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Biomedical subjects

H Bach

Publications and source records attributed to H Bach.

At least 19 recordsLinked to original sources

Inhibition of MMP-9 expression by PPARgamma activators in human bronchial epithelial cells.

BACKGROUND: The release of matrix degrading enzymes such as matrix metalloproteinase 9 (MMP-9) from bronchial epithelial cells is critically involved in airway wall remodelling in chronic inflammatory processes of the respiratory system. MMP-9 expression is induced by inflammatory mediators such as tumour necrosis factor (TNF)-alpha, but to date nothing is known about the mechanisms of inhibition of MMP-9 expression in these cells. METHODS: A study was undertaken to examine whether activators of the nuclear transcription factor peroxisome proliferator activated receptor gamma (PPARgamma) might modulate MMP-9 expression in two different bronchial epithelial cell lines. RESULTS: PPARgamma was expressed and was functionally active in NL20 and BEAS cells. Activation of PPARgamma by rosiglitazone or pioglitazone significantly reduced TNF-alpha and PMA induced MMP-9 gelatinolytic activity in a concentration dependent manner in both cell lines, but did not alter the expression of tissue inhibitor of MMPs type 1 (TIMP-1), the local inhibitor of MMP-9. Northern blot analysis revealed a decrease in MMP-9 mRNA expression following treatment with PPARgamma which resulted from the inhibition of NF-kappaB activation in these cells, as determined by transient transfection assays and electromobility shift assays. CONCLUSION: Activation of PPARgamma in human bronchial epithelial cells limits the expression of matrix degrading MMP-9. This might have therapeutic applications in chronic inflammatory processes of the respiratory system.

Blotting, Northern↗

Escherichia coli maltose-binding protein as a molecular chaperone for recombinant intracellular cytoplasmic single-chain antibodies.

Recombinant single-chain antibodies (scFvs) that are expressed in the cytoplasm of cells are of considerable biotechnological and therapeutic potential. However, the reducing environment of the cytoplasm inhibits the formation of the intradomain disulfide bonds that are essential for correct folding and functionality of these antibody fragments. Thus, scFvs expressed in the cytoplasm are mostly insoluble and inactive.Here, we describe a general approach for stabilizing scFvs for efficient functional expression in the cell cytoplasm in a soluble, active form. The scFvs are expressed as C-terminal fusions with the Escherichia coli maltose-binding protein (MBP). We tested a large panel of scFvs that were derived from hybridomas and from murine and human scFv phage display and expression libraries by comparing their stability and functionality as un-fused versus MBP fused proteins. We found that MBP fused scFvs are expressed at high levels in the cytoplasm of E. coli as soluble and active proteins regardless of the redox state of the bacterial cytoplasm. In contrast, most un-fused scFvs can be produced (to much lower levels) in a functional form only when expressed in trxB(-) but not in trxB(+) E. coli cells. We show that MBP-scFv fusions are more stable than the corresponding un-fused scFvs, and that they perform more efficiently in vivo as cytoplasmic intrabodies in E. coli. Thus, MBP seems to function as a molecular chaperone that promotes the solubility and stability of scFvs that are fused to it.

ATP-Binding Cassette Transporters↗

Engineering bacterial biopolymers for the biosorption of heavy metals; new products and novel formulations.

Bioremediation of heavy metal pollution remains a major challenge in environmental biotechnology. One of the approaches considered for application involves biosorption either to biomass or to isolated biopolymers. Many bacterial polysaccharides have been shown to bind heavy metals with varying degrees of specificity and affinity. While various approaches have been adopted to generate polysaccharide variants altered in both structure and activity, metal biosorption has not been examined. Polymer engineering has included structural modification through the introduction of heterologous genes of the biosynthetic pathway into specific mutants, leading either to alterations in polysaccharide backbone or side chains, or to sugar modification. In addition, novel formulations can be designed which enlarge the family of available bacterial biopolymers for metal-binding and subsequent recovery. An example discussed here is the use of amphipathic bioemulsifiers such as emulsan, produced by the oil-degrading Acinetobacter lwoffii RAG-1, that forms stable, concentrated (70%), oil-in-water emulsions (emulsanosols). In this system metal ions bind primarily at the oil/ water interface, enabling their recovery and concentration from relatively dilute solutions. In addition to the genetic modifications described above, a new approach to the generation of amphipathic bioemulsifying formulations is based on the interaction of native or recombinant esterase and its derivatives with emulsan and other water-soluble biopolymers. Cation-binding emulsions are generated from a variety of hydrophobic substrates. The features of these and other systems will be discussed, together with a brief consideration of possible applications.

Bacteria↗

A morphological and immunohistological study of the human and rabbit appendix for comparison with the avian bursa.

Diversification of the primary antibody repertoire occurs in young rabbit appendix. As a prelude to molecular investigation of whether human appendix has a similar role, we compared the lymphoid morphology and distribution of common B- and T-cell subsets in frozen and/or paraffin-embedded normal appendix specimens at various ages. IgA, IgM and IgG staining patterns were similar in frozen human and rabbit appendices. The elongated follicles of the young human and rabbit appendices regressed with age to resemble Peyer's patches. Although similar in morphology to the bursa, human and rabbit appendix follicles differ in that they do not involute completely with age and contain significant numbers of germinal center (GC) T cells although the number is low early in life. If the human appendix functions as a primary lymphoid organ, it may occur during the first few months of age when the GC T-cell density is low.

ADP-ribosyl Cyclase↗

Specific detection of the gene for the extracellular neutral protease of Bacillus cereus by PCR and blot hybridization.

A pair of primers and a gene probe for the amplification and detection of the Bacillus cereus neutral protease gene (NPRC) were developed. Specificity for the npr genes of the B. cereus group members B. cereus, B. mycoides, and B. thuringiensis was shown. Restriction polymorphism patterns of the PCR products confirmed the presence of the NPRC gene in all three species.

Bacillus cereus↗

Psychosocial characteristics of asthma.

The objective of this study was to compare psychosocial characteristics of children with asthma and children with bronchial hyperreactivity with those of normal children. A population-based study of 2634 children (mean age, 10 years) was carried out. Pulmonary function tests of children were performed in children before and after cold air hyperventilation challenge to determine bronchial hyperreactivity. Parental assessment of children's behavior was evaluated with 15 questions about school/learning habits, level of activity, communication/affection, and sleeping patterns. A factor analysis was performed and the factor loading adjusted for confounders compared in the different groups. Asthmatic children sleep less well than normal and hyperreactive children (p < 0.001). Unexpectedly, however, all other single items did not differ significantly. As a result of the factorial analysis we obtained two factors. On the first factor, measuring school behavior and learning, there was a small difference between asthmatic and normal children, which could not be found on the second factor indicating activity and communication. We conclude that psychosocial differences of asthmatic children are less remarkable than expected. As a result of the examination of the hyperreactive children it is likely that asthmatic children are influenced more by secondary psychosocial factors than by any primary effect of asthmatic disease.

Asthma↗

Congenital toxoplasmosis transmitted from an immunologically competent mother infected before conception.

Congenital transmission of Toxoplasma gondii from a mother who was apparently immunologically competent and who had toxoplasmic lymphadenitis 2 months before conception is described. Since no T. gondii-specific serological data were available for this mother from the time her lymph node biopsy specimen was obtained, the specimen was studied by polymerase chain reaction (PCR) to determine whether the T. gondii B1 gene was present. The predictive diagnostic value of histologic findings previously considered to be classic signs of T. gondii lymphadenitis also was studied. This was done by correlation of serological tests diagnostic of acute acquired T. gondii infection and presence of characteristic findings in biopsy specimens from persons without known immunocompromise. Both PCR and review of the characteristic features of her lymph node biopsy specimen confirmed the diagnosis of preconceptual infection in the mother. We also discuss two other cases in which apparently immunologically competent mothers with preconceptually acquired infection transmitted this parasite to their fetuses.

Animals↗

Life style, subsistence and mortality in the Slavonic village at Espenfeld (Kr. Arnstadt, FRG). A trace element study.

Since the burial site of the Slavonic settlement at Espenfeld, Germany (10th to 12th century AD), has been completely excavated, the skeletons are representative of the historic population. This skeletal series has also been intensively investigated both archaeologically and anthropologically. It thus belongs to the kind of museum specimens which should not be left apart from any further study made possible by technological improvements. Analysis of elements Ca, P, Sr, Ba, Zn, Pb and As from compact bone specimens of a subsample of this series was carried out to get a more detailed knowledge on the population's life style. After a consideration of site-specific diagenesis, reconstruction of subsistence was possible for both adults and children. The assessment of weaning practice revealed insights into childcare. Special consideration was given to hazardous elements and their influence on infant morbidity. Also, a presumed genetic relationship between certain individuals based on morphological traits was paralleled by a striking similarity of trace element profiles, suggesting that bone chemistry might also permit the differentiation of microenvironments.

Adult↗

[Evaluation of biological variables in the human].

The analysis of the biological variability is one of the most important problems of anthropology and human genetics. However, describing the objective reality a conscious or unconscious valuation of this reality comes of frequently. Such a valuation can be motivated in a very different way and can achieve a considerable importance concerning the view of man. Experiences from history and presence make it clear that the sensitiveness for these problems must be a never renounced and a constant concern of all anthropologists and human genetists.

Abortion, Eugenic↗