Biomedical subjects

M Stadler

Publications and source records attributed to M Stadler.

At least 19 recordsLinked to original sources

PubMed2003

Optimization of a formulation containing viable lactic acid bacteria.

In the present study, gastric juice resistant tablet formulations of lactic acid bacteria (LAB) were developed, using hydroxypropylmethylcellulose acetate succinate (HPMCAS) as well as alginates, apple pectin and Metolose as matrix forming components. To optimize the formulation-using survival rate in acid medium, and disintegration time in intestinal fluid as test parameters-tablets were modified with respect to LAB content, amount of applied excipients per tablet, and compaction forces. A decrease of viable cells of not more than one log unit after 2h of incubation in acid medium was desired, as well as a disintegration time of 1h in phosphate buffer pH 6.8. It was found that the amount of HPMCAS in the tablet correlates with gastric juice resistance. As HPMCAS also leads to a decrease of disintegration time in intestinal fluid, slight amounts of this excipient were preferred. The best protective qualities against artificial gastric juice were observed when tablets were prepared from compaction mixtures of LAB, HPMCAS and sodium alginate.

Colony Count, Microbial↗

PubMed2003

Neuromagnetic correlates of perceived contrast in primary visual cortex.

When a target grating is flashed into a larger, surrounding grating, its contrast is perceived to be lower when both gratings are oriented collinearly rather than orthogonally. This effect can be used to dissociate the perceived contrast from the physical contrast of a target grating. We recorded the transient electric potentials and magnetic fields evoked by flashed target gratings and compared them with psychophysical judgments of perceived contrast. Both early (100 ms) and late (150 ms) transients were reduced in amplitude when targets were flashed into a collinear rather than orthogonal surround, thus paralleling the reduction in perceived contrast. Although targets in orthogonal backgrounds required 40% lower physical contrast to match the perceived contrast of collinear targets, the amplitudes of electrophysiological transients of matching stimuli were almost identical. Thus the responses correlated better with perceived than with physical target contrast. This holds especially for the late transient response. Source localization indicated that the transients in question may originate in primary visual cortex. Our results therefore identify the activity of primary visual cortex as one possible neural correlate of perceived contrast.

Adult↗

PubMed2003

Comparison of different concentrations of levobupivacaine for post-operative epidural analgesia.

BACKGROUND: The relative effects of the mass, volume and concentration of local anaesthetic solution used for epidural anaesthesia and analgesia are still under debate. Clinical studies have shown discrepancies, probably because of limited consideration of total dose. METHODS: This prospective, randomized and blinded study evaluated the spread, the quality of post-operative analgesia and the incidence of side-effects of continuous thoracic epidural levobupivacaine 15 mg/h in three different concentrations: 1.5 mg/ml, 10 ml/h (n = 26), 5 mg/ml, 3 ml/h (n = 33) or 7.5 mg/ml, 2 ml/h (n = 31). The following variables were registered within 48 h: sensory block, pain scores, rescue morphine consumption, motor blockade, haemodynamics, sedation, nausea and vomiting, and patient satisfaction. RESULTS: The three groups were similar with regard to demographics, quality of analgesia, morphine consumption, and satisfaction rate. The upper level of sensory block was two segments higher in the 1.5 mg/ml group. Motor blockade in the lower limbs was low in the three groups. Haemodynamic profile was more stable in the higher concentration groups compared with the 1.5 mg/ml patient group (P < 0.001). Nausea was more frequent in the 1.5 mg/ml group (P = 0.02). CONCLUSION: The same dose of levobupivacaine provides an equal quality of analgesia in low or high volume continuous thoracic epidural infusion with reduced haemodynamic instability and nausea in the low volume/high concentration groups.

Abdomen↗

PubMed2003

The emergence of a C/EBPalpha mutation in the clonal evolution of MDS towards secondary AML.

Recently, mutations in the transcription factor CCAAT/ enhancer binding protein alpha (C/EBPalpha) have been described in acute myeloid leukemia (AML). We performed a mutational analysis of the C/EBPalpha gene in the myelodysplastic syndromes and AML with antecedent MDS. No mutations were found in patients with refractory anemia (0/27), refractory anemia with ringed sideroblasts (0/7), refractory anemia with excess of blasts (RAEB 0/16) or chronic myelomonocytic leukemia (CMML 0/5). One out of 13 patients with RAEB-T/AML secondary to MDS showed a mutation in the C/EBPalpha gene. In this patient a 4 bp insertion disrupted codon 69 in one allele. This novel +1 frame shift is predicted to result in a truncated protein of 107 amino acids. However, the dominant protein translated was the C/EBPalpha isoform p30, which was previously shown to inhibit the DNA-binding and transactivation properties of C/EBPalpha p42. Interestingly this mutation could not be detected at diagnosis in the initial RAEB and RAEB-T stage. The mutation appeared at relapse after chemotherapy for RAEB-T. We conclude that the C/EBPalpha mutation was not essential for the initial blast accumulation. The emergence of a bast clone carrying a C/EBPalpha mutation at relapse indicates that this mutation may confer a growth advantage in a myeloid cell with an established differentiation block.

Adult↗

PubMed2002

Favourable response to antithymocyte or antilymphocyte globulin in low-risk myelodysplastic syndrome patients with a 'non-clonal' pattern of X-chromosome inactivation in bone marrow cells.

OBJECTIVE: Antithymocyte and antilymphocyte globulin (ATG/ALG) have a therapeutic effect in about 30% of patients with myelodysplastic syndromes (MDS). We were interested to know whether responding patients achieve clonal or polyclonal remissions. PATIENTS: Ten women with low-risk MDS received either ALG or ATG. Before treatment and 3, 6, and 12 months later, X-chromosome inactivation patterns of peripheral blood T lymphocytes were compared with those of peripheral blood granulocytes or bone marrow cells, using the human androgen receptor gene assay and the phosphoglycerate kinase-1 assay. RESULTS: Six women did not respond to therapy. Prior to treatment, four of them had a monoclonal, one had an oligoclonal, and one had a skewed X-chromosome inactivation pattern (XCIP). Four patients responded to ATG/ALG. Three of them were informative in our X-inactivation assays, and showed a non-clonal XCIP which did not change significantly after treatment with ATG/ALG. CONCLUSION: A non-clonal XCIP in the bone marrow was associated with a response to ATG/ALG. Non-clonal XCIPs do not necessarily imply that there is no pathological clone. By definition, they just indicate that there is no evidence of a clone contributing more than 50% of cells in a sample. Non-clonal XCIPs may therefore be attributable to incomplete clonal expansion. This, in turn, might be explained by a vigorous immune attack against the MDS clone, which simultaneously causes collateral damage in the remaining normal haemopoiesis. In such patients, ATG/ALG may improve normal haemopoiesis by relieving the immunological pressure on the innocent bystanders.

Aged↗

PubMed2002

Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation.

Mycophenolate mofetil (MMF) is increasingly used for prophylaxis and therapy of GVHD in allogeneic stem cell transplantation. In some recent reports of use of MMF in solid organ transplantation a high incidence of CMV disease has been described. We evaluated the frequency and course of active CMV infection in patients who received MMF compared to those who did not receive MMF after allogeneic stem cell transplantation. We retrospectively analyzed 48 adult patients who consecutively underwent unmanipulated allogeneic bone marrow (n = 15) or peripheral stem cell transplantation (n = 33) from HLA-compatible family donors (n = 30) or unrelated donors (n = 18) from February 1997 to September 2000 at our institution. Only patients who were evaluable for the first 100 days were included in this analysis. Sixteen patients received MMF post transplant (MMF+). CMV-antigenemia was monitored by CMV-pp65 antigen. CMV-antigenemia occurred in 14 patients and was virtually only observed in CMV-IgG+ recipients (13/23, 56%). CMV-IgG+/MMF+ patients developed a higher incidence of CMV-antigenemia (8/9, 89%) compared to the CMV-IgG+/MMF- patients (5/14, 35%; P < 0.05). Moreover, five of six patients with persistent or recurrent CMV-antigenemia received MMF. No patient in either group developed CMV disease or died of CMV-related complications. In multivariate analysis including MMF treatment, unrelated vs related donor, GVHD, CMV-serostatus of the donor and stem cell graft type, only MMF treatment was found to be a significant risk factor for both overall and complicated CMV infection.

Adult↗

PubMed2002

Systemic sclerosis and occupational risk factors: a case-control study.

AIMS: A case-control study was carried out between 1998 and 2000 to investigate the relation between systemic sclerosis and occupational exposure. METHODS: Eighty cases of systemic sclerosis admitted consecutively to the Department of Internal Medicine at the University Hospital of Tours from 1998 to 2000 were included. For each case, two age, gender, and smoking habits matched controls hospitalised during the same period in the same department were selected. A committee of experts was set up retrospectively to assess occupational exposure. Exposure to silica dust and organic solvents (such as trichlorethylene and other chlorinated solvents, and benzene and other aromatic solvents) was investigated using semiquantitative estimates of exposure. An exposure score was calculated for each subject based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained, taking into account all periods of employment. RESULTS: Significant associations with SS were observed for crystalline silica, trichlorethylene, chlorinated solvents, toluene, aromatic solvents, ketones, white spirit, epoxy resins, and welding fumes. Risk of SS was significantly associated with a high final cumulative exposure score of occupational exposure to crystalline silica, trichlorethylene, chlorinated solvents, welding fumes, and any types of solvents. CONCLUSION: Results confirm the influence of occupational risk factors in the occurrence of SS in both men and women. The link is not only with silica but also with other compounds such as solvents.

Case-Control Studies↗

PubMed2001

Molecular modifications in factor VIII concentrates produced from different plasma pools.

We defined the main cause for the increased immunogenicity of the commercial factor VIII (fVIII) plasma-derived concentrates reported to induce formation of inhibitory antibodies in haemophilia A patients in Germany and Belgium. Formation of these antibodies directed against the C2 domain of fVIII was previously attributed to the use of solvent/detergent (S/D) treatment and pasteurisation for virus inactivation of fVIII concentrate. Since fVIII concentrates associated with increased immunogenicity were prepared from plasma pools characterised by elevated levels of coagulation markers, we examined whether the plasma source or S/D treatment and pasteurisation are responsible for structural changes within the C2 domain causing its abnormal immunogenicity. We found that samples of fVIII concentrate that originated from the abnormal plasma pool had a reduced ability to bind to phospholipid and conformationally sensitive anti-C2 domain antibodies, this effect being mostly pronounced in the samples that underwent both S/D treatment and pasteurisation. Thus, our study suggests that insufficient quality of the starting plasma pools is the major factor determining the structural alterations in the C2 domain of fVIII, whereas combination of S/D treatment and pasteurisation aggravates these changes.

Antithrombin III↗

PubMed2001

Antifungal actinomycete metabolites discovered in a differential cell-based screening using a recombinant TOPO1 deletion mutant strain.

In the course of a natural product screening for inhibitors of fungal topoisomerase 1 (TOPO 1), extracts from the actinomycete strains WS 1410 and BS 1465 exhibited promising activities. Bioguided fractionation of the culture broth by preparative HPLC methods yielded the collismycins A (1) and B (2) as active principles of strain WS 1410. Out of the mycelial extracts of strain BS 1465 the bioactive new natural products, cyclo-homononactic acid (3) and cyclo-nonactic acid (5) and the structurally related but inactive homononactic acid (4), were isolated. Both collismycin isomers inhibited the recombinant yeast strains ScAL 141 and ScAL 143 (TOPO 1 deletion mutant) in a non-specific manner with an MIC in the range of 2 micrograms/ml. The novel cyclo-homononactic acid (3) and cyclo-nonactic acid (5) showed higher selectivity towards the wild type strain (MIC = 2 micrograms/ml as compared to 10 micrograms/ml for the deletion mutant). All compounds obviously address a target other than TOPO 1 since they do not exhibit activities in a concurrent TOPO 1 enzyme assay.

2,2'-Dipyridyl↗

PubMed2001

Concentricol, a taxonomically significant triterpenoid from Daldinia concentrica.

In the course of a chemotaxonomic study of xylariaceous Ascomycetes, a major metabolite was isolated and identified from the ascostromata of Daldinia concentrica. The compound, for which the name concentricol is proposed, constitutes a highly oxidised squalene derivative. A survey of several Daldinia spp. from around the world (including several type materials), employing analytical HPLC-UV/Vis (with diode array detection) and positive electrospray HPLC-MS of stromatal MeOH extracts revealed that concentricol was omnipresent in the stromata of D. concentrica, as well as in those of several collections of the pantropical Daldinia eschscholzii. All other investigated Daldinia spp. were found devoid of concentricol but contained binaphthalenes, benzophenones and/or azaphilones as further taxonomically relevant main metabolites.

Ascomycota↗

PubMed2000

Reversal-rate dependent differences in the EEG gamma-band during multistable visual perception.

It is an often reported observation in the literature on multistable perception that the reversal rate within a given observation time is subject to a high interindividual variability. Recently, we reported frontal gamma-band enhancement during multistable visual perception. The aim of the present study was to investigate whether changes in the gamma-band correspond to the variability of the reversal rate. Therefore, a total of 25 observers were divided into two subgroups according to their reversal rate during a 400-s observation period of a reversible pattern based on apparent motion. Subjects with more than 40 reversals within the 400-s were defined as high-rate switchers (HRS). Subjects with a reversal rate below 40 switches were defined as low-rate switchers (LRS). EEG was recorded from frontal, central, parietal, and occipital locations of both hemispheres. The results showed significantly higher gamma activity for the HRS in both phase-locked and non-phase-locked oscillations. Both subgroups showed the highest gamma amplitudes at frontal locations. The results support the involvement of attentional top-down processing in figure reversal. It is concluded that the higher gamma activity for the HRS reflects states of higher arousal, alertness and/or attention according to their fast reversal rate.

Adolescent↗

PubMed2000

Alpha activity decreases during the perception of Necker cube reversals: an application of wavelet transform.

Since the first observation of perceptual reversal by Necker, many theoretical approaches have been proposed. In a previous study, we showed that a positive wave appeared approximately 250 ms prior to the button press of the subjects, indicating perceptual reversal during the observation of the Necker cube figure. A basic difficulty in this type of study is the possible jitter in the latency of the button press due to the variability of the subjects' reaction time during a recording session. To overcome this difficulty, a pattern selection method based on the wavelet transform was proposed in the previous study. A dominant positive wavelet coefficient in the delta band was found to represent the perceptual-reversal-related positivity. In the present study, we aim to analyze the changes in the alpha frequency band during perceptual reversal by using the Necker cube. The RMS values of the alpha frequency band were measured for two time periods: +/- 3 SD around the mean peak latency of the perceptual-reversal-related positivity and a time window of the same length before the positive wave. We found significantly increased delta power and decreased alpha power during the perceptual-reversal-related positivity.

Adult↗

PubMed2000

Noise improves three-dimensional perception: stochastic resonance and other impacts of noise to the perception of autostereograms.

Autostereograms can be perceived in different well-defined spatial levels. Therefore they are an excellent tool with which to examine spatiotemporal processes of multistable three-dimensional perception. We study properties of spatial ambiguity such as phase transitions between different spatial levels and hysteresis in perception with and without noise. We show that the perception of physical noise-which is added to the autostereograms in the form of a random dot pattern-is dependent on the perceived spatial level. We demonstrate that noise can be helpful for the perception of depth in some cases. We show that the signal-to-noise ratio of depth perception is enhanced at an intermediate level of noise strength that is the signature of stochastic resonance in depth perception.

Artifacts↗

PubMed2000

Endotoxin-induced lung inflammation is independent of the complement membrane attack complex.

Several products of the activated complement system are known to modulate endothelial cell function in vitro. It has been shown that the membrane attack complex (MAC) (C5b-C9) can enhance tumor necrosis factor alpha (TNF-alpha)-induced expression of P- and E-selectin and intercellular adhesion molecule type 1 in cell cultures of human umbilical vein endothelial cells. In the present study the potential role of this synegism for lung injury during endotoxin-mediated septic shock in vivo was examined using a model of C6-deficient PVG (C-) (RT1(C)) rats and the congenic PVG (C+) (RT1(C)) strain. Following administration of a high (5 mg/kg) or low (0.5 mg/kg) dose of lipopolysaccharide (LPS) (Escherichia coli O55:B5), we determined the expression of cytokines, chemokines, and adhesion molecules as well as the recruitment of leukocytes in the lung. Challenge with intraperitoneal i.p. injections of LPS resulted in a strong induction of TNF-alpha, interleukin-1alpha/beta, cytokine-induced neutrophil chemoattractant, interferon-inducible protein 10, macrophage inflammatory proteins 1alpha and 2, macrophage chemotactic protein 1, and P-selectin. However, there were no significant differences between PVG (C-) and PVG (C+) rats. Immunoperoxidase staining showed a similar increase of lung infiltration by CD11b/c(+) leukocytes in both rat strains. We therefore conclude that the described synergism between TNF-alpha and the MAC of the complement system on the induction of endothelial adhesion molecules is dispensable for inflammatory processes during endotoxin-mediated septic shock in vivo.

Animals↗

PubMed1999

VEP-interhemispheric transfer time in 20-32 Hz band in man.

This research aimed to investigate callosal transfer in the different frequency bands of VEP to lateralized reversal of checkerboard pattern as stimuli. The chosen band pass filters (4-8 Hz, 8-15 Hz, 15-20 Hz, 20-32 Hz) were applied to the VEPs of subjects, and four different components for each VEP were obtained. Latency differences between hemispheres for digitally unfiltered and filtered VEPs were computed to estimate IHTT. Different IHTTs in the theta (17 ms), alpha (9 ms) and beta1 (7 ms) bands from right to left and from left to right were estimated, supporting the previous report. Furthermore, a transfer within 4.5 ms from right to left in the 20-32 Hz band for the occipital lobe was found. In conclusion, our findings suggest that the frequency analysis of VEP to lateralized stimuli give us additional information, relating to the types of callosal fibers.

Adult↗

PubMed1999

Pigs aerogenously immunized with genetically inactivated (ghosts) or irradiated Actinobacillus pleuropneumoniae are protected against a homologous aerosol challenge despite differing in pulmonary cellular and antibody responses.

Aerosol immunization is a safe way to induce complete protection against pleuropneumonia in pigs caused by the lung pathogenic bacterium Actinobacillus pleuropneumoniae. In order to determine the local immune responses of vaccinees in concomitant with protection, lung lining fluid before and 3 weeks after immunization from pigs immunized three times with aerosols of either genetically inactivated ghosts which represent whole cell envelope preparations, or irradiated bacteria were examined following an homologous aerosol challenge. Specific antibody isotypes in the bronchoalveolar lavage were assayed by whole cell ELISAs. Total and relative numbers of cells including lymphocyte subsets were determined. In both vaccinated groups a net influx of plasma cells and lymphocytes, as well as a significant increase of specific IgG occurred. Concurrently, the CD4+/CD8+ ratio was found to increase after aerosol immunization. The lymphocyte subsets of IgG+ and IgA+ cells were found significantly higher in the group immunized with irradiated bacteria when compared to pigs immunized with bacterial ghosts. The latter group showed a significant increase of IgA, IgM, and a net influx of lymphoid blasts and granulocytes in the bronchoalveolar lining fluid. Although differences between the local immune responses of both immunized groups occurred, a significant increase of specific IgG and a net influx of plasma cells and lymphocytes were found to be associated with complete protection against a homologous aerosol challenge infection.

Actinobacillus Infections↗

PubMed1999

TIF1gamma, a novel member of the transcriptional intermediary factor 1 family.

We report the cloning and characterization of a novel member of the Transcriptional Intermediary Factor 1 (TIF1) gene family, human TIF1gamma. Similar to TIF1alpha and TIF1beta, the structure of TIF1beta is characterized by multiple domains: RING finger, B boxes, Coiled coil, PHD/TTC, and bromodomain. Although structurally related to TIF1alpha and TIF1beta, TIF1gamma presents several functional differences. In contrast to TIF1alpha, but like TIF1beta, TIF1 does not interact with nuclear receptors in yeast two-hybrid or GST pull-down assays and does not interfere with retinoic acid response in transfected mammalian cells. Whereas TIF1alpha and TIF1beta were previously found to interact with the KRAB silencing domain of KOX1 and with the HP1alpha, MODI (HP1beta) and MOD2 (HP1gamma) heterochromatinic proteins, suggesting that they may participate in a complex involved in heterochromatin-induced gene repression, TIF1gamma does not interact with either the KRAB domain of KOX1 or the HP1 proteins. Nevertheless, TIF1gamma, like TIF1alpha and TIF1beta, exhibits a strong silencing activity when tethered to a promoter. Since deletion of a novel motif unique to the three TIF1 proteins, called TIF1 signature sequence (TSS), abrogates transcriptional repression by TIF1gamma, this motif likely participates in TIF1 dependent repression.

Amino Acid Sequence↗

PubMed1999

Visual evoked potential interhemispheric transfer time in different frequency bands.

OBJECTIVE: Visual evoked potentials (VEP) have been used to estimate interhemispheric transfer time (IHTT). However, the complex wave of VEP is most probably formed by different generators of neural populations that act through different frequency channels. If the main peaks of VEP are established by different types of generators, which can also be connected to each other by a different type of callosal fibres, we would be able to estimate a wide range of various IHTT by measuring the latency between time-locked peaks of narrow band-pass filtered VEP. This research aimed to test this hypothesis. METHODS: Nine right-handed men were presented with a reversal of a checkerboard pattern as stimuli at RVF or LVF, and EEG was recorded at O1, O2, P3, P4. The grand-averaged VEPs were transformed to the frequency domain by means of the fast Fourier transform to obtain the amplitude frequency characteristics. Band-pass filters were chosen adequately, according to tuning frequencies indicated by clear peaks in the amplitude frequency characteristics. The chosen band pass filters (4-8 Hz, 8-15 Hz, 15-20 Hz, 20-32 Hz) were applied to the VEP of the subjects, and 4 different components of VEPs for each VEP were obtained. The latency of P100 and N160 of unfiltered VEP was measured. In the band-pass digital filter applied VEPs, positive and negative peaks, which are consistent with P100 and N160, were measured for each subject. Latency differences between hemispheres for digitally unfiltered and filtered VEPs were computed to estimate IHTT. RESULTS: In the different frequency bands, different IHTTs were estimated, ranging from 3 ms to 30 ms. Approximately 16 ms for theta band, 11 ms for alpha band, 6 ms for 15-20 Hz and 3 ms for 20-32 Hz bands were found. CONCLUSIONS: Our findings support the hypothesis which states that unfiltered VEPs provide us with only a rough estimation of IHTT. Also, they are consistent with anatomical findings that describe callosal fibres of varying dimensions, predicting various velocities between hemispheres.

Adult↗