Biomedical subjects
Publications and source records attributed to C Steffen.
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.
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.
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.
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.
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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.
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.
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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.
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.
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.
The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter. In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man. Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells. Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity (p less than 0.001 or less than 0.01) and to a lesser extent (p less than 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients. Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation. Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone. Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections.
Preformed immune complexes were deposited in kidney glomeruli of rabbits after i.v. injection. In vivo disintegration of these complexes by orally administered enzymes was investigated. 3 rabbits were given labelled trypsin and papain and the radioactivity and enzyme activity determined in the blood. The radioactive fraction showed an active enzyme concentration of 3-5 mg%. 13 experimental rabbits and 3 control animals received three i.v. injections of 5 ml preformed soluble immune complexes at 12-hour intervals. 24 hours after the last injection the experimental animals were fed 1600 mg enzyme mixture. All animals were sacrificed 4 hours later and the glomeruli of the kidney were investigated by immunofluorescence. All control animals showed large amounts of immune complexes in the glomeruli. Experimental animals, which had all received oral enzymes showed no immune complexes any more, or only residual immune complexes in some glomeruli. This observation pointed to in vivo disintegration of immune complexes by orally-administered enzymes as providing the basis for the treatment of immune complex diseases.
Oligodendrocytes were isolated from mixed glial cultures of neonatal mouse forebrain and further grown in serum-free hormone supplemented culture medium. Cell populations were identified by indirect immunofluorescence using a range of specific antibodies, revealing a predominantly immature population of oligodendrocytes, the majority expressing the myelin glycolipids galactocerebroside and sulfatide on their plasma membrane. Astroglial contamination was found to be minimal. Simultaneous autoradiography and immunofluorescence demonstrated the presence of a transport system for the major inhibitory neurotransmitter GABA in the oligodendrocytes. The transport system was found to be energy, sodium and temperature dependent. Kinetic analysis revealed a high affinity system, with a Km of 6.27 microM and Vmax of 0.714 nmol/min/mg protein, which is comparable to that found previously for CNS neurons and astrocytes.
Carcinoma of the splenic flexure is uncommon and the diagnosis should be kept in mind, particularly in patients with recurring upper gastrointestinal symptoms. Resection is usually possible and operative complications are few. The site of the tumor does not affect long-term survival. Subtotal colectomy with ileosigmoid anastomosis would seem to be a safe method of treating patients with an obstructed carcinoma at that site.
The changes in fuel metabolism during fast and exercise were compared to the tissue total CoA levels in mice maintained on pantothenate-deficient and pantothenate-supplemented (control) diets. In nonexercised mice maintained on a pantothenate-deficient diet for 65 to 105 days, the total CoA levels of many tissues were significantly lower than in controls (liver 18%, kidney 23%, spleen 21%, heart 38%, and leg skeletal muscle 66%). However, no differences in total CoA levels in brain or epididymal fat pads were observed. During a 48-hour fast, the total CoA levels increased in the heart and liver of both pantothenate-deficient and control mice (heart 32 and 19%, respectively; liver 39 and 45%, respectively), but the level of total CoA remained lower in the deficient mice. Liver glycogen levels were 17% lower in deficient mice than in controls and liver ketone bodies were 17% higher in pantothenate deficient mice than in controls. Separate groups of mice on deficient and supplemented diets were trained to run to exhaustion. Compared to trained mice on pantothenate-supplemented diets, the trained pantothenate-deficient mice had lower running times until exhaustion, lower body weights, lower liver and muscle glycogen content (even after rest), and elevated liver ketone bodies both during rest and after running. In summary, the pantothenate-deficient mice were unable to maintain normal glycogen stores, but had a normal ketogenic response to fast and exercise in spite of the lower levels of liver total CoA.
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