Erythrocyte lead-binding protein after occupational exposure. I. Relationship to lead toxicity.
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Biomedical subjects
Publications and source records attributed to H C Gonick.
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This study compares the usefulness of serum and urine fibrin split products and the urinary enzyme, beta-glucuronidase, in the diagnosis and management of renal transplant rejection. Fibrin split products, determined by a tanned human red cell agglutination inhibition immunoassay, were measured as a reflection of the secondary fibrinolysis from fibrin deposited in the renal microvasculature as a result of rejection. Urinary beta-glucuronidase, expressed as the ratio of enzyme activity to creatinine concentration, was determined by a colorimetric technique following dialysis of urine to remove endogenous activators and inhibitors. Activity of this lysosomal enzyme is thought to reflect tubular injury. Twenty-nine renal transplant recipients (15 from living donors and 14 from cadaver donors) were evaluated. Both serum and urinary fibrin split products and urinary beta-glucuronidase were markedly elevated in the immediate postoperative period, probably reflecting ischemic trauma. Acute rejection occurring within the first three months was associated with elevations of fibrin split products (particularly urine) and beta-glucuronidase. Elevated values returned to normal following successful treatment with steroids and/or heparin, but remained high in the presence of continued rejection. After the first 48 hours post-transplant, in the absence of rejection, values for fibrin split products were within the normal range. Urinary beta-glucuronidase remained elevated if the transplanted kidney was recovering from acute tubular necrosis. Fibrin split products and urinary beta-glucuronidase were usually normal in chronic rejection.
This report summarizes the results of baseline neurologic testing in a group of apparently healthy workers from a secondary lead smelter and a group of controls from nearby aluminum processing plants. The test battery included a standard neurologic examination nerve conduction measurements, quantitative oculomotor function tests and detailed audiologic studies. Lead workers and controls were intermixed so that the examiners were unaware of the status of any individual being tested. Although the lead workers reported significantly more neurologic symptoms than the controls, relatively few differences were found on quantitative neurologic testing. Decreased deep tendon reflexes occured more frequently in the lead workers than in the controls (22% vs. 11%) but the difference was of borderline significance (p=0.06) and other signs of peripheral neuropathy occurred with equal frequency in both groups. The mean motor conduction velocity and sensory latency measurements were not significantly different in the lead workers and in the controls and, of the six oculomotor function measurements, only the mean accuracy of saccadic eye movements was significantly (p less than 0.01) different in the two groups. High frequency hearing loss occurred with equal frequency and severity in both groups, consistent with the level of noise exposure in the lead and control plants.
1. Serum was collected from normal rats and from rats volume-expanded with isotonic sodium chloride solution. 2. The serum was fractionated by gel filtration on Sephadex G-25 and each fraction was tested for inhibitory activity against sodium-potassium-activated adenosine triphosphatase prepared from rat kidney homogenate. 3. A single low-molecular-weight fraction, eluting after the salts and after exogenously added lysine-vasopressin, had significantly greater enzyme inhibitory activity when obtained from serum of volume-expanded animals than from control serum. 4. As this fraction has been shown in previous independent studies to contain a natriuretic factor, it may be concluded that one property of this factor is the ability to inhibit sodium-potassium-activated adenosine triphosphatase.
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Cadmium ion (Cd++) significantly increased potential difference (PD) and short-circuit current (SCC) across isolated frog skin when added to the outside Ringer's solution at 10(-4), 10(-3) and 5 X 10(-3) M concentration. Resistance was reduced by 10(-4) 7 cd++ but not significantly changed by the higher concentrations. When SCC was first stimulated by vasopressin, 10(-4) and 10(-3) M Cd++ produced additive stimulation which was reversible by washing with Cd++-free Ringer's. If SCC was first stimulated by Cd++, further stimulation by vasopressin was additive with 10(-4)M Cd++ but dompletely inhibited by 10(-3)M Cd++. Elevating the calcium ion (Ca++) concentration of the outer Ringer's from 10(-3) M to 5 X 10(-3)M or 10(-2)M prior to Cd++ treatment did not reduce the magnitude of SCC stimulation by Cd++. Removal of Ca++ from the outside Ringer's with 2 X 10%-3)M EDTA increased SCC as predicted. Subsequent addition of 5 X 10(-3) M Cd++ drastically reduced SCC below control levels while equimolar concentrations of Cd++ and EDTA reduced SCC only to control levels. These results suggest that Cd++ interacts with the components of the apical plasma membranes of epithelial cells which are associated with the stimulation of SCC by vasopressin and Ca++ removal and may be a useful probe for elucidating these components.
Boiled homogenates of kidneys from volume-expanded and hydropenic rats were subjected to column chromatography. The fraction eluting within the range of partition coefficients (Kav) 0.76-0.89 (fraction III) was lyophilized and the effects of this semipurified preparation were assessed on short-circuit current (SCC) across isolated frog skin, on rat kidney cortex Na-K-ATPase activity, and on sodium excretion by the rat in vivo. At a dose of 500 mug/ml, fraction III from expanded rat kidney inhibited SCC by 21 +/- 5% (P less than 0.01), whereas the same fraction from hydropenic rat kidney produced an insignificant change in SCC of 2 +/- 8 %. In a dose-response study, 50, 150, 500, and 1,500 mug/ml of fraction III from expanded rat kidney inhibited SCC by 4, 8, 19, and 28%, respectively; 500, 1,000 and 1,500 mug/ml inhibited Na-K-ATPase activity by 11, 22, and 49%, respectively. An identical study with fraction III from hydropenic animals showed no significant effect in either assay. Also, fractions from expanded and hydropenic rats, eluted after fraction III (fractions IV and V), had no effect on SCC or Na-K-ATPase activity. Fraction III also produced significant natriuresis in vivo at a dose of 500 mug/ml, confirming our observations that a natriuretic principle may be recovered from the kidneys of volume-expanded rats. We suggest that this natriuretic principle may act by reducing active sodium transport via inhibition of Na-K-ATPase.
Ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was administered in a dose of 20 mg/kg/d to 21 patients with symptomatic Paget's disease. All patients were treated for 6 months and then followed for an additional 6 months. There was a striking decline in serum alkaline phosphatase and urinary hydroxy-proline excretion observed after 3 months of therapy which was not significantly improved in the succeeding 3 months. Concomitantly there was marked improvement in clinical symptoms and bone scans. Following cessation of therapy, continued biochemical and clinical evidence of remission persisted. Several patients on repeat treatment with EHDP appeared to respond promptly. Side effects were minimal except for a possibly related osteomalacia and increased incidence of pathologic fractures.
A patient with excessive industrial exposure to silicon and an elevated silicon content in his renal tissue was found to have a distinctive nephropathy, characterized pathologically by changes in the glomeruli and proximal tubules, and manifested clinically by albuminuria and hypertension. Proximal tubular function was intact. From a biochemical standpoint, this finding correlates with the demonstration in vitro that, in contrast to cadmium, a known cause of Fanconi syndrome, silicon does not inhibit renal cortical sodium-potassium-adenosine triphosphatase (Na-K-ATPase).
Homogenates of kidneys from hydropenic and volume-expanded rats were subjected to gel filtration with Sephadex G-25. A fraction of the eluate coincident with the fourth UV peak was injected into the aorta of rats with one kidney excluded. A fraction eluting before the albumin peak was utilized as a control. Significant natriuresis and diuresis were observed after infusion of the fraction obtained from volume-expanded kidneys but not after infusion of the fraction from hydropenic kidneys or the control fraction. The natriuresis occurred in in the absence of changes in mean blood pressure, hematocrit, plasma sodium and potassium, glomerular filtration rate, and potassium excretion. The response was apparent immediately after infusion and persisted for up to 150 min. These results verify the existence of a low molecular weight natriuretic substance which may be preferentially bound to the kidney after its volume-stimulated release into the circulation.
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