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Biomedical subjects

S Steinemann

Publications and source records attributed to S Steinemann.

14 recordsLinked to original sources

Role of the lipopolysaccharide (LPS)-binding protein/CD14 pathway in LPS induction of tissue factor expression in monocytic cells.

Endotoxic shock is associated with a coagulopathy, organ failure, and death. Tissue factor (TF) expression by monocytes exposed to bacterial endotoxin (lipopolysaccharide [LPS]) may mediate the coagulopathy and contribute to the high mortality of this disease. We examined the role of the LPS-binding protein (LBP)/CD14 receptor pathway in the LPS induction of TF expression in human monocytic THP-1 cells and peripheral blood monocytes. In THP-1 cells, the threshold concentration of LPS required to induce TF activity in serum-free medium was reduced 20-fold by purified LBP, which also enhanced TF mRNA synthesis. Similarly, monocytes cultured in the presence of serum were induced to express TF antigen at LPS concentrations 100 times lower than monocytes cultured in serum-free medium. An anti-LBP monoclonal antibody indicated that this effect was dependent on the presence of LBP in serum. LPS/LBP induction of TF activity and TF antigen expression in these monocytic cells were also inhibited by an anti-CD14 monoclonal antibody, indicating a requirement for the CD14 receptor. Thus, we suggest that low levels of LPS (5 to 100 pg/mL) present during sepsis induce TF expression in monocytes via the LBP/CD14-dependent pathway.

Acute-Phase Proteins

Lipopolysaccharide (LPS) recognition in macrophages. Participation of LPS-binding protein and CD14 in LPS-induced adaptation in rabbit peritoneal exudate macrophages.

Exposure of rabbit peritoneal exudate macrophages (PEM) or whole blood to picomolar concentrations of LPS induces adaptation or hyporesponsiveness to LPS. Because of the importance of plasma LPS-binding protein (LBP) and the macrophage cell membrane protein CD14 in recognition of LPS, we examined the effect of LBP on LPS-induced adaptation in PEM. PEM exposed to LPS in the presence of LBP for 8 h were markedly less responsive to subsequent stimulation by LPS than monocytes/macrophages (M phi) adapted in the absence of LBP. LPS-induced expression of TNF was sharply reduced in LBP-LPS-adapted PEM, but in contrast these cells remained fully responsive to Staphylococcus aureus peptidoglycan. We considered that specific hyporesponsiveness in LPS-adapted M phi or in blood monocytes could be due to decreased expression of CD14 or diminished binding of LBP-LPS complexes to CD14. However, flow cytometry analysis revealed only minimal reduction of CD14 expression or CD14-dependent binding of a fluorescent LPS derivative when normo- and hyporesponsive cells were compared. These results show that complexes of LPS and LBP are more effective than LPS alone in inducing adaptation to LPS, and LPS-induced hyporesponsiveness probably results from changes in cellular elements distinct from CD14 that are involved in either LPS recognition or LPS-specific signal transduction.

Acclimatization

Degenerating Y chromosome of Drosophila miranda: a trap for retrotransposons.

In Drosophila miranda, the larval cuticle protein (Lcp) genes are located on the X2 and Y chromosomes, while in other Drosophila species the Lcp genes are inherited on the autosomes. We chose the D. miranda species as a model system to analyze the molecular bases of Y chromosome degeneration, a phenomenon observed in many species. DNA sequence analysis of the Y chromosomal Lcp gene locus reveals dense clustering of trapped retrotransposons. Once inserted at the Y chromosomal location they cannot easily be eliminated by unequal crossing-over, as recombination is a rare event in Drosophila males. In addition, we have uncovered an example of a completely inactive allele on the degenerating Y chromosome. The existence of such inactive Y-specific alleles was originally predicted in H. J. Muller's model for Y chromosome degeneration. We demonstrate that the Y chromosomal Lcp4 allele is no longer transcribed. From the divergence in DNA sequence organization of former homologous chromosome regions we conclude that changes in chromosome structure and destruction of genetic activity in degenerating Y chromosomes are based on one major mechanism, which operates by means of transposable elements.

Alleles

Influence of surface characteristics on bone integration of titanium implants. A histomorphometric study in miniature pigs.

The purpose of the present study was to evaluate the influence of different surface characteristics on bone integration of titanium implants. Hollow-cylinder implants with six different surfaces were placed in the metaphyses of the tibia and femur in six miniature pigs. After 3 and 6 weeks, the implants with surrounding bone were removed and analyzed in undecalcified transverse sections. The histologic examination revealed direct bone-implant contact for all implants. However, the morphometric analyses demonstrated significant differences in the percentage of bone-implant contact, when measured in cancellous bone. Electropolished as well as the sandblasted and acid pickled (medium grit; HF/HNO3) implant surfaces had the lowest percentage of bone contact with mean values ranging between 20 and 25%. Sandblasted implants with a large grit and titanium plasma-sprayed implants demonstrated 30-40% mean bone contact. The highest extent of bone-implant interface was observed in sandblasted and acid attacked surfaces (large grit; HCl/H2SO4) with mean values of 50-60%, and hydroxylapatite (HA)-coated implants with 60-70%. However, the HA coating consistently revealed signs of resorption. It can be concluded that the extent of bone-implant interface is positively correlated with an increasing roughness of the implant surface.

Animals

Preferential Y chromosomal location of TRIM, a novel transposable element of Drosophila miranda, obscura group.

We have isolated a novel transposable element from the Y chromosome of Drosophila miranda (obscura group) which shows an organization intermediate between that of typical retroviruses and the I factor of Drosophila melanogaster. The site of integration of this element, TRIM, is an inverted repeat. On the 5' side the central region of TRIM is bordered by a sequence homologous to the tRNA primer binding site (PBS) and on the 3' side by a sequence homologous to the polypurine tract (PPT). The 5' LTR (long terminal repeat) contains transcription signals, such as a TATA box and a polyadenylation sequence. Three long open reading frames (ORFs) are found within the central region of the transposon. ORF1 and ORF2 show amino acid homology to the I factor of D. melanogaster and to conserved amino acid residues of retroviral reverse transcriptases. When used as a probe for in situ hybridization the TRIM element labels about 25 euchromatic sites and the chromocenter in polytene nuclei of D. miranda females. In the chromosome complement of males the polytenized part of the Y chromosome shows about the same number of additional TRIM homologous elements. Thus, as a result of this enrichment of TRIM elements in the Y chromosome, the genomic size of the TRIM population in D. miranda males is approximately doubled.

Amino Acid Sequence

[Experimental studies of the stability behavior of the coxal end of the femur after montage and removal of DHS implants in the intact cadaver femur].

After experimental implantation in non-fractured cadaver femora, the ASIF dynamic hip screw system supported the femoral neck and the lateral proximal femur and prevents deformation, depending on the vector of the resultant force. Three positions of weight-bearing were simulated: near-axial loading of the femoral neck, standing on one leg and standing on two legs. After removal of the metal the bone breaking point was markedly lowered.

Biomechanical Phenomena

The limited contact dynamic compression plate (LC-DCP).

To realize the new concept of biological internal fixation the limited contact dynamic compression plate was developed. It minimizes vascular damage to the plated bone segment. It should lead to a more versatile and efficient application of internal fixation using plates.

Bone Plates

Implications of admission hypothermia in trauma patients.

Hypothermia is common after severe injury, and has been associated with an increased mortality rate in patients stratified by anatomic indices of injury severity. In this retrospective study of 173 patients, early post-traumatic hypothermia was found to correlate with physiologic indicators of volume deficit, independently of the amount of intravenous fluid received. There was no correlation found between admission core temperature and time from injury, blood alcohol, or presence of severe closed head injury. Hypothermic patients (less than 35 degrees C) had a lower predicted probability of survival and a higher mortality rate than euthermic patients (greater than or equal to 35 degrees C). However, when patients were stratified by physiologic and anatomic indicators of injury severity, mortality rates among the euthermic and hypothermic patients were not significantly different. Early post-traumatic hypothermia does not appear to exert an independent effect upon outcome.

Adult

[Stress protection in plate osteosynthesis: myth or reality?].

It is generally admitted that plate fixation of fractures results in reduced stress (stress protection) and subsequent structural adaptation of bone (bone loss). The analysis of the stress pattern and the reduction of deformation work in plated bones is a prerequisite for the assertion that bone loss is stress related. The strain field within bones under eccentric axial load has been analyzed theoretically and verified experimentally. The difference between the reduction of stress obtained using the flexible plate materials is small. Reduction of plate stiffness does not result in proportional improvement of the bone strain.

Bone Plates