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Biomedical subjects

C Steffen

Publications and source records attributed to C Steffen.

At least 37 records · Page 2Linked to original sources

Varicose vein surgery: patient satisfaction.

Surgery for varicose veins is a common surgical procedure performed for various indications including cosmesis. Patient satisfaction with the eventual outcome is therefore important. A total of 311 patients (68%), who underwent varicose vein surgery during a 10-year period, replied to a postal survey of 456 patients [National Health Service (NHS) 327: private patients (PP) 129]. Of those 311, 19% of the NHS patients compared with 34% of the PP were completely satisfied with the surgery, the communication and had had no post-operative complications (P < 0.01). Twenty-six per cent of the NHS patients were very dissatisfied with their treatment compared with 13% of the PP (P < 0.025). The majority of dissatisfied patients were female (P < 0.005). These results suggest that while varicose vein surgery is regarded as a safe and often minor procedure, it is associated with a significant surgical morbidity and patient dissatisfaction. Patients should be made aware of the potential outcome prior to surgery.

Female↗

Characterization of myocardial protein composition in dilated cardiomyopathy by two-dimensional gel electrophoresis.

In order to identify alterations in the myocardial protein pattern that characterize dilated cardiomyopathy (DCM), we compared, by two-dimensional gel electrophoresis, right atrial protein patterns from five patients with DCM and four with normal left ventricular function (two gels per patient). Using computer assisted analysis (PDQUEST, 4.1) we found reproducible protein patterns in the 18 gels (23 x 30 cm, pH 4-9, molecular weight 10-150 kDa). In the two gels from the same patient, 91% of proteins were identical in their position in the pattern and the relative intensities of these protein species correlated with r = 0.85. Three hundred and two +/- 50 protein species were found in several gels, 186 in all 18 gels. Seven proteins in the DCM group were decreased in their relative intensity by > 100%, six were increased by > 100%. Significant quantitative differences between DCM and control patients were found for 25 protein species. Based on seven external marker proteins, a pH and molecular weight value could be calculated for each protein. So far, 30 protein species have been identified by antibodies, amino acid analysis or sequencing procedures. From the 25 proteins that are significantly different between DCM and controls, three have been identified. Expression of the mitochondrial creatine kinase and alpha cristallin B chain was significantly increased in DCM; the malate dehydrogenase family was also significantly decreased in DCM. Two-dimensional electrophoresis appears to be a powerful method for the detection of disease-associated alterations in the myocardial protein pattern.

Adult↗

Myocardial cyclic AMP and norepinephrine content in human heart failure.

Impaired production of myocardial cyclic adenosine monophosphate (cAMP) is thought to contribute to contractile dysfunction in end stage heart failure, but myocardial cAMP content has not yet been evaluated in heart failure patients in comparison with controls. We therefore measured the myocardial content of cAMP by radioimmunoassay in endomyocardial biopsies from patients in different stages of heart failure and in controls and correlated it with biochemical and functional parameters. The myocardial content of norepinephrine was determined by HPLC in the same biopsies in order to assess if the myocardium studied was affected by heart failure. Myocardial cAMP (in fmol.microgram-1 non-collagen protein) in 20 patients with heart failure (LVEF: 27 +/- 8%, cAMP: 5.8 +/- 2.0) was unchanged in comparison with eight controls (LVEF: 64 +/- 4.7%, cAMP, 4.9 +/- 2.1). In contrast, myocardial norepinephrine (in pg.microgram-1 non-collagen protein) in the same biopsies was significantly reduced in heart failure (4.0 +/- 3.0) in comparison with the same controls (11.5 +/- 3.0, P < 0.0002). Plasma cAMP in 20 heart failure patients (22.0 +/- 4.2 pmol.l-1) was not different from controls(22.0 +/- 7.8), whereas plasma norepinephrine was increased (heart failure: 460 +/- 257 pg.ml-1, controls 182 +/- 49, P < 0.001). Myocardial cAMP levels are indistinguishable from controls in human heart failure and therefore do not contribute to a further characterization of the cardiac adrenergic system in these patients. This is most likely due to the impossibility of obtaining biopsies with truly unstimulated adenylyl cyclase activity.

Adult↗

Chlorate poisoning: mechanism of toxicity.

Intoxications with chlorate salts are characterized by methaemoglobin formation, haemolysis and renal insufficiency. The toxic effects on the erythrocyte can be reproduced in vitro. Incubation of human and rabbit erythrocytes with chlorates induces a concentration-dependent oxidation of haemoglobin. This methaemoglobin formation is followed by denaturation of the globin, a cross-linking of erythrocyte membrane proteins and an inactivation of membrane enzymes. The high sensitivity of glucose-6-phosphate dehydrogenase to denaturation by chlorate explains the inefficacy of methylene blue to reduce methaemoglobin formed, as the antidotal effect of methylene blue depends on NADPH formed mainly by the oxidation of glucose-6-phosphate. The observed changes occur only in the presence of methaemoglobin which forms a destabilising complex with chlorate. Methaemoglobin thus autocatalytically increases methaemoglobin formation and destruction of the erythrocyte. As the rabbit is known to have a high methaemoglobin-reduction capacity, human and rabbit erythrocytes were compared. In vitro, the rabbit erythrocyte is less sensitive to oxidative attack than the human red cell. In vivo, an oral dose of sodium chlorate (1 g/kg body wt.) resulted in high serum (16 +/- 4 mM) and urine concentrations (246 +/- 99 mM) in the rabbit. Methaemoglobin was not formed nor could a nephrotoxic effect be observed. These experiments also indicate that the nephrotoxicity of chlorate is mediated by methaemoglobin catalysis.

Adenosine Triphosphate↗

Mantleoma. A benign neoplasm with mantle differentiation.

Four cases of neoplasms with mantle differentiation are presented. The mantle (sebaceous mantle) is a well-described but little known part of the sebaceous gland cycle. In the resting phase of that cycle, the mantle is seen as cords of undifferentiated cells that emanate from the infundibulum of a hair follicle and droop down aside the follicle in the form of a mantle or skirt. Cyclically, vacuolated sebocytes appear at the terminus of these cords, singly, then in groups, and finally as fully developed sebaceous lobules and glands. Presumably, sebaceous glands involute to become undifferentiated mantles. Clinically, neoplasms with mantle distribution occur on the face. Three of our cases were found fortuitously in sections of tissue removed because of basal-cell carcinoma. One was thought by the clinician to be a basal-cell carcinoma. Histopathologically, mantleomas vary in complexity. Presumably early neoplasms consist only of cords and columns of undifferentiated epithelial cells that radiate from an infundibulum. Later on, these cords interweave in a retiform pattern that contains sebocytes of varying degrees of vacuolization and sebaceous ductal structures. Mantleomas are benign because none in our series recurred after surgical removal and no atypical neoplastic cells were seen histopathologically.

Epithelium↗

Actinic granuloma of the conjunctiva.

Few cases of actinic granuloma of the conjunctiva have been reported. A 39-year-old woman developed a pinguecula. A biopsy study revealed actinic granuloma histopathologically. This case is an example of the interface between dermatology and other fields, and helps to confirm the existence of actinic granuloma of the skin as a distinct entity.

Adult↗

Effect of orotic acid on the generation of reactive oxygen and on lipid peroxidation in rat liver.

The pyrimidine precursor orotic acid (OA) is a constituent of dairy products and therapeutic drugs. Several recent publications point towards a tumor promoting activity of OA in rat liver. An increased production of reactive oxygen has been discussed as a possible mechanism, leading to lipid peroxidation and DNA single strand breaks. In view of contradictory results, this postulated prooxidative action of OA was reexamined with new experimental techniques. Weanling Sprague-Dawley rats were fed 1% OA in different diets for 4-35 days. The NADPH-mediated lipid peroxidation in liver homogenate and microsomes was determined in vitro by analysis of low-level chemiluminescence (CL) and the strongly correlated formation of malondialdehyde (MDA). In no case did treatment with OA result in an increase of lipid peroxidation in vitro nor did such treatment enhance the generation of reactive oxygen as measured by lucigenin CL. In accordance, the total cytochrome P-450 content as well as the activity of individual P-450 isoenzymes were unchanged. Treatment with OA did not elevate the MDA content of fresh liver homogenate when butylated hydroxytoluene (BHT) was present in the test system. However, when the antioxidant was omitted, increased levels of thiobarbituric acid reactive material were found which correlated with the triglyceride content. This could explain some published data that have been taken as indication for a prooxidative action of OA. Evidence against an increased lipid peroxidation in vivo is given by the analysis of ethane exhalation. Furthermore, no increase in DNA single strand breaks by OA treatment could be observed by the alkaline elution technique. These results do not support the hypothesis of a prooxidative activity of OA. The observed reversible decrease of the GSH/GSSG ratio is assumed to result from the reduced size of the phosphopyridine nucleotide pool due to purine deficiency and an increased consumption of NADPH by the enhanced reductive degradation of pyrimidines.

Administration, Oral↗

Short-term effect of whole milk and milk fermented by Pseudomonas fluorescens on plasma lipids in adult boars.

The short-term effects of whole milk and milk fermented by Pseudomonas fluorescens, of the amino acid composition of the diet and of feeding frequency on the level of plasma lipids, were investigated in six 1-year-old adult boars. The experimental diets contained equal amounts of protein, carbohydrates, fat and cholesterol. After an adaptation period of 5 d for each experimental treatment, blood was collected at regular intervals during 48 h and plasma levels of cholesterol, triacylglycerol, high-density-lipoprotein (HDL)-cholesterol and low-density-lipoprotein (LDL)-cholesterol were examined. All variables except HDL-cholesterol showed distinct diurnal fluctuations, which were substantially influenced by feeding frequency. Variations in the amino acid composition of the experimental diets, which were within a physiological range, had no effect on the level of plasma lipids. Plasma lipid levels were significantly lower when the animals received the diets containing milk instead of the diet without milk: cholesterol, triacylglycerol, and LDL-cholesterol were reduced by 5.6, 5.8 and 10% respectively (pondered means) while HDL-cholesterol remained unaffected. Fermentation of whole milk by P. fluorescens reduced the lipid-lowering effect. Our findings suggest that the intake of diets containing milk results in a lower plasma cholesterol and LDL-cholesterol level than the intake of diets with a similar nutrient content which do not contain milk.

Amino Acids↗

N-acetyl-L-aspartate is a major source of acetyl groups for lipid synthesis during rat brain development.

The function of N-acetyl-L-aspartate (NAA), a predominant substance in the CNS, has not yet been determined. To investigate the possible function of NAA as a lipid precursor [14C]-N-acetyl-L-aspartate (NAA) or [14C]-acetate (AcA) was injected intracerebrally into 8, 15- and 22-day-old rats. These time points were selected because NAA concentration and the activity of the NAA synthetizing enzyme L-aspartate-N-acetyltransferase (ANAT) were low in 8-day-old rats, intermediate in 15-day-old rats and high in 22-day-old rats. During an incubation period of 4 h the radioactive acetyl group of NAA is incorporated into the lipid fraction in amounts of 42.9 to 65.7% of recovered total radioactivity, increasing with the age of the rats. In contrast, radioactivity incorporated from AcA is constant for all three ages. With NAA as precursor only 7.2-9.4% of the recovered total radioactivity is incorporated into the protein fraction. With AcA as precursor 27.0-18.1% of recovered radioactivity is incorporated into the protein fraction, the amounts decreasing with age. Taking into account that in vivo NAA concentration in the brain is much higher than the AcA concentration, NAA is clearly the more efficient precursor for lipid synthesis than AcA. Further, we compared NAA and AcA as lipid precursors by analyzing the radioactivity in single lipid fractions, expressed as normalized specific incorporation or normalized incorporation. The measured differences between NAA and AcA in normalized specific and normalized incorporation of acetyl groups imply that NAA is not simply degraded to AcA before incorporated into lipids. We conclude that NAA is a major source of acetyl groups for lipid synthesis during rat brain development.

Acetyltransferases↗

Nucleotide sequence analysis and expression studies of a chloramphenicol-acetyltransferase-coding gene from Clostridium perfringens.

The nucleotide sequence of a CmR determinant, located on the Clostridium perfringens plasmid pIP401, was determined and its gene product was identified as chloramphenicol acetyltransferase (CAT). The cat structural gene is preceded by transcription-initiation signals characteristic for Escherichia coli sigma 70 or Bacillus subtilis sigma 43 promoters. By promoter probing in the heterologous hosts the direction of transcription of the clostridial cat gene was analysed and the cat mRNA start point was determined in vitro using the RNA polymerases of E. coli and B. subtilis. Comparison of the amino acid sequences of C. perfringens CAT and other CAT proteins of Gram-positive and Gram-negative origin shows a remarkable degree of homology between the various enzymes.

Amino Acid Sequence↗

Induction of anti-pepsin antibodies after immunization with pepsin-extracted collagen.

Immunization with pepsin-extracted human type II collagen purified by different precipitation steps, although not showing any contamination with the enzyme on SDS-polyacrylamide gel electrophoresis, resulted in the generation of antibodies to the enzyme in addition to an immune response to collagen. These antibodies could be removed by immune absorption on a pepsin affinity column, leaving reactivity to type II collagen unaltered. High performance liquid chromatography on hydroxylapatite columns indicated that pepsin remained associated with the collagen molecules even after repeated precipitation and coeluted with a fraction of the collagen preparation. These results demonstrate that pepsin-extracted collagens may contain minimal amounts of the enzyme. On immunization, these impurities may induce the formation of unwanted antibodies, which might simulate a false specificity of the antibody preparation.

Antibodies↗

Autoimmunity and T-cell subpopulations in old age.

To investigate the interrelationship between T-cell-dependent immune functions and autoimmune phenomena in old age we determined T-cell subpopulations in 20 aged healthy individuals (80-96 years old) using monoclonal antibodies. These persons were also investigated as to humoral parameters such as antinuclear antibodies, rheumatoid factors (IgG-, IgA-, IgM-RF), antibodies to collagen types I-IV as well as autoantibodies to organ-specific antigens. In addition, immune complexes were determined. We found that aged individuals have an increased frequency of autoantibodies as compared to a young control population, each aged subject presenting with at least one autoantibody species. Immune complexes, however, were only rarely detected. Three individuals showed a slightly increased T-helper/T-suppressor cell ratio, four had a decreased ratio. An increased number of T-suppressor cells was significantly correlated with a lowered incidence of anticollagen antibodies. Other parameters tested by us: fibronectin, laminin, procollagen type III, C3 and C4 complement components, immunoglobulins and acid alpha 1-glycoprotein. Aged individuals have significantly higher serum levels of fibronectin, while laminin and procollagen concentrations are in the normal range. A large percentage of old individuals had increased serum levels of C3 and/or C4. The acute phase protein orosomucoid, however, was in the normal range.

Adult↗

Dyskeratosis and the dyskeratoses.

Darier first described dyskeratotic cells as infectious agents, but he later wrote that they were caused by abnormal keratinization. He grouped various inflammatory, infectious, and neoplastic skin diseases under the term "dyskeratoses." It is argued herein that the dyskeratotic cell and the so-called dyskeratoses have not been defined in a consistent manner because Darier's concepts were incorrect. Darier's dyskeratotic cell is classified here as one type of necrotic keratinocyte. Some conditions in which dyskeratotic and necrotic keratinocytes occur are described.

Acantholysis↗

Actinic granuloma (O'Brien).

Twelve cases of actinic granuloma (O'Brien) are reported. It is concluded that actinic granuloma is a specific disease characterized by clinical lesions indistinguishable from granuloma annulare, but occurring on solar damaged skin. Histologically, elastic tissue is destroyed by the granulomatous process in actinic granuloma, but not in granuloma annulare. It would appear that actinic granuloma, granuloma multiforme, necrobiosis lipoidica of the face and scalp (Wilson-Jones) and Miescher's granuloma of the face (Mehregan and Altman) are the same disease.

Adult↗