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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 289 records · Page 16Linked to original sources
PubMed1996

Syn/anti isomerization of 2,4-dinitrophenylhydrazones in the determination of airborne unsymmetrical aldehydes and ketones using 2,4-dinitrophenylhydrazine derivation.

Aldehydes and ketones readily react with 2,4-dinitrophenylhydrazine (2,4-DNPH) to form the corresponding hydrazones. This reaction has been frequently used for the quantification of airborne carbonyl compounds. Since unsymmetrical aldehydes and ketones are known to form isomeric 2,4-dinitrophenylhydrazones (syn/ anti-isomers), the influence of isomerization on the practicability and accuracy of the 2,4-DNPH-method using 2,4-dinitrophenylhydrazine-coated solid sorbent samplers has been studied with three ketones (methyl ethyl ketone (MEK), methyl isopropyl ketone (MIPK), and methyl isobutyl ketone (MIBK)). With all three ketones the reaction with 2,4-DNPH resulted in mixtures of the isomeric hydrazones which were separated by HPLC and GC and identified by mass spectroscopy and (1)H nuclear magnetic resonance spectroscopy. The isomers show similar chromatographic behaviour in HPLC as well as in GC, thus leading to problems in quantification and interpretation of chromatographic results.

Journal Article↗
PubMed1996

Dynamics of human flight on skis: improvements in safety and fairness in ski jumping.

This study of ski jumping includes three areas of research: Wind tunnel measurements with world class athletes in various flight positions, field measurements during the World Championships in Ski Flying 1994 in Planica (Slovenia) and a highly reliable mapping of ski jumping to a computable simulation model. The results explain the effects of equipment, flight style changes, the reason for the enhanced tumbling risk and high gust sensitivity observed. Consequences can be drawn for changes to the FIS regulations, the design of jumping hills and training methods. The internationally induced anorexia of the athletes could be prohibited by a new ski length regulation. Women jumpers could become a real competitive threat.

Accidental Falls↗
PubMed1996

Biphenyl-derivatives of 2-amino-7-phosphonoheptanoic acid, a novel class of potent competitive N-methyl-D-aspartate receptor antagonist--I. Pharmacological characterization in vitro.

Omega-Phosphono-substituted alpha-amino acids have long been known to be antagonists at the N-methyl-D-aspartate (NMDA) receptor. D-2-Amino-5-phosphonopentanoic (D-AP5) and D-2-amino-7-phosphonoheptanoic (D-AP7) acids are the "prototype" compounds of this kind. Insertion of a biphenyl-moiety in the middle of the AP7 chain results in increased affinity and reverses the enantioselectivity from a D- to an L-form preference (Müller et al., (1992) Helv. Chim. Acta 75: 855-864). We describe here a series of substituted biphenyl-AP7-derivatives, the most potent of which have affinities (in a [3H]CGP-39653 binding assay using native and recombinant receptors) and potencies (antagonism of NMDA-induced depolarizations in a cortical wedge preparation; inhibition of glutamate-stimulated [3H]MK-801 binding under non-equilibrium conditions) in the low nanomolar range. Structure-activity relationships show that hydroxy-substitution at the C5-atom in the AP7-chain as well as substitution in the second phenyl ring with space filling (such as chloro-)groups in the para- and especially the ortho-position (extending the torsion angle of the two rings) increase affinity and potency of these compounds. They have no relevant affinities for the strychnine-insensitive glycine co-agonist site or the MK-801/PCP channel blocking site on the NMDA receptor complex. AMPA- and kainate-induced responses were not affected by biphenyl-analogues. These compounds also do not interact with a number of other neurotransmitter receptor sites, and they do not inhibit the uptake of [3H] glutamate in rat brain synaptosomes. However, they display affinities in the (sub)micromolar range for a non-NMDA, non-AMPA, non-kainate binding site for [3H]glutamate, measured in the presence of calcium chloride, the functional correlate of which has not yet been elucidated.

2-Amino-5-phosphonovalerate↗
PubMed1996

Biphenyl-derivatives of 2-amino-7-phosphono-heptanoic acid, a novel class of potent competitive N-methyl-D-aspartate receptor antagonists--II. Pharmacological characterization in vivo.

A selection of biphenyl-analogues of 2-amino-7-phosphonoheptanoic acid (AP7), N-methyl-D-aspartate (NMDA) receptor antagonists with high affinity in vivo efficacy. The lead compound SDZ EAB 515 was found to inhibit L-phenylalanine uptake by the large neutral amino acid carrier in vitro and in vivo; active transport may thus confer a good bioavailability to this class of compounds. CNS effects were demonstrated by significant changes in 2-deoxyglucose-uptake in various brain regions at doses from 1 to 10 mg/kg i.p. With the most active agent, SDZ 220-581, full protection against maximal electroshock seizures (MES) was obtained at oral doses of 10 mg/kg in rats and in mice. The compound had a fast onset (< or = 1 hr) and a long duration (> or = 24 hr) of action. Motor-debilitating effects (impairment of rotarod performance) occurred at doses about 10 times higher than those required for protection against MES. Neuroprotective activity was demonstrated by the ability of the compounds to reduce the extent of quinolinic acid-induced striatal lesions in rats, in the dose range of 3-15 mg/kg (i.p.) or 10-50 mg/kg (p.o.). In the middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia in rats, the test compounds reduced the infarct size by 40-50% when given i.v. before or by 20-30% when given i.v. 1 hr after MCAO. SDZ 220-581 provided 20-30% protection at > or = 2 x 10 mg/kg p.o. This compound also showed analgesic activity at low oral doses in a model of neuropathic pain, although higher doses were required in model of mechanical inflammatory hyperalgesia. Unexpectedly, SDZ 220-581 at low s.c. doses counteracted the antiparkinsonian effects of L-DOPA in MPTP-treated marmosets. (Sub)chronic administration of SDZ 220-581 did not reduce its ability to protect against quinolinic acid neurotoxicity, and no upregulation of NMDA receptors was detected using a [3H]CGP-39653 binding assay. In conclusion, from a series of biphenyl-AP7-derivatives, SDZ 220-581 is clearly the most active compound in vivo. Its pharmacological profile with a good, long-lasting oral activity might open up novel therapeutic applications for competitive NMDA receptor antagonists.

Amino Acids↗
PubMed1996

Color-flow Doppler-assisted duplex imaging fails to detect ulceration in high-grade internal carotid artery stenosis.

PURPOSE: Pathoanatomic studies suggest that plaque surface disruption, particularly ulceration, plays a key role in the destabilization of internal carotid artery stenosis. Until now, the validity of color-flow Doppler-assisted duplex imaging in detecting such pathoanatomically defined plaque surface abnormalities is unclear. METHODS: We prospectively determined the interobserver reliability and validity of detecting plaque ulceration by means of preoperative color-flow Doppler-assisted duplex imaging in 43 consecutive patients with high-grade (> or = 70%) internal carotid artery stenosis, comparing these ultrasonographic findings with pathoanatomic evaluations of the corresponding endarterectomy specimens. RESULTS: Interobserver reliabilities for detecting carotid plaque ulceration were kappa= 0.57 for ultrasonography and kappa = 0.82 for the pathologic reference method. Color-flow Doppler-assisted duplex imaging (observer consensus) failed to detect pathoanatomically defined ulceration (chi square = 0.43; p = 0.51). Likewise, sensitivity, specificity, overall accuracy, and positive predictive value were poor (33%, 67%, 56%, and 46%, respectively). CONCLUSIONS: We conclude from our data that color-flow Doppler-assisted duplex imaging is not a reliable or valid means to identify plaque ulceration in high-grade carotid artery lesions.

Adult↗
PubMed1996

Prolonged islet allograft acceptance in the absence of interleukin 4 expression.

Murine CTLA4/Fc therapy leads to permanent engraftment of islet allografts in interleukin 4 (IL-4) knockout (IL-4-/- mice. Interestingly, IL-4+/- hosts were more resistant to tolerance induction than IL-4-/- mice. An IL-2/Fc fusion protein abrogates the effect of CTLA4/Fc therapy while an IL-4/Fc fusion protein tends to inhibit rather than enhance the effect of CTLA/Fc treatment in IL-4-/- recipients. We conclude that allograft acceptance requires principally a blockade of T cell activation rather than 'immune deviation' of the T cell activation program to Th2 cytokines (i.e. IL-4).

Animals↗
PubMed1996

Surrogate light chain expression is required to establish immunoglobulin heavy chain allelic exclusion during early B cell development.

Allelic exclusion at the IgH locus was examined in B lineage cells of wild-type mice and mice unable to express the surrogate light chain molecule lambda 5 using a single-cell PCR approach. By analyzing B precursor cells containing two VHDHJH rearrangements, we found that in wild-type animals, cells are allelically excluded as soon as mu chains are expressed. Furthermore, we provide evidence that in cells expressing D mu proteins VH-->DHJH rearrangement is inhibited. In contrast, in the absence of lambda 5 protein, B precursor cells were allelically "included", indicating that allelic exclusion at the IgH locus requires expression of the pre-B cell receptor either containing a mu chain or a D mu chain. However, although mu chain double-producing B precursor cells are generated in lambda 5-deficient mice, such cells were not detected among surface immunoglobulin positive B cells.

Alleles↗
PubMed1996

Immunohistochemical study on the prognostic value of MIB-1 in gastric carcinoma.

The prognostic significance of tumour cell proliferation was investigated in a series of 418 gastric carcinomas using the monoclonal antibody MIB-1. Owing to strong intratumoural heterogeneity of MIB-1 expression three different proliferation indices (PIs) were determined in all carcinomas: (1) PImax in areas of maximal tumour cell proliferation, (2) PIrand in areas randomly distributed over the whole tumour. (3) PIfront in areas exclusively located at the tumour invasion front. There was a strong intertumoral heterogeneity with PImax ranging from 4.9% to 92.2%, PIrand ranging from 3.4% to 81.4% and PIfront ranging from 4.2% to 87.1%. The mean values were 51.3% +/- 19.7 for PImax, 34.2% +/- 18.3 for PIrand and 37.2% +/- 19.5 for PIfront. Whereas no statistically significant correlation could be found between proliferative activity and the clinicopathological parameters depth of invasion, lymph node involvement or grade of tumour differentiation, there was a positive correlation between a high proliferation index at the tumour invasion front (PIfront) and the presence of blood or lymphatic vessel invasion. No significant correlation could be demonstrated between the different proliferation indices and survival, even when different subgroups of patients were analysed separately. The present results suggest that the immunohistochemical evaluation of the proliferation activity has no predictive value for the prognosis of gastric cancer patients or the identification of subgroups of patients who may be at higher risk.

Adult↗
PubMed1996

Differential effects of parathyroid hormone fragments on collagen gene expression in chondrocytes.

The effect of parathyroid hormone (PTH) in vivo after secretion by the parathyroid gland is mediated by bioactive fragments of the molecule. To elucidate their possible role in the regulation of cartilage matrix metabolism, the influence of the amino-terminal (NH2-terminal), the central, and the carboxyl-terminal (COOH-terminal) portion of the PTH on collagen gene expression was studied in a serum free cell culture system of fetal bovine and human chondrocytes. Expression of alpha1 (I), alpha1 (II), alpha1 (III), and alpha1 (X) mRNA was investigated by in situ hybridization and quantified by Northern blot analysis. NH2-terminal and mid-regional fragments containing a core sequence between amino acid residues 28-34 of PTH induced a significant rise in alpha1 (II) mRNA in proliferating chondrocytes. In addition, the COOH-terminal portion (aa 52-84) of the PTH molecule was shown to exert a stimulatory effect on alpha1 (II) and alpha1 (X) mRNA expression in chondrocytes from the hypertrophic zone of bovine epiphyseal cartilage. PTH peptides harboring either the functional domain in the central or COOH-terminal region of PTH can induce cAMP independent Ca2+ signaling in different subsets of chondrocytes as assessed by microfluorometry of Fura-2/AM loaded cells. These results support the hypothesis that different hormonal effects of PTH on cartilage matrix metabolism are exerted by distinct effector domains and depend on the differentiation stage of the target cell.

Animals↗
PubMed1996

Impaired immunosuppressive response to ultraviolet radiation in interleukin-10-deficient mice.

Exposure to mid-range ultraviolet radiation (UVR) [280-320 nm, ultraviolet B (UVB) radiation] inhibits the acquisition of delayed-type hypersensitivity in mice and contact hypersensitivity in rodents and humans. Intraperitoneal administration of interleukin 10 (IL-10) inhibits the sensitization of mice to alloantigens for a delayed-type hypersensitivity reaction and administration of neutralizing antibodies to IL-10 largely, but not totally, blocks the UVR-mediated suppression of the ability to sensitize mice. This suggests that these inhibitory effects of UVB radiation may be mediated by release of IL-10. To test this hypothesis directly, IL-10 gene-targeted (IL-10T) mice lacking expression of IL-10 were examined for the ability of UVB radiation to suppress induction of delayed-type hypersensitivity to alloantigens. IL-10T mice were completely resistant to UVB-induced immunosuppression in this system. Interestingly, UVB radiation could suppress in IL-10T mice the induction of contact hypersensitivity to a hapten applied to the skin at a site distant of irradiation, supporting the concept that regulation pathways of delayed-type hypersensitivity and contact hypersensitivity responses by UVR differ. These data provide additional understanding of the mechanisms of immunosuppression induced by UVR and suggest that IL-10 release subsequent to UVB radiation may play a role in the growth immunogenic UVB-induced cutaneous malignancies in the primary host.

Animals↗
PubMed1996

Inhaled nitric oxide during extracorporeal membrane oxygenation for the treatment of severe persistent pulmonary hypertension of the newborn.

Inhaled nitric oxide (NO) as a complementary treatment was studied in 10 neonates during extracorporeal membrane oxygenation (ECMO) therapy of various persistent pulmonary hypertension of the newborn (PPHN)-associated diseases. At individually different levels of inhaled NO (20-80 ppm), the mean Pao2 increased by 59.7% in 6 responders, but it remained unchanged in 4 nonresponders. Adverse side effects of the NO inhalation were tolerable. It was associated with a reversible decrease of the mean arterial blood pressure in 1 patient. During prolonged NO inhalation, the methemoglobin (met-Hb) level increased to 0.9-4.6% in 6 patients. Based on these preliminary results, we conclude that inhaled NO during ECMO can improve oxygenation in some PPHN patients. Further studies with control groups are needed to determine whether inhaled NO can shorten ECMO treatment or improve the rate of survival among PPHN patients.

Administration, Inhalation↗
PubMed1996

Microheterogeneity of acute-phase glycoproteins in patients with pulmonary sarcoidosis.

This study was designed to investigate qualitative changes in the carbohydrate side-chains of two acute-phase glycoproteins, alpha 1-acid glycoprotein (AGP) and alpha 1-antichymotrypsin (ACT), in 37 patients with pulmonary sarcoidosis. The glycosylation profile of AGP and ACT was studied using affinity immunoelectrophoresis with the lectin concanavalin A (conA). Serum concentration of soluble receptor for interleukin-2 (sIL-2R) and activity of serum angiotensin converting enzyme (ACE) were measured by specific enzyme-linked immunosorbent assay (ELISA) and enzyme kinetic assay, respectively. Rocket immunoelectrophoresis and nephelometric assay were used to determine serum concentration of AGP, ACT and C-reactive protein (CRP). In 11 patients with active disease, a decreased reactivity of AGP with conA was found as compared with controls (n = 44) and patients with nonactive sarcoidosis (n = 26). A similar tendency was seen with ACT. In the same group, increased concentrations of serum AGP and higher levels of sIL-2R were detected compared with patients with nonactive sarcoidosis. In the entire sarcoidosis group, there was a negative correlation between ACE activity and AGP and ACT affinity for conA (r = -0.6358, and r = -0.5019, respectively) and a positive correlation with sIL-2R level (r = 0.8241). In nine patients with elevated concentrations of serum CRP, no differences were found in disease activity and glycosylation profile of AGP and ACT when compared to patients with normal serum CRP. The results suggest that in active pulmonary sarcoidosis changes in the glycosylation pattern of acute-phase glycoproteins exist, which are similar in trend and magnitude to those found in other chronic inflammatory diseases. The synthesis and glycosylation of acute-phase proteins in pulmonary sarcoidosis are probably regulated independently.

Adult↗
PubMed1996

Changes in agalactosyl IgG levels correlate with radiological progression in early rheumatoid arthritis.

Immunoglobulin G-lacking galactose (Gal[0]) appears to be helpful in differential diagnosis of early synovitis, and correlates with disease activity in rheumatoid arthritis (RA). Its utility for RA monitoring and prognosis has been evaluated in the present study. Forty-eight patients with early RA were observed for 3 years. Hand radiographs were assessed according to Larsen and results were expressed as damage score (DS) and progression of damage score (PDS). Gal[0], DS, and PDS were evaluated at the onset of the study and after 1 and 3 years. The average values of Gal[0] in RA patients at the onset of the observation were significantly higher as compared to healthy controls (0.43 +/- 0.22 vs. -0.03 +/- 0.09, P < 0.05). The findings of Gal[0] after a 3-year follow-up were also higher as compared to healthy controls (0.37 +/- 0.21 vs. -0.03 +/- 0.09, P < 0.05). Radiological progression (PDS > 15) was observed in 16 patients. This group was characterized by a constantly high level of Gal[0]. The level of Gal[0] in patients without or with moderate radiological progression (PDS < 15) was significantly lower at the onset of the study and remained low during the observation. The relationship between Gal[0] and radiological progression was shown. The data thus far obtained suggest that Gal[0] may serve as an indicator for the disease course in patients with RA. Secondly, we cannot exclude the possibility that the constantly elevated level of Gal[0] causes erosions.

Adult↗
PubMed1996

[Complications of laparoscopic interventions in urology].

From April 1987 to November 1995, we performed 741 laparoscopic procedures, in which we observed 14 major complications (1.9% complication rate). The complication rate was 4% in the first 100 procedures--more than twice as many as in the following 631 procedures, which had a complication rate of 1.6%. Although between 1987 and 1990 laparoscopy was mainly used for the diagnosis of cryptorchidism, we then progressed to therapeutic measures with the help of the laparoscopic technique. After performing laparoscopic orchiectomy (1990), we introduced fenestration of lymphoceles (1991), varicocelectomy (1991), pelvic staging lymphadenectomy (1992), nephrectomy (1992), and adrenalectomy (1994) into clinical practice, in addition to other, more rarely occurring procedures. The complications we observed demonstrate a clear learning curve and show that critical, gradual practice of the laparoscopic technique is necessary.

Female↗
PubMed1996

Pathogenetic aspects of responsiveness to ondansetron (5-hydroxytryptamine type 3 receptor antagonist) in patients with primary fibromyalgia syndrome--a preliminary study.

OBJECTIVE: To study the efficacy of 5-hydroxytryptamine type 3 receptor (5-HT-3R) antagonist (ondansetron) vs paracetamol in primary fibromyalgia (FM) syndrome. METHODS: A double blind, crossover, latin square study of 21 patients with FM. Visual analog scale (VAS) and body drawings were used to record pain intensity. Functional symptoms were determined for using a Likert-type self-developed protocol. Quantitative dolorimetry was applied to assess the number of painful tender points and the average pain threshold. Serum serotonin levels were measured by a commercial ELISA. RESULTS: A marked improvement in pain intensity measured by VAS (p < 0.005), pain score (p < 0.05), tender points (p < 0.05), and average pain threshold (p < 0.01) was obtained with ondansetron, whereas no improvement was seen with paracetamol. After ondansetron treatment, there was also significant reduction in both functional symptoms (p < 0.01) and headache intensity (p < 0.05). In patients who did not respond to ondansetron there was higher baseline pain intensity measured by VAS (p < 0.05) and pain score (p < 0.01), and a lower pain threshold (p < 0.05) compared to those who did respond well. In the responsive group, no significant differences were seen in the serotonin level before and after therapy. Whereas a significant increase in serum serotonin concentration (p < 0.01) was observed in nonresponders after ondansetron treatment. CONCLUSION: Ondansetron appears to be an effective drug in about 50% of patients with FM. There may be 2 subsets of patients with FM that differ clinically and pathogenetically with regard to the disturbance in the 5-HT-3R system.

Acetaminophen↗