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Biomedical subjects

S Breit

Publications and source records attributed to S Breit.

At least 37 records · Page 2Linked to original sources
PubMed2001

On biomechanical properties of the sacroiliac joint in purebred dogs.

Relative to the Yorkshire Terriers and Maltese dogs the mean expected sacroiliac joint load was calculated to be 1.4-1.6 times higher in other small breeds and 1.7-2.7 times higher in large breeds. The statistically significantly different (p < 0.01, p < 0.001) and mechanically less efficient inclination angles of the wings of the sacrum in adult large breeds (especially German Shepherd Dogs) suggest even higher forces acting on their sacroiliac ligaments. Unlike the case in small breeds, the sacral auricular surface was concave in large dogs to improve interlocking between sacrum and ilium and to reduce craniocaudal translation. An additional ossification center forming the ventral aspect of the transverse process of the second sacral vertebra was present in large breeds, occasionally in midsized and small, but never in toy breeds. This and the relationship between age and inclination angles of the wings of the sacrum in juvenile specimens indicate an affection of the three-dimensional modeling of the wings of the sacrum by formative stimuli such as body weight and locomotion.

Aging↗
PubMed2001

Breed specific osteological features of the canine lumbosacral junction.

Inefficient facet geometry suggests the lumbosacral junction to be mechanically imperfect in a large number of dogs (especially German Shepherd Dogs) resulting in a significantly higher prevalence of osteophyte formation and increase in the longitudinal extension of the articular surface covering the caudal articular process of the seventh lumbar vertebra. Such osteological features give evidence for lumbosacral craniocaudal translation, were predominantly noticed in combination with axial rotation and are taken to be anatomic risk factors that can predispose to the development of lumbosacral stenosis. The statistically significant relationship between age and the magnitude of the caudal facet inclination angles of the seventh lumbar vertebra in juvenile specimens indicate an affection of the three-dimensional modeling of the immature caudal articular processes by formative stimuli such as body weight and locomotion. However, results additionally indicate an association between the magnitude of these inclination angles and vertebral body dimensions also suggesting a congenital influence on facet geometry.

Aging↗
PubMed2001

Changing serine-485 to alanine in the opossum parathyroid hormone (PTH)/PTH-related peptide receptor enhances PTH stimulation of phospholipase C in a stably transfected human kidney cell line: a useful model for PTH-analog screening?

Using site-directed mutagenesis, we have introduced a serine-485-to-alanine mutation in the opossum parathyroid hormone (PTH) receptor. This amino acid is considered to be phosphorylated by protein kinase A upon ligand binding. Both wild-type (WT) and mutant receptor were stably expressed in 293-EBNA HEK cells. The mutant receptor showed comparable binding characteristics and only a slight increase in cAMP production compared with WT. However, the PTH dose-dependent increase in inositol phosphate production was 24-fold for the mutant receptor vs. 6-fold for the WT receptor. This mutant might prove useful in the sensitive detection of phospholipase C activation through various ligands, as the PTH receptor becomes a target of therapeutic intervention in osteoporosis.

Alanine↗
PubMed2001

Unilateral lesion of the nigrostriatal pathway induces an increase of neuronal activity of the pedunculopontine nucleus, which is reversed by the lesion of the subthalamic nucleus in the rat.

The role of the pedunculopontine nucleus (PPN) in the pathophysiology of Parkinson's disease is still unclear. Using microrecordings, we investigated the changes occurring in PPN neurons after lesions of the substantia nigra compacta (SNc) and the role of the subthalamic nucleus (STN) in these changes. In normal rats the firing rate of PPN neurons was 10.6 +/- 1.4 spikes/s, the majority of neurons (91%) having a regular firing pattern, 6% irregular and 3% in bursts. In rats with 6-hydroxydopamine lesions of the SNc, the firing rate increased significantly to 18.3 +/- 3.0 spikes/s compared with normal rats. In addition, the firing pattern changed significantly: 70% of the neurons discharged regularly, 27% irregularly and 3% in bursts. In rats with ibotenic acid lesions of the STN, the firing rate decreased significantly to 7.2 +/- 0.9 spikes/s and the firing pattern changed significantly: 50% of the neurons discharged regularly, 43% irregularly and 7% in bursts. The rats with combined SNc and STN lesions showed no change in the firing rate (8.5 +/- 1.0 spikes/s) compared to normal rats. The firing pattern changed significantly: 69% of the cells discharged regularly, 26% irregularly and 5% in bursts. These findings demonstrate that PPN neurons are overactive and more irregular in the 6-hydroxydopamine-lesioned rats, suggesting the implication of this nucleus in the pathophysiology of parkinsonism. Moreover, the fact that STN lesions induced a reduction in the firing rate of the PPN in normal rats and a normalization of the firing rate in rats with 6-hydroxydopamine lesions suggests that this nucleus is under major control of the STN.

Action Potentials↗
PubMed2001

Osteological features in pure-bred dogs predisposing to cervical spinal cord compression.

Relative to body size, midsagittal and interpedicular diameters of the cranial and caudal aspects of cervical vertebral foramina (C3-C7) were found to be significantly (P < 0.05) larger in small breeds than in large breeds and Dachshunds, and also larger in Dachshunds (P < 0.05) than in large breeds. This condition increases the risk for spinal cord compression resulting from relative stenosis of the cervical vertebral foramina, especially in large dogs, and this is also exacerbated by the typical shape of the vertebral foramina (i.e. dorsoventrally flattened cranially and bilaterally narrowed caudally). Within large dogs those breeds highly predisposed to cervical spinal cord compression were Great Danes (the breed with the smallest midsagittal vertebral foramen diameters from cranial C6 to cranial T1) and Doberman Pinschers, because of the most strikingly cranially dorsoventrally narrowed cone-shaped vertebral foramina at C6 and C7. The existence of a small midsagittal diameter in the cranial cervical spine was a high risk factor predisposing to spinal cord compression in small breeds and Dachshunds. Remarkable consistency was noted between the spinal level of the maximum enlargement of the spinal cord which previously was reported to be at C6, and the site of maximum enlargement of the vertebral canal currently stated in Dachshunds and small breeds. In large breeds the maximum enlargement of the vertebral canal tended to be located more caudally at the caudal limit of C7. The average age at which large dogs were most susceptible to noxious factors causing abnormal growth of the pedicles was determined to be 16 wk.

Animals↗
PubMed2001

The position and shape of osteophyte formations at canine vertebral endplates and its influence on radiographic diagnosis.

The relationship between the risk of missing osteophytes in lateral radiographs and their position was determined in a sample of German shepherd dogs (GSDs, n = 42) and dachshunds (DHs, n = 36). Only 10% of osteophytes which were not detected on radiographs were located in the ventral median area (position 1) and classified as type 1 (small spur with narrow base). The highest risk for being affected next to the intervertebral foramen and/or the dorsal area of the vertebral endplate (position 3) was noticed in the lumbar segment (95% CI: 5.2-9.8% in DHs; 11.9-17.7% in GSDs). The minimum risk of missing osteophytes in this position radiologically was 33.3% in the GSDs and 26.4% in the DHs. In the GSDs a higher proportion of type 2 osteophytes (spur with broader base of origin, tending to extend up to half the way along the disc space) was not visualized on radiographs. Peak incidences of osteophytes in positions 1 and 3 were located at the centres of spinal flexion and extension. Therefore, distribution patterns of osteophytes in these positions confirmed mechanical factors being important in pathogenesis of vertebral osteophytosis.

Animals↗
PubMed2000

The N-myc oncogene in human neuroblastoma cells: down-regulation of an angiogenesis inhibitor identified as activin A.

Angiogenesis, the formation of new blood vessels, is seen during embryonic development and tumor progression, but the mechanisms have remained unclear. Recent data indicate that developmental and tumor angiogenesis can be induced by cellular oncogenes, leading to the enhanced activity of molecules stimulating angiogenesis. However, activated oncogenes might also facilitate angiogenesis by down-regulating endogenous inhibitors of angiogenesis. We report here that enhanced expression of the N-myc oncogene in human neuroblastoma cells down-regulates an inhibitor of endothelial cell proliferation, identified by amino acid sequencing as being identical with activin A, a developmentally regulated protein. Down-regulation appears to involve interaction of the N-Myc protein with the activin A promoter. In addition, activin A inhibits both endothelial cell proliferation in vitro and angiogenesis in vivo, and it induces hemorrhage in vivo. We suggest that the N-myc-induced down-regulation of activin A could contribute to developmental and tumor angiogenesis.

Activins↗
PubMed2000

N-myc down-regulates activin A.

N-myc oncogene amplification is frequent in human neuroblastoma and predicts poor prognosis, but the molecular consequences have remained obscure. We report here that enhanced N-myc expression correlates with low or undetectable expression of activin A, but not other closely related members of the transforming growth factor-beta superfamily. N-myc interacts with the activin A promoter, eventually inducing down-regulation of activin A mRNA and protein. This study demonstrates for the first time N-myc-induced down-regulation of a gene implicated in signal transduction. Down-regulation of activin A could deprive neuroblastomas from a signal with growth-inhibitory activities toward the tumor and its stroma and thereby permit neuroblastoma progression.

Activins↗
PubMed2000

MYCN oncogene and angiogenesis: down-regulation of endothelial growth inhibitors in human neuroblastoma cells. Purification, structural, and functional characterization.

Angiogenesis, the formation of new blood vessels, is seen during embryonic development and tumor progression, but the mechanisms have remained unclear. Recent data indicate that tumor angiogenesis can be induced by cellular oncogenes, leading to the enhanced activity of molecules stimulating angiogenesis. However, activated oncogenes might also facilitate angiogenesis by down-regulating endogenous inhibitors of angiogenesis. We report here that enhanced expression of the N-myc oncogene in human neuroblastoma cells down-regulates three inhibitors of endothelial cell proliferation. One of them was identified by amino acid sequencing as being identical with activin A, a developmentally-regulated protein. Down-regulation involves interaction of the N-myc protein with the activin A promoter. Work is ongoing to characterize the other two endothelial cell inhibitors. We suggest that the N-myc induced down-regulation of angiogenesis inhibitors could contribute to tumor angiogenesis.

Activins↗
PubMed1999

Arginine deiminase inhibits cell proliferation by arresting cell cycle and inducing apoptosis.

We have previously demonstrated that arginine deiminase inhibits the proliferation of vascular endothelial cells, but the mechanisms leading to growth inhibition have remained unclear. We report here that low concentrations of arginine deiminase purified from Mycoplasma arginini inhibit proliferation of various cultured cells by arresting the cell cycle in G(1) and/or S phase with higher arginine deiminase concentrations leading to subsequent apoptosis. Our results demonstrate that arginine deiminase inhibits cell proliferation not only by depletion of arginine, but also by mechanisms involving the cell cycle and death signals.

Apoptosis↗
PubMed1999

Vascular endothelial growth factor expression in human neuroblastoma: up-regulation by hypoxia.

Enhanced angiogenesis apparently contributes to the poor clinical outcome of human neuroblastoma, but the mechanisms have remained unclear. We report here that cultured human neuroblastoma cells express a bioactive endothelial cell growth factor indistinguishable from the angiogenesis stimulator vascular endothelial growth factor (VEGF). VEGF is present in neuroblastoma but not vascular endothelial cells, whereas the corresponding VEGF receptors (Flt-1 and Flk-1/KDR) are expressed in endothelial but not neuroblastoma cells. Exposure of neuroblastoma cells to hypoxia induces a marked increase in bioactive VEGF. VEGF is also present in human neuroblastoma specimens, with substantial amounts in apparently hypoxic neuroblastoma cells, eventually accumulating in tumor microvessels. Our results indicate that VEGF (i) is present in human neuroblastomas, (ii) is up-regulated by tumor hypoxia and (iii) may stimulate neuroblastoma angiogenesis by paracrine mechanisms, thereby contributing to the progression of human neuroblastomas. We suggest that inhibition of VEGF activity may represent a novel approach for the therapy of human neuroblastoma.

Cell Division↗
PubMed1999

Tremorlytic activity of budipine in Parkinson's disease.

In order to objectively quantify the tremorlytic activity of budipine in Parkinson's disease (PD) we performed longterm tremor recordings in a subset of patients enrolled in two clinical trials. Eleven PD patients with marked tremor participating in an open-label study underwent longterm recording before and during medication. Nine patients completed the study. Tremor occurrence was reduced from 52 +/- 18.6% to 34.7 +/- 19.3% (p < 0.05); tremor intensity decreased from 15.3 +/- 4.8 (SNR) to 11.3 +/- 4.8 (p < 0.01). UPDRS tremor subscores were also significantly improved. Fourteen patients who enrolled in a multicenter, double-blind, placebo-controlled study underwent longterm tremor analysis in addition to the Columbia University Rating Scale (CURS). Tremor occurrence was improved in the budipine group (n = 7) from 24.7 +/- 15.5% to 14.8 +/- 14.5% (p < 0.05). Tremor intensity decreased from 9.1 +/- 2.5 (SNR) to 7.2 +/- 1.6. However, the latter result was statistically not significant, probably due to the small patient number. In the placebo-group (n = 7) there was no reduction of tremor occurrence or of tremor intensity. The CURS sum score was improved from 5.7 to 3.0 in the budipine group, whereas there was only a smaller improvement in the placebo group (from 7.1 to 5.5). These data suggest that budipine is an effective tremorlytic agent in PD, which may be used as an alternative to anticholinergics.

Aged↗
PubMed1999

Side-controlled intradermal injection of botulinum toxin A in recalcitrant axillary hyperhidrosis.

BACKGROUND: Although topical application of aluminium chloride is the most common measure against axillary sweating, severely affected patients often undergo surgical procedures that are expensive and may have considerable side effects. Recently botulinum toxin A (BT-A) has been reported as a potentially effective antihyperhidrotic agent. OBJECTIVE: Our purpose was to determine the therapeutic strength, safety, and mode of application of BT-A in severe axillary hyperhidrosis. METHODS: Intradermal injection of BT-A (Dysport) was given in an open left-versus-right side trial with each patient being his own control for initial efficacy, followed by treatment of the contralateral side. RESULTS: Seven days after initial treatment sweat production fell to below 10% of the untreated contralateral axilla as determined by gravimetry. Satisfaction was rated unanimously as "very good," the highest of 5 rankings. No side effects such as skin irritation or muscle weakness were noted in any patient. CONCLUSION: Intradermal injection of BT-A is a potent and well-accepted therapeutic option in patients with recalcitrant axillary hyperhidrosis.

Adult↗
PubMed1999

Down-regulation of endothelial cell growth inhibitors by enhanced MYCN oncogene expression in human neuroblastoma cells.

Recent evidence indicates that the genetic alterations of the multistage process of malignant transformation appear to activate tumor neovascularization by altering the balance between stimulators and inhibitors of angiogenesis. In the present study, we have attempted to define the effect of enhanced MYCN oncogene expression on the profile of endothelial cell growth modulators in neuroblastoma cells. We report here that conditioned medium of human neuroblastoma cells with normal MYCN expression contains three inhibitors of endothelial cell proliferation, which appear to be novel proteins as judged by their physicochemical, immunological and biological properties. All three inhibitors are diminished or become undetectable upon experimental increase of MYCN expression. Our results suggest that enhanced MYCN expression in human neuroblastoma cells alters the angiogenic balance by down-regulating endothelial cell growth inhibitors but leaving the expression of the stimulators unaffected. These data shed light on the molecular mechanisms linking the genetic changes of malignant transformation with initiation of tumor angiogenesis. Moreover, our observations might explain the poor prognosis of human neuroblastomas following MYCN oncogene amplification through initiation of angiogenesis and subsequent tumor growth and spread.

Cell Division↗