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Biomedical subjects

J Funder

Publications and source records attributed to J Funder.

At least 37 records · Page 2Linked to original sources

[Differential diagnosis of papilledema].

Terminology, pathogenesis and differential diagnosis of papilloedema are discussed. A series of 100 consecutive patients with optic disc swelling is reviewed. Increased intracerebral pressure accounted for 32% of the cases. Vascular disease, such as central vein occlusion, central arterial occlusion and ischaemic neuropathy were the underlying diagnoses in the second largest group (22%) and in 18% of cases inflammatory disease caused the papillitis.

Diagnosis, Differential

Effects of mineralocorticoids and glucocorticoids on compensatory adrenal growth in rats.

The rapid compensatory growth seen in the remaining adrenal gland of the rat after unilateral adrenalectomy appears to require a functioning neural arc between the adrenal glands and the hypothalamus, but the role of adrenal or pituitary hormones is unclear. We have examined the effect of several steroids on the compensatory adrenal growth (CAG). Female and male rats (average wt 140 g) were unilaterally adrenalectomized and treated with aldosterone (2.1 micrograms/day), corticosterone (B, 28 micrograms/day), dexamethasone (28 micrograms/day), 9 alpha-fluorocortisol (9 alpha FC, 28 micrograms/day), or deoxycorticosterone (DOC, 28 micrograms/day) by continuous infusion for 3 days and then killed. The growth in the remaining adrenal was compared both with sham-operated rats treated with steroid infusions and with noninfused controls. In rats of this size females have larger adrenals than males; untreated male rats have significantly heavier left than right adrenals. In male rats the extent of CAG after no treatment or treatment with aldosterone B, 9 alpha FC, or DOC depended on the size of the adrenal gland removed. In both male and female rats CAG was not significantly affected by aldosterone, in contrast with a recent report, nor by B, 9 alpha FC, or DOC; no significant CAG was seen after dexamethasone. Taken together, these results and previous reports suggest that neurally mediated activation of pituitary and/or local adrenal growth factors may be responsible for CAG.

Adrenal Glands

Behavioural effect of adrenalectomy: reversal by glucocorticoids or [D-Ala2,Met5]enkephalinamide.

Rats adrenalectomized 4-6 d before a 15-min swimming test showed levels of immobility indistinguishable from controls. Retested 24 h later, adrenalectomized rats showed significantly reduced (28%) immobility compared with controls (70%) or hypophysectomized rats (60%), but not hypophysectomized-adrenalectomized rats (41%). The effect of adrenalectomy was reversed by the administration (within 1 h of initial test, but not subsequently) of dexamethasone (6-20 micrograms; 65% immobility) and corticosterone (6 mg; 74%), but not by the mineralocorticoid deoxycorticosterone (6 mg; 33%). [D-Ala2,Met5]enkephalinamide (5-50 micrograms) also restored immobility (66%). We postulate that hormones from both adrenal medulla and cortex are involved in the retention of information post-stress, and that these hormones act directly on the CNS rather than via the pituitary, since the response to adrenalectomy is not dependent on the presence of the pituitary gland.

Adrenalectomy

Reliability of steroid hormone receptor assays: an international study.

The reproducibility of oestrogen and progestin receptor assays performed by laboratories participating in an international breast cancer treatment trial has been assessed. Three tissue reference powders containing low, medium and high oestrogen receptor levels (22 +/- 4, 88 +/- 7, 227 +/- 13 fmol/mg cytosol protein respectively) were prepared in Louisville, KY, U.S.A., assayed repeatedly and multiple samples of each shipped on solid CO2 to the coordination-distribution centre in Berne, Switzerland. Samples were dispatched from Berne to Cantons within Switzerland, to Yugoslavia, South Africa, Australia, New Zealand and also back to the United States for oestrogen and progestin receptor assays. Results were returned to Berne, Switzerland. There was a decrease in the levels of oestrogen and progestin receptors during the time of storage and transit. However, the ability to assign a powder to either the low, medium or high level of oestrogen receptor was not affected. Laboratories also determined progestin receptor. All laboratories clearly identified the powder containing the low level of progestin receptor, but there was poor quantitation with the other two assay standards. It is recommended that clinical hormone receptor laboratories, especially those participating in clinical trials, establish regular quality control procedures for both daily evaluation internally and periodic outside monitoring of interlaboratory variation.

Animals

Expression of the prolactin gene in human decidua-chorion.

Messenger RNA (mRNA) purified from human decidua-chorion hybridizes with a 32P-cDNA probe for human prolactin. In contrast, mRNA from human trophoblast and amnion does not hybridize to prolactin cDNA. The migration position on agarose gels of prolactin-specific mRNA from human decidua-chorion is similar to that for mRNA from ovine pituitary, suggesting a similar sized mRNA coding for prolactin in these different tissues and species. These data demonstrate unambiguously that the prolactin gene is expressed in human decidua-chorion, confirming previous immunochemical reports of prolactin production by this tissue in culture.

Amnion

Alkali metal cation transport through the human erythrocyte membrane by the anion exchange mechanism.

This work deals with the possibility that cations may be transported through the human red blood cell membrane as negatively charged ion pairs of the type XCO3-. Passive sodium influx into human erythrocytes was increased 4-fold when 150 mM chloride was substituted with bicarbonate in the medium. This increased permeability to sodium was completely abolished when the cells were pretreated with a specific inhibitor of anion transport (DIDS). Both bicarbonate-induced sodium influx and chloride exchange were linearly related to DIDS-binding. Both transport processes were completely inhibited by the binding of 1.1 X 10(6) DIDS molecules per cell. The presence of bicarbonate and/or pretreatment of the cells with DIDS did not change the permeability of the erythrocyte membrane to K+, Rb+, and Cs+ to any significant extent. The experimental findings support the hypothesis that Li+ and Na+, but not K+, Rb+, and Cs+ form monovalent negatively charged ion pairs with CO3--, which traverse the membrane through the anion exchange system.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid

Autoradiographic localization of 3H-glucocorticoids and 3H-cortexolone in mouse pituitary.

Autoradiograms of mouse pituitaries were prepared 30 min after injection of 3H-dexamethasone (3HDM), 3H-corticosterone (3HB) and 3H-cortexolone (3HS) either alone or in the presence of competing unlabelled steroids. 3H-dexamethasone accumulated in cell nuclei of both the pars distalis and the pars nervosa but not in those of the pars intermedia. This preferential accumulation (nuclear/cytoplasmic grain density, 4 : 1) was abolished by the concurrent administration of excess dexamethasone. 3H-corticosterone, to a much less marked extent than 3H-dexamethasone, accumulated in cell nuclei of the pars distalis but not in those of the pars intermedia and the pars nervosa. Excess unlabelled corticosterone diminished nuclear grain density in the pars distalis. After 3-h-cortexolone injection, preferential nuclear uptake was not observed. In a second series of experiments, excess dexamethasone (10 x, 100 x), corticosterone (100 x, 300 x) and cortexolone (100 x, 300 x) administered with 3H-dexamethasone were without effect on cytoplasmic grain density but totally abolished preferential nuclear accumulation. Parallel biochemical studies on kidney cytoplasmic preparations from the same animals showed no differences in total cytoplasmic radioactivity between treatments but marked differences in cytoplasmic bound 3H-dexamethasone. The results demonstrate: i) that dexamethasone binds specifically to cell nuclei of the pars distalis and the pars nervosa and that this nuclear concentration is abolished by competing corticosterone and cortexolone as well as dexamethasone; ii) that corticosterone localizes in cell nuclei of the pars distalis but much less markedly than dexamethasone; iii) that cortexolone fullfils the criteria of a glucocorticoid antagonist at the pituitary cell level.

17-Hydroxycorticosteroids

Effects of bicarbonate on lithium transport in human red cells.

Lithium influx into human erythrocytes increased 12-fold, when chloride was replaced with bicarbonate in a 150 mM lithium medium (38 degrees C. pH 7.4). The increase was linearly related to both lithium- and bicarbonate concentration, and was completely eliminated by the amino reagent 4, 4'- diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). DIDS binds to an integral membrane protein (mol wt approximately 10(5) dalton) involved in anion exchange. Inhibition of both anion exchange and of bicarbonate-stimulated lithium influx was linearly related to DIDS binding. 1.1 X 10(6) DIDS molecules per cell caused complete inhibition of both processes. Both Cl- and Li+ can apparently be transported by the anion transport mechanism. The results support our previous proposal that bicarbonate-induced lithium permeability is due to transport of lithium-carbonate ion pairs (LiCO-3). DIDS-sensitive lithium influx had a high activation energy (24 kcal/mol), compatible with transport by the anion exchange mechanism. We have examined how variations of passive lithium permeability, induced by bicarbonate, affect the sodium-driven lithium counter-transport in human erythrocytes. The ability of the counter-transport system to establish a lithium gradient across the membrane decrease linearly with bicarbonate concentration in the medium. The counter-transport system was unaffected by DIDS treatement. At a plasma bicarbonate concentration of 24 mM, two-thirds of the lithium influx is mediated by the bicarbonate-stimulated pathway, and the fraction will increase significantly in metabolic alkalosis.

Bicarbonates

Chloride transport in human erythrocytes and ghosts: a quantitative comparison.

1. Homogeneous preparations of resealed ghosts with intracellular KCl concentrations between 15 and 900 mM could be prepared. Virtually all ghosts sealed to chloride. The chloride transport system was found not to be damaged: a quantitative comparison of the self-exchange of 36Cl- across intact and resealed membranes showed that both the transport capacity and a number of characteristic properties were identical (saturation kinetics, temperature dependence and the effect of inhibitors). 2. Due to the absence of intracellular titratable buffers intracellular chloride concentration in ghosts vary only slightly between pH5 and 11. The unidirectional exchange flux was constant between pH 7 and 11, showing that the transport system does not have a functionally important titratable group in the alkaline range, as previously assumed. The decrease of transport below pH 7 is similar in intact erythrocytes and ghosts. 3. Mean cellular volume of the resealed ghosts was a function of the amount of KCl added at 'reversal', before the ghosts are sealed. The ghosts shrank by osmosis when KCl was added to the suspension of 'unsealed' ghosts. The reflexion coefficient of sucrose (and therefore the osmotic effect) is larger than that of KCl. It was, therefore, possible to demonstrate that volume changes do not affect the chloride transport across the human red cell membrane. Unidirectional chloride fluxes at a KCl concentration of 165 mM were independent of ghost volume (100-40 mum3).

Biological Transport