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Biomedical subjects

D Kaiser

Publications and source records attributed to D Kaiser.

At least 19 recordsLinked to original sources

Evolution of sensory complexity recorded in a myxobacterial genome.

Myxobacteria are single-celled, but social, eubacterial predators. Upon starvation they build multicellular fruiting bodies using a developmental program that progressively changes the pattern of cell movement and the repertoire of genes expressed. Development terminates with spore differentiation and is coordinated by both diffusible and cell-bound signals. The growth and development of Myxococcus xanthus is regulated by the integration of multiple signals from outside the cells with physiological signals from within. A collection of M. xanthus cells behaves, in many respects, like a multicellular organism. For these reasons M. xanthus offers unparalleled access to a regulatory network that controls development and that organizes cell movement on surfaces. The genome of M. xanthus is large (9.14 Mb), considerably larger than the other sequenced delta-proteobacteria. We suggest that gene duplication and divergence were major contributors to genomic expansion from its progenitor. More than 1,500 duplications specific to the myxobacterial lineage were identified, representing >15% of the total genes. Genes were not duplicated at random; rather, genes for cell-cell signaling, small molecule sensing, and integrative transcription control were amplified selectively. Families of genes encoding the production of secondary metabolites are overrepresented in the genome but may have been received by horizontal gene transfer and are likely to be important for predation.

Deltaproteobacteria↗

[Surgical curriculum. A model from thoracic surgery].

There is a shortage of new surgeons in Germany. The blame for this is laid on poor working and training conditions in German hospitals. Professional associations suggest restructuring teaching plans to improve surgical education. The study conditions, postgraduate education, and surgical training in a thoracic surgical department are presented as a model curriculum. Surgical training can be structured. Curricula can be delineated for colleagues and applicants and comply with quality management standards. Clear and fair courses would improve surgical training and satisfy the expectations of contemporary surgeons.

Curriculum↗

Interaction field based and hologram based QSAR analysis of propafenone-type modulators of multidrug resistance.

Overexpression of membrane bound, ATP-dependent transport proteins is one of the predominant mechanisms leading to multiple drug resistance in tumor therapy as well as in the treatment of bacterial and fungal infections. In tumor therapy, P-glycoprotein (P-gp, ABCB1) is responsible for transport of a wide variety of natural product toxins out of tumor cells leading to decreased accumulation of cytotoxic drugs within the cells. Inhibition of P-gp thus gives rise to a resensitization of multidrug resistant tumor cells and represents a versatile approach for modulation of multidrug resistance. Within this paper, a set of propafenone-type inhibitors of P-gp were analyzed using both interaction field based methods such as CoMFA and CoMSIA and Hologram QSAR. With both methods, highly predictive models with q2-values>0.65 were obtained. Models using logP as additional descriptor generally yielded higher predictive power. On basis of unfavorable steric and favorable electrostatic and hydrophobic interaction fields, these models were able to explain all outlayers identified in previous Hansch-analyses. For HQSAR analysis, models with q2-values up to 0.72 were obtained. Positive influences were found for electron donating groups on the aromatic systems. Highly negative influences were found for diphenylalkylamine substituents, which is a further hint for steric hindrance. The models with highest predictive power were used for screening of a small virtual library. Synthesis and pharmacological testing of a sub set of this library showed that the external predictivity of the HQSAR models generally is lower than the internal one.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Complications of malignant tumors--malignant pleural effusions].

Malignant pleural effusion is a complication of malignant diseases that has an appreciable negative impact on the patient's quality of life. In view of the greatly reduced life expectancy of between 3 and 12 months (median), diagnostic and therapeutic management must be orientated to the principles of palliation. Diagnostic measures comprise cytological/histological confirmation of the malignant effusion and, where necessary, of the underlying malignant disease and the extent of the intrathoracic tumor growth. In view of the tendency of malignant pleural effusion to relapse, pleurodesis is indicated, which is most effectively accomplished by video-assisted thoracoscopic talcum poudrage.

Biopsy↗

Melanoma associated antigen (MAGE)-A3 expression in Stages I and II non-small cell lung cancer: results of a multi-center study.

OBJECTIVES: Adjuvant immunotherapy is an innovative therapeutic option that might potentially improve outcome of early-stage non-small cell lung cancer. Melanoma associated antigen (MAGE)-A3 is a promising target for immunotherapy because it is exclusively presented on the cell surface of cancer cells and might be associated with an aggressive cancer phenotype. The present study was performed to determine the rate of MAGE-A3 expression in early-stage non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Primary tumor samples from 204 patients with operable clinical Stages I or II NSCLC were collected between March and November 2001. Pathological Stage was determined by the local pathologist in each of the 16 participating institutions. Tissue samples were stored immediately after surgery in a RNA-stabilizing solution and were frozen at -20 degrees C. MAGE-A3 expression was analyzed by detection of MAGE-A3 transcripts using reverse-transcriptase polymerase chain reaction. RESULTS: MAGE-A3 expression was observed in 80 out of the 204 (39.2%) examined Stages I-II primary tumors. Stratification into UICC-Stages showed that 31 out of 105 (29.5%) Stage I non-small cell lung cancers and 49 out of 99 (49.5%) Stage II non-small cell lung cancers expressed MAGE-A3. In comparison to Stage I, the rate of MAGE-A3 positive tumors was significantly increased in Stage II (P=0.004; Chi-square test). CONCLUSION: The MAGE-A3 expression rate showed that a promising proportion of operable patients with early-stage non-small cell lung cancers are possible candidates for trials investigating adjuvant therapy with MAGE-A3 immunization. Currently, a phase two trial of adjuvant MAGE-A3 vaccination is in progress.

Antigens, Neoplasm↗

Plastic reconstruction of an extended corrosive injury of the posterior tracheal wall with an autologous esophageal patch.

We report on a patient with an extended corrosive injury of the posterior tracheal wall and left-sided tracheo-esophageal fistula after severe inhalative trauma. Resection of the fistula and necrotic tissue was followed by reconstruction of the posterior tracheal wall with an esophageal patch. Interposition of the stomach was performed to restore upper gastro-intestinal continuity. Revision was necessary due to an anastomotic insufficiency and a recurrent fistula between the trachea and the esophago-gastrostomy on the left side. The stomach was resected and the fistula was covered with a sternocleidomastoideus muscle flap. Several weeks later interposition of the right hemicolon was performed to establish the gastro-intestinal tract and the patient recovered completely, thereafter.

Adult↗

[Benign fibrous histiocytomas as a differential diagnosis in cavitary lung disease].

Benign fibrous histiocytomas (BFH) are uncommon pulmonary tumours. These lesions usually present as slow-growing, solid masses. We report the rare case of a young man with cavitary BFH. The 20-year-old patient, a non-invasive drug abuser, had suffered from hemoptysis for two months. The chest X-ray showed a solitary pulmonary nodule with a diameter of 2 cm in the left lower lobe with central cavitation. Fiberoptic bronchoscopy showed a normal bronchial system, biopsies were not diagnostic and no acid fast bacilli were found. Considering the patient's history and the cavitary process, a non-specific abscess was suspected and an antimicrobial treatment was started. Since no treatment effect was observed, biopsies from a second bronchoscopy were suspicious of a malignant mesenchymal tumour. Lower lobe resection with lymphadenectomy revealed a benign fibrous histiocytoma. This is--to our knowledge--the first reported case of a BFH presenting with cavitation.

Adult↗

Mechanosensitive induction of apoptosis in fibroblasts is regulated by thrombospondin-1 and integrin associated protein (CD47).

Fibroblasts are cultured in three-dimensional collagen matrices to investigate the effect of mechanical tension on the regulation of apoptosis. Under the influence of mechanical loading, the cells show little apoptosis whereas releasing of tension leads to an increase up to tenfold during the first 24 h and remains constant for further 48 h. An autocrine loop of the integrin alpha(V)beta(3)/CD47 receptor complex and thrombospondin-1 is identified as the molecular coupling device between mechanical loading and apoptosis: The integrin alpha(V)beta(3) is expressed under mechanical loading as well as unloading whereas the CD47 could only be identified after the release of tension. The secreted thrombospondin binds to the active receptor and induces apoptosis. The presented mechanosensitive regulation of apoptosis in fibroblast cultures could be an essential mechanism for the regression of the granulation tissue by apoptosis in the process of wound healing.

Antigens, CD↗

Long-term changes in soft tissue height on the facial surface of dental implants.

The success of osseous healing around dental implants has allowed for an increased emphasis on soft tissue healing and esthetic results. However, there is limited information profiling the long-term healing of the soft tissues following prosthesis placement. The purpose of this study was to assess the long-term changes in the position of the facial soft tissue margins following restoration of a one-stage implant system. One hundred and six one-stage ITI implants were evaluated in 39 patients. Implants were placed in maxillary and mandibular anterior regions. Clinical assessment of the soft tissues on the midfacial aspect of the implants was performed over a 2-year period, at 3 and 6 month intervals, following placement of the final restoration. A total of 63 implants were placed as multiple units in the mandible, 23 as single units in the maxilla, and 20 as multiple units in the maxilla. There were no implant failures over this time period. Overall, on the facial aspect of 61% of the 106 implants there was 1 mm or more of soft tissue recession, whereas 19% of the implants showed 1 mm or more of gain in soft tissue height. There was a significantly (P < 0.01) greater number of implants showing a gain in soft tissue levels in the mandibular implants compared with the maxillary implants. Of the 39 patients assessed, 24 showed a loss and five showed a gain of 1 mm or more of the soft tissue levels around the implants. Overall, there was a significant decrease in the mean levels of tissue height of 0.6 mm within the first 6 months, with relatively little change afterward. However, in evaluating only patients showing a loss in tissue height around one or more implants, the mean loss in tissue height was 1.6 mm after 24 months. These results suggest that the potential for significant changes in soft tissue levels after completion of restorative therapy need to be considered for implant therapy in esthetic areas.

Adolescent↗

Effects of antiplatelet agents on platelet-induced thrombin generation.

OBJECTIVES: The influence of antiplatelet agents on platelet-induced thrombin generation may increase the risk of bleeding. Assessment of the endogenous thrombin potential (ETP), is therefore a parameter deserving attention in early pharmacodynamic studies with antiplatelet drugs. The aim ofthis study was to assess whether an automated ETP-assay can be used to determine possible inhibitory effects of antiplatelet drugs on platelet-associated thrombin generation. METHODS: We first characterized the in vitro dose-response relationship of several platelet agonists (ADP, collagen, U46619, TRAP (amino acid sequence: SFLLRNP) and tissue factor (TF) using the generation of ETP. One submaximal concentration of each agonist was then used to assess the influence of in vivo treatment with aspirin (single oral dose of 500 mg as inhibitor of thromboxane synthesis) and clopidogrel (given orally for 6 days, as an inhibitor of the purinergic P2Y12-receptor on platelets) and in vitro treatment with abciximab (which inhibits the platelet glycoprotein IIb/IIIa-receptor for fibrinogen), on the ETP. RESULTS: The effect of TF and the other platelet inducers on thrombin generation was dose-dependent. Repeat measurements on samples from the same subject, with the same inducer concentration on 2 different occasions showed a variability of approx. 22% (absolute difference between 2 measurements as % of mean). The coefficient on variation of repeat measurements of one sample varied between 7% and 17%, depending on the inducer. After a single dose of aspirin, ETP was reduced by 25-40%, depending on the platelet activating agent used. The reduction in ETP with abciximab in vitro was more pronounced. In contrast, TF-induced ETP was not influenced by aspirin or abciximab. Clopidogrel, administered for 6 days, reduced the ETP by 60% when platelets were stimulated using 20 microM ADP, whereas collagen-induced ETP and TF-induced ETP remained unchanged. CONCLUSIONS: The ETP-method is a sensitive and reproducible method for the detection of drug effects on platelet-induced thrombin generation of high throughput, and can be recommended for studies on the pharmacodynamic profile of drugs interfering with platelet function.

Adult↗

Pattern formation and traveling waves in myxobacteria: theory and modeling.

Recent experiments have provided new quantitative measurements of the rippling phenomenon in fields of developing myxobacteria cells. These measurements have enabled us to develop a mathematical model for the ripple phenomenon on the basis of the biochemistry of the C-signaling system, whereby individuals signal by direct cell contact. The model quantitatively reproduces all of the experimental observations and illustrates how intracellular dynamics, contact-mediated intercellular communication, and cell motility can coordinate to produce collective behavior. This pattern of waves is qualitatively different from that observed in other social organisms, especially Dictyostelium discoideum, which depend on diffusible morphogens.

Models, Biological↗

Cell behavior in traveling wave patterns of myxobacteria.

Cells in the early stages of starvation-induced fruiting body development migrate in a highly organized periodic pattern of equispaced accumulations that move as traveling waves. Two sets of waves are observed moving in opposite directions with the same wavelength and speed. To learn how the behavior of individual cells contributes to the wave pattern, fluorescent cells were tracked within a rippling population. These cells exhibit at least three types of organized behavior. First, most cell movement occurs along the same axis as the rippling movement. Second, there is a high degree of cell alignment parallel to the direction of rippling, as indicated by the biased movement. Third, by controlling the reversal frequency, cell movement becomes periodic in a rippling field. The periodicity of individual cells matches the period of macroscopic rippling. This last behavior is unique to a rippling population and, on the basis of Myxococcus xanthus genetic data, we conclude that this periodicity is linked to the C signal, a nondiffusible cell contact-mediated signaling molecule. When two cells moving in opposite directions meet end to end, they transmit the C signal to each other and in response reverse their gliding direction. This model of traveling waves represents a new mode of biological pattern formation that depends on cell-contact interactions rather than reaction diffusion.

Chemotaxis↗

Proatherogenic flow conditions initiate endothelial apoptosis via thrombospondin-1 and the integrin-associated protein.

Recently it has been shown that vascular endothelial cells (EC) are completely devoid of apoptosis if cultivated under a steady laminar flow and that apoptosis is induced by turning off the flow. An autocrine loop of thrombospondin-1 (TSP-1) and the alpha(v)beta(3) integrin/integrin-associated protein (IAP) complex has been identified as the molecular coupling device between flow and apoptosis. Lack of blood flow is a rare and mostly transient phenomenon whereas irregular flow conditions are permanently present at arterial bifurcations and sites of abnormal vessel morphology. Irregular flow conditions are established here either by the action of a cone-and-plate type flow apparatus generating a uniform turbulent flow or in a flow chamber by insertion of a local hindrance creating a zone of unsteady laminar flow with vortex formation and lowered shear stress. In both cases apoptosis is induced either throughout the entire monolayer or restricted to the locally defined area. Flow disturbance and apoptosis are coupled by the described autocrine loop of TSP-1 and the integrin/IAP receptor complex. In vivo atherosclerotic lesions occur predominantly at sites of flow irregularities, which are thought to be pro-atherogenic. Thus we propose a key role of the identified mechanosensitive apoptosis induction for the initiation of atherosclerosis.

Antigens, CD↗

Vascular endothelial cells express a functional fas-receptor due to lack of hemodynamic forces.

The fas system is present in atherosclerotic lesions. However, its role in the initiation and progression is still unclear. Here we show that in endothelial cells (EC) the expression of the fas receptor is regulated by flow conditions. The EC of the vascular system are regularly exposed to a range of hemodynamic forces with great impact on cellular structures and functions. Recently it was reported that in endothelial cells the lack of hemodynamic forces as well as irregular flow conditions trigger apoptosis by induction of a mechanosensitive autocrine loop of thrombospondin-1 and the alpha(V)beta(3) integrin/integrin-associated protein complex. Here we show that EC cultivated under regular laminar flow conditions are devoid of the fas-receptor whereas cultivation under static conditions as well as under turbulence leads to its expression. Stimulation of the fas-receptor by its ligand increases the amount of apoptotic cells by twofold; the increase can be prevented by blocking the fas-receptor. The availability of the expressed fas receptor for stimulation by its ligand hints at a role as a tool for progression of atherosclerosis.

Apoptosis↗

The act operon controls the level and time of C-signal production for Myxococcus xanthus development.

The C-signal is a morphogen that controls the assembly of fruiting bodies and the differentiation of myxospores. Production of this signal, which is encoded by the csgA gene, is regulated by the act operon of four genes that are co-transcribed from the same start site. The act A and act B genes regulate the maximum level of the C-signal, which never rises above one-quarter of the maximum wild-type level of CsgA protein in null mutants of either gene. The act A and act B mutants have the same developmental phenotype: both aggregate, neither sporulates, both prolong rippling. By sequence homology, act A encodes a response regulator, and act B encodes a sigma-54 activator protein of the NTRC class. The similar phenotypes of act A and act B deletion mutants suggest that the two gene products are part of the same signal transduction pathway. That pathway responds to C-signal and also regulates the production of CsgA protein, thus creating a positive feedback loop. The act C and act D genes regulate the time pattern of CsgA production, while achieving the same maximum level. An act C null mutant raises CsgA production 15 h earlier than the wild type, whereas an act D null mutant does so 6 h later than wild type. The loop explains how the C-signal rises continuously from early development to a peak at the time of sporulation, and the act genes govern the time course of that rise.

Bacterial Proteins↗

Characterizations of highly expressed genes of four fast-growing bacteria.

Predicted highly expressed (PHX) genes are characterized for the completely sequenced genomes of the four fast-growing bacteria Escherichia coli, Haemophilus influenzae, Vibrio cholerae, and Bacillus subtilis. Our approach to ascertaining gene expression levels relates to codon usage differences among certain gene classes: the collection of all genes (average gene), the ensemble of ribosomal protein genes, major translation/transcription processing factors, and genes for polypeptides of chaperone/degradation complexes. A gene is predicted highly expressed (PHX) if its codon frequencies are close to those of the ribosomal proteins, major translation/transcription processing factor, and chaperone/degradation standards but strongly deviant from the average gene codon frequencies. PHX genes identified by their codon usage frequencies among prokaryotic genomes commonly include those for ribosomal proteins, major transcription/translation processing factors (several occurring in multiple copies), and major chaperone/degradation proteins. Also PHX genes generally include those encoding enzymes of essential energy metabolism pathways of glycolysis, pyruvate oxidation, and respiration (aerobic and anaerobic), genes of fatty acid biosynthesis, and the principal genes of amino acid and nucleotide biosyntheses. Gene classes generally not PHX include most repair protein genes, virtually all vitamin biosynthesis genes, genes of two-component sensor systems, most regulatory genes, and most genes expressed in stationary phase or during starvation. Members of the set of PHX aminoacyl-tRNA synthetase genes contrast sharply between genomes. There are also subtle differences among the PHX energy metabolism genes between E. coli and B. subtilis, particularly with respect to genes of the tricarboxylic acid cycle. The good agreement of PHX genes of E. coli and B. subtilis with high protein abundances, as assessed by two-dimensional gel determination, is verified. Relationships of PHX genes with stoichiometry, multifunctionality, and operon structures are also examined. The spatial distribution of PHX genes within each genome reveals clusters and significantly long regions without PHX genes.

Amino Acyl-tRNA Synthetases↗

Building a multicellular organism.

Multicellular organisms appear to have arisen from unicells numerous times. Multicellular cyanobacteria arose early in the history of life on Earth. Multicellular forms have since arisen independently in each of the kingdoms and several times in some phyla. If the step from unicellular to multicellular life was taken early and frequently, the selective advantage of multicellularity may be large. By comparing the properties of a multicellular organism with those of its putative unicellular ancestor, it may be possible to identify the selective force(s). The independent instances of multicellularity reviewed indicate that advantages in feeding and in dispersion are common. The capacity for signaling between cells accompanies the evolution of multicellularity with cell differentiation.

Biological Evolution↗

[Drainage technique in thoracic trauma and pneumothorax].

In most cases of perforating thoracic injury, thoracotomy is performed immediately. In blunt thoracic trauma with pneumothorax, the drain--24-32 Ch--is inserted via a minithoracotomy on the anterior/intermediate axillary line in the fifth intercostal space. In spontaneous pneumothorax, a trocar is inserted at the same site and the lung inspected thorascopically for so-called ELCs. The drain--in this case 24 Ch--is then directed dorsally into the dome of the pleura, this being essential for optimal evacuation of air and secretion. So-called Pleuracaths are unsuitable because they are 50% coated with fibrin. Drainage on the medioclavicular line in the second or third intercostal space is inappropriate for various reasons. Emergency management of tension pneumothorax comprises pressure relief via a cannula.

Chest Tubes↗