Biomedical subjects

M Müller

Publications and source records attributed to M Müller.

At least 901 records · Page 50Linked to original sources

PubMed1994

Role of excitatory amino acid and GABAB receptors in the generation of epileptiform activity in disinhibited hippocampal slice cultures.

Selective excitatory amino acid- and GABAB-receptor antagonists were used to examine the role these receptors play in epileptiform burst discharge elicited by blocking GABAA receptor-mediated inhibition in hippocampal slice cultures of the rat. Application of bicuculline caused a single ictal burst followed by interictal bursting. The N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonovalerate, reduced the depolarizing envelope underlying interictal discharge, and accentuated the appearance of concomitant slow oscillatory potentials, which occurred synchronously in all CA3 cells. The non-N-methyl-D-aspartate receptor antagonists, 6-nitro-7sulphamoyl-benzo(F) quinoxaline and 6-cyano-7-nitro-quinoxaline-2,3-dione, blocked interictal bursting at high concentrations, and low concentrations of 6-cyano-7-nitro-quinoxaline-2,3-dione selectively eliminated the slow oscillations in an all-or-none manner, leaving the depolarizing envelope. No effects of either metabotropic glutamate receptor antagonists or of dihydropyridine Ca2+ channel agonists or antagonists on evoked interictal discharge were observed. 6-Cyano-7-nitro-quinoxaline-2,3-dione-resistant interictal-like discharge could be obtained in the presence of bicuculline when the external Mg2+ concentration was reduced from 1.5-0.5 mM. The GABAB receptor antagonist CGP 35348 prolonged individual evoked interictal bursts, and caused the appearance of spontaneous ictal-like discharges. The implications of these results are discussed with regard to the mechanisms of epileptogenesis and to potential therapeutic intervention.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1994

Preferred intervals in birds and mammals: a filter response to noise?

Quasi-periodic spontaneous activity (preferred intervals, PIs) has been reported from avian primary auditory afferents. In mammals, PIs have not been reported, as yet. As the length of PIs is close to 1/characteristic frequency, it has been suggested that this type of spontaneous activity indicates particular mechanisms in avian inner ear transduction. However, the present paper shows that pigeon auditory fibres possessing preferred intervals in their spontaneous activity always belong to the most sensitive and the most sharply-tuned fibres recorded. This leads to the assumption that preferred intervals are the response of narrow-band filters to noise. This view is supported by three additional findings: (i) Near-threshold noise provokes PIs in avian fibres that show no spontaneous PIs. (ii) Similarly, PIs can also be evoked in mammalian (gerbil) auditory afferents by low level noise. (iii) Phase-locking of auditory afferents can be achieved by sound stimuli 10-20 dB below rate threshold. It is argued that no conclusions may be drawn from the presence of PIs about the nature of the underlying filter.

Acoustic Stimulation↗

PubMed1994

Event-related and motor responses to probes in a forewarned reaction time task in schizophrenic patients.

Surface-negative brain potentials indicate increased excitability of the underlying cortical neural networks. Consequently, deviant patterns of event-related potentials in schizophrenic patients reveal an atypical regulation of cortical excitability. Twelve patients with a chronic schizophrenic disorder and 12 matched control subjects were investigated using a probe paradigm: A contingent negative variation (CNV) was evoked in a forewarned reaction time paradigm. Clicks were presented before, during and after elicitation of the CNV. Click-evoked responses allow one to 'probe' the current brain state, particularly neuronal excitability, which is also reflected by the slow potentials. During the measurements, subjects pressed one button in response to the offset of the visual warning stimulus and a different button in response to the acoustic probes, the latter button press being a behavioral indication of the brain's excitability. In the forewarned reaction time task, patients developed a CNV with a frontal maximum, while the CNV in control subjects was predominantly centro-parietal. This atypical topographical pattern of the CNV may indicate a different spatio-temporal regulation of cortical preparatory processes in schizophrenics. Motor responses were accelerated during negative potential shifts in both patients and controls, with responses being slower overall in patients. In patients, probe-evoked potentials revealed a smaller N100, but a larger P300, than in controls. The covariation of these brain waves with slow potentials, however, turned out to be similar for both groups.

Adult↗

PubMed1994

Species differences in lectin binding to pulmonary cells: Soybean agglutinin (SBA) as a marker of type I alveolar epithelial cells and alveolar macrophages in mini pigs.

We compared lectin staining patterns in rat and mini pig tissues of normal and fibrotic (irradiation-induced) lungs. Two lectins were studied: Dolichos biflorus (DBA) and Soybean (SBA). Both lectins strongly stained a subpopulation of alveolar macrophages. In the rat, DBA positive macrophages were a subpopulation of the SBA binding cells. In mini pig lungs, a further specific binding of DBA and SBA was observed: DBA reacted with endothelia, and SBA stained the alveolar type I cells. Double immunofluorescence experiments using a type II cell-specific cytokeratin antibody confirmed the selective reactivity of SBA with type I cells, which was also present in fibrotic areas with epithelial cell proliferation.

Animals↗

PubMed1994

Modulation of pan-cadherin expression in alveolar epithelial cells of mini pigs with pulmonary fibrosis.

The expression of pan-cadherin was investigated immunohistochemically in normal and irradiated mini pig lungs. Using a double labelling immunofluorescence technique, pan-cadherin expression was also compared with that of cytokeratin 18, which is selectively present in type II cells. In untreated animals pan-cadherin was detected in type I pneumocytes, in alveolar macrophages and in endothelial cells of larger blood vessels. Radiation caused increased pan-cadherin immunoreactivity of bronchial epithelial cells and interstitial cells. In addition, pan-cadherin expression was induced in type II pneumocytes. These changes in the distribution of epithelial cadherin molecules may implicate a role of cadherins for epithelial remodeling in response to radiation-induced lung injury.

Animals↗

PubMed1994

Immunohistochemical localization of the beta subunit of prolyl 4-hydroxylase in human alveolar epithelial cells.

The beta subunit of prolyl 4-hydroxylase, the protein-disulfide isomerase (PDJ), catalyzes the hydroxylation of proline residues of collagens and proteins with collagen-like structure, a step essential for the folding of the procollagen chains to form triple-helices. In the present study, we report the selective immunohistological localization of PDI in type II alveolar and bronchial epithelial cells. The detection of the hidden antigen with the monoclonal antibody 5B5 is usually not successful in paraffin sections but was possible after microwave pretreatment of tissue sections. In cases of severe lung injury (fibrosing alveolitis) enhanced immunoreactivity was found for this enzyme in epithelial, endothelial as well as interstitial cells and in alveolar macrophages. The results indicate a possible involvement of the pulmonary epithelial cells in the upregulation of collagen production during the process of fibrosis.

Antibodies, Monoclonal↗

PubMed1994

The value of the AgNOR staining method in identifying carcinoma in situ testis.

An early and reliable diagnosis is necessary in order to have the chance of a curative therapy of Carcinoma in situ testis (Cis). Forty-six testicular biopsies were investigated to assess the value of the AgNOR staining method in comparison to placental alkaline phosphatase (PLAP) immunostaining. Both methods provided corresponding results and identical tumor cells were recognized in serial sections. The mean AgNOR counts per nucleus were 26.86 (19-52, SD: 2.68) for CIS cells, 8.18 (5-14, SD: 2.20) for spermatogonia and 12.96 (9-18, SD: 2.44) for Sertoli cells, without the counts overlapping within these three groups. Even single CIS cells are easily and reliably recognizable by their typical AgNOR pattern and their high AgNOR count per nucleus. The independent estimation of 9 testicular biopsies with the AgNOR staining method and the PLAP immunostaining correspondingly revealed 7 biopsies with CIS. Two biopsies lacked tumor cells. The AgNOR staining method can be recommended as an additional diagnostic tool in identifying CIS, because of the short and convenient staining procedure, low costs and the applicability on formalin-fixed and paraffin-embedded material.

Alkaline Phosphatase↗

PubMed1994

Bauhinia purpurea lectin (BPA) binding of rat type I pneumocytes: alveolar epithelial alterations after radiation-induced lung injury.

In the rat lung, we found that the Bauhinia purpurea lectin (BPA) specifically binds to the type I alveolar epithelial cells and to the alveolar macrophages. Double label fluorescence employing FITC-coupled Maclura pomifera lectin (MPA) and bBPA-avidin-Texas Red showed that BPA binding was confined to type I cells. In addition, a minor staining of the luminal border of the terminal bronchiolar epithelium was found. The sequence of tissue injury following X-radiation was examined in rats. BPA is a suitable marker which indicates epithelial changes during the early stage of pneumonitis and the subsequent development of fibrosis.

Animals↗

PubMed1994

Scalp distribution of slow cortical potentials in schizophrenic patients.

Surface-negative slow cortical potentials (SPs) indicate increased excitability of the underlying cortical networks. Deviant patterns of SPs in schizophrenic patients may reveal in atypical regulation of cortical excitability. This hypothesis was examined by comparing SP-scalp distribution between patients with a chronic schizophrenic disorder and matched control Ss using reaction time paradigms. In study I (12 Ss/group) a CNV was evoked during a 3-s visual S1, while the parallel presentation of clicks at various time intervals should "probe" the brain state during the CNV. The CNV showed a frontal predominance in patients compared to a centroparietal maximum in controls, suggesting an atypical spatio-temporal regulation of SPs in patients. Similar modulation of probe-evoked responses parallel to the CNV in both groups indicated the functional significance of SPs to be similar in schizophrenics and controls. In study II (17 Ss/group) association between a visual S1 and a lateralised tactile S2 allowed fast responses with the respective hand. This association could be formed in one trial series, while the side of tactile stimulation was unpredictable in another. Feedback of response adequacy was provided 1.5 s after S2. Groupds did not differ in mean CNV-amplitudes or -lateralisation. On the other hand, patients developed a pronounced, broadly distributed feedback-preceding negativity (FNP) on all trials, while controls exhibited a right-hemisperic FPN only, when the side of S2 was unpredictable and feedback became salient.

Adult↗

PubMed1994

[Accidental anesthetic overdose caused by anesthesia respirators Servo 900 C and D].

When working with the anaesthetics vaporizers/respirators of the type Siemens Servo 900 C/D we found differences between the values adjusted at the instrument and those measured by the anaesthetic gas monitor (Sirecust 734 G). Control measurements yielded differences of inspiratory concentrations of halothane and isoflurane that were in excess by up to 80%. We found that the reason for this was the absence of reducing valves at the respirator that would reduce the static pressure of central gas supply from 5.3-5.5 bar to the values of not more than 4.0 bar that are permissible for the vaporizer. It is pointed out that the operation of respirators of this type is safe only provided the prescribed gas supply pressures are observed, if necessary with the help of the appropriate reducing valves, to ensure accurate dosage of volatile anaesthetics.

Anesthesia, Inhalation↗

PubMed1994

[Quantification of disorders of the blood-aqueous humor barrier in retinitis pigmentosa--initial results].

BACKGROUND: Clinical findings in patients with retinitis pigmentosa (RP) frequently include cystoid macular edema (CME) and vitreous pigment dusting (VPD) indicating alterations of the blood-ocular barriers. It was the aim of this study to determine whether alterations of the blood-aqueous barrier (BAB) are present in RP. PATIENTS AND METHODS: Aqueous flare was quantitatively determined in 56 eyes of 29 patients (mean age 36.4 +/- 11.2 years) with RP using the noninvasive laser flare-cell photometer (Kowa FC-1000, Tokyo, Japan). All RP patients had common forms of RP with markedly reduced or nondetectable ERG. The presence of CME and VPD was determined semiquantitatively by biomicroscopy. Fifty-eight eyes of 58 normal controls (mean age 38.2 +/- 8.5 y.) were also examined. RESULTS: Aqueous-flare values were significantly higher in RP eyes (mean 9.65 +/- 3.24 photon counts/ms, range 4.0-18.1) than in the normal control eyes (mean 3.89 +/- 1.05, range 1.9-6.0, p < 0.0001, Mann-Whytney test). Forty-eight of the 56 RP eyes (86%) showed increased flare values (> 6.0 photon counts/ms). RP eyes with moderate to marked CME (n = 11) had significantly higher flare values (mean 14.66 +/- 1.92) than RP eyes without or with only questionable CME (8.52 +/- 2.18, p < 0.0001), and RP eyes with moderate to marked VPD (n = 17) had significantly higher (12.05 +/- 2.84) flare values than RP eyes without or with only minimal VPD (8.74 +/- 2.22, p < 0.0005). CONCLUSIONS: Our findings show that the majority of patients with RP have alterations of the BAB with consecutively increased aqueous protein concentrations. The impairment of the BAB appears to be associated with CME and VPD. Measurement of aqueous flare in RP allows quantification of the impairment of the BAB and may be helpful in the future in choosing and monitoring patients with RP and CMP for possible antiinflammatory or antiedematous therapeutic measures.

Adult↗

PubMed1994

Transgenic strategies to increase disease resistance in livestock.

Approaches to modify disease resistance or susceptibility by transgenic means will be a major asset to animal welfare as well as to the economics of animal production. Candidates for gene transfer experiments include all genes known to influence non-specific and specific host defence mechanisms against infectious pathogens. Additional strategies such as 'intracellular immunization', 'genetic and congenital immunization', antisense RNA approaches and targeted disruption of disease susceptibility genes promise to gain importance in conferring increased disease resistance. The cytokine network regulates cellular viability, growth and differentiation in physiological and pathophysiological states. Detailed understanding of cytokine signal transduction pathways and transcriptional activators will provide not only new target molecules for modulating the immune response but will also facilitate the elucidation of host-pathogen interactions.

Animals↗

PubMed1994

Interaction of bioactive hydrophobic peptides with the human multidrug transporter.

In this report we demonstrate that various biologically active hydrophobic peptide derivatives, e.g., proteinase inhibitors, chemoattractants, ionophores, enkephalins, and immunosuppressants, stimulate a membrane ATPase activity associated with the human multidrug transporter (MDR1). The stimulation of the MDR1-ATPase by these agents does not correlate with their known biochemical or pharmacological activities but rather with their hydrophobicity. The peptides that show high-affinity interaction with the MDR1-ATPase also interfere strongly with fluorescent dye extrusion catalyzed by the multidrug transporter in intact cells and some have been shown to reverse drug resistance in cultured cells. These data suggest that several hydrophobic peptides behave as substrates of the multidrug transporter and may be used to modulate the chemotherapy resistance of tumor cells.

3T3 Cells↗

PubMed1994

Insect iridescent virus type 6 encodes a polypeptide related to the largest subunit of eukaryotic RNA polymerase II.

Cytoplasmic DNA viruses encode a DNA-dependent RNA polymerase (DdRP) that is essential for transcription of viral genes. The amino acid sequences of known large subunits of DdRPs contain highly conserved regions. Oligonucleotide primers, deduced from two conserved domains [RQP(T/S)LH and NADFDGDE] were used in PCR experiments for the detection of the corresponding gene of the genome of insect iridescent virus type 6, also known as Chilo iridescent virus (CIV). A specific DNA product of about 150 bp could be amplified and was used as a hybridization probe against the CIV gene library to identify the corresponding gene. The gene encoding the DdRP was identified within the EcoRI fragments M (7099 bp) and L (7400 bp) of CIV DNA, between map units 0.310 and 0.347 (7990 bp). The DNA nucleotide sequence (3153 bp) of the gene encoding the largest subunit of DdRP (RPO1) was determined. Northern blot hybridization revealed the presence of a 3.4 kb RNA transcript in CIV-infected cells that hybridized to the CIV DdRP gene. This predicted viral protein consists of 1051 amino acid residues (120K) and showed considerably higher similarity to the largest subunit of eukaryotic RNA polymerase II than to the homologous proteins of vaccinia virus and African swine fever virus. Phylogenetic analysis suggested that the putative RPO1 of CIV could have evolved from RNA polymerase II after the divergence of the three types of eukaryotic RNA polymerases. The putative RPO1 of CIV lacked the C-terminal domain that is conserved in eukaryotic, eubacterial and other viral RNA polymerases and in this respect was analogous to the RNA polymerases of Archaea. It is hypothesized that the equivalent of the C-terminal domain may reside in another subunit of CIV DdRP encoded by an unidentified viral gene.

Amino Acid Sequence↗

PubMed1994

Fermentation of fructans by epiphytic lactic acid bacteria.

A total of 712 strains of lactic acid bacteria isolated from forage grasses were studied for their ability to ferment fructans of phlein- as well as inulin-type. Only 16 strains utilized phlein and eight of these also fermented inulin. They were identified as Lactobacillus paracasei subsp. paracasei, Lact. plantarum, Lact. brevis and Pediococcus pentosaceus. In the species Lact. paracasei subsp. paracasei, all strains gave positive results, whereas the other positive strains possessed unique properties within their own species. In all but two cases (strains of the species Lact. plantarum), the phlein was more intensively fermented than the inulin, as indicated by a lower pH and a higher lactic acid concentration. On the basis of the outcome of this study it seems worthwhile to inoculate grasses of low sugar content before ensiling with an active strain that can ferment fructans.

Fermentation↗

PubMed1994

High-pressure freezing of cell suspensions in cellulose capillary tubes.

A procedure for efficient cryoimmobilization of large volumes of cell suspensions or micro-organisms by high-pressure freezing is described. This procedure uses transparent, porous cellulose capillary tubes with an inner diameter of 200 microns, into which the suspensions are drawn by capillary action. The tubes are processed by high-pressure freezing and freeze-substitution as if they were tissue samples. Centrifugation of suspensions at low temperatures is no longer necessary and cryopreparation is greatly facilitated. A very high yield of adequately frozen specimens is obtained due to the constant, defined sample geometry. This approach can also be used to process suspensions by conventional chemical fixation, eliminating the need to embed pellets in low-melting-point agarose, for example, prior to chemical fixation. The preparation procedure is demonstrated with suspensions of nematodes, paramecia and bacteria.

Animals↗

PubMed1994

Interferon response pathways--a paradigm for cytokine signalling?

Considerable progress has been made in the past few years elucidating the molecular mechanisms of cytokine signalling. The interferons (IFNs) have provided a singular system allowing the detailed characterization of a specific cytokine signalling pathway. Studies on the IFN signal transduction pathway have identified protein tyrosine kinases (PTKs) that phosphorylate signal transducers (STATs) which then bind to DNA promoter sequences and activate gene transcription. Related work has shown that JAKs and STATs are also activated in response to a variety of the cytokines. Thus the novel type of signal transduction pathway identified for the IFNs promises to be more widely utilized than anticipated.

Animals↗

PubMed1994

Enhanced expression of IL-8 in normal human keratinocytes and human keratinocyte cell line HaCaT in vitro after stimulation with contact sensitizers, tolerogens and irritants.

To investigate the interleukin-8 production of keratinocytes after stimulation in vitro we have used various agents: (i) contact sensitizer (2,4-dinitrofluorobenzene, 3-n-pentadecylcatechol); (ii) tolerogen (5-methyl-3-n-pentadecylcatechol); (iii) irritant (sodium lauryl sulfate). Interleukin-8 gene expression was assessed by northern blot hybridization of the total cytoplasmic RNA extracted from subconfluent normal human keratinocyte cultures and the keratinocyte cell line HaCaT using a radiolabeled DNA probe specific for human interleukin-8. Interleukin-8 gene expression was markedly increased upon in vitro stimulation after 1-6 h with contact sensitizers, tolerogen and the irritant. In contrast, interleukin-8 production was not detectable in unstimulated normal human keratinocytes or the HaCaT keratinocyte cell line. These results suggest that the induction and production of interleukin-8 is a response to nonspecific stimuli and may play a critical role in the early response to immunogenic or inflammatory signals in man.

Catechols↗