Search PubMed⌕ Search

Biomedical subjects

L Vogt

Publications and source records attributed to L Vogt.

At least 37 records · Page 2Linked to original sources
PubMed1998

Neurite fasciculation mediated by complexes of axonin-1 and Ng cell adhesion molecule.

Neural cell adhesion molecules composed of immunoglobulin and fibronectin type III-like domains have been implicated in cell adhesion, neurite outgrowth, and fasciculation. Axonin-1 and Ng cell adhesion molecule (NgCAM), two molecules with predominantly axonal expression exhibit homophilic interactions across the extracellular space (axonin- 1/axonin-1 and NgCAM/NgCAM) and a heterophilic interaction (axonin-1-NgCAM) that occurs exclusively in the plane of the same membrane (cis-interaction). Using domain deletion mutants we localized the NgCAM homophilic binding in the Ig domains 1-4 whereas heterophilic binding to axonin-1 was localized in the Ig domains 2-4 and the third FnIII domain. The NgCAM-NgCAM interaction could be established simultaneously with the axonin-1-NgCAM interaction. In contrast, the axonin-1-NgCAM interaction excluded axonin-1/axonin-1 binding. These results and the examination of the coclustering of axonin-1 and NgCAM at cell contacts, suggest that intercellular contact is mediated by a symmetric axonin-12/NgCAM2 tetramer, in which homophilic NgCAM binding across the extracellular space occurs simultaneously with a cis-heterophilic interaction of axonin-1 and NgCAM. The enhanced neurite fasciculation after overexpression of NgCAM by adenoviral vectors indicates that NgCAM is the limiting component for the formation of the axonin-12/NgCAM2 complexes and, thus, neurite fasciculation in DRG neurons.

Animals↗
PubMed1998

Lack of evidence of kappa2-selective activation of G-proteins: kappa opioid receptor stimulation of [35S] GTPgammaS binding in guinea pig brain.

Although only one gene for kappa opioid receptors has been cloned to date, kappa1 and kappa2 receptors have been defined pharmacologically, with drugs such as bremazocine binding to both putative kappa receptor subtypes. To examine whether kappa receptor subtypes can be distinguished at the level of the G-protein, the ability of the kappa1 agonist (trans-(dl)-3,4-dichloro-N- methyl-N-[2-(1 -pyrrolidinyl)cyclohexyl]-benzeneacetamide) methane sulfonate (U-50488H) to stimulate [35S]guanosine-5'-O-(gamma-thio)-triphosphate ([35S]GTPgammaS) binding in guinea pig brain was compared with that of bremazocine and dynorphin. In membranes prepared from guinea pig striatum, both bremazocine and U-50488H stimulated [35S]GTPgammaS binding with the same relative efficacy, while dynorphin produced at least two-fold greater efficacy than the other two agonists. In vitro autoradiography of agonist-stimulated [35S]GTPgammaS binding revealed similar regional distributions of bremazocine- and U-50488H-activated G-proteins. In striatal membranes, the kappa antagonist nor-binaltorphimine (nor-BNI) blocked both bremazocine- and U-50488H-stimulated [35S]GTPgammaS binding with similar Ke values. In agonist additivity experiments, the stimulation of [35S]GTPgammaS binding by the delta agonist [D-pen2'5, p-Cl-Phe4]enkephalin (p-Cl-DPDPE) was approximately additive with the two kappa agonists. Stimulation of [35S]GTPgammaS binding by the mu agonist [D-Ala2, N-Me4, Gly5-ol]-enkephalin (DAMGO) was additive with U-50488H, but not with bremazocine, reflecting the mu antagonist properties of this compound. The combination of bremazocine and U-50488H together produced no greater stimulation of binding than either agonist alone, indicating that they were binding to the same site. These results demonstrate that bremazocine and U-50488H activate G-proteins in guinea pig brain through the same receptor, and suggest that kappa2 receptors are not coupled through the same signal transduction mechanisms as kappa1 receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1997

Diabetes and hypertension in rodent models.

As shown by ourselves and others, animals models closely resembling human complex diseases like IDDM in BB/OK and hypertension in SHR/Mol rats can be used to dissect a complex disease into discrete genetic factors as has been done for hypertension in (BB/OK x SHR/Mol) cross hybrids. Discrete genetic factors, so-called QTLs, were detected on chromosomes 1, 10, 18, 20, and X. To gain additional information about the physiologic effect of the mapped blood pressure QTLs, genetically defined regions of the SHR rat were transferred onto the genetic background of diabetes-prone BB/OK rats. Four new congenic BB.SHR rats named BB.Sa, BB.Bp2, BB.1K, and BB.Xs were generated and characterized telemetrically for blood pressure, heart rate, and motor activity. The data demonstrate clearly that each single blood pressure QTL of the SHR rat causes a significant increase of the systolic blood pressure and has a different influence on diastolic blood pressure, heart rate, and motor activity. The effects were modified differently by the diabetic state in BB.Sa, BB.Bp2, and BB.Xs rats carrying all diabetogenic genes of the BB/OK rats. The results demonstrate that these newly established congenic strains are a unique tool to study the physiological control of blood pressure by a single blood pressure QTL on the one hand and their interaction with hyperglycemia on the other. It is well within the bounds of possibility that diabetic congenics reflect the diabetic hypertension seen in diabetic patients. Because of the synteny conservation in gene order between different mammals, genes of the appropriate human region could therefore be candidate genes for hypertension in diabetics. Furthermore, these congenic strains can also be used to study interactions between a blood pressure QTL and various selected environmental conditions. In this way, one could learn which QTL can be influenced by environmental factors and to what extent. Another point is the study of gene interactions. Because congenics are genetically identical except for the defined transferred region, congenics can be crossed to investigate the interaction between two or three blood pressure QTLs selected by the investigator and not by nature. These QTL combinations can be studied in the nondiabetic as well as diabetic state. Although the advantage of congenic strains has been shown, the transferred chromosomal regions are too large to pinpoint the gene responsible for the phenotypic change. Therefore, regions on each chromosome must be systematically whittled down, which can be done by crossing the congenics with BB/OK rats and intercrossing their progeny to generate recombinants. These can then be used for the creation of new congenic lines carrying a much smaller region of the SHR/Mol rat. This has been started for the region on chromosome 1 spanning a 16-cM region from the Sa to the Igf2 gene. BB.Sa rats were therefore backcrossed onto BB/OK rats and the resulting progeny were intercrossed. The aim will be to create at least three new congenic BB.Sa rat strains homozygous for the SHR alleles of Sa, Lsn, or Igf2 genes. However, new problems will emerge with these new congenics. To genetically define small regions requires more dense polymorphic markers than are currently available. Dense polymorphic markers will also be necessary to split the other regions on chromosomes 10, 18, 20, and X. We expect that in the near future it will be possible using this approach to define small regions of < 0.5 cM. The recent progress in gene mapping in the rat gives hope that the use of such congenic lines will allow the identification and recovery of the blood pressure genes in the near future.

Animals↗
PubMed1997

[Selenium in phenylketonuria patients. Effects of sodium selenite administration].

PATIENTS AND METHOD: 17 patients (8 female, 9 male; age 8.2 +/- 3.7 years) with phenylketonuria under phenylalanin restricted diet were investigated prior to and after 3 months of selenium substitution (sodium selenite, 115 micrograms Se/m2 BSA/d). Different parameters in blood were determined: selenium, glutathione peroxidase (Gpx) activity, thyroid hormones, blood cell count, lymphocytic antigen expression, muscle function and -enzymes, cardiac ultrasound. RESULTS: The main significant results of selenium substitution are: increased plasma-selenium, blood cell selenium, plasma-Gpx activity and left ventricular cardiac index as well as decreased plasma thyroxin, free thyroxin, reverse triiodthyronin, total cholesterol, mean erythrocyte and thrombocyte volume and lymphocytic CD2 expression. CONCLUSION: The data indicate metabolic and functional signs of selenium deficiency in patients with phenylketonuria without selenium substitution. We conclude that, despite of lacking clinical symptoms, a selenium supply in phenylketonuria patients under diet is necessary and should be performed with usefull peroral sodium selenite (115 micrograms Se/m2 BSA/d) initially, followed by a dosage between 30 and 60 micrograms Se/m2 BSA/d).

Antioxidants↗
PubMed1997

The neuronal cell-adhesion molecule axonin-1 is specifically released by an endogenous glycosylphosphatidylinositol-specific phospholipase.

Axonin-1, a member of the immunoglobulin/fibronectin type-III family of cell-adhesion molecules, occurs both as a glycosylphosphatidylinositol-(glycosylPtdIns)-anchored membrane-bound and a soluble form. In vivo observations show that the major part of axonin-1 is found in the soluble fraction and that soluble axonin-1 perturbs neurite fasciculation and pathfinding in the developing chicken embryo. This has prompted further investigations into the mechanism of the axonin-1 release. We demonstrate here that axonin-1 released from dorsal root ganglion neurons contains ethanolamine and inositol, components of the glycosylPtdIns anchor. Secreted axonin-1 does not exhibit the cross-reacting determinant epitope, an indication that the cleavage of the anchor is not mediated by a phosphatidylinositol-specific phospholipase C. Treatment of dorsal root ganglion neurons with 1,10-phenanthroline, an inhibitor of glycosylPtdIns-specific phospholipase D, reduces the release of axonin-1 by 56%. Moreover, glycosylPtdIns-specific phospholipase D activity was detected in dorsal root ganglion neurons and brain. These results suggest that axonin-1 is released from the membrane by an endogenously expressed glycosylPtdIns-specific phospholipase D in vivo. With domain-swaping experiments between axonin-1 and its non-released relative F11, deletion mutants and monoclonal antibodies, we demonstrate that the fourth fibronectin type-III-like domain of axonin-1 is required for the generation of the soluble form of axonin-1.

Animals↗
PubMed1997

Dynamic testing of the motor stereotype in prone hip extension from neutral position.

OBJECTIVE: The purpose of the study was to identify a sequential activation of lumbar and hip muscles in active prone hip extension from neutral position in subjects without a history of low back pain. DESIGN: Using surface electromyography, the myoelectric activity onsets of agonistic and antagonistic hip muscles were recorded. BACKGROUND: The development of low back pain is ascribed to changes of the muscle firing order in prone hip extension. There appeared to be no normative data on muscle firing order of the lumbar and hip musculature to provide a basis for recognizing variations. METHODS: Fifteen healthy subjects performed standardized right hip extensions. Time-normalized onset of EMG activity in each muscle was measured for each trial. RESULTS: A MANOVA revealed significant (P < 0.01) differences between the activity onsets of synergistic muscles in hip extension. CONCLUSIONS: On the results it was concluded that the consistent muscle firing order of ipsilateral lumbar erector spinae, semitendinosus, contralateral lumbar erector spinae, tensor fasciae latae, and gluteus maximus demonstrate the characteristic pattern in prone hip extension. In future studies it is essential to evaluate also the hip extension pattern in functional upright conditions during gait and their relationship to spinal mechanics.

Journal Article↗
PubMed1997

Circadian variations in blood pressure and heart rate in diabetes prone and resistant rat strains compared with spontaneously hypertensive rats.

Circadian blood pressure (BP), heart rate (HR) and motor activity (MA) of nondiabetic (nd) and spontaneously diabetic (d) BB/OK rats were compared with that of spontaneously hypertensive rats (SHR). In addition a diabetes-resistant and non-hypertensive rat strain (LEW.1W) was monitored for the same parameters. Systolic and diastolic BP (SBP, DBP), HR and MA were measured telemetrically. In d BB rats, the 24 h mean value of SBP (132 +/- 0.15 mm-Hg) was significantly increased compared to nd BB rats (125 +/- 0.18 mmHg). No differences were found in DBP between d and nd BB rats (93 +/- 0.13 v.s. 94 +/- 0.15 mmHg). Both, d and nd BB rats were significantly different in SBP and DBP to that of SHR (155 +/- 0.19 and 110 +/- mmHg). Nondiabetic BB rats did not significantly differ from LEW.1W rats in SBP and DBP (125 vs. 123 mmHg and 94 vs. 94 mmHg). The heart rate was lowest in diabetic BB rats compared with all other strains. Compared to nd BB the diabetic rats had an altered daily rhythm in BP. The results demonstrate that the diabetic BB rats develop circadian variations in BP and HR similar to those observed in hypertensive rats.

Animals↗
PubMed1997

Kinematic and neuromuscular changes of the gait pattern after Achilles tendon rupture.

After long immobilization periods in equinovalgus with operated Achilles tendon rupture, long-lasting changes of motor patterns in functional movement can be expected. In the present study, possible alterations in gait pattern have been analyzed based on kinematic and neuromuscular parameters. Ten patients 1 year after surgery and a healthy control group performed 10 gait cycles in natural walking cadence. Ankle motion, pressure distribution, and electromyographic data were recorded and analyzed in defined phases. Kinematic and neuromuscular changes are still evident 1 year after surgery with a temporal phase shift and a neuromuscular deficit of the lateral gastrocnemius muscle. The objective of rehabilitation should be the facilitation of the temporal innervation pattern of the lateral gastrocnemius muscle in the functional movement.

Achilles Tendon↗
PubMed1996

Continuous renewal of the axonal pathway sensor apparatus by insertion of new sensor molecules into the growth cone membrane.

BACKGROUND: Growth cones at the tips of growing axons move along predetermined pathways to establish synaptic connections between neurons and their distant targets. To establish their orientation, growth cones continuously sample for, and respond to, guidance information provided by cell surfaces and the extracellular matrix. To identify specific guidance cues, growth cones have sensor molecules on their surface, which are expressed differentially during the temporospatial progress of axon outgrowth, at levels that depend on the pattern of neural activity. However, it has not been elucidated whether a change in gene expression can indeed change the molecular composition and, hence, the function of the sensor apparatus of growth cones. RESULTS: We have constructed adenoviral gene transfer vectors of the chicken growth cone sensor molecules axonin-1 and Ng-CAM. Using these vectors, we initiated the expression of axonin-1 and Ng-CAM in rat dorsal root ganglia explants during ongoing neurite outgrowth. Using specific surface immunodetection at varying time points after infection, we found that axonin-1 and Ng-CAM are transported directly to the growth cone and inserted exclusively in the growth cone membrane and not in the axolemma of the axon shaft. Furthermore, we found that axonin-1 and Ng-CAM do not diffuse retrogradely, suggesting that the sensor molecules are integrated into multimolecular complexes in the growth cone. CONCLUSIONS: During axon outgrowth, the pathway sensor apparatus of the growth cone is continuously updated by newly synthesized sensor molecules that originate directly from the transcription/translation machinery. Changes in the expression of sensor molecules may have a direct impact, therefore, on the exploratory function of the growth cone.

Animals↗
PubMed1996

Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance.

A differing individual expression of fructosyllysine-specific receptors has been found on the monocytes of 90 insulin-dependent diabetic patients and 101 healthy control subjects. The degree of receptor expression is neither age- nor sex-dependent; however, in the diabetic group it correlates significantly with the severity and age of onset of diabetic microangiopathy. To interpret the results of the human study, spontaneously diabetic and non-diabetic BB/OK rats were used to estimate tissue content of glucose-modified proteins and capillary basement membrane thickness in relation to the receptor expression on macrophages. In non-diabetic and diabetic rats no correlation was found between receptor expression and tissue content (i.e. artery, nerve) of fructosyllsine and fluorescent advanced glycation end products. However, animals which express the fructosyllysine receptor showed a greater increase in muscle capillary basement membrane thickness. There are indications that fructosyllysine receptor expression is positively associated with indices of diabetic complications such as microangiopathy and/or capillary basement membrane thickening.

Adult↗
PubMed1995

The gene of chicken axonin-1. Complete structure and analysis of the promoter.

We have isolated and characterised the gene encoding the chicken axonal cell adhesion molecule axonin-1. This gene comprises 23 exons distributed over approximately 40 kb. Each of the six immunoglobulin-like domains and the four fibronectin-type-III-like domains of axonin-1 is encoded by two exons. The introns between two domains are exclusively phase I. Their exon/intron borders correspond to the domain borders of the protein, suggesting that the gene of axonin-1 had been generated by exon shuffling. Three transcripts with a length of 4.3 kb, 5 kb, and 8 kb are found, and we provide evidence that they result from alternative use of polyadenylation signals. In situ hybridization revealed co-localisation of these transcripts in time and space in the developing chicken retina. Several identical transcription initiation sites were found in retina, brain, and cerebellum by RNase protection assay and anchored polymerase chain reaction. By transfection of HeLa cells, rat PC-12 phaeochromocytoma cells, and chicken embryonic fibroblasts with serially truncated segments of the 5'-flanking region linked to a luciferase reporter gene, we have found that the sequence from -91 to +56 relative to the transcription initiation site is sufficient to promote efficient gene expression. Tissue-specific expression of the axonin-1 gene seems to be regulated in part by sequences more than 1 kb upstream of the transcription initiation site. As revealed by computer analysis, the sequence immediately upstream of exon 1 contains an AP-2 binding site, a tumor phorbol-ester-responsive element, and a homeodomain protein binding site, but no canonical TATA box. A second AP-2 binding site and a homeodomain protein binding site are located within exon 1.

Amino Acid Sequence↗
PubMed1995

[The value of selenotherapy in patients with mucoviscidosis].

In cystic fibrosis (CF) patients the antioxidative-oxidative balance is chronically disturbed. Free radicals were generated by bronchial-pulmonal infection and additional exist a deficiency of antioxidative substances by enteral malabsorption especially vitamin E and selenium. Because selenium is an essential content of glutathione peroxidase, which is acting in cytosol and cell membranes, for the present we tested a selenium therapy (peroral sodium selenite 155 micrograms (Se/m2 BSA/d i. e. 4 micrograms Se/kg/d; 4 fold of recommended supply) in 32 CF patients. After three months of this therapy we have seen positive metabolic (normalized content of plasma-selenium, -glutathione peroxidase), endocrine (enhanced efficacy of thyroid hormones, mild increased IgF-I reduced LDL-chol) and clinical consequences (enhanced left ventricular cardiac output), but in three patients side effects (anorexia, nausea, mild hair loss) were observed. Longtime sodium selenite therapy only with 60 micrograms Se/m2 BSA/d over 1 year, stabilized the favourable influences without side effects. For CF patients therefore we recommend a sodium selenite substitution therapy, the best in combination with vitamin E.

Administration, Oral↗
PubMed1995

Impact of metabolic activity of beta cells on cytokine-induced damage and recovery of rat pancreatic islets.

The influence of beta cell activity on cytokine-induced functional and structural impairments as well as the ability of those damaged cells to recover were investigated. Rat islets cultured for 4 days in the presence of 5, 10, and 30 mmol/l glucose were exposed to interferon-gamma (IFN, 500 U/ml) and tumor necrosis factor-alpha (TNF, 250 U/ml) for the last 24 h. After cytokine removal islets were allowed to recover spontaneously in culture medium containing 10 mmol/l glucose for a further 7 days. Cytokines significantly inhibited insulin release into culture medium, insulin storage, glucose-stimulated insulin secretion, protein, and DNA synthesis. In the presence of cytokines there was a six- to eightfold increase in nitrite production by the islets. The functional impairments were more pronounced in metabolically stimulated beta cells. In addition, cytokines caused membrane alterations as indicated by increased spontaneous chromium-51 release. The cytokines specifically induced the synthesis of two proteins (72 and 88 kDa, respectively). By immunoblotting, the 72-kDa protein was identified as heat shock protein. After a 1-week recovery period, insulin storage and stimulated insulin secretion of cytokine-treated islets were still significantly diminished. However, protein and DNA synthesis of cytokine-exposed islets returned to pre-exposure levels. In conclusion, high beta cell activity increases islet susceptibility to TNF+IFN. Cytokine-induced, long-lasting, inhibitory effects are primarily directed to beta-cell-specific functions, while general vital cell functions clearly recover after cytokine removal. The induction of certain proteins and the increased protein synthesis and replication rate after cytokine removal might reflect activated repair processes.

Animals↗