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I Mitchell

Publications and source records attributed to I Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1982

Photometric assessment of glyoxylic acid-induced fluorescence of dopamine in the caudate nucleus.

New procedure for quantitative photometric assessment of glyoxylic acid-induced fluorescence of dopamine in the caudate nucleus are presented. A recently published cryostat method was used to process a series of 24 micrometer sections taken from the caudate nucleus of each animal. Fluorescent light contained within a circular field (0.8 mm diameter) was measured photometrically. Several defined positions within the caudate nucleus on each tissue section were selected for measurement. Thus, a grid of measurements taken throughout the caudate nucleus provided a three-dimensional description of fluorescence intensity within this structure on both sides of the brain. Several experiments were performed to evaluate both the reliability and validity of these procedures as an index of the relative regional content of dopamine within the caudate: (1) the relative distribution of fluorescence intensity within the mouse striatum was in good agreement with previously reported distributions based on biochemical determination of regional dopamine levels within the rodent brain; (2) pharmacological manipulation of dopamine levels with gamma-butyrolactone and alpha-methyl-p-tyrosine combined with amphetamine produced predictable changes in the fluorescence intensity measurements of mouse caudate relative to untreated controls; (3) in rats pre-treated with alpha-methyl-p-tyrosine, unilateral electrical stimulation of the substantia nigra caused overall differences in fluorescence intensity between the caudate nucleus on each side of the brain, which were a function of both the duration of stimulation and the stimulating pulse frequency; (4) local injections of 6-hydroxydopamine unilaterally into the ventral tegmentum of animals pretreated with desmethylimipramine caused significant reductions in the intensity of fluorescence recorded from the ipsilateral striatum. It is concluded that the photometric procedures presented in this report constitute a significant improvement in the description of regional variations in the intensity of dopamine-related fluorescence in the caudate nucleus.

Animals↗
PubMed1982

Functional validation of projection topography in the nigrostriatal dopamine system.

Anatomical investigations have revealed that the nigrostriatal pathway is topographically organised. In two experiments, nigrostriatal topography was investigated with catecholamine specific procedures, using paradigms which reflect the functional activity of dopaminergic neurones. Data were analysed with the intention of discovering possible relationships between the mesencephalic location of stimulating electrodes or injection cannulae, the extent and location of dopamine histofluorescence depletion within the striatum, and the effects of amphetamine and apomorphine on rotational behaviour. In animals pretreated with 250 mg/kg alpha-methyl-p-tyrosine it was found that unilateral stimulation with medially-placed nigral electrodes produced maximal depletion of dopamine histofluorescence in anterior dorso-medial regions of the striatum, while laterally-located electrodes principally depleted posterior, ventro-lateral areas. In the second experiment, 2 micrograms of 6-hydroxydopamine in a volume of 0.5 microliter was injected unilaterally at varying loci within the ventral midbrain of animals pre-treated with desmethylimipramine (25 mg/kg). It was discovered that the lateral injection coordinate was significantly associated with both the extent and location of the depletion of dopamine-related fluorescence from the ipsilateral striatum. Rotational behaviour, induced by dopamine-agonists was related firstly, to the overall extent of dopamine depletion from the striatum, and secondly, the contraversive turning induced by apomorphine in particular was related to the dorsoventral coordinate of the mesencephalic 6-hydroxydopamine injection. The results provide functional validation for the pattern of topographical projection within the nigrostriatal dopaminergic system proposed on the basis of intracellular tracing techniques.

Amphetamine↗
PubMed1981

Further observations on the hormonal regulation of alpha-glycerolphosphate dehydrogenase in rat mammary gland: a possible role for prolactin and thyrotropin.

The roles of prolactin and thyrotropin (TSH) in the regulation of alpha-glycerolphosphate dehydrogenase (alpha-GPDH) activity in rat mammary gland were investigated by the administration of thyroid releasing hormone, bromocriptine, prolactin, TSH and triiodothyronine (T3). TRH administration failed to induce alterations in the glands from intact animals but stimulated the activity in castrated and adrenalectomized animals. Bromocriptine administration was without any effect in either group of animals. Administration of ovine prolactin to hypophysectomized rats did not affect the activity, on the other hand, treatment with either TSH or T3 resulted in a highly significant increase in the activity. Combined administration of prolactin and TSH to hypophysectomized animals showed that prolactin is capable of partially inhibiting the TSH-induced increase. It is suggested that glucocorticoids exert primary control over the enzyme's activity with the pituitary hormones only playing a permissive role in its regulation.

Adrenalectomy↗
PubMed1981

Thallium myocardial perfusion scans for the assessment of right ventricular hypertrophy in patients with cystic fibrosis. A comparison with other noninvasive techniques.

The incidence of right ventricular hypertrophy in 32 patients with cystic fibrosis was studied using thallium 201 (TI-201) myocardial perfusion scans, and compared with other noninvasive techniques including electrocardiography, vectorcardiography, and M-mode echocardiography. The patients (mean age, 17.3 yr; range, 7 to 33) had a wide range of clinical and pulmonary abnormalities (mean Shwachman-Kulczycki score, 66.6). In the total study group, TI-201 scans, like the vectorcardiograms and the M-mode echocardiograms, gave a surprisingly high proportion of positive predictions for right ventricular hypertrophy (RVH) (44%). The correlations with all other noninvasive methods were uniformly poor, so caution must be exercised in using this technique to predict early RVH in order to follow the natural history of cor pulmonale in cystic fibrosis. At the time of the study, 6 patients had clinical evidence of right ventricular failure, and in this disease setting must have had RVH. In 3 patients, RVH was confirmed at autopsy, and it was successfully predicted by TI-201 scans in 5 of the 6 patients. The false negative scan may have been due to regional myocardial ischemia secondary to severe right ventricular failure. In contrast, the vectorcardiogram, using Fowler's new criteria, made a successful prediction of RVH in all 6 patients, and the electro cardiogram in only 3. Although the M-mode echocardiogram was abnormal in all patients, it would have predicted RVH (with increased right ventricular anterior wall thickness) in only 1 patient. We concluded that TI-201 myocardial perfusion cans are good at confirming RVH in cases with established right ventricular failure, but have no advantage over vectorcardiographic assessments, which are logistically easier to perform and carry no radiation risks.

Adolescent↗
PubMed1980

Hormone synthesis by primary breast carcinomas and prognosis in human breast cancer.

The ability of human breast carcinomas to convert pregnenolone to progesterone and dehydroepiandrosterone to delta 4-androstene-3,17-dione (delta 4) was investigated as a potential aid for prognosis, and the following observations were recorded. 1. Neither the amounts of progesterone or delta 4 synthesized nor delta 4/progesterone ratios correlated with tumour size or lymph node involvement. 2. delta 4 synthesis was lower in carcinomas from patients who had recurrences within 2 years of mastectomy than in carcinomas from those who remained free of metastases. 3. Life table analysis of the results indicated that these parameters appeared unlikely to be useful aids for prognosis.

Androgens↗
PubMed1980

Prolactin, thyrotrophin interaction in the regulation of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities in rat mammary glands.

The roles of prolactin and thyrotrophin (TSH) in the regulation of glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) activities in rat mammary glands were investigated by the administration of thyroid hormone-releasing hormone (TRH), bromocriptine, prolactin, TSH and triiodo-1-thyronine (T(3)). TRH failed to induce changes in the activities of these enzymes in glands from intact animals but the releasing hormone significantly increased the activities of both the enzymes in the glands of ovariectomized and adrenalectomized animals. Bromocriptine administration had no effect on the activities in both, intact and ovariectomized-adrenalectomized animals. Administration of ovine prolactin to hypophysectomized rats did not affect the activities of these enzymes. On the other hand treatment with TSH resulted in significant increases in the activities. On the other hand treatment with TSH resulted in significant increases in the activities. Similarly, administration of T(3) to these animals resulted in changes similar to those observed after TSH administration. Combined administration of prolactin and TSH showed that prolactin is capable of partially inhibiting the TSH-induced increases. It is concluded that TSH is involved in the channelling of substrates into the pathways of nucleic acid synthesis and prolactin probably plays a regulatory role in this process.

Animals↗
PubMed1980

Effects of testosterone propionate and cyproterone acetate on carbohydrate metabolism in rat mammary glands.

The effects of administration of testosterone propionate on the activities of seven of the enzymes of carbohydrate metabolism in normal rat mammary glands were investigated and the validity of the results was confirmed by simultaneous injection of the hormone and cyproterone acetate. The administration of the androgen increased the activities of phosphofructokinase (PFK), glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH) and lactate dehydrogenase (LDH) in glands from both intact and from ovariectomized and adrenalectomized animals. Administration of cyproterone acetate alone resulted in a significant reduction in the activities of PFK and G6PDH and when given together with the androgen it inhibited increases in the activities of PFK, G6PDH, 6PGDH and LDH induced by testosterone. It was concluded that these results did not explain the known inhibitory effects of the androgen on normal mammary gland growth and function.

Adrenalectomy↗
PubMed1980

Evidence for the participation of opioids in the regulation of carbohydrate metabolism in rat mammary glands.

The possible involvement of opioids in carbohydrate metabolism in rat mammary glands was investigated by studying the effects of administration of morphine and naloxone on six enzymes. Morphine inhibited phosphofructokinase (PFK) and stimulated phosphohexose isomerase (PHI) activities. Nalozone treatment alone, to both intact and ovariectomized/adrenalectomized animals, resulted in stimulation of PFK and inhibition of PHI activities. A combined dose of morphine and naloxone to intact animals showed that the opiate antagonist was able to reverse the morphine-induced changes. Evidence is presented to show that the changes observed in PHI activity may be the result of the indirect action of opioids on luteinizing hormone releasing hormone. However, the changes observed in PFK activity might be the result of direct action of opioids. Failure to observe changes in enzyme acstivities after naloxone treatment of hypophysectomized animals suggests the opiate antagonist might be acting on the pituitary gland to block the release of endorphins.

Adrenalectomy↗
PubMed1978

Microbial assays for mutagenicity: a modified liquid culture method compared with the agar plate system for precision and sensitivity.

A microbial assay system for mutagenicity was developed in which bacterial cells divided in liquid culture. The statistical and practical problems associated with dividing cells were avoided or reduced, whilst the advantages in precision and reliability resulting from the determination of mutation per colony-forming unit (survivor) and of separating the mutation and selection systems were retained. Seven mutagens, two of which required microsomal activation, were evaluated by this liquid-medium method and by the agar-plate method with two strains of Salmonella typhimurium to determine which assay system was the more sensitive. At highly mutagenic and/or very toxic concentrations of the test substance the liquid-medium assay was markedly more sensitive than the agar-plate assay, but at weakly mutagenic and less toxic concentrations the advantage of the liquid-medium test was reduced; however in only one case was the agar-plate assay obviously the more sensitive. There was a clear indication that the liquid-medium assay would be superior to the agar-plate assay for the detection of mutagenic agents active only at toxic concentrations, and also could be more easily and exactly quantified.

Animals↗