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Biomedical subjects

G Scharf

Publications and source records attributed to G Scharf.

9 recordsLinked to original sources
PubMed1999

Biological activity of GLP-1-analogues with N-terminal modifications.

Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion and improves glycemic control in type 2 diabetes. In serum the peptide is degraded by dipeptidyl peptidase IV (DPP IV). The resulting short biological half-time limits the therapeutic use of GLP-1. Therefore, various GLP-1 analogues with alterations in cleavage positions were synthesized. GLP-1-receptor binding was investigated in RINm5F cells. Biological activity of the GLP-1 analogues was investigated in vitro by measuring cAMP production in RINm5F cells. GLP-1 analogues with modifications in position 2 were not cleaved by DPP IV and showed receptor affinity and in vitro biological activity comparable to native GLP-1. Analogues with alterations in positions 2 and 8, 2 and 9 or 8 and 9 showed a significant decrease in receptor affinity and biological activity. In vivo biological activity was tested in pigs. GLP-1 analogues were administered subcutaneously followed by an intravenous bolus injection of glucose. Plasma glucose and insulin were monitored over 4 h. Compared to native GLP-1, analogues with an altered position 2 showed similar or increased potency and biological half-time. Other GLP-1 analogues were less active. Despite the lack of degradation of these GLP-1 analogues by DPP IV in vitro, their biological action is as short as that of GLP-1, except for desamino-GLP-1, indicating that other degradation enzymes are important in vivo. Alterations of GLP-1 in positions 8 or 9 result in a loss of biological activity without extending biological half-time.

Cyclic AMP↗
PubMed1999

Comparison of the effect of native glucagon-like peptide 1 and dipeptidyl peptidase IV-resistant analogues on insulin release from rat pancreatic islets.

BACKGROUND: Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and may improve glycaemic control in type 2 diabetes. Therapeutic use is limited by its rapid degradation, primarily by dipeptidyl peptidase IV. MATERIALS AND METHODS: Five GLP-1 analogues with alterations at cleavage positions were synthesized according to the Fmoc strategy and tested for metabolic stability by incubation with rat kidney membranes containing dipeptidyl peptidase IV activity. Their insulinotropic effect was compared in isolated rat pancreatic islets after 24 h maintenance in tissue culture. Ten islets per vial were incubated for 30 min; insulin was measured radioimmunologically. Each analogue was compared with GLP-1 in the same experiment. RESULTS: All analogues were biologically active in isolated islets in the potency order da2d8 = da2 > d2d9 > da2ds8 > desamino. At 16.7 mmol L-1 glucose, GLP-1 and GLP-1 analogues altered as position 2, or 2 and 8 significantly (P < 0.05) increased insulin release at 10(-9) mol L-1. N-terminal modification of GLP-1 confers resistance to dipeptidyl peptidase IV degradation in rat kidney membranes in vitro. CONCLUSIONS: The analogues tested are biologically active and resistant to degradation by dipeptidyl peptidase IV. Their greater metabolic stability may help to realize the potential of GLP-1 analogues in diabetes therapy.

Amino Acid Sequence↗
PubMed1997

Kinematic analysis of articulatory movements in central motor disorders.

The various components of the central motor system are expected to play a similar role in speech production and in upper limb control. Slowed articulatory performance, therefore, must be expected in disorders of the corticobulbar tracts, cerebellum, and basal ganglia. Using an optoelectronic device, the present study recorded lower lip trajectories during production of sentence utterances in patients with Parkinson's disease (PD), Huntington's disease (HD), cerebellar atrophy (CA), and pseudobulbar palsy (PB). The various subject groups showed a similar range of overall motor disability. Patients with CA and PB exhibited slowed movement execution in terms of a reduced ratio of peak velocity to maximum amplitude ("stiffness"). In contrast to upper limb motor control, the lip excursions showed an uncompromised shape of velocity profiles. Two different patterns emerged in HD. A single patient suffering from the akinetic-rigid Westphal variant of this disease had articulatory hypometria, whereas the remaining subjects showed significant bradykinesia under increased temporal demands, concomitant with normal movement amplitudes. The PD patients had unimpaired velocity-displacement relationships. Presumably, biomechanical constraints such as the rather small excursions of articulatory lower lip gestures or the scarce spindle supply of facial muscles account for the observed discrepancies between upper limb and speech motor control in PD.

Aged↗
PubMed1995

Kinematic analysis of lower lip movements in ataxic dysarthria.

The present study investigates the influence of cerebellar disorders on articulatory performance. A linear trend between peak velocity and movement amplitude seems to represent a basic organizational principle both of upper limb and speech motor control. This relationship is preserved in arm movements of patients with cerebellar dysfunction. However, these subjects show a decreased slope of the respective regression lines under the instruction to perform movements as fast as possible. In order to find out whether these findings also hold for speech motor control, peak velocity, range, and duration both of the opening and closing gestures during production of /pap/- as well as /pa:p/-sequences-embedded into a carrier phrase each-were measured using an optoelectric system. In addition, vowel length (/a/, /a:/) was determined at the acoustic speech signal: (a) The cerebellar patients showed a prolongation of both vowel targets. Most of them, nevertheless, presented with discernible durational contrasts; (b) The articulatory gestures were characterized by a highly linear relationship between peak velocity and movement range in the cerebellar as well as in the control group; (c) As a rule, the cerebellar subjects had decreased velocity-displacement ratios as compared to the normals; (d) The discrepancy in slope of the computed regression lines between the controls and the patients varied according to the type of movement (opening vs. closing gesture) and-to a lesser decree-linguistic demands (short vs. long vowel). These data indicate an impaired ability of cerebellar patients to increase muscular forces in order to produce adequately scaled articulatory gestures of short duration.

Adult↗
PubMed1984

[The Rostock artificial heart--current status and perspectives].

The authors report on their experiences gained by animal experiments (calf) and their attempts (human corpses) concerning adaptation of the apparatus to the human thorax. At the present time they do not see a chance for its routine clinical use. The main reason why is the impossibility to install the extrathoracic driving system into the thoracic cage and last not least the wear of the material used for the heart chambers.

Animals↗