary biliary cirrhosis.

10 sera were studied from patients with primary biliary cirrhosis (PBC), that were anomalous in their reactivity against mitochondrial antigens as detected by Western blotting. They had low reactivity against the major, M2 reactive antigen (Mr for beef heart mitochondria, 74 Kd) but reacted against an antigen of Mr 52 Kd (species independent) which was apparently inaccessible in submitochondrial particles (SMP) on ELISA and which was not present in chloroform-released ATPase preparations. In all respects this differed from the characteristics of the M2 antigens and it is concluded that these sera are detecting predominantly the M4-reactive antigen.

Animals↗

Carpal tunnel syndrome and acromegaly.

50 patients with acromegaly and carpal tunnel syndrome have been examined electrophysiologically before and after transnasal operation of the pituitary adenoma. 32 of the 50 patients (64%) had symptoms of carpal tunnel syndrome. 13 of them had neurological deficits. 28 of the examined patients had pathological neurographical findings only. About 1 week post-operatively DL was decreased in 43%; in 10 out of 13 patients with neurological deficits DL decreased. GH was normalized in 80% and reduced to 5-10 micrograms/l in a further 10%. The investigation did not show whether the carpal tunnel syndrome only depended on a GH increase or on other factors also such as e.g., on the duration of symptoms or tissue changes. None of the patients had the transversal carpal ligament operated on. The coincidence between acromegaly and carpal tunnel syndrome was 64%. In 3 cases the carpal tunnel syndrome was the leading sign to the diagnosis of acromegaly.

Acromegaly↗

Tissue-specific and constitutive alpha-tubulin genes of Drosophila melanogaster code for structurally distinct proteins.

We have determined the nucleotide sequences of all four Drosophila alpha-tubulin genes (alpha 1, alpha 2, alpha 3, and alpha 4). Two of the genes, alpha 1 and alpha 3, are constitutively expressed and code for proteins that are very similar to previously sequenced alpha-tubulins. They differ from each other by only two amino acid substitutions. These two genes also have blocks of homology between the noncoding leader regions of their transcription units. In contrast to these constitutive genes, the tissue-specific alpha 2 and alpha 4 genes code for tubulins with different structures. The alpha 2 mRNA is male-specific in adults and codes for a tubulin that differs from alpha 1 at 21 of the 450 residues. Six nonconservative substitutions are clustered within the 14 carboxyl-terminal amino acids, a region implicated in the regulation of microtubule assembly. The alpha 4 mRNA is maternal and is found only in ovarian nurse cells, eggs, and early embryos. It codes for the most highly divergent alpha-tubulin yet reported and differs from alpha 1 at 149 positions.

Amino Acid Sequence↗

Chemiosmotic coupling in cytochrome oxidase. Possible protonmotive O loop and O cycle mechanisms.

Using the principle of specific vectorial ligand conduction, we outline directly coupled protonmotive O loop and O cycle mechanisms of cytochrome oxidase action that are analogous to protonmotive Q loop and Q cycle mechanisms of QH2 dehydrogenase action. We discuss these directly coupled mechanisms in the light of available experimental knowledge, and suggest that they may stimulate useful new research initiatives designed to elucidate the osmochemistry of protonmotive oxygen reduction in cytochrome oxidase.

Biological Transport↗

The role of iron in ferritin- and haemosiderin-mediated lipid peroxidation in liposomes.

Ferritin and haemosiderin were shown, by the measurement of malondialdehyde production and loss of polyunsaturated fatty acids, to stimulate lipid peroxidation in liposomes. At pH 7.4 ascorbate was additionally required to achieve peroxidation; however, peroxidation occurred at pH 4.5 in the presence of iron-proteins alone. The damage was completely inhibited by the incorporation of chain-breaking antioxidants (alpha-tocopherol and butylated hydroxytoluene) into the liposomes. Metal chelators (desferrioxamine and EDTA) also completely inhibited lipid peroxidation. These and further results indicate that, at pH 4.5, even in the absence of a reducing agent, iron is released from haemosiderin and can mediate oxidative damage to a lipid membrane.

Deferoxamine↗

Studies on the nature of adenosine diphosphatase activity from rat liver mitochondria.

Adenosine diphosphatase (ADPase) activity was studied in rat liver with [beta-32P]ADP as a substrate. Mitochondria and outer mitochondrial membrane fractions were isolated and assayed for ADPase and various marker enzymes. ADPase activity was strikingly reduced when the outer membranes were removed from the mitochondria whether by digitonin treatment or osmotic shock. Addition of the inter-membrane space subfraction to the purified outer membranes resulted in enhanced ADPase activity. Addition of the inter-mitochondrial membrane enzyme adenylate kinase to outer membranes also produced a large stimulation of activity. The ADPase activity could also be reconstituted in vitro with adenylate kinase and either mitoplast ATPase or ouabain-sensitive (Na+ + K+ + Mg2+)-ATPase. Chloroform-released ATPase, however, was not capable of producing an ADPase activity when combined with adenylate kinase. Gel permeation chromatography of Triton-solubilised outer mitochondrial membranes was unable to resolve ADPase activity from contaminating ATPase. These results suggest that the majority of ADPase activity in rat liver mitochondria consists of the coupled activity of adenylate kinase and ATPase.

Adenosine Triphosphatases↗

Comparison of effects of inhibitors on adenosine triphosphatase and adenosine diphosphatase activities in rat-liver mitochondria.

Adenosine diphosphatase (ADPase) activity and ATPase activity were assayed in rat liver mitochondria and outer mitochondrial membrane preparations with [beta-32P]ADP and [gamma-32P]ATP as substrates. Inhibition studies were performed with the mitochondrial ATPase inhibitor oligomycin and the adenine nucleotide transport inhibitor, carboxyatractyloside. Kinetic studies were also performed with the nucleotide thiophosphate analogs adenosine 5'-O-thiophosphate, adenosine 5'-O-(2-thiodiphosphate) and adenosine 5'-O-(3-thiotriphosphate) which can act as inhibitors of phosphohydrolases. It is concluded that part of the apparent ADPase activity of intact mitochondria is mediated via ATPase, presumably in conjunction with adenylate kinase. In addition the outer mitochondrial membrane appears to show a distinct ADPase not attributable to contamination by inner membrane ATPase.

Adenosine Diphosphate↗

Correlation of oligomycin-sensitive ATPase activity in trypanosomes with their content of an antigen to primary biliary cirrhosis.

The amounts of an antigen to primary biliary cirrhosis (PBC) which occur in subcellular fractions of Trypanosoma rhodesiense and T. lewisi correlate positively with the oligomycin-sensitive (OS) ATPase activity of these fractions. This result is consistent with the mitochondrial ATPase association of the antigen in mammalian and other cells. Higher levels of OS-ATPase and of PBC antigen in T. lewisi accord with a more extensive mitochondrial development in this species.

Adenosine Triphosphatases↗

26-hydroxycholesterol: regulation of hydroxymethylglutaryl-CoA reductase activity in Chinese hamster ovary cell culture.

The effect of 26-hydroxycholesterol and other intermediates in bile acid synthesis on HMG-CoA reductase activity was studied in Chinese hamster ovary (CHO) cell culture. Incubation of CHO cells for 5 hr in 0.25 microM 26-hydroxycholesterol caused a 40% inhibition of HMG-CoA reductase activity. All other intermediates tested including 3 beta-hydroxy-5-cholenoic acid and cholest-5-ene-3 beta,7 alpha,26-triol, oxidation products of 26-hydroxycholesterol, had little or no inhibitory effect. It is proposed that 26-hydroxycholesterol has a selective biological role in the regulation of cholesterol synthesis.

Animals↗

Antimitochondrial antibodies (AMA) in primary biliary cirrhosis. I. Separation of the PBC antigen activity from mitochondrial ATPase activity.

Antimitochondrial antibodies are found in a variety of autoimmune liver diseases, particularly primary biliary cirrhosis. The antigen against which these antibodies are directed is localized on the inner mitochondrial membrane. Earlier work suggested that this antigen was associated with the mitochondrial ATPase. However, we have succeeded in separating the enzyme activity from the antigenic activity using gel filtration and ion-exchange chromatography. Furthermore, the antigenic activity is not affected by modulators of ATPase enzymatic activity like aurovertin or oligomycin. The antigenic activity is, however, very susceptible to reagents which block thiol groups. The mitochondrial antigen, in contrast to the ATPase enzyme, is found in high amounts in brown fat mitochondria. Identification of this antigen may help to explain why specific antimitochondrial antibodies arise in the sera of patients with primary biliary cirrhosis.

Adenosine Triphosphatases↗