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Biomedical subjects

D Kaiser

Publications and source records attributed to D Kaiser.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Multimodality therapy concept in stage I-IIIA small cell bronchial carcinoma. Case follow-up over 15 years].

We analysed our results of multimodal therapy including chemotherapy, radiotherapy and surgery in 150 consecutive patients with SCLC stage I-IIIa operated on in our hospital between 1983 and 2000. Median age: 58 years, stages see Table 2. Patients with proven SCLC had induction chemotherapy prior to surgery. All patients received three cycles of adjuvant chemotherapy, some with additional radiotherapy. Perioperative mortality: 2%. Median survival: 22.4 months. R0 resection was possible in 84% of all patients. Pre- and post-surgery staging differed in the majority of the patients. Rotes of 1-, 2- and 5-year survival were 79%, 47%, and 32%, respectively. A median survival of 22.4 months in multimodally treated LD-SCLC, most of them stage IIb/IIIa appears promising. Randomized studies based on clinical staging procedures are not recommended. Survival data are promising.

Carcinoma, Bronchogenic↗
PubMed2001

[Non-small-cell bronchial carcinoma with pathological N2 involvement: adjuvant radiotherapy versus adjuvant chemo-radiotherapy].

Fifty-eight patients, 28 of them included in a German multicenter study, were treated either with radiotherapy (5 x 2 Gy/50 Gy) or combined radio-chemotherapy (cisplatin 75 mg/m2 d1 in cases with pneumonectomy etoposide 120 mg/m2 d1-3) and Ifosfamid 1.5 mg/m2 d1-4, 3 cycles) following surgery in pN2-NSCLC. Metastatic disease or local failure was seen in 24 patients (43%), in the majority with distant metastasis (n = 21), in 4 patients combined local and distant failure. Time to progression (TTP) was 27 to 1172 days, median 244 days. Median survival of the whole group was 873 days (= 29 months), the 3-year survival 49%. Comparing the two groups there was an advantage (not significant) in favor of the combined treated group with a median survival of 1449 days versus 765 days (p = 0.22).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Bacterial motility: how do pili pull?

Forceful retraction of a bacterial pilus has been directly observed for the first time. As retraction clarifies the basic mechanochemistry of single cell twitching and gliding movements, so cell-to-cell signalling by contact clarifies the coordination of multicellular gliding movements.

Bacterial Physiological Phenomena↗
PubMed2000

Integrin-associated protein and thrombospondin-1 as endothelial mechanosensitive death mediators.

Recently, it was reported that the offset of hemodynamic forces induces an unusual pattern of apoptosis in vascular endothelium (1). Although the apoptotic trigger covers all cells and is maintained for a longer time period, only few cells become apoptotic. So, in contrast to common apoptosis inducers, the lack of hemodynamic forces initiates only a low basal level of apoptosis, however steadily increases with time, this way preventing the complete vessel destruction upon an only transient offset of blood flow. The molecular means by which the mechanical stimulus and apoptosis are smoothly coupled have now been identified as an autocrine loop of thrombospondin-1 (TSP-1) and the alpha(v)beta(3) integrin/integrin-associated protein (IAP) complex as its receptor. Vascular EC (EC) secrete TSP-1 only in postconfluent static monolayers and not under flow. This also holds true for the IAP whereas the alpha(v)beta(3) integrin is present under static conditions, as well as under flow, assigning the IAP an essential and new switch function in the receptor complex.

Antibodies, Monoclonal↗
PubMed2000

MRP8/MRP14, CD11b and HLA-DR expression of alveolar macrophages in pneumonia.

Activation of alveolar macrophages is characterised by specific alterations to the expression pattern of surface markers under certain pathological conditions. MRP8/MRP14 and CD11b are involved in the regulation of macrophage migration and adhesion. HLA-DR regulates the antigen presentation by alveolar macrophages. The aim of this study was to investigate the phenotype of alveolar macrophages in pneumonia particularly in relationship to the changes in concentrations of TGF-beta1 and IL-8. Using cytofluorimetry, we analysed the surface expression of MRP8/MRP14, CD11b, and HLA-DR on alveolar macrophages of 42 pneumonia (PN) patients, 14 patients with interstitial lung diseases (ILD), five patients with chronic obstructive lung disease (COPD), and 58 patients without lung disease. Phenotypic characteristics were correlated to the concentration of TGF-beta1 and IL-8 in the bronchoalveolar lavage fluid (BALF) of the same patients. The direct influence of TGF-beta1 and IL-8 on expression of MRP8/MRP14, CD11b and HLA-DR of cultured monocytes and MonoMac cells was analysed. Significantly more MRP8/MRP14 and CD11b positive macrophages and less HLA-DR-positive macrophages were found in PN but not in ILD or COPD. The percentage of CD11b-positive macrophages correlated with the TGF-beta1 as well as the IL-8 concentrations. The amount of HLA-DR-positive macrophages correlated negatively to the concentration of TGF-beta1 and IL-8. These findings document a significant activation of alveolar macrophages during pneumonia. TGF-beta1 led to a modulation of HLA-DR and MRP8/MRP14-antigen expression in vitro. In conclusion, it was shown that in pneumonia but not in ILD or COPD alveolar macrophages were characterised by an increased MRP8/MRP14 and CD11b expression and a diminished HLA-DR expression. The characterisation of subpopulations within the alveolar macrophages may be a useful tool for the monitoring of disease progression.

Antigens, Differentiation↗
PubMed2000

A common step for changing cell shape in fruiting body and starvation-independent sporulation of Myxococcus xanthus.

Myxococcus xanthus can sporulate in either of two ways: at the end of the program of fruiting body development or after exposure of growing cells to certain reagents such as concentrated glycerol. Fruiting body sporulation requires starvation, while glycerol sporulation requires rapid growth, and since the two types of spores are structurally somewhat different, it has generally been assumed that the two processes are different. However, a Tn5 Lac insertion mutation, Omega7536, has been isolated which simultaneously blocks the development of fruiting body spores as well as glycerol-induced spores. Both sporulation pathways are blocked in the mutant within the process that converts a rod-shaped cell into a spherical spore. The Omega7536 locus is expressed at the time of cell shape change appropriate to each process, early after glycerol induction and late after starvation induction. On the C-signal response pathway, it is possible to identify positions for the normal function of the Omega7536 locus and for the inducing stimulus from glycerol that are unique and consistent with the observations. Although the two sporulation pathways differ in certain respects, it is shown that they share at least one step for changing a rod-shaped cell into a spherical spore.

Bacterial Proteins↗
PubMed2000

A sigma(54) activator protein necessary for spore differentiation within the fruiting body of Myxococcus xanthus.

Insertion of an internal DNA fragment into the act1 gene, which encodes one of several sigma(54)-activator proteins in Myxococcus xanthus, produced a mutant defective in fruiting body development. While fruiting-body aggregation appears normal in the mutant, it fails to sporulate (<10(-6) the wild-type number of viable spores). The A and C intercellular signals, which are required for sporulation, are produced by the mutant. But, while it produces A-factor at levels as high as that of the wild type, the mutant produces much less C-signal than normal, as measured either by C-factor bioassay or by the total amount of C-factor protein detected with specific antibody. Expression of three C-factor-dependent reporters is altered in the mutant: the level of expression of Omega4414 is about 15% of normal, and Omega4459 and Omega4403 have alterations in their time course. Finally, the methylation of FrzCD protein is below normal in the mutant. It is proposed that Act1 protein responds to C-signal reception by increasing the expression of the csgA gene. This C-signal-dependent increase constitutes a positive feedback in the wild type. The act1 mutant, unable to raise the level of csgA expression, carries out only those developmental steps for which a low level of C-signaling is adequate.

Adaptor Proteins, Signal Transducing↗
PubMed2000

A putative enolpyruvyl transferase gene involved in nikkomycin biosynthesis.

The nikO gene encoding a putative enolpyruvyl transferase has been identified within the Streptomyces tendae Tü901/8c nikkomycin gene cluster. nikO encodes a deduced protein of 471 amino acid residues which exhibits significant sequence similarity to UDP-N-acetylglucosamine enolpyruvyl transferase and 5-enol-pyruvylshikimate 3-phosphate synthase from various origin. The nikO gene was inactivated by inserting a kanamycin resistance cassette; the mutant did not produce biologically active nikkomycins I, J, X, and Z nor the nucleoside moieties, nikkomycins C(x) and C(z), but accumulated the novel component RT 2.0. RT 2.0 has been isolated from culture filtrate and its structure was determined by using mass spectrometry and NMR analyses as ribofuranosyl-4-formyl-4-imidazolone which represents a novel nucleoside. The putative activity of the nikO gene product in nikkomycin biosynthesis will be discussed.

Alkyl and Aryl Transferases↗
PubMed1999

Myxococcus cells respond to elastic forces in their substrate.

Elasticotaxis describes the ability of Myxococcus xanthus cells to sense and to respond to elastic forces within an agar gel on which they rest. Within 5 min of the application of stress, each cell begins to reorient its long axis perpendicular to the stress force. The cells then glide in that direction, and the swarm becomes asymmetric. A quantifiable assay for the strength of elasticotaxis is based on the change in swarm shape from circular to elliptic. By using a collection of isogenic motility mutants, it has been found that the ability to respond to stress in agar depends totally on adventurous (A) motility, but not at all on social (S) motility or on the frz genes. In fact, S- mutants (which are moving only by means of A motility) respond to the applied stress more strongly than does the wild type, despite the fact that their spreading rates are slower than that of the wt strain. Based on the swarming and elasticotactic phenotypes of isogenic frizzy strains that were also defective either in A or S motility, frz behaves as if part of the S motility system.

Agar↗
PubMed1999

Cell fate and organogenesis in bacteria.

Intercellular signaling through the Notch receptor and its ligands leads to the spatial differentiation of cell fate in vertebrates and invertebrates. In Myxococcus xanthus, fruiting-body development requires the transmission of a cell-bound intercellular signal by the protein called C-factor, which is functionally equivalent to the eukaryotic Notch ligands. Functional parallels between these two signaling systems include strong positive and negative feedback, and a consequent role in spatial differentiation. Consideration of these parallels enables us to make testable experimental predictions about Notch and C-signaling.

Animals↗
PubMed1999

N-hydroxy peptides as substrates for alpha-chymotrypsin.

An N-hydroxylated peptide bond was found to be cleaved faster by an endopeptidase than the corresponding peptide bond. This preferred enzymatic cleavage was detected during proteolytic studies of the N-hydroxy peptide SIINFpsi[CO-N(OH)]GKL in the presence of the serine protease alpha-chymotrypsin in comparison with the natural SIINFEKL epitope and related analogs. For the first time, the replacement of the peptide bond by another motif afforded an oligomer which is degraded faster than the natural peptide. The N-hydroxy peptide is also more sensitive to the enzymatic degradation than the Gly-containing analog SIINFGKL. A tentative explanation for the unexpected higher cleavage rate of the CO-N(OH) bond is given on the basis of the N-OH intramolecular H-bonding capacity as indicated by NMR experiments. This property of the hydroxamate group may be of particular advantage for the introduction of a specific cleavage site within peptidomimetics or in prodrugs.

Amino Acid Sequence↗
PubMed1999

Type IV pili and cell motility.

Type IV pili (Tfp) mediate the movement of bacteria over surfaces without the use of flagella. These movements are known as social gliding in Myxococcus xanthus and twitching in organisms such as Pseudomonas aeruginosa and Neisseria gonorrhoeae. Tfp are localized polarly. Type IV pilins have a signature N-terminal domain, which forms a coiled-coil with other monomer units to polymerize a pilus fibre. At least 10 more proteins at the base of the fibre are conserved; they are related to the type II secretion system. Movements produced by Tfp range from short, jerky displacements to lengthy, smooth ones. Tfp also participate in cell-cell interactions, pathogenesis, biofilm formation, natural DNA uptake, auto-aggregation of cells and development. What is the means by which Tfp bring about the movement of cells?

Adenosine Triphosphatases↗
PubMed1999

[Bronchial carcinoma in young adults].

Lung cancer in young adults has been differently described in publications from various regions of the world, in respect of relative incidence, distribution of morphology and stages, and prognosis of the disease. We analysed retrospectively the data from the cancer registry of the Lungenklinik Heckeshorn in Berlin between 1986 and 1995 with regard to this topic. 106/4939 patients were 40 years old or younger (2.1%). The proportion of female patients was higher in the younger group (42 vs. 29%). Adenocarcinoma was the leading subtype in young patients (33 vs. 24%). The younger group showed a higher proportion of inoperable stages IIIB and IV for non-small cell lung cancer (71 vs. 46%). Younger patients with operable stages I to IIIA non-small cell lung cancer underwent surgery much more often than patients older than 40 years (90 vs. 49%), but for all patients with this morphology there was no difference in survival between younger and older patients (302 vs. 314 patients). We conclude that lung cancer presents a clearly different clinical picture in younger patients but not a better prognosis.

Adult↗
PubMed1999

[Irrigation drainage and fibrinolysis for treatment of parapneumonial pleural empyema].

UNLABELLED: We report on our experiences on 336 patients suffering from manifest pleural empyema within a period of 10 years (1985-1995). Considering the pathogenesis, particularly the results of 218 patients with "parapneumonic pleural empyema" were analysed retrospectively. Definite healing could be achieved by chest tube placement and pleural irrigation in 201 patients (= 92.2%). Other 11 patients finally needed surgical interventions (= 5%). Only 6 patients could not be cured: An indwelling tube was palliatively inserted once and 5 patients died in the course of the medical treatment (mortality = 2.3%). Within the first years the irrigation therapy was performed using a single chest tube (n = 38%) but since 1989 a double-lumen drainage was used (n = 158). Since 1987 in most cases (n = 182) intrapleural medicinal fibrinolysis was performed by instillation of streptokinase (Varidase N). If outward invasively pretreated patients (n = 30) are analysed separately, a statistical dependency can be found between the duration and the way of treatment. Without significant difference between the groups (Gr) the average duration of treatment using a single tube without fibrinolysis (Gr1) was 31.8 days, but 26.5 days using a single tube combined with fibrinolysis (Gr2). A clear shortening of the duration is detectable if patients were treated with a combination of double lumen drainage and fibrinolysis: If 2 tubes were used (Gr4) the treatment lasted 20.6 days, using one double-lumen tube (Gr5) it took 19.8 days. There is a proof of significance at comparison of Gr4 with Gr1 (p = 0.005). Gr5 with Gr1 (p < 0.001) and Gr5 with Gr2 (p = 0.014) respectively. A significant longer duration of treatment (40.6 days, p < 0.001) is found for the group of the pretreated patients, if compared with the corresponding groups Gr4 or Gr5. CONCLUSION: Parapneumonic empyemas most often can be cured by irrigation drainage. The mortality is comparatively low. The shortest duration of treatment is needed using the combination of a double-lumen tube with intrapleural instillation of a fibrinolytic agent (Varidase N). Invasively pretreated patients need significantly longer durations at same form of treatment.

Adolescent↗
PubMed1999

Increased release of transforming growth factor (TGF)-beta1, TGF-beta2, and chemoattractant mediators in pneumonia.

Transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8), and leukotrienes are potent neutrophil chemoattractants that are released in several lung diseases. There is limited information about the release of TGF-beta in bronchoalveolar lavage fluid (BALF) of patients with pneumonia. Furthermore, it is not clear if TGF-beta is differentially expressed in different lung diseases. The aim of our study was to compare the concentrations of TGF-beta1 and TGF-beta2 in the BALF of patients with pneumonia and other lung diseases. Furthermore, correlation of the TGF-beta levels with the concentration of chemoattractant mediators as well as with indicators of macrophage and granulocyte activation should be investigated. Patients with pneumonia, interstitial lung disease (ILD), or chronic obstructive pulmonary diseases (COPD) were included. Patients with ischemic heart disease without pulmonary involvement served as controls. The concentrations of TGF-beta1 and TGF-beta2, of the chemoattractant cytokine IL-8, of leukotriene B4, and of the leukotrienes C4, D4, and E4 were measured. Neutrophil elastase and granulocyte content (PMN) were used as markers for granulocyte activation, and neopterin was used as a marker for the activation of macrophages. Significantly elevated levels of TGF-beta1 (mean = 0.216 ng/ml, p < 0.01) were found in patients with microbiologically positive pneumonia but not in patients with ILD or COPD. A significant (p < 0.001) correlation was found between the TGF-beta1 concentrations and the IL-8 levels and the percentage of granulocytes (r = 0.76, and r = 0.44, respectively). Elevated TGF-beta2 concentrations were measured in the BALF of patients with pneumonia (mean = 1.4 ng/ml, p < 0.01) and with ILD. Pneumonia was also associated with increased concentrations of leukotrienes C4, D4, and E4 (mean = 91.61 pg/ml, p < 0.05) and leukotriene B4 (mean = 203.9 pg/ml, p < 0.01), significantly elevated levels of PMN elastase (mean = 2958.26 ng/ml, p < 0.01), and neopterin (mean = 0.42 nmol/L). Our results strongly suggest that different lung diseases do differ with regard to the released cytokines. TGF-beta1 probably plays a key role in regulation of pulmonary inflammation, particularly in pneumonia.

Bronchoalveolar Lavage Fluid↗
PubMed1999

The Myxococcus xanthus pilQ (sglA) gene encodes a secretin homolog required for type IV pilus biogenesis, social motility, and development.

The Myxococcus xanthus sglA1 spontaneous mutation was originally isolated because it allowed dispersed cell growth in liquid yet retained the ability to form fruiting bodies. Consequently, most of today's laboratory strains either contain the sglA1 mutation or were derived from strains that carry it. Subsequent work showed that sglA was a gene for social gliding motility, a process which is mediated by type IV pili. Here sglA is shown to map to the major pil cluster and to encode a 901-amino-acid open reading frame (ORF) that is homologous to the secretin superfamily of proteins. Secretins form a channel in the outer membrane for the transport of macromolecules. The closest homologs found were PilQ proteins from Pseudomonas aeruginosa and Neisseria gonorrhoeae, which are required for type IV pili biogenesis and twitching motility. To signify these molecular and functional similarities, we have changed the name of sglA to pilQ. The hypomorphic pilQ1 (sglA1) allele was sequenced and found to contain two missense mutations at residues 741 (G-->S) and 762 (N-->G). In addition, 19 independent social (S)-motility mutations are shown to map to the pilQ locus. In-frame deletions of pilQ and its downstream gene, orfL, were constructed. pilQ is shown to be essential for pilus biogenesis, S-motility, rippling, and fruiting body formation, while orfL is dispensable for these processes. The pilQ1 allele, but not the DeltapilQ allele, was found to render cells hypersensitive to vancomycin, suggesting that PilQ1 alters the permeability properties of the outer membrane. Many differences between pilQ1 and pilQ+ strains have been noted in the literature. We discuss some of these observations and how they may be rationalized in the context of our molecular and functional findings.

Amino Acid Sequence↗
PubMed1999

Gliding mutants of Myxococcus xanthus with high reversal frequencies and small displacements.

Myxococcus xanthus cells move on a solid surface by gliding motility. Several genes required for gliding motility have been identified, including those of the A- and S-motility systems as well as the mgl and frz genes. However, the cellular defects in gliding movement in many of these mutants were unknown. We conducted quantitative, high-resolution single-cell motility assays and found that mutants defective in mglAB or in cglB, an A-motility gene, reversed the direction of gliding at frequencies which were more than 1 order of magnitude higher than that of wild type cells (2.9 min-1 for DeltamglAB mutants and 2.7 min-1 for cglB mutants, compared to 0.17 min-1 for wild-type cells). The average gliding speed of DeltamglAB mutant cells was 40% of that of wild-type cells (on average 1.9 micrometers/min for DeltamglAB mutants, compared to 4.4 micrometers/min for wild-type cells). The mglA-dependent reversals and gliding speeds were dependent on the level of intracellular MglA protein: mglB mutant cells, which contain only 15 to 20% of the wild-type level of MglA protein, glided with an average reversal frequency of about 1.8 min-1 and an average speed of 2.6 micrometers/min. These values range between those exhibited by wild-type cells and by DeltamglAB mutant cells. Epistasis analysis of frz mutants, which are defective in aggregation and in single-cell reversals, showed that a frzD mutation, but not a frzE mutation, partially suppressed the mglA phenotype. In contrast to mgl mutants, cglB mutant cells were able to move with wild-type speeds only when in close proximity to each other. However, under those conditions, these mutant cells were found to glide less often with those speeds. By analyzing double mutants, the high reversing movements and gliding speeds of cglB cells were found to be strictly dependent on type IV pili, encoded by S-motility genes, whereas the high-reversal pattern of mglAB cells was only partially reduced by a pilR mutation. These results suggest that the MglA protein is required for both control of reversal frequency and gliding speed and that in the absence of A motility, type IV pilus-dependent cell movement includes reversals at high frequency. Furthermore, mglAB mutants behave as if they were severely defective in A motility but only partially defective in S motility.

Bacterial Proteins↗