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Biomedical subjects

M Kröger

Publications and source records attributed to M Kröger.

At least 19 recordsLinked to original sources
PubMed2004

Modern diagnostics in chronic myeloproliferative diseases (CMPDs).

According to the new WHO classification a group of chronic myeloproliferative diseases (CMPDs) were defined: chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), chronic eosinophilic leukemia and hypereosinophilic syndrome (CEL/HES), polycythemia vera (PV), chronic idiopathic myelofibrosis (with extramedullary hematopoiesis, CIMF), essential thrombocythemia (ET), and so called CMPD/unclassifiable. As clinical features and laboratory findings differ widely between these diseases several diagnostic approaches are mandatory at diagnosis for classification and are needed also for follow up studies, especially for the measurement of minimal residual disease (MRD). We here outline the laboratory set up at diagnosis and during follow up in CMPDs with specific focus on the respective therapeutical consequences. Only by using a comprehensive diagnostic panel including cytomorphology, cytogenetics, and molecular genetic methods establishing the correct diagnosis, optimizing treatment as well as evaluating treatment response is possible in CMPDs today.

Blood Cell Count↗
PubMed2004

Low-level viraemia of hepatitis B virus in an anti-HBc- and anti-HBs-positive blood donor.

summary In many countries, screening of hepatitis B virus (HBV) in blood donors is limited to HBsAg testing. However, if anti-HBc testing and sensitive HBV nucleic acid amplification testing (NAT) for routine screening are not prescribed, HBV viraemia might remain unrecognized. A clinically inconspicuous HBsAg-negative 35-year-old female blood donor was detected with anti-HBc antibodies following the introduction of anti-HBc screening of donors. Based on her history, she had seroconverted to anti-HBs positive (titre >7000 IU/L) after vaccination. Blood donations were routinely tested HBV-DNA negative by minipool NAT. The individual donor samples were reinvestigated by an ultrasensitive NAT with a lower detection limit of 3.8 IU/mL. Intermittent HBV viraemia was detected over a 7-year period from this donor, with a concentration ranging from 8 to 260 IU/mL. In the subsequent donor-directed lookback study, no post-transfusion hepatitis was detected. Low-level HBV viraemia in simultaneous anti-HBc- and anti-HBs-positive blood donors could only be identified with enhanced sensitivity individual polymerase chain reaction assays and is not detectable by pool HBV NAT.

Adult↗
PubMed2003

Reduced intensity conditioning for allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia: disease status by marrow blasts is the strongest prognostic factor.

We analyzed predictive factors for the outcome of 113 acute myeloid leukemia patients receiving reduced-intensity conditioning prior to allogeneic hematopoietic stem cell transplantation (HSCT). Patients were ineligible for conventional-intensity HSCT. Conditioning consisted of fludarabine and 50% of the conventional dose of busulfan (n=93) or total body irradiation (n=20). The source of stem cells was blood in 102 patients, marrow in 10, and both in one. In total, 50 (44.2%) donors were HLA-matched siblings, 50 (44.2%) unrelated fully matched and 13 (11.5%) partially mismatched family (n=1) or unrelated (n=12) donors. In all, 107 (94.6%) patients showed neutrophil and platelet engraftment after a median time of 13.5 and 13 days. The probabilities of event-free survival (EFS) (median follow-up: 12 months) were 49% for patients with less than 5% blasts in the marrow, 24% for patients with 5-20% blasts (P=0.002) and 14% with >20% blasts (P<or=0.001). Death occurred because of relapse in 29 patients (25.6%), infection in 12 patients (10.6%), acute graft-versus-host disease in eight patients (7.0%) and organ toxicity in nine patients (7.9%). In multivariate analysis, higher number of blasts in the marrow, alternative donors and low Karnofsky performance score were independent adverse prognostic factors for EFS.

Adolescent↗
PubMed2001

Thermophysical properties of gases, liquids, and solids composed of particles interacting with a short-range attractive potential.

A short-range polynomial interaction potential is introduced which has both a repulsive core and an attractive part. It is cut off smoothly such that its first and second derivatives vanish at the cutoff distance. The potential therefore enables efficient simulation studies of a model material that exhibits similarities to a full (but computationally expensive) classical Lennard-Jones system. Thermophysical properties of the model are calculated by (nonequilibrium) molecular dynamics computer simulations and compared with analytical results. Among the quantities studied is the pressure as a function of the density for various temperatures. Equations of state for the fluid and the solid are tested. The coexistence of gaseous, (metastable) liquid, and fcc solid phases is found for a range of temperatures. Bulk and shear moduli are computed. The response of the system to a shear deformation with a constant shear rate is analyzed. The liquid shows viscoelastic behavior that can be described with a Maxwell model. The solid behaves as an elastic medium up to a finite deformation and then undergoes a transition to plastic flow, which is stick-slip-like at small shear rates and continuous at higher ones.

Journal Article↗
PubMed2000

Recognition and catabolism of synthetic heterotrimeric collagen peptides by matrix metalloproteinases.

BACKGROUND: The general consensus is that interstitial collagens are digested by collagenases and denatured collagen by gelatinases, although processing of fibrillar and acetic-acid-soluble collagen by gelatinase A has also been reported. One of the main difficulties in studying the mechanism of action of these matrix metalloproteinases (MMPs) derives from the physicochemical properties of the natural triple-helical collagen, which makes it difficult to handle. RESULTS: Synthetic heterotrimeric collagenous peptides that contain the collagenase cleavage site of human collagen type I and differ in the thermal stability of the triple-helical fold were used to mimic natural collagen and gelatin, respectively. Results from digestion of these substrates by fibroblast and neutrophil collagenases (MMP-1 and MMP-8), as well as by gelatinase A (MMP-2), confirmed that the two classes of enzymes operate within the context of strong conformational dependency of the substrates. It was also found that gelatinases and collagenases exhibit two distinct proteolytic mechanisms: gelatinase digests the gelatin-like heterotrimer rapidly in individual steps with intermediate releases of partially processed substrate into the medium, whereas collagenases degrade the triple-helical heterotrimer by trapping it until scission through all three alpha chains is achieved. CONCLUSIONS: The results confirm the usefulness of synthetic heterotrimeric collagenous peptides in the folded and unfolded state as mimics of the natural substrates collagen and gelatin, respectively, to gain a better a insight into the proteolytic mechanisms of matrix metalloproteinases.

Binding Sites↗
PubMed1999

[Economic effects of integrated RIS-PACS solution in the university environment].

PROBLEM: The goal of the current article is to demonstrate how qualitative and monetary effects resulting from an integrated RIS/PACS installation can be evaluated. METHODS: First of all, the system concept of a RIS/PACS solution for a university hospital is defined and described. Based on this example, a generic method for the evaluation of qualitative and monetary effects as well as associated risks is depicted and demonstrated. To this end, qualitative analyses, investment calculations and risk analysis are employed. RESULTS: The sample analysis of a RIS/PACS solution specially designed for a university hospital demonstrates positive qualitative and monetary effects of the system. Under ideal conditions the payoff time of the investments is reached after 4 years of an assumed 8 years effective life of the system. Furthermore, under conservative assumptions, the risk analysis shows a probability of 0% for realising a negative net present value at the end of the payoff time period. CONCLUSION: It should be pointed out that the positive result of this sample analysis will not necessarily apply to other clinics or hospitals. However, the same methods may be used for the individual evaluation of the qualitative and monetary effects of a RIS/PACS installation in any clinic.

Cost-Benefit Analysis↗
PubMed1999

Shiga toxins even when different are encoded at identical positions in the genomes of related temperate bacteriophages.

The nucleotide sequence of an 11,142-bp region including the stx2 operon in the genome of the temperate bacteriophage 933W in the EDL933 strain of Escherichia coli O157 was determined and compared to the respective regions derived from other lambdoid bacteriophages. In phage 933W, a region of ORFs interlinked by overlapping start-stop codons (ATGA) was detected preceding the toxin gene. These ORFs show a high degree of sequence identity to genes of the nin region of phage lambda. Immediately downstream of these nin genes we identified an ORF that may code for an anti-terminator similar to the lambda Q protein. It is concluded that toxin expression is directly associated with the initiation of cell lysis. Downstream of the stx2 operon we identified an ORF that is homologous to the holin gene S of bacteriophage PA-2. PCR primers were designed, which, based on a comparison of the phage sequences, appeared to be common to both stx1- and stx2-harbouring phages. However, only seven of the 22 STEC strains investigated from serogroups O157, O26, O103 and O111 yielded the expected PCR amplification product. The data reported here may be useful in developing new strategies for inhibiting the expression of Stx and for developing universal diagnostic primers for use in tracking the origin and evolution of Shiga toxins and the phages that carry them.

Amino Acid Sequence↗
PubMed1999

Mesoscopic model for the viscosities of nematic liquid crystals.

Based on the definition of the mesoscopic concept by Blenk et al. [Physica A 174, 119 (1991); J. Noneq. Therm. 16, 67 (1991); Mol. Cryst. Liq. Cryst. 204, 133 (1991)] an approach to calculate the Leslie viscosity coefficients for nematic liquid crystals is presented. The approach rests upon the mesoscopic stress tensor, whose structure is assumed similar to the macroscopic Leslie viscous stress. The proposed form is also the main dissipation part of the mesoscopic Navier-Stokes equation. On the basis of the correspondence between microscopic and mesoscopic scales a mean-field mesoscopic potential is introduced. It allows us to obtain the stress tensor angular velocity of the free rotating molecules with the help of the orientational Fokker-Planck equation. The macroscopic stress tensor is calculated as an average of the mesoscopic counterpart. Appropriate relations among mesoscopic viscosities have been found. The mesoscopic analysis results are shown to be consistent with the diffusional model of Kuzuu-Doi and Osipov-Terentjev with the exception of the shear viscosity alpha(4). In the nematic phase alpha(4) is shown to have two contributions: isotropic and nematic. There exists an indication that the influence of the isotropic part is dominant over the nematic part. The so-called microscopic stress tensor used in the microscopic theories is shown to be the mean-field potential-dependent representation of the mesoscopic stress tensor. In the limiting case of total alignment the Leslie coefficients are estimated for the diffusional and mesoscopic models. They are compared to the results of the affine transformation model of the perfectly ordered systems. This comparison shows disagreement concerning the rotational viscosity, whereas the coefficients characteristic for the symmetric part of the viscous stress tensor remain the same. The difference is caused by the hindered diffusion in the affine model case.

Journal Article↗
PubMed1998

Compilation of DNA sequences of Escherichia coli K12: description of the interactive databases ECD and ECDC.

We have compiled the DNA sequence data for Escherichia coli K12 available from the GenBank and EMBL data libraries and independently from the literature. We provide the most definitive version of the ECD Escherichia coli database now exclusively via the World Wide Web System (http://susi.bio.uni-giessen.de/ecdc.html ). Our database encloses the completed genome sequence recently published by two competing groups and an assembled set of all elder sequences. The organisation of the database allows precise physical location of each individual gene or regulatory region, even taking into consideration discrepancies in nomenclature. The WWW program allows to the user to branch into the original EMBL and SWISS-PROT datafiles. A number of links to other WWW servers dealing with E. coli is provided. A FASTA and BLAST search may be performed online. Besides the WWW format a flat file version may be obtained via ftp. A number of discrepancies between the two systematic sequence determinations and/or the literature have not yet been resolved. However, our database may serve as a reference source for resolution and/or the assignment of strain difference.

Computer Communication Networks↗
PubMed1997

Cloning, expression and activation of a truncated 92-kDa gelatinase minienzyme.

The matrix metalloproteinases (MMPs) are a family of highly homologous zinc-endopeptidases that degrade extracellular matrix components. Human 92-kDa gelatinase (MMP-9) represents one of the MMPs that cleaves native collagen type IV. As a basis for structural investigations, the short form (catalytic domain, amino acid residues 113-450) of the 92-kDa gelatinase cDNA was cloned and expressed in E. coli as a minienzyme. By combination of reverse transcription (RT) and polymerase chain reaction (PCR), the truncated 92-kDa gelatinase-cDNA was amplified from the corresponding mRNA derived from ovarian carcinoma cells. The cDNA fragment obtained was cloned in E. coli and sequenced. With the exception of one nucleotide inversion at position 745 (gt-->tg) the cDNA sequence was identical to the nucleotide sequence of the 92-kDa gelatinase as has been previously reported. The protein was expressed in E. coli using the vector pET-12b. The recombinant protein was stored in inclusion bodies and extracted as a 38 kDa species from the inclusion bodies by solubilization in 8 M urea. The product was purified by affinity chromatography and gel filtration. Amino-terminal sequence analysis confirmed the identity with the catalytic domain of 92-kDa gelatinase. The recombinant protein was refolded in the presence of Ca2+ and Zn2+ and yielded an active minienzyme with gelatinolytic activity. It degrades the native substrate collagen type IV and the synthetic substrate Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2 x AcOH like the full-length 92-kDa gelatinase. The catalytic activity could be inhibited by the specific MMP inhibitors TIMP-1 and TIMP-2.

Base Sequence↗
PubMed1997

Compilation of DNA sequences of Escherichia coli K12: description of the interactive databases ECD and ECDC (update 1996).

We have compiled the DNA sequence data forEscherichia coliavailable from the GenBank and EMBL data libraries and independently from the literature. We provide the most definitive version of the ECDEscherichia colidatabase now exclusively via the World Wide Web System: http://susi.bio.uni-giessen.de/usr/local/www/ html/ecdc.html . Our database encloses an assembled set of contiguous sequences. Each of these contigs compiles all available sequence information, including those derived from a variety of elder sequences. The organisation of the database allows precise physical location of each individual gene or regulatory region, even taking into consideration discrepancies in nomenclature. The WWW program allows to branch into the original EMBL and SWISSPROT datafiles. A number of links to other WWW servers is provided. A FASTA and BLAST search may be performed online. Besides the WWW format a flat file version may be obtained via ftp. The ftp version may also be obtained from the EMBL data library as part of the CD-ROM issue of the EMBL sequence database, which is released and updated every 3 months. After deletion of all detected overlaps a total of 3 588 706 individual bp has been determined up to the end of September 1996. This corresponds to a total of 77.09% of the entire E.coli chromosome consisting of approximately 4655 kb. About 479 kb (10.3%) are additionally available from Kyoto (Japan). Another 94 kb (2%) are available, but mapping has not been confirmed. Thus the total may have reached 89.4%.

Base Sequence↗
PubMed1996

Compilation of DNA sequences of Escherichia coli K12 (ECD and ECDC; update 1995).

We have compiled the DNA sequence data for Escherichia coli available from the GenBank and EMBL data libraries and independently from the literature. Unlike the previous updates of our E.coli databases, we provide the most recent version preferentially via the World Wide Web System (use URL: http://susi.bio.unigiessen.de/usr/local/www++ +/html/ecdc.html). Our database includes an assembled set of contiguous sequences. Each of these contigs compiles all available sequence information, including those derived from a variety of elder sequences. The organization of the database allows one to find the exact physical location of each individual gene or regulatory region, even regarding discrepancies in nomenclature. The WWW program allows access into the original EMBL and SWISSPROT datafiles. A FASTA and BLAST search may be performed online. Besides the WWW format a flat file version may be obtained via ftp. The complete compilation, including a full set of genetic map data and the E.coli protein index, can be obtained in machine readable form from the EMBL data library as a part of the CD-ROM issue of the EMBL sequence database, released and updated every three months. After deletion of all detected overlaps a total of 3 333 878 individual bp was determined by the end of September 1995. This corresponds to a total of 71.71% of the entire E.coli chromosome consisting of about 4720 kbp. About 94 kbp (2%) are available additionally, but have not yet been definitely mapped.

Base Sequence↗
PubMed1996

Effects of vitamin B12 on performance and circadian rhythm in normal subjects.

This preliminary study investigates effects of methyl- and cyanocobalamin on circadian rhythms, well-being, alertness, and concentration in healthy subjects. Six women (mean age 35 years) and 14 men (mean age 37 years) were randomly assigned to treatment for 14 days with 3 mg cyano-(CB12) or methylcobalamin (MB12) after 9 days of pre-treatment observation. Levels in the CB12 group increased rapidly in the first, then slowly in the second treatment week, whereas increase in the MB12 group was linear. Urinary aMT6s excretion was reduced by both forms of vitamin B12 over 24 hours with a significant decrease between 0700-1100 hours, whereas urinary excretion of potassium was significantly increased between 0700-1100 hours. Activity from 2300-0700 hours increased significantly under both forms of vitamin B12. Sleep time was significantly reduced under MB12 intake. In this group the change in the visual analogue scales items "sleep quality," "concentration," and "feeling refreshed" between pretreatment and the first week of treatment showed significant correlations with vitamin B12 plasma levels. Cortisol excretion and temperature were not affected by either medication. We conclude that vitamin B12 exerts a direct influence on melatonin. Only MB12 has a positive psychotropic alerting effect with a distribution of the sleep-wake cycle toward sleep reduction.

Adult↗
PubMed1995

Evidence for an evolutionary relationship among type-II restriction endonucleases.

Type-II restriction-modification (R-M) systems comprise two enzymes, a DNA methyltransferase (MTase) and a restriction endonuclease (ENase), each of which specifically interact with the same 4-8 bp sequence. All type-II MTases share several amino acid (aa) sequence motifs, which makes an evolutionary relatedness among these enzymes probable. The type-II ENases, in contrast, except for some homologous isoschizomers, do not share significant aa sequence similarity. Therefore, ENases in general have been considered unrelated. Here we show that in addition to the analysis of the genotype (aa sequence), a comparison of the phenotype (recognition sequence) of these enzymes can provide independent information regarding evolutionary relationships, and thereby, help to analyze the significance of weak aa sequence similarities. Multistep Monte-Carlo analyses were employed to demonstrate that the recognition sequences of those ENases, which were found to be related by a progressive multiple aa sequence alignment, are more similar to each other than would be expected by chance. This analysis supports the notion that not only type-II MTases, but also type-II ENases did not arise independently in evolution, but rather evolved from one or a few primordial DNA-modifying and DNA-cleaving enzymes, respectively.

Amino Acid Sequence↗
PubMed1995

Organization and gene expression within restriction-modification systems of Herpetosiphon giganteus.

We have characterized a family of related restriction-modification (R-M) systems from the soil bacterium Herpetosiphon giganteus (Hgi). A comparison of their genetic organization reveals two types of regulatory proteins, called controlling ORF C. While one of these small reading frames derived from RM.HgiCI seems to be an enhancer of its own promoter, evidence is provided for a silencer function of the other ORF C derived from the closely related AvaII-type systems RM.HgiBI/CII/EI. The respective silencer function is detected during our various attempts to clone three isoschizomers with unusually high differences in their specific activity. Sequencing and site-directed mutagenesis revealed just two amino acids as being responsible for a massive increase in specific activity of these endonucleases.

Base Sequence↗