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Biomedical subjects

H Baum

Publications and source records attributed to H Baum.

At least 55 records · Page 3Linked to original sources

M2 mitochondrial antibodies and urinary rough mutant bacteria in patients with primary biliary cirrhosis and in patients with recurrent bacteriuria.

Primary biliary cirrhosis (PBC) patients have a higher incidence of recurrent urinary tract infection and an increased prevalence of rough forms (mutants) of E. coli in their stool samples than other chronic liver disease patients. PBC patients exhibit autoantibody reactivity against mitochondria, the most common antigen (M2) being a family of antigens with the major components having approximate molecular weights of 74, 56, 52 and 48 kD. Cross-reactivity between M2 antigen components and corresponding antigenic bands of bacteria has been demonstrated with PBC sera. Patients with recurrent urinary tract infections, all of whom had normal liver function and were taking prophylactic antibiotic treatment, had weak anti-mitochondrial antibody (AMA) reactivity (69%), with reactivity against the 74-kD antigen alone being the most common. When antibody to the 74-kD band was eluted, it was found to cross-react with bacterial membrane fractions. In the controls, 12/77 chronic liver disease patients and 2/24 normals possessed AMA. Rough forms of bacteria were found in the urine of patients with significant bacteriuria: 39% PBC, 5.3% chronic liver disease and 41% of the recurrent urinary tract infection group. M2 antibodies may be induced by urinary organisms in 'normal' women with recurrent bacteriuria and in females with PBC.

Autoantibodies↗

Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin.

Plasma coenzyme Q (CoQ) was measured in 20 hyperlipidaemic patients treated with diet and simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase); 22 hyperlipidaemic patients treated with diet with alone; and 20 normal controls. Patients treated with simvastatin had a significantly lower plasma CoQ and CoQ: cholesterol ratio than either patients receiving diet alone or normal controls. Use of simvastatin was inversely and independently correlated with both CoQ (p < 0.0001) and CoQ: cholesterol ratio (p < 0.01). There was a significant inverse association between CoQ and dose of simvastatin (p < 0.001). It is concluded that simvastatin may lower the plasma CoQ concentration and this may be greater than the reduction in cholesterol. The possible adverse effect of simvastatin on the metabolism of CoQ may be clinically important and requires further study.

Adult↗

Demonstration of peptide-specific and cross-reactive epitopes in proteins reacting with antimitochondrial antibodies of primary biliary cirrhosis.

Recently the main targets of antimitochondrial antibodies (AMA) of primary biliary cirrhosis have been identified as parts of three related mitochondrial multienzyme complexes, namely pyruvate dehydrogenase (PDH), branched chain alpha-ketoacid dehydrogenase (BKDH) and alpha-ketoglutarate dehydrogenase (alpha-KGDH). Usually AMA-positive PBC serum samples show reactivity to more than one of these, raising the question whether they are exclusively different antibodies or are, at least in part, the result of cross-reactive specificities. With Western immunoblotting, four antigens with molecular masses of 74, 52, 51 and 43 kDa, are recognized by PBC sera. In this study, using affinity purified antibodies from mitochondrial proteins immobilized on nitrocellulose blots, we demonstrate the presence of peptide-specific and cross-reactive epitopes in some targets. In particular, at least three different epitopes present in the 74-kDa protein (presumed to by PDH-E2) are also present in the 51-kDa protein (probably PDH-X), and two in the 52-kDa peptide (possibly BCKDH-E2). Moreover, the 43-kDa mitochondrial protein (the identity of which is more problematic) has three epitopes. One of these is also present in the 74-, 52- and 51-kDa proteins, a second in the 74- and 51-kDa, and a third seems to be peptide-specific. These results show that different sera with the same immunoblotting pattern of reactivity can have antibodies with different antigenic specificities and, conversely, that the same specificity can be responsible for more than one band.

Adult↗

Serum catalase as the protective agent against inactivation of alpha 1-proteinase inhibitor by hydrogen peroxide; comparison between normal and rheumatoid sera.

Human serum contains catalase activity, which can protect alpha 1-proteinase inhibitor from inactivation by H2O2. The primary source of serum catalase is probably erythrocytic. The enzyme activity correlates with haemoglobin concentration in sera from control subjects but not in sera from patients with rheumatoid arthritis. Catalase is inactivated by oxidants, such as H2O2 and hypochlorous acid and it is suggested that the decrease in catalase/haemoglobin ratio observed in rheumatoid serum is due to oxidant stress associated with inflammation.

Arthritis, Rheumatoid↗

Purification and characterisation of bovine spleen ADPase.

ADPase has been purified from bovine spleen. Electrophoresis revealed a minor contaminent in the preparation that may represent ADPase that has been decreased in size by limited proteolysis during extraction and purification. The native enzyme behaves on SDS/PAGE as a 100-kDa protein but ADPase is a glycoprotein and so its electrophoretic behaviour may be anomalous. The apparent molecular mass is decreased to 70 kDa after removal of carbohydrate by treatment with a glycosidase. The use of a cross-linking reagent followed by electrophoresis suggests that the enzyme is composed of a single subunit. The specific activity of the purified material was 115 U/mg protein. The enzyme catalyses the hydrolysis of nucleoside di- and tri-phosphates but nucleoside monophosphates are not acted upon. The Km for ADP (approx. 10-15 microM) is unaffected by the state of purification of the enzyme, but catalytic activity of the purified material is stimulated by inclusion of detergent in the assay system and by calcium ions. Maximum activity is seen at pH 8.0-8.5 with ADP as substrate but the optimum shifts to 7.5-8.0 for ATP hydrolysis.

Adenosine Triphosphatases↗

Enhanced adhesion of polymorphonuclear leukocytes to anoxic cultured vascular endothelium.

This study showed that the adherence of human polymorphonuclear leukocytes (PMN) to monolayer cultures of human umbilical vein endothelial cells (HUVEC) was increased when the latter were rendered anoxic. This adhesion was greater after 4-5 h than after 8 h of anoxia, but even at 8 h was significantly above the level of adhesion to HUVEC maintained under normoxic conditions for the same period. The changes in adhesion were not dependent on the viability of HUVEC during anoxia. Anoxia-induced adhesion was prevented by addition of cycloheximide (5 micrograms/ml) to the cultures, suggesting that it depended on HUVEC protein synthesis. Enhanced adhesion was also prevented by addition of a monoclonal antibody directed against the cytokine, interleukin-1 alpha (IL-1 alpha). These findings are consistent with a role of endogenous IL-1 alpha as a mediator of the anoxia-induced adhesion of PMN to HUVEC.

Antibodies, Monoclonal↗

The susceptibility of elastin-fatty acid complexes to elastolytic enzymes.

Elastin in vivo is likely to be complexed with amphipathic ligands such as lipids. The susceptibility of stable [3H] elastin-fatty acid complexes to the action of porcine pancreatic elastase (PPE) and to human neutrophil lysates over time was assessed. Elastolysis by PPE of substrates prepared with oleic or linoleic acids was initially higher (for up to 2 hours) than that of uncomplexed elastin. Stearic acid and elaidic acid (the trans isomer of oleic acid) did not enhance the elastolytic rate above control. The stimulatory effect of oleic and linoleic acids appeared to derive from increased adsorption of PPE onto elastin; the loss of stimulatory activity over time occurred in parallel with a progressive decrease in adsorption. All fatty acids tested inhibited elastolysis by neutrophil lysates, the effect being particularly marked with oleic and elaidic acids. These results indicate that 1). Complexed fatty acids can modulate the rate of elastin breakdown by elastases; 2). The effects observed with PPE are due to differences in adsorption of enzyme onto substrate, possibly as a result of steric considerations; 3). Since elastolysis by neutrophil lysates is inhibited by all fatty acids, the properties of different elastolytic enzymes should be considered in in vitro model systems of connective tissue breakdown.

Adsorption↗

Allergic contact dermatitis from diphenylthiourea in Vulkan heat retainers.

11 cases of contact dermatitis from Vulkan heat retainers are reported. The skin eruptions started on days 1-11 after the 1st day of exposure. The clinical picture varied from eczema through urticaria to purpura. In some cases, the symptoms were severe. Patch testing was performed in 10 individuals and all reacted positively to the heat retainer and/or the rubber glue used in the heat retainer. A series of rubber chemicals was patch tested in 7 patients and all showed positive reactions to diphenylthiourea (DPTU), and all but one to ethylene thiourea (ETU). TLC examination revealed a spot with the same RF-value as DPTU in extracts of the adhesive, but no spot corresponding to ETU. There were no indications of impurities in the test preparations of DPTU and ETU. By HPLC, the content of DPTU in the adhesive was determined as 0.6% w/w.

Adhesives↗

Treatment of Wilms' tumor. Results of the Third National Wilms' Tumor Study.

The Third National Wilms' Tumor Study sought to reduce treatment for low-risk patients and find better chemotherapy for those at high risk for relapse. Eligible patients (1439) were randomized according to stage (I-IV) and histology (favorable [FH] or unfavorable [UH]), and contributed data to survival and relapse-free survival (RFS) analyses. Four-year (postnephrectomy) survival percentages and randomized treatment regimens for low-risk patients were 96.5% for 607 Stage I/FH patients who received dactinomycin (Actinomycin D [AMD], Merck Sharp & Dohme, West Point, PA) and vincristine (VCR) for 10 weeks versus 6 months; 92.2% for 278 Stage II/FH patients; and 86.9% for 275 Stage III/FH patients who received AMD + VCR +/- Adriamycin (ADR, Adria Laboratories, Columbus, OH) for 15 months. Stage II/FH patients also had either zero or 2000 cGy irradiation (RT) postoperatively and Stage III/FH patients either 1000 or 2000 cGy. Four-year survival was 73.0% for 279 high-risk patients (any Stage IV, all UH) who received postoperative radiation therapy (RT) and AMD + VCR + ADR +/- cyclophosphamide (CPM). Statistical analysis of survival and RFS experience shows that the less intensive therapy does not worsen results for low-risk patients and CPM does not benefit those at high risk.

Adolescent↗

Iron release from haemosiderin and ferritin by therapeutic and physiological chelators.

Iron release from both human and horse spleen haemosiderin to desferrioxamine was substantially less than that released from ferritin samples. This finding contradicts a previous report [Kontoghiorges, Chambers & Hoffbrand (1987) Biochem. J. 241, 87-92]. Differences in phosphate content of cores and in core size between haemosiderin and ferritin did not account for the different iron-release rates. Iron released to acetate was found to stimulate lipid peroxidation in liposomes, whereas that released to stronger chelators such as citrate and desferal did not. Absorption spectra and gel-filtration studies suggest that the acetate-solubilized iron was in the form of low-molecular-mass (less than 5 kDa) ferrihydrite fragments.

Acetates↗

Antimitochondrial antibodies in primary biliary cirrhosis recognize both specific peptides and shared epitopes of the M2 family of antigens.

Sera from patients with primary biliary cirrhosis exhibit variable autoantibody reactivity against mitochondria, the commonest antigen (designated M2) including three structures of approximate M.W. 70, 50 and 40 kD. The nature of these antigens has only recently been established; the 70 and 50 kD are the transacetylase E2 and component X, respectively, of the pyruvate dehydrogenase complex and are distinct polypeptides. We have demonstrated, by immunoblotting, elution and rebinding of antibodies, unequivocal cross-reactivity between the major bands of the M2 antigen. In addition, cross-reactivity has been shown between antibodies binding to each of the three M2 bands of mitochondria and two major antigenic bands of both Gram-negative and Gram-positive bacteria. Conversely, antibodies eluted from these two bands of Escherichia coli were found to bind all three M2 bands of mitochondria. These results suggest that the antibodies of primary biliary cirrhosis contain both peptide-specific and cross-reacting antibodies, the latter recognizing a common "M2 epitope" that might include nonprotein components of the peptides. However, direct and competitive enzyme-linked immunosorbent assays failed to implicate the coenzyme of the pyruvate dehydrogenase complex, lipoic acid or its amide, as the common antigenic moiety.

Autoantibodies↗

Retained intraspinal bullet--an illustrative case report.

In a 35 year old male who had suffered a gunshot injury one bullet remained in the spine at level C 5. Clinically, a complete high tetraplegia was found. Already during the first months after trauma the patient complained of dysaesthesia and hyperaesthesia in the segments at, and above, the lesion. Five years later, when the authors saw the patient, he reported on an increase of intensity of this pain since some months. This gave occasion to radiological investigations to rule out morphological changes as the origin of the increase in pain. CT showed a compact bullet exactly intraspinal, with a syringiform cyst projecting into the myelon. Since former CT scans did not exist, an objective statement on progress could not be given. However, it is suspected that chronic inflammation caused by metal breakdown products of the bullet may have contributed to the increasing pain. It is pointed out that it is necessary to take account the kind of metal when deciding for or against the removal of a foreign body.

Adult↗