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Biomedical subjects

M J Harvey

Publications and source records attributed to M J Harvey.

At least 37 records · Page 2Linked to original sources

The use of a bovine plasma progesterone ELISA kit to measure progesterone in equine, ovine and canine plasmas.

A commerical kit designed to measure the concentration of progesterone in bovine plasma using an enzyme-linked immunosorbent assay (ELISA) has been assessed for measuring progesterone in the plasma of horses, sheep and dogs. Without validation, an immunoassay developed for progesterone in one species should not be used to measure progesterone in the plasma of other species. The kit was assessed by using the criteria of parallelism to a standard curve, the recovery of added progesterone, the correlation with an established radioimmunoassay and the detection of physiological change for each of the species tested. The ELISA kit proved to be acceptable for the analysis of progesterone in the plasma of each species, and in particular for the detection of the low concentrations found during the follicular phase and of the subsequent rise during the luteal phase of the oestrous cycle.

Animals↗

The effect of tetrachlorohydroquinone on hexachlorobenzene-induced porphyria in Japanese quail.

Female Japanese quail received either hexachlorobenzene (HCB, 100 mg/kg . d) or tetrachlorohydroquinone (TCHQ, 175 mg/kg . d) for 10 d as a primary treatment. Following this, a secondary treatment of HCB (100 mg/kg . d) or TCHQ (175 mg/kg . d), alone or in combination, was administered for 1, 5, 10 or 15 d. The primary HCB treatment caused elevated delta-aminolevulinic acid synthetase (ALA-S) activities and small increases in porphyrin concentrations. Subsequent treatment of these birds with lactose resulted in no further increases in porphyrins or ALA-S. TCHQ treatment caused increases in porphyrins similar to those seen with continued HCB treatment. Apparently, despite the fact that TCHQ alone had no affect on ALA-S or porphyrin levels, this compound is able, in the presence of elevated ALA levels to cause porphyria. A combination of HCB and TCHQ administered to HCB-pretreated animals caused a more severe porphyria than did follow-up treatment with either HCB or TCHQ alone.

5-Aminolevulinate Synthetase↗

Routine induction of farrowing with dinoprost in a commercial sow breeding unit over a year.

Details were recorded on a commercial sow breeding unit where dinoprost was used to induce farrowing in groups of sows every second week. Criteria considered were the interval from injection to start of farrowing, called the induction interval, the time required for farrowing to be completed, called the duration of farrowing, litter size and percentage of piglets born dead. Data were analysed to look for the effect on these of the day of gestation on which the injection was given, the parity status of the sow and the litter size.

Age Factors↗

Relative in vitro affinity of hepatic metallothionein for metals.

The ability of selected metals (Ag, Al, As, Ca, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Tl and V) to displace Zn from Zn-metallothionein (Zn-MT) was quantitated. Of the metals tested Cd had the highest affinity for MT, with 1.33 microM displacing 50% of the 65Zn bound to MT (EC50), followed by Pb (1.46 microM), Cu (1.93 microM), Hg (3.93 microM), Zn (8.06 microM), Ag (10.4 microM), Ni (474 microM) and Co (880 microM). As, Ca and Mo had a limited ability to displace Zn from MT while Al, Cr, Fe, Mg, Mn, Tl and V had no effect on Zn binding even at 1.0 mM.

Animals↗

Role of enzootic abortion and toxoplasmosis in an outbreak of abortion in a Scottish sheep flock.

During 1978-79 there was an outbreak of abortion in a large sheep flock during which approximately 10 per cent of the breeding ewes aborted. Both Toxoplasma gondii and Chlamydia ovis (the agent of enzootic abortion of ewes) were considered to be involved. In the year following this outbreak (1979-80), 156 ewes (11.4 per cent) aborted and the majority of cases were diagnosed as enzootic abortion: only one case showed gross pathology typical of toxoplasmosis. Serology carried out on sera collected from ewes at the time of abortion and at two post abortion samplings demonstrated that large numbers of animals had high titres against enzootic abortion of ewes while the prevalence of sheep with titres against toxoplasmosis was relatively low. Following the introduction of control measures to reduce the spread of enzootic abortion of ewes, the abortion rate in 1980-81 fell to 2.2 per cent. A small-scale trial was carried out to investigate the prophylactic effect of long acting oxytetracycline against enzootic abortion of ewes when given to pregnant sheep three weeks before lambing. Results indicated that treatment reduced the number of abortions in comparison with untreated controls.

Abortion, Veterinary↗

Familial cerebellar ataxia with hydrocephalus in bull mastiffs.

A family of bull mastiff pups in which 16 animals developed certain neurological signs is described. It is probable that the disease is inherited in an autosomal recessive manner. Clinical and pathological examination of six animals revealed ataxia, behavioural abnormalities and a visual defect associated with symmetrical lesions in the cerebellar nuclei, lateral vestibular nucleus and inferior colliculus together with a communicating hydrocephalus. The cerebellar lesions consisted of vacuolation, gliosis and axonal degeneration. Evidence for both axonal and oligodendroglial abnormalities was present and these probably result from a genetically determined metabolic disturbance in the affected neurones.

Animals↗

Hepatic phase I and phase II biotransformations in quail and trout: comparison to other species commonly used in toxicity testing.

The ability of quail and trout to perform a number of representative phase I and phase II biotransformations was examined. To facilitate interspecies comparisons, metabolism of the same substrates was examined simultaneously under uniform conditions for rat, mouse, rabbit, guinea pig, cat, and dog. Both nonmammalian species can metabolize four representative substrates of phase I mixed-function oxidases and one substrate of epoxide hydrolase, though activity tended to be lower than that of the mammals. Important differences in the conjugative pathways were also noted. Among these differences were the quail's relative deficiency in glutathione conjugation and the trout's low ability to conjugate sulfate compounds. Trout liver UDP-glucuronosyltransferase activity was remarkably high toward testosterone and bilirubin, while quail liver formed glucuronides of naphthol, p-nitrophenol, and digitoxigenin-monodigitoxoside. Also noteworthy was the high N-acetyltransferase activity of both quail and trout toward isoniazid, beta-naphthylamine, and 2-aminofluorene. Differences in substrate specificity for a given enzymatic pathway may be an indication that multiple forms of drug metabolizing systems also occur in these nonmammalian species. Observation of several hundred- or even thousand-fold differences between species in their enzyme activities for certain substrates under uniform conditions re-emphasizes the need for caution in extrapolation of xenobiotic metabolism from one species to another.

Acetylation↗

Interaction of metals and carbon tetrachloride on lipid peroxidation and hepatotoxicity.

Rats were administered ferrous sulfate, cadmium chloride, or sodium vanadate alone and in combination with carbon tetrachloride (CCl4) to determine if lipid peroxidation is associated with the toxicity of the three metals and to determine if there is an interaction between these metals and CCl4 in producing lipid peroxidation and hepatotoxicity. Expired ethane was used as an index of lipid peroxidation while serum alanine aminotransferase (ALT) and histopathology were used to assess liver damage. Lipid peroxidation did not appear to be associated with the hepatotoxicity of cadmium since no measurable increase in ethane production was observed when serum ALT concentrations were doubled relative to controls. Cadmium did not increase ethane when administered with CCl4 and the increase in ALT was additive. Iron and vanadate produced small significant increases in ethane production but no increase in ALT and only minor histopathologic changes, yet potentiated lipid peroxidation and liver damage when administered with CCl4. Thus, Cd did not produce lipid peroxidation and did not potentiate the lipid peroxidation and hepatotoxicity of CCl4, while iron or vanadate which produced lipid peroxidation alone potentiated the lipid peroxidation and hepatotoxicity of CCl4.

Alanine Transaminase↗

The rapid purification of 3-hydroxybutyrate dehydrogenase and malate dehydrogenase on triazine dye affinity matrices.

3-Hydroxybutyrate dehydrogenase (EC 1.1.1.30) and malate dehydrogenase (EC 1.1.1.37) were purified to homogeneity on a large scale involving only two sequential affinity-chromatography steps on two triazine dye-Sepharose matrices. Recoveries of both enzymes were in excess of 60%. Malate dehydrogenase could also be purified by a combination of triazine dye affinity chromatography and gel filtration on Ultrogel AcA-44, but this offered no significant advantage over the purely affinity procedure.

Chromatography, Affinity↗

On the disulfiram-like activity of moxalactam.

A three-way crossover study was undertaken in 10 healthy subjects to characterize the reported disulfiram-like activity of moxalactam and to assess its influence on ethanol and acetaldehyde metabolism. On different occasions separated by at least 2 wk subjects were given in random order: 0.5 gm/kg ethanol orally, 0.5 gm/kg ethanol followed in 1 hr by 1.0 gm IV moxalactam, and 1.0 gm IV moxalactam every 8 hr for four doses followed by 0.5 gm/kg ethanol. Mean ethanol elimination rates of 13.1 +/- 0.76, 10.1 +/- 1.11, and 10.9 +/- 1.06 mg/dl/hr (mean +/- SEM) were observed in the three protocols, respectively. Corresponding mean estimated acetaldehyde clearance rates were 103.7 +/- 15.55, 92.8 +/- 13.79, and 97.3 +/- 10.41 l/min (mean +/- SEM). While no consistent moxalactam effect on ethanol or acetaldehyde elimination was observed, two subjects experienced mild disulfiram-like reactions to ethanol after moxalactam pretreatment. In one subject this reaction was associated with markedly elevated blood acetaldehyde concentrations. We conclude that moxalactam pretreatment may induce a disulfiram-like reaction after ethanol ingestion in some, probably due to inhibition of aldehyde dehydrogenase, and that alcoholic beverages are contraindicated in patients receiving moxalactam. We suggest, however, that such reactions will not occur when moxalactam is given after ethanol ingestion.

Acetaldehyde↗

Shaking pups: a disorder of central myelination in the Spaniel dog. Part 1. Clinical, genetic and light-microscopical observations.

A new disorder of central myelination has been recognised in male Springer Spaniel pups which is probably inherited in a sex-linked recessive mode. The affected animals were much reduced in weight an size and showed gross generalised tremor, particularly when aroused, at about 10-12 days of age. Affected pups were studied between 1 and 3 months of age. There was severe hypomyelination throughout the CNS which was more marked in the cerebrum and optic nerves than in the spinal cord. The amount of myelin at each location increased with age. Axonal calibre also increased and there was no difference between the axonal diameters of affected and age-matched normal pups. Axons were either naked or surrounded by a disproportionately thin layer of myelin. Myelinated internodes tended to be short and heminodes were frequent. Vacuoles were present adjacent to axons or within glia but there was no evidence of demyelination. Total glial numbers were not reduced and numerous oligodendroglial and astrocytic nuclei identified. Peripheral, cranial and autonomic nerves were myelinated normally. It is suggested that there is an abnormality of oligodendroglial metabolism such that they cannot form and maintain normal myelin. Consequently the radial and longitudinal extensions of their plasma membranes are reduced. The vacuoles may represent a breakdown of defective myelin lipids as suggested in certain murine mutants. This defect of myelination provides a further model in which normal and disordered myelinogenesis can be studied.

Animals↗

Phenotypic intersex (female pseudohermaphroditism) in a dachshund dog.

A male miniature rough-haired dachshund, presented with episodic haematuria, was found to be a female pseudohermaphrodite. A littermate also had an abnormality of the urogenital tract and their dam had received a progesterone implant during pregnancy. Chromosome analysis of the intersex revealed XX/XY mosaicism in certain tissues.

Animals↗

Hormonal and histological studies in a 61XXY bull.

A Friesian bull with bilateral testicular hypoplasia was diagnosed as having a pure 61XXY karyotype. The bull displayed normal sexual behaviour but was azoospermic. At 17 months, the animal's peripheral plasma androgen levels appeared to be lower than normal, and one testicle removed one month later showed small seminiferous tubules totally lacking in germ cells. The Leydig cell volume of this testis was well within the normal range but the tubule length was rather short. At 33 months of age an increase in peripheral plasma androgen levels was noted. In the remaining testis there had been both a considerable rise in Leydig cell volume and a fall in tubule length. These findings may be explained by the interaction of three factors; the effects of the abnormal karyotype, the increased maturity of the animal at 33 months and the reaction of the remaining testis to unilateral castration.

Androgens↗

The selective retardation of NADP+-dependent dehydrogenases by immobilized procion red HE-3B.

The capacities of Procion Red HE-3B and Cibacron Blue F3G-A immobilized to Sepharose CL-4B and Matrex 201R for NAD+-, NADP+- and NAD(P)+-dependent dehydrogenases were measured. Procion Red HE-3B columns retarded NADP+-dependent dehydrogenases more effectively than NAD+-dependent dehydrogenases, whilst immobilized Cibacron Blue F3G-A retarded NAD+-dependent dehydrogenases more effectively than NADP+-dependent dehydrogenases. The capacity of procion Red HE-3B-Sepharose CL-4B for five dehydrogenases was highest in the region of 70nmol of immobilized ligand/ml of settled gel. The effects of using poly(ethyleneimine) as a spacer for both porous and pellicular supports were also examined. Four NADP+-dependent dehydrogenases were purified from yeast extract by using Procion Red HE-3B-Sepharose CL-4B. Two NAD+-dependent dehydrogenases were purified from the same source using Cibacron Blue F3G-A-Sepharose CL-4B. These results are discussed in relation to the use of immobilized Procion Red HE-3B to purify dehydrogenases. This immobilized dye's chromatograhic behaviour is compared with that of immobilized nucleotides. The most important feature of immobilized tirazine dyes seems to be their high operational capacities when compared with group-specific nucleotide adsorbents.

Chromatography, Affinity↗