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M Hartmann

Publications and source records attributed to M Hartmann.

At least 73 records · Page 4Linked to original sources
PubMed1996

Toxicokinetics of isoprene in rodents and humans.

A physiological toxicokinetic model (PT model) was developed for inhaled isoprene in mouse, rat and man. Partition coefficients blood:air and tissue:blood were determined in vitro by a headspace method. Parameters of a saturable isoprene metabolism in B6C3F1 mice, Sprague-Dawley rats and volunteers were obtained from gas uptake experiments in closed systems, analyzed by means of a two-compartment model. Incorporation of these parameters into the PT model revealed that isoprene was metabolized not only in the liver but also in extrahepatic organs. Endogenous production of isoprene in man was quantified from experiments with volunteers breathing into a closed system. The PT model was validated for mice, rats and humans by comparing simulated values with data determined by other authors.

Adult↗
PubMed1996

Specificity of antibodies directed against Env protein of human endogenous retroviruses in patients with germ cell tumors.

We report here that 85% of the patients with germ cell tumors (GCTs) produce antibodies directed against Env protein of human endogenous retroviruses. Individuals that received antitumor treatment showed a decrease with time in their antibody titers. Importantly, of the rare cases of non-GCT individuals with Env-antibodies (n= 15, 0.8%), none produced antibodies directed against the transmembrane domain (TM), whereas all tested Env-positive GCT patients (n= 49) generated such antibodies at high titers. TM is required for Env to be expressed at the cell surface. Thus, anti-TM antibodies constitute highly specific markers for GCT and may hint at a function of Env during tumorigenesis.

Animals↗
PubMed1996

Structure-activity relationships of novel hematoregulatory peptides.

Hematopoiesis is a lifelong cell renewal process regulated by a family of lineage specific hematopoietic growth factors. Several hematopoietic growth factors such as G-CSF, GM-CSF, and M-CSF have been clinically evaluated for enhancement of host defense in normal and immunocompromised patients and for the treatment of infectious diseases. This paper reports the structure-activity relationships of low molecular weight hematoregulatory peptides based on a nonapeptide (1, SK&F 107647). Like the macromolecular growth factors, these peptides modulate host defense. A molecular target for this class of compounds has not yet been identified. However, the structure-activity relationships established by this study implicate a very specific molecular recognition event that is pivotal for the biological activities of 1 and its analogues.

Amino Acid Sequence↗
PubMed1996

High-Resolution Molecular Spectroscopy of van der Waals Clusters in Liquid Helium Droplets

Small van der Waals clusters of sulfur hexafluoride (SF6) and mixed SF6-rare gas clusters were prepared inside large droplets of helium-4, with each droplet consisting of about 4000 helium atoms. A diode laser was used to measure the high-resolution infrared spectra of these clusters in the vicinity of the nu3 vibrational mode. In all cases rotational structure was observed, indicating that the embedded species rotate nearly freely, although they had been cooled to a temperature of 0.37 kelvin. The results indicate that helium droplets are probably superfluid and thereby provide a uniquely cold yet gentle matrix for high-resolution spectroscopy.

Journal Article↗
PubMed1996

A correlation between thermal stability and structural features of staphylokinase and selected mutants: a Fourier-transform infrared study.

Variants of recombinant staphylokinase (Sak) were investigated by Fourier-transform infrared spectroscopy: Sak (wild type), Sak-M26A, Sak-M26L, and Sak-G34S/R36G/R43H (Sak-B). Estimation of the secondary structure and hydrogen-deuterium exchange experiments revealed the existence of fast-exchanging and strongly solvent-exposed fractions of the helical structures in the two samples Sak and Sak-M26L. These two samples are also thermally less stable with unfolding transition temperatures of 43.7 degrees C (Sak) and 43.5 degrees C (Sak-M26L), respectively. On contrast, Sak-M26A and Sak-G34S/R36G/R43H have a slower hydrogen-deuterium exchange, have a smaller solvent-exposed portion of the helical part, and are more resistant against thermal unfolding; the transition temperatures are 51.7 degrees C and 59.3 degrees C, respectively. The secondary structure analysis was performed by two different approaches, by curve-fitting after band narrowing and by pattern recognition (factor analysis) based upon reference spectra of proteins with known crystal structure. Within the limits of the used methods, we are unable to detect significant differences in the secondary structure of the four variants of Sak. According to the results of the factor analysis, the portions of secondary structure elements were obtained to 16-20% alpha-helix, 28-30% beta-sheet, 23-27% turns, 28-30% irregular (random) and other structure. The sharp differences in the specific plasminogen-activating capacity (Sak, Sak-G34S/R36G/R43H and Sak-M26L are fully active, but Sak-M26A does not form a stable complex with plasminogen) are not reflected in the structural features revealed by the infrared spectra of this study.

Deuterium↗
PubMed1996

Phosphorylation of MRP14, an S100 protein expressed during monocytic differentiation, modulates Ca(2+)-dependent translocation from cytoplasm to membranes and cytoskeleton.

MRP8 and MRP14 are two Ca(2+)-binding proteins expressed in myelomonocytic cells. Complexes of MRP8 and MRP14 colocalize with membranes and intermediate filaments in a Ca(2+)-dependent manner. MRP14, unlike MRP8, exists in two isoforms, the smaller of which (MRP14') has been shown to lack the first four amino acids; both MRP14 and MRP14' are also present as phosphorylated forms. As shown in the present work by metabolic labeling of monocytes with [35S]methionine, MRP14 and MRP14' are translated simultaneously. By PCR analysis we found no evidence for the presence of different mRNA species. Since MRP14 is encoded by a single copy gene, our data indicate that MRP14' formation is due to alternative translation of a single mRNA species. Two-dimensional electrophoresis of [32P]orthophosphate-labeled monocyte proteins followed by Western blotting and autoradiography revealed that the two phosphorylated MRP14 isoforms incorporated the bulk of the radioactivity found in monocytic proteins. Using differential centrifugation we demonstrated the presence of distinct isoform patterns in different subcellular locations. Further, in response to elevated Ca2+ concentrations we observed a preferential translocation of phosphorylated MRP14 isoforms from the cytosol toward membranes and the cytoskeleton. This might be caused by altered calcium binding, and indeed, using isoelectric focusing and 45Ca2+ overlay the MRP14 band containing phosphorylated MRP14 revealed increased Ca2+ binding compared with bands containing other MRP14 isoforms. This represents the first evidence for functional differences in phosphorylated MRP14 isoforms compared with nonphosphorylated MRP14 isoforms. These functional differences suggest that MRP14 represents the regulatory subunit of MRP8/MRP14 complexes.

Antigens, Differentiation↗
PubMed1996

[High dosage administration of paramagnetic contrast media in diagnosis of focal brain lesions].

In analogy with high-dose contrast-enhanced CT, there have been a few studies during recent years that have dealt with high-dose paramagnetic contrast dyes in MRI. One reason for these studies was the development of new and low-osmolar contrast agents in the MR field. Depending on the clinical problem, a high-dose contrast study in MRI is rarely indicated: (1) in metastatic disease, MR imaging with high-dose contrast material is indicated when the standard dose study is negative or only shows a solitary cerebral lesion or a number of lesions just suitable for radiosurgery; (2) in patients with malignant glioma the high-dose study allows better definition of the tumor margins. If a radical surgical approach is planned, the diagnostic potential should be fully used; if only a biopsy or subtotal debulking is planned, a standard dose study is enough. (3) in patients with MS, a high-dose study is only recommended within therapeutic trials in which the number of active plaques is a primary variable.

Brain↗
PubMed1996

Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man.

OBJECTIVE: Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon. METHODS: Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30-40% of normal within the first 5-9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11-15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria. RESULTS: The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95-1.09), thus fulfilling predetermined bioequivalence criteria (0.70-1.43). The pharmacokinetic characteristics AUC0-24h and Cmax of S(-)- and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0-24h and of Cmax of S(-)-phenprocoumon (0.93, 0.87-1.00 for AUC0-24h; 0.95, 0.88-1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82-0.96; 0.9, 0.83-0.98) were within the accepted range of 0.8-1.25. CONCLUSION: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Expression of HLA class I molecules in human first trimester and term placenta trophoblast.

Expression of HLA class I molecules in trophoblast cells from various locations in normal human first trimester and term placenta was investigated by immunohistochemistry with a panel of monoclonal antibodies against the heavy chains or complete HLA class I molecules complexed with beta2-microglobulin. These reagents were also employed to distinguish between the products of different HLA class I loci. In addition to previously characterized reagents, a novel monoclonal antibody against HLA-A molecules (TU155) was used. Various choriocarcinoma and transfected cell lines served as controls for the specificities of the monoclonal antibodies. Cells in close contact with maternal cells, such as invading trophoblast cells and cells of the basal plate, expressed beta2-m micro globulin in association with HLA-G and HLA-C heavy chains. These class I heavy chains may also have been present as isolated molecules, although not in each of the cells. In contrast, cells of the chorion laeve exclusively expressed HLA-G, and not HLA-A, -B, or -C antigens. Our data support the often discussed immune protective function and the regulatory function of the HLA-G molecule, during invasion. In addition, by using monoclonal antibodies HCA2 (anti-HLA-A and -G), HC10 (anti-HLA-B and -C), TU149 (anti-HLA-B, -C, and some -A alleles), SFR8-B6 (anti-HLA-Bw6 and some -C), LA45 (some HLA-A and -B), TU48 (anti-HLA-Bw4 and some -A), and TU155 (anti-HLA-A), we show the presence of HLA-C molecules in all extravillous trophoblast cells of the cell columns and in the basal plate; the trophoblast cells of the chorion laeve lack this antigen. The function of this molecule is not clear, although a protective function against natural killer cell activity in the endometrium is postulated.

Blotting, Western↗
PubMed1996

The monoclonal antibody GZS-1 detects a maturation-associated antigen of human spermatozoa that is also present on the surface of human mononuclear blood cells.

A monoclonal antibody (GZS-1) has been generated by fusion of mouse myeloma cells with spleen cells from BALB/c mice immunised with human sperm cells. The antibody was determined to be an IgG1. The corresponding antigen is present on the whole surface of ejaculated human spermatozoa. It is not detectable on spermatozoa of other mammalian species (rabbit, cat, dog, sheep, boar, bull, horse). In human male genital organs, immunostaining with GZS-1 is observed on sperm cells in the epididymis and the ductus deferens together with the lining epithelium of those organs. No reactivity of sperm cells or germ cell precursors in the testis has been detected. Functional tests using the antibody show a strong inhibitory effect of human sperm in the hamster egg penetration assay. Furthermore, the GZS-1 antigen is detectable on the surface of human lymphocytes and monocytes by immunogold electron microscopy and FACS analysis. By Western blotting of human sperm and seminal plasma performed under reducing conditions immunostaining was detected at 21-25, 31, 51-54, and 62 kDa. The reaction with human lymphocytes shows one major band at 62 kDa and additional bands at 31 and 54 kDa. The results suggest that the monoclonal antibody GZS-1 may recognise an antigen which is secreted from the epithelial cells of the epididymis and binds to ejaculated spermatozoa as a sperm coating antigen. This component may be involved in the capacitation of the sperm and the acrosome reaction. Molecules that are expressed both on sperm and on immunocompetent cells may be relevant for the regulation of immunological processes or for the development of the related immunological tolerance of sperm in the female reproductive tract.

Antibodies, Monoclonal↗
PubMed1996

Multiple sclerosis: prospective analysis of TNF-alpha and 55 kDa TNF receptor in CSF and serum in correlation with clinical and MRI activity.

The possibility of antagonizing tumor necrosis factor-alpha (TNF-alpha) in vivo with antibodies or soluble TNF receptor has focused much interest on the role of this cytokine in the natural course of MS. We studied nine patients prospectively and serially for one year (14 time points, 131 observations). TNF-alpha and the 55 kDa soluble TNF receptor were measured every 4 weeks in the serum and at defined time points in the CSF. Each value was correlated to clinical symptoms and to MRI measurements obtained on the same day. All patients with relapsing-remitting disease showed periodic increases of TNF concentrations. Overall, the association between serum TNF-alpha levels and bursts of Gd-DTPA enhancement on cranial MRI was not sufficiently tight to reach statistical significance. However, serum TNF levels > 50 pg/ml and measurable CSF levels were always associated with Gd-DTPA enhancing MRI lesions. Isolated high serum TNF peaks were noted during episodes of infection, hay fever or psychic stress. After treatment with glucocorticoids, TNF levels were suppressed for several months, whereas new Gd-DTPA enhancing lesions continued to appear. The concentrations of the soluble 55 kDa TNF receptor did not show marked fluctuations. These results are consistent with an active role of TNF-alpha in MS during periods of disease activity and provide further support for the clinical evaluation of anti-TNF therapies.

Adult↗
PubMed1996

Lack of pharmacokinetic interaction of pantoprazole with diazepam in man.

Pantoprazole, a substituted benzimidazole, is a potent and well tolerated inhibitor of the gastric H+,K(+)-ATPase with a low potential to inhibit cytochrome P450. In this randomized, placebo-controlled two-period crossover study, 12 healthy volunteers received placebo (reference) and 240 mg of pantoprazole (test) i.v. within 2 min once daily for 7 days each. On day 4 of either period, a 1 min bolus of diazepam (0.1 mg kg-1 body weight) was additionally injected. Pantoprazole was well tolerated and did not cause clinically relevant changes in heart rate, blood pressure, ECG and routine clinical laboratory parameters. There was no effect on diazepam clearance (0.021 1 h-1 kg-1 for test and reference) and elimination half-life (36.8 for test, 40.4 h for reference). Diazepam metabolism to desmethyldiazepam was not affected by pantoprazole. In conclusion, pantoprazole and diazepam may be administered concomitantly without dose adjustment even when high doses of pantoprazole are required.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

[Does the administration of a high dose of a paramagnetic contrast medium (Gadovist) improve the diagnostic value of magnetic resonance tomography in glioblastomas?].

PURPOSE: To assess the efficacy of high-dose contrast enhanced magnetic resonance imaging (MRI) in detection and delineation of infiltrating tumour in glioblastoma. MATERIAL AND METHODS: In a phase II clinical trial 14 patients with suspected supratentorial glioblastoma underwent MRI with Gd-DO3A-butriol (Gadovist, Schering AG, Berlin) with doses of 0.1 up to 0.3 mmol/kg. RESULTS: Increasing the dose of Gd-DO3A-butriol resulted in improved enhancement (14/14) and better delineation of infiltrating tumour (9/14) up to 2 cm beyond enhancement after standard dose. In two of the 9 patients additional enhancement in the peritumoural oedema was only seen after the third injection. CONCLUSIONS: Successful surgery requires precise preoperative delineation of tumour borders. After high-dose MRI it might be possible to select those patients who would benefit from more radical attempts at eradicating the macroscopic as well as most of the microscopic compartment of glioblastoma.

Contrast Media↗
PubMed1996

[Magnetic resonance tomography of vasogenic brain edema in animal experiments].

PURPOSE: To systematically evaluate modern magnetic resonance imaging (MRI) techniques of studying brain oedema, an animal model of vasogenic oedema is needed. MATERIAL AND METHODS: We developed such a model by stereotactically cannulating the caudate nucleus in 11 Wistar-rats and infusing a solution of albumin. The way the oedema developed was imaged by MRI and then correlated histologically (three animals) and macroscopically after infusion of Evans' blue (two animals). RESULTS: The extension of the infusion oedema was the same in both MRI and histology as well as at direct inspection of the specimen after infusion of Evans blue. With continuous acquisition of T1-weighted images after infusion of a 1% solution of Gd-DTPA we were able to demonstrate the dynamics of oedema evolution and bulk flow. CONCLUSION: We believe that this infusion oedema is a suitable model for systematically investigating both signal behaviour and pathogenesis of vasogenic brain oedema by MRI.

Animals↗