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Biomedical subjects

L G Hunsicker

Publications and source records attributed to L G Hunsicker.

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

Polycation binding to glomerular basement membrane. Effect of biochemical modification.

The polycation hexadimethrine (HDM) binds to anionic sites in the glomerular basement membrane (GBM) and causes heavy proteinuria when infused in vivo. An in vitro assay of 3H-HDM binding to isolated dog GBM was developed, to permit further analysis of the GBM components binding HDM. 3H-HDM binding to isolated GBM was saturable, reversible in dose-dependent fashion by competing polycations, and inhibited by increasing salt concentration and low pH. The pH dependence of binding suggested that most of the HDM binds to carboxyl groups rather than to the sulfate groups of proteoglycans. Removal of heparan sulfate by heparinase or purified heparatinase had no detectable effect on HDM binding. Treatment of GBM with neuraminidase, hyaluronidase, or chondroitinase reduced binding of HDM by a maximum of 20 to 38%. However, substitution of carboxyl anions with nonionizable glycine methyl ester residues resulted in complete elimination of HDM binding. Parallel results were obtained in studies of glomerular localization of cationized ferritin (CatF), pI 8.5. After carboxyl substitution, GBM did not bind CatF; heparinase-treated GBM bound CatF in a distribution not demonstrably different from normal. Cellulose acetate electrophoresis of glycosaminoglycan fractions prepared from treated GBM confirmed that carboxyl modification did not alter the content or charge of the heparan sulfate of GBM, but heparinase treatment removed at least 90% of heparan sulfate. The results indicate that carboxyl groups are quantitatively more important than heparan sulfate for binding of HDM in vitro. Since HDM causes proteinuria in vivo, carboxyl groups may be important for maintenance of normal permselectivity.

Animals↗
PubMed1985

Urinary albumin excretion after donor nephrectomy.

Surgical ablation of renal tissue in animals leads to compensatory hyperfiltration, hypertension, and focal glomerular sclerosis in remnant nephrons, in association with albuminuria; the detection of slightly elevated urinary albumin (microalbuminuria) has been shown to predict later, more severe renal disease in diabetics. To determine whether unilateral nephrectomy in humans initiates a similar pathogenetic sequence, we measured urinary albumin excretion (UalbV), total protein excretion (UprotV), creatinine clearance (Ccreat) and blood pressure in 22 transplant donors before and at intervals up to 3 years after donor nephrectomy. Urinary albumin was determined using a sensitive enzyme immunoassay (ELISA). Mean Ccreat fell on average to 68% of prenephrectomy values at all times after nephrectomy, indicating a rise of 33% in average single nephron filtration rate. Mean absolute and fractional albumin excretion rates and UprotV values were transiently elevated one week postnephrectomy, but returned thereafter to values not significantly different from prenephrectomy values. Blood pressure rose slightly, but significantly, with time after nephrectomy. Average increases of 10 mm and 5 mm in systolic and diastolic pressures, respectively, were noted by 2 years after surgery. In this study, there was no evidence of glomerular injury from hyperfiltration in the 3 years following donor nephrectomy.

Adult↗
PubMed1985

Impact of cyclosporine on cadaveric renal transplantation: a summary statement.

CsA has now been used in this country for about four years and has been widely available for a little more than one year. Both the experience of those centers that have been using it longest, and total US national experience, suggest that CsA is now, with the sole exception of recipients matched for both HLA-DR antigens, the immunosuppressive of choice for all cadaveric renal allografts, conferring approximately a 10% advantage in graft survival. The advantages of CsA seem particularly apparent in the management of high-risk patients such as those over 50 years old and those with diabetes. CsA appears to reduce the frequency of rejection episodes and to permit reduction of steroid dosage. These factors, together with the improved graft survival rate, may contribute to a substantially higher rate of patient rehabilitation. The role of transfusion and HLA matching in association with CsA remains somewhat controversial. While large multicenter studies show the continued importance of both transfusion and optimal HLA matching, it has been argued that avoidance of pretransplant transfusions has avoided presentation of potential recipients, and that simplification of matching requirements has saved money and has permitted speedier transplantation of patients, favoring improved rehabilitation. Careful monitoring of the experience with this major new immunosuppressive agent over the next several years may answer these remaining questions.

Blood Transfusion↗
PubMed1985

Glomerular sieving of anionic and neutral bovine albumins in proteinuric rats.

To characterize the defect in glomerular permeability leading to albuminuria in rats made nephrotic acutely by infusion of hexadimethrine (HDM) or chronically by administration of Adriamycin (doxorubicin) (Adria), we developed and validated a tissue accumulation method for simultaneous determination of the glomerular sieving coefficients (GSC) of anionic 131I-labeled bovine albumin (BSA-pI 4.9) and 125I-labeled charge-modified neutral BSA (nBSA-pI 7.5 to 8.0). Total filtered marker was calculated by adding marker excreted in the urine to that filtered but reabsorbed by the tubules. The latter was determined by subtracting interstitial marker present in the left kidney, rendered non-filtering by ureteral ligation during mannitol diuresis, from the total marker accumulating within the right, filtering kidney. Experiments showed that markers circulated and were excreted intact and were neither degraded nor deiodinated during the period of the clearance studies. In control animals the GSC of nBSA (0.026 +/- 0.004) greatly exceeded that of BSA (0.0006 +/- 0.0002), demonstrating the normal charge dependence of permeability. Both proteinuric groups had marked increases in the GSC of BSA (HDM: 0.021 +/- 0.005; Adria: 0.025 +/- 0.004), which correlated with appearance of rat albumin in their urine. HDM rats also had a twofold increase in the GSC of nBSA (0.049 +/- 0.005), indicating alteration of the size dependence of permeability. The absolute increase of GSC of BSA and nBSA was similar, suggesting that albuminuria resulted from appearance of new "pores" in the glomerular filter that were not charge selective for proteins of the size of albumin. Thus, infusion of HDM, which binds to and neutralizes GBM anions, appears to produce albuminuria by inducing a structural change in the glomerular filter. Conversely, Adria rats had no significant increase in the GSC of nBSA (0.031 +/- 0.005), indicating no significant change in the size dependence of permeability for proteins of the size of albumin. In these animals, the GSC of the anionic BSA approached that of the neutral nBSA, indicating that Adriamycin induces albuminuria by markedly reducing the normal charge dependence of permeability.

Animals↗
PubMed1984

Stainable glomerular basement membrane polyanions and renal hemodynamics during hexadimethrine-induced proteinuria.

To clarify the mechanism of hexadimethrine-induced proteinuria, we studied the changes in stainable glomerular basement membrane anions and renal hemodynamics during hexadimethrine (HDM) infusion. To determine whether glomerular anions were neutralized in vivo, animals infused with HDM received cationized ferritin intravenously, or their kidneys were perfused in situ with lysozyme. During its infusion, HDM bound heavily within the glomerular basement membrane, and binding of the cationic probes was virtually abolished. During recovery after HDM infusion, HDM deposits diminished and the binding of the cationic probes recovered to normal. The inverse correlation between HDM binding and binding of the cationic probes confirms that the glomerular binding of HDM is associated with neutralization or shielding of the glomerular basement membrane anions in vivo. Renal hemodynamic parameters and urinary protein excretion rate were measured before, during, and after infusion of HDM. Heavy proteinuria appeared during HDM infusion and persisted for 1 hour after its discontinuation. Although glomerular filtration rate, renal plasma flow, and urine flow rate decreased transiently at the onset of proteinuria, they returned to baseline levels before resolution of proteinuria. Filtration fraction never changed significantly. Thus, proteinuria cannot be attributed solely to renal hemodynamic factors. These results strengthen our hypothesis that HDM induces proteinuria as a consequence of its binding to and neutralization of glomerular basement membrane fixed anions.

Animals↗
PubMed1981

Acute reversible proteinuria induced by infusion of the polycation hexadimethrine.

To test the hypothesis that neutralization of polyanions of the glomerular filter in vivo will lead to loss of charge-dependent glomerular permselectivity, we have infused i.v. the polycation hexadimethrine (HDM) into rats. Heavy proteinuria resulted after a lag period of 30 to 50 min, and it resolved when the infusion was stopped. Concurrent administration of heparin prevented the proteinuria. Urinary proteins were examined by immunoelectrophoresis, isoelectric focusing with immunofixation, and sodium dodecylsulfate polyacrylamide electrophoresis. The major protein was rat albumin, but there were also large quantities of intact rat IgG. HDM was bound at known sites of glomerular polyanion in the laminae rarae of the basement membrane and on the epithelial cell glycocalyx. Associated with this binding were reversible abnormalities of the epithelial cells similar to those seen during in vitro neutralization of glomerular polyanion. Aside from proteinaceous tubular casts, no other histologic abnormality was noted. These studies provide direct evidence that neutralization of glomerular polyanions in vivo results in heavy proteinuria. The appearance of substantial quantities of rat IgG in the urine implies that abnormalities of size as well as charge-dependent permselectivity occur, suggesting that the polyanions of the glomerular filter may be important in maintaining its structure as well as its function.

Animals↗
PubMed1980

Transfusion and renal allograft survival: beneficial effect of transfusions given on day of transplantation.

To determine if the beneficial effect of blood transfusion on renal allograft survival can be obtained without risk of presensitization, we examined the effect of transfusions given on the day of transplant surgery in a series of 180 primary cadaveric renal allografts. Three-month graft survival of those transfused only on the day of transplant was significantly better than the graft survival of those never transfused, and was not significantly different from graft survival of those transfused during the dialysis waiting period. Maximal beneficial effect was achieved by administration of as few as two to three units. We conclude that the benefits of transfusion can be obtained while minimizing the risks of presensitization if transfusion is minimized during the dialysis waiting period and patients are electively transfused at the time of transplant.

Adolescent↗
PubMed1980

Effect of timing of administration and quantity of blood transfusion on cadaver renal transplant survival.

Graft and patient survival rates were analyzed in 239 consecutive first cadaver renal transplants as a function of time of administration of blood transfusion and the number of units given. There was no statistically significant difference in patient survival in comparing patients who were never transfused, patients not previously transfused who received blood peroperatively, those who received blood before transplantation only, and those who were transfused before transplantation and peroperatively. In fact, the best survival rates were achieved in patients who were not transfused previously. Graft survival rates were significantly better in the prior transfused groups compared to either the never transfused group or the larger no prior transfused group which included the peroperatively transfused patients. Graft survival of the peroperatively transfused patients was intermediate between the never transfused and the prior transfused patients. There was no statistically significant difference between graft survival rates of patients who received more than 6 units of blood with those receiving less than 6 units. Also, the time interval from the last transfusion to transplantation appeared to have no effect on graft survival. Since an intentional transfusion protocol carries the real risk of sensitization and delay or elimination of the transplantation option, a prospective study comparing peroperative with preoperative transfusions is suggested. Such a study would answer the questions of the risk of sensitization with prior transfusion and the value of peroperative transfusions.

Blood Transfusion↗
PubMed1980

A rapid method for embedding tissues for electron microscopy using 1,4-dioxane and Polybed 812.

A rapid method for embedding tissues for electron microscopy is described. This method, which can be completed within 5 hr, uses 1,4-dioxane as the final dehydrating agent and Polybed 812 as the embedding medium. Satisfactory preservation of cellular structures is consistently achieved with a variety of normal and diseased tissues. This method may be of particular value to diagnostic electron microscopy laboratories where time and simplicity are critical.

Animals↗
PubMed1979

The role of monocytes in serum sickness nephritis.

We have investigated the pathogenesis of glomerular hypercellularity seen in acute serum sickness nephritis induced in rabbits with bovine serum albumin (BSA). The increase in cellularity began with the first stages of immune clearance of BSA, with a peak cellularity occuring at the time of onset of proteinuria. Although there was a significant increase in the fraction of glomerular cells incorporating [3H]thymidine, first seen at the onset of proteinuria, this increase occurred too late and was too small to explain the observed rate of increase in glomerular cellularity. On the other hand, a striking monocytic infiltration of the glomeruli was documented by electron microscopy and by staining for nonspecific esterase. This monocytic infiltration paralleled the observed course of glomerular hypercellularity and was quantitatively sufficient to explain the total increase seen. It appears, therefore, that glomerular hypercellularity seen in this model is principally a result of monocyte infiltration.

Animals↗
PubMed1976

Acute renal failure following halothane anesthesia.

Acute renal failure was observed postoperatively in a patient after halothane anesthesia. The clinical and pathologic findings in this case were remarkably similar to those found in patients with renal failure after methoxyflurane anesthesia.

Acute Kidney Injury↗