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Biomedical subjects

M Krause

Publications and source records attributed to M Krause.

At least 109 records · Page 6Linked to original sources
PubMed1999

Analysis of rpoS mRNA in Salmonella dublin: identification of multiple transcripts with growth-phase-dependent variation in transcript stability.

In Salmonella dublin, rpoS encodes an alternative sigma factor of the RNA polymerase that activates a variety of stationary-phase-induced genes, including some virulence-associated genes. In this work, we studied the regulation and transcriptional organization of rpoS during growth. We found two transcripts, 2.3 and 1.6 kb in length, that represent the complete rpoS sequence. The 2.3-kb transcript is a polycistronic message that also includes the upstream nlpD gene. It is driven by a weak promoter with increasing activity when cells enter early stationary growth. The 1.6-kb message includes 566 bp upstream of the rpoS start codon. It is transcribed from a strong sigma70 RNA polymerase-dependent promoter which is independent of growth. The decay of this transcript decreases substantially in early stationary growth, resulting in a significant net increase in rpoS mRNA levels. These levels are approximately 10-fold higher than the levels of the 2.3-kb mRNA, indicating that the 1.6-kb message is mainly responsible for RpoS upregulation. In addition to the 2.3- and 1.6-kb transcripts, two smaller 1.0- and 0.4-kb RNA species are produced from the nlpD-rpoS locus. They do not allow translation of full-length RpoS; hence their significance for rpoS regulation remains unclear. We conclude that of four transcripts arising from the nlpD-rpoS locus, only one plays a significant role in rpoS expression in S. dublin. Its upregulation when cells enter stationary growth is due primarily to an increase in transcript stability.

Bacterial Proteins↗
PubMed1999

Ablation of vitreous tissue with erbium:YAG laser.

PURPOSE: Using a noncontact erbium (Er):yttrium--aluminium--garnet (YAG) laser, ablation of vitreous was compared to distilled water in vitro. METHODS: The porcine vitreous body and distilled water were ablated in vitro at different pulse lengths and pulse energies. Selected pulse energies were 25, 35, 45, 75, and 100 mJ (pulse rate: 1 Hz; laser beam diameter at the surface of the sample: 2 mm). Pulse lengths were at 140 +/- 3 microsec, 190 +/- 4 microsec, and 240 +/- 5 microsec. The loss of weight in vitreous tissue and distilled water was measured using precision scales and corrected for evaporation, respectively. The Mann-Whitney U test was used to assess the significance of differences in ablation rates of water and vitreous. P < 0.05 was considered statistically significant. RESULTS: Reproducible and constant ablation rates were found in both vitreous and distilled water in each of 10 consecutive series of 50 laser pulses at constant laser parameters. Ablation rates per pulse (microg/microsec) of vitreous tissue were as follows: 3.0 microg to 45.8 microg (140 microsec), 10.4 microg to 53.8 microg (190 microsec), and 17.9 microg to 24.2 microg (240 microsec). The ablation rates exhibited a linear correlation with increasing pulse energies and also with decreasing pulse lengths. Considering the pulse lengths of 190 microsec and 240 microsec with all pulse energies tested, the ablation rates of distilled water were significantly higher (P < 0.05) than ablation of vitreous tissue. The ablation rates at a pulse length of 140 microsec were not significantly different. The differences per pulse were as follows: 0.5 microg to 2.1 microg (140 microsec), 1.9 microg to 6.0 microg (190 microsec), and 3.5 microg to 8.7 microg (240 microsec). CONCLUSIONS: Vitreous ablation is possible using Er:YAG laser. The ablation characteristics of vitreous have proved to be similar but not equal to that of water.

Animals↗
PubMed1998

von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.

BACKGROUND: Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of von Willebrand factor-cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders. METHODS: Plasma samples were obtained from 53 patients with thrombotic thrombocytopenic purpura or hemolytic-uremic syndrome. Von Willebrand factor-cleaving protease was assayed in diluted plasma samples with purified normal von Willebrand factor as the substrate. The extent of the degradation of von Willebrand factor was assessed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. To determine whether an inhibitor of von Willebrand factor-cleaving protease was present, we measured the protease activity in normal plasma after incubation with plasma from the patients. RESULTS: We examined 30 patients with thrombotic thrombocytopenic purpura and 23 patients with the hemolytic-uremic syndrome. Of 24 patients with nonfamilial thrombotic thrombocytopenic purpura, 20 had severe and 4 had moderate protease deficiency during an acute event. An inhibitor found in 20 of these patients was shown to be IgG in five of five tested plasma samples. Of 13 patients with nonfamilial hemolytic-uremic syndrome, 11 had normal levels of activity of von Willebrand factor-cleaving protease during the acute episode, whereas in 2 patients, the activity was slightly decreased. All 6 patients with familial thrombotic thrombocytopenic purpura lacked von Willebrand factor-cleaving protease activity but had no inhibitor, whereas all 10 patients with familial hemolytic-uremic syndrome had normal protease activity. In vitro proteolytic degradation of von Willebrand factor by the protease was studied in 5 patients with familial and 7 patients with nonfamilial hemolytic-uremic syndrome and was normal in all 12 patients. CONCLUSIONS: Nonfamilial thrombotic thrombocytopenic purpura is due to an inhibitor of von Willebrand factor-cleaving protease, whereas the familial form seems to be caused by a constitutional deficiency of the protease. Patients with the hemolyticuremic syndrome do not have a deficiency of von Willebrand factor-cleaving protease or a defect in von Willebrand factor that leads to its resistance to protease.

ADAM Proteins↗
PubMed1998

4-Alkynylphenyl imidazolylpropyl ethers as selective histamine H3-receptor antagonists with high oral central nervous system activity.

In search for potent and therapeutically useful H3-receptor antagonists, we prepared novel 4-alkynylphenyl ether derivatives of 3-(1H-imidazol-4-yl)propanol in a convenient synthetic route. All compounds were tested for in vitro and in vivo H3-receptor antagonist activity as well as for H3-receptor selectivity versus H1- and H2-receptors. The presented 4-alkynylphenyl ethers are highly potent and selective H3 antagonists showing oral activity and improved brain penetration. Particularly 4-ethynylphenyl 3-(1H-imidazol-4-yl)propyl ether (14a) displays striking in vitro and in vivo activity with a -log Ki value of 8.6 and an ED50 value of 0.12 mg/kg. At present 14a is the most potent H3-receptor antagonist in vivo and may therefore be a potential drug for the therapy of H3-receptor-dependent diseases of the central nervous system (CNS).

Administration, Oral↗
PubMed1998

Analysis of a Caenorhabditis elegans Twist homolog identifies conserved and divergent aspects of mesodermal patterning.

Mesodermal development is a multistep process in which cells become increasingly specialized to form specific tissue types. In Drosophila and mammals, proper segregation and patterning of the mesoderm involves the bHLH factor Twist. We investigated the activity of a Twist-related factor, CeTwist, during Caenorhabditis elegans mesoderm development. Embryonic mesoderm in C. elegans derives from a number of distinct founder cells that are specified during the early lineages; in contrast, a single blast cell (M) is responsible for all nongonadal mesoderm formation during postembryonic development. Using immunofluorescence and reporter fusions, we determined the activity pattern of the gene encoding CeTwist. No activity was observed during specification of mesodermal lineages in the early embryo; instead, the gene was active within the M lineage and in a number of mesodermal cells with nonstriated muscle fates. A role for CeTwist in postembryonic mesodermal cell fate specification was indicated by ectopic expression and genetic interference assays. These experiments showed that CeTwist was responsible for activating two target genes normally expressed in specific subsets of nonstriated muscles derived from the M lineage. In vitro and in vivo assays suggested that CeTwist cooperates with the C. elegans E/Daughterless homolog in directly activating these targets. The two target genes that we have studied, ceh-24 and egl-15, encode an NK-2 class homeodomain and an FGF receptor (FGFR) homolog, respectively. Twist activates FGFR and NK-homeodomain target genes during mesodermal patterning of Drosophila and similar target interactions have been proposed to modulate mesenchymal growth during closure of the vertebrate skull. These results suggest the possibility that a conserved pathway may be used for diverse functions in mesodermal specification.

Amino Acid Sequence↗
PubMed1998

Polycyclic aromatic hydrocarbons (PAH) and diesel engine emission (elemental carbon) inside a car and a subway train.

Significant concentrations of potentially harmful substances can be present in the interior of vehicles. The main sources of PAHs and elemental carbon (EC) inside a car are likely to be combustion emissions, especially from coal and traffic. The same sources can also be important for the interior of a subway train for which there are specific sources in the tunnel system, for example diesel engines. Twice, in summer 1995 and winter 1996 polycyclic aromatic hydrocarbons (PAH) and diesel motor emission (estimated as elemental carbon) were determined in the interior of a car (a 2-year-old VW Golf with a three-way catalytic converter) and in the passenger compartment of a subway train (below ground). On each sampling day (in total 16 daily measurements in the car and 16 in the subway) the substances were determined in the breathing zone of the passengers from 07:00 h to 16:00 h under different meteorologic conditions (winter- and summertime). The car followed the route of the subway from the western Berlin borough of Spandau to the south-eastern borough of Neukölln, and back. The sampling represented a realistic exposure model for driving in a high traffic and polluted urban area. The electric subway train (also 2 years in use) connected the same parts of Berlin (31 km underground). The mean values obtained during the two measurement periods (summer/winter) inside the car were 1.0 and 3.2 ng/m3 for benzo[a]pyrene, 10.2 and 28.7 ng/m3 for total-measured-PAHs, 14.1 and 8.2 micrograms/m3 for EC and in the subway 0.7 and 4.0 ng/m3 for benzol[a]pyrene, 30.2 and 67.5 ng/m3 for total PAHs, 109 and 6.9 micrograms/m3 for EC. A comparison between subway and car exposures shows significantly higher concentrations of PAHs in the subway train, which can be explained by relatively high concentrations of fluoranthene and pyrene in the subway. So far a satisfactory explanation has not been found, but one source might be the wooden railway ties which were formerly preserved with tar based products. In wintertime in both transportation systems the concentrations of beno[a]pyrene are three to four times higher than in summer corresponding to the changing of the ambient air concentrations.

Berlin↗
PubMed1998

[Dog, cat and human bites].

Animal and human bites carry a high risk of infectious complications. Human bites and in particular clenched-fist injuries as well as cat bites are highly prone to infection as are wounds that involve the hand or deep structures including joints, bones and tendons. The management of bite wounds consists of intensive irrigation with large volumes of normal saline and a cautions debridement of devitalized tissues. Generally, it appears prudent to leave the wounds open, however, in cases carrying a low risk of infection, a primary surgical closure might be appropriate. If a bite wound is infected, an antibiotic course with amoxycillin/clavulanic acid (first choice) or tetracyclines (second choice) for 10-14 days is recommended. In patients who present early after the injury, an antibiotic prophylaxis for 3-5 days is appropriate, particularly when the risk for the development of infection is high. Furthermore, a tetanus booster and in case of possible transfer of rabies, a rabies vaccination with immunoglobulins and inactivated virus preparation is recommended.

Animals↗
PubMed1998

Unique organization of the dnaA region from Prochlorococcus marinus CCMP1375, a marine cyanobacterium.

In order to study DNA replication control elements in cyanobacteria we cloned and sequenced the dnaA gene from the marine cyanobacterium Prochlorococcus marinus. The dnaA gene is ubiquitous among bacteria and encodes the DNA replication initiation factor DnaA. The deduced amino acid sequence of the P. marinus DnaA protein shows highest similarity to the DnaA protein from the freshwater cyanobacterium Synechocystis sp. PCC6803. Using a solid-phase DNA binding assay we demonstrated that both cyanobacterial DnaA proteins specifically recognize chromosomal origins, oriC, of Escherichia coli and Bacillus subtilis in vitro. The genetic environment of dnaA is not conserved between the two cyanobacteria. Upstream of the P. marinus dnaA gene we identified a gene encoding a putative ATP-binding cassette (ABC) transport protein. The gor gene encoding glutathione reductase lies downstream of dnaA. Comparison of the genetic structure of dnaA regions from 15 representative bacteria shows that the pattern of genes flanking dnaA is not universally conserved among them.

Amino Acid Sequence↗
PubMed1998

[Two contact lens holders for vitreoretinal surgery].

Two new lens holders for contact lens use in vitreoretinal surgery were developed: (1) a flexible hand-fixed lens holder and (2) a lid-retractor-fixed lens holder. Advantages are: better stabilization and centering of the lens, reduction of air bubbles and blood in the interface between cornea and contact lens.

Contact Lenses↗
PubMed1998

Effect of therapeutic concentrations of nitric oxide on bacterial growth in vitro.

OBJECTIVES: Besides its vasodilative actions, nitric oxide (NO) is also involved in host defense on a cellular level. We studied the antimicrobial properties of NO in concentrations used with inhaled NO therapy for the treatment of pulmonary hypertension in neonates. DESIGN: In vitro study of bacterial growth of five species, with and without NO exposure. SETTING: Level IV neonatal intensive care unit at a university children's hospital. SUBJECTS: In vitro bacterial cultures. INTERVENTIONS: We tested ten different strains of five bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, group B streptococcus [GBS/Streptococcus agalactiae], Escherichia coli, and Pseudomonas aeruginosa), derived from the tracheal isolates of ventilated premature and term infants. Cultures were exposed to three different concentrations of NO (40, 80, and 120 parts per million [ppm]) and bacterial growth was compared with the same strains incubated in ambient air for 24 hrs. After incubation (with or without NO), colony-forming units were counted. MEASUREMENTS AND MAIN RESULTS: Bacterial growth of S. aureus, E. coli, and P. aeruginosa was not reduced with the NO concentrations applied. The number of colony-forming units of S. aureus increased at 80 ppm of NO. Growth of S. epidermidis and GBS was significantly affected at 120 ppm, resulting in decreased numbers of colony-forming units as compared with controls exposed to ambient air. CONCLUSIONS: We conclude that NO has a selective bacteriostatic effect on some of those bacteria most commonly cultured in tracheal specimens of premature infants and neonates. This effect appears to be dose-dependent and occurs in the upper range of dosages used with inhaled NO therapy. However, in the range of dosages applied in ongoing controlled trials of inhaled NO in neonates and premature infants (1 to 80 ppm), a bacteriostatic effect of NO is not to be expected.

Administration, Inhalation↗
PubMed1998

Modulation of the Ca2+-activated K+ current sIAHP by a phosphatase-kinase balance under basal conditions in rat CA1 pyramidal neurons.

The slow Ca2+-activated K+ current, sIAHP, underlying spike frequency adaptation, was recorded with the whole cell patch-clamp technique in CA1 pyramidal neurons in rat hippocampal slices. Inhibitors of serine/threonine protein phosphatases (microcystin, calyculin A, cantharidic acid) caused a gradual decrease of sIAHP amplitude, suggesting the presence of a basal phosphorylation-dephosphorylation turnover regulating sIAHP. Because selective calcineurin (PP-2B) inhibitors did not affect the amplitude of sIAHP, protein phosphatase 1 (PP-1) or 2A (PP-2A) are most likely involved in the basal regulation of this current. The ATP analogue, ATP-gamma-S, caused a gradual decrease in the sIAHP amplitude, supporting a role of protein phosphorylation in the basal modulation of sIAHP. When the protein kinase A (PKA) inhibitor adenosine-3', 5'-monophosphorothioate, Rp-isomer (Rp-cAMPS) was coapplied with the phosphatase inhibitor microcystin, it prevented the decrease in the sIAHP amplitude that was observed when microcystin alone was applied. Furthermore, inhibition of PKA by Rp-cAMPS led to an increase in the sIAHP amplitude. Finally, an adenylyl cyclase inhibitor (SQ22, 536) and adenosine 3',5'-cyclic monophosphate-specific type IV phosphodiesterase inhibitors (Ro 20-1724 and rolipram) led to an increase or a decrease in the sIAHP amplitude, respectively. These findings suggest that a balance between basally active PKA and a phosphatase (PP-1 or PP-2A) is responsible for the tonic modulation of sIAHP, resulting in a continuous modulation of excitability and firing properties of hippocampal pyramidal neurons.

Adenylyl Cyclases↗
PubMed1998

Treatment of respiratory failure with inhaled nitric oxide and high- frequency ventilation in an infant with respiratory syncytial virus pneumonia and bronchopulmonary dysplasia.

In a 7-month-old infant with bronchopulmonary dysplasia and respiratory syncytial virus (RSV) pneumonia, we have shown an additive effect of high-frequency ventilation (HFV) and inhaled nitric oxide (iNO) in terms of improved oxygenation and the avoidance of extracorporeal membrane oxygenation. Apparently, the combined therapy of HFV and iNO is superior to either therapeutic modality alone in the treatment of hypoxemic respiratory failure due to RSV pneumonia. The mechanism of increased lung expansion and alveolar recruitment appears to be responsible for a favorable clinical outcome. We conclude that the combined therapy of HFV and iNO should be considered in hypoxemic respiratory failure in pediatric patients.

Administration, Inhalation↗
PubMed1998

High-frequency ventilation augments the effect of inhaled nitric oxide in persistent pulmonary hypertension of the newborn.

Does inhaled nitric oxide (iNO) during high-frequency ventilation (HFV) lead to a more pronounced improvement in oxygenation than iNO during conventional ventilation? We report two cases of newborn infants with profound hypoxaemia, who did not respond with an increase in arterial oxygenation following iNO therapy during conventional mechanical ventilation. The first infant was a term neonate with persistent pulmonary hypertension of the newborn (PPHN) following postnatal hypoxia, the second patient a premature infant of 29 weeks of gestation with PPHN secondary to lung hypoplasia and perinatal asphyxia. After the initial failure of iNO we switched both neonates to HFV without NO, which did not lead to a significant improvement of oxygenation in either case. Shortly after the initiation of HFV a second trial of iNO was started. Both infants responded favourably to iNO with a marked and sustained increase in arterial oxygenation and absent right-to-left shunting via the ductus arteriosus and the foramen ovale. We conclude that the favourable response to inhaled nitric oxide is dependent on the degree of lung expansion and is more readily achieved by the use of high-frequency ventilation than conventional ventilation.

Administration, Inhalation↗
PubMed1998

MyoD and the specification of muscle and non-muscle fates during postembryonic development of the C. elegans mesoderm.

Basic-helix-loop helix factors of the myoD/myf5/ myogenin/MRF4 family have been implicated in acquisition and elaboration of muscle cell fates. Here we describe both myogenic and non-myogenic roles for the Caenorhabditis elegans member of this family (CeMyoD) in postembryonic mesodermal patterning. The postembryonic mesodermal lineage in C. elegans provides a paradigm for many of the issues in mesodermal fate specification: a single mesoblast ('M') divides to generate 14 striated muscles, 16 non-striated muscles, and two non-muscle cells. To study CeMyoD function in the M lineage, we needed to circumvent an embryonic requirement for the protein. Two approaches were used: (1) isolation of mutants that decrease CeMyoD levels while retaining viability, and (2) analysis of genetic mosaics that had lost CeMyoD in the M lineage. With either manipulation, we observed a series of cell-fate transformations affecting a subset of both striated muscles and non-muscle cells. In place of these normal fates, the affected lineages produced a number of myoblast-like cells that initially failed to differentiate, instead swelling to acquire a resemblance to sex myoblasts (M-lineage-derived precursors to non-striated uterine and vulval muscles). Like normal sex myoblasts, the ectopic myoblast-like cells were capable of migration and proliferation followed by differentiation of progeny cells into vulval and uterine muscle. Our results demonstrate a cell-intrinsic contribution of CeMyoD to specification of both non-muscle and muscle fates.

Animals↗
PubMed1998

CHR3: a Caenorhabditis elegans orphan nuclear hormone receptor required for proper epidermal development and molting.

CHR3 is a Caenorhabditis elegans orphan nuclear hormone receptor highly homologous to Drosophila DHR3, an ecdysone-inducible gene product involved in metamorphosis. Related vertebrate factors include RORalpha/RZRalpha, RZRbeta and RevErb. Gel-shift studies show that CHR3 can bind the DR5-type hormone response sequence. CHR3 is a nuclear protein present in all blastomeres during early embryogenesis. During morphogenesis, both CHR3 protein and zygotically active reporter genes are detectable in epidermal cells and their precursors. Inhibition of the gene encoding CHR3 results in several larval defects associated with abnormal epidermal cell function, including molting and body size regulation, suggesting that CHR3 is an essential epidermal factor required for proper postembryonic development.

Animals↗
PubMed1998

CT appearances of hepatic involvement in systemic varicella-zoster.

In a patient suffering from T-cell non-Hodgkin's lymphoma and systemic varicella-zoster, contrast enhanced CT showed multiple hypodense nodular lesions in the liver which corresponded to areas of focal liver necrosis. This appearance on CT may be characteristic of varicella-zoster involvement of the liver.

Female↗