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Biomedical subjects

D B Lee

Publications and source records attributed to D B Lee.

At least 55 records · Page 3Linked to original sources
PubMed1989

Erythropoietin in renal transplant recipients: studies based on recombinant human erythropoietin radioimmunoassay.

In posttransplant patients, modest increases in endogenous EPO induce erythropoiesis similar to that observed in uremic patients who are given large doses of exogenous rHuEPO that generate vastly higher circulating EPO levels. Moreover, once it is initiated, erythropoiesis may be sustained by normal levels of EPO. These observations raise the possibility that the restoration of renal function may alter the EPO-erythropoiesis response pattern. It is also possible that the resolution of uremic anemia is dependent on factors in addition to the level of circulating EPO.

Biomarkers↗
PubMed1988

Cyclosporine-A transport in isolated renal proximal tubular cells: inhibition by calcium channel blockers.

We have studied the transport characteristics of cyclosporine A (CSA) in isolated rabbit renal proximal tubular cells (PTC). The uptake as well as efflux was very rapid and dependent on temperature. PTC accumulated CSA by several fold above the incubation medium concentration. Kinetic analysis yielded an apparent Km and Vmax values of 5.1 microM and 47 Pmoles/10(6) cells/min respectively. Calcium channel blockers verapamil or diltiazem, at concentrations (0.5-1.0 mM) that inhibited calcium uptake, reduced CSA uptake significantly. Other calcium transport modulators A23187 (5 microM), trifluoroperazine (50 microM) and ruthenium red (100 microM) induced anticipated changes in calcium uptake but had no effect on CSA uptake. These results suggest a close association or interaction between the calcium channels and the CSA transporting/binding sites on PTC membranes.

Animals↗
PubMed1988

Renal osteodystrophy: some new questions on an old disorder.

The two major lesions of renal osteodystrophy are osteitis fibrosa cystica (OFC) and osteomalacia (OM). OFC is the characteristic bone lesion of uremic hyperparathyroidism. Although renal failure causes predictable parathyroid hyperplasia, the precise pathogenetic mechanism is still not defined. The "hyperphosphatemia-hypocalcemia-parathyroid hormone (PTH) hypersecretion" sequence of events is no longer an adequate model for the pathogenesis of uremic hyperparathyroidism. Other abnormalities associated with uremia include reduced 1,25-dihydroxyvitamin D (1,25D) synthesis, changes in intracellular phosphorus content or transcellular phosphate fluxes, or alteration in PTH metabolism, eg, change in set-point for PTH secretion. Each abnormality interacts with others and contributes to PTH hypersecretion, but none can completely account for the development and persistence of hyperparathyroidism in renal failure. The possibility that uremia may directly cause parathyroid hyperplasia remains open. It is also possible that factor(s) that initiate hyperparathyroidism may turn out to be quite different from that which sustains the hyperparathyroid state. Although both vitamin D-deficient and vitamin D-resistant OM may develop in patients with renal failure, the majority of uremic OM seen currently is "vitamin D-refractory." Although now there is persuasive evidence implicating aluminum (Al) accumulation as the major pathogenetic cause for the mineralization defect seen in this disorder, additional disturbances may play important contributory roles. Such factors would include extraskeletal effects of Al, differences in host-susceptibility to this element, the localization of Al within bone, uremia per se, and the participation of other metals and toxins. Finally, possible interactions between hyperparathyroidism and OM of uremia are speculated on.

Aluminum↗
PubMed1988

Influence of prostaglandins on unidirectional zinc fluxes across the small intestine of the rat.

1. The regulatory role of prostaglandins (PGs) E2 and F2 alpha on the zinc transport rate across the jejunal segments of rats was examined by employing the Ussing chamber technique. The Zn flux rate from mucosa to serosa across jejunal segments (Jms) was 5.24 (SE 1.54) nmol/h per cm2 (n 48) and that from serosa to mucosa (Jsm) was 15.16 (SE 2.38) nmol/h per cm2 (n 48) when both sides of the segment were bathed with Ringer's bicarbonate solution containing 0.5 mM-zinc chloride and 3 mM-L-histidine. 2. When 5.0 or 50 microM of either PGE2 or PGF2 alpha were added to the serosal side of the tissue, Jsm generally decreased and Jms generally increased, compared with controls. On the other hand, when PGE2 or PGF2 alpha was added to the mucosal side of the tissue, Jms either did not change or increased while Jsm had a tendency to decrease. 3. The Zn uptake capacity of tissue increased significantly when PG was added to the serosal side of the tissue-bathing medium, but not when PG was added to the mucosal side. The uptake capacity of mucosal Zn by jejunal segments was approximately twice that of serosal Zn. 4. When PG was included in the tissue-bathing medium, the short-circuit current, potential difference and conductance between the mucosa- and serosa-bathing media generally decreased. 5. These results suggest that (a) PGs influence Zn flux rate not by chelating Zn and carrying it across the mucosal cell membrane but by interacting with the cytosolic components, (b) it is the serosal PGs which control the Zn flux rate and (c) PGs play a part in triggering a transduction mechanism in the intestinal Zn transport process.

Animals↗
PubMed1987

A kinetic study of cation transport in erythrocytes from uremic patients.

We previously described in red blood cells (RBCs) from uremic patients on dialysis a reduction in sodium (Na) efflux through the Na, potassium (K) cotransport system (Na,K CoT) while Na efflux through the Na,K pump was normal. We then examined Na efflux in fresh cells and in cells loaded to obtain one level of intracellular sodium (Nai) concentration at about 25 mmol/liter cell. In the present study we used similar cation flux methodology to examine the kinetics of cation efflux through the Na,K pump and Na,K CoT in uremic patients on dialysis. RBCs were Na-loaded to attain five different levels of Nai concentration over a range of 5 to 50 mmol/liter cells using the ionophore nystatin. At each level of Na-loading, the Nai achieved was similar in RBCs from controls and patients. Ouabain-sensitive Na efflux through the Na,K pump showed no difference in rate between normals and dialysis patients. When the kinetic parameters of this transport pathway were considered, the apparent affinity (K0.5) for sodium was not significantly different between controls and patients (18.4 +/- 2.3 vs. 20.0 +/- 2.6 mmol/liter cell) and the maximal velocity of efflux (Vmax) was also not different between controls and patients (9.6 +/- 0.7 vs. 8.5 +/- 1.2 mmol/liter cell/hr). Comparison of Nai-activated Na versus K efflux rates through the Na,K CoT in normal subjects demonstrated similar saturation kinetics, (K0.5 15.8 +/- 3.3 vs. 12.2 +/- 2.8 mmol/liter cell, Vmax 0.81 +/- 0.1 vs. 0.78 +/- 0.1 mmol/liter cell/hr) consistent with the known stoichiometric ratio of 1 Na:1 K:2 Cl described for this mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Effect of high calcium intake on pressor responsivity in hypertensive rats.

Some proposed mechanisms for the hypotensive effect of high calcium intake involve reduction in vascular responsivity. To assess the effect of dietary calcium on vascular responsivity, spontaneously hypertensive rats (SHR) were placed on normal (N-Ca; 0.4%) or high (H-Ca; 2.8%) casein-based synthetic diet for 4 wk. Intraarterial pressure, pressor response to graded intravenous infusion of norepinephrine (NE) and angiotensin II (ANG II), and in vitro vascular reactivity of tail artery segments to NE and transmural nerve stimulation (TNS) were studied. Urinary electrolyte excretion, plasma renin activity (PRA), aldosterone, NE, and epinephrine (EPI) were also determined. H-Ca SHR had a lower intraarterial systolic and diastolic pressure. However, H-Ca SHR had greater in vivo pressor response to both ANG II and NE. Maximal contractile force developed by tail artery segments in vitro in response to NE and TNS was slightly, but not significantly, higher in H-Ca SHR. In vitro dose-response curves to NE and TNS were not significantly different. Although H-Ca SHR had increased urinary excretion of sodium throughout the study period, PRA and aldosterone levels were similar in both groups. Plasma NE and EPI levels in the two groups were also not different. Despite lowered intra-arterial blood pressure, H-Ca SHR exhibited enhanced pressor response to ANG II and NE in vivo and a similar in vitro vascular reactivity to NE and TNS when compared with N-Ca SHR. Our results do not support a role for alterations in vascular reactivity to NE or ANG II in the hypotensive effect of high calcium intake in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1987

Effect of cyclosporin on blood pressure and renin-aldosterone axis in rats.

Although hypertension is a frequent complication of cyclosporin A (CSA) therapy in clinical practice, little experimental information is available on the nature and the mechanism of this form of hypertension. We studied the effect of currently recommended therapeutic dosages of CSA, i.e., 5 (CSA5) and 20 (CSA20) mg.kg-1.day-1, on blood pressure and the renin-aldosterone system (RAS) in spontaneously hypertensive rats (SHR). Influence of in vivo CSA treatment on in vitro angiotensin II (ANG II)-stimulated aldosterone secretion by isolated adrenal glomerulosa cells (AGC) was also measured. CSA treatment in SHR resulted in a consistent increase in systolic blood pressure. This increase in blood pressure occurred in the absence of significant changes in creatinine clearance in CSA5 rats, whereas in CSA20 rats a significant reduction in creatinine clearance was observed. Sodium balance and serum calcium and magnesium concentrations were not different between the control group and either of the two CSA-treated groups of rats. Plasma renin concentration (PRC) and inactive renin (IR) were markedly elevated, but plasma renin substrate remained unchanged with CSA administration. Despite the presence of hyperreninemia, plasma aldosterone was not elevated, suggesting that CSA may induce relative adrenal resistance to ANG II. This possibility was tested using AGC isolated from CSA-treated rats. ANG II-stimulated aldosterone secretion in AGC was diminished by low dose and aborted by high dose CSA-treatment. Thus CSA administration in SHR induces a predictable increase in blood pressure in association with "hyperreninemic hypoaldosteronism."

Adrenal Cortex↗
PubMed1987

Cyclosporin A-induced hyperreninemic hypoaldosteronism. A model of adrenal resistance to angiotensin II.

We studied the effects of cyclosporin A on the renin-aldosterone axis in Sprague-Dawley rats. Two weeks of intragastric administration of cyclosporin A (5 mg/kg/day or or 20 mg/kg/day) resulted in large increases in plasma renin concentration (23 +/- 5, 70 +/- 12, and 79 +/- 11 ng/ml/hr in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively), with no parallel increments in plasma aldosterone. In vitro angiotensin II (ANG II)-stimulated aldosterone secretion by zona glomerulosa cells obtained from cyclosporin A-treated rats was also reduced (4.8 +/- 0.5, 1.5 +/- 0.2, and 0.2 +/- 0.2 ng/10(5) cells in control rats and rats receiving 5 mg and 20 mg of cyclosporin A, respectively). In contrast, in vitro aldosterone response to graded increments of potassium (3.7-10.7 mmol/L) or adrenocorticotropic hormone (ACTH) (10(-11)-10(-8) M) was preserved in cyclosporin A-treated rats. When added in vitro to zona glomerulosa cells from untreated rats, cyclosporin A also attenuated ANG II-stimulated aldosterone secretion, but did not affect potassium or ACTH-mediated aldosterone production. Thus, cyclosporin A-induced hyperreninemic hypoaldosteronism in the rat depends on opposing renal and adrenal effects, with a direct or feedback stimulation of renin secretion and a specific blockade of ANG II-mediated aldosterone production.

Adrenal Glands↗
PubMed1987

Clinical disorders of phosphorus metabolism.

Deranged phosphorus metabolism is commonly encountered in clinical medicine. Disturbances in phosphate intake, excretion and transcellular shift account for the abnormal serum levels. As a result of the essential role played by phosphate in intracellular metabolism, the clinical manifestations of hypophosphatemia and hyperphosphatemia are extensive. An understanding of the pathophysiology of various phosphate disorders is helpful in guiding therapeutic decisions.

Humans↗
PubMed1987

Epidemiologic study of Kawasaki disease in Korea.

The cumulative number of K.D. patients for the past 15 years in Korea was 2,224. There were two epidemics, in winter of 1979 and summer of 1983. The increase in patient numbers accelerated remarkably after each epidemic. This disease had a tendency to occur in urban areas with high density of population and was more likely to occur in male infants under two years of age than in females. When it is taken into consideration that the first and second epidemics occurred in this country at intervals of seven months and 1 1/4 years, respectively, after epidemics in Japan, it is possible that the third epidemic in Korea may occur in the near future, in view of the large epidemic in Japan in the beginning of 1986.

Child↗
PubMed1987

Cyclosporine A--calcium channels interaction: a possible mechanism for nephrotoxicity.

Rabbit PTC concentrated CsA rapidly and reached saturation by two to three minutes. CsA uptake was temperature dependent but was not altered by replacement of uptake medium Na with K or mannitol, changes in extracellular pH, and the presence of metabolic inhibitors or organic anions and cations. The organic Ca channel blockers verapamil and diltiazem and the inorganic Ca channel blocker cadmium caused significant inhibition in both Ca and CsA uptake by PTC. Other Ca transport modulators, ruthenium red and trifluoroperazine, decreased PTC Ca uptake, and A23187 increased PTC Ca uptake, but they were all without effect on CsA uptake. We propose that the CsA uptake pathway through PTC is situated at or close to Ca channels so that changes induced by Ca channel blockers also affect transit of CsA through the CsA "passageway." The close spatial relationship between CsA and Ca channels also raises the possibility that CsA uptake may intiate Ca channel-related activities, thereby leading to a cascade of Ca-dependent processes and causing nephrotoxicity. A hypothesis is depicted in Fig 1.

Animals↗
PubMed1986

Sodium transport in red blood cells from dialyzed uremic patients.

Studies on red blood cell (RBC) sodium (Na) transport in chronic renal failure have described abnormalities in the ouabain-sensitive Na, K pump. We now report Na transport in RBC using cation flux methodology, measuring both the ouabain-sensitive Na, K pump and the ouabain-insensitive Na, K cotransport (CoT) and Na, lithium (Li) countertransport (CTT) in 28 subjects on hemodialysis, eight subjects on chronic ambulatory peritoneal dialysis (CAPD) and 29 control subjects. Intracellular cation content and passive permeability of Na were also examined. Mean Na efflux through the ouabain-sensitive Na, K pump was not reduced in dialysis patients when compared to normal subjects, whether measured in fresh cells (1.41 +/- 0.05 vs. 1.30 +/- 0.03 mmole/liter RBC/hr; P less than 0.05) or in Na-loaded cells (7.10 +/- 0.24 vs. 6.90 +/- 0.22; NS). There was, however, a marked and uniform suppression of the CoT pathway in Na-loaded cells from dialysis patients versus controls (0.14 +/- 0.02 vs. 0.41 +/- 0.05 mmole/liter RBC/hr; P less than 0.001). Mean CTT activity, as measured by Li efflux, was not different between dialysis and normal subjects. Uremic and normal RBC had similar intracellular Na or K content as well as passive permeability for either ion. This indicates that intracellular cationic homeostasis is maintained, perhaps secondary to balanced changes in cationic flux activity through these transport pathways.

Adult↗
PubMed1986

Intestinal phosphate absorption: influence of vitamin D and non-vitamin D factors.

The transport of inorganic phosphate (P) was measured in the absence of electrochemical gradients across rat jejunum in vitro. Active P absorption was demonstrated in young, vitamin D-deficient (-D) rats, whereas active P secretion was found in normal, non-vitamin D-deficient adult rats, suggesting regulation of intestinal P transport by age-dependent but vitamin D-independent mechanisms. 1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulated mucosal-to-serosal P flux (Jm----s) without affecting serosal-to-mucosal P flux (Js----m), causing further increases in net P absorption (Jnet) in -D rats and reduction in net P secretion in normal adult rats, confirming a previously described role of this hormone on P absorption. We then examined the effect of increasing extracellular (buffer) P concentration [P] on this 1,25(OH)2D3-stimulated active P absorption in jejunum from -D rats. At [P] of 0.024, 0.24, and 2.4 mM, 1,25(OH)2D3 consistently stimulated Jm----s without affecting Js----m, causing an increment in Jnet. At 7.5 mM [P], however, this Jm----s stimulatory effect of 1,25(OH)2D3 was no longer observed. Moreover, at this [P] the Js----m exceeded Jm----s in both -D and 1,25(OH)2D3-repleted rats, converting the active P absorption into active P secretion in both treatment groups. These observations suggest the participation of local mechanisms, such as the ambient [P] of the transporting enterocytes, in the regulation of intestinal P absorption. Finally, the influence of dietary P deprivation on P absorption was studied in -D rats, with or without either vitamin D3 or 1,25(OH)2D3 repletion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Phosphate transport across rat jejunum: influence of sodium, pH, and 1,25-dihydroxyvitamin D3.

Inorganic phosphate (Pi) transport in intact, rat jejunal epithelium was measured in vitro under short-circuited conditions. Transepithelial net absorptive Pi flux increased linearly with increases in extracellular sodium concentration ([Na]) up to 144 mM. Transmucosal border Pi influx, in contrast, displayed a biphasic Na dependency. Pi influx increased as [Na] was raised from 0 to 100 mM. A further increase in [Na] to 144 mM caused unanticipated reduction in Pi influx. The reason for this dissociation between transmucosal border influx and transepithelial absorptive flux is not clear. We then examined the effect of changes in extracellular pH on Pi influx. Reduction in pH from 7.4 to 6.0 was associated with 150% increase in Pi influx, an observation consistent with the reported reciprocal relation between intestinal brush-border membrane vesicles (BBMV) Pi uptake and extravesicular pH. In contrast to BBMV data, however, a smaller increase (50%) in mucosal Pi influx was noted in intact epithelium when pH was increased from 7.4 to 8.5. Under optimized conditions for Pi influx, i.e., [Na] = 90 mM and pH 6.0, the effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on Pi influx was measured. The total influx could be resolved into a saturable, Na-dependent and a nonsaturable, Na-independent component. 1,25(OH)2D3 stimulated the saturable component of Pi influx.

Animals↗