Search PubMed⌕ Search

Biomedical subjects

S Monaco

Publications and source records attributed to S Monaco.

At least 19 recordsLinked to original sources
PubMed1995

Experimental induction of myelin changes by anti-MAG antibodies and terminal complement complex.

We investigated the role of anti-myelin-associated glycoprotein (MAG) IgM and complement (C) in the pathogenesis of myelin alterations occurring in patients with anti-MAG-associated polyneuropathy. For this purpose, we separately studied the effects of anti-MAG antibodies and terminal C complex (TCC) after injection into the rabbit sciatic nerve. The two different local treatments produced identical ultrastructural abnormalities such as intramyelinic edema, myelin vesiculation and, in particular, separation of the major dense lines with the formation of widely spaced myelin, a peculiar feature encountered in human peripheral nerve disorders with circulating anti-myelin monoclonal IgM. In nerves treated with anti-MAG IgM ultrastructural myelin alterations were concurrent with activation of the rabbit's own C to the formation of TCC. Contrary to the immunological and ultrastructural findings obtained in C-sufficient animals, in C6-deficient rabbits injected with anti-MAG IgM no myelin alterations nor C completion were observed. This study identifies anti-MAG IgM as the mediator and the C as the effector of myelin changes observed in the present model and, for extension, in human neuropathies associated with anti-MAG IgM.

Animals↗
PubMed1995

Expression and distribution of GAP-43 in human astrocytes in culture.

By combining mRNA analysis and immunocytochemistry, we investigated the expression of the growth associated protein 43 (GAP-43) in enriched populations of astrocytes, obtained from mixed cultures of human fetal brains. Total cellular RNA was extracted from cell pellets and reverse transcribed into cDNA; cDNA was subjected to PCR amplification using primers specific for GAP-43 and PCR products were separated through polyacrylamide gels. Double immunofluorescence staining was performed on dissociated cell cultures using antibodies to glial fibrillary acidic protein (GFAP) and to GAP-43. Results showed that both transcription and translation for GAP-43 occur in cultured astrocytes. GAP-43 immunoreacting material was detected in the cell processes and diffusely in the cytoplasm of GFAP-positive astrocytes, during early stages of maintenance in vitro. In older cultures, GAP-43 immunoreactivity persisted in a large percentage of cells, with a tendency to accumulate in perinuclear areas. These observations provide evidence that GAP-43 is not restricted to neuronal cells. The close spatial association with cytoskeletal constituents, as observed in astrocytes, suggests a role for this protein in the control of cell shape, motility and adhesion processes.

Astrocytes↗
PubMed1994

Increased serum levels of ICAM-1, ELAM-1 and TNF-alpha in inflammatory disorders of the peripheral nervous system.

Endothelial intercellular adhesion molecule-1 (ICAM-1) and glycoprotein E-selectin (ELAM-1) allow the homing of leukocytes to inflammation sites. A circulating form of ICAM-1 markedly increases in inflammatory CNS disorders. In the present study, the serum levels of ICAM-1, ELAM-1 and tumor necrosis factor-alpha (TNF-alpha) were measured in patients with acute (AIDP) and chronic (CIDP) inflammatory demyelinating polyneuropathies and cryoglobulinemic neuropathy (CGN). Immunoenzymometric assays revealed increased sICAM-1 levels in some of these patients; furthermore, high titres of ELAM-1 and TNF-alpha were detected in two patients with AIDP and one patient with CGN. Our data extend previous observations on inflammatory PNS disorders by showing that, in addition to ICAM-1, ELAM-1 also represents a useful marker of endothelial activation and that, taken together, the two molecules may serve as an indicator of specific pathogenetic mechanisms.

Adult↗
PubMed1992

MHC-positive, ramified macrophages in the normal and injured rat peripheral nervous system.

Resident endoneurial macrophages form a prominent, but little recognized component of the PNS. We have studied immunocytochemically the distribution, morphology and immunophenotype of endoneurial macrophages in several normal peripheral nerves of the rat. In addition, we investigated the macrophage response following crush injury of the sciatic nerve. Resident endoneurial macrophages had a ramified morphology with processes oriented parallel to the long axis of nerve fibres. They were positive for several monocyte/macrophage markers such as ED1, ED2 and the recently-described MUC 101 and MUC 102 antibodies. They furthermore expressed the complement type three receptor, the CD4 antigen and MHC class I and II molecules. These results were consistent in all the peripheral nerves studied. In addition, 1000 rad of gamma-irradiation led to a strong reduction in the number of MHC class II-positive ramified cells in the peripheral nerves similar to that observed in other peripheral organs such as the heart. A considerable percentage of resident macrophages in the PNS and/or their precursor cells are therefore radiosensitive and could be related to the lineage of dendritic cells. Following crush injury, ED1-3-, OX-42-, MUC 101- and MUC 102-positive round macrophages were observed from 24 h postlesion onward at the site of trauma. In the distal part, they were observed to form strings of round, foamy macrophages probably involved in myelin phagocytosis. In contrast, the number of MHC class II-positive resident macrophages was only slightly increased at the site of trauma and in the distal part. These cells transformed from a ramified to a round morphology, but did not appear as typical strings of foamy macrophages. These results demonstrate that the PNS is provided with a resident macrophage population analogous in many respects to microglial cells in the CNS. These constitutively MHC class II-positive PNS microglial-like cells could act as the major antigen-presenting cells in the peripheral nerve. They may thus constitute a local immune defense system of the PNS with a function similar to that of microglial cells in the CNS.

Animals↗
PubMed1992

AZT-induced mitochondrial myopathy.

Histochemical, electron microscopy and biochemical studies were performed on muscle biopsy specimens from 11 AIDS patients treated with zidovudine. A peculiar association of structural abnormalities and mitochondrial dysfunction was found. Focal cytochrome c oxidase (COX) deficiency was evident in muscle sections from 9 patients, 8 of whom had received long-term treatment while one had been treated for 1 month only. Electron microscopy showed changes in number, size and structure of mitochondria. Biochemical studies proved partial COX and succinate cytochrome c reductase (SCR) deficiency in 4 patients; one patient had only reduced SCR activity. Our data confirm that AZT therapy can cause toxic myopathy with mitochondrial dysfunction.

Adult↗
PubMed1992

Complement neoantigen and vitronectin are components of plaques in amyloid AL neuropathy.

We studied three patients with late onset, chronic sensorimotor and autonomic neuropathy in course of plasma cell dyscrasia with Bence Jones proteinuria. Histopathological findings of nerve biopsies consisted in diffuse loss of myelinated and unmyelinated fibers associated with perivascular deposits of amorphous material with physico-chemical and ultrastructural features of amyloid. By immunohistochemistry, light chains of the same type as Bence Jones protein, components of the classic and lytic pathways of the complement and vitronectin were detected at the level of amyloid nodules. The colocalization of complement neoantigen and vitronectin suggests that this complex derives from the circulation. The elucidation of the chemical composition of amyloid might shed some light in the pathogenesis of these disorders.

Amyloidosis↗
PubMed1992

Inherited neuroaxonal dystrophy in C6 deficient rabbits.

We report the occurrence of a progressive neurological syndrome clinically characterized by subacute motor neuropathy in offspring of C6 deficient rabbits. On the basis of the pedigree analysis, the disease appears to be genetically transmitted, most probably with an autosomal recessive mode of inheritance. Pathological studies of affected animals revealed: transmitted, most probably with an autosomal recessive mode of inheritance. Pathological studies of affected animals revealed: 1) severe axonal degeneration in the sciatic nerve system involving mainly motor fibers; 2) occasional peripheral axonal enlargement closely associated with axonal degeneration; 3) presence of structured abnormal material in normal-size myelinated fibers of central nervous system (CNS) and peripheral nervous system (PNS); and 4) widespread occurrence of dystrophic axons and axonal spheroids in the gray matter of CNS. By ultrastructural examination, dystrophic axons are filled with tubulovesicular material, stalks of parallel membranes and dense bodies similar to what is described in human neuroaxonal dystrophies (NAD). The disease manifested by C6 deficient rabbits may represent an animal model of primary human NAD.

Animals↗
PubMed1991

Cytoskeletal changes induced by 2,5-hexanedione on developing human neurons in vitro.

Dissociated dorsal root ganglion cells from human fetuses were exposed to 2,5-hexanedione (2,5-HD) for 2 weeks. Morphological changes induced by 2,5-HD consisted in focal neurofilament (NF)-containing enlargements preferentially located in distal, preterminal regions of unmyelinated fibers. Tangles of NF were also observed in the perikarya of nerve cells. Morphometric analysis disclosed that the cross-sectional areas of the 2,5-HD treated axons were 30% smaller than those of control axons. This alteration was associated with reduction of number of NF per unit area. These findings demonstrate that 2,5-HD treatment induces a generalized disorganization of neuronal and axonal NF responsible for focal enlargements as well as atrophic changes of unmyelinated fibers.

Axons↗
PubMed1991

Computer-assisted work station timing analysis of instrument labor efficiency.

Labor use ratings assigned to instruments by the Workload Recording Method (WRM) do not change with batch size or walk-away time use. The authors evaluated the effect of both on the labor use of the analyzers Paramax B6100 (Baxter Paramax, Irvine, CA) and Ektachem 700 (Eastman Kodak, Rochester, NY) by timing all worked and walk-away intervals on both instruments. Extrapolation of the data to a workload of slightly more than 1.1 million tests showed that reapportionment of tests to various batch sizes caused Paramax-Ektachem labor cost differences to fluctuate between $37,254 and $34,995. When the minimum usable walk-away interval length was varied from 1 to 20 minutes, Ektachem savings over Paramax increased from $8,700 to $61,400. The WRM predicted a constant $29,050 labor cost advantage for Ektachem over Paramax. If other instruments show similar labor use characteristics with respect to batch size and walk-away utility, laboratory managers who do not consider these factors may fail to select the most cost-effective instruments for their laboratories.

Computer Systems↗
PubMed1990

Giant axonopathy characterized by intermediate location of axonal enlargements and acceleration of neurofilament transport.

It has previously been shown that 2,5-hexanedione (2,5-HD) and its 3,4-dimethyl derivative (3,4-DMHD) induce neurofilamentous accumulations at prenodal sites in distal and proximal, respectively, regions of peripheral axons. For 2,5-HD, neurofilament (NF) transport is accelerated and this is thought to be directly related to the appearance of the axonal enlargements. For 3,4-DMHD, however, the rate of NF transport cannot be assessed owing to the very proximal position of NF accumulation. In the present study, it is shown that administration to rats of 3-methyl-2,5-hexanedione, the structural 'average' of 2,5-HD and 3,4-DMHD, induces NF accumulations at midway axonal positions of the sciatic and optic systems, and results in acceleration of NF in the sections of optic axons proximal to the enlargements. These results suggest that a common mechanism underlies all gamma-diketone neuropathies, and that the proximodistal pattern of axonal enlargements represents pharmacokinetic variables rather than differences in mode of action. The neurotoxicity of gamma-diketones probably arises from pyrrolation of lysine epsilon-amino groups in crucial regions of NF or related proteins responsible for maintaining the proper supramolecular organization of the cytoskeleton. Acceleration of NF transport appears to be a common characteristic of chemically induced axonopathies, regardless of location, and this is contrary to the theory that gamma-diketone-induced NF accumulation results primarily from a progressive cross-linking of NF occurring subsequent to pyrrole formation.

Actins↗
PubMed1990

Complement-mediated demyelination in patients with IgM monoclonal gammopathy and polyneuropathy.

We investigated the role of complement in the pathogenesis of the demyelinating polyneuropathy that occurs in some patients with IgM monoclonal gammopathy. Seven patients with chronic sensorimotor polyneuropathy and IgM monoclonal gammopathy were examined. In six patients, the monoclonal protein recognized an epitope shared by myelin-associated glycoprotein and two peripheral-nerve glycolipids, whereas in one patient, IgM bound to an unidentified myelin antigen. Direct and indirect immunofluorescence and immunoperoxidase assays showed colocalization along the myelin sheaths of peripheral-nerve fibers of monoclonal protein with complement components C1q, C3d, and C5. In addition, terminal-complement complex that was not associated with S protein was detected in myelin sheaths. It appeared that alterations in myelin geometry caused by the separation of myelin lamellae corresponded to sites at which terminal-complement complex was deposited. We conclude that demyelination in polyneuropathy associated with IgM monoclonal gammopathy may be mediated by complement.

Aged↗
PubMed1990

AIDS--associated predominantly sensory neuropathy. The role of herpes viruses.

Three patients with predominantly sensory neuropathy in course of HIV-1 infection are reported. In all cases ultrastructural examination showed herpes virus-like particles in the axoplasmic matrix of myelinated fibers and in endoneurial macrophages. In 2 cases clinical patterns of posterior column involvement were observed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Axonal transport of neurofilament is accelerated in peripheral nerve during 2,5-hexanedione intoxication.

The neurotoxic compound 2,5-hexanedione (2,5-HD) causes an axonopathy characterized by the presence of neurofilament (NF)-containing enlargements in the preterminal segments of central and peripheral axons. The 2,5-HD axonopathy is a good model for human acquired and inherited giant axonal neuropathies. Recently, we reported that following 2,5-HD administration, axonal transport of NF is markedly and selectively accelerated in the primary visual system. We have now studied slow axonal transport in the sciatic system of rats intoxicated with 0.5% 2,5-HD in drinking water. Following radiolabeling, transported proteins were examined after polyacrylamide gel electrophoresis and fluorography. The bulk of radiolabeled NF subunits was located 30-50 mm from the spinal cord in 2,5-HD treated animals and 10-25 mm in controls. The rate of transport of the three NF subunits was 0.7 mm/day in controls and 1.2 mm/day in 2,5-HD treated animals. The rate of transport of tubulin was not significantly changed. Electrophysiological studies of soleus nerve and muscle showed no evidence of denervation after 6 weeks of intoxication. It is concluded that, following 2,5-HD administration, transport of NF is preferentially accelerated in both central and peripheral axons. A pathogenetic mechanism based on the acceleration of NF transport is proposed, which may explain the formation and the distal or proximal location of NF-containing axonal enlargements in giant axonopathies.

Action Potentials↗
PubMed1989

Experimental increase of neurofilament transport rate: decreases in neurofilament number and in axon diameter.

In 2,5-hexanedione (2,5-HD)-induced axonal neuropathy, the rate of neurofilament (NF) transport increases in optic axons. To test the prediction that increases in the rate of polymer transport in any one locality of the axon lead directly to a decrease in the number of NF in that locality, NF and microtubules (MT) were quantitatively analyzed in axonal cross sections. In 2,5-HD axons the number of NF was 38% of that in control axons while the number of MT was not significantly changed; it appears that the drug treatment decreases NF number in the proximal axon regions, most directly through an increase in rate of NF transport. In those regions, the cross-sectional areas of the 2,5-HD-treated axons were 45% smaller than those of control axons; although the axons had shrunk in diameter, they retained their normal cylindrical shapes as measured by the index of circularity. Reduced internal expansive forces in the axon, working in conjunction with the normal external compressive forces, appear to reduce the radius of the axon. Quantitative analyses demonstrated that the average and the maximum lateral spacings between NF-NF, NF-MT, and MT-MT were all 30% larger in 2,5-HD-treated axons than in control axons. This suggests that polymers are relatively free to move laterally away from one another and to fill the available space within the axon. These observations are not consistent with models wherein 2,5-HD acts to crosslink the NF into an immobile network that can no longer advance within the axon. Instead, it appears more likely that 2,5-HD acts selectively on the interaction between some NF and the slow transport mechanism to increase the rate of NF transport.

Animals↗
PubMed1988

Polyneuropathy in hypereosinophilic syndrome.

We investigated two patients with the idiopathic hypereosinophilic syndrome and peripheral neuropathy. Clinical, EMG, and pathological findings were consistent with axonal polyneuropathy. Morphologic changes of the nerve biopsies suggested axonal damage secondary to increased endoneurial pressure from leakage of capillaries. We postulate that endothelial cell damage, followed by nerve edema, is the first step in the pathogenesis of peripheral neuropathy in these patients.

Biopsy↗
PubMed1987

Binding of monoclonal anti-myelin-associated glycoprotein antibodies to human foetal peripheral neurons in culture.

Dorsal root ganglion cells, obtained from 8-10-week human foetuses, were isolated by enzymatic procedure and grown on poly-L-lysine-coated coverslips. Most of the cultured cells showed the ultrastructural and immunological features of normal peripheral neurons. By immunocytochemistry neurons reacted with IgM antibodies with specificity for myelin-associated glycoprotein (MAG) from patients affected with IgM k gammopathy and peripheral neuropathy. The antigen was located on the plasmalemma of both perikarion and axon. We suggest that anti-MAG antibodies do not recognize neuronal MAG, but rather an epitope shared with different glycoproteins.

Antibodies, Monoclonal↗