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PubMed1984

Delayed neurotoxicity produced by an organophosphorus compound (Sumithion). A case report.

A case of late-onset manifestation of organophosphorous insecticide poisoning is described. The patient was a 70-year-old female who ingested 40 ml Sumithion emulsion (50% fenitrothion). At first, no toxic symptoms were apparent. However, 48 h after ingestion certain signs became apparent. An impediment in consciousness was observed. Fasciculation and muscular weakness were noted, while plasma and urinary 4-nitro-3-methylphenol (NMC), the degradation product of Sumithion, reached a maximum. Neither atropine sulfate nor PAM (pyridine 2-aldoxime methiodine) were effective. For 3 weeks the patient required ventilatory support, and consequently her muscle strength and neurological status gradually recovered with falling NMC levels.

Aged↗
PubMed1995

The temporal relationship between intraocular pressure and extraocular muscle activation in cats.

The temporal relationship between intraocular pressure and extraocular muscle activation was studied in cats in response to the administration of the depolarizing muscle relaxant, succinylcholine (i.e. bolus doses of 0.1 and 1.0 mg/kg). Simultaneous changes in intraocular pressure, extraocular muscle force, extraocular electromyograms (EMGs), limb muscle EMGs and hindlimb muscle afferent activity were recorded. Increases in intraocular pressure were associated with extraocular muscle activation and had two components: (1) an initial abrupt increase (lasting seconds) which correlated with fasciculations within the extraocular and hindlimb muscles; and (2) a latter more sustained component (minutes) presumably due to tonic muscle activation which correlated with increases in hindlimb muscle afferent activity (e.g. due to sustained activation of bag 1 intrafusal fibers by succinylcholine). In a separate group of animals, in which the extraocular muscles were detached from the right eye bilateral intraocular pressures were measured: depolarization by succinylcholine caused a significant increase in intraocular pressure only for the eye with intact muscles. Thus, increases in intraocular pressure following the administration of succinylcholine are directly related to the changes in extraocular muscle tension which is dependent on both tonic and phasic muscle fiber responses.

Animals↗
PubMed1978

Experimental barbiturate dependence. I. Barbiturate dependence development in rats by drug-admixed food (DAF) method.

A method for testing a rat's physical-dependence liability to sedaditive-hypnotic agents and for evaluating that dependence was studied by using the method. Rats received phenobarbital- or barbital-admixed food on a graded-increase dosage schedule over 30-40 days. Manifestations of CNS-suppressing action of either drug (e.g., systemic muscle relaxation, motor incoordination, staggering gait, and ptosis) persisted day and night during the drug medication. Twenty-four to 48 h after withdrawal of either drug, abstinence symptoms (e.g., muscle fasciculation, nuchal twitching, vocalization, increased irritability, ataxia, hyperthermia, and clonic-tonic and grand mal-type convulsions) were evidenced in all animals (N = 6), some of which died after convulsions. These withdrawal signs in rats were classified and found to be closely correlated with the magnitude of weight loss during the withdrawal. The calssification provides a basis for quantitatively assessing physical-dependence liability. The data obtained in the present study suggest that rats, like dogs and monkeys, are suitable experimental animals for tests in early stages of dependence liability, and that the administration of drug-admixed food is a useful method of developing dependence on both barbiturate and morphine-type drugs.

Animal Feed↗
PubMed1981

[Neuroanatomy of the optic, trigeminal, facial, glossopharyngeal, vagus, accessory and hypoglossal nerves (author's transl)].

1. The intracranial and intraorbital course of the optic nerve is described concisely, the intracanicular one in full details. Apart from the wide and small sections of the optic canal, its axis opposite to the cranial planes, the coating of the canal and the adjacency to the paranasal sinuses and arteries are exactly described. 2. At the trigeminal nerve the trigeminal ganglion, its roots and also the mandibular nerve have great importance in the practical medicine considering thermo-coagulation or surgery of the trigeminal nerve. This segments and also the adjacency of the fifth nerve to the internal carotid artery and subarachinoid brain vessels are exactly, the nuclei areas and central tracts are briefly explained. 3. The nuclei of the facial nerve the intracerebral and intracisternal course and its development, the facial canal and its narrow passes are described. Also the position of the internal acoustic pore in the skull, the dimensions of the internal acoustic meatus and the relations between nerves and vessels are explained. In addition to the geniculate ganglion and the chorda tympani the communications of the facial nerve inside the temporal bone, the tympanic intumescentia (ganglion) and the nervus intermedius, also the petrosal nerves are included in the description. The sheaths of the segments of the seventh cranial nerve and also the fasciculation are exactly, the somatotopic organization is briefly described. 4. The extracranial course of the glossopharyngeal nerve is briefly, its intracranial sections are included exactly in the investigation. 5. The nuclei of the vagus nerve and the intra- und extracranial course are described. 6. The accessory nerve, its nucleus and the intra- and extracranial course are concisely explained. 7. The hypoglossal nerve, its nucleus, the emergence of the fibres and also the relations of nerves and vessels in the posterior cranial fossa are described. The hypoglossal canal and also the extracranial course are explained as briefly as possible.

Accessory Nerve↗
PubMed1995

Transplantation of postnatal vomeronasal organ in the CNS of newborn rats.

The present study was conducted to examine the survival and development of intracerebral transplanted neonatal rat vomeronasal organs (VNs). Complete neonatal (P5-P10) VNs were transplanted into the parietal cortex region of littermates and examined at 10-100 days by light microscopy. The VN survived and was organized into a series of vesicles lined by respiratory and/or sensory epithelia. Sensory neurons grew long axons that fasciculated and invaded the surrounding brain parenchyma. The newly developed axons did not prefer a specific brain region. The axons developed a complex fiber plexus either at the interface between transplant and host tissue or deep within the host brain parenchyma. Vomeronasal axons consistently formed glomerular-like structures within the fiber plexus. Our results suggest that glomerular formation is not dependent on specific target of length of axon development, but rather on a set of complementary axons that display mutual recognition.

Animals↗
PubMed1987

Motor neuron disease, parkinsonism and dementia. Report of a case with diffuse Lewy body-like intracytoplasmic inclusions.

The clinicopathological findings in a 49-year-old man who presented multisystemic neurological degenerative disease are reported. The patient presented, at the age of 36, distal upper limb amyotrophy and 8 years later pyramidal signs with fasciculations. In his last year of life, he suffered extrapyramidal hypertonus and mental deterioration. Neuropathological examination showed anterior spinal root and cerebral atrophy. Myelin pallor was mild and predominated on posterior cords. Anterior horn neuronal loss was noted in the spinal cord as well as Alzheimer-type changes in the brain. Inclusion bodies consistent with Lewy bodies were diffusely apparent. The peculiar clinical progression in this case and the extension of neuropathological lesions with inclusion bodies mainly in the substantia nigra and cerebral cortex are an interesting subject of discussion.

Brain↗
PubMed1987

Malignant triton tumour in the cerebellopontine angle. Report of a case.

A report is given of a 24-year-old woman with a malignant cerebellopontine angle tumour, which appeared to have arisen from the 8th nerve sheath. It had a predominantly fasciculated, spindle-cell, Schwannoma-like structure, but also included rhabdomyoblastic elements and a diagnosis of malignant triton tumour is proposed. The patient did not have Von Recklinghausen's disease.

Adult↗
PubMed1996

Hereditary neuropathy with liability to pressure palsies: the same molecular defect can result in diverse clinical presentation.

Hereditary neuropathy with liability to pressure palsies (HNPP) is a peripheral nerve disorder characterized by autosomal dominant inheritance, recurrent pressure palsies, reduced motor and sensory conduction velocities and sausage-like swellings (tomacula) of myelin sheaths in nerve biopsy. Two young adult patients are reported as index cases of two families in which HNPP was diagnosed. The first patient presented with recurrent pressure palsies, whereas the second suffered from fasciculations and myokymias in his right hand, with difficulty in writing, and upper and lower limb paraesthesias of 3 years' duration. Electrodiagnostic studies revealed slowing of conduction primarily in common sites of compression in both patients. Sural nerve biopsy revealed the characteristic tomaculous swellings in both patients. DNA analysis showed that both patients have a deletion in chromosome 17p11.2 which is found in the majority of HNPP cases. In light of the common molecular defect, the different clinical symptomatology of the two patients is discussed.

Adult↗
PubMed1991

In vivo alterations in lactate dehydrogenase (LDH) and LDH isoenzymes patterns by acute carbofuran intoxication.

Intoxication with an acute dose of carbofuran (1.5 mg/kg, sc) in male Sprague-Dawley rats evoked severe toxic manifestations characteristic of hypercholinergic preponderance with profound muscle fasciculations and convulsions during 30-60 min, lasting for about 2 h. Lactate dehydrogenase, a "biomarker" cytoplasmic enzyme catalyzing the reversible reaction of lactate-pyruvate, was represented by five electrophoretically distinct isoenzymes in the serum and tissues. The amounts of each isoenzyme in different tissues were widely varied and consequently the patterns were tissue specific. A 24-h time-course following carbofuran administration indicated a two-fold increase in the activity of total LDH in serum and more than 30% in hemidiaphragm and liver. The patterns of LDH isoenzymes in serum revealed a significant (P less than 0.01) increase in all the isoenzymes except LDH-4 (64% decrease). Analysis of each tissue revealed characteristic changes in LDH isoenzyme patterns indicating organ-specific tissue damage. These alterations in LDH and its isoenzymes, in addition to acetylcholinesterase inhibition, may be directly or indirectly related to the mechanism(s) of the toxic action, and also provide insight into the site/organ(s) of toxic injury, thus providing an early prognostic indicator.

Animals↗
PubMed1993

Microtubule-associated protein 2 and the organization of cellular microtubules.

Microtubule-associated proteins (MAPs) are prominent components of the neuronal cytoskeleton that can promote microtubule formation and whose expression is under strong developmental regulation. They are thought to be involved in organizing the structure of microtubule fascicles in axons and dendrites, although whether they form active cross-links between microtubules or serve as strut-like spacer elements has yet to be resolved. In the experiments reported here we explored their influence on microtubules by expressing them in non-neuronal cells using DNA transfection techniques. We confirm earlier reports that microtubule-associated proteins of the MAP2/tau class can induce bundling of microtubules. In addition we find that MAP2 causes the rearrangement of microtubules in the cytoplasm in a manner that is dependent on the length of the microtubule bundles. Short bundles are straight and run across the cytoplasm whereas long bundles form a marginal band-like array at the periphery. We suggest that the latter arrangement is produced when microtubule bundles that are too long to fit inside the diameter of the cell bend under the restraining influence of the cortical cytoskeleton. In confirmation of this, we show that when the cortical actin network is depolymerized by cytochalasin B the MAP2-containing microtubule bundles push out cylindrical extensions from the cell surface. These results suggest that the induction of stiff microtubules bundles by MAP2, coupled with a breach in the cortical actin network, can confer two of the properties characteristic of neuronal processes; their cylindrical form and the presence of fasciculated microtubules.

Cytochalasin B↗
PubMed1994

Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves.

By combining both immunocytochemical and functional investigations, a hypothetical framework will be developed for the molecular mechanisms underlying neuron-glia interactions during development and regeneration of peripheral nerves. In particular, the immunoglobulin-like molecules L1, N-CAM, MAG and P0, the extracellular matrix molecules laminin and tenascin, and the carbohydrates PSA and L2/HNK-1 will be considered. During early stages of limb bud innervation in embryos, L1 and N-CAM are expressed on axons and Schwann cells and are involved in axonal fasciculation, whereas tenascin is thought to be involved in forming a scaffold around the nerve possibly preventing axons and/or Schwann cells from leaving the nerve. PSA has been shown to be involved in pathway selection at initial stages of limb bud innervation. Later on, when motor axons enter muscles, the carbohydrates determine the branching pattern of the nerves. During myelination, L1 appears to play a pivotal role during the formation of the first Schwann cell loops around the prospective myelin-containing axons. MAG and P0 appear also to be functionally involved at initial stages of myelin formation. Additionally, MAG may contribute to the formation and maintenance of non-compacted myelin and axon-Schwann cell apposition whereas P0 is involved in myelin compaction. Under regenerative conditions, L1, N-CAM, laminin, and tenascin are strongly up-regulated by denervated Schwann cells. In vitro observations strongly suggest that these molecules might foster axonal regeneration. The carbohydrate PSA is confined to regrowing axons and is also a candidate to support axonal regrowth. L2/HNK-1, which is found on motor axon-associated Schwann cells, may provide regenerating motor axons with a selective advantage over others resulting in appropriate reinnervation of motor pathways. Since many of the functional studies this review refers to have been performed in vitro, some of the conclusions drawn need reexamination in vivo. Gene manipulations, such as the generation of null mutants followed by a thorough morphological and immunocytochemical investigation may be a powerful tool to resolve this problem.

Animals↗
PubMed1989

Three-dimensional scanning electron microscopic study of the normal hamster olfactory epithelium.

The olfactory epithelium of the adult hamster (Mesocricetus auratus) was studied using the scanning electron microscope. A method that produced fractures in the epithelium exposed structures below the surface and made it possible to examine the morphological and structural relationships among cells. Three cell types were studied: supporting cells, olfactory neurons (receptor cells) and basal cells. Supporting cells were observed spanning the full extent of the epithelium, and had basal foot processes that terminated at or near the basal lamina. Along the lateral margin of supporting cells, cellular processes were observed extending outwards, reaching olfactory neurons and adjacent supporting cells. These cellular contacts among supporting cells and olfactory neurons were present at different levels of the epithelium. Olfactory neurons were located primarily in the middle and lower epithelial regions. Their dendritic processes reached the epithelial surface in a straight or tortuous manner, passing between the supporting cells. Olfactory axons were observed as thin unbranched processes that emerged from a conical hillock region, passed basally, and fasciculated into larger sensory bundles within the lamina propria. Basal cells were observed adjacent to the basal lamina as a row of single cells or clustered in groups. Within the lamina propria connective tissue, blood vessels, axon bundles and Bowman's glands were examined. Bowman's glands were composed of pyramidal secretory cells arranged about a single duct that extended to the epithelial surface. Scanning electron microscopy provided a unique three-dimensional analysis of cell structure within the olfactory epithelium. The results provide new and different observations on the detailed morphology and intimate relationships that exist among epithelial cells, and complement previous light and transmission EM observations.

Animals↗
PubMed1989

Scanning electron microscopic study of degeneration and regeneration in the olfactory epithelium after axotomy.

The olfactory epithelium of the adult hamster (Mesocricetus auratus) was examined with the scanning electron microscope following olfactory nerve axotomy. Axotomy results in retrograde degeneration of mature olfactory neurons. Maximum degeneration was observed around day 4. During the degeneration period the epithelium consists primarily of supporting and basal cells. Microvillar columnar supporting cells were observed to have fine cellular processes extending from their lateral border to neighbouring cells. Supporting cells extended to the basal lamina where they terminated in foot-like processes of variable shapes (club, splay and hook). Basal cells which gave rise to new replacement olfactory neurons were observed near the basal lamina. They had a rough cellular surface covered with small granules and fine cellular extensions. Bowman's gland duct cells extended unbranched through the epithelium where they formed funnel duct openings covered with microvilli. During early recovery periods (5-30 days) the number of olfactory neurons in the lower epithelium region increased. We observed olfactory neurons with developing axon and dendritic processes. Specialized growth cone structures were seen at the tips. Olfactory neuron growth cones were elongated or club-shaped and had a ruffled membrane surface. Several thin filopodia extended from the growth cone and made contact with adjacent cells. At late recovery periods (35-120 days) there was a marked increase in the number of olfactory neurons within the middle and lower epithelium regions. Numerous dendritic processes extended to the epithelial surface and terminated in knob-like ciliated structures. Olfactory axons passed basally, forming small intra-epithelial bundles that penetrated the basal lamina then fasciculated into larger bundles within the lamina propria. This study provides detailed three-dimensional observations of the olfactory epithelium following neuron injury, and describes neural degenerative changes, replacement of olfactory neurons, development and maturation. In addition, we describe the structure and basal attachment of supporting cells and their glial-like relation with olfactory neurons.

Animals↗
PubMed1992

Immunocytochemical localization of the L1 and N-CAM cell adhesion molecules and their shared carbohydrate epitope L2/HNK-1 in the developing and differentiated gustatory papillae of the mouse tongue.

The localization of the cell adhesion molecules L1 and N-CAM, and their shared carbohydrate epitope L2/HNK-1, was investigated at the light and electron microscopic levels in developing and adult fungiform and circumvallate gustatory papillae of the mouse tongue. At embryonic day 13, the earliest stage investigated, the tongue epithelium was still undifferentiated and was not yet innervated by sensory fibres. At this stage none of the three molecules was detectable within the tongue epithelium. At embryonic day 15 the primordia of the gustatory papilla became unequivocally discernible when the papillary epithelium was already innervated by few sensory axons. At this stage N-CAM was the first molecule expressed on epithelial cells and was confined to those parts of the papillary epithelium destined to become the chemosensory cells of the taste buds. The sensory axons were N-CAM-, L1- and L2/HNK-1-positive when fasciculating or contacting their accompanying Schwann cells or the cells of the papillary epithelium. Contacts between Schwann cells were also prominently labelled by antibodies to the three antigens. The mesenchymal tissue underlying the prospective sensory epithelium expressed N-CAM at all embryonic stages, but ceased to be N-CAM positive within the first six postnatal days. From embryonic day 16 onward a weak L1 immunoreactivity was detectable within the basal and intermediate layers of the lingual epithelium and remained present in adulthood. Cytodifferentiation of epithelial cells into spindle-shaped sensory cells and organization into taste buds began at postnatal day two. Simultaneously, L1 and L2/HNK-1 immunoreactivity increased on taste bud cells and N-CAM disappeared from the non-sensory extragemmal parts of the papillary epithelium. At approximately postnatal day six, taste bud formation was complete and the pattern of cell adhesion molecule expression was comparable to that found in the adult in that L1 was strongly expressed on the apposing surfaces of all cells, whereas N-CAM was confined to cell contacts between a subpopulation of intragemmal cells. The L2/HNK-1 epitope was visible on the surfaces of taste bud cells, on intragemmal axons, and in a small portion of extracellular matrix directly underlying the taste buds, but was no longer expressed on those parts of the sensory fibres embedded in the subepithelial mesenchyme. The L2/HNK-1 epitope may thus be regarded as a cell surface marker for the cellular elements of mature taste buds. The highly sialylated form of N-CAM was not detectable at any stage investigated.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1979

Axonal-ependymal associations during early regeneration of the transected spinal cord in Xenopus laevis tadpoles.

The nature and organization of the cellular substrate supporting axonal outgrowth during early regeneration of the spinal cord following transection and/or segment removal were examined in Xenopus tadpoles. Longitudinal axonal compartments, formed by radial ependymal processes in unoperated spinal cords, were maintained within the rostral and caudal stumps throughout the early post-operative period. The first neuritic sprouts to appear near the cut ends of the cord were frequently associated with these processes. Between 5 and 7 days after transection either single or multiple cellular aggregates, which consisted primarily of ependyma, began occupying the lesion zone and were encompassed by numerous small fibres. Ependymal processes subsequently extended among the neurites within the lesion gap and re-established longitudinal axonal channels and a surrounding glia limitans. A concurrent outgrowth of fibres and ependyma from the rostral and caudal stumps was also initiated by 5-7 days following resection of the cord. Axons were seen further within the ablation gap at 10 and 12 days either coursing along the surfaces of the emerging ependyma or organized into small fascicles by the radial processes of these cells. Intermediate stages of axonal fasciculation by the underlying ependyma were also seen. In contrast with previous reports, axonal elongation beyond the cut ends of the cord did not consistently entail the formation of pre-existing ependymal channels. These observations provide additional evidence emphasizing the importance of the ependymal cell surface during axonal outgrowth in the regenerating spinal cord. Guided neuritic elongation, however, does not appear to be dependent upon the prior establishment of a specific type of cytoarchitecture.

Animals↗
PubMed1992

Influence of an endogenous lectin substrate on cultured dorsal root ganglion cells.

Dorsal root ganglion neurons normally contain a 14,500 molecular weight lactose-binding lectin, designated L-14. Although this lectin is developmentally regulated, and is localized to specific neurons as well as to specific areas of the rat spinal cord, its function in the nervous system is not known. In an effort to study the possible role of this lectin on peripheral neurons, they were dissociated and grown on substrates consisting of either L-14 or laminin, a molecule known to support neurite outgrowth. In contrast to the random distribution and fine neurites displayed by neurons on laminin, those growing on L-14 formed large aggregates with highly fasciculated neurite bundles. Experiments using plant lectins with sugar-binding specificity similar to that of L-14, as well as another endogenous rat lectin not present in neurons, resulted in essentially no neuronal attachment or neurite outgrowth. In addition, the effects induced by L-14 were not blocked by high concentrations of competing sugars, suggesting that it interacts with neurons by a domain distinct from its carbohydrate-binding site.

Animals↗
PubMed1992

Morphological heterogeneity and phenotypical instability versus metastatic stability in the murine tumor model ER 15-P.

At clinical presentation, the majority of malignant tumors are composed of multiple clonal subpopulations of tumor cells with different phenotypic characteristics. Using the experimental tumor model ER 15-P, a methylcholanthrene-induced pleomorphic sarcoma of the C57 Bl6J mouse, we studied a system of long-term in vivo passages of this primary tumor for cell morphological changes, and alterations in the potential for spontaneous lung metastases. Transplants from the primary after the 4th, 20th, 40th and 80th i.m. passage (referred to as T4, T20, T40, and T80 respectively) together with their lung metastases were investigated by light microscopy, immunohistochemistry, and electron microscopy. In addition, the potential for metastasis to the lungs in each group was determined and compared with that of the parent T4 tumors. T4 tumors were mainly composed of spindle-shaped tumor cells with the ultrastructural features of fibroblasts and myofibroblasts, often arranged in a storiform or fasciculated growth pattern, and intermingled with tumor giant cells. Some small areas contained polygonal or rounded tumor cells, ultrastructurally undifferentiated, and sometimes arranged in a hemangiopericytoma-like growth pattern. Although electron-microscopical findings clearly demonstrated the mesenchymal origin of these tumor cells, immunostaining with a polyclonal antibody to vimentin was unspecific in all tumor cells and normal mouse tissue. Monoclonal antibodies to vimentin from different sources were completely negative in tumor cells and murine stromal components. In contrast, myofibroblast-like tumor cells showed immunohistochemically, a moderate to strong co-expression with monoclonal antibodies to desmin, muscle actin and alpha-smooth muscle actin. On the basis of these morphological findings, the primary ER 15-P was classified as a pleomorphic myofibrosarcoma. The lung metastases of T4 tumors were mainly composed of undifferentiated round to polygonal tumor cells, while the number of desmin-positive, muscle- and alpha-smooth muscle-actin-positive cells was reduced. The morphological features of T20 tumors and their lung metastases were the same as in T4, indicating a relative stability of the phenotype up to that stage. In contrast, T40 and T80 tumors and their lung metastases were found to contain almost exclusively undifferentiated tumor cells and many tumor giant cells. While fibroblast-like tumor cells were seen only occasionally, myofibroblast-like tumor cells had almost completely disappeared. The potential for lung metastases was nearly constant in all groups, suggesting metastatic stability. Obviously, the undifferentiated tumor cells of this model are associated with a higher metastatic potential.

Actins↗
PubMed1990

Retinal axons in Xenopus laevis recognise differences between tectal and diencephalic glial cells in vitro.

Explants of retina from Xenopus laevis were cultured on monolayers of tectal and diencephalic glial cells in order to determine whether the glia, normally encountered by optic nerve fibres as they grow to the optic tectum, can influence the growth of these neurons in any way. Explants of nasal retina produced prolific radial outgrowth patterns on both tectal and diencephalic monolayers. Explants of temporal retina produced similar outgrowth patterns on diencephalic glia, but on tectal glia the outgrowth was restricted and fibres were fasciculated in short, fat bundles.

Animals↗