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Biomedical subjects

R Morgenstern

Publications and source records attributed to R Morgenstern.

At least 127 records · Page 7Linked to original sources
PubMed1990

[Liver and spleen surgery using cavitating ultrasound].

Liver and spleen can be selectively skeletized by means of ultrasonosurgery (10-200 W/cm2, 20-40 kHz). These are technological solutions which have provided major prerequisites for low-risk oncosurgery. The technique (ultrasonic sealing) can as well be used in conjunction with monomeric tissue glues to safely and hermetically seal areas of resection of injuries in parenchymatous organs. It has yielded good clinical results in liver and spleen surgery. Based on stringent indication, ultrasonosurgery can provide benefits to patient and surgeon in both oncosurgery and traumatology of liver and spleen.

Adolescent↗
PubMed1989

Activity of rat liver microsomal glutathione transferase toward products of lipid peroxidation and studies of the effect of inhibitors on glutathione-dependent protection against lipid peroxidation.

Rat liver microsomal glutathione transferase displays glutathione peroxidase activity with linoleic acid hydroperoxide, linoleic acid ethyl ester hydroperoxide, and dilinoleoyl phosphatidylcholine hydroperoxide, with rates of 0.2, 0.3, and 0.3 mumol/min/mg, respectively. The activities are increased between three- and fourfold when the enzyme is activated with N-ethylmaleimide. Microsomal glutathione transferase can also conjugate 4-hydroxynon-2-enal with a specific activity of 0.5 mumol/min/mg. These findings show that the enzyme can remove harmful products of lipid peroxidation and thereby possibly protect intracellular membranes against oxidative stress. A set of glutathione transferase inhibitors (rose bengal, tributyltin acetate, S-hexylglutathione, indomethacin, cibacron blue, and bromosulfophtalein) which abolish the glutathione-dependent protection against lipid peroxidation in liver microsomes have been characterized. These inhibitors were found to be effective in the micromolar range and could prove valuable in studying the factor responsible for glutathione-dependent protection against lipid peroxidation.

Animals↗
PubMed1989

Activation of rat liver microsomal glutathione transferase by limited proteolysis.

The activity of rat liver microsomal glutathione transferase is increased by limited tryptic proteolysis; the membrane-bound and purified forms of the enzyme are activated about 5- and 10-fold respectively. The cleavage sites that correlate with this activation were determined by amino acid sequence analysis to be located after Lys-4 and Lys-41. Differences in the relative extent of cleavage at these two sites did not consistently affect the degree of activation. Thus the data support the conclusion that cleavage at either site results in activation. The trypsin-activated enzyme was compared with the form activated with N-ethylmaleimide, which modifies Cys-49. These two differently activated forms were found to have similar kinetic parameters, which differ from those of the unactivated enzyme. The relatedness of the two types of activation is also demonstrated by the observation that microsomal glutathione transferase fully activated by N-ethylmaleimide is virtually resistant to further activation by trypsin. This is the case despite the fact that the N-ethylmaleimide-activated enzyme is much more susceptible to trypsin cleavage at Lys-41 than is the untreated enzyme. The latter observation indicates that activation with N-ethylmaleimide is accompanied by a conformational change involving Lys-41.

Amino Acid Sequence↗
PubMed1989

Ornithine decarboxylase in resting human mononuclear leucocytes: evidence for an endogenous inhibitor.

1. Ornithine decarboxylase (ODC) was measured in human mononuclear leucocytes (HML) by retention of putrescine on cation exchange paper. 2. The method was validated with unstimulated HML, phytohemagglutinin-stimulated HML, and a commercial preparation of ODC. The average enzyme activity of unstimulated HML (50 samples) was 22.6 +/- 7.3 pmol/hr 10(7) cells, with 29 values less than 5 pmol/hr 107 cells. 3. The results show that an endogenous inhibitor or inactivator of ODC exists in unstimulated HML: enzyme activity in extracts of mitogen-stimulated cells were inhibited by extracts of unstimulated cells (37-55%) inhibition under the conditions used.

Cation Exchange Resins↗
PubMed1989

[Basic studies of ultrasound surgery. VIII. Experimental animal studies of power ultrasound surgery of the swine pancreas].

The technique of the power ultrasound was tested in vitro and in vivo in 20 porcine pancreas. Simultaneous temperature measurements and laboratory tests do not produce any restriction. Enzymatic disorders were provable adequate to the clinical course. The ultrasonic effect guarantees a nearly riskless dissection in the layer. Joining processes, by adding Ligament-FIMOMED, produced a waterproof occlusion of parenchymal wounds. The cross-section of the pancreas with the pancreatic duct was sealed sufficiently. Also the jointed pancreato-jejunostomy remained sufficient. The reaction of the pancreatic parenchyma to the power ultrasound was small. A scarred metaplasia evolved immediately at the adhesive as a chronic atrophic interstitial pancreatitis. Only in case of occlusion of the pancreatic duct this alteration comprehended the whole pancreas.

Animals↗
PubMed1988

Gene expression of rat and human microsomal glutathione S-transferases.

We have isolated and characterized cDNA clones for both the rat and human liver microsomal GSH S-transferase (mGST) mRNAs. The rat sequence is 883 nucleotides long with 5'- and 3'-untranslated regions of 55 and 360 nucleotides, respectively, and contains two polyadenylation signals. The highest level of mRNA expression occurs in the rat liver, with widely varied levels of expression in extrahepatic tissues. Primer extension of rat liver poly(A) RNAs showed that only 12 nucleotides exist beyond the isolated cDNA. Southern blotting analysis of rat genomic DNA showed that this gene resides in a single EcoRV band of approximately 23 (kilobases) kb. Digestions with other restriction enzymes were consistent with the microsomal GST gene being a single copy gene with at least 3 exons spanning less than 12 kb. Human microsomal GST cDNAs were also characterized, and a 909 nucleotide sequence was determined with 5'- and 3'-untranslated regions of 74 and 368 nucleotides, respectively. RNA blot hybridization of human liver mRNA demonstrated that the human mGST is very similar in size to the rat mGST poly(A) RNA. Both the rat and human sequences contain a 154-amino acid reading frame and both show the same seven amino acid changes compared to the previously published protein sequence which upon reevaluation reveals the cDNA-deduced sequence to be correct. These two transcripts share 77% nucleotide similarity in the coding region, 47% in the 5'-untranslated regions and 61% in the 3'-untranslated regions. The rat and human microsomal GSTs show 95% conservation in amino acids. Several lines of evidence suggest that neither transcript contains a membrane-directing cleavable signal sequence.

Amino Acid Sequence↗
PubMed1988

Studies on the activity and activation of rat liver microsomal glutathione transferase, in particular with a substrate analogue series.

A number of potential substrates for the microsomal glutathione transferase have been investigated. Out of 11 epoxides tested, only two, i.e. androstenoxide and benzo(a)pyrene-4,5-oxide, were found to be substrates. Upon treatment of the enzyme with N-ethylmaleimide, its activity toward only certain substrates is increased. It appeared upon inspection of the bimolecular rate constants from the corresponding nonenzymatic reactions that the substrates for which the activity is increased are the more reactive ones. This hypothesis was investigated further using a series of para-substituted 1-chloro-2-nitrobenzene derivatives as substrates. Activation was seen only with the more reactive nitro-, aldehyde-, and acetaldehyde-substituted compounds and not with the amide and chloroanalogues, thus demonstrating the predicted effect with a related series of compounds. Interestingly, kcat values are increased 7-20-fold by N-ethylmaleimide treatment, whereas the corresponding kcat/Km value is increased only for the p-nitro derivative. Effective molarity and rate enhancement values were found to increase with decreasing reactivity of the substrate, attaining maximal values of 10(5) M and 10(8), respectively. It is concluded that the glutathione transferases are quite effective catalysts with their less reactive substrates. Hammett rho values for the kcat values of unactivated and activated enzyme were 0.49 and 2.0, respectively. The latter value is close to those found for cytosolic glutathione transferases, indicating that activation changes the catalytic mechanism so that it more closely resembles that of the soluble enzymes. The rho values for kcat/Km values were 3 and 3.5 for the unactivated and activated enzyme, respectively, values close to those observed for the nonenzymatic bimolecular rate constants and thereby demonstrating that these reactions have similar properties. The high coefficients of correlation between resonance sigma- values and all of these parameters demonstrate a strong dependence on substrate electrophilicity, as expected for nucleophilic aromatic substitution.

Animals↗
PubMed1988

Features of microsomal and cytosolic glutathione conjugation of hexachlorobutadiene in rat liver.

Hepatic GSH conjugation is the initial step in the mammalian biotransformation of hexachloro-1,3-butadiene (HCBD) and analogous haloalkenes. The present paper reports an in vitro investigation of the glutathione-dependent conversion of HCBD to water-soluble products, i.e. the enzyme-catalyzed conjugation of HCBD with GSH. The method employed avoids artifacts due to the volatility, low solubility and hydrophobic nature of the chloro-carbon substrate. In order to assess the relative importance of membrane-bound and cytosolic glutathione S-transferase in the conjugation process, microsomal and cytosolic fractions from adult rat liver were tested separately for their ability to promote water solubilisation of the substrate. In addition, microsomal purified and liposomally reconstituted glutathione S-transferase, were tested. The reaction exhibited Michaelis-Menten kinetics, and conjugation rates were linear for at least 20 min. The hepatic microsomal fraction metabolized HCBD 116 times faster than the cytosolic fraction when substrate saturated. Both mono- and bis-substituted conjugates were formed by microsomal as well as by the cytosolic fraction. Treatment of animals with inducers and the use of specific inhibitors indicated absence of cytochrome P-450 involvement in the formation of water soluble HCBD metabolites and supported the view that microsomal glutathione S-transferase is more important in catalyzing GSH conjugation of this haloalkene than the cytosolic forms of transferases.

Animals↗
PubMed1987

[Basic research in ultrasound surgery. VII. Comparative animal experiments after intestinal anastomosis by suturing, ligament gluing with Fimomed and ultrasound sealing with ligament Fimomed].

Animal experimental anastomoses in the small intestine of Mini-Lewe-pigs showed that even sufficient anastomoses free of stenosis can be obtained by using the sticking respectively the ultrasound sealing method. The foreign-body reaction in the surroundings of the suture was approximately equally strong as on the gluten. All animals did not show any specialty in the postoperative course. The use of butylcyanidacrylic is possible in the human intestine as also shown in the literature. The use is indicated if advantages are to be expected in face of a suture anastomosis in clinical sight.

Anastomosis, Surgical↗
PubMed1987

[Ultrasonic sealing of the lung parenchyma after atypical resection].

Surfaces of lung parenchyma after resection or lesion can be sealed reliably by means of monomeric tissue adhesive with immediate polymerization by ultrasound sealing. No bronchopleural fistula was observed during the animal experimental testing. Necrotic areas of the lung parenchyma are avoidable extensively. This technique is simple. It offers reliability for patient and operator in emergency situations.

Animals↗
PubMed1986

Induction of unscheduled DNA synthesis in human mononuclear leukocytes by oxidative stress.

The effect of unscheduled DNA synthesis (UDS) of different agents that induce oxidative stress was investigated using human mononuclear leukocytes (HML). It was found that Xanthine plus Xanthine oxidase increased UDS by 47%. Hydrogen peroxide had no significant effect. Cumene hydroperoxide increases UDS by 50% with a large interindividual variation (7-100%). Bleomycin and Mitomycin C increase UDS 189% and 295%, respectively. The validity of UDS induced by these agents for screening interindividual differences in susceptibility to oxidative stress is discussed.

Benzene Derivatives↗