Inhibition and enhancement of mixed-fuction oxidases by nitrogen heterocycles.
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Aniline Hydroxylase↗
Biomedical subjects
M Murray
Publications and source records attributed to M Murray.
A quantitative study of regenerative sprouting by optic axons in goldfish.
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Animals↗
A quantitative study of the reinnervation of the goldfish optic tectum following optic nerve crush.
Stereological and quantitative morphometric methods were used to study changes in the stratum fibrosum et griseum superficialis (SFGS), the major retinal target, in optic tectum of goldfish, during regeneration of the optic nerve. Orthograde transport of HRP by optic axons was used to characterize the retinal projection in SFGS. Profiles of HRP-labeled optic terminals contained rounded vesicles, contacted small dendrites, and were distributed uniformly throughout the area of SFGS sampled; labeling density estimates indicate that at least 37% of the total terminal population in SFGS is retinal in origin. Partial denervation of the tectum by optic nerve crush is accompanied by a loss of 40% of the total terminal population in SFGS and by a marked decrease of SFGS thickness. Entry of massive numbers of regenerating optic axons into SFGS begins about 3 weeks postoperatively, about the time that some visual function recovers and produces a marked increase in SFGS thickness which persists for several months postoperatively. The area occupied by regenerating axons and the number of terminals in the tectum only approach preoperative levels 3 months postoperatively. The recovery of normal synaptic number is therefore delayed several months beyond the time of entry of regenerative axonal sprouts. The results indicate that return of synaptic number to normal is temporally associated with the reduction of the excess number of regenerating optic axons and that both these processes are prolonged.
Animals↗
Target regulation of synaptic number in the compressed retinotectal projection of goldfish.
In order to determine the morphological consequences of the formation of a compressed retinotectal projection, the optic neuropil lamina (stratum fibrosum et griseum superficialis, SFGS) was examined in large goldfish 3 months to 4 years after ablation of the caudal half of the tectum both with crush of the optic nerve (HTX) without (HT). In semithin sections, the SFGS, as delineated with orthograde HRP labeling, shows a persistent hypertrophy of about 25% in HTX and HT groups. Comparison of ultrastructural stereological data with similar data on control and regenerated projections to intact tecta (Murray and Edwards, '82) indicated that this hypertrophy can be attributed largely to an increased number of axons and not to increases in terminal or dendritic compartments. A normal number of synaptic terminals per column through SFGS is conserved in HTX and HT groups. Planimetric analysis and observations using orthograde HRP labeling reveal no group differences in size and shape of terminal profiles. The same number of retinal ganglion cells project to a half-tectum as to an intact tectum, as indicated by estimates of ganglion cell number and of the minimum percentage of them which project to the tectum using retrograde HRP labeling. The results suggest that the regenerating and sprouting optic axons participating in the formation of a compressed retinotopic projection compete for a limited accommodation inthe SFGS and that this capacity to accept synaptic input becomes saturated at the control innervation density. The results are consistent with the formation of a smaller than normal number of terminals per optic axon, numerical estimates for which are given. If the percentage of terminals which are optic does not change, then the number of terminals per axon is reduced by about 40%.
Animals↗
Lack of sprouting and its presence after lesions of the cat spinal cord.
Degeneration methods were used to study the dorsal root and descending projections after chronic partial denervation of adult cat spinal cord. Conventional mapping methods were used, supplemented in some cases by densitometric measurements of the amounts of degeneration present. The amount of shrinkage of spinal gray matter in some sections was estimated by planimetric measurement. Two preparations were used: (1) partial unilateral rhizotomy in which all dorsal roots caudal to T4 were cut except L6 (spared root preparation); (2) complete unilateral deafferentation. The projection of L6 dorsal roots was examined in spared root preparations. T13 dorsal root projections were examined in deafferented preparations in which T13 was the lowest remaining root. The projection of descending systems was mapped in spared root and deafferented preparations. The spared root displayed an increased projection in the lateral portion of the dorsal horn, in the zona intermedia, Clarke's nucleus and in the base and reticular zone of nucleus gracilis. The lowest remaining root (T13) increased its projection to laminae VII and VIII and to the base and reticular zone of nucleus gracilis. In all cases, when an increased projection resulted from prior denervation, the increase never exceeded the boundaries of the normal projection. No sprouting was observed in those regions with the strictest topographical organization, the cell nests of nucleus gracilis or lamina IX of the spinal cord, even though these regions were partially denervated by the chronic lesions. Descending projections were increased on the experimental side of deafferented preparations12 but not of spared root preparations, suggesting that the presence of the spared root may prevent sprouting by descending systems. Because measurements of gray matter indicated that maximal sprouting occurred in segments showing least shrinkage (sprouting of L6 spared root into L6 segment), in this case shrinkage cannot account for the increased density of degeneration. These results suggest that certain conditions are important for the regulation of sprouting in the adult CNS. Firstly, sprouting is limited by a requirement for proximity and/or overlap. Secondly, the strictness of topographical localization within a particular region may limit the likelihood of sprouting into that region. Finally, a competitive or hierarchical relationship among the remaining systems may modify the capacity of a particular system to sprout.
Afferent Pathways↗
Early events following challenge of cattle with tsetse infected with Trypanosoma congolense: development of the local skin reaction.
A local skin reaction (chancre) was elicited in susceptible cattle after the successful feeding of Glossina morsitans morsitans infected with one of two different cloned isolates of Trypanosoma congolense. The chancre first appeared as a small 2 to 3 mm nodule at the site of the challenge as early as day 5 and reached maximum activity by days 10 to 13 when it had developed into a raised, indurated, hot, painful swelling measuring up to 100 mm in diameter. Thereafter it declined in size and activity and by days 20 to 30 was undetectable. Histologically the lesion was characterised by an intense inflammatory reaction and a four- to 10-fold increase in total cellularity. Initially, polymorphonuclear leucocytes were numerous but these were soon replaced by a mononuclear cellular infiltrate consisting mainly of small to medium lymphocytes. Development of the chancre and detection of parasites in the skin preceded by several days parasitaemia and other clinical signs. It was concluded that the skin was acting as a focus not only for establishment of infection but also as a site for localised proliferation of the parasite before dissemination into the bloodstream. The bite of an uninfected tsetse fly produced no detectable reaction and experimental intradermal inoculation of metacyclic T congolense resulted in chancre formation followed by infection. Bloodstream forms given by the same route caused infection but failed to induce a chancre.
Animals↗
The response of the murine lymphoid system to a chronic infection with Trypanosoma congolense. II. The lymph nodes, thymus and liver.
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Animals↗
Host susceptibility to African trypanosomiasis: trypanotolerance.
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Age Factors↗
Inhibition of rat hepatic microsomal aminopyrine N-demethylase activity by benzimidazole derivatives. Quantitative structure-activity relationships.
Eight-two benzimidazole derivatives have been prepared and tested for the ability to inhibit cytochrome P-450 mediated enzyme activity (aminopyrine N-demethylase) from phenobarbitone-induced rat hepatic microsomes. Using physicochemical parameters and multiple regression analysis, we derived a quantitative structure-activity relationship (QSAR) that describes up to 87% of the data variance in terms of hydrophobic and electronic effects and the molar refractivity of the substituent in the 2-position of the benzimidazole ring.
Aminopyrine N-Demethylase↗
African trypanosome antigens recognized during the course of infection in N'dama and Zebu cattle.
The humoral immune responses to Trypanosoma brucei infection were examined in N'dama and in Zebu, two breeds of cattle recognized for their differing susceptibility to trypanosomiasis. Regardless of the clinical course, animals of both breeds produced antibodies to nonsurface trypanosome antigen(s) detectable by both immunodiffusion and immune fluorescence. As a new approach to assessment of the humoral response to trypanosome infection, protein antigens responded to were isolated by immune precipitation, and their molecular weights were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This allowed the detection of differences in the immune response which correlated with the clinical course of the disease. All cattle of both breeds which exhibited a capacity to control the disease recognized at least one of three specific antigens: protein of 110,000, 150,000, and 300,000 daltons. The N'dama, which proved less susceptible to the disease, generally responded to more of the three identified trypanosome protein antigens than did the Zebu. Animals which died of trypanosomiasis failed to produce detectable antibodies to any of the three specific proteins, although they sometimes exhibited antibodies to another trypanosome antigen.
Animals↗
Immunization of cattle with a variant-specific surface antigen of Trypanosoma brucei: influence of different adjuvants.
Nine different adjuvants were examined for their ability to potentiate the humoral and cell-mediated immune responses of cattle to a soluble glycoprotein antigen prepared from Trypanosoma brucei. Serological responses as measured by the Farr assay were best augmented by the oil-based adjuvants and saponin. Cell-mediated immunity, as assessed by specific lymphocyte transformation in vitro, was enhanced by all oil-based adjuvants at different intervals after immunization. Results from a challenge infection of immunized cattle with the homologous clone of T. brucei and from neutralization tests indicated that protection against infection was better correlated with specific antibodies than with cell-mediated responses. From these considerations, and the absence of tissue reactions at the site of inoculation, saponin was considered more practical than the oil-based or bacterial adjuvants for the elicitation in cattle of antibodies to purified soluble antigens.
Acetylmuramyl-Alanyl-Isoglutamine↗
A comparative evaluation of the parasitological techniques currently available for the diagnosis of African trypanosomiasis in cattle.
The parasitological techniques currently in use for the diagnosis of African trypanosomiasis were compared in a series of experiments for their capacity to detect Trypanosoma congolense, T. vivax and T. brucei in the blood of cattle. The darkground/phase contrast buffy coat method proved to be more sensitive than the haematocrit centrifugation technique, thick, thin and wet blood films in detecting T. congolense and T. vivax. On the other hand with T. brucei, mouse inoculation was the most sensitive method, followed by the haematocrit centrifugation technique. In a further series of experiments involving cattle infected with either T. congolense or T. vivax, the darkground/phase contrast buffy coat method was consistently more sensitive in detecting parasites than haematocrit centrifugation, capillary concentration using glycerol and miniature anion-exchange/centrifugation techniques. As well as showing superior sensitivity, the darkground/phase contrast buffy coat method allowed species identification, estimation of parasitaemia and simultaneous assessment of anaemia (packed red cell volume).
Animals↗
Potassium problems: which patient's in danger?
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Humans↗
Observations on the infectivity and pathogenicity of three isolates of Ostertagia spp sensu lato in calves.
After experimental infection of three groups of calves with three different defined isolates of Ostertagia spp sensu lato a marked variation in the infectivity and degree of pathological change was noted. The most highly infective and pathogenic isolate contained approximately 30 per cent O leptospicularis in addition to O ostertagi (70 per cent) and a negligible number of Skrjabinagia lyrata. The other two isolates consisted solely of O ostertagi (approximately 90 per cent) and S lyrata (approximately 10 per cent) and showed comparable infectivity and pathogenicity to that commonly recorded. The greater pathogenicity of the isolate containing O leptospicularis was attributed to the higher infectivity and the greater damage caused to the gastric mucosa by individual parasites when compared with O ostertagi.
Abomasum↗
Interference in the establishment of superinfections with Trypanosoma congolense in cattle.
To examine the influence of an established infection on subsequent challenge with another unrelated trypanosome serodeme, cattle were subjected to two challenges, 5 to 6 wk apart, with unrelated isolates of Trypanosoma congolense. The primary infection inhibited the establishment of the second infection despite the initial absence of detectable antibody to the trypanosomes used for the second challenge. This was true whether the second challenge consisted of bloodstream forms of the parasite or metacyclics from infected Glossina m. morsitans. Rechallenge with bloodstream forms resulted in a slight antibody response, which was only detectable by immunofluorescence and was much less than in the challenge controls. Although animals subjected to the second challenge by tsetse flies showed no appreciable increase in parasitemia and, in most instances, no chancre reaction at the site where the tsetse bit, they developed readily detectable neutralizing antibody to the metacyclic trypanosomes. That this interference effect was not the result of specific immunity and required an active infection was confirmed by the finding that when infected animals were treated with Berenil prior to rechallenge, they were fully susceptible to the infection.
Animals↗
Field study on the epidemiology and pathogenicity of different isolates of bovine Ostertagia spp.
The epidemiological features of three different isolates of bovine Ostertagia spp under similar initial levels of larval challenge were compared in the field. Two of the isolates, consisting mainly of Ostertagia ostertagi, and a low proportion of Skrjabinagia lyrata conformed in epidemiological behaviour with those investigated by previous workers, though the worm burdens which established did not give rise to the expected clinical signs. The third isolate behaved in a different way, yielding very high faecal egg counts which were followed by high pasture larval counts, heavy worm burdens and severe clinical disease. This isolate, while consisting mainly of O ostertagi and a few S lyrata, also contained a proportion of O leptospicularis, and it is suggested that this species may influence the dynamics of the host-parasite relationship in bovine ostertagiasis.
Animals↗
Spinal neurons mediate return of substance P following deafferentation of cat spinal cord.
Deafferentation of the cat dorsal horn by complete unilateral lumbosacral dorsal rhizotomy produces a loss and subsequent partial recovery of substance P (SP) immunoreactivity as visualized by the peroxidase-antiperoxidase technique. The present experiments aimed to determine whether this return of SP represents a generalized response of all fiber systems afferent to the denervated segments or a more selective response of a specific spinal system. Although a contribution from other sources cannot be excluded by this qualitative immunocytochemical technique, several observations indicate that the return of SP staining depends on interneurons which contain SP immunoreactivity: (1) the amount of SP staining in the chronically deafferented dorsal horn deprived of extrinsic fiber systems is comparable to that seen after deafferentation alone; (2) SP-containing neurons are present within the lumbar segments; and (3) destruction of lumbar neurons by the intraspinal injection of kainic acid abolishes SP staining from the chronically deafferented dorsal horn. From these observations it would appear that the anatomical plasticity of SP-containing fibers in the deafferented dorsal horn is due to the response of a particular system rather than to a generalized response of all systems which terminate there.
Afferent Pathways↗
Susceptibility to African trypanosomiasis of N'Dama and Zebu cattle in an area of Glossina morsitans submorsitans challenge.
The use of trypanotolerant livestock is considered to be an important strategy for the control of African animal trypanosomiasis. In order to define the extent of the differences in susceptibility and productivity, 10 Zebu cows (a breed considered trypanosusceptible) and 10 N'Dama cows (a breed recognised for trypanotolerance) were exposed to a natural field challenge from Glossina morsitans submorsitans Newstead. The animals were two-and-a-half to three years old and had not been previously exposed to trypanosomiasis. All Zebu died of trypanosomiasis within eight months of first exposure. In contrast, only three N'Dama died of trypanosomiasis; they had all been suckling calves before they succumbed 11 to 14 months after initial exposure. The prevalence, level and duration of parasitaemia were significantly less in the N'Dama, which, unlike the Zebu, did not become febrile during parasitaemia. The differences in parasitaemia were largely attributable to Trypanosoma vivax. The N'Dama also developed much less severe anaemia than the Zebu. The mean and standard deviation of the packed red cell volume of the N'Dama was not significantly different between eight months after exposure when all Zebu were dead, and 21 months when the experiment was terminated. The relative productivity of the N'Dama was impressive. In addition to reduced mortality, the N'Dama experienced no abortions and produced five calves, three of which were alive at the end of the experiment, at which time three of the surviving N'Dama were pregnant. In the Zebu, in marked contrast, abortions occurred both in early and late pregnancy and no live calves were produced. The study confirmed that N'Dama cattle are innately less susceptible to trypanosomiasis than Zebu cattle and can survive and be productive in endemic areas of trypanosomiasis where Zebu perish.
Animals↗