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Biomedical subjects

L A Hebert

Publications and source records attributed to L A Hebert.

At least 73 records · Page 4Linked to original sources
PubMed1987

Interactions between precipitating and nonprecipitating antibodies in the formation of immune complexes.

In the present study, we used monoclonal antidinitrophenol (DNP) antibodies to determine certain of the biophysical characteristics of precipitating and nonprecipitating antibodies. In addition, we studied the dynamics of immune complex (IC) formation when precipitating antibodies react with antigen in the presence of nonprecipitating antibodies. The antigen utilized in these studies was DNP-bovine serum albumin. All isolated nonprecipitating anti-DNP antibodies were of the IgG2b isotype, whereas all antibodies with other isotypes (IgG1, IgG3, IgM, IgA and IgE) were precipitating. Nonprecipitating antibodies did not differ significantly from precipitating antibodies in affinity, valence, or isoelectric point. Nonprecipitating antibodies inhibited the formation of precipitable IC between antigen and precipitating antibodies. In addition, preformed IC precipitates were solubilized by nonprecipitating antibodies. The solubilization of IC precipitates was influenced by the isotype of the precipitating antibody and by the antibody:antigen ratio in the IC precipitate. By isokinetic sucrose density centrifugation, we determined that solubilization of IC precipitates by nonprecipitating antibodies was associated with release of free precipitating antibody and formation of soluble IC between the antigen and the nonprecipitating antibody. In conclusion, in this study the nonprecipitating property of mouse anti-DNP antibodies is isotype-specific. Nonprecipitating antibodies compete and displace precipitating antibodies from the antigen, resulting in inhibition of IC precipitation and in IC solubilization. On the basis of the present results, we postulate that antibody-antibody interactions are important determinants of precipitating ability, and that these interactions are a characteristic of antibody isotype.

Animals↗
PubMed1987

Clearance of human antibody/DNA immune complexes and free DNA from the circulation of the nonhuman primate.

The present study evaluated the participation of the primate erythrocyte immune complex (IC) clearing mechanism in the clearance and organ uptake of double-stranded DNA (dsDNA) and of soluble ICs formed with human anti-DNA antibodies and dsDNA (dsDNA-ICs). Five baboons received 51Cr-labeled autologous erythrocytes and after a period of equilibration received separate intraarterial injections of [125I]free dsDNA and [125I]dsDNA-IC. Four of these five baboons were studied on a second occasion. To assess clearance from the arterial circulation and organ uptake, multiple blood samples were obtained from aorta, hepatic vein, and renal vein after injection of each probe. Two minutes after injection, a mean of 85% of dsDNA-ICs were bound to erythrocytes. By contrast, free dsDNA did not bind significantly to blood cells. The clearance rate of dsDNA-ICs from the arterial circulation was significantly faster than that of free dsDNA in all animals but one. Erythrocyte-bound dsDNA-ICs were cleared at a rate similar to that of total dsDNA-ICs. The liver was the major site of uptake of free dsDNA and of dsDNA-ICs. The hepatic uptakes of free dsDNA (17 +/- 8%/5 min) and dsDNA-ICs (27 +/- 8%/5 min) were not significantly different. 51Cr-labeled erythrocytes were not sequestered in the liver. There was not detectable uptake of free dsDNA or dsDNA-ICs by the kidney but with one exception. Thus, the primate erythrocyte IC clearing mechanism is involved in the clearance of dsDNA-ICs from the circulation but not in the clearance of free dsDNA.

Animals↗
PubMed1987

The living donor in kidney transplantation.

Kidney transplantation using either kidneys from living or nonliving donors is now generally regarded as the primary therapy for most patients with end-stage kidney failure. In 1984, 32% of all kidney transplantations done in the United States involved living donors. Reasons justifying the use of kidneys from living donors are the higher success rate and the inadequate supply of cadaveric kidneys. In addition, with a living donor, it is easier to arrange for kidney transplantation before dialysis therapy needs to be started. An analysis of 2495 donor nephrectomies reported in the literature, and 5698 donor nephrectomies reported from the 12 largest centers that do kidney transplantation with living donors, indicates an approximate incidence of 1 donor death per 1600 nephrectomies. Although long-term follow-up in kidney donors has shown only that mild, nonprogressive proteinuria develops in about 33% and that the frequency of hypertension may increase, we advise that the kidney donor have a careful long-term follow-up and avoid a high protein intake because of its potential to lead to progressive glomerular damage.

Family↗
PubMed1987

A comparison of taste acuity for salt in renal patients vs. normal subjects.

In this pilot study, 30 patients with renal disease receiving renal replacement therapy (10 each in the following groups: continuous ambulatory peritoneal dialysis [CAPD] patients, hemodialysis [HD] patients, and renal transplant recipients) and 10 control subjects were given salt solutions of varying concentrations (0 to 600 mmol/L) and asked to rate them subjectively according to their perceived taste intensity. The mean age in each of the four groups ranged from 31.9 to 34.1 years. No significant differences were found in the ratings of perceived salt intensity among patients and control subjects. On the basis of 3-day food records plus recall of seasonings used, mean intake of sodium was estimated to be higher in CAPD patients and control subjects than in HD and transplant patients (p less than 0.02). Patients on CAPD stated a preference for salty items, whereas control subjects preferred the less salty items despite similar estimated sodium intakes. It thus appears that the ability to perceive various salt tastes may not be impaired in patients on renal replacement therapy. In addition, inappropriate salt intake commonly seen in those patients may be due to increased salt appetite, specifically in those patients managed by CAPD.

Adult↗
PubMed1986

Differential binding of immunoglobulin A and immunoglobulin G1 immune complexes to primate erythrocytes in vivo. Immunoglobulin A immune complexes bind less well to erythrocytes and are preferentially deposited in glomeruli.

Primate erythrocytes appear to play a role in the clearance of potentially pathogenic immune complexes (IC) from the circulation. This study was undertaken to compare the clearance from the circulation and tissue uptake of two monoclonal IC probes: one of which, IgG1-IC, was bound well by erythrocytes, the other of which, IgA-IC, was bound relatively poorly by erythrocytes. The IC probes were labeled with different iodine isotopes and infused either concomitantly or sequentially into the arterial circulation. The results indicate that, compared with IgG1-IC, IgA-IC bind less well to primate erythrocytes, are cleared from the circulation more quickly despite their smaller size, and show increased uptake in kidney and lung but decreased uptake in liver and spleen. Evidence is presented which suggests that this pattern of clearance from the circulation and systemic uptake of IgA-IC is the result of decreased binding of IgA-IC to circulating erythrocytes. These findings support the hypothesis that the primate erythrocyte-IC clearing mechanism may be critically important for the safe removal of IC from the circulation.

Animals↗
PubMed1986

Primary hypothyroidism in chronic renal failure.

Serum thyroid hormone concentrations have been measured in 8 patients with chronic renal failure (CRF) who are currently enrolled on a chronic hemodialysis program. Three of these patients were diagnosed to be suffering from coexistent primary hypothyroidism whereas the other 5 were considered euthyroid. There was a variable decline in serum thyroid hormone levels in both groups. However, the serum TSH response to TRH was normal or blunted in the euthyroid group but was characteristically brisk in subjects with CRF and coexistent primary hypothyroidism. The TRH test may be useful in the diagnosis of primary hypothyroidism coexistent with CRF.

Adult↗
PubMed1986

Simple method for monitoring 24-hour urinary urea nitrogen excretion.

The urine urea nitrogen/urine creatinine excretion ratio (UUN/UCr) of a "spot" urine specimen obtained approximately 5 hours after the last meal of the day can be used to accurately calculate the urinary urea excretion for the previous 24-hour period. Because UUN excretion is largely determined by dietary intake of protein nitrogen, this method can be used to estimate dietary protein intake for the previous 24-hour period. Strategies for using this simple method for inexpensively and continuously monitoring dietary protein intake are discussed.

Creatinine↗
PubMed1985

Glomerular basement membrane splitting and microaneurysm formation associated with nitrosourea therapy.

A patient who developed renal insufficiency following nitrosourea therapy is reported. Light, immunohistochemical, and electron microscopic studies of the renal biopsy disclosed an unusual glomerular basement membrane injury. Light microscopy showed extensive basement membrane splitting and capillary aneurysm formation. Electron microscopic examination revealed an extensive subendothelial accumulation of electron-lucent granular material. The glomerular basement membrane was separated from the mesangium and showed splitting of the lamina densa. Immunofluorescent and immunoperoxidase staining of the glomeruli was negative for immunoglobulin, complement, and fibrinogen. This form of nitrosourea-associated glomerular injury has not been described previously.

Adenoma, Islet Cell↗
PubMed1985

Adverse effect of exercise on immune complex-mediated glomerulonephritis.

To assess the effect of strenuous daily exercise on immune complex-mediated glomerulonephritis (GN), rabbits were randomly assigned to one of three experimental groups: Group I (n = 12): treadmill exercise for 28 days plus twice weekly intravenous injections of saline. Group II (n = 10): treadmill exercise for 28 days plus twice weekly intravenous bovine serum albumin (BSA) injection. Group III (n = 9): intravenous doses of BSA, as in group II, but no exercise. Blood and urine samples were collected from each animal periodically during the 28-day experimental period. On the 29th day of the study all animals were sacrificed and tissue taken for renal histopathologic studies. We found that in group II (exercise + GN) abnormal albuminuria was more frequent (p less than 0.001), blood urea nitrogen (BUN) levels rose significantly with time (p less than 0.02) and hematuria (blood in renal tubules) was more common (p less than 0.05), compared to group III (GN only). The differences between groups II and III could not be explained by the effect of exercise alone since group I (exercise only) developed no abnormal albuminuria, BUN levels or hematuria during the course of the study. These findings suggest that strenuous exercise superimposed on active immune complex-mediated GN results in worsening of the abnormal glomerular function.

Animals↗
PubMed1984

Factors influencing the binding of large immune complexes to the primate erythrocyte CR1 receptor.

This study was undertaken to ascertain the relationship between the size of immune complexes and their capacity to be bound by primate erythrocytes, and to examine the role of complement in the binding of very large immune complexes to erythrocytes. Preformed bovine serum albumin-rabbit anti-bovine serum albumin immune complexes were solubilized in a fivefold antigen excess, and the supernatant fluids were subjected to differential centrifugation to select immune complexes of varying size. The size profile of immune complexes was measured on isokinetic sucrose gradients. Immune complexes were incubated with erythrocytes, and unbound immune complexes were separated from erythrocyte-bound immune complexes by centrifugation on Percoll. The results indicate that large immune complexes were bound more efficiently by primate erythrocytes than were smaller immune complexes. Depletion of complement by a variety of procedures abrogated binding of immune complexes to erythrocytes. Only the erythrocytes of primates had the capacity to bind immune complexes. Baboon or rabbit sera supported immune complex binding to baboon or human erythrocytes. In contrast, human and guinea pig sera supported immune complex binding to human erythrocytes, but these sera failed to support immune complex binding to baboon erythrocytes. These data indicate that the immune complex size and the source of serum complement are important factors which influence the binding of immune complexes to primate erythrocytes.

Adult↗
PubMed1984

Complement depletion accelerates the clearance of immune complexes from the circulation of primates.

Binding of immune complexes (IC) to erythrocytes in vitro is the result of interaction between C3b sites on the IC, and complement receptors type I (CRI) expressed on primate erythrocytes. Recent evidence indicates that primate erythrocytes can also rapidly bind large, preformed IC in vivo. This study was undertaken to determine if the binding of IC to baboon erythrocytes in vivo is complement dependent and to examine the effect of complement depletion on IC clearance from the circulation. The results indicate that complement depletion in vivo reduced the binding of IC to erythrocytes. There was relatively little binding of IC to leukocytes in both the complement-depleted and complement-repleted condition. Thus, the majority of IC not bound to erythrocytes remained free in the plasma and, consequently, IC infusion during the complement-depleted state resulted in increased plasma IC concentrations. This was associated with a rapid disappearance of IC from the circulation. By contrast, in the normal or complement-repleted state, a large fraction of the IC became bound to erythrocytes during IC infusion, which resulted in lower plasma IC concentrations. Under these conditions, a more gradual rate of disappearance of IC from the circulation was observed. The relatively abrupt clearance of IC from the circulation in the complement-depleted state could not be accounted for by increased hepatic or splenic uptake. These data indicate that, in contrast to previous studies in nonprimates, complement depletion in primates results in accelerated removal of IC from the circulation. This suggests that factors such as hypocomplementemia and deficient expression of erythrocyte CRI, which are known to occur in certain IC-mediated diseases, may promote IC uptake by organs vulnerable to IC-mediated injury.

Animals↗
PubMed1983

Primate erythrocyte-immune complex-clearing mechanism.

Previous in vitro studies have shown that immune complexes (IC) that fix complement can bind to the C3b receptor on primate erythrocytes. The in vivo function of this erythrocyte receptor, however, is unknown. This study was undertaken to determine whether the binding of IC to erythrocytes in vivo might play a role in the removal of IC from the circulation. Baboons and rhesus monkeys were prepared with a catheter in the ascending aorta to infuse IC and in the abdominal aorta, renal, hepatic, and portal veins to monitor changes in binding and clearance of IC across kidney, liver, and spleen + gut, respectively. Autologous 51Cr-labeled erythrocytes were infused intravenously and allowed to equilibrate. Preformed IC (125I-labeled bovine serum albumin [BSA] rabbit anti-BSA) were then infused into the ascending aorta at a constant rate for 120 s. Blood samples were drawn at frequent intervals for 30 min from all catheters below the IC injection site. Each blood sample was then centrifuged on percoll to separate IC bound to erythrocytes from IC in plasma or bound to buffy coat cells. This resulted in an "erythrocyte fraction" beneath the percoll that contained the IC bound to erythrocytes, and a "plasma/buffy coat fraction" above the percoll that contained the IC in plasma and IC bound to buffy coat cells. Analysis of these data showed that the majority of the IC infused into the circulation rapidly became bound to erythrocytes. However, by 5 min after beginning the IC infusion, most of this IC load had been removed from the erythrocytes as they traversed the liver. In contrast, IC on erythrocytes did not deposit in kidney. The IC-bearing erythrocytes themselves were not trapped or detained by any organ. IC in the plasma/buffy coat fraction of blood were removed from the circulation but at a relatively low rate and almost entirely by the liver. These findings suggest that primate erythrocytes intercept large complement-fixing IC in the circulation causing the IC to adhere to the erythrocyte until th e IC-bearing erythrocyte traverses liver where the IC is deposited, and the erythrocyte is returned to the circulation. This primate erythrocyte-IC-clearing mechanism may be important in the protection against diseases mediated by deposition of circulating IC.

Animals↗
PubMed1982

Rapidly progressive glomerulonephritis superimposed on diabetic glomerulosclerosis. Recognition and treatment.

Two patients with long-standing diabetes mellitus and diabetic retinopathy were evaluated for declining renal function and heavy albuminuria. Initially, diabetic glomerulosclerosis was suspected as the cause of progressive glomerulopathy. However, in both patients the rate of loss of glomerular filtration rate was greater than that usually seen in diabetic glomerulosclerosis, and the urine sediment contained many RBC casts. These findings led to renal biopsy, which demonstrated crescentic glomerulonephritis superimposed on diabetic glomerulopathy. Both patients were treated with prednisone and cyclophosphamide and both experienced substantial improvement in renal function. These experiences demonstrate the importance of searching for evidence of a superimposed treatable glomerulopathy in the diabetic patient with glomerulopathy and advancing renal insufficiency.

Adult↗
PubMed1982

Habitual excessive dietary salt intake and blood pressure levels in renal transplant recipients.

We observed that renal transplant recipients with good graft function (mean serum creatinine level 1.5 mg/dl +/- 0.5 SD, N = 68) had dietary salt intakes (estimated from serial measurements of 24-hour sodium excretion rate) which averaged 43 percent higher than that of a comparable group of healthy subjects. There was no correlation between blood pressure levels and salt intake and, despite the high dietary salt intake, hypertension was present in only 29 patients and was usually mild; mean systolic and diastolic blood pressures were 132 +/- 10 mm Hg and 89 +/- 7 mm Hg, respectively while the patients were receiving antihypertensive medication (median number of standard doses of antihypertensive medication was 1.0 doses/patient patient per day). These observations suggest that high dietary salt intake does not exert a powerful blood pressure elevating effect, since any effect of high dietary salt intake to raise blood pressure should have been magnified in the renal transplant recipients because of their reduced renal mass and their chronic glucocorticoid therapy.

Adult↗
PubMed1981

Method for detecting a progressive renal disorder superimposed on a preexisting progressive renal disorder.

We describe a patient with declining renal function due to polycystic kidney disease, who then insidiously develops bilateral renal artery stenosis. The major clue which led to the discovery of the bilateral renal artery stenosis was the finding of an unexpected increase in the rate of loss of renal function. This assessment was based on analysis of the slope of a plot of the reciprocal of the patient's serum creatinine concentration vs. time (reciprocal creatinine plot). The rationale for the use of the reciprocal creatinine plot to detect a progressive renal disorder superimposed upon a preexisting progressive renal disorder, is discussed.

Creatinine↗