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Biomedical subjects

J Funder

Publications and source records attributed to J Funder.

At least 19 recordsLinked to original sources
PubMed1991

Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with diabetic nephropathy.

Genetic predisposition to essential hypertension, as indicated by increased maximal velocity of Na+/Li+ countertransport in red cells, has been suggested as a marker for the risk of developing diabetic nephropathy. To evaluate the validity of this concept in non-insulin-dependent diabetics, we measured the maximal velocity of Na+/Li+ countertransport in red cells in 18 male diabetics suffering from proteinuria due to biopsy proven diabetic glomerulosclerosis (GFR: 51 [range 27 to 146] ml/min/1.73 m2), 17 male diabetics with normoalbuminuria, and in 18 sex-, age-, and body mass index-matched healthy control subjects. Na+/Li+ countertransport was identical in patients with and without diabetic nephropathy, 0.43 (0.24 to 0.92) versus 0.44 (0.20 to 0.83) mmol/(liter cells x hr), but was elevated compared to control subjects, 0.32 (0.09 to 0.73; P less than 0.05). Arterial blood pressure was elevated in patients with nephropathy (162/92 +/- 21/9 mm Hg) compared to normoalbuminuric patients (132/82 +/- 15/7) and control subjects (133/83 +/- 14/7 mm Hg; P less than 0.001). Our study does not support the hypothesis that the risk of diabetic nephropathy in non-insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Diabetes per se seems to enhance Na+/Li+ countertransport activity.

Antiporters↗
PubMed1990

Increased blood pressure and erythrocyte sodium/lithium countertransport activity are not inherited in diabetic nephropathy.

Genetic predisposition to essential hypertension, represented by maximal erythrocyte sodium/lithium countertransport activity, has been suggested as a marker for the risk of developing clinical nephropathy in Type 1 (insulin-dependent) diabetes mellitus. To evaluate this hypothesis we measured arterial blood pressure and maximal sodium/lithium countertransport activity of erythrocytes in 80 parents of 49 Type 1 diabetic patients with clinical nephropathy, 78 parents of 49 normoalbuminuric patients and 17 age-matched non-diabetic individuals. The two diabetic groups were carefully matched. In the two groups of parents blood pressure and cell sodium/lithium countertransport activity showed no significant differences (137/83 vs 133/81 mm Hg and 0.33 vs 0.32 mmol/(1 cells x h) respectively). The proportion of parents who had died or received antihypertensive drugs was similar in the two groups. The patients with Type 1 diabetes had significantly higher sodium/lithium countertransport compared to the 39 non-diabetic control subjects independently of the presence or absence of nephropathy (p less than 0.002). However, patients with nephropathy tended to have higher sodium/lithium countertransport activity than normoalbuminuric patients (0.48 vs 0.41 mmol/(1 cells x h), p = 0.06). We conclude that genetic predispositions to essential hypertension and increased maximal erythrocyte sodium/lithium countertransport activity do not appear to be risk markers for the development of clinical nephropathy in Type 1 diabetic patients.

Antiporters↗
PubMed1989

The action of corticosterone on schedule-induced wheelrunning.

Previous studies have shown that schedule-induced wheelrunning is dependent on an intact pituitary-adrenal axis, and thus the presence of circulating corticosterone. In the present study, the mechanism of action of corticosterone on schedule-induced wheelrunning was explored in two ways. In the first series of studies, the effect of different levels of corticosterone on schedule-induced wheelrunning in adrenalectomized rats was investigated; the results of this study show a dose-response relationship between levels of corticosterone and schedule-induced wheelrunning. In the second study, the glucocorticoid receptor subtype involved was determined by examining the effect of dexamethasone, a synthetic glucocorticoid, on schedule-induced wheelrunning in adrenalectomized rats. A low dose of dexamethasone effectively reversed the suppressant effect of adrenalectomy, suggesting that the behavioural action of glucocorticoids is mediated through classical (Type II) glucocorticoid receptors, and not through Type I, corticosterone-preferring receptors.

Adrenalectomy↗
PubMed1989

Generation of Met-enkephalin Arg6Phe7 immunoreactivity by proteolytic cleavage of mammalian plasma precursors by pepsin.

A region-specific antiserum raised against the C-terminal heptapeptide of proenkephalin A (Met-enk Arg6Phe7) was used in RIA studies to show that rat, human, and ovine plasma contain substrates (mol wt, 68K) that yield nanomolar amounts of Met-enk Arg6Phe7 (ME-RF) after treatment with pepsin under acid conditions. This ovine plasma-derived immunoreactivity diluted in parallel to the ME-RF standard in RIA and chromatographed as two low mol wt species (approximately 1K) which were less hydrophobic than the standard on size exclusion and reverse phase chromatography. The pepsin-generated material displaced [3H]naloxone from rat brain binding sites; its potency was about 1000-fold that of ME-RF, assuming near 100% cross-reactivity with the antiserum. Taken together these observations suggest that the pepsin-generated material is of similar mol wt and amino acid sequence to ME-RF, but differs with respect to opiate-binding efficacy, and that the plasma precursor is distinct from proenkephalin in both size and processing sites.

Animals↗
PubMed1988

Na+/H+ exchange and aggregation of human platelets activated by ADP: the exchange is not required for aggregation.

Isolated human blood platelets, loaded with the pH-sensitive fluorescence dye 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein show cytoplasmic alkalinization upon stimulation with thrombin but acidification with ADP stimulation. In both cases a Na+/H+ exchange is activated. This can be revealed by the sensitivity of the induced pH changes to amiloride and to 5-N-(3-aminophenyl)amiloride (APA), known inhibitors of the Na+/H+ exchanger, and by a dependence on sodium in the external medium. ADP-induced platelet aggregation is not affected by omission of sodium from the external medium. Furthermore, aggregation is barely inhibited (less than 10%) by amiloride or APA at concentrations up to 50 microM while the Ki values in affecting the Na+/H+ exchange are 5.9 and 1.6 microM for amiloride and APA, respectively. Platelet aggregation is inhibited by amiloride or APA at concentrations higher than 50 microM, but this inhibition is apparently due to a secondary effect of the agents. It is concluded that platelet aggregation induced by ADP is not dependent on activation of Na+/H+ exchange.

Adenosine Diphosphate↗
PubMed1988

Traumatic lesion of the optic nerve.

The problems of therapy are described by comparing a retrospective (17 cases) to a prospective (12 cases) study of cases of traumatic lesions of the optic nerve. Intensive cooperation between specialists and a quick diagnosis facilitate the decision regarding treatment and lead to better results. Indication for surgical treatment-transcranial or transethmoidal approach-should be confined to posttraumatic deterioration of optic nerve function in combination with fractures of the optic canal, and to its deterioration in spite of proper conservative treatment-shock treatment and cortisone infusions-.

Accidents, Traffic↗
PubMed1988

Ectopic hormone production by a prostatic small cell carcinoma xenograft line.

The xenograft line, UCRU-PR-2, has been characterized further. Established from a primary human undifferentiated small cell carcinoma of the prostate, it has been maintained as a stable xenograft line in nude mice and is currently in passage 9. The tumor has maintained the features of small cell undifferentiated carcinoma but shows epithelial as well as neuroendocrine characteristics. In this paper, we describe synthesis and secretion of peptide hormones, ACTH, beta-endorphin and somatostatin in vivo and ACTH and beta-endorphin in vitro by the tumor, UCRU-PR-2. This suggests that the gene for proopiomelanocortin is expressed and that processing of the molecule occurs. This line may yield insights into the histogenesis of the subtypes of prostate cancer, and also aid studies of regulation of ectopic hormone production.

Adrenocorticotropic Hormone↗
PubMed1987

Further evidence for coupling of sodium and proton movements in dog red blood cells.

Using 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) and tributyltin the sodium transport pathway activated by shrinkage in dog red blood cells is shown to behave as expected for an electroneutral Na+/H+ exchanger. When the driving forces for sodium and protons are equal, flow through the pathway stops. Amiloride inhibits the shrinkage-induced Na+/H+ exchange.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Hippocampal and renal type I receptors are differentially regulated.

Previously, we have shown that renal mineralocorticoid receptors and hippocampal "corticosterone-perferring" sites have identical intrinsic steroid specificity in vitro. Others have shown that the aldosterone binding species in kidney and hippocampus have identical trypsin fragmentation patterns on isoelectric focusing. To further explore possible areas of identity, we determined levels of type I receptors in hippocampus, renal outer medulla cortex, and renal inner medulla papilla from 22 min to 16 days after adrenalectomy. Available type I sites in kidney fractions increased postadrenalectomy to plateau levels in 22 (inner medulla papilla) or 90 min (outer medulla cortex). In contrast, available hippocampal receptors attained maximal levels 24-48 h postadrenalectomy. Animals, 24-h adrenalectomized, showed no differences in steroid uptake or washout between kidney and hippocampus, determined by in vitro tracer binding 22 or 90 min after intravenous aldosterone or corticosterone. We interpret the marked difference in receptor levels between kidney and hippocampus postadrenalectomy as evidence for tissue-specific differences in the control of receptor levels by endogenous steroids.

Adrenalectomy↗
PubMed1986

[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↗
PubMed1985

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↗
PubMed1979

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↗
PubMed1978

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↗
PubMed1976

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↗