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Biomedical subjects

G Brunner

Publications and source records attributed to G Brunner.

At least 91 records · Page 5Linked to original sources

Selective cell culture of brain cells by serum-free, hormone-supplemented media: a comparative morphological study.

We cultured single cell suspensions derived from enzymatically digested rat and mouse brains in the serum-free, hormone-supplemented media originally established for culturing glioma (C6) and neuroblastoma cell lines (B104). We succeeded in selecting different cell types by varying the hormones added to the culture medium. In addition to the medium the attachment factors used for coating the culture dishes proved important for the establishment of a selective culture system. In a comparative morphological study we show that different particular microenvironmental conditions determine the growth and/or survival of different cell types of dissociated brain cells.

Animals

Properties of agarose-encapsulated adsorbents. II. Elimination of endogenous and exogenous phenolic compounds from human serum.

Phenolic compounds derived from the amino acid tyrosine are endogenous toxins, which are believed to be involved in the pathogenesis of hepatic coma. There are also xenobiotic phenolic substances, such as p-hydroxy-acetanilide (paracetamol or acetaminophen), which can lead to serious complications if taken in an overdose. In both cases, a drastic therapeutic measure such as haemoperfusion may be indicated to eliminate the toxin from the blood. In the present work, human serum has been dosed with the phenolic compounds of immediate relevance in exogenous and endogenous intoxication, and the effectiveness of various adsorbent materials for the elimination of the toxins from the serum has been investigated. Resins and charcoal in the native state have been compared with those encapsulated into large agarose beads, a process which improves the haemocompatibility and thus the practicability of the adsorbents. A certain degree of specificity has been observed. Whereas phenolic acids are adsorbed quite effectively onto the strongly basic ion exchange resins of the Dowex 1X type, particularly 1X8 or 2X8, phenol or paracetamol are less effectively eliminated. In contrast to many other classes of toxin, the Amberlite XAD-type resins are ineffective for all the phenolic substances investigated. Charcoal is the most effective adsorber in most cases, particularly when encapsulated in powder form into agarose beads.

Absorption

Properties of agarose-encapsulated adsorbents. I. Adsorption of digoxin from human serum.

The elimination of the cardioactive steroid, digoxin, from human serum by a range of adsorbent phases has been investigated. In the native state, the uncharged resins of the Amberlite XAD-type proved more effective than the ion-exchange resins, Dowex 1X, or active charcoal. Of the materials tested, Amberlite XAD-8 is by far the best suited resin for haemoperfusion in cases of digoxin overdose, whereby the less efficient XAD-4 is more commonly employed at present in clinics. In order to improve the haemocompatibility of the adsorbent materials, the technique of encapsulation into large agarose beads has been employed. In contrast to the effects observed with many other classes of xenobiotics, encapsulation into agarose beads results in a considerable loss of adsorptive capacity of digoxin by Amberlite XAD-8. The poor performance of active charcoal in form of granules can be improved by an order-of-magnitude using charcoal powder encapsulated in agarose. Thus, the latter material, or uncoated XAD-8 resin should be considered as a better alternative to materials in current use for extracorporeal detoxification in cases of digoxin overdose.

Anion Exchange Resins

[Treatment of meniscus lesions: personal results].

We examined 167 patients 10-14 years after meniscectomy to investigate the dependence of the frequency or arthrosis on operative technique. The relationship between the first clinical signs of meniscus lesion and the time of operation is discussed. The frequency and severity of post-operative alterations is considered in connection with age of the patient at the time of operation. We agree with other authors that the late results in patients under 20 years of age are clearly worse than those in adult patients. The long-term results shown radiological alterations in 72%; however, the functional late results are good or very good in nearly 84%.

Adolescent

Gas chromatographic method for the quantitative assay of alkane thiol S-methyltransferase.

A method is described for the quantitative assay of the methylation of alkane-thiols from the methyl-donor S-adenosylmethionine, catalysed by the microsomal enzyme S-adenosyl-L-methionine:thiol S-methyltransferase (E.C. 2.1.1.9). The reaction is carried out in sealed vials, one fifth of whose volume is taken up by an aqueous phase containing the enzyme and reactants. The volatile substrates and products of the reaction, thiols and thioethers, respectively, are present in equilibrium both in the liquid and gas phases in the reaction vessels. Aliquots of the gas phase are removed at intervals in gas-tight syringes, and analysis is performed directly on a gas chromatograph fitted with a flame-ionization detector. The amounts of thiol and thioether detected are then related to the total amounts of substance in the reaction vessels from calibration measurements, so that the kinetics of the enzymatic process can be evaluated. This technique offers distinct advantages over previously reported methods, in that no radioactively labelled compounds are required. Furthermore, decreases in substrate and increases in product can be assayed simultaneously, and the methylation of a mixture of thiols can be monitored in a single set of analyses.

Chromatography, Gas

[Arteritis in cerebral inflammatory diseases. Diagnostic value of angiography (author's transl)].

Cerebral angiography may sometimes show up inflammatory changes in the brain arteries in cases of tuberculous and acute purulent bacterial meningitis. The arteries at the base of the brain are predominantly affected, in some cases together with peripheral branches. Normal angiograms or non-specific alterations may be expected in patients suffering from non-purulent meningitis and encephalitis. Patients with luetic diseases show circumscribed or diffuse vessel wall lesions which cannot be differentiated from alterations caused by arteriosclerosis. The results are presented of 15 patients suffering from inflammatory diseases of the central nervous system of different aetiology. The morphology and the distribution of the arterial changes in the cerebral angiogram are discussed.

Adult

[The cerebral angiogram in cases of stroke in youth (author's transl)].

Sixty-seven patients (ages: 11-40 years) suffering from ischemic cerebral circulatory disturbances were investigated clinically and angiographically. In 34 cases, transient ischemic attacks or reversible ischemic neurological defects were diagnosed; 33 patients suffered from completed strokes. In most cases the completed stroke took place without previous transient ischemic attacks. A very good tendency toward recovery was observed in 60 of 67 cases. Stenoses or occlusions were found in only 21.5% of the clinically affected vessel regions. However, 50% of those patients, on whom panangiography was performed, were shown to have stenoses or occlusions. Stenotic vessel wall lesions are also obviously to be expected in clinically nonaffected vessel regions; consequently, in cases of cerebral circulatory disturbances, angiographic investigation of all craniocervical vessels is advisable.

Adolescent

Effects of cerebral gangliosides in the alcoholic polyneuropathies.

In chronic alcoholic patients with a slight or moderate polyneuropathy the effect of gangliosides at a daily dosage of 20 mg was investigated. A clinical improvement represented by a reappearance of the Achilles reflex and/or marked reduction of hypoaesthesia was found in the treated group. No significant changes in motor function were observed. No significant variation of the electrophysiological examination was found.

Action Potentials

The capillary-isotachophoretic analysis of reactants and products of glucuronidation. A new method for the assay of UDPGlucuronosyltransferase.

UDPglucuronosyltransferase competes with a nucleotide pyrophosphatase for UDPglucuronate as a substrate. Both enzyme systems are located in the microsomal fraction of mammalian liver homogenates, and the pyrophosphatase is present in all but the purest preparations of UDP-glucuronosyltransferase, since solubilisation procedures yield both activities in the 100 000 x g supernatant. In glucuronidation studies, it is important to be able to ascertain the degree of hydrolysis of the substrate UDPglucuronate due to the pyrophosphatase activity. A new method is reported using analytical capillary isotachophoresis whereby reactants and products of both glucuronidation and hydrolysis can be assayed simultaneously. The example presented in this paper is the glucuronidation of paracetamol (4-acetamidophenol) an important phenolic drug of toxicological interest. Rabbit liver microsomes glucuronidate this substance much more slowly than other phenolic compounds, so that hydrolysis of the donor molecule UDPglucuronic acid becomes of primary importance. Furthermore, the ionic mobility of 4-acetamidophenyl glucuronoside is much less than the other constitutents of assay mixtures under the analytical conditions employed, so that a well-defined separation from other reaction species is afforded.

Acetaminophen

[A modified oesophagoscope for sclerotherapy of bleeding oesophageal varices (author's transl)].

A flexible oesophagoscope with a wide angle optic, an inflatable balloon and a slit at the tip of the instrument has been developed to facilitate the sclerosing of bleeding oesophageal varices. While until today most investigators use a rigid oesophagoscope under general anaesthesia for a better view of the oesophagus and the possibility of compressing the varix to prevent rapid disappearance of the sclerosing fluid, with the new "Scleroscope" a general anaesthesia is not necessary any more. The wide angle optic allows good view of the operational field. The inflated balloon widens the lumen and prevents an intravascular deposit of sclerosing fluid from disappearing before the therapist wants it to leave the varix. The balloon can further be used to stop bleeding occuring from the injection canal. The slit at the tip of the instrument allows to hold the swollen varix and to inject it longitudinally with little danger of perforating the injection needle through the varix into the oesophageal tissue or mediastinum. By adding contrast medium to the sclerosing fluid the filling of the varices can be observed under x-ray control. This way intravascular sclerosing of varices of the fundus can be achieved. First experience with this new instrument is encouraging; its use should make the application of the rigid instrument unnecessary.

Contrast Media

Thiols and hepatic coma.

The plasma concentrations of methane and ethane thiols have been determined during the course of acute liver failure by a gas-chromatographic technique, and a prognostic evaluation is possible using this analysis. Further, the effects of some therapeutic measures, notably hemoperfusion, on the thiol levels have been investigated. It is concluded that these toxins, which are to a large extent covalently protein-bound, are extremely difficult to remove in an extracorporeal liver support system. Since the cause of the pathological thiol concentrations is probably the elevated plasma methionine levels associated with severe liver disease, it is suggested that the most hopeful course of action against the accumulation of thiols in the body might be a preventative therapy involving the normalization of methionine at an early stage of the disease.

Charcoal

The application of immobilized enzymes in an artificial liver support system.

A novel method of extracorporeal support for fulminant liver failure is reported whereby the most important detoxification processes of the liver are reproduced in an enzyme reactor. Most of the endogenous toxins involved in hepatic coma can be deactivated directly by conjugation with a hydrophilic residue such as glucuronic acid or glutathione, or by the neutralization of active groups through structural modification by methyl transfer. The enzymes responsible for these processes have been isolated and purified from rabbit liver, and covalently bound onto a hemocompatible form of agarose matrix. This system has been shown to be capable of catalyzing the desired reactions with endogenous toxins such as phenols and mercaptans in vitro, and phenols in rabbits in vivo.

Acetaminophen

Enzymatic methylation of alkane thiols.

A membrane-bound enzymatic activity has been found in rabbit liver microsomes, which catalyses the transmethylation from S-adenosylmethionine to a series of C1-C3 alkane thiols. Methane and ethane thiols are known to be endogenous toxins, which may play an important role in the pathogenesis of hepatic coma, and methylation could provide an important pathway for the metabolic 'detoxification' of this class of compounds through neutralisation of the highly reactive sulph-hydryl group.

Animals

Preparation and fractionation of membrane vesicles of thymocytes after osmotic cell disruption.

The isolation of plasma membranes is often accompanied with a loss of sensitivity to stimulatory agents (e.g. mitogens). Changes in the structure of the cell membranes after cell breakage have also been reported. Concerning this problem, "mild" cell disruption conditions were tested by using osmotic shock. Different membrane fractions were isolated, resulting in an enrichment of plasma membranes in one fraction. All fractions were characterized by plasma membrane marker enzymes (alkaline phosphatase, gamma-glutamyltransferases), the amount of cholesterol, the molar ratio of cholesterol and phospholipid, by dodecyl sulfate-gelectrophoresis and by electronmicroscopy. Total balance sheets of the fraction were made for each of the different biochemical parameters. The enriched plasma membranes resulting by using the described method had also lost the sensitivity to the stimulatory effect caused by mitogens such as Concanavalin A.

Animals

Large agarose beads for extracorporeal detoxification systems. Preparation and enzymatic properties of agarose-bound UDP-glucuronyltransferase.

UDP-glucuronlytransferase, E.C. 2.4.1.17, has been solubilised from the microsomal fraction of liver homogenate from phenobarbital pretreated rabbits by lipase or detergent treatments. A 110-fold purification of the enzyme with respect to the crude homogenate was achieved by precipitation and column separations. The cholate-detergent solubilised enzyme was far more stable than that prepared by the lipase method. The partially purified UDP-glucuronyltransferase has been covalently bound to cyanogen bromide-activated agarose in the form of large haemocompatible beads to the extent of 0.22 mg protein per mg agarose dryweight, equivalent to about 25 mg of swollen gel. The acceptors for glucuronidation employed were the non-physiological phenolic compounds p-nitrophenol and 1-naphthol, and an exogenous and endogenous substance of physiological importance, namely paracetamol and phenol respectively. The immobilised enzyme exhibited at least 80% of the original activity of the solubilised enzyme, and the catalytic function was preserved for a much longer period of time in the carrier-bound form. The system described in this publication could well be applied in an extracorporeal liver assist device for the replacement of glucuronidation function.

Animals