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Biomedical subjects

D B Lee

Publications and source records attributed to D B Lee.

At least 37 records · Page 2Linked to original sources
PubMed1993

Intestinal magnesium absorption.

Available data on the mechanism of Mg absorption is mainly descriptive in nature. There is data to support the existence of both gradient-driven and saturable Mg absorption. It is not clear, however, which process predominates under normal conditions. Evidence for a saturable process is based on a curvilinear relationship between dietary or luminal [Mg] and Mg uptake. Whether this is due to a carrier-mediated mechanism or due to alterations in absorption through the paracellular route remains to be determined. A careful review of the literature indicates that the predominate site of Mg absorption is the distal small intestine. Most of these studies, however, have been done in isolated segments which may not adequately reflect absorption in an undisturbed gastrointestinal tract. Future work will need to focus on identifying and characterizing Mg transport at the cellular and paracellular level as well as developing more sophisticated strategies for examining Mg absorption in the whole animal.

Animals↗
PubMed1993

Identification of calcium-activated neutral protease activity and regulation by parathyroid hormone in mouse osteoblastic cells.

Calcium-activated neutral protease activity was detected in mouse MC3T3-E1 cell extracts. Inclusion of the cysteine protease inhibitor, E64c, reduced the activity, while pretreatment of intact cells with 10 nM parathyroid hormone for 90 minutes increased it. The presence of calpains in solubilized cells was confirmed by Western blotting using an antibody specific for the 80 K catalytic subunit. These results, combined with the observation that preincubation with a membrane-permeable cysteine protease inhibitor ablates 50% of the PTH-induced osteoblastic retraction, suggest that calpain-catalyzed hydrolysis of regulatory enzymes or structural proteins plays a role in mediating its short-term effects in bone.

Animals↗
PubMed1991

Magnesium absorption: mechanisms and the influence of vitamin D, calcium and phosphate.

Magnesium absorption has been studied in both humans and animals under diverse experimental conditions. As a result, the data often appear confusing and conflicting. In this review we attempt to summarize information concerning Mg absorption and, where possible, to reconcile apparently conflicting observations. Most studies suggest that Mg is absorbed predominantly in the distal intestine. At usual Mg intakes, Mg absorption occurs primarily by intercellular diffusional and solvent drag mechanisms. There is evidence for a saturable component of Mg absorption in the small intestine and the descending colon that is important at low dietary Mg intakes. Pharmacological doses of vitamin D increase Mg absorption in both vitamin D-deficient and vitamin D-replete animals. A substantial amount of Mg absorption, however, occurs independent of vitamin D. In addition, vitamin D may reduce Mg retention through increases in urinary Mg excretion. Intestinal interactions between Mg and calcium or phosphate have been demonstrated in both humans and animals. The nature of these interactions cannot be readily explained by data currently available.

Animals↗
PubMed1991

Influence of recombinant human erythropoietin on blood pressure and tissue renin-angiotensin systems.

In humans, blockade of the renin-angiotensin system with angiotensin converting-enzyme inhibitors (ANG CEI) prevents the rise in blood pressure associated with the administration of recombinant human erythropoietin (rhEPO). This study was conducted to determine whether rhEPO elevates blood pressure in normal Wistar rats and whether the renin-ANG system is affected. Groups of 10 rats each were given rhEPO, ANG CEI (enalapril), rhEPO + ANG CEI, or vehicle. Renin and/or renin substrate mRNA was measured in aortas, kidney, and heart; renin activity (PRA), inactive renin, and renin substrate were measured in plasma. rhEPO raised blood pressure in the normal rat without changing the plasma renin system. ANG CEI prevented this blood pressure rise. Renin-specific mRNA was increased by rhEPO in renal tissue, and renin substrate mRNA was significantly elevated in the kidney and aorta. mRNA for renin and renin substrate were not altered in the heart. In both aorta and kidney, a significant correlation was observed between renin substrate mRNA and blood pressure. The data indicate that rhEPO modulates specific tissue renin-ANG systems, which may contribute to blood pressure elevation.

Animals↗
PubMed1991

The importance of non-vitamin D-mediated calcium absorption.

In rapidly growing neonatal rats, the intestine is insensitive to vitamin D, and Ca absorption is solely mediated through a non-energy-dependent process. Changes in Ca absorption associated with pregnancy and lactation are qualitatively similar in vitamin D-replete and vitamin D-deplete rats. Moreover, in vivo studies in man and the rat have demonstrated that the bulk of Ca absorption is accomplished in the ileum, a segment with limited capacity for active Ca absorption and is relatively insensitive to the action of 1,25-dihydroxyvitamin D. In patients with intestinal bypass operations the degree of Ca malabsorption and bone mineral loss is proportional to the length of ileum, not duodenum or proximal intestine, removed. Bile salts and lactose are examples of agents which can augment vitamin D-independent ileal Ca absorption through the intercellular pathway.

Animals↗
PubMed1991

Role of parathyroid hormone in rat remnant kidney ammonium metabolism.

The role of parathyroid hormone (PTH) in ammonium metabolism in the rat remnant kidney was studied by examining the effects of parathyroidectomy (PTx) in rats with intact kidneys and with 5/6 nephrectomy (Nx). PTx in rats with intact kidneys caused a rise in urine pH and a decrease in urinary ammonium excretion without affecting in vitro ammonium production rate or the ammonium content in the cortex. Unexpectedly, the ammonium content in the medulla was markedly reduced by PTx so that the corticomedullary ammonium gradient was inverted. As compared to control rats, rats with 5/6 Nx had a lower urinary ammonium excretion rate, a higher in vitro ammonium production rate, and an increase in ammonium content in both cortex and medulla with reduced corticomedullary ammonium gradient. PTx in rats with 5/6 Nx led to a further decrease in urinary ammonium excretion, attenuated the increase in the in vitro ammonium production rate, and lowered the ammonium content in both cortex and medulla with inverted corticomedullary ammonium gradient. These effects of PTx in Nx rats were corrected by continuous PTH infusion with Alzet minipump. In summary, results from these studies indicate that PTH plays an important role in maintaining the urinary ammonium excretion. In rats with intact kidneys, PTH contributes to urinary ammonium excretion by increasing urinary acidification and medullary ammonium accumulation. In rats with reduced nephron mass, PTH enhances urinary ammonium excretion by stimulating ammonium production and retaining medullary ammonium in the remnant kidney.

Ammonia↗
PubMed1991

Interrelationship between erythropoietin and erythropoiesis: insights from renal transplantation.

In successful renal transplant recipients, transient and modest increases in endogenous erythropoietin (Epo) reverse anemia, whereas in dialysis patients, sustained administration of large doses of exogenous Epo is required for the correction of uremic anemia. Moreover, in transplant recipients, serum Epo returns to normal as the hematocrit level increases to greater than 32%. Thereafter, the hematocrit continues to increase to normal levels, while serum Epo remains in the normal range. Thus, the restoration of renal function may improve the erythropoietic response to Epo, and/or erythropoiesis in transplant patients may be stimulated by factors other than, or in addition to, Epo. In early posttransplant patients who develop erythrocytosis, serum Epo levels are often elevated, while in long-term transplant recipients, erythrocytotic patients (with normal serum ferritin) have normal serum Epo levels. On the other hand, in long-term transplant recipients with low serum ferritin, circulating Epo levels are elevated, even in patients with no overt anemia. This suggests a possible interaction between body iron store status and the synthesis of Epo.

Anemia↗
PubMed1990

Monoclonal antibody to the interferon-inducible protein Leu-13 triggers aggregation and inhibits proliferation of leukemic B cells.

Interferon (IFN)-alpha inhibits DNA synthesis stimulated by low molecular weight B-cell growth factor (BCGF) in hairy cells in vitro, suggesting that the therapeutic efficacy of IFN-alpha in hairy cell leukemia (HCL) involves growth inhibition of malignant B cells. Evidence that the 16-Kd cell surface protein Leu-13 mediates an antiproliferative signal in T lymphocytes and is IFN-inducible in endothelial cells prompted us to examine the expression and functional role of this molecule in leukemic B cells. Leu-13 density, determined by flow cytometry, was upregulated in vitro and in vivo by IFN-alpha on malignant B cells from patients with HCL, chronic lymphocytic leukemia, and prolymphocytic leukemia. Monoclonal anti-Leu-13 triggered homotypic aggregation of leukemic B cells via an adhesion pathway that was not inhibited by antibodies to leukocyte function associated antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1). Moreover, anti-Leu-13 potentiated the inhibitory effects of IFN-alpha on BCGF-stimulated DNA synthesis, assessed by [3H]-thymidine and [3H]-deoxyadenosine incorporation into DNA. These results indicate that Leu-13 is part of a novel IFN-inducible signaling pathway which may modify the growth and adhesive properties of leukemic B cells under physiologic or therapeutic conditions.

Antibodies, Monoclonal↗
PubMed1990

Comparison of calcium and magnesium absorption: in vivo and in vitro studies.

Transport characteristics of Ca and Mg were compared at three different levels of the absorptive process in male (120-170 g) Wistar rats. Balance studies in intact rats revealed that fractional Ca absorption decreased with increased Ca intake so that net Ca absorption remained constant. Fractional Mg absorption decreased modestly with increased Mg intake so that net Mg absorption increased proportionately with increased dietary Mg. Everted duodenal sacs demonstrated the presence of active Ca absorption with serosal-to-mucosal (S/M) ratio of 2.65 +/- 0.20 (n = 6), which was greater than unity (P less than 0.001). In contrast, the S/M for Mg did not exceed unity. Mucosal duodenal Ca uptake exhibited a large saturable (Michaelis constant of 4.80 +/- 0.34 mM, maximal velocity of 4.71 +/- 0.13 nmol.min-1.mg-1) and a small nonsaturable component (0.12 +/- 0.01 nmol.min-1.mg-1) in 5-wk-old rats (120 g). In 72-wk-old rats (600 g) the diffusional component of Ca uptake became predominant, and the slope increased significantly to 0.32 +/- 0.01 (P less than 0.05). Duodenal Mg uptake was completely concentration dependent and exhibited no age-related changes.

Animals↗
PubMed1990

Vitamin D-independent regulation of calcium and phosphate absorption.

Convincing evidence for the stimulatory action of 1,25-dihydroxyvitamin D (1,25(OH2)D) on transcellular absorption of calcium (Ca) and inorganic phosphate (P) has led to the consensus that this hormone is the major regulator of Ca and P absorption. Careful review of the literature, however, suggests important regulation of Ca and P absorption by factors and agents other than those mediated by vitamin D. Thus, in rapidly growing neonatal rats, the intestine is insensitive to vitamin D and Ca absorption is entirely mediated through passive mechanisms. Patterns of change in Ca absorption associated with pregnancy and lactation are identical in vitamin D-replete and vitamin D-deplete rats. The presence of active Ca and P absorption in young, growing rats rigidly deprived of vitamin D and of active Ca and P secretion in mature rats optimally replete with vitamin D, also suggests the participation of non-vitamin D factors in the regulation of intestinal Ca and P absorption. The possibility that Ca and P in the peri-enterocyte environment may regulate their own absorption is discussed. Kinetic analysis of 1,25(OH2)D-induced transport mechanisms indicates that saturation would occur at low substrate concentrations, thus raising the question whether these mechanisms would have major regulatory roles under normal dietary conditions. There is also suggestive evidence indicating that even under conditions of low dietary Ca or P intake, the adaptive changes in intestinal absorption may not be mediated by vitamin D alone. Bile salts, lactose and prolactin are discussed as examples of agents which can stimulate Ca and/or P absorption through vitamin D-independent mechanisms.

Aging↗
PubMed1990

Site and mechanism of intestinal magnesium absorption.

Despite considerable research on magnesium (Mg) absorption there is still uncertainty regarding the site and mechanism of intestinal Mg transport. A careful review of the literature indicates that while Mg is absorbed throughout the intestine, the predominate site is the distal small intestine. There are three mechanisms by which Mg has been shown to cross the intestine:passive diffusion, solvent drag, and active transport. The importance of each of these mechanisms to total Mg absorption is discussed. Studies in both humans and experimental animals indicate that passive diffusion through the paracellular pathway accounts for the majority of Mg absorbed. Investigators have also consistently demonstrated the existence of a saturable component. Studies in everted gut sacs, however, have failed to demonstrate that Mg is actively transported against a concentration gradient in young or adolescent rats. Recent studies using the Ussing chamber have documented that Mg is actively transported in the descending colon.

Animals↗
PubMed1989

Serum erythropoietin levels after renal transplantation.

We measured serum erythropoietin levels serially in 31 renal-transplant recipients treated with cyclosporine, using the recently developed recombinant human erythropoietin-based radioimmunoassay. The mean (+/- SEM) serum erythropoietin concentration in these patients before transplantation (14 +/- 2 U per liter) was similar to that in normal subjects who did not have anemia. A transient postoperative 9-fold increase (range, 0- to 74-fold) in the serum erythropoietin levels was followed by a smaller (3-fold) and sustained (28 +/- 3 days) second elevation. The initial increase occurred in the absence of graft function and was not accompanied by an erythropoietic response, whereas the second increase was associated with graft recovery and the complete resolution of the anemia. Serum erythropoietin levels returned to normal as the hematocrit rose above 0.32. Thereafter, the hematocrit continued to rise toward normal, while the serum erythropoietin levels remained normal. The patients in whom erythrocytosis or iron-deficiency anemia developed had persistently elevated serum erythropoietin levels. We conclude that in patients who have undergone renal transplantation, slight increases in endogenous erythropoietin levels induce erythropoiesis to the same extent as do large doses of exogenous erythropoietin in patients with uremia. Moreover, once initiated, erythropoiesis in renal-transplant recipients may be sustained by normal serum erythropoietin levels. These results suggest that the restoration of renal function improves the erythropoietic response to erythropoietin.

Adult↗
PubMed1989

Increased Na+/H+ antiport activity in the renal brush border membrane of SHR.

Defect in renal salt excretion may play an important role in the pathogenesis of hypertension. We examined sodium (Na+) uptake by brush border membrane (BBM) vesicles of young (6 week old) spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) of the same age. SHR had lower urinary Na+ excretion (223.1 +/- 9.3 vs. 266.3 +/- 3.7 microEq/day/100 g, N = 8, P less than 0.01) and higher systolic blood pressure (98.9 +/- 1.2 vs. 82.9 +/- 1.8 mm Hg, N = 8, P less than 0.01) than WKY. BBM vesicle Na+ uptake, measured by rapid filtration technique, was higher in SHR when compared to WKY (1.44 +/- 0.03 vs. 1.01 +/- 0.06 nmol/mg/5 sec, N = 4, P less than 0.01). This increase in Na+ influx was apparent only in the present of an outward-directed proton (H+) gradient and was abolished by 1 mM amiloride. BBM permeability to H+ as assessed by acridine orange quenching was not different between SHR and WKY. Kinetic analyses of the amiloride-sensitive BBM Na+ uptake revealed a higher Vmax (2.13 +/- 0.27 vs. 0.70 +/- 0.30 nmol/mg/5 sec, N = 4, P less than 0.01) and a higher km for Na+ (3.55 +/- 0.32 vs. 1.23 +/- 0.14 mM, N = 4, P less than 0.05) in SHR. These findings thus demonstrate an intrinsic derangement in BBM Na+ transport in young SHR which is characterized by increased Na+/H+ antiport activity. This alteration in antiport activity is not attributable to changes in membrane permeability to H+, and is characterized by higher Vmax and km.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Stimulation by uraemic plasma of frusemide-sensitive sodium efflux in erythrocytes from normal women.

1. Reduced Na+,K+ pump activity has been reported in uraemic erythrocytes, and this has been attributed to the presence of a circulating ouabain-like inhibitor. Since we have previously reported marked suppression of Na+,K+ co-transport activity in erythrocytes from dialysis patients, we have now examined the effect of incubation with uraemic plasma on Na+ efflux through the Na+,K+ pump and the co-transport pathway in normal erythrocytes from both men and women. 2. The results show that Na+ efflux via the Na+,K+ pump is not different between men and women (3.14 +/- 0.14 vs 3.68 +/- 0.18 mmol h-1 litre-1 of cells) and is not inhibited by incubation with uraemic plasma. 3. In contrast, co-transport-mediated Na+ efflux is lower in erythrocytes from normal women when compared with normal men (0.17 +/- 0.02 vs 0.25 +/- 0.05 mmol h-1 litre-1 of cells, P less than 0.001). 4. Moreover, incubation with uraemic plasma causes stimulation of Na+ efflux through the co-transport pathway in erythrocytes of healthy women (0.17 +/- 0.02 vs 0.27 +/- 0.03 mmol h-1 litre-1 of cells, P less than 0.005), but not in erythrocytes of healthy men (0.27 +/- 0.03 vs 0.25 +/- 0.05 mmol h-1 litre-1 of cells). 5. Our data do not support the presence of either a Na+,K+ pump or a co-transport inhibitor in plasma from dialysed uraemic patients. Thus, the suppressed co-transport activity demonstrated in uraemic erythrocytes cannot be attributed to a circulating inhibitor, and may reflect an acquired membrane or transport defect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Altered vascular responses in cyclosporine-treated rats.

Administration of cyclosporine to allograft recipients and patients with immunologically mediated disorders is associated with a high incidence of the development of hypertension. We studied the effect of CsA on blood pressure and on the in vitro tail artery contractile response to transmural nerve stimulation (TNS) and exogenous norepinephrine (NE) in the spontaneously hypertensive rat (SHR). Fourteen days of p.o. administration of CsA 5 mg/kg/day (CsA5) or CsA 20 mg/kg/day (CsA20) resulted in significant increases in blood pressure. The effective level of TNS that resulted in a 50% of maximal response (ED50) was significantly (P less than 0.05) decreased in the CsA5 and CsA20 animals compared to controls. The values for controls (n = 7), CsA5 (n = 10), and CsA20 (n = 9) were 4.3 +/- 0.3, 3.2 +/- 0.3, and 3.1 +/- 0.4 pulses/sec, respectively. In the CsA20 group, the dose-response curve to NE was significantly shifted to the left, and the ED50 was significantly (P less than 0.01) decreased compared to controls (5.7 +/- 0.8 x 10(-5) mol/L, n = 11, vs. 8.9 +/- 0.6 x 10(-5) mol/L, n = 12). We conclude that the in vitro contractile response to nerve stimulation is augmented by CsA. Some of the increase may be related to an enhancement of NE response, but a direct effect on neurovascular function is also suggested. This effect of CsA may be important in the development of hypertension and the changes in neurovascular tone seen with the clinical administration of this immunosuppressant.

Animals↗
PubMed1989

Modulation of aortic smooth muscle cell membrane potential by extracellular calcium.

Removal of extracellular calcium may result in depolarization of the resting cell membrane potential. This has been attributed to the stabilizing action of calcium on the ionic permeability of the cell membrane. It is unknown whether this phenomenon is exclusively mediated by extracellular calcium or through associated changes in intracellular calcium. To examine this, we exposed rat aortic smooth muscle cells in culture to different calcium concentrations and studied their effects on the resting membrane potential and intracellular calcium activity. The resting membrane potential was dependent on the extracellular potassium concentration. Exposure to reduced extracellular calcium concentrations (0.25 and 0.5 mM) caused a steep and reversible depolarization of the membrane potential, but intracellular calcium, measured with fura 2-AM, was not reduced below that measured in control conditions (1.8 mM). Atomic absorption spectrophotometric measurements did not indicate a measurable gain in cell sodium after reduction of extracellular calcium levels. We conclude that extracellular calcium controls the resting cell membrane potential of vascular smooth muscle through a mechanism that is independent of cytosolic Ca2+ activity.

Action Potentials↗