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Biomedical subjects

C Steffen

Publications and source records attributed to C Steffen.

At least 55 records · Page 3Linked to original sources

Effects of antimicrobial agents used for therapy of CNS infections on dissociated brain cell cultures.

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.

Amikacin↗

[In vivo degradation of immune complexes in the kidney by orally administered enzymes].

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.

Administration, Oral↗

High-affinity uptake of gamma-[3H]aminobutyric acid by isolated mouse oligodendrocytes in culture.

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.

Animals↗

Carcinoma of the splenic flexure.

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.

Aged↗

The effect of pantothenate deficiency in mice on their metabolic response to fast and exercise.

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.

Animals↗

[Immune complexes in myocardial infarct].

604 patients were investigated with C1q solid phase RIA in regard to circulating immune complexes (CIC) shortly after myocardial infarction. 118 (19.6%) of these 604 patients had CIC, which disappeared in 99 patients (83.7%) or decreased significantly in 9 cases (7.6%) after 2-4 weeks. Only 10 patients (8.3%) showed persisting CIC. 12 parameters assessing clinical features and laboratory data were compared with the results of CIC investigation in altogether 251 patients, of whom 54 (21.5%) were CIC-positive. No differences between CIC-positive and CIC-negative patients were observed with regard to generally accepted factors predisposing to infarction. However, CIC-positive patients differed significantly from CIC-negative cases in the higher incidence of a history of respiratory tract infection before infarction (p less than 0.001) and the more frequent absence of a family history of cardiac and circulatory disease (p less than 0.0005). Interpretation of these results indicates a transient appearance of CIC after liberation of heart - tissue antigens during infarction, but does not exclude the possible existence of a group of patients manifesting CIC already before the onset of infarction, whereby the CIC may have contributed towards triggering off the infarction. In this case persistence of CIC after infarction may be regarded as an unfavourable sign.

Antigen-Antibody Complex↗

Change in collagen synthesis of human chondrocyte culture. I. Development of a human model, demonstration of collagen type conversion by immunofluorescence.

A research system constituted entirely of components of human origin was developed to study conversion of collagen synthesis by human chondrocytes. Type specificity of affinity chromatography-purified antibodies to human type II or type I collagen was proven by ELISA inhibition and immunofluorescence analysis. Human chondrocytes were isolated from articular cartilage and kept in monolayer cultures for eight subpassages. Conversion of type II to type I synthesis by chondrocytes was investigated by immunofluorescence. Staining with anti-type II collagen antibodies could be detected during primary cultures and in the first subpassage, whereas staining with anti-type I collagen antibodies occurred beginning from the end of primary cultures and was present up to the eighth subpassage. Results are compared to observations obtained in animal systems and their relevance to conditions in osteoarthritis is discussed.

Adult↗

[Basic studies on enzyme therapy of immune complex diseases].

Several in vitro investigations and animal experiments are described which may be used as experimental basis for the enzymatic treatment of rheumatoid arthritis and, possibly, also other immune complex diseases. Demonstration of absorption of unaltered orally-administered radiolabelled enzymes is shown in guinea pigs and rabbits. In vitro experiments with 4 types of soluble immune complexes which were incubated with gradually increasing amounts of enzymes showed dose-dependent cleavage of complexes. Antigen-induced experimental arthritis of rabbits, fed different amounts of a therapeutically used mixture of enzymes at different times, could be inhibited by this treatment, in dependence of dosage and time of feeding. With respect to the therapeutic applications of this study, the results favour the use of a high dosage repeated daily administration, since duration of effect seems limited.

Animals↗

Effect of ammonia on plasma and cerebrospinal fluid amino acids in dogs with and without portacaval anastomoses.

To elucidate the possible connection between ammonia-induced changes of plasma and cerebrospinal fluid (CSF) amino acid levels and the development of hepatic encephalopathy in dogs, beagle dogs were given an ammonium acetate infusion both before and following portacaval shunt (PCS). During ammonia-induced coma and after recovery in the dogs prior to PCS the plasma and CSF concentrations of most amino acids were decreased. Following PCS the plasma and CSF concentrations of the aromatic amino acids (AAA), phenylalanine and tyrosine, increased and the levels of the branched chain amino acids (BCAA), valine, leucine, and isoleucine, decreased during ammonia-induced coma. The CSF/plasma molar ratio for the AAA exhibited a marked increase after recovery as compared to the value during coma in the Eck-fistula dogs. With respect to the AAA, no correlation was observed between signs of neurologic impairment in the animals and the following parameters: glutamine and methionine levels of CSF, and the plasma molar ratio (Formula: see text). The data obtained do not support the hypothesis that high concentrations of phenylalanine and tyrosine in the brain may be primarily responsible for altered neurotransmission leading to the development of hepatic encephalopathy.

Amino Acids↗

Eosinophilic pustular folliculitis (Ofuji's disease) with response to dapsone therapy.

A 50-year-old man had eosinophilic pustular folliculitis (Ofuji's disease) characterized by follicular pustular papules on the face, confluent vesicles on the fingers, and a papulopustular area on the upper portion of the back. Extensive examinations and cultures of both pustular material and tissue revealed no organisms, except Staphylococcus epidermidis. The disease responded to dapsone therapy.

Dapsone↗