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H E Lowndes

Publications and source records attributed to H E Lowndes.

At least 37 records · Page 2Linked to original sources
PubMed1988

Histochemical study of Sarcocystis sp. intramuscular cysts in gastrocnemius and soleus of the cat.

Histochemical investigations of Sarcocystis microcysts found in two hindleg muscles of cats were carried out. Genus identification was based on the reinforced cyst membrane structure and its dimensions, the structure of the sarcocysts, and an electron microscopic survey of bradyzoite characteristics. The cyst membrane is partly contributed by the host myofiber, the characteristic histochemical features of which it retains. Materials adjacent to the limiting membrane make it appear thicker than it actually is, particularly when the PAS method as well as techniques for the demonstration of alpha-glycerophosphate dehydrogenase and ATPase activities are used. The ground substance occupying the parasitophorous vacuole is not amorphous and metabolically inert, but rather displays a fairly strong and definite ATPase activity, suggesting a trophic role in the support of metrocytes and zoites embedded therein. Cysts tend to adapt their biochemical characteristics to the particular metabolism of the muscle fibers in which they are located. All of these findings are discussed in terms of host-parasite relationships.

Animals↗
PubMed1988

Unusual neurofibrillary accumulations induced by beta,beta'-iminodipropionitrile (IDPN).

Beta,beta'-iminodipropionitrile (IDPN) is a synthetic compound known to induce massive focal accumulations of neurofilaments almost exclusively in the proximal segments of motor and sensory axons. The present paper deals with a cat intoxicated with IDPN for five weeks. Swellings filled with skeins of maloriented neurofilaments were observed in the initial (non-myelinated) segment of intraparenchymal spinal axons in addition to the swellings consistently located in the first internodes. Filamentous masses in the initial segment were in some cases intermingled with focal accumulations of mitochondria and smooth vesicles to give the proximal axon the classical appearance of 'spheroid'. In some motoneurons, clumps of neurofilaments occupied the axon hillock and extended well into the perikaryon and some dendritic stems, making the borderlines between cell body and processes undistinguishable. Cytoplasmic organelles were displaced and rearranged in the presence of somal neurofibrillary changes. In a few neurons, regardless of the presence of swellings in the axon initial segment, signs of central chromatolysis were noticed, in the form of nuclear caps of Nissl substance and eccentricity of the nucleus. These findings are discussed with reference to other neurotoxic models of neurofibrillary pathology and the immunochemical differences recently detected between neurofilaments in perikarya, dendrites and axons.

Animals↗
PubMed1988

Occurrence of lipofuscin pigment granules and "dense microspheres" in the spinal cord of young cats treated with beta,beta'-iminodipropionitrile (IDPN).

Spinal cords of cats treated with the neurotoxic compound beta,beta'-iminodipropionitrile (IDPN) were observed to contain rounded homogeneous bodies, 1-12 microns in diameter, termed "dense microspheres" (DMS). These bodies, absent in control animals, were consistently found only in the ventral horns. No relationship with blood vessels was evident. When stained with PAS and a modified von Kossa's silver nitrate technique, DMS remained negative, showing only very slight metachromasia in some toluidine blue-stained sections. They were consistently acidophilic as evidenced by destaining and differentiation investigations. DMS were observed more frequently in the proximity of nerve cell bodies or closely adjacent to dendrites and their location was mainly extracytoplasmic; with the electron microscope, however, some DMS were also found in glial processes. Rounded osmiophilic bodies, 0.1-0.8 microns in diameter, were noticed in mitochondria of both neurons and glial cells; however, whether they were special forms of DMS or different inclusions was not assessed. Both intra- and extracytoplasmic DMS were similar in ultrastructure, appearing as single membrane-bound spherical or pear-shaped bodies containing a cottony or finely granular matrix. Additionally, both perikaryon and processes of large motoneurons were found to contain pigment granules identified as lipofuscin, which seemed to increase in number and to spread centrifugally in the processes in correlation with duration of the intoxication and size of axonal swellings induced by IDPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Cross talk between intraspinal elements during progression of IDPN neuropathy.

Unusual electrical interactions between neuronal elements of cat spinal cord were examined during the evolution (7-70 days) of proximal paranodally demyelinated axonal enlargements in alpha motor axons induced by beta, beta'-iminodipropionitrile (IDPN) treatment, 50 mg/kg ip, once weekly for up to 5 weeks. The electrical cross talk was observed as early as 7 days of the neuropathy, at which time it occurred in 17.0% of all motoneuron perikaryal recordings. The incidence was greater at 14 (39.1%) and 35 (26.1%) days, without preferential involvement of any motoneuron type. The frequency of recordings from axonal swellings increased from 7 to 35 days but without an increase in cross talk per recording. At 70 days of the neuropathy, L7 ventral root was stimulated repetitively to examine a possible influence of potassium on cross talk. Subsequently, action potentials could be elicited in motoneurons by stimulation of additional other ventral root filaments. These studies are in agreement with the lack of direct electrical apposition between excitable membranes in IDPN neuropathy but suggest support for a role for an accumulation of extracellular potassium, due to paranodal demyelination as the axon enlarges, in the pathogenesis of these aberrant electrical interactions.

Action Potentials↗
PubMed1986

Structural correlates of physiological abnormalities in beta, beta'-iminodipropionitrile.

beta, beta'-Iminodipropionitrile (IDPN) produces neurofilamentous giant axonal swellings in proximal internodes of large myelinated axons. Secondary demyelinative changes result from the production of these axonal enlargements. Electrophysiological studies have demonstrated profound alterations in the electrical properties of motor neurons (MN) within the spinal cord. On the basis of intracellular recordings, it has been suggested that electrical contacts may exist between swollen axons and neighboring MN. In addition, the possibility remained that synaptic contacts develop on demyelinated axonal swellings. In the present study, we report the lack of either synapses on demyelinated axonal swellings or direct electrical contacts between neighboring MN. Axonal swellings are surrounded by attenuated processes of glial cells (probably fibrillary astrocytes), a finding discussed in terms of its possible role in the production of ephaptic transmission. There was considerable variation in the degree of axonal enlargements and in the extent of secondary (passive and active) demyelination. It is suggested that these morphological changes may represent structural correlates of some electrophysiological alterations observed in IDPN neuropathy.

Animals↗
PubMed1986

Prejunctional effects of vecuronium in the cat.

This study explored the prejunctional actions of vecuronium using the in vivo cat soleus nerve-muscle preparation. Vecuronium doses of 1 to 5 micrograms/kg iv suppressed the repetitive firing of the motor nerve endings, and the obligatory potentiation of the twitch response following high-frequency conditioning at 400 Hz for 10 s without attenuating neuromuscular transmission at 0.4 Hz. It was also found that extremely low doses of vecuronium had excitatory effects at the cat soleus motor nerve endings: doses of 0.5 and 1 microgram/kg iv evoked a modest postdrug repetitive firing of the nerve endings and a concomitant potentiation of the muscle responses. These dose-related agonist and antagonist activities suggest that at the motor nerve endings, vecuronium is a weak partial agonist. The major action of vecuronium at the motor nerve endings, however, was suppressive, and this antagonist action contributed to the neuromuscular blocking action of this muscle relaxant.

Action Potentials↗
PubMed1985

Communicating hydrocephalus in rodents treated with beta,beta'-iminodipropionitrile (IDPN).

Beta,beta'-Iminodipropionitrile (IDPN), a neurotoxic compound known to induce swellings in the proximal internodes of sensory and motor axons in several parts of the central nervous system (CNS), was also found to cause hydrocephalus in rats and guinea pigs. In both species, ventricular dilatation was observed within 1 week following a single i.p. injection of IDPN. While in rats the severity of hydrocephalus correlated with dose and duration of IDPN exposure, in guinea pigs studies with high doses yielded inconclusive results, and no significant temporal correlation was noted. Parallel investigations with another neurotoxic agent, acrylamide, in rats, and with IDPN in cats failed to demonstrate any change in size and shape of the cerebrospinal fluid (CSF) pathways. No signs of spontaneously occurring hydrocephalus were found in control animals. In both rats and guinea pigs intoxicated with IDPN, macroscopic and microscopic findings were consistent with the diagnosis of communicating hydrocephalus. Treatment of hydrocephalic rats with acetazolamide (500 mg/kg) markedly attenuated ventricular distention, suggesting that an overproduction of CSF by the choroid plexus is responsible for the communicating hydrocephalus following IDPN intoxication.

Acetazolamide↗
PubMed1985

Evolution of axonal swellings in cats intoxicated with beta,beta'-iminodipropionitrile (IDPN). An electrophysiological and morphological study.

beta,beta'-Iminodipropionitrile (IDPN) causes formation of axonal swellings in the proximal internodes of spinal motor axons. The swellings enlarge and demyelinate with the progression of the neuropathy. The correlation between axonal swellings and electrophysiologic function of motoneurons was examined in cats 2 to 35 days after initial administration of IDPN. Morphologic changes in intraspinal motor axons, occasionally observed 2 days after the first injection, became progressively more evident at later times, with enlargement at the first internode in some axons and appearance of fusiform or balloon-like axonal swellings. At 7 days axonal swellings were infrequently observed and the main structural feature was a reduction in myelin thickness in affected nerve fibers. Despite scant histopathologic changes, motoneuron action potential discharge at this time was significantly altered in latency to onset of spike and rate of rise. Abnormal motoneuron firing patterns were observed at this time. As the neuropathy progressed, both the frequency of occurrence and the size of axonal swellings increased markedly but at no time was there morphologic evidence of chromatolysis. At 14 and 35 days, (after two or five IDPN injections) action potential discharge became further altered in latency to spike onset, rate of rise, initial segment conduction time and somal-dendritic threshold. The incidence of repetitive firing increased and axonal conduction block was observed in several motoneuron recordings. The electrophysiologic changes closely resemble those reported in chromatolytic motoneurons after axotomy. The axonal swellings induced by IDPN may produce an axotomy-like condition which becomes more prominent as the neuropathy progresses but without morphologic evidence of chromatolysis.

Action Potentials↗
PubMed1985

Inhibition of glyceraldehyde-3-phosphate dehydrogenase in tissues of the rat by acrylamide and related compounds.

In previous investigations acrylamide was found to inhibit several enzymes of glycolysis both in vitro and in vivo. The present study examines the characteristics of the in vitro inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and compares the in vivo effects of acrylamide on GAPDH activity to other analogs. Inhibition of GAPDH produced by acrylamide was characteristic of an irreversible or slowly reversible mechanism. In vivo, GAPDH activity was determined in sciatic nerve, brain, skeletal muscle and liver after cumulative doses of 250, 350 or 500 mg/kg of acrylamide. Specific activities were significantly lower in extensor muscle and liver after the 250 mg/kg dose. Activities in brain and sciatic nerve tended to be decreased but the differences were not statistically significant. Specific activity of GAPDH was decreased in medulla pons, cerebellum and the rest of the brain after a 350 mg/kg cumulative dose of acrylamide, although protein concentrations were not different from those in controls. The maximum decrease was about 20%. Treatment with acrylamide, methylene-bis-acrylamide (non-neurotoxic), or N-isopropylacrylamide (neurotoxic) significantly decreased the weight of the cortex and associated brain areas as well as general body weights. No signs of developing neuropathy were observed during treatment with methylene-bis-acrylamide to a cumulative dose (8.1 mmoles/kg) equivalent to that of acrylamide causing frank paralysis. Although the compound exhibited some ability to inhibit GAPDH in vitro, no decrease in GAPDH activity was found in rat brain. Treatment with N-isopropylacrylamide resulted in progressive neurologic impairment. After treatment to a cumulative dose of the compound causing a severe hind-limb paralysis (9.2 mmoles/kg), a small but significant decrease in GAPDH was found in the three areas of brain examined.

Acrylamides↗
PubMed1985

Electrophysiological investigation of IDPN neuropathy--initial studies.

beta,beta'-iminodipropionitrile (IDPN) causes giant axon swellings in proximal internodes of spinal motor axons and in stem processes of dorsal root ganglia neurons. The electrophysiological consequences of the swellings were investigated in cats given IDPN (50 mg/kg i.p.) weekly for 0 (control), 1 (7 days), 2 (14 days), or 5 (35 days) weeks; some additional animals were studied 15 (50 days) or 65 (100 days) days following the fifth injection. Extracellular recordings of the spinal monosynaptic reflex revealed amplitudes of efferent responses to be equally reduced at 35, 50 and 100 days. Single stimulation of dorsal roots, or soleus or medial gastrocnemius afferents often evoked doublet efferent responses which arose intraspinally. Similar repetitive responses were observed in dorsal root (afferent) input upon single stimulation of peripheral nerves. Latencies to monosynaptic responses became progressively prolonged over 100 days; spinal cord contribution to the increased latencies was maximal by 35 days. Conduction velocities in single soleus and medial gastrocnemius axons declined to 70 and 64% of normal by 50 days and to 56 and 50% of normal by 100 days respectively. Maximal recurrent inhibition was reduced 42-49% by 35 days and quantitatively similar at 50 and 100 days. Intracellular recordings from spinal motoneurons revealed that, at 35 days, action potentials could be elicited by orthodromic but not by antidromic stimulation in 14% of cells tested. This was taken as evidence of block of impulse conduction by the intervening axonal swelling upon antidromic stimulation. The possibility of abnormal electrical interactions between swollen and demyelinated intraparenchymal axons was tested by determining the number of ventral root fibers via which antidromic stimulation would elicit an action potential in the same motoneuron perikaryon. Electrical crosstalk, never seen in normal animals, varied in incidence during the evolution of the neuropathy (7-35 days), reaching a maximum of 30% at 14 days. Many motoneuron action potentials were remarkably similar to those observed in chromatolytic motoneurons, exhibiting, among other features, decreased SD thresholds and IS conduction times, reduced amplitudes and durations of afterhyperpolarization, delayed depolarizations and an enhanced propensity to fire repetitively upon single stimulation. There was no morphological evidence of chromatolysis in the motoneurons. The concept of "functional axotomy" is introduced to accommodate these findings and discussed in terms of altered dendritic excitability. Not all motoneuron types are equally compromised in the neuropathy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Electrophysiological investigation of beta,beta'-iminodipropionitrile neuropathy: intracellular recordings in spinal cord.

beta,beta'-Iminodipropionitrile (IDPN) was given to cats (50 mg/kg/week for 5 weeks) to induce giant axonal swellings in the proximal internodes of motor axons. Conventional intracellular recording techniques were used to investigate the influence of the axon swellings on axonal impulse conduction and generation of action potentials in unidentified lumbosacral motoneurons (MN). Action potentials recorded from axon swellings, verified by lack of orthodromically or antidromically elicited EPSPs or IPSPs, afterhyperpolarization potentials or initial segment-somaldendritic (IS-SD) inflections, were variable in shape. Some were indistinguishable from recordings in normal axons. Component or extra potentials occurred in 45% of recordings from axon swellings; their position on the action potential depended on the direction of impulse invasion into the swelling. Many action potentials were broad, with amplitudes less than 30 mV. Impulse conduction was estimated to be blocked in 19% of motor axons tested. Action potentials recorded in MN of IDPN treated cats resembled in many aspects those recorded in chromatolytic MN, with increased latencies upon antidromic stimulation and decreased IS conduction times and SD thresholds; other parameters did not differ significantly. The minimal interval between two stimuli which each evoked action potentials increased from 3.3 +/- 0.1 to 5.8 +/- 0.5 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Peripheral nerve phospholipids in acrylamide neuropathy.

Treatment of cats with acrylamide, either 7.5 or 15 mg/kg IM, once a day for 10 days, resulted in increases of 31 and 47% in the phospholipid content of sciatic nerve, respectively, from a control level of 41.1 +/- 2.7 mg/kg wet weight. Determination of the distribution of individual phospholipids indicated no significant differences between control cats and those receiving a cumulative dose of 150 mg/kg acrylamide. In a separate experiment, cats were treated with the 150 mg/kg dose of acrylamide and the sciatic nerve was divided into proximal and distal portions at the level of the triceps surae nerve. Significant increases in phospholipid content were observed in both the proximal and distal portions of peripheral nerve of the acrylamide-intoxicated cats. This effect was present even when the phospholipid content was expressed in terms of total protein, dry weight or total lipid. Total weight of nerve segments, however, was significantly decreased in the neuropathic animals. The data are consistent with a focal degeneration of axons with relative sparing of phospholipids.

Acrylamide↗
PubMed1984

Electrophysiological investigation of beta, beta'-iminodipropionitrile neurotoxicity: monosynaptic reflexes and recurrent inhibition.

beta-beta'-iminodipropionitrile (IDPN) neurotoxicity is morphologically characterized by the presence of giant axon swellings in the first proximal internodes of motor axons. The electrophysiological consequences of these proximal giant axon swellings on monosynaptic reflexes and recurrent inhibition were investigated along dorsal root-ventral root, medial gastrocnemius-ventral root and soleus-ventral root pathways of IDPN-intoxicated cats 35, 50 and 100 days following initial administration of the toxin (50 mg/kg/wk for 5 weeks). Monosynaptic reflex action potentials, normally relatively synchronous spike potentials, frequently appeared as doublet potentials which did not represent temporal fractionation of the spike potential. Latencies to the monosynaptic reflex action potentials were prolonged. Amplitudes of unconditioned monosynaptic reflex action potentials were significantly decreased at all time points, although there was a tendency for the amplitudes to recover with time. Post-tetanic potentiation was variously altered. Recurrent inhibition was reduced by 42-49% along monosynaptic reflex pathways. These results demonstrate that electrophysiological function in the spinal cord of IDPN-intoxicated cats is profoundly altered and the dysfunction partly results from the presence of the giant axon swellings.

Animals↗
PubMed1983

Neurotoxicology of vincristine in the cat. Morphological study.

Vincristine is a vinca alkaloid widely utilized in cancer chemotherapy. Its major clinical limitation is due to a drug induced sensory-motor neuropathy, the pathogenesis of which is poorly understood. This communication describes the morphological basis of a vincristine neuropathy in cats. Major pathological lesions were focal axonal swellings (giant axon formations) due to malaligned accumulations of neurofilaments and secondary demyelination of the paranodal type. These were primarily confined to the proximal portions of the peripheral nerves. The distal portions of the peripheral nerves contained only a few giant axon formations. Wallerian degeneration was noted to involve a small number of nerve fibers in the distal regions.

Animals↗
PubMed1981

Neurotoxicology of vincristine in the cat. Electrophysiological studies.

Cats were given vincristine sulfate (50 micrograms/kg i.v. every 4 days) and studied after 7-29 injections when neurological deficits became evident. The conduction velocity spectrum of individual afferent nerves from soleus muscles was shifted toward slower velocities. Relatively few functional muscle spindles or other proprioceptors which responded to muscle stretch were encountered. Those primary endings of soleus muscle spindles which did respond were significantly reduced in dynamic but not length sensitivity. Length sensitivity of secondary endings was unchanged. Thresholds of secondary but not primary endings were elevated. The average conduction velocity of soleus motor axons was reduced 30% but no deficit was detected in motor nerve terminal function. Indirectly-elicited contractile tension of the soleus muscles of the neuropathic cats was not significantly lower than that in untreated animals. Amplitudes of spinal monosynaptic reflexes were unaffected. These data indicate, that in the cat, neurological impairment results partly from dysfunction in muscle spindles and peripheral nerves.

Afferent Pathways↗
PubMed1981

Group Ia primary afferent terminal defect in cats with acrylamide neuropathy.

Group la primary afferent terminal (PAT) function was assessed in cats with acrylamide neuropathy. Spinal monosynaptic input-output relationships, critical input, the ability to maintain repetitive discharge at low frequencies, and apparent transmitter turnover parameters were determined in animals with subthreshold, moderate and severe degrees of acrylamide neuropathy (75, 150, and 300 mg/kg, respectively. The monosynaptic pathways of the soleus and medial gastrocnemius motoneuron pools were elicited by stimulation of their respective muscle nerves. The threshold for activation of the monosynaptic reflex (MSR) evoked by both SOL and MG nerves was increased 50% (critical input), regardless of dose regimen. Repetitive stimulation of the MSR at low frequencies (2-10 Hz) produces a slow decline in amplitude until it reaches a plateau. The height of the plateau attained in neuropathic cats was considerably lower than the controls. Determination of apparent transmitter turnover parameters in neuropathic cats showed that the constant fraction of neurotransmitter released from group la PAT remained the same while the rate of replenishment of transmitter available for release was attenuated in both SOL-VR and MG-VR pathways. The increase in the critical input and decrease in the rate of replenishment points up a functional defect in a group la PAT in cats with acrylamide neuropathy.

Acrylamide↗
PubMed1980

The etiology of toxic peripheral neuropathies: in vitro effects of acrylamide and 2,5-hexanedione on brain enolase and other glycolytic enzymes.

The in vitro effects of the neurotoxic compounds, acrylamide and 2,5-hexanedione, on several glycolytic enzymes including enolase, phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactic dehydrogenase (LDH) were studied in rat brain. A differential sensitivity of the enzymes to the inhibitory effects of the neurotoxins was observed. The order of increasing sensitivity to 2,5-hexanedione was enolase -- GAPDH -- PFK and to acrylamide the order was PFK -- enolase -- GAPDH. Neither neurotoxin inhibited LDH. The inhibition of enolase by acrylamide exhibited a mixed type pattern in double reciprocal plots. The inhibition could be completely reversed by dialysis indicating that it did not involve covalent bond formation. In the presence of dithiothreitol (DTT) or glutathione the inhibition of enolase by either acrylamide or 2,5-hexanedione was potentiated. Activity of enolase inhibited by both acrylamide and DTT could not be restored to pre-inhibition rates following dialysis indicating that an irreversible interaction between acrylamide and enolase had taken place. The results suggest that neurotoxic compounds which produce distal axonopathies have a common pattern of attack on glycolytic enzymes and that interruption of glycolysis is the underlying biochemical basis for both the physiological and morphological damage caused by these compounds.

Acrylamides↗