PubMed Health⌕ Search

Biomedical subjects

H Veldman

Publications and source records attributed to H Veldman.

At least 19 recordsLinked to original sources
PubMed2006

Intraspinal administration of an antibody against CD81 enhances functional recovery and tissue sparing after experimental spinal cord injury.

We previously demonstrated that the tetraspanin protein CD81 is up-regulated by astrocytes and microglia after traumatic spinal cord injury in rats and that CD81 is involved in adhesion and proliferation of cultured astrocytes and microglia. Since these reactive glial cells contribute to secondary damage and glial scar formation, we studied the effect of local administration of an anti-CD81 antibody in experimental spinal cord injury. Adult rats were subjected to a moderate spinal cord contusion injury and treated for 2 weeks with different doses of the anti-CD81 antibody AMP1 (0.5-5 microg/h) or non-immune IgG (5.0 microg/h). A technique was developed to infuse the antibodies directly into the lesion site via an intraspinal cannula connected to a pump. Functional recovery was monitored during 8 postoperative weeks by means of the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, the BBB subscore and Grid-walk test. At the end of the study, quantitative histology was performed to assess tissue sparing. Our data showed that by itself cannulation of the lesion site resulted in minimal functional and histological impairments. Application of 0.5 microg/h AMP1 resulted in a marked functional recovery (BBB 2 points; Grid-walk 30% less errors compared to control). This recovery was accompanied by an 18% increase in tissue sparing at the lesion epicentre. No gross histological changes in glial scarring were apparent. Our data demonstrate beneficial effects of an anti-CD81 antibody on functional recovery in spinal cord injured rats and suggest that this effect is mediated through a reduction in secondary tissue loss.

Animals↗
PubMed2005

Gene dosage-dependent transmitter release changes at neuromuscular synapses of CACNA1A R192Q knockin mice are non-progressive and do not lead to morphological changes or muscle weakness.

Ca(v)2.1 channels mediate neurotransmitter release at the neuromuscular junction (NMJ) and at many central synapses. Mutations in the encoding gene, CACNA1A, are thus likely to affect neurotransmitter release. Previously, we generated mice carrying the R192Q mutation, associated with human familial hemiplegic migraine type-1, and showed first evidence of enhanced presynaptic Ca(2+) influx [Neuron 41 (2004) 701]. Here, we characterize transmitter release in detail at mouse R192Q NMJs, including possible gene-dosage dependency, progression of changes with age, and associated morphological damage and muscle weakness. We found, at low Ca(2+), decreased paired-pulse facilitation of evoked acetylcholine release, elevated release probability, and increased size of the readily releasable transmitter vesicle pool. Spontaneous release was increased over a broad range of Ca(2+) concentrations (0.2-5mM). Upon high-rate nerve stimulation we observed some extra rundown of transmitter release. However, no clinical evidence of transmission block or muscle weakness was found, assessed with electromyography, grip-strength testing and muscle contraction experiments. We studied both adult ( approximately 3-6 months-old) and aged ( approximately 21-26 months-old) R192Q knockin mice to assess effects of chronic elevation of presynaptic Ca(2+) influx, but found no additional or progressive alterations. No changes in NMJ size or relevant ultrastructural parameters were found, at either age. Our characterizations strengthen the hypothesis of increased Ca(2+) flux through R192Q-mutated presynaptic Ca(v)2.1 channels and show that the resulting altered neurotransmitter release is not associated with morphological changes at the NMJ or muscle weakness, not even in the longer term.

Acetylcholine↗
PubMed2003

Zinc amplifies mSOD1-mediated toxicity in a transgenic mouse model of amyotrophic lateral sclerosis.

Transgenic mice overexpressing the human mutated form (G93A) of Cu,Zn-superoxide dismutase (mSOD1) develop motor neuron degeneration resembling amyotrophic lateral sclerosis. In vitro studies have shown that mSOD1-induced, reactive oxygen species-mediated apoptosis of motor neurons depends on the presence of copper and the relative absence of zinc. Oral intake of zinc sulphate induces the expression of metallothioneins, enzymes that decrease oxidative stress, and leads to higher serum zinc, and lower copper levels. We therefore tested the effect of chronic oral administration of zinc sulfate (0.075 and 0.375 g/kg) on disease onset and survival of mSOD1 transgenic mice. We observed that zinc sulfate, rather than prolonging survival, decreased survival. We conclude that zinc sulfate amplifies the mSOD1 transgenic mouse phenotype. This finding may shed more light on the role of zinc in mSOD1-mediated toxicity.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Cellular changes in motoneurons in a transgenic mouse model for amyotrophic lateral sclerosis as revealed by monoclonal antibody Py.

Transgenic mice (G93A) carrying the human amyotrophic lateral sclerosis (ALS) linked superoxide dismutase 1 (SOD1) mutations develop a motoneuron disease resembling human ALS. The affected motoneurons are characterized by the presence of cellular alterations. The antigen recognized by the monoclonal antibody Py is suggested to be associated with the neurofilamentous and microtubular elements of the cytoskeleton of specific neuron populations including the spinal motoneurons. The aim of the present study was to measure changes in the relative Py-immunoreactivity per identified Choline-Acetyl-Transferase (ChAT)-immunoreactive motoneuron during the disease progression. The relative Py-immunoreactivity of identified spinal motoneurons was measured on double stained (Py and ChAT) motoneurons using a digital imaging system coupled to an inverse microscope. A significant decrease of Py-immunoreactivity was already noted in the pre-symptomatic stages of the disease even before the onset of massive motoneuron degeneration. It is concluded that the Py-antibody detects early intracellular abnormalities related to neurodegenerative changes in spinal motoneurons of transgenic SOD1-(G93A) mice.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Rimmed vacuoles and the added value of SMI-31 staining in diagnosing sporadic inclusion body myositis.

Problems in diagnosing sporadic inclusion body myositis may arise if all clinical features fit a diagnosis of polymyositis, but the muscle biopsy shows some rimmed vacuoles. Recently, immunohistochemistry with an antibody directed against phosphorylated neurofilament (SMI-31) has been advocated as a diagnostic test for sporadic inclusion body myositis. The aims of the present study were to define a quantitative criterion to differentiate sporadic inclusion body myositis from polymyositis based on the detection of rimmed vacuoles in the haematoxylin-eosin staining and to evaluate the additional diagnostic value of the SMI-31 staining. Based on clinical criteria and creatine kinase levels in patients with endomysial infiltrates, 18 patients complied with the diagnosis of sporadic inclusion body myositis, and 17 with the diagnosis of polymyositis. A blinded observer counted the abnormal fibres in haematoxylin-eosin-stained sections and in SMI-31-stained sections. The optimal cut-off in the haematoxylin-eosin test was 0.3% vacuolated fibres. Adding the SMI-31 staining significantly increased the positive predictive value from 87 to 100%, but increased the negative predictive value only to small extent. We conclude that (1) patients with clinical and laboratory features of polymyositis, including response to treatment, may show rimmed vacuoles in their muscle biopsy and that (2) adding the SMI-31 stain can be helpful in differentiating patients who respond to treatment from patients who do not.

Adult↗
PubMed2001

Diagnostic value of sural nerve demyelination in chronic inflammatory demyelinating polyneuropathy.

The objective of the study was to determine the diagnostic value of features of demyelination and inflammation in sural nerve biopsy specimens of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The features of (i) demyelination, (ii) axonal de- and regeneration and (iii) inflammation were investigated by measuring the number of onion bulbs, g ratio (axon diameter/total nerve fibre diameter), myelinated nerve fibre density, number of clusters and endoneurial area in 21 patients with CIDP, as well as in 13 patients with chronic idiopathic axonal polyneuropathy (CIAP) and six autopsy controls. In addition, teased fibres were classified and lengths of internodes measured. We found no difference in demyelinating features between patients with CIDP and CIAP, as the percentage of fibres with segmental de- and remyelination and the number of onion bulbs were similar in both polyneuropathy groups. The g ratio, expected to be higher in a demyelinating disease due to thinner myelin sheaths, was significantly lower in CIDP than CIAP. Evidence for axonal degeneration was found in both CIDP and CIAP, as both showed a decrease in myelinated nerve fibre density. There was no evidence of endoneurial oedema in CIDP, as the endoneurial area did not differ between CIDP, CIAP and the autopsy controls. Although significant differences of features of demyelination, axonal degeneration and inflammation were found in sural nerve biopsy specimens, there was a considerable overlap between abnormalities in CIDP and CIAP patients. In the majority of patients, quantitative analysis of light microscopical abnormalities in sural nerves was similar in CIDP and CIAP. Therefore, a sural nerve biopsy is of limited diagnostic value in CIDP.

Adult↗
PubMed2000

Collagen IV deposits do not prevent regrowing axons from penetrating the lesion site in spinal cord injury.

Scarring is suggested to impede axon regrowth across the lesion site in the injured adult mammalian central nervous system. Collagen Type IV, as a major component of the scar formed after injury, is an impediment for successful axonal regeneration and a decrease in its amount is a prerequisite for regrowing axons to cross the lesion in the postcommissural fornix in the injured adult rat (Stichel et al. [1999] Neurosci. 93:321-333). The aim of the present study was to analyze the relationship between collagen IV deposits and regrowing axons at various times after dorsal hemi-section of the adult rat spinal cord. Immunohistochemical double staining revealed that penetrating neurofilament-positive axons and collagen IV deposits were co-localized in the lesion site in the initial stages of axonal sprouting (between 7 and 14 days post-operatively) and were still present 1 and 2 months post-operatively. Interestingly, collagen IV-immunoreactive areas located around cystic cavities formed at the site of injury 1 month post-operatively, were devoid of axons. In conclusion, our observations indicate that collagen IV deposits after spinal cord injury do not prevent neurofilament-positive regrowing axons from penetrating the lesion site.

Animals↗
PubMed2000

Pre- and postsynaptic localization of RC3/neurogranin in the adult rat spinal cord: an immunohistochemical study.

RC3 (neurogranin; BICKS) is a neuron-specific calmodulin-binding protein kinase C substrate. Thus far, immunohistochemical studies on the localization of RC3 revealed its presence in all neuronal phenotypes, which were restricted to specific areas in the neostriatum, the neocortex, and the hippocampus. RC3 was mostly found in cell bodies and dendrites, with some infrequent presence in axonal profiles, i.e. in the internal capsule. Until now, RC3 expression was reported to be absent in the adult rat spinal cord. RC3 might, however, act as an intermediate of protein kinase C-mediated signaling pathways during synaptic development and plasticity. We hypothesized a role for this 78-amino-acid protein in dendritic plasticity occurring after spinal cord injury. To our surprise, an immunohistological analysis of the uninjured adult rat spinal cord revealed the presence of RC3-positive cell bodies and dendrites in specific regions in the gray matter. Interestingly, axon-containing structures, such as the dorsal and ventral corticospinal tract, were also found to be RC3-positive. This axonal labeling was confirmed by preembedding electron microscopy. In conclusion, we demonstrate here that RC3 is present in the adult rat spinal cord in pre- and postsynaptic structures.

Animals↗
PubMed2000

Thickness of endoneurial vessel basal lamina area in chronic idiopathic axonal polyneuropathy.

For chronic idiopathic axonal polyneuropathy (CIAP), even after extensive evaluation, no cause has yet been found. Considering the age and sex distribution of patients with this disease, it is possible that vascular disease plays a role in the development of this polyneuropathy. As endoneurial vessel abnormalities can be related to ischemia, we investigated endoneurial vessels in sural nerve biopsies of 18 patients with CIAP. As controls we used sural nerves of 4 patients with diabetes mellitus, 6 patients with hereditary motor and sensory neuropathy type II (HMSN type III) and 10 autopsy cases. Basal lamina area thickness, endothelial cell area, lumen area, and the number of basal laminae, endothelial cells and periendothelial cell nuclei were investigated. Basal lamina area thickness, endoneurial cell area and number of endothelial cell nuclei in CIAP were increased in comparison with HMSN type III, whereas the basal lamina area thickness of patients with CIAP and diabetes mellitus were in the same range. The structure of the basal lamina area in CIAP differed from diabetes mellitus; in diabetes mellitus there was a larger number of lamellae, whereas in CIAP there was an increase in collagen. There was no correlation between basal lamina area thickness and age. In CIAP patients with peripheral vascular disease of the legs, basal lamina area thickness was increased. The relation between basal lamina area thickening and peripheral vascular disease of the legs in CIAP may indicate a role for ischemia in the development of this polyneuropathy.

Adult↗
PubMed2000

Unmyelinated nerve fiber degeneration in chronic inflammatory demyelinating polyneuropathy.

To determine whether unmyelinated nerve fibers escape degeneration as one might expect in an immune response exclusively directed at myelin, we performed a morphometric examination of unmyelinated axons and myelinated nerve fibers in sural nerve biopsy specimens of 14 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) and of 12 age-matched normal controls. The numbers of unmyelinated axons, myelinated nerve fibers, denervated Schwann cell units and collagen pockets were quantified and related to the clinical and electrophysiological data of the patients with CIDP. In 4 patients with a rapid onset of the neuropathy and a highly elevated CSF protein, the numbers of both unmyelinated axons and myelinated nerve fibers were decreased equally. In 8 patients we found that the unmyelinated axons were relatively spared compared with the loss of myelinated nerve fibers. In these patients, however, the presence of denervated Schwann cell units and of collagen pockets was increased. We conclude that unmyelinated nerve fibers are affected in patients with CIDP.

Adult↗
PubMed1999

The diagnostic value of sural nerve T cells in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: T-cell infiltrates in sural nerve biopsy specimens of patients with inflammatory neuropathies have been reported, suggesting a role for T cells in the pathogenesis, but the specificity of the presence and localization of sural nerve T cells in chronic inflammatory demyelinating polyneuropathy (CIDP) is unknown. OBJECTIVE: To study the diagnostic value of the number and distribution of sural nerve T cells in CIDP. METHODS: We performed a quantitative immunohistochemical examination of T cells in sural nerve biopsy specimens taken from 23 patients with a CIDP and compared them with sural nerves of 15 patients with a chronic idiopathic axonal polyneuropathy (CIAP), 5 patients with a vasculitic neuropathy, and 10 normal controls. RESULTS: T cells were found in sural nerves of all CIDP patients as well as in all disease and normal controls. Only six CIDP patients had increased numbers and densities of T cells compared with CIAP patients and controls. Based on the distribution of endoneurial or epineurial T cells, it was not possible to differentiate CIDP patients from CIAP patients or normal controls. In patients and controls perivascular epineurial T cells predominated. Increased numbers and densities of sural nerve T cells in patients with CIDP were associated with female sex, a more severe disease course, worse outcome, highly elevated CSF protein level, and a larger sural nerve area, but not with loss of myelinated nerve fibers in the sural nerve biopsy sample or demyelinating features on electrophysiologic examination. CONCLUSIONS: In the majority of CIDP patients, the number and distribution of T cells in sural nerve biopsy samples were similar to patients with noninflammatory neuropathies and normal controls. Only large numbers of sural nerve T cells are specific for inflammatory neuropathies and therefore of diagnostic value for CIDP.

Adult↗
PubMed1999

Differential distribution of immunoreactivity in the developing rat spinal cord revealed by the monoclonal antibody Py.

Monoclonal antibody Py was developed as a useful tool for the identification of large diameter neurons of the adult rat central nervous system [Woodhams et al., J. Neurosci., 9 (1989) 2170-2181]. Here, we present a detailed light-microscopic study of the distribution of Py-immunoreactivity in the developing rat spinal cord. The first cells which demonstrated Py-immunoreactivity were the motoneurons in layer IX of the gray matter at embryonic day 15. These cells, including their axons and dendrites, remained Py-immunoreactive throughout subsequent developmental stages into adulthood and were the most intensely stained cells in the adult rat spinal cord. Other cell populations which became Py-immunoreactive during development were neurons in layers III-VIII, and large-to-medium diameter neurons of the dorsal root ganglion (DRG). Transient Py-immunoreactivity was observed in the distal portions of DRG axons as well as in the ascending fibers in the dorsal funiculus. Py-immunoreactive fibers could be detected in the ventral most part of the dorsal funiculus (corticospinal tract area), even at embryonic ages prior to the arrival of corticospinal fibers. The localization and transient expression of the antigen recognized by the Py-antibody in developing rat spinal cord strongly suggests an important role of this molecule in stabilization and/or plasticity of the neuronal cytoskeleton. The results presented here form the foundation for the use of Py-immunocytochemistry to study well-defined cell populations under a range of experimental and pathological conditions.

Animals↗
PubMed1998

Oxidant treatment causes a dose-dependent phenotype of apoptosis in cultured motoneurons.

Evidence is growing that reactive oxygen species (ROS), by-products of (normal) cellular aerobic metabolism, are involved in the pathogenesis of neurodegenerative diseases. One of these diseases is amyotrophic lateral sclerosis (ALS), in which motoneurons die, leading to paralysis and death. It remains uncertain whether ROS are the cause of (apoptotic) motoneuron death in ALS. To further understand the role of ROS in motoneuron death, we investigated the effects of ROS on isolated spinal rat motoneurons in culture. ROS were generated with a combination of iron(III) and ascorbate, or with hydrogen peroxide. Both toxic treatments resulted in a dose-dependent motoneuron death. Iron(III)/ascorbate toxicity was completely prevented with the hydrogen peroxide detoxifying enzyme catalase and partially prevented with the antioxidant vitamin E. SOD1, the enzyme that removes superoxide, did not protect against iron(III)/ascorbate toxicity. ROS treatment caused apoptotic motoneuron death: low doses of iron(III)/ ascorbate or hydrogen peroxide resulted in complete apoptosis ending in nuclear fragmentation, while high doses of ROS resulted in incomplete apoptosis (nuclear condensation). Thus, depending on the dose of ROS, the motoneurons complete the apoptotic pathway (low dose) or are stopped somewhere during this route (high dose).

Animals↗
PubMed1998

Absence of characteristic features in two patients with inclusion body myositis.

According to recently published criteria a diagnosis of definite sporadic inclusion body myositis is made if the typical histopathological abnormalities (rimmed vacuoles and abnormal accumulations of proteins, in addition to mononuclear cell infiltrates) are present. The two women described here presented with myositis which was unresponsive to treatment. Patient 1 had features of non-progressive sporadic inclusion body myositis clinically, whereas patient 2 had a very slowly progressive limb girdle syndrome. The cryostat sections of the first biopsies did not show rimmed vacuoles, even in retrospect. Only a repeated biopsy, 12 years after presentation in one patient and 18 years after presentation in the other, disclosed the typical features of sporadic inclusion body myositis. The initial absence of abnormal fibres probably represents a real absence or scarcity rather then a sampling error due to a multifocal nature of the histological abnormalities. It is of importance for the clinician to realise that some patients with myositis unresponsive to treatment, even if both clinical and histological features do not suggest sporadic inclusion body myositis, may prove to have the disease on repeated histopathological examination.

Adult↗
PubMed1996

Clinically distinct codon 69 mutations in major myelin protein zero in demyelinating neuropathies.

Mutations in the major peripheral myelin protein zero (P0) gene on chromosome 1q21-q23 have been found with the hereditary demyelinating polyneuropathy Charcot-Marie-Tooth type 1B. Here, we describe 2 patients with distinct neurological characteristics, carrying different substitutions at the same codon--Arg69His and Arg69Cys. The patients were heterozygous for the mutation, which in both appeared to be de novo. Histological examination of sural nerve biopsy specimens revealed defective myelin as well as marked differences, confirming the importance of P0 in the compaction of myelin.

Adult↗
PubMed1995

Botulinum toxin-induced myopathy in the rat.

We have used histological and histochemical techniques at the light microscopical level, and electron microscopy to examine the myopathological changes in rat muscle up to 30 weeks following botulinum toxin injection. Apart from muscle fibre atrophy and related myofibrillar structural changes, the results show a number of striking abnormalities which developed and disappeared at different stages. During the first 4 weeks after toxin injection, vacuoles of variable size were seen in the sarcoplasm near myonuclei, both at and away from endplates. Following this, between 4 and 10 weeks post-injection, progressive degeneration of junctional folds and separation of some nerve terminals from the simplified postsynaptic membranes were observed. At different time points following recovery from the toxin-induced paralysis (evidenced by the increase in muscle fibre size and return of function) a number of abnormalities were still detectable in muscle fibres. These included the appearance within them of multiple arrays of sarcotubular profiles, focal areas lacking myofibrillar organization and mitochondria, abnormal mitochondrial aggregates showing crystalline inclusions, and extension of the postsynaptic densities along the full depth of junctional folds. Furthermore, targetoid-like areas were detected histochemically following recovery from the toxin-induced paralysis. The early extensive vacuolation of the sarcoplasm and the degeneration of junctional folds suggest a myotoxic effect of botulinum toxin. The late changes are likely to be (at least in part) related to the process of recovery following reinnervation.

Animals↗
PubMed1995

A new variant of sensory ataxic neuropathy with autosomal dominant inheritance.

We describe a Dutch family with sensory ataxia in two generations, late onset of symptoms (over the age of 40 years) and slow progression. Clinical, electrophysiological and sural nerve biopsy findings revealed a sensory polyneuropathy due to axonal degeneration of myelinated nerve fibres in four of five investigated siblings. Other neurological abnormalities in the affected family members consisted only of mild eye movement disturbances, probably due to cerebellar involvement. Five other family members were investigated and found unaffected. As the disease is inherited from the affected father to his sons and daughters, this is the first description of a probably autosomal dominant form of late onset hereditary sensory neuropathy with predominant sensory ataxia and minor other neurological abnormalities.

Cerebellar Ataxia↗