Biomedical subjects

J Weis

Publications and source records attributed to J Weis.

At least 19 recordsLinked to original sources

PubMed1995

Human ciliary neurotrophic factor: a structure-function analysis.

Ciliary neurotrophic factor (CNTF) promotes survival in vitro and in vivo of several neuronal cell types including sensory and motor neurons. The primary structure of CNTF suggests it to be a cytosolic protein with strong similarity to the alpha-helical cytokine family which is characterized by a bundle of four anti-parallel helices. CNTF exerts its activity via complexation with CNTF receptor (CNTF-R). This complex consists of a CNTF-binding protein (CNTF-R) and two proteins important for signal transduction [gp130 and leukaemia inhibitory factor receptor (LIF-R)]. We have shortened the cDNA coding for CNTF at both the 5' and the 3' end and expressed the truncated proteins in bacteria. Biological activities of the protein preparations were determined by their ability to induce proliferation of BAF/3 cells that were stably transfected with CNTF-R, gp130 and LIF-R cDNAs. CNTF proteins with 14 amino acid residues removed from the N-terminus were biologically active whereas the removal of 23 amino acids resulted in an inactive protein. In addition, 18 amino acid residues could be removed from the C-terminus of the CNTF protein without apparent loss of bioactivity, but further truncation at the C-terminus yielded biologically inactive proteins. The introduction of two point mutations into the CNTF protein at a site that presumably interacts with one of the two signal-transducing proteins resulted in a CNTF mutant with no measurable bioactivity. In addition, a model of the three-dimensional structure of human CNTF was constructed using the recently established structural co-ordinates of the related cytokine, granulocyte colony-stimulating factor. CD spectra of CNTF together with our mutational analysis and our three-dimensional model fully support the view that CNTF belongs to the family of alpha-helical cytokines. It is expected that our results will facilitate the rational design of CNTF mutants with agonistic or antagonistic properties.

Amino Acid Sequence↗

PubMed1995

Central nervous system lesions and cervical disc herniations in amateur divers.

Permanent neuropsychological changes such as memory disturbances and depression have been found in professional divers, even in those who have never had decompression sickness. The changes are probably the result of intravascular gas bubbles insufficient to cause acute symptoms. We examined amateur divers with long histories of self-contained underwater breathing apparatus diving by magnetic resonance imaging and compared them with normal controls. Hyperintense lesions of the subcortical cerebral white matter and degenerative changes of the cervical disks were significantly more common in the divers. 27 of 52 divers had a total of 86 focal hyperintensities versus 10 of 50 controls with 14 focal hyperintensities (p < 0.01). 32 divers had at least one degenerated intravertebral disc versus 9 controls (p < 0.0001). These results suggest that amateur divers are at risk of accumulating lesions in the central nervous system and in cartilage.

Adult↗

PubMed1995

Site-directed mutagenesis of human CNTF: functional analysis of recombinant variants.

Ciliary neurotrophic factor (CNTF), interleukin-6 (IL-6), leukemia inhibitory factor (LIF), and oncostatin M (OSM) share functional properties, a predicted common helical framework, and partially identical receptor components. CNTF is a survival promoting factor for various types of neurons in vitro and in vivo. In the present study, structural features essential for the biological function of human CNTF were investigated. Several recombinant CNTF variants were constructed by PCR and expressed in E. coli. Their survival promoting activities were determined using cultures of embryonic chick and newborn rat dorsal root ganglion cells. Deletion of 14 N-terminal and 18 C-terminal amino acids significantly increased bioactivity compared to wild-type (wt) CNTF. Further truncation of the CNTF molecule at the N- or C-terminus resulted in a significant reduction or complete loss of activity. Substitution of two amino acids (Lys154Glu and Trp157Pro) abolished the survival promoting effect. Recently described analogous substitutions in IL-6 had resulted in a partial IL-6 receptor antagonist. However, the double substitution variant had no significant inhibitory effect on wtCNTF activity in assays with both wt and mutant factor. The CNTF variants constructed had almost identical effects on both chick and rat neurons indicating a close similarity of the avian and the mammalian CNTF receptor complex. The present results also demonstrate that a core segment of the CNTF molecule is indispensable for biological function. Analogous segments important for activity have already been identified in the related molecules IL-6, LIF, and OSM. Thus, our data confirm the close structural relationship of CNTF to these "neuropoietic" cytokines. In addition, they demonstrate that site-directed mutagenesis of recombinant human CNTF can yield molecules which show increased survival promoting activity on mammalian neurons.

Animals↗

PubMed1995

Measurements of magnetic field variations in the human brain using a 3D-FT multiple gradient echo technique.

A magnetic resonance 3DFT multiple gradient-echo technique was used for measurements of the proton spectrum for each voxel in the measured slice. Water, fat, magnetic field and T2 distributions in the head of a normal volunteer and a patient with intracerebral hematoma were computed. Magnetic field variations caused by the head were calculated after correction for the static magnetic field inhomogeneity. Large local magnetic field variations up to 3 ppm were found in the human brain near interfaces between air or bone and brain tissues and 0.5 ppm between hematoma and brain tissue. Information about magnetic field variations could be useful for shimming procedures in vivo and for correcting artifacts in imaging and spectroscopy.

Aged↗

PubMed1995

Nerve conduction changes and fine structural alterations of extra- and intrafusal muscle and nerve fibers in streptozotocin diabetic rats.

Streptozotocin-induced diabetes mellitus is known to cause a reduction of both conduction velocity and axon caliber in sciatic nerves and also a decrease in muscle fiber size. The present study investigates whether the distal parts of the peripheral nervous system, including extra- and intrafusal muscle fibers, are more severely affected than the proximal segments in the diabetic state. Proximal and distal sensory nerve conduction velocities were monitored during a period of 3 months in rats rendered diabetic by injection of streptozotocin. Segments of the sciatic and ventral coccygeal nerves, and of the biceps femoris and lumbrical muscles, were studied by light and electron microscopy, including morphometric analysis. In contrast to previous studies, daily suboptimal insulin injections were given to prevent acute metabolic complications. Sensory conduction velocity in the ventral coccygeal nerve was significantly (P < 0.05) decreased in the diabetic rats compared to controls. Proximal and distal nerve segments were equally affected. Mean cross-sectional axon area of the sciatic nerve was moderately, but significantly (P < 0.05), smaller in insulin-treated diabetic rats than in controls. In both the sciatic nerve and the terminal, intrafusal nerve segments, occasional axons showed moderate dystrophic changes. Fibers of the intrafusal nerve segments appeared to be equally affected compared to the fibers in the sciatic nerve, although no quantitative comparison was made. The increase of small caliber skeletal muscle fibers in experimental streptozotocin-induced diabetes was confirmed. These findings indicate that proximal and distal segments of peripheral nerves are affected equally in the early stages of experimental diabetic neuropathy.

Animals↗

PubMed1995

Morphology of cardiac muscle in septic shock. Observations with a porcine septic shock model.

The morphology of cardiac muscle was investigated in a porcine model of septic shock, created by intermitted application of Escherichia coli-endotoxin. The earliest lesions, found after 18 h of septic shock, were endothelial cell swelling, marked leucostasis and slight ischaemic alterations of the muscle fibres. At the end point of the experiments, after 48 h, some fibrin thrombi were found associated with more pronounced ischaemic alterations of cardiac muscle cells and some necrotic fibres. Comparing these findings with the severe endothelial and muscle fibre lesions found in skeletal muscle, the endothelial cells of the heart microvasculature, are clearly more resistant to the attack of the endotoxins and mediators liberated in septic shock.

Animals↗

PubMed1995

Assessment of the narrow cervical spinal canal: a prospective comparison of MRI, myelography and CT-myelography.

This study was designed to compare the accuracy of magnetic resonance imaging (MRI), myelography and computed tomography in the assessment of degenerative cervical spinal stenosis. We prospectively examined a total of 75 spinal segments in 18 patients with suspected cervical spinal canal stenosis, using sagittal spin-echo and axial gradient-echo sequences generated by a 1.5 Tesla imager, conventional myelography, and computed tomography with intrathecal contrast medium (CT-myelography). The degree of stenosis was often overestimated using MRI. This error was most prominent in cases of severe stenosis but was significant with minor to moderate stenosis. In these cases, the clinical consequences of such an overestimation can be serious, because treatment is misdirected. The error is probably caused by pulsation of the cerebrospinal fluid and truncation artefact (Gibbs phenomenon). MRI at 1.5 Tesla is thus frequently inadequate for diagnostic assessment of degenerative cervical spinal stenosis. Myelography and myelographic CT are still useful for decisions on operative treatment, especially in cases of moderate stenosis. This may, however, not apply to imagers operating at 0.5 Tesla as below.

Adult↗

PubMed1995

A motoneuron-selective stop signal in the synaptic protein S-laminin.

Motor axons preferentially reinnervate original synaptic sites on denervated muscle fibers. We have shown that components of synaptic basal lamina direct this selectivity, and we identified a protein, s-laminin, that is concentrated in synaptic basal lamina. Here, we report that a recombinant s-laminin fragment inhibits neurite outgrowth promoted by laminin. A tripeptide sequence in this fragment, Leu-Arg-Glu (LRE), contributes to this inhibition and is itself sufficient to inhibit outgrowth. LRE-mediated inhibition is selective for motoneuron-like cells and is observed in mixtures with several, but not all, outgrowth-promoting substrates. Growth cones extending on laminin stop for up to several hours upon contacting deposits of the s-laminin fragment. Thus, LRE may serve as a cell type-selective and context-dependent target-derived signal that plays a role in synapse formation.

Amino Acid Sequence↗

PubMed1995

Oculopharyngeal muscular dystrophy: clinical and morphological follow-up study reveals mitochondrial alterations and unique nuclear inclusions in a severe autosomal recessive type.

Oculopharyngeal muscular dystrophy (OPMD) is usually a late onset, autosomal dominant dystrophy that affects extraocular eye muscles, pharyngeal muscles, and the trunk and limb musculature. In the present presumably recessively inherited case, with a clinical history of oculopharyngeal myopathy and distal weakness, paracrystalline mitochondrial inclusions and unique nuclear inclusions were found. In a biopsy obtained from the erector spinae muscle, marked muscle fibre atrophy and hypertrophy, occasional muscle fibre necrosis, and considerable fibrosis of the endomysium were noted. Similar signs of a chronic myopathy could already be detected in a biopsy from the anterior tibial muscle that had been obtained 10 years before. In both muscles, nuclear inclusions were seen in numerous severely affected, atrophic muscle fibres. These inclusions consisted of straight or helically wound 2-4 nm filaments. The outer diameter of the double helix was 12-15 nm and the periodicity of its repeats was about 15 nm. The filaments were often accumulated in clusters with a paracrystalline arrangement. No nuclear inclusions consisting of 8.5 nm tubular filaments, typically found in cases of OPMD, were detected. In addition, paracrystalline inclusions were present in a large number of mitochondria in several muscle fibres of the erector spinae muscle indicating that mitochondria could be primarily involved in the disease.

Actin Cytoskeleton↗

PubMed1995

Extracellular matrix proteins in colorectal carcinomas. Expression of tenascin and fibronectin isoforms.

BACKGROUND: Interactions of tumor cells and extracellular matrix (ECM) components are crucial determinants of tumor cell spreading and metastatic activity. Particularly tenascin (TN) as a member of the adhesion modulating family of ECM and its alternatively spliced isoforms became the matter of interest in ECM changes associated with malignancy. EXPERIMENTAL DESIGN: We analyzed the composition of the stromal- and basement membrane-associated ECM of colorectal adenomas and carcinomas using indirect immunofluorescence. Tenascin was investigated by immunoblot of snap frozen tumor specimens. RESULTS: Fibronectin (FN), TN, and chondroitin sulfate proteoglycan were the major components of the tumor stroma. Normal basement membrane components like laminin (LM), collagen type IV, and heparan sulfate proteoglycan were down-regulated. In the center of the tumor, tumor glands were surrounded by discontinuous basement membranes. At the tumor-host interface and in solid, poorly differentiated tumors, no immunoreactivity with normal basement membrane components was found. However, in cases with pericellular anti-LM staining, LM immunoreactivity was also found at the tumor-host interface. An alternatively spliced isoform of TN with a molecular weight of 330 kDa was found in seven of 15 carcinomas. In four of these cases, an alternatively spliced isoform of FN containing the ED-B segment was present. CONCLUSIONS: The coexpression of alternative splicing of FN and TN suggests that there may be common regulation mechanisms. The matrix composition found in the present study resembles that of healing wounds and probably favors the invasive spread of tumor cells.

Adenoma↗

PubMed1994

Skeletal muscle oedema and muscle fibre necrosis during septic shock. Observations with a porcine septic shock model.

In domestic pigs, intermitted application of Escherichia coli-endotoxin was used to create an animal model for a prolonged hypo- and hyperdynamic septic shock-like state and to investigate mechanisms of multiple organ failure. Here, we describe the changes in skeletal muscle after 18 h (2 animals) and 48 h (6 animals) of septic shock. Two pigs for each observation period that received physiologic saline solutions instead of endotoxin served as controls. The earliest lesions were endothelial cell damage with endomysial oedema and swelling of mitochondria in muscle fibres. With increasing degree of endothelial cell damage, pericytes showed degenerative changes with cytoplasmic fragmentation and karyolysis. After 48 h of shock, endomysial oedema was increased with fibrinogen present. Muscle fibre diameters were increased and swollen mitochondria and segmental necrosis of muscle fibres were frequently observed. However, phagocytic reaction or regenerative changes were not detected. In this respect, skeletal muscle lesions in septic shock differ from ischemic damage, which is characterized by early phagocytosis. Tumour necrosis factor alpha (TNF alpha) was increased greatly and significantly in the serum of the pigs that received endotoxin. The lesions described may be the result of both direct damage to muscle fibres by the endotoxin and/or the increased levels of TNF alpha and indirect damage because of the increased diffusion distance, due to the endomysial oedema. The loss of blood proteins into the endomysium may also play a role in generating hypoproteinemia in patients with septic shock.

Animals↗

PubMed1994

Fine structural and immunohistochemical identification of perineurial cells connecting proximal and distal stumps of transected peripheral nerves at early stages of regeneration in silicone tubes.

Perineurial cells are specialized connective tissue cells that form a barrier between endoneurium and epineurium in normal nerves. In the present study, the formation of the perineurium after transection of rat sciatic nerves was investigated. The cord bridging the gap between proximal and distal stumps through silicone tubes was studied 3, 7, 12, 18, and 21 days after surgery using electron microscopy and antibodies against epithelial membrane antigen (EMA), a marker for perineurial cells that has thus far not been applied to the study of differentiating cells in nerve tubulation systems. Initially, a thin cord consisting of fibrin bridged the gap between the stumps. At 7 days, longitudinal cells had migrated from both stumps toward the center of the tubes on the surface of the fibrin cord. These cells were immunoreactive with anti-EMA. At 12 days, ultrastructural features of perineurial cells (desmosomes, tight junctions, actin filaments with dense bodies, tonofilaments) were prominent in these cells. Subsequently, the gap was bridged through the perineurial tube by endothelial cells, pericytes, fibroblasts, Schwann cells, and axons. At 21 days, a single large nerve fascicle ensheathed by a mature perineurium was found between the stumps. Thus, the first cells to connect proximal and distal stumps in the investigated nerve regeneration silicon chamber system are perineurial cells. Through the tube formed by these cells, blood vessels and nerve fibers bridge the gap. Therefore, establishment of a perineurial connection between nerve stumps appears to be important in the sequence of events during nerve regeneration.

Animals↗

PubMed1994

Jun, Fos, MyoD1, and myogenin proteins are increased in skeletal muscle fiber nuclei after denervation.

After denervation, mRNA levels of the jun and fos protooncogenes and of the muscular differentiation factors myoD1 and myogenin are increased. Here, immunohistochemistry was used (a) to show that this increase in mRNA is followed by an increase in the transcription factor proteins, and (b) to determine which cell populations in skeletal muscle express these factors after denervation. Rat diaphragms were denervated and analyzed after periods of 90 min-8 days. An increase in Fos and Jun as well as MyoD1 and Myogenin immunoreactivity was found after 2-2.5 days of denervation. Fos, MyoD1, and Myogenin immunoreactivity was mostly confined to muscle cell nuclei, whereas Jun antibodies stained muscle cell and some interstitial cell nuclei. A selective expression of any of the four transcription factors in muscle cell nuclei closely associated with motor endplates could not be detected in either denervated or innervated muscle at any time point examined, indicating that synaptic and extrasynaptic muscle cell nuclei are activated simultaneously after denervation. These results suggest that a genetic program which includes protooncogenes and myogenic differentiation factors is activated in skeletal muscle after denervation.

Amino Acid Sequence↗

PubMed1994

Measurement of magnetic susceptibility and MR contrast agent concentration.

This paper describes an MR imaging method for determining magnetic susceptibility constants of solutions containing paramagnetic contrast agents. The method's validity is demonstrated on Gd(DTPA) and Dy(DTPA) water solutions. The method can be used for measurement of the volume magnetic susceptibility or concentration of contrast agents in biological tissues.

Animals↗

PubMed1994

[18FDG-PET in intracranial meningiomas versus grading, proliferation index, cellular density and cytogenetic analysis].

62 intracranial meningiomas in 60 patients were studied with 18FDG-PET prior to neurosurgery in order to evaluate the relationship between 18FDG uptake and biological aggressiveness of the tumors. Histopathological grading, cellular density, Ki-67 proliferation index and evidence of chromosomal aberrations were used to assess tumor aggressiveness. Significantly elevated 18FDG uptake was found in grade 2- and 3- compared to grade 1-meningiomas, in tumors of high cellularity compared with those of low cellularity, and in meningiomas with an elevated Ki-67 proliferation index (above 2%). The two meningiomas with the most pronounced chromosomal aberrations revealed the highest 18FDG uptake of all cytogenetically studied meningiomas. We conclude that 18FDG-PET is useful for estimating the biological aggressiveness of intracranial meningiomas.

Adult↗

PubMed1993

Renaut bodies contain elastic fiber components.

Renaut bodies (RB) are fusiform endoneurial structures preferentially found at sites of nerve entrapment, often occupying more than 30% of the cross-sectional area of a nerve fascicle. Their composition and significance, however, are still incompletely understood. In this study, further evidence for the link between the appearance of RB and nerve entrapment is presented. Reanaut bodies were already found at the age of 1 year in the median nerve at the level of the wrist, i.e. in the carpal tunnel, a possible site of entrapment. Here, their number increased with age. Renaut bodies were absent, however, in fetal nerves at this site. Many of the cells in RB resembled perineurial cells or pericytes. They were stained with antibodies against vimentin and epithelial membrane antigen and were partially covered by a basal lamina reactive with antibodies against collagen IV, laminin, and s-laminin. Focally accumulated filaments and bundles of 30-40 nm collagen fibrils were major extracellular components of RB. The diameter of the filaments (8-12 nm) corresponded to the size of the microfibril, i.e. the oxytalan component of elastic fibers. Renaut bodies were intensely stained with antibodies against these microfibrils and several types of collagen glycoproteins. On the basis of these results, we conclude that RB are composed of cells that show perineurial differentiation. These cells produce an extracellular matrix highly enriched in elastic fiber components.

Adult↗

PubMed1993

[Experience in psychosocial management of cancer patients undergoing bone marrow transplantation].

Psychosocial care of cancer patients undergoing bone marrow transplantation. During the last years bone marrow transplantation (BMT) has emerged as a treatment of choice especially for cancer diseases of the haemopoietic system as well as for certain solid tumours. BMT is a very invasive treatment with high dose chemotherapy and total body irradiation, which is accompanied by special psychosocial strains for the patient. Therefore psychosocial care during the acute treatment is needed. In this paper a psychosocial liaison service in a BMT unit as part of a comprehensive psychosocial care on different oncology wards of an acute clinic is presented. Based on a systematic clinical documentation of the psychosocial interventions the practice and problems of the psychosocial care are described. Apart of common problems of psychosocial liaison services known from the literature the experiences show special demands reflecting the special environment of the treatment setting. These problems are discussed with regard to the different target groups (patients, relatives, medical staff). Following the reported experiences some proposals concerning structure and integration of psychosocial care in an BMT unit are given.

Adaptation, Psychological↗

PubMed1992

Rat gastric relaxation induced by stimulation of endothelin-1 selective receptors.

We have investigated the smooth muscle activity of ET-1 and ET-3 on rat fundus strips in vitro as well as the effects of the peptides on gastric motility in vivo. In the isolated tissue with no precontraction ET-1 and ET-3 were potent spasmogens which produced half maximal contractions at concentrations 4.5 and 8.0 nM, respectively. In contrast, under conditions where the isolated tissue was precontracted to approx. 50% of maximum by prostaglandin E2, ET-1 dose-dependently (5 x 10(-10) - 10(-8) M) and temporarily relaxed the fundus strip, whereas ET-3 further increased the contraction. The relaxing capacity of ET-1 was absent when the tissue was precontracted by potassium yet was resistant to pretreatments with tetrodotoxin, capsaicin, propranolol, indomethacin, NG-methyl-L-arginine or glibenclamide. In addition in vivo ET-1 and ET-3 (less than 1 nmol/kg) showed opposite effects on gastric motility as the former reduced basal tonus and spontaneous activity, whereas the latter increased the motor activity of the gastric ventricle. The results support the notion that ET-1 may induce gastric relaxation by stimulation of selective receptors whereas stimulation of nonselective receptors may promote gastric smooth muscle contraction.

Animals↗