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Biomedical subjects

A Fletcher

Publications and source records attributed to A Fletcher.

At least 217 records · Page 12Linked to original sources

Expression of blood group antigens by cultured human epidermal cells.

The presence of blood group antigens on the surface of cultured human epidermal cells has been demonstrated using monoclonal antibody supernatants in indirect immunoperoxidase and immunofluorescence tests. An isoantigen pattern, consistent with the blood group of the donor infant, was detected in cultures derived from 10 different foreskin specimens, and in sections of the epidermis of 5 of these specimens. The A, B, and H antigens were found on the surface of cultured keratinocytes which resembled those of the spinous and granular cell layers of the in vivo epidermis. These antigens were readily detectable throughout the majority of the lifespan of the cells in vitro. This finding may be of relevance to those contemplating allograft transplantation of cultured human epidermis.

ABO Blood-Group System↗

Effects of inhibitors of eicosanoid synthesis on insulin release by neonatal pancreatic islets.

In the pancreatic islet, eicosanoids may arise from both cyclooxygenase- and lipoxygenase-dependent metabolism of arachidonic acid. The inclusion of inhibitors of selective steps in these pathways indicated that in cultured neonatal rat islets, arachidonic acid may be metabolised through both pathways, concurrent with insulin release stimulated by D-glucose, D-glyceraldehyde and 2-ketoisocaproate. The effects of the inhibitors suggested that the products of the lipoxygenase pathway were necessary for the stimulatory effects of nutrients to be observed. In contrast to glucose, where insulin release was stimulated in the presence of inhibitors of cyclooxygenase, the stimulatory action of D-glyceraldehyde, 2-ketoisocaproate and melittin was only minimally affected by these inhibitors, although it was inhibited by lipoxygenase inhibition. These findings support a major stimulatory role for products of the lipoxygenase pathway of arachidonic acid metabolism in nutrient-induced secretion, and a negative or modulatory role of cyclooxygenase pathway products on glucose-stimulated insulin release in the neonatal islet.

Animals↗

Monoclonal antibodies specific for blood groups A and B.

Monoclonal antibodies have been produced with specificity for human blood group A following the immunization of mice with group A1 cells. The antibodies produced were of low titre and poor avidity and were therefore unsuitable as manual grouping reagents. However, in 6,524 automated tests on the Technicon BG15 monoclonal anti-A performed as well as the standard human anti-A reagent. Monoclonal anti-B antibodies were produced from a BALB/c mouse immunized with a combination of group B cells and B substance. One antibody, B/C9/F7, performed well in screening tests with avidity reactions less than 10 seconds with all B, A1B and A2B cells tested. This antibody performed with 100% accuracy in an automated test trial involving 1,018 samples. The suitability of these antibodies as blood grouping reagents is discussed.

ABO Blood-Group System↗

Hypertension produced by chemical renal medullectomy: evidence for a renomedullary vasodepressor function in the rat.

The rat renal papilla was selectively destroyed by 2-bromoethylamine hydrobromide; increasing doses produced a graded severity of histological damage, polyuria and a reduction in urinary prostaglandin E2 excretion. Destruction of at least half of the papilla caused significant hypertension, but plasma renin concentration and plasma creatinine did not change. After graded medullary damage Goldblatt two-kidney, one-clip hypertension was induced. Four weeks later the severity of hypertension was similar in medulla-damaged and medulla-intact groups. When Goldblatt two-kidney, one-clip hypertension was reversed by removal of the renal artery clip, the blood pressure fall was less when the inner renal papilla was ablated than when it was intact, although plasma renin concentration and sodium balance were similar. The final blood pressure was similar to that observed in normal rats treated with 2-bromoethylamine compared with their respective controls. These findings are consistent with the hypothesis that the inner renal medulla produces a vasodepressor that influences blood pressure in normal rats, and also lowers blood pressure when two-kidney, one-clip hypertension is reversed surgically.

Animals↗

An interesting monoclonal anti-N produced following immunization with human group O, NN erythrocytes.

Spleen cells from Balb/c mice given multiple injections of intact human erythrocytes (group O, NN) were fused with NS1 myeloma cells. Culture fluids from the resulting hybrid cells were screened for agglutinating antibody against a panel of erythrocytes. One cell line, 2/23, secreted an IgM antibody which reacted more strongly with NN than with MM cells. Neuraminidase or papain treatment of erythrocytes abolished agglutination whereas trypsin treatment did not. Reactions with U- erythrocytes of different MN phenotypes confirmed the anti-N specificity of monoclonal antibody 2/23. This is the first report of monoclonal anti-N stimulated by the immunization of mice with intact erythrocytes.

ABO Blood-Group System↗

Thermogenic properties of ciclazindol and mazindol in rodents.

Ciclazindol, a noradrenaline (NA) uptake inhibitor originally introduced as an antidepressant, has recently been shown to produce weight loss in experimental animals and patients. Unlike CNS-stimulant anti-obesity drugs, such as amphetamine, ciclazindol may induce weight loss in animals by stimulating thermogenesis in brown adipose tissue (BAT), and it is known to stimulate resting metabolic rate (RMR) of rats and depress energetic efficiency. These effects can be achieved in the absence of overt CNS stimulation and with certain analogues of ciclazindol may be due to an exclusive peripheral action. Mazindol, a structural analogue of ciclazindol also produces an increase in RMR. However the increment is qualitatively and quantitatively different from that observed with ciclazindol and cannot be dissociated from central stimulant actions. In this report we examine some of the physiological and behavioural effects of ciclazindol and mazindol analogues in rats.

Amphetamine↗

Chemical renal medullectomy: effect on blood pressure in normal rats.

The renal medulla may have a vasodepressor function in blood pressure control. We have studied the effect of selective ablation of the medulla produced with 2-bromoethylamine hydrobromide on blood pressure in the rat. Increasing doses of bromoethylamine produced a corresponding degree of histological damage. Five weeks after medullary ablation intra-arterial blood pressure was elevated only in those groups of animals which had confluent necrosis of the papilla. The degree of hypertension was not related to plasma renin concentration but showed a significant correlation with urinary prostaglandin E2 excretion. Hypertension in medullectomized animals is probably due to a loss of a medullary vasodepressor function.

Animals↗

A regional study of 4-aminobutyrate metabolism and amino acid levels in rat brain following chronic oral administration of ethanolamine O-sulphate.

Ethanolamine O-sulphate (EOS) dissolved in the drinking water (5 mg . ml(-1) was administered ad libitum to rats for 26 days. At the end of this period, glutamate decarboxylase (GAD) and GAA-transaminase (GABA-T) activities, 4-aminobutyrate (GABA) concentration, and the levels of six other amino acids were measured in various brain regions. Significant inhibition of GABA-T accompanied by significant increases in GABA content were observed throughout the brain, although the magnitudes of these effects varied according to region. GAD activity was significantly reduced in most brain regions, although this effect was apparently not related to cofactor availability or the direct actions of EOS or increased GABA concentration. Glutamine levels were significantly reduced to approximately 72% of control values in all brain regions. Aspartate levels were significantly reduced to approximately 84% of control values in all regions except the striatum and cerebellum. Minor changes in other amino acid levels were also detected. These neurochemical changes which accompanied the primary effect of EOS on GABA-T are discussed in terms of indirect secondary metabolic changes rather than nonspecific enzyme inhibition by EOS.

4-Aminobutyrate Transaminase↗

Granulomatous mastitis: a report of seven cases.

The clinical history and histological features of seven cases of granulomatous mastitis are presented. The lesion occurs in young parous women as a tender extra-areolar breast lump. Histologically, non-caseating discrete granulomas are present, confined to breast lobules with, in three cases, coalescence of the granulomas and microabscess formation. Pathogenesis of the changes is discussed. It is thought that granulomatous mastitis is an entity morphologically distinct from duct ectasia/plasma cell mastitis and the commoner forms of granulomatous breast diseases.

Adult↗

Changes in the rat sleep-wake cycle produced by DL-6-fluorotryptophan, a competitive inhibitor of tryptophan hydroxylase.

DL-6-Fluorotryptophan (6-FT), a competitive inhibitor of tryptophan hydroxylase, produced a transient disruption of sleep in rats chronically implanted with EEG recording electrodes. In the 4 h period following the administration of 6-FT (120 mg/kg) awake time was increased, paradoxical sleep time was decreased and slow-wave sleep remained unchanged. These sleep changes were accompanied by significant reductions in brain 5-HT levels. L-Tryptophan (100 mg/kg) co-administration with 6-FT prevented the major sleep changes whereas L-leucine (100 mg/kg) was without effect. The major sleep changes produced by 6-FT were prevented by the pineal indole melatonin (20 mg/kg) but not by L-5-hydroxytryptophan (5 mg/kg). These neurochemical and drug interaction data raise the possibility that 5-hydroxytryptamine is involved in the control of paradoxical rather than slow-wave sleep in the rat.

Amino Acids↗

Chemical renal medullectomy; effect upon reversal of two-kidney, one-clip hypertension in the rat.

1. Chemical renal medullectomy was produced in rats by injection of 2-bromoethylamine hydrobromide. Plasma creatinine and blood pressure were unchanged although urine volume was increased fourfold. 2. Left renal artery constriction resulted in similar degrees of hypertension in both intact and medullectomized rats. This was associated with a significantly smaller rise in plasma renin concentration in the latter. 3. Blood pressure in conscious intact hypertensive rats became normal within 24 h of unclipping whereas blood pressure of medullectomized rats remained significantly elevated. 4. The presence of an intact renal medulla is essential to the complete reversal of two-kidney, one-clip hypertension in the rat. This may reflect the loss of a medullary vasodepressor system.

Animals↗