Search PubMed⌕ Search

Biomedical subjects

M Richter

Publications and source records attributed to M Richter.

At least 181 records · Page 10Linked to original sources

Investigation of the conformational behaviour of permethylated cyclodextrins by molecular modelling.

Conformations of manually built native and permethylated alpha-, beta-, and gamma-cyclodextrins (CD) were investigated using various computer assisted molecular modelling methods. Calculations were carried by applying the MM+ and the Tripos force field. The influences of atomic charges on the macrocyclic conformations during the optimization procedure were analyzed. The permethylation of hydroxyl groups of cyclodextrins changes bond and torsion angles between the glucose monomers and of the primary substituents. A method to determine the diameters of the cyclodextrin cavity by a modelling approach is described. It is shown that due to permethylation the larger cavity opening is increased and the primary substituents are canted outwards. As a consequence, the torus shape of the molecule changes, which is an important feature for docking and fitting studies.

Algorithms↗

4-Chloro-m-cresol: a specific tool to distinguish between malignant hyperthermia-susceptible and normal muscle.

Single-channel recordings have indicated that ryanodine receptor (RyR1) mutation Arg615Cys of porcine malignant hyperthermia-susceptible (MHS) muscle is not directly associated with the enhanced caffeine sensitivity of MH(S) muscle [1]. In the present study, the effect of a novel activator of RyR1, 4-chlorom-cresol (4-CmC), was investigated on high-affinity [3H]ryanodine binding to porcine skeletal sarcoplasmic reticulum. The 4-CmC affinity of [3H]ryanodine binding to MHS vesicles was 2-fold higher compared to that in normal tissue. This enhanced affinity was confirmed when the effect of 4-CmC on [3H]ryanodine binding to the isolated CHAPS-solubilized MHS RyR1 was investigated. 4-CmC is, therefore, suggested to be a potent tool to distinguish between Ca2+ release from MHS and normal muscle.

Animals↗

4-Chloro-m-cresol, a potent and specific activator of the skeletal muscle ryanodine receptor.

The aim of the present study was to determine the effects of 4-chloro-m-cresol (4-CmC), a preservative often added to drugs intravenously administered, on the skeletal muscle sarcoplasmic reticulum (SR) Ca2+ release channel/ryanodine receptor. In heavy SR vesicles obtained from rabbit back muscles, 4-CmC stimulated (Ca2+)-activated [3H]ryanodine binding with an EC50 of about 100 microM. In the same concentration range, 4-CmC directly activated the isolated Ca2+ release channel reconstituted into planar lipid bilayers. The sensitivity to 4-CmC was found to be higher when applied to the luminal side of the channel suggesting binding site(s) different from those of nucleotides and caffeine. In skeletal muscle fibre bundles obtained from biopsies of patients susceptible to malignant hyperthermia, a skeletal muscle disease caused by point mutations in the ryanodine receptor, 4-CmC evoked caffeine-like contractures. Contrary to caffeine which induces contractures in millimolar concentrations, the threshold concentration for 4-CmC was 25 microM compared to 75 microM for non-mutated control fibres. Since these data strongly indicate that 4-CmC specifically activates SR Ca2+ release also in intact cell systems, this substance might become a powerful tool to investigate ryanodine receptor-mediated Ca2+ release in muscle and non-muscle tissue.

Animals↗

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.

OBJECTIVE: To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). METHODS: A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. RESULTS: Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. CONCLUSION: This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Health Status Indicators↗

Synthesis of estrogen sulfamates: compounds with a novel endocrinological profile.

Estrogen sulfamates are promising hormones by oral administration. Therefore, generally applicable and convenient methods for the multigram synthesis of these derivatives are desirable. Numerous estra-1,3,5(10)-trienes derived from estrone, estradiol. 14 alpha,15 alpha-methylenestradiol, ethinylestradiol, and estriol have been esterified with sulfamoyl chloride and N-methylsulfamoyl chloride by a novel approach involving the use of 2,6-di-tert-butylpyridines as bases and chemoselective hydroxy group protections. These pathways circumvent the nonselective formation of esters and side reactions by in situ generated azasulfenes. For toxicological and clinical studies a new synthesis of estrone sulfamate on a 100-g scale was developed using dimethylformamide as the solvent and base.

Estradiol↗

Use of force-plate analysis of gait to compare two surgical techniques for treatment of cranial cruciate ligament rupture in dogs.

OBJECTIVE: To use ground reaction forces and related impulses as an objective measurement of limb function in the comparison of 1 extracapsular and 1 intracapsular surgical technique for repair of cranial cruciate ligament rupture in dogs. ANIMALS: 18 healthy dogs. DESIGN: All dogs underwent force-plate analysis of gait prior to transection of the left cranial cruciate ligament. The dogs were randomly allotted to 3 groups. The ligamentous instability was corrected, using a modified retinacular imbrication technique (MRIT) in 1 group and an under-and-over technique in another group. No attempt was made to correct the ligamentous instability in a control group. Clinical grading of lameness and force-plate analysis of gait were performed at 4, 8, 12, 16, and 20 weeks after surgery. PROCEDURE: Peak vertical force and vertical, braking, and propulsion impulses were recorded for each limb at each time. The degree of clinical lameness was graded at each time. RESULTS: Left hind limb peak vertical forces and vertical impulses were significantly decreased at all times after surgery in the control and under-and-over technique group, compared with values before surgery. Dogs of the MRIT group had improved by 20 weeks, with no significant differences between left hind limb peak vertical forces or vertical impulses recorded before surgery and at 20 weeks. CONCLUSION: Peak vertical forces and vertical impulses in dogs undergoing MRIT repair after experimentally created cranial cruciate ligament rupture are not significantly different when values recorded for the operated limb at 20 weeks after surgery are compared with those recorded prior to surgery.

Analysis of Variance↗

[Treatment of rectum adenoma. Retrospective study of the treatment of inpatients (1987-1991)].

In carrying out an evaluation prior to acquisition of equipment for transanal endoscopic microsurgery (TEM), we wished to examine current concepts in the treatment of rectal adenoma, i.e.: What form of surgery was chosen in relation to the dimension and localization of the adenoma? Should the indications for the particular procedure be changed to render it less invasive? Should the new endoscopic surgical method TEM be introduced? 134 inpatients covering a 5-year period were evaluated. We analyzed the correlation between localization of the adenoma in the rectum (42% low, 22% middle, 36% high position), diameter of the tumor (37% < 2 cm, 38% 2-4 cm, 11% 4-6 cm, 10% > 6 cm) and type of surgery (endoscopic 27%, transanal 45%, anterior resection 25%). We found a high percentage of anterior resections in the middle rectum which could be reduced by introduction of the less invasive TEM. 29 (22%) of our patients could have been treated with TEM.

Adenoma↗

[Facial asymmetry and obstructive sleep apnea syndrome].

When unilateral mandibular growth disturbances appear early in childhood, they usually lead to maxillomandibular deformities. Facial asymmetry, mandibular retrusion, and malocclusion are signs also found in hemifacial microsomia. Some of these patients develop an obstructive sleep apnea syndrome, which can be resolved by surgical-orthognathic treatment. Pre and post-operative polysomnograms with recording of oxygen saturation are objective measures of good surgical results. Two patients with facial asymmetry and obstructive sleep apnea syndrome are presented. Special emphasis is made on treatment planning.

Adult↗

Biochemical characterization of the 8-hydroxy-5-deazaflavin-reactive hydrogenase from Methanosarcina barkeri Fusaro.

The membrane-associated coenzyme F420-reactive hydrogenase of the anaerobic methanogenic archaeon Methanosarcina barkeri Fusaro has been purified 95-fold to apparent homogeneity. A new purification procedure and altered storage conditions gave substantially higher yield (13.4% versus 4.3%) and specific coenzyme F420-reducing activity (82.8 mumol.min-1.mg protein-1 versus 11.5 mumol.min-1.mg protein-1) than reported previously [Fiebig, K. & Friedrich, B. (1989) Eur. J. Biochem. 184, 79-88]. The predominant coenzyme F420-reactive form of the hydrogenase has an apparent molecular mass of 198 kDa and is composed of three non-identical subunits with apparent molecular masses of 48 (alpha), 33 (beta), and 30 kDa (gamma), apparently in a stoichiometry of alpha 2 beta 2 gamma 1. This minimal coenzyme F420-reducing hydrogenase formed aggregates with apparent molecular masses of approximately 845 kDa. 1 mol of the 198-kDa form of hydrogenase contained 2 mol FAD, 2 mol nickel, 28-32 mol non-heme iron, and 34 mol acid-labile sulfur; in addition, 0.2 mol selenium was detected. The isoelectric point was 5.30. The amino acid sequence PXXRXEGH, where X is any amino acid, was found to be conserved in the N-termini of the putative nickel-binding subunits of most [NiFe]- and [NiFeSe]hydrogenases of methanogenic Archaea and Bacteria. However, this motif was not detected in the protein sequences of [Fe]hydrogenases. Maximal coenzyme F420-reducing activity was obtained with reductively reactivated enzyme at 55 degrees C in the pH range 6.5-7.25. The Km values of the purified enzyme for H2 with coenzyme F420 or methylviologen as electron acceptor were extremely low, namely 3 microM and 4 microM. The catalytic efficiency coefficients (kcat/Km) for H2 with both reducible cosubstrates were high: 2.5 x 10(7) M-1.s-1 with coenzyme F420 and 6.9 x 10(7) M-1.s-1 with methylviologen.

Amino Acid Sequence↗