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Z Sahenk

Publications and source records attributed to Z Sahenk.

At least 55 records · Page 3Linked to original sources
PubMed1987

Studies on the pathogenesis of vincristine-induced neuropathy.

The pathogenesis of the peripheral neuropathy induced by vincristine is poorly understood, but interference of vinca alkaloids with microtubule assembly suggests that microtubule changes could be important. This possibility was studied by directly exposing the rat sciatic nerve to graded concentrations of vincristine sulfate. Microtubule length histograms prepared from randomly selected axons showed a unimodal distribution in vincristine and control axons. In vincristine-exposed axons, however, there was a shift to shorter length microtubules, and the mean measured length of microtubules (0.42 +/- 0.37 micron) was significantly (P less than 0.001) shorter than controls (0.67 +/- 0.55 micron). On cross-sections, the vincristine-exposed axons showed a decrease in the number of microtubules per square micrometer of axonal area compared to controls. These findings fit best with a loss of portion(s) of each microtubule and support the possibility that microtubules changes were associated with malorientation of microtubules and neurofilaments, accompanied by free vesicle accumulation and fragmentation of the smooth endoplasmic reticulum. These structural alterations would account for the previously observed abnormalities in axoplasmic transport and would also provide insight into the commonly observed peripheral neuropathy induced by vincristine treatment.

Animals↗
PubMed1987

Toxic neuropathies.

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Anti-Bacterial Agents↗
PubMed1985

Polyneuropathy and IgM monoclonal gammopathy: studies on the pathogenetic role of anti-myelin-associated glycoprotein antibody.

Attention has recently been directed toward patients having a polyneuropathy and a monoclonal IgM anti-myelin-associated glycoprotein (anti-MAG) antibody. The possibility of a pathogenetic role for the anti-MAG antibody in the evolution of the polyneuropathy and in the development of central nervous system signs, including tremor and ataxia, remains unresolved. In 5 patients with this syndrome whose clinical courses were followed closely, in 1 of whom a complete postmortem examination of the nervous system was performed, we made the following observations: the anti-MAG antibody did not localize to the compact layer of the myelin sheath in affected nerves, but did localize to areas of myelin splitting; anti-MAG antibody present in the sural nerve of an affected individual for 7 years was not associated with progressive pathology; anti-MAG antibody was not deposited in the central nervous system of an affected individual, although the antibody did bind to these same tissues in vitro; deposition of anti-MAG antibody observed at postmortem examination did not correlate with the degree of pathological change; and study of the peripheral nervous system favored a primary axonal neuropathy with secondary demyelination.

Adult↗
PubMed1985

Plasma exchange and prednisone in acute inflammatory polyradiculoneuropathy: a controlled randomized trial.

A controlled-randomized trial of plasma exchange combined with prednisone was compared to supportive care alone in patients with acute inflammatory polyradiculoneuropathy (AIP). The design of this study differs from other reported trials of plasma exchange in AIP because prednisone was used in the treatment group to prevent the possibility of antibody rebound. Furthermore, in this study, detailed muscle strength testing formed the principal basis for assessment of therapeutic efficacy while in the British, North American, and French studies, a functional assessment scale was used. Analysis of our data revealed no significant improvement in the treated group over the controls. The sample size, albeit small (12 treated and 13 controls), had the power (95% chance) to detect a change of two British Medical Research Council grades of strength between the groups. The difference in our results versus others (North American and French studies) probably reflects the adverse effects of prednisone on recovery in AIP. An additional consideration is that plasma exchange may have an overall modest effect on the course of AIP, less appreciated when individual muscles are tested compared to assessment by large functional categories.

Acute Disease↗
PubMed1985

Plasma exchange and prednisone in Guillain-Barré syndrome: a controlled randomized trial.

A controlled randomized trial of plasma exchange combined with prednisone was compared with supportive care alone in patients with Guillain-Barré syndrome (GBS). There was no significant improvement in the treated group over the controls. The sample size, albeit small (12 treated and 13 controls), had the power (95% chance) to detect a change of 2 British Medical Research Council grades of strength between the groups. The difference in our results and others that indicated a beneficial effect of plasma exchange may reflect an adverse effect of prednisone on recovery in GBS. Failure to find a benefit of plasma exchange in our patients also raises the possibility that GBS may be a heterogeneous disorder with humoral factors playing a role in some but not all patients.

Adolescent↗
PubMed1983

Studies on the morphologic alterations of axonal membraneous organelles in neurofilamentous neuropathies.

Alterations in the membraneous organelles were studied in two experimental neuropathies: 2,5-hexanedione (2,5-HD) and beta,beta'-iminodiproprionitrile (IDPN), both of which exhibit massive neurofilamentous accumulation. The membranous organelles were stained using the diaminobenzidine potassium ferrocyanide (DPF) method. In 2,5-HD, where there is a progressive impairment of fast axoplasmic transport, studies of the smooth endoplasmic reticulum (SER) revealed a fragmentation and disruption of the continuity of the longitudinally oriented interconnecting tubules and a significant increase in the number of free vesicles. In IDPN, where studies of fast transport have been normal, the longitudinal orientation of the smooth SER tubules was not disturbed although channels of longitudinally oriented tubules of SER were clustered with microtubules and mitochondria. This study suggests that in 2,5-HD the accumulation of vesicles in association with fragmentation and disorganization of the SER is one of the morphologic correlates of the impaired fast anterograde transport system.

Animals↗
PubMed1983

The experimental production of Renaut bodies.

Renaut bodies are loosely-textured whorled, cell-sparse structures found in the subperineurial space of peripheral nerves. Although described in 1881, their significance is still debated. Rats were placed in wire-mesh cages for 4 days to 6 weeks and the lateral and medial plantar nerves were sequentially removed. The initial change was the presence of endoneurial edema which dissected and displaced nerve fibers producing an endoneurial cleft. With the influx of fibroblasts, these clefts became discretely separated by circumferentially oriented processes. Over time the clefts enlarged and became filled with loosely-textured amorphous and fibrillar material as well as collagen. The Renaut bodies ranged from 15 to 80 microns in diameter. In this model the Renaut bodies formed at the maximum site of compression of the lateral plantar nerve. The fibroblasts appeared to be derived from the endoneurial connective tissue and were not the result of degenerating endoneurial structures. Renaut body formation was independent of axonal degeneration. The present study strongly suggests that Renaut bodies are a response to repeated mechanical stress.

Animals↗
PubMed1983

Changes in sciatic nerve cathepsin D after ligation or exposure to neurotoxins.

The content and distribution of cathepsin D, a lysosomal acidic endopeptidase, were determined by immunochemical methods in rat sciatic nerve near the site of a ligature or after exposure of animals to neurotoxins. In normal sciatic nerve, cathepsin D was localized predominantly in the perinuclear regions of Schwann cells. In ligated nerve, cathepsin D increased equally in both the proximal and distal nerve segments adjacent to the ligature. Although orthograde and retrograde axonal transport of cathepsin D may have contributed to this increase, immunocytochemical methods indicated that Schwann cells or other phagocytic cells accounted for the bulk of the increased cathepsin D content of nerve. Axonal function was nontraumatically altered by the administration of 2,5-hexanedione, acrylamide, B,B'-iminodipropionitrile or zinc pyridinethione. Exposure to any of these neurotoxins raised cathepsin D content throughout the sciatic nerve twofold or more, and greater amounts of immunoreactive cathepsin D in the cytoplasm of Schwann cells could be demonstrated immunocytochemically. These results indicate that changes in cathepsin D content of Schwann cells may be a reflection of their catabolic activity. The increased Schwann cell cathepsin D content in toxic axonopathies is further proof for an enhanced Schwann cell role as a phagocyte resulting from axonal injury.

Animals↗
PubMed1981

Acrylamide and 2,5-hexanedione neuropathies: abnormal bidirectional transport rate in distal axons.

Events taking place in the distal axon including delivery, turn-around and return of labelled materials toward the cell body were examined in 2,5-hexanedione (2,5-HD) and acrylamide-induced neuropathies. Retrograde transport profiles obtained from 2,5-HD as well as acrylamide intoxicated axons demonstrated a delay in the time of onset of accumulation and a decrease in the amount of returning activity to the distal collection segment. Integral analysis of the data indicated a decrease in bidirectional transport rate within the distal axons rather than a failure in the turn-around process at the nerve terminal.

Acrylamides↗
PubMed1981

The spontaneously diabetic BB Wistar rat. Morphologic and physiologic studies of peripheral nerve.

The spontaneously diabetic "BB" Wistar rat was examined for evidence of peripheral nerve abnormalities by a combined morphologic and physiologic approach. The studies were done on rats kept severely hyperglycemic and frequently ketotic. The peripheral nerves of the lower extremities, including the most distal nerves of the intrinsic foot muscles, revealed only minimal abnormalities by histologic and morphometric examination. Sciatic nerve conduction studies, however, measured over a 2-month period did not show a significant slowing in diabetics compared with age-matched controls, as well as between diabetics and weight-matched controls. In addition, fast anterograde axoplasmic transport studies were correlated with serum glucose results. Rats maintained severely hyperglycemic with or without ketosis had abnormal down flow rats of [3H]leucine compared to controls. Diabetic rats maintained with normal blood glucose levels showed no change in transport rates. These results suggested that persistent hyperglycemia in the "BB" Wistar rat produces significant physiologic but not significant structural abnormalities in the peripheral nerve.

Animals↗
PubMed1980

Axoplasmic transport in zinc pyridinethione neuropathy: evidence for an abnormality in distal turn-around.

Axoplasmic transport studies were done in rats with a zinc pyridinethione-induced dying-back neuropathy characterized by the accumulation of branched interconnected tubulovesicular profiles in the motor nerve terminals. Fast anterograde transport studies in sensory and motor systems were significantly reduced compared to controls but there was a wide variation in results and a lack of correlation with clinical involvement. Retrograde transport studies showed a delay in the time of onset and a reduction in the amount of retrograde transported materials. Analysis of the integrals of retrograde transport indicated that the defect was related to a failure in the turn-around process in the distal axon as opposed to a decreased rate of retrograde transport. Similar changes were not present in the proximal morphologically normal portion of the axon where retrograde transport was provoked with a crush injury.

Animals↗
PubMed1980

Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency.

A 1-month-old boy was admitted because of failure to thrive. He was floppy and had bilateral ptosis, diminished reflexes, and poor suck. He had aspiration pneumonia, developed seizures, and died at age 3 1/2 months. Laboratory data showed lactic acidosis, proteinuria, glycosuria and generalized aminoaciduria. He was an only child, and family history was negative. Muscle biopsy showed large clumps of granules positive with oxidative enzyme stains and increased lipid droplets. Ultrastructural studies showed large aggregates of mitochondria, many of which were greatly enlarged and contained disoriented or concentric whorls of cristae and paracrystalline inclusions. Cytochrome c oxidase was absent in fresh frozen sections by histochemical staining. By biochemical assay, cytochrome c oxidase (cytochrome aa3) was 6% of normal in muscle biopsy and undetectable in autopsy muscle; spectra and content of cytochromes showed lack of cytochrome aa3, decreased cytochrome b and normal cytochrome cc1. In kidney, cytochrome-c-oxidase activity was 38% of normal and spectra showed decreased cytochromes aa3 and b. The association of fatal infantile mitochondrial myopathy, lactic acidosis and renal dysfunction was previously reported by Van Biervliet et al and appears to be a distinct nosologic entity, one of the few biochemically defined mitochondrial myopathies.

Carnitine O-Palmitoyltransferase↗
PubMed1979

Analysis of fast axoplasmic transport in nerve ligation and adriamycin-induced neuronal perikaryon lesions.

Fast axoplasmic transport was examined in experimental nerve ligation and adriamycin-induced neuronal perikaryon lesions. Animals were sacrificed at precisely 3 and 4 h following the injection of [3H]leucine. In single ligated nerves, the 3 and 4 h down-flow rates, which include the time for neuronal processing of labelled material, were 379.2 +/- 23.51 and 370.8 +/- 26.93 mm/day, respectively, compared to the calculated rate of fast axoplasmic transport of 345.6 +/- 25.22 mm/day. In double-ligated nerves the down-flow rates were 364.8 +/- 40.32 and 342 +/- 32.2 mm/day, respectively, while the fast axoplasmic transport rate was 273.6 +/- 36.16 mm/day. In contrast, in adriamycin toxicity the down-flow rates were 363.9 +/- 21.54 and 378 +/- 14.69 mm/day with a normal calculated rate of fast axoplasmic transport of 420 +/- 18 mm/day. These studies illustrate that evaluation of two (or more) different time intervals can be used to assess the site of impaired delivery of labelled materials to the peripheral portions of the nerve. Furthermore, a single time interval examination of transport should not be equated with axoplasmic transport especially under pathological conditions.

Animals↗
PubMed1979

Ultrastructural study of zinc pyridinethione-induced peripheral neuropathy.

This study describes, for the first time, the neuropathy of zinc pyridinethione (ZPT) toxicity in rats. Although hind-limb weakness has been previously reported as a consequence of dietary ZPT ingestion in rats and rabbits, the cause of the paralysis has been unexplained. Sequential morphologic studies in rats fed a diet containing 166 ppm of ZPT revealed a dying-back neuropathy characterized by the early accumulation of tubulo-vesicular profiles in the motor nerve terminals. Continued exposure resulted in similar abnormalities in the intrasmuscular nerves and later in the peroneal and posterior tibial nerves and nerve branches to individual muscles. Axonal degeneration and regeneration followed the initial pathologic changes. There was relative sparing of the sensory nerve terminals of the muscle spindles. Central nervous system axons in the long descending tracts of the spinal cord and in the cerebellar vermis showed similar but quantitatively fewer axonal changes compared to the peripheral nerves. The central effects occurred only after prolonged administration of ZPT.

Animals↗
PubMed1978

Polyneuropathy from inhalation of N2O cartridges through a whipped-cream dispenser.

A generalized toxic polyneuropathy was identified in a 23-year-old woman after excessive intentional inhalation of compressed N2O delivery from cartridges through a whipped-cream dispenser. The chronology of the patient's N2O abuse correlated clearly with two episodes of recurrent polyneuropathy. The toxic effects were limited to the nervous system, primarily involving the peripheral nerves, although some signs suggested a possible effect on the cerebellum or its connections. The findings on sural nerve biopsy were nonspecific, characterized principally by axonal degeneration. Gas chromatographic analysis of the N2O cartridges dispensed through the whipped-cream canister revealed an exposure to N2O and 26 other compounds. Three of these, trichloroethylene, toluene, and phenol, are known neurotoxins.

Adult↗
PubMed1977

Alterations of fast axoplasmic transport in experimental methyl n-butyl ketone neuropathy.

Methyl n-butyl ketone (MBK) is known to produce a giant axonal neuropathy in man and experimental animals characterized pathologically by a gradual increase in the number of neurofilaments which become associated with focal areas of axonal swelling and thinning of the myelin sheath. Fast axoplasmic transport was studied in rats exposed to MBK. In 10 severely paralyzed rats exposed to MBK there was a significant impediment of fast axoplasmic transport following dorsal root ganglion injections (x +/- S.D. = 283.2 +/- 20.34 mm/day) compared to normal controls (417.6 +/- 23.78 mm/day). In rats undergoing injections into the ventral horn of the spinal cord there was a gradual impairment of the mean down flow rate for transport of [3H]leucine which correlated with the severity of the MBK induced neuropathy. Quantitative morphological determinations showed that the total number of neurotubules per unit cross-sectional myelin area and the number of neurotubules associated with mitochondria in swollen axons was unchanged from normal. The total number of mitochondria in randomly sampled axons varied significantly from controls but the absolute number of mitochondria associated with neurotubules was unchanged from normal. The results of these studies suggest that the impediment of fast axoplasmic transport may be related to the increased neurofilaments producing focal areas of axonal blockage.

Animals↗
PubMed1977

Polyradiculoneuropathy accompanying procainamide-induced lupus erythematosus: evidence for drug-induced enhanced sensitization to peripheral nerve myelin.

Factors involved in the development of an insidious polyradiculoneuropathy in association with a procainamide-induced, lupuslike syndrome were explored. A 73-year-old man with this clinical syndrome had sural nerve changes consisting of loss of large myelinated fibers with evidence of remyelination and Schwann cell proliferation. The patient's lymphocytes showed marked incorporation of tritiated thymidine when cultured with either procainamide or extracts of human peripheral nerve myelin, and there was an enhanced response with the combination. We also found that procainamide-treated rats showed acceleration of lymphocyte sensitization to peripheral nerve myelin as judged by the early development of inhibition of macrophage migration and positive skin tests to extracts of peripheral nerve myelin. These studies suggest that procainamide can enhance lymphocyte sensitization to peripheral nerve myelin and may have predisposed this individual to development of a polyradiculoneuropathy.

Aged↗