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Biomedical subjects

F Bauer

Publications and source records attributed to F Bauer.

At least 37 records · Page 2Linked to original sources

Reactive oxygen species as mediators of tissue protection and injury.

Extensive research efforts during the last three decades resulted in a large body of experimental evidence that suggests an important role of the disbalance between generation and elimination of the oxygen and xenobiotic derived free radicals in physiological and pathological processes. Reactive oxygen species (ROS) are generated in many metabolic pathways, and are entering the organisms from exogenous sources, dominantly via airways and gut. ROS induced injuries, e.g. thermal, chemical, radiation, ischaemia/reperfusion, inflammation, hyperoxia, etc., result in diseases like atherosclerosis, ulcerative colitis, autoimmune diseases, asthma, etc. The current paper is designed to provide an overview of the effects ROS may exert in various tissues. Because of the effective defense systems, the tolerance of viable human cells to ROS is relatively high. The oxidant stress induced dysfunction of various systems, such as the gut, airways, nervous, cardiovascular system, etc., involve both direct and indirect mechanisms. Understanding of these molecular mechanisms is essential for a rational antioxidant therapy.

Animals↗

Effects of acute administration of ethanol and the mu-opiate agonist etonitazene on thyroid hormone metabolism in rat brain.

The effects of acute, low-dose administration of ethanol (1 g/kg bodyweight) and the mu-opioid receptor agonist etonitazene (30 microg/kg bodyweight) on the activities of the iodothyronine deiodinase isoenzymes were investigated in nine regions of the rat brain. The experiments were performed at three different times of the 24-h cycle (1300, 2100 and 0500 hours) and the rats were decapitated 30 and 120 min after administration of the respective drugs. Interest was focused on changes in the two enzymes that catalyze 1) 5'-deiodination of thyroxine (T4) to the biologically active triiodothyronine (T3), i.e. type II 5'-deiodinase (5'D-II) and 2) 5 (or inner-ring) deiodination of T3 to the biologically inactive 3'3-T2, i.e. type III deiodinase (5D-III). 120 min after administration of ethanol and etonitazene 5D-III activity was selectively inhibited in the frontal cortex (at 1300 and 1700 hours) and the amygdala (at all three measuring times). The 5'D-II activity was significantly enhanced 30 min after administration of etonitazene in the frontal cortex, amygdala and limbic forebrain, and after administration of ethanol in the amygdala alone. These effects on 5'D-II activity were seen at 2100 hours only. In conclusion, the two different addictive drugs both reduced the inactivation of the physiologically active thyroid hormone T3 and enhanced its production. These effects occurred almost exclusively in the brain regions which were most likely to be involved in the rewarding properties of addictive drugs. As thyroid hormones have stimulating and mood-elevating properties, an involvement of these hormones in the reinforcing effects of addictive drugs seems conceivable.

Animals↗

The NA"null" phenotype of a young man is caused by an Fc gammaRIIIB gene deficiency while the products of the neighboring Fc gammaRIIA and Fc gammaRIIIA genes are present.

A 27-year-old man with an allergy to house dust mites was found to lack the Fc gammaRIIIb on his neutrophils. Cell surface marker and PCR techniques were used to investigate possible reasons for this deficiency. Agglutination and immunofluorescence assays using the man's neutrophils together with NA1- and NA2-specific antibodies were negative, and there was no reaction with the Fc gammaRIII-specific mAb 3G8. Indirect immunofluorescence demonstrated the presence of the CD24 molecule, which, like the Fc gammaRIIIb, is anchored to the cell membrane by glycosylphosphatidylinositol. Thus a lack of the Fc gammaRIIIb cell membrane anchor was excluded. PCR analysis confirmed the absence of the NA1 and NA2 alleles. The individual was therefore typed as NA"null". The products of those genes located together with the Fc gammaRIIIB gene within a complex on chromosome 1 (q23-24) were examined. Fc gammaRII was demonstrated on monocytes and B cells with the use of Fc gammaRII-specific monoclonal antibodies. About 5% of the individual's peripheral blood monocytes were positive with the 3G8 antibody, indicating the presence of Fc gammaRIIIa. From these data we concluded that the Fc gammaRIIIb deficiency on the neutrophil cell surface of this individual is due to a lack of the Fc gammaRIIIB gene while excluding a lack of the Fc gammaRIIA and the Fc gammaRIIIA genes.

Adult↗

Rapid typing of the human Fc gamma receptor IIA polymorphism by polymerase chain reaction amplification with allele-specific primers.

BACKGROUND: The human Fc gamma receptor IIa (Fc gamma RIIa) is expressed in two polymorphic forms, Fc gamma RIIa-H131 and Fc gamma RIIa-R131, that differ by the replacement of histidine by arginine at position 131. This replacement is caused by a single-nucleotide exchange of A-->G. The resulting receptor forms differ in their binding to human IgG2 and mouse IgG1, which may lead to a different immunologic defense to bacterial polysaccharides and encapsulated bacteria. STUDY DESIGN AND METHODS: A rapid and easy polymerase chain reaction(PCR) method of genotyping the Fc gamma RIIa was developed. Allele-specific primers discriminate between the Fc gamma RIIa-H131 and the Fc gamma RIIa-R131 forms of the receptor. The results were compared with those obtained by another DNA-based genotyping method, in which PCR-amplified DNA was hybridized with allele-specific oligonucleotides, and with a functional phagocytosis assay using mouse IgG1-coated red cells as target antigens. RESULTS: The genotypes deduced from the PCR with allele-specific primers were in complete accordance with those obtained by the data from the hybridization of PCR-amplified DNA with allele-specific oligonucleotides. Furthermore, the Fc gamma RIIa genotypes of 28 individuals in all cases corresponded to the functional phenotypes. CONCLUSION: The use of PCR with allele-specific primers provides a rapid and easily performed method for the determination the Fc gamma RIIa polymorphism.

Alleles↗

Engineering pathways for malate degradation in Saccharomyces cerevisiae.

Deacidification of grape musts is crucial for the production of well-balanced wines, especially in colder regions of the world. The major acids in wine are tartaric and malic acid. Saccharomyces cerevisiae cannot degrade malic acid efficiently due to the lack of a malate transporter and the low substrate affinity of its malic enzyme. We have introduced efficient pathways for malate degradation in S. cerevisiae by cloning and expressing the Schizosaccharomyces pombe malate permease (mae1) gene with either the S. pombe malic enzyme (mae2) or Lactococcus lactis malolactic (mleS) gene in this yeast. Under aerobic conditions, the recombinant strain expressing the mae1 and mae2 genes efficiently degraded 8 g/L of malate in a glycerol-ethanol medium within 7 days. The recombinant malolactic strain of S. cerevisiae (mae1 and mleS genes) fermented 4.5 g/L of malate in a synthetic grape must within 4 days.

Bacterial Proteins↗

Actin cytoskeleton and budding pattern are altered in the yeast rvs161 mutant: the Rvs161 protein shares common domains with the brain protein amphiphysin.

The actin cytoskeleton cells is altered in rvs161 mutant yeast, with the defect becoming more pronounced under unfavorable growth conditions, as described for the rvs167 mutant. The cytoskeletal alteration has no apparent effect on invertase secretion and polarized growth. Mutations in RVS161, just as in RVS167, lead to a random budding pattern in a/alpha diploid cells. This behavior is not observed in a/a diploid cells homozygous for the rvs161-1 or rvs167-1 mutations. In addition, sequence comparisons revealed that amphiphysin, a protein first found in synaptic vesicles of chicken and shown to be the autoantigen of Stiff Man syndrome, presents similarity with both Rvs proteins. Furthermore, limited similarities with myosin heavy chain and tropomyosin alpha chain from higher eukaryotic cells allow for the definition of a possible consensus sequence. The finding of related sequences suggests the existence of a function for these proteins that is conserved among eukaryotic organisms.

Actins↗

The influence of proteins on silver staining of nucleic acids following polyacrylamide gel electrophoresis.

The influence, on silver staining, of proteins and restriction enzymes in polymerase chain reaction (PCR) products was studied in 12-20% polyacrylamide gels. For small DNA fragments (74, 41 and 33 bp) best results were achieved using 20% polyacrylamide gels. In 12% gels, restriction enzymes and also proteins used for PCR (bovine serum albumin, Taq-DNA polymerase) interfere with silver staining of nucleic acids.

DNA↗

The mae1 gene of Schizosaccharomyces pombe encodes a permease for malate and other C4 dicarboxylic acids.

The mae1 gene of the yeast Schizosaccharomyces pombe was identified on the basis of its ability to complement a mutant defective in the transport of malic acid. Analysis of the DNA sequence revealed an open reading frame of 1314 base pairs, encoding a polypeptide of 438 amino acids with a predicted molecular weight of 49 kDa. A hydropathy profile of the predicted amino acid sequence revealed a protein with ten membrane-spanning or associated domains and hydrophilic N- and C- termini. The predicted secondary structure of the protein in similar to models proposed for other integral membrane proteins from both prokaryotes and eukaryotes. The S. pombe mae1 gene encodes a single mRNA of 1.5 kb. The mea1 gene is expressed constitutively and is not subject to catabolite repression as was previously reported for the malate permease systems of Candida utilis and Hansenula anomala. The mae1 gene was mapped 2842 bp 5' to the MFml gene on chromosome I. Transport assays revealed that the mae1 gene encodes a permease involved in the uptake of L-malate, succinate and malonic acid.

Amino Acid Sequence↗

Marked resistance of RAR gamma-deficient mice to the toxic effects of retinoic acid.

Excessive intake of retinol or of retinoic acid causes a syndrome of characteristic toxic effects known as hypervitaminosis A. To test the role of the nuclear retinoic acid receptor (RAR gamma) in this process we produced mice with a targeted disruption of the RAR gamma gene and examined toxic effects of repeated doses of retinoic acid and two other synthetic retinoids, Ro 15-1570 and Ro 40-6055. Surprisingly, homozygous mutant mice were resistant to fourfold higher doses of retinoic acid than wild-type mice as well as to elevated doses of the synthetic retinoids, indicating that RAR gamma may have a major role in mediating retinoid toxicity, a finding that possibly has practical implications for reducing the toxicity of synthetic retinoids in clinical use.

Animals↗

Analysis of mast cell subpopulations (MCT, MCTC) in cutaneous inflammation using novel enzyme-histochemical staining techniques.

In order to gain insights into the dynamics of mast cell subpopulations in normal and diseased skin, a novel enzyme-histochemical double and triple staining method was employed that allowed the detection of metachromasia (toluidine blue) and the mast cell proteases tryptase and chymase within the same cell. Cryostat sections were used of skin biopsies from the following specimens: normal skin (N = 4), psoriasis (N = 13), atopic eczema (N = 7), lichen planus (N = 6), interferon alpha 2a injection sites (N = 1) of a leukemic infiltrate and corresponding normal skin of the same patient before and after treatment. (i) Equal numbers of tryptase- and chymase-positive mast cells (MCTC) were obtained in all normal and diseased specimens in papillary and reticular dermis, with threefold increases around appendages. (ii) Tryptase-positive mast cells (MCT) were absent in normal skin, but were markedly increased in a disease-specific pattern within the papillary dermis, the inflammatory infiltrate and around appendages. (iii) Marked increases of MCT were also noted at interferon injection sites within the leukemic infiltrate, but not in the normal skin of the same patient. These data suggest that disease-dependent mast cell dynamics involve only MCT in cutaneous inflammation and that MCT numbers are controlled by distinct, disease-specific local tissue factors.

Amino Acid Sequence↗

Coincidental polycythemia vera and multiple myeloma: case report and review.

Polycythemia vera (PCV) and multiple myeloma are both clonal disorders of hematopoietic stem cells. The simultaneous occurrence of these diseases in an individual patient is rare. A case of synchronous PCV and smoldering myeloma is presented and the literature is reviewed. The issues of clinical importance in this unusual case include the mechanisms of anemia in multiple myeloma, the difficulty in using anemia as a parameter on which to base the initiation of therapy for myeloma, and the risks of treatment-induced leukemia and myelodysplasia.

Aged↗

Alteration of a yeast SH3 protein leads to conditional viability with defects in cytoskeletal and budding patterns.

Mutations in genes necessary for survival in stationary phase were isolated to understand the ability of wild-type Saccharomyces cerevisiae to remain viable during prolonged periods of nutritional deprivation. Here we report results concerning one of these mutants, rvs167, which shows reduced viability and abnormal cell morphology upon carbon and nitrogen starvation. The mutant exhibits the same response when cells are grown in high salt concentrations and other unfavorable growth conditions. The RVS167 gene product displays significant homology with the Rvs161 protein and contains a SH3 domain at the C-terminal end. Abnormal actin distribution is associated with the mutant phenotype. In addition, while the budding pattern of haploid strains remains axial in standard growth conditions, the budding pattern of diploid mutant strains is random. The gene RVS167 therefore could be implicated in cytoskeletal reorganization in response to environmental stresses and could act in the budding site selection mechanism.

Amino Acid Sequence↗

A retinoic acid receptor alpha antagonist selectively counteracts retinoic acid effects.

Retinoic acid (RA) exerts its pleiotropic effects on cell growth and differentiation through the activation of a family of transcription factors-the RA receptors (RARs). Three subtypes of these receptors exist, RAR alpha, RAR beta, and RAR gamma. The receptors are differentially expressed in different cell types and stages of development, suggesting that they may regulate different sets of genes. We have identified a synthetic retinoid with the characteristics of a selective RAR alpha antagonist. This antagonist counteracts RA effects on HL-60 cell differentiation and on B-lymphocyte polyclonal activation. Beyond its potential practical relevance, this and other specific antagonists will be useful to dissect the RAR system and to assign to one given receptor each of the many RA-regulated functions.

Animals↗

Nosocomial transmission of hepatitis B virus associated with the use of a spring-loaded finger-stick device.

BACKGROUND AND METHODS: From June 1989 through March 1990, 26 patients, of whom 23 had diabetes, contracted acute hepatitis B virus (HBV) infection in a hospital in California. All 26 patients and one HBV carrier (also a diabetic) had been admitted to a single medical ward during the six months before the case patients became infected with HBV. To determine the source of the infection, we conducted a retrospective cohort study of the 72 patients with diabetes who had been admitted to the ward from January through December 1989 and a case-control study comparing the 3 nondiabetic patients who contracted hepatitis with 20 nondiabetic controls. RESULTS: The retrospective cohort study of all the patients with diabetes who were admitted to the ward during 1989 found that those who underwent capillary blood sampling by finger stick with a spring-loaded lancet device were more likely to contract HBV infection than those who did not have finger sticks (attack rate, 42 percent vs. 0 percent; P = 0.08). In addition, a dose-response relation was observed between the number of finger sticks received and the frequency of hepatitis B (P = 0.002). The case-control study found that all 3 of the nondiabetic patients who contracted hepatitis underwent finger-stick blood sampling with the device, as compared with none of the 20 nondiabetic controls (P = 0.0006). A review of nursing procedures indicated that the platform of the device was not routinely changed after each use; this finding suggested that contamination of the platform by HBV-infected blood was the mechanism of percutaneous transmission of HBV. CONCLUSIONS: Proper use of finger-stick devices as well as strict adherence to universal precautions to avoid contamination by blood are required to decrease the possibility of transmission of blood-borne pathogens among hospitalized patients.

Acute Disease↗

[Effect of heat on the solubility and the electrophoretic behavior of myoglobin].

The heat stability of beef myoglobin was investigated by means of its solubility and intensity of protein bands separated by isoelectric focusing. A method for the sensitive determination of myoglobin in the extracts was developed based on its ability to form a red dye by the oxidative coupling of 2,4-dichlorophenol and 4-aminoantipyrine in the presence of hydrogen peroxide. By this method, myoglobin could be determined to a concentration of 0.01 mg/ml. For the detection of electro-focused myoglobins, o-dianisidine has proved to be the most sensitive compound. The myoglobin content of the extracts, according to the intensity of the myoglobin bands in the electrophoretic gel, decreased with increasing temperature and heating-time. However, the position of the bands was not changed by the heat treatment.

Animals↗

Effects of setting eggs small end up on hatchability and posthatching performance of broilers.

1. Hatchability of fertile eggs incubated with their small ends up (SEU) was 16 to 27% lower than for eggs set with their large ends up (LEU). In addition, the SEU position produced more nonviable chicks. 2. There were no differences in post-hatching performance between the two incubation treatments. 3. A survey in a commercial hatchery revealed that the frequencies of eggs set upside down by mistake varied from 0.3% to 3.4%. The setting of eggs upside down was attributed not to difficulties in distinguishing the large and small ends of the eggs but to human error. A decrease in the number of Grade-A chicks of about 0.2% was observed for every 1% of eggs set upside down, suggesting it may be of economic importance to ensure that the eggs are set properly with their large ends up.

Animals↗

[Diagnostic value of the early auditory evoked potentials in acute cranio-cerebral trauma in children].

The brainstem auditory evoked potentials were recorded in 54 children within the first 48 hours after a head trauma of different degree. In comparison with an age--appropriate standard group there are changed BAEP in 51% of the examined children after head trauma. The abnormalities mainly consist in changes of the wave--morphology, the latencies of the waves 1, 3 and 5 were significantly prolonged. The interpeak--intervals only unessentially differ from the standard group. The detected BAEP--changes are of different kind and incidence. A typical change of the potential for the infantile head trauma cannot be found. The regression of the traumatically conditioned BAEP--changes begins during the first days after trauma and it is finished within 6 months in half of the children. In the particular case changes can be detected after two years yet.

Adolescent↗