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Biomedical subjects

R Nemni

Publications and source records attributed to R Nemni.

At least 37 records · Page 2Linked to original sources
PubMed1997

Motor nerve biopsy studies in motor neuropathy and motor neuron disease.

The clinical presentation of motor neuropathy often resembles that of motor neuron disease, sometimes leading to an erroneous diagnosis. Moreover, the underlying pathological process in motor neuropathy has been rarely investigated and there are no systematic studies of the affected motor nerves. We describe a new motor nerve biopsy procedure, performed in 15 patients: 6 with motor neuropathy and 9 with motor neuron disease. The motor branch from the anterior division of the obturator nerve to the gracilis muscle in the thigh was biopsied. In both groups of patients the motor nerves exhibited depletion of myelinated nerve fibers. In motor neuropathy there was a significantly higher density of regenerative clusters of small myelinated fibers in comparison to motor nerves from patients with motor neuron disease. In addition, in 3 patients with motor neuropathy there was evidence for demyelination with thinly myelinated axons and small onion bulb formations. These pathological studies of motor nerve biopsies can help to differentiate motor neuropathy from motor neuron disease.

Adult↗
PubMed1997

Axonal neuropathy associated with interferon-alpha treatment for hepatitis C: HLA-DR immunoreactivity in Schwann cells.

A 44-year-old man developed a peripheral neuropathy during treatment with interferon-alpha for chronic hepatitis C. The onset was insidious, beginning symmetrically in the hands with paresthesia. Neurophysiological investigation revealed a predominantly sensory axonal neuropathy. A sural nerve biopsy confirmed primary axonal damage. Immunofluorescence studies showed increased expression of HLA-DR molecules prevalently on Schwann cells of non-myelin-forming type.

Adult↗
PubMed1997

Circulating fragments of myelin-associated alpha 6 beta 4 integrin in Guillain-Barré syndrome.

Guillain-Barré-Strohl syndrome (GBS) is an acute peripheral neuropathy causing reversible myelin damage. alpha 6 beta 4 is a laminin receptor of Schwann cells and myelin. Along with myelin breakdown, alpha 6 beta 4 immunoreactivity might be detected in patients' sera and provide a marker for monitoring GBS course. MAbs to beta 4 and alpha 6 were used in an ELISA test to detect protein in GBS serum samples as in normal individuals. In 66% GBS patients, alpha 6 beta 4 immunoreactivity was detected while controls were negative. The level of beta 4 was followed in different patients and found to fluctuate, always being positive in at least one sample. Treatment lowered immunoreactivity in two beta 4-positive GBS sera. Then, circulating alpha 6 beta 4 fragments represent a novel marker of extensive peripheral myelin damage and may be used to validate clinical diagnosis of GBS, evaluate its course and activity.

Acute Disease↗
PubMed1997

Atypical hereditary neuropathy with liability to pressure palsies (HNPP): the value of direct DNA diagnosis.

We report two patients with suspected hereditary liability to pressure palsies. Neurophysiological studies showed a mixed axonal-demyelinating sensory-motor polyneuropathy with focal slowing of conduction velocities at the common sites of entrapment. Morphological studies on sural nerve biopsy from the proband showed active axonal regeneration without typical tomacula. Molecular analysis confirmed the presence of a deletion of chromosome 17p11.2 in both patients. Our observation confirms the heterogeneity of hereditary liability to pressure palsies and the relevance of DNA testing for the diagnosis of this hereditary neuropathy.

Adolescent↗
PubMed1997

Toward a transgenic mouse model of remyelination.

The molecular mechanisms necessary for remyelination by oligodendrocytes remain unexplored. We previously characterized a myelin basic protein promoter-lacZ (MBP-lacZ) transgene whose expression is regulated uniquely during development, and also in pathological situations, suggesting that it may be a useful reporter of molecular mechanisms during remyelination. As a first step toward creating a transgenic mouse model of remyelination, we cultured oligodendrocytes from these transgenic mice and showed that expression of MBP-lacZ appeared in parallel with a marker of oligodendrocyte maturation, galactocerebroside (GC). In addition, basic fibroblast growth factor blocked the expression of both MBP-lacZ and GC in these cells. Therefore, expression of MBP-lacZ reflects not only the developmental stage of oligodendrocytes, but also extrinsic influences on oligodendrocytes. These data suggest that MBP-lacZ may be a useful marker in transgenic mouse models of remyelination.

Animals↗
PubMed1997

Intravenous immunoglobulin treatment in multifocal motor neuropathy and other chronic immune-mediated neuropathies.

This review deals with the use of intravenous IVIg immunoglobulins in the treatment of chronic immune-mediated neuropathies: multifocal motor neuropathy, chronic inflammatory demyelinating polyneuropathy, neuropathies associated with monoclonal gammopathies. A particular attention is given to case series and trials which compare IVIg to other therapies, such as steroid treatment immunosuppressors and plasma exchange. At present clinical and instrumental data seem to indicate the short term efficacy of IVIg in multifocal motor neuropathies, especially as early treatment; further studies are need in order to prove its long term efficacy in this disease. Concerning chronic inflammatory demyelinating polyneuropathies, short term IVIg efficacy is comparable to that of plasma exchange and in the long term most patients need repeated treatments. Most patients respond to the initial therapy and the initial nonresponders usually improve with a second treatment modality.

Autoimmune Diseases↗
PubMed1997

Autoimmunity and diabetic neuropathy.

Autoimmunity has been implicated in the pathogenesis of diabetic neuropathy. A number of putative target antigens have been investigated in the attempt to find a relationship between the presence of autoantibodies and the presence of neuropathy. Attention has been given to antibodies against nerve growth factor, adrenal medulla, sympathetic and parasympathetic structures, glutamic acid decarboxylase and phospholipids. Data in the literature do not support a clear-cut difference in frequency of positivity or titres between patients with or without diabetic neuropathy. Moreover, it is not clear whether autoantibodies to the above-mentioned antigens, whenever present, play a role in causing nerve damage or if they simply reflect the presence of nerve damage. Longitudinal studies are needed to clarify some conflicting data in the literature.

Adrenal Medulla↗
PubMed1996

Beta 4 integrin and other Schwann cell markers in axonal neuropathy.

Schwann cell gene expression is dynamically regulated after peripheral nerve injury and during regeneration. We hypothesized that the changes in protein expression described after rat peripheral nerve injury could be used to identify single Schwann cell-axon units in human axonal neuropathy. Therefore, we performed immuno-fluorescence staining on sections of injured rat sciatic nerves compared with sections of neuropathic human sural nerves. We chose the markers beta 4 integrin, P0 glycoprotein, and glial fibrillary acidic protein (GFAP) to characterize Schwann cells, and neurofilament-heavy (NF-H) to recognize axons. Normal rat or human myelin-forming units demonstrated a sharp ring of beta 4 staining at their outer surface, P0 staining in the myelin sheath, and NF-H staining in the axon. Acutely denervated rat units transited from broken rings of beta 4 and P0 staining, to diffuse beta 4 and absent P0 and NF-H staining. Chronically denervated rat Schwann cells re-expressed beta 4 more highly, but in a diffuse, non-polarized pattern. In contrast, regenerating units re-expressed beta 4, P0, and NF-H; beta 4 staining was polarized to the outer surface of Schwann cells. Finally, GFAP staining increased progressively after injury and decreased during regeneration in the distal nerve stump. In neuropathic human sural nerves, we identified units exhibiting each of these beta 4, P0, and NF-H staining patterns; the proportion of each pattern correlated best with the extent and chronicity of axonal injury. Thus, synchronous injury of rat sciatic nerve predicts patterns of Schwann cell marker expression in human axonal neuropathy. In addition, the unique changes in the polarity of beta 4 integrin expression, in combination with changes in P0 and NF-H expression, may distinguish normal from denervated or reinnervated myelin-forming Schwann cells in human sural nerve biopsies.

Adult↗
PubMed1996

Alpha6 beta4 and alpha6 beta1 integrins in astrocytomas and other CNS tumors.

Laminin may alter the biological behavior of gliomas. Therefore, we investigated the expression of two laminin receptors, alpha6 beta1 and alpha6 beta4 integrins in normal brain, astrogliotic brain, and astrocytomas as compared to other central nervous system (CNS) tumors. In most CNS tumors, the expression of these integrins was unchanged in neoplastic as compared to normal counterpart cells. In contrast, increased numbers of reactive and neoplastic astrocytes expressed beta4 integrin as compared to normal astrocytes, whereas alpha6 and beta1 integrin expression did not change. Conversely, lower numbers of astrocytoma blood vessels expressed beta4, whereas all blood vessels in normal brain expressed beta4. These data suggest that the profile of laminin receptors changes in neoplastic astrocytes and in astrocytoma blood vessels; this change may play an important role in astrocytoma pathogenesis.

Astrocytoma↗
PubMed1995

Evidence of peripheral axonal neuropathy in primary restless legs syndrome.

Restless legs syndrome (RLS) is a well-defined clinical entity characterized by an unpleasant creeping sensation arising in the legs with an irresistible need to move them. The trouble is more pronounced when the affected people lie in a prolonged rest position and try to fall asleep. It is known that RLS may be consequent to systemic disorders and to diseases affecting the central or peripheral nervous system. The International Classification of Sleep Disorders states that peripheral neuropathy should be ruled out by medical history and clinical grounds before diagnosing primary RLS (pRLS). The present study extended peripheral nerve investigation in eight consecutive pRLS patients with normal neurological examination results and showed that all patients exhibited two or more electrical, psychophysiological, and/or morphological features of peripheral axonal neuropathy. Morphometric analysis of sural nerve showed a significant reduction in myelinated fiber density and g ratio (axon diameter/fiber diameter) in the pRLS group compared with eight control biopsy specimens. These results suggest that axonal neuropathy is often present in patients with RLS. A comprehensive peripheral nerve investigation should be considered in RLS patients.

Adult↗
PubMed1995

Connective tissue proliferation and growth factors in animal models of Duchenne muscular dystrophy.

The difference in the lifespan of dy and mdx mice could be due to different muscle regeneration capabilities. In mdx an involvement of bFGF in stimulating regeneration has been postulated. The aim of our work was to detect the presence, and to study the distribution, of muscular and connective tissue growth factors in mdx and dy mice at different stages of muscle pathology. From 7 to 10 weeks of age the difference between the two dystrophic mice becomes evident. At 13 weeks the dy mouse presents a predominance of fibrosis and degenerative muscular phenomena while the main pathological feature in mdx mouse is the muscle regeneration. In both animal models fibrosis proliferation is correlated to the presence of EGF and its receptor and TGF beta 1. bFGF was localized to regenerating and degenerating fibers in both dy and mdx mice. The bFGF presented a normal pattern in mdx mice at 20 weeks when regenerative and degenerative phenomena were no longer present. Our data suggest that growth factors could influence the outcome of muscular regenerative and degenerative processes.

Animals↗
PubMed1994

Autoantibodies to glutamic acid decarboxylase in palatal myoclonus and epilepsy.

We report the presence of serum autoantibodies directed against glutamic acid decarboxylase in a patient with epilepsy and palatal myoclonus not associated with brain lesions. Glutamic acid decarboxylase antibody reactivity was dependent on the presence of carboxy-terminal amino acids, similar to that reported in patients with stiff-man syndrome. Marked reduction in the frequency of epileptic attacks and improvement in palatal myoclonus occurred when benzodiazepine was administered and phenytoin was gradually tapered. Testing for anti-glutamic acid decarboxylase antibodies may be indicated in patients with palatal myoclonus and with convulsive disorders refractory to therapy.

Adult↗
PubMed1994

Clinical and neurophysiological assessment of immunoglobulin therapy in five patients with multifocal motor neuropathy.

High dose intravenous immunoglobulin (IVIg) is an effective treatment for demyelinating neuropathies. IVIg was given to five patients with multifocal motor neuropathy, a motor neuropathy showing a clinical syndrome of asymmetrical weakness and amyotrophy, electrophysiological evidence of motor conduction block and, in many cases, high titres of serum anti-GM1 antibodies. Muscle strength was evaluated by a conventional score before and after each IVIg course. In all patients there was relevant improvement on muscle strength after each immunoglobulin course, but in most cases the clinical benefits partially declined after three to eight weeks. At the eight month follow up, however, the pretreatment examination showed a significant improvement compared with the initial evaluation. The effects of each IVIg course were still present after a number of courses. Electrophysiological study revealed a decrease in conduction block in one or more nerves in all patients. However, conduction block was unchanged or increased in other sites. IVIg treatment did not affect anti-GM1 antibody titres.

Adult↗
PubMed1994

Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating neuropathy not responsive to other treatments.

Nine patients with chronic inflammatory demyelinating poliradiculoneuropathy (CIDP) were treated with intravenous immunoglobulin. All patients had been previously treated with prednisone and/or plasma exchange without effect. Objective improvement in clinical condition occurred in six patients. One patient became refractory after two treatment courses, two patients had no response. The results indicate that intravenous immunoglobulin has beneficial effects in a high percentage of patients with CIDP who are unresponsive to other treatments.

Adult↗
PubMed1994

Beta 4 integrin expression in myelinating Schwann cells is polarized, developmentally regulated and axonally dependent.

In developing and regenerating peripheral nerve, Schwann cells interact with axons and extracellular matrix in order to ensheath and myelinate axons. Both of these interactions are likely to be mediated by adhesion molecules, including integrins, which mediate cell-cell and cell-extracellular matrix interactions. Recently, the beta 4 integrin subunit was reported to be expressed by Schwann cells in peripheral nerve. We have examined the expression of beta 4, beta 1 and their common heterodimeric partner, the alpha 6 integrin subunit, in developing and regenerating rat peripheral nerve. beta 4 and alpha 6 are enriched in peripheral nerve and they co-localize at the abaxonal surface of myelinating Schwann cells, opposite the Schwann cell basal lamina, which contains possible ligands of alpha 6 beta 4. In contrast, beta 4 and alpha 6 are expressed in a different pattern in non-myelinating Schwann cells. The level of beta 4, but not alpha 6 or beta 1 mRNAs, increases progressively in developing nerves, reaching a peak in adult nerves well after the peak of the myelin-specific mRNAs. After axotomy, the expression of beta 4 mRNA and protein, but not alpha 6 or beta 1 mRNAs, fall rapidly but subsequently are reinduced by regenerating axons. Similarly, in cultured Schwann cells, the expression of beta 4 mRNA, but not alpha 6 mRNA, is significantly modulated by forskolin, a drug that elevates cAMP and mimics some of the effects of axonal contact. beta 4 integrin expression in Schwann cells, therefore, is regulated by Schwann cell-axon interactions, which are known to be critical in determining the Schwann cell phenotype. Furthermore, the polarized expression of alpha 6 beta 4 to the abaxonal surface of myelinating Schwann cells suggests that alpha 6 beta 4 may mediate in part the morphological changes required of Schwann cells in the process of myelination in the peripheral nervous system.

Amino Acid Sequence↗