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Biomedical subjects

B Müller

Publications and source records attributed to B Müller.

At least 199 records · Page 11Linked to original sources
PubMed1997

Immunohistochemical localization of the Ca2+ binding S100 proteins in normal human skin and melanocytic lesions.

The purpose of this study was to evaluate the expression of the Ca(2+)-binding S100 proteins S100A1, S100A2, S100A3, S100A4, S100A6 and S100B in normal skin. These immunohistochemical staining patterns were compared with those in melanocytic lesions. Paraffin-embedded tissue of normal skin adjacent to 26 naevi, 39 primary cutaneous melanomas and 14 cutaneous melanoma metastases was incubated with polyclonal antibodies against the recombinant human S100 proteins (S100A1, S100A2, S100A3, S100A4, S100A6, S100B) using the alkaline phosphatase anti-alkaline phosphatase method. The S100A2 antibody stained the basal layer of the epidermis and hair follicles of normal skin. Four of 39 primary cutaneous melanomas were positive for S100A2, whereas none of the metastases or naevi showed any immunoreactivity. The S100A3 antibody only stained the inner root sheath cuticle of some hair follicles but no melanocytes or melanocytic lesions. Staining of S100A4 was weak and thus omitted to further analysis. S100A6 faintly labelled keratinocytes. Langerhans' cells, melanocytes and sweat glands. S100A6 immunoreaction was found in two of seven junctional naevi, five of seven compound naevi, and all dermal and blue naevi. There was an intense cytoplasmatic reaction for S100A6 in all primary cutaneous melanomas and in nine of 14 (64%) metastases, S100B was positive in melanocytes and Langerhans' cells, all primaries as well as in the metastases, S100A1 protein was not detected on any of the tissue specimens examined. Whereas S100B and S100A6 antibodies are useful markers for malignant melanoma, expression of S100A4 antibody is too low to be used for immunohistochemical staining. S100A1 and S100A3 antibodies are not expressed in melanocytic lesions and S100A2 is only found in selected tumours. The investigated S100 proteins, including S100B and S100A6, are also expressed in selected elements of normal skin. These findings are important for correct interpretation of staining patterns, when S100 antibodies are used as markers for melanoma or other tumours.

Antibodies, Monoclonal↗
PubMed1996

Stabilization of chlorophyll a-binding apoproteins P700, CP47, CP43, D2, and D1 by chlorophyll a or Zn-pheophytin a.

Stabilization of chlorophyll a-binding apoproteins P700, CP47, CP43, D2, and D1 against proteolytic degradation has been investigated through in vitro synthesis of chlorophyll a or Zn-pheophytin a in intact etioplasts from barley. Stabilization of the apoproteins was dependent on the concentration of chlorophyll a or Zn-pheophytin a. Zn-pheophytin a was superior to chlorophyll a with respect to the concentration of pigment required for an equal yield of the stabilized chlorophyll a protein CP47, CP43, and P700 and for the total yield of chlorophyll a proteins. Zn-pheophytin a was most efficient for stabilizing CP47 and, at an increased concentration, efficient for stabilizing CP43, P700, and D1. Stabilization of apoproteins was highest after de novo synthesis of 90-300 pmol of Zn-pheophytin a or of about 400-600 pmol of chlorophyll a/4.2 x 10(7) etioplasts. The yield of stabilized chlorophyll proteins decreased at higher concentrations of Zn-pheophytin a, but was unaffected by higher concentrations of chlorophyll a.

Apoproteins↗
PubMed1996

Stabilization of the chlorophyll binding apoproteins, P700, CP47, CP43, D2, and D1, by synthesis of Zn-pheophytin a in intact etioplasts from barley.

Chlorophyll a was compared with Zn-pheophytin a for stabilization of chlorophyll binding apoproteins, P700, CP47, CP43, D2, and D1, in intact etioplasts from barley (Hordeum vulgare L.). Intact etioplasts were shown to effectively translate the chlorophyll apoproteins, to take up and esterify the exogenously added substrates, chlorophyllide a and Zn-pheophorbide a, with geranylgeraniolpyrophosphate. For stabilization of P700, CP47, D2, and D1, the product, Zn-pheophytin a, was shown to substitute for chlorophyll a. Stabilization of CP43 was selectively increased in the presence of Zn-pheophytin a. The degree of stabilization was shown to depend on the amount of newly synthesized Zn-pheophytin a and on the central atom of the chlorophyll molecule.

Chlorophyll↗
PubMed1996

p53 Protein exhibits 3'-to-5' exonuclease activity.

Highly purified p53 protein from different sources was able to degrade DNA with a 3'-to-5' polarity, yielding deoxynucleoside monophosphates as reaction products. This exonuclease activity was dependent on Mg2+ and inhibited by addition of 5 mM nucleoside monophosphates. This exonuclease activity is intrinsic to the wild-type p53 protein: it copurified with p53 during p53 preparation; only purified wild-type p53, but not identically purified mutant p53 proteins displayed exonuclease activity; the exonuclease activity could be reconstituted from SDS gel-purified and urea-renatured p53 protein and mapped to the core domain of the p53 molecule; and finally, purified p53 protein could be UV-cross-linked to GMP. A p53-intrinsic exonuclease activity should substantially extend our view on the role of p53 as a "guardian of the genome."

Antibodies, Monoclonal↗
PubMed1996

Evolution of legumin genes: loss of an ancestral intron at the beginning of angiosperm diversification.

The polymerase chain reaction was used to survey gymnosperm legumin genes. Characterization of 46 cloned amplificates, differing in sequence and size (1.2-1.6 kb), revealed the ubiquitous occurrence of legumin genes and their organization in small subfamilies in the 22 species investigated. The 3' portions of the genes, coding for the legumin beta-polypeptides, show a highly conserved intron/exon structure divergent from those of angiosperms: an additional intron (intron IV) uniformly interrupts the region coding for the C-terminal part of the beta-polypeptides. Phylogenetic analysis of the respective coding sequences as well as the organization of the Magnolia B14 legumin gene also investigated here both indicate that intron IV is ancestral and was lost during early angiosperm evolution. Taking into account the intron/exon structures from all legumin genes known, our results suggest that legumin genes evolved by subsequent loss of introns, providing also further evidence for a common origin of legumins and vicilins.

Amino Acid Sequence↗
PubMed1996

Linkage studies in alcohol-responsive myoclonic dystonia.

A large German family with "myoclonic dystonia with lightning jerks responsive to alcohol" was identified. Eleven affected pedigree members and six obligate gene carriers from five generations were identified. A description of one branch of this pedigree was published in 1964. Our examination 30 years after the initial report confirms the clinical syndrome of a nonprogressive movement disorder characterized by myoclonic jerks affecting the proximal muscles and the muscles of the trunk, accompanied by mild dystonic features in some affected family members. Segregation analysis favors autosomal dominant inheritance with high, but incomplete, penetrance in males and much lower penetrance in females. Linkage analysis was performed using simple sequence repeat polymorphisms (CA repeats) closely associated with or spanning the chromosomal regions containing 15 candidate genes: the gene for early-onset generalized torsion dystonia, DYT1 (chromosome 9q34); the genes for subunits alpha 2, beta 1, and gamma 1 (chromosome 4p12-4q13); for alpha 1, alpha 6, beta 2, and gamma 2 (chromosome 5q31.1-5q31.3); for alpha 4, alpha 5, beta 3, and gamma 3 (chromosome 15q11-15q13); for rho 1 and rho 2 (chromosome 6q14-6q21) of the gamma-aminobutyric acid A receptor; and for the alpha subunit of the glycine receptor (chromosome 5q31). By a combination of pairwise and multipoint linkage analysis, it could be excluded that any of these candidate gene-bearing chromosomal regions contain the disease gene in this family. We also excluded major portions of three chromosomal regions syntenic with mouse chromosome 3, which carries the murine beta subunit of the glycine receptor.

Adolescent↗
PubMed1996

Non-classical-MHC genetics of immunological disease in man and mouse. The key role of pro-inflammatory cytokine genes.

For a series of immunological diseases including asthma, inflammatory arthritis and experimental allergic encephalomyelitis the non-classical major histocompatibility complex (MHC) genetics of man and mouse has been making rapid progress. Information is available not only for the disease associations of individual candidate genes but also from the first genome scans. In both species the proinflammatory cytokine genes and/or their related receptors and inhibitors (IL-1, IL-1r, IL-1ra, IL-2, IL-6r, TNF-alpha), and to a lesser extent the anti-inflammatory cytokine IL-4 are implicated as candidate control elements. In contrast, genes for the signalling and adhesion CD molecules have so far been inconspicuous. Most of the polymorphisms so far detected have been in the regulatory sequences of these genes, rather than in the exons. It is suggested that the benefit conferred on an individual by greater flexibility in its immunoregulatory machinery may be responsible for maintaining this form of polymorphism.

Animals↗
PubMed1996

Population study of the G1691A mutation (R506Q, FV Leiden) in the human factor V gene that is associated with resistance to activated protein C.

The mutation G1691A (R506Q) in the human factor V gene is associated with the resistance to activated protein C (APC) that represents a major risk of development of venous thrombosis. A population study of 180 unrelated individuals from south Germany was performed. Examination of the allelic frequencies revealed a high prevalence of this disease-related mutation (Q506, FV Leiden). The heterozygosity rate was 7.8% with a confidence interval between 4% and 11%.

Base Sequence↗
PubMed1996

A novel sequence polymorphism in the promoter region of the human B2-bradykinin receptor gene.

The distribution of a nucleotide polymorphism in the core promoter of the human B2-bradykinin receptor gene was examined in the population of southern Germany. The allelic frequencies were 0.595 for C allele and 0.405 for the T allele. The allele frequencies were in Hardy-Weinberg equilibrium. This new marker provides a valuable tool to assess the risk for putative bradykinin-associated disorders with genetic determinism.

Alleles↗
PubMed1996

Building intelligent alarm systems by combining mathematical models and inductive machine learning techniques.

In this article a technique is described to develop knowledge-based alarm systems for ventilator therapy, using mathematical modeling and machine learning. With a mathematical model airway pressure, expiratory gas flow and CO2 concentration at the endotracheal tube are simulated for patients, undergoing volume-controlled ventilation with constant ventilator settings, during normal functioning of the breathing circuit and during breathing circuit mishaps (leaks and obstructions). Simulations were performed for 94 physiologically different 'patients', by varying airway resistance and lung/thorax compliance values in the model. Each simulated breath was described by a set of derived signal features and a label that constituted during which event (normal function or mishap) the breath was recorded. With an inductive machine learning algorithm rules, linking signal feature values to breathing circuit events, were created from data of 54 of the simulated patients. The resulting set of rules was able to classify 99% of events in the data of the remaining 40 patients correctly. Of signals, measured at a ventilated lung simulator, 100% of events were classified correctly.

Airway Resistance↗
PubMed1996

Building intelligent alarm systems by combining mathematical models and inductive machine learning techniques Part 2--sensitivity analysis.

In an earlier study an approach was described to generate intelligent alarm systems for monitoring ventilation of patients via mathematical simulation and machine learning. However, ventilator settings were not varied. In this study we investigated whether an alarm system could be created with which a satisfactory classification performance could be obtained under a wide variety of ventilator settings, by varying inspiratory to expiratory time (I:E) ratio, tidal volume and respiratory rate. In a first experiment three patient data sets were modeled, each with a different I:E ratio. A part of each data set was used to construct an alarm system for each I:E ratio. The remaining part was used to test the performance of the alarm systems. The three training sets were also combined to construct one alarm system, which was tested with the three test sets. Finally, all alarm systems were tested with data generated by a patient simulator. Similar experiments were performed for the tidal volume and the respiratory rate. It was concluded that an optimally functioning alarm system should contain a library of rule sets, one for each set of ventilator settings. A second best alternative is to take all possible settings into consideration when constructing the training set. Classification performance of the trees that were trained with multiple ventilator settings ranged from 98 to 100% for all test sets. When tested with the independent patient simulator data the classification performance of these trees ranged from 80 to 100%.

Airway Resistance↗
PubMed1996

The RNA binding protein HuD: rat cDNA and analysis of the alternative spliced mRNA in neuronal differentiating cell lines P19 and PC12.

HuD belongs to a family of neurospecific RNA binding proteins found in man, frog and fly [49]. To investigate whether this protein is involved in regulation of neuronal differentiation of rodent cells in vivo and in vitro, the cDNA of the rat homolog gene (r-HuD) was cloned, its expression was studied in rat brain and in neurogenic cell lines, and the splicing of its RNA was analyzed. Coding sequences of HuD from man and rat were found to be 99.5 and 95% identical at protein and DNA level, respectively. In rat brain r-HuD transcripts 3.7 and 4.2 kb in length were detected by Northern blot analysis. RT-PCR and in situ hybridization revealed that rodent homologues of HuD transcripts are present in P19 mouse embryo carcinoma and in PC12 rat pheochromocytoma cell lines both able to differentiate into neurons. In contrast, r-HuD transcripts were not detectable in the rat glioma cell line C6. In P19 cells a strong induction of HuD mRNA was observed after triggering neuronal differentiation by retinoic acid, whereas in PC12 cells the mRNA was present before and after nerve growth factor (NGF) induced neuronal differentiation. In both neuronal cell lines and in brain of adult rat and mouse HuD mRNA is alternatively spliced in a region which encodes a proline rich linker domain between the second and third RNA recognition motif. This RNA processing event seems to be differently regulated in PC12 cells on the one hand, and in P19 cells and brain of rat and mouse on the other.

Alternative Splicing↗
PubMed1996

Inhibition of cytokine-inducible nitric oxide synthase in rat microglia and murine macrophages by methyl-2,5-dihydroxycinnamate.

Microglial cells are resident macrophages in the central nervous system (CNS) which serve specific functions in the defence of the CNS against microorganisms, the removal of tissue debris in neurodegenerative diseases or during normal development, and in autoimmune inflammatory disorders of the brain. Microglia express a cytokine-inducible isoform of nitric oxide synthase, which leads to the production of nitric oxide (NO). Since NO is highly toxic to neurons and oligodendrocytes, we were interested to test down-regulating neuropeptides and second messenger de-activators in order to identify novel antagonists of cytokine-induced NO production. We found that only the tyrosine kinase inhibitor methyl-2,5-dihydroxycinnamate suppressed cytokine-induced NO production by rat microglial cells and murine macrophages, while a range of other tyrosine kinase inhibitors, neuropeptides and growth factors was ineffective. Since NO production may play a role in the pathogenesis of experimental neuro-immunological disorders like experimental autoimmune encephalomyelitis and experimental autoimmune neuritis, our findings suggest a possible therapeutic role for tyrosine kinase inhibitors.

Animals↗