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Biomedical subjects

F Marx

Publications and source records attributed to F Marx.

At least 19 recordsLinked to original sources
PubMed2000

[The Marjolin's ulcer": a malignant and rarely complication after burn trauma of the upper extremity - a case report].

The,Marjolin's ulcer" is a malignant lesion which is developed especially at chronic wounds after burn trauma. The latency from primary trauma to the malignant transformation is about 30 years. The lesion is more aggressive than other squamous cell carcinomas. We report on the combined radiation and surgical therapy of an 65-year-old patient with this lesion on the right hand and regional lymph node metastases. The extensive tissue defect after wide excision was reconstructed with a reversal radial forearm flap.

Aged↗
PubMed1999

Transfected human B cells: a new model to study the functional and immunostimulatory consequences of APP production.

The ubiquitously expressed Alzheimer amyloid precursor protein (APP) has raised wide interest in view of its connection with Alzheimer's disease. We now provide a novel extraneuronal cell model in which human Epstein-Barr virus transformed B cells that constitutively hardly produce APP are transfected with wild-type or mutated APP695, harboring the Swedish mutation APPsw, or a dilysine endoplasmic reticulum retrieval motif--APP(ER). This leads to the generation of three types of cells, one with a high secretion of soluble APPs but low levels of intracellular APP, another with a high intracellular APP retention but a low APP secretion, and a third in which APP maturation and secretion are strongly impaired. The suitability of our cell model for various purposes is proven by its usage in different systems. We demonstrate that it is a useful tool for studies on the physiology of APPs and represents a good model system to analyze the cellular mechanisms of Abeta-directed autoimmune reactivity.

Amyloid beta-Protein Precursor↗
PubMed1999

TNFalpha plus IFNgamma induce the production of Alzheimer beta-amyloid peptides and decrease the secretion of APPs.

The appearance of inflammatory markers associated with amyloid plaques indicates a state of chronic inflammation in Alzheimer's disease (AD). Multiple epidemiological studies also suggest that patients taking anti-inflammatory drugs have a decreased risk of developing AD. Here we present evidence that inflammatory cytokines can alter the metabolism of the beta-amyloid precursor protein (betaAPP). We show that the combination of tumor necrosis factor alpha and interferon gamma triggers the production of beta-amyloid peptides and inhibits the secretion of soluble APPs by human neuronal and extraneuronal cells. The results demonstrate a new mechanism by which inflammatory components can exacerbate the fundamental pathology in AD.

Alzheimer Disease↗
PubMed1999

Mechanisms of immune regulation in Alzheimer's disease: a viewpoint.

The immune system may play an important role in the neurodegenerative process in Alzheimer's disease (AD). Complement components, eicosanoids and cytokines are found in cerebral amyloid plaques. These inflammatory proteins may stimulate the amyloid beta (Abeta) production, support its aggregation and increase its cytotoxicity, thus aggrevating the pathology of AD. Abeta may trigger their release from activated microglia and astrocytes which are the main sources of these proteins. However, there are also indications for a protective role of the immune system against the development of AD. Microglial cells have been shown to degrade Abeta and recent evidence suggests a role of autoreactive Abeta-specific T cells in the elimination of the peptide. This mechanism seems to be impaired in the majority of patients with AD. An Abeta-specific immune reaction may thus represent a natural defence mechanism directed against the accumulation of dangerous amyloidogenic substances. Impairment of the immune system and the failure to eliminate a toxic metabolite can be the basis for a chronic non-specific inflammatory process in the brain, as described above. AD is a good example how an immune response may lead to tissue destruction and neuronal loss instead of maintaining the integrity of the body.

Alzheimer Disease↗
PubMed1997

Kidney function in rats after 5/6 nephrectomy (5/6 NX); effort of treatment with vitamin E.

In adult female rats various kidney functions were measured 3 weeks after 5/6 nephrectomy (5/6 NX). The distinct rises in blood urea nitrogen and in renal excretion of proteins indicate the impairment of the kidney. In 5/6 NX rats, the renal excretion of creatinine, glucosaminoglycan, and of p-aminohippurate was diminished. The concentrations of hydroxypyroline and of free hydrogen ions were distinctly increased in urine samples from 5/6 NX rats. The concentration of lipid peroxides was enhanced in kidney tissue whereas 3 weeks after 5/6 NX the concentration of GSH and GSSG in the remnant kidney tissue was unchanged. Long-term administration of vitamin E increased its concentration in plasma, kidney, and liver. Nevertheless, daily treatment with vitamin E (1 or 10 mg/100 g b.w. s.c. for 5 weeks) did not reduce the degree of impairment of kidney function following 5/6 NX.

Animals↗
PubMed1996

Sequence analysis and expression of the Penicillium chrysogenum nitrate reductase encoding gene (niaD).

The nitrate reductase gene (niaD) of the filamentous fungus Penicillium chrysogenum encodes a protein of 864 amino acids. The derived protein sequence shows 78% and 72% sequence identity to the corresponding Aspergillus niger and A. nidulans proteins, respectively. The coding region of the Penicillium gene is interrupted by six small introns, as deduced by comparison with the niaD sequences of A. niger and A. nidulans, whereby the positions of the introns are perfectly conserved between these three fungal genes. Northern blot analysis indicated a 2.8 kb transcript and showed that expression of this gene is controlled at the level of mRNA accumulation depending on both induction by nitrate and nitrogen metabolite derepression. Induction of transcription of niaD was found to be paralleled by expression of the major nitrogen regulatory gene nre.

Amino Acid Sequence↗
PubMed1996

[Detection of treatment of chicken breast with ionized rays and gradation of radiation dosage with the help of headspace gas chromatography and discriminant analysis evaluation].

Chicken breast was irradiated with doses of 3, 5, and 7 kGy. Headspace gas chromatographical analysis demonstrated the tendency that the amounts of volatile compounds (mainly pentanal, hexanal and heptanal) are higher in irradiated samples in comparison with non irradiated. Statistical evaluation of the gas chromatograms by discriminant analysis enabled the detection of irradiation. Unknown samples could be classified in the groups "un-irradiated" or "irradiated" in most cases.

Aldehydes↗
PubMed1995

Cloning, structural organization and regulation of expression of the Penicillium chrysogenum paf gene encoding an abundantly secreted protein with antifungal activity.

An abundantly secreted, highly basic 12-kDa protein (PAF) was purified from the culture medium of Penicillium chrysogenum (Pc). Based on the N-terminal amino acid (aa) sequence of the protein, an oligodeoxyribonucleotide probe was derived and used for amplification of the encoding cDNA by PCR. This cDNA fragment encodes a Cys-rich preproprotein of 92 aa which appears to be processed to a mature product of 55 aa. The deduced aa sequence of the preproprotein reveals 42.6% identity to an antifungal protein (AFP) of Aspergillus giganteus. Agar diffusion tests confirmed that the Pc protein exhibits antifungal activity. In order to investigate the promoter region and the structural organization of the paf gene, a genomic 6-kb fragment was isolated and partially sequenced. Comparison of the nucleotide sequence of the genomic fragment and the cDNA clone revealed the presence of a coding region of 279 bp which is interrupted by two introns of 76 and 68 bp in length. In the promoter region, a typical TATA box, a motif resembling the fungal carbon catabolite repression element, as well as several putative GATA factor binding motifs, were found. Northern blot analysis indicated that the regulation of paf expression occurs at the level of mRNA transcription and is under control of carbon catabolite and nitrogen metabolite repression regulatory circuits.

Amino Acid Sequence↗
PubMed1995

Sequence and structure of Penicillium chrysogenum phoG, homologous to an acid phosphatase-encoding gene of Aspergillus nidulans.

A Penicillium chrysogenum (Pc) gene (phoG), homologous to an Aspergillus nidulans (An) gene which confers phosphate-non-repressible acid phosphatase (APase) activity, has been cloned and sequenced. The 2.9-kb genomic sequence corresponds to two ORFs of 149 and 1630 bp encoding a protein of 593 amino acids (aa). As verified by cDNA sequencing, the coding region is interrupted by an 85-bp intron. The deduced aa sequence of phoG reveals 61% aa identity to the translated long ORF of the An APase-encoding gene. Northern blot analysis indicated a 2.3-kb transcript in approximately equivalent amount in mycelia grown under different phosphate concentrations.

Acid Phosphatase↗
PubMed1994

Glutathione status, lipid peroxidation and kidney function in streptozotocin diabetic rats.

In adult female rats diabetic nephropathy was induced by i.v. administration of streptozotocin (6 mg/100 g b.w.). The animals survive for 3 weeks when very low daily doses of insulin (0.3 IU/animal) are administered. High blood urea concentrations and distinct proteinuria indicate the impairment of kidney function in streptozotocin diabetic rats. Streptozotocin induces mild polyuria and increased renal excretion of potassium; there is also an increase in renal excretion of administered p-aminohippurate. Three weeks after administration of streptozotocin the formation of lipid peroxides is increased in the kidney. At this time glutathione content (GSH, GSSG) is unchanged in liver and kidney of streptozotocin diabetic rats. Impairment of kidney function in streptozotocin diabetic rats can be prevented by daily supplementation with sufficient doses of insulin (about 3 IU/animal).

Animals↗
PubMed1993

The effects of storage on the retention of enzyme activity in cryostat sections. A quantitative histochemical study on rat liver.

The effect of storage of unfixed cryostat sections from rat liver for 4 h, 24 h, 3 days and 7 days at -25 degrees C was studied on the activities of lactate dehydrogenase, glucose-6-phosphate dehydrogenase, xanthine oxidoreductase, glutamate dehydrogenase, succinate dehydrogenase (all demonstrated with tetrazolium salt procedures), glucose-6-phosphatase (cerium-diaminobenzidine method), 5'-nucleotidase (lead salt method), dipeptidyl peptidase II, acid phosphatase (both simultaneous azo coupling methods), D-amino acid oxidase (cerium-diaminobenzidine-cobalt-hydrogen peroxide procedure) and catalase (diaminobenzidine method). The effect of drying of the cryostat sections at room temperature for 5 and 60 min was investigated as well. The enzyme activities were quantified by cytophotometric measurements of test and control reactions. The test minus control reaction was taken as a measure for specific enzyme activity. It was found that the activities of all the enzymes investigated, with one exception, were affected neither by storage of the cryostat sections at -25 degrees C for up to 7 days, nor by drying of the sections at room temperature for up to 60 min. The exception was xanthine oxidoreductase, whose activity was reduced by 20% after 5 min drying of sections or after 4 h storage. Therefore, only incubations for xanthine oxidoreductase activity have to be performed immediately after cutting cryostat sections, whereas for the other enzymes a considerable margin appears to exist.

Animals↗
PubMed1993

Short-term biventricular circulatory support in the regionally stunned pig myocardium.

Mechanical circulatory support is only meaningful when reversible myocardial damage exists. Prompt biventricular assistance during reperfusion for six hours was tried in the regionally sublethally injured pig myocardium which has perspective for recovery. Postmortem tissue was examined with a quickly performed histochemical technique for tissue viability. Animals underwent five coronary occlusions (5 min occlusion/10 min reperfusion). Postischemic systolic wall thickening, observed by direct echocardiography, fell about 50% (p < 0.05 vs base line) before treatment which paralleled cardiac inosine and lactate efflux. Biventricular unloading (n = 5) resulted in contractile recovery to 94 +/- 19% (p < 0.05 vs stunning), untreated pigs remained depressed (33 +/- 12%, n = 5). During circulatory support the arterial lactate levels rose three-fold, concomitant with a drop in pH of 0.2 units (p < 0.05). Post-mortem histochemistry showed scattered areas with decreased activities of cytoplasmic lactate dehydrogenase and mitochondrial beta-hydroxybutyrate dehydrogenase, irrespective of treatment. Transmission electron microscopy revealed irreversible damage to mitochondria in depleted areas in contrast to areas where enzyme activity was present. We conclude that prompt volume unloading during reperfusion accelerated contractile recovery of sublethally postischemic myocardium.

Animals↗
PubMed1993

A histochemical procedure for light microscopic demonstration of xanthine oxidase activity in unfixed cryostat sections using cerium ions and a semipermeable membrane technique.

Xanthine oxidoreductase exists in two functionally distinct forms. Under normal conditions, the larger part of the enzyme occurs as an NAD(+)-dependent dehydrogenase form which produces NADH and urate. The dehydrogenase can be transformed under various (patho)physiological conditions to an oxygen-dependent oxidase form which produces oxygen radicals and/or hydrogen peroxide and urate. Tetrazolium salts are used to demonstrate the total activity of both the dehydrogenase and the oxidase form of the enzyme. We have developed a procedure to detect the oxidase form only in unfixed cryostat sections with the use of cerium on the basis of the semipermeable membrane technique. The incubation medium contained hypoxanthine as substrate, cerium ions, and sodium azide to inhibit catalase and peroxidase activity. In a second-step reaction, diaminobenzidine was polymerized in the presence of cobalt ions by decomposition of cerium perhydroxide. Large amounts of final reaction product were found in milk droplets in the acini of lactating bovine mammary gland, whereas milk-secreting epithelial cells contained hardly any final reaction product. In rat duodenum, enzyme activity was found in the cytoplasm of enterocytes and goblet cells but not in the mucus. Control reactions performed in the absence of substrate or in the presence of substrate and allopurinol, a specific inhibitor of xanthine oxidase, were completely negative in both tissues, with the exception of polymorphonuclear leukocytes in the lamina propria of duodenum. The positive nonspecific reaction in these cells was caused by myeloperoxidase activity. We conclude that the present method is specific for the detection of xanthine oxidase activity. Moreover, conversion of the dehydrogenase form into the oxidase form can be prevented by omission of chemical fixation of the tissue in the present procedure.

Animals↗
PubMed1993

In situ kinetic measurements of D-amino acid oxidase in rat liver with respect to its substrate specificity.

D-Amino acid oxidase activity was demonstrated in peroxisomes of rat liver using unfixed cryostat sections and a histochemical technique using cerium ions as capture reagent for hydrogen peroxide and diaminobenzidine, cobalt ions and exogenous hydrogen peroxide to visualize the final reaction product for light microscopical analysis. Cytophotometric analysis of liver sections revealed similar zero-order reaction velocities of D-amino acid oxidase with activity twice as high in periportal areas as in pericentral areas of liver lobuli when using either D-proline or D,L-thiazolidine-2-carboxylic acid as substrates. On the other hand, a 4-5 times higher KM value was found for D-proline than for D,L-thiazolidine-2-carboxylic acid. The KM values in periportal and pericentral areas were similar for each substrate. These findings support the suggestion that the physiological substrate for D-amino acid oxidase may be D,L-thiazolidine-2-carboxylic acid, the adduct of cysteamine and glyoxylic acid. D-Amino acid oxidase may play a role in vivo in the production of oxalate which may participate in metabolic control processes as an intracellular messenger molecule.

Animals↗
PubMed1993

Experimental evidence that the physiological position of the liver within the circulation is not a major determinant of zonation of gene expression.

Many enzymes are distributed heterogeneously within the liver lobule. The factors that play a determining role in the establishment and maintenance of these heterogeneous expression patterns have not yet been identified. To investigate whether the composition of the afferent hepatic blood plays a crucial role in the maintenance of the heterogeneity of gene expression of the parenchymal cells within the liver lobule, we changed the source of the afferent hepatic blood by microsurgical techniques. Three different groups of experimental animals were studied: rats with livers that are perfused with portal blood only (ligation of the hepatic artery), with caval blood only (portocaval transposition and ligation of the hepatic artery) and arterial blood only (portocaval shunt, arterialization of the distal end of the portal vein and ligation of the hepatic artery). To study differences in gene expression patterns, we chose enzymes that have a heterogeneous expression pattern within the liver lobule: the periportally located enzymes carbamoylphosphate synthase, succinate dehydrogenase, phosphoenolpyruvate carboxykinase and the pericentrally located enzymes glutamine synthase, glutamate dehydrogenase and NADPH-cytochrome P-450 reductase. To eliminate the potential interference of the long half-lives of some of these proteins on the interpretation of the results, we also studied the distribution of the mRNAs of carbamoylphosphate synthase, glutamine synthase, glutamate dehydrogenase and phosphoenolpyruvate carboxykinase. The animals were studied 2 wk after the operations. On the basis of their changes in body weight the animals were in steady state for at least a week. The patterns of gene expression of the enzymes studied did not change, regardless of the source of the altered afferent hepatic blood. The changes in gene expression that were observed in animals that did not regain their preoperative weight were shown to be caused by a limited intake of food. This study demonstrates that the physiological position of the liver within the circulation (i.e., between the gastrointestinal tract and the systemic circulation) is not as critical as is often stated and is certainly not essential for the maintenance of liver cell heterogeneity. The data suggest that the direction of the bloodstream (i.e., the existence of an upstream and a downstream compartment) is a major determinant of zonation of gene expression.

Animals↗
PubMed1993

The effect of ischaemia on xanthine oxidase activity in rat intestine and liver.

Effects of 60 and 120 minutes of in-vitro ischaemia on the localization of xanthine oxidase activity were studied in rat intestine and liver. A histochemical method was applied on unfixed cryostat sections using a semipermeable membrane. The incubation medium contained hypoxanthine as substrate, cerium ions which capture the enzyme product, hydrogen peroxide, and sodium azide to inhibit catalase and peroxidase activities. In a second step reaction diaminobenzidine was polymerized in the presence of cobalt ions and hydrogen peroxide by decomposition of cerium perhydroxide. Large amounts of final reaction product were found in the cytoplasm of enterocytes and goblet cells of control small intestine. When the incubation was performed in the absence of substrate or in the presence of substrate and allopurinol, a specific inhibitor of xanthine oxidase activity, no reaction product was found. After 60 and 120 minutes of storage of tissue blocks at 37 degrees C enzyme activity was significantly reduced in the apical region of epithelial cells, whereas a high activity was present in the basal region of these cells. A very low xanthine oxidase activity was found in rat liver. Highest activity was present in endothelial cells, whereas in liver parenchymal cells, a more pronounced activity was found in pericentral than in periportal hepatocytes. Ischaemia up to 120 minutes did not affect the enzyme activity in livers. It was concluded that increased xanthine oxidase activity during ischaemia may not be responsible for cell damage during reperfusion in contrast with assumptions in the literature.

Animals↗
PubMed1992

The use of unfixed cryostat sections for electron microscopic study of D-amino acid oxidase activity in rat liver.

Unfixed cryostat sections of rat liver were incubated to demonstrate D-amino acid oxidase activity at the ultrastructural level. Incubation was performed by mounting the sections on a semipermeable membrane which was stretched over a gelled incubation medium containing D-proline as substrate and cerium ions as capture reagent for hydrogen peroxide. After an incubation period of 30 min, ultrastructural morphology was retained to such an extent that the final reaction product could be localized in peroxisomes, whereas the crystalline core remained unstained. Control incubations were performed in the absence of substrate; the lack of final reaction product in peroxisomes indicated the specificity of the reaction. We conclude that the semipermeable membrane technique opens new perspectives for localization of enzyme activities at the ultrastructural level without prior tissue fixation, thus enabling localization of the activity of soluble and/or labile enzymes.

Animals↗