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Biomedical subjects

J Weissgarten

Publications and source records attributed to J Weissgarten.

At least 55 records · Page 3Linked to original sources

Renal uric acid handling in non-insulin-dependent diabetic patients with elevated glomerular filtration rates.

1. Hypouricaemia is prevalent in diabetic patients. In most of the studies, the diabetic patients had some degree of diabetic nephropathy as evidenced by a decreased glomerular filtration rate and proteinuria. Therefore we studied renal uric acid handling in a group of type II diabetic patients with elevated glomerular filtration rates. 2. Eighteen type II diabetic patients with normal kidney functions and elevated glomerular filtration rate and a group of 18 healthy, age- and weight-matched control subjects, were studied. Serum fructosamine, creatinine and uric acid levels were determined. Twenty-four hour urine collections were obtained, and microalbumin, glucose, creatinine and uric acid, were measured. 3. The creatinine clearance was higher and the serum uric acid concentration was lower in the diabetic patients (P < 0.05). The 24 h urinary uric acid excretion and filtered uric acid load were similar in both groups. However, the derived parameters of uric acid clearance and fractional excretion were significantly higher in the diabetic patients (P < 0.002 and P < 0.05, respectively). A negative correlation was apparent between serum fructosamine concentration and serum uric acid concentration (r = -0.76). A positive correlation was found between serum fructosamine concentration and fractional uric acid excretion (r = 0.64) and between serum fructosamine concentration and filtered uric acid load (r = 0.66). A positive correlation was found between creatinine clearance and 24 h uric acid excretion (r = 0.61) and between creatinine clearance and filtered uric acid load (r = 0.82).(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine↗

Effect of dietary manipulations on glomerular filtration rate of mice offspring of nephrectomized mothers.

We have previously reported that mice, offspring to uninephrectomized mothers, have greater than normal kidneys with supernumerary glomeruli. In this study we assessed glomerular filtration rate (GFR) in 40 mice offspring of nephrectomized mothers and 40 mice offspring of sham-nephrectomized animals aged 7 weeks. Each group was divided into 4 equal subgroups according to the following dietary manipulations: regular, high protein, high salt and high protein/high salt. At the end of 1 week, GFR was determined by 51Cr EDTA. In the first group, GFR was significantly greater in each experimental subgroup compared to control. In the offspring of sham-nephrectomized mothers, only the subgroup on the combined diet had a significantly greater GFR. We conclude that the capacity to raise GFR in response to dietary manipulations is greater in offspring of nephrectomized mothers. It remains to be elucidated whether the difference results from the increased number of nephrons or from an augmented single nephron GFR reserve.

Animals↗

Renal mononuclear cells secrete a factor triggering mesangial cell proliferation.

Thirty-six Charles River rats underwent left unilateral nephrectomy and 18 counterparts had sham nephrectomy. After 48 h the kidneys of all animals were removed, and renal mononuclear cells (RMNC) harvested. The RMNC were cultured in RPMI 1640 medium supplemented with either 20% fetal calf serum or sera procured from sham operated rats, or from nephrectomized animals. Ten days later the conditioned media of RMNC cultures were collected. Peripheral blood mononuclear cells (PBMC) from sham-operated or nephrectomized rats were also grown in RPMI 1640 supplemented with 20% fetal calf serum, sham serum or post-nephrectomy serum. The conditioned media of PBMC cultures were also collected after 10 days. Mesangial cells procured from kidneys of different normal animals were cultured in DMEM/F12HAM cell culture medium supplemented with 50% of the various RMNC- or PBMC-conditioned media. Proliferation of mesangial cells grown in conditioned medium of post-nephrectomy RMNC which had been precultured with post-nephrectomy serum was significantly augmented compared with control or any other experimental situation. There was no statistically-significant difference between proliferation rates of mesangial cells cultured in any other medium of control or experimental RMNC or PBMC. We conclude that following unilateral nephrectomy, RMNC of the remaining kidney are activated to secrete, under a sustained signal of post-nephrectomy serum, a growth factor(s) stimulating proliferation of normal mesangial cells.

Animals↗

Effect of exercise training on glomerular filtration rate of mice with various degrees of renal mass reduction.

We studied the effect of repeated heavy physical activity on glomerular filtration rate (GFR) in healthy, uninephrectomized and experimentally uremic mice. Exercise consisted of running uphill in the inner surface of a rotating cylinder in ideal environmental temperature. In the control groups, no extra physical activity was imposed. In sham-operated and nephrectomized mice, GFR rose significantly following training. By contrast, GFR did not change significantly in the exercised mice with experimental renal failure 24 h following the last exercise session. During the same period, no significant change was observed in GFR of any of the control groups. Following training in each experimental group, mean aortic blood pressure as well as fractional kidney weight (kidney weight/body weight) were not different from the respective controls. Our results indicate that the capacity to augment GFR by physical training is dependent upon the amount of remaining functional renal tissue.

Animals↗

Postnephrectomy mesangial cells secrete a factor(s) that stimulate(s) tubular cell growth in vitro.

Rat kidney mesangial cells were procured from 5 sham-operated and 10 previously uninephrectomized rats. They were grown in cell culture medium supplemented with 20% fetal calf serum. Cell free conditioned medium was collected on the 10th day. Tubular cell cultures were then prepared from 18 normal unoperated 3-week-old rats. Tubular cells from each separate kidney sample were grown in pooled-mesangium conditioned medium from sham-operated or from nephrectomized rats, supplied with 20% pooled serum from either sham-operated or nephrectomized animals. 3H-thymidine incorporation of normal tubular cell cultures grown in nephrectomy mesangium conditioned medium supplemented with sera from nephrectomized animals proved to be significantly greater than that of any of the other three experimental variations. No statistically significant difference was evident when either preconditioned medium of postnephrectomy mesangial cells or postnephrectomy serum were used alone.

Animals↗

Lack of correlation between urea kinetic indices and clinical outcomes in CAPD patients.

We examined the predictive value of urea kinetics for patient outcomes in CAPD by measuring dialysis index (DI; a means of quantifying CAPD dose using urea kinetics), KT/V and normalized protein catabolic rate (PCRN) on 222 occasions in 76 new patients at the time of starting CAPD and at subsequent six month intervals. We investigated how these indices altered with time and in relation to each other, and how they correlated with a wide range of subsequent patient outcomes. DI, KT/V and PCRN all tended to decrease with time on CAPD (P less than 0.0004, less than 0.0001 and 0.0005, respectively). DI and KT/V were highly correlated with each other (r = 0.89, P less than 0.0001) and both correlated with PCRN (r = 0.57, P less than 0.0001 and r = 0.60, P less than 0.0001, respectively). DI and KT/V both correlated inversely with subsequent values for serum creatinine (P less than 0.0001), urea (P less than 0.0002), potassium (P less than 0.02) and phosphate (P less than 0.002), and directly with bicarbonate (P less than 0.0001). PCRN correlated inversely with serum creatinine (P less than 0.0002) and directly with urea (P less than 0.0001) and with the number of blood transfusions received (P less than 0.03). None of these indices correlated with levels of hemoglobin, PTH, alkaline phosphatase or albumin, or with nerve conduction velocity or any other subsequent clinical outcomes including death, technique failure, hospital days, peritonitis rate and subjective indices of fatigue, pruritus and insomnia. We conclude that the urea kinetic model is predictive of some biochemical outcomes but not of clinical outcomes in CAPD patients.

Adolescent↗

Pulse oximetry in the evaluation of the painful hand after arteriovenous fistula creation.

Five patients with a side-to-side arteriovenous fistula complaining of pain, numbness, and cold sensation were evaluated by pulse oximetry. Low SaO2 was noticed in all five. Closure of a major proximal venous collateral vessel eliminated the steal and resulted in SaO2 correction and was followed by clinical amelioration. Pulse oximetry proved to be a helpful adjunct in the evaluation of the painful hand after creation of an arteriovenous fistula. By applying the pulse oximeter to the patient's affected limb, we were able to determine whether the pain was a result of ischemia and if the correction of the steal improved oxygenation.

Arteriovenous Shunt, Surgical↗

Interleukin-2 receptor is similarly expressed by activated lymphocytes from patients on chronic hemodialysis and healthy subjects.

We studied peripheral blood mononuclear cells (PBMC) from 10 patients on chronic hemodialysis vs 10 healthy controls. T cells were counted by E rosette formation. Interleukin (IL)-2 receptor (IL-2R) carrier cells were identified by Dako-IL-2R, which was chosen as a monoclonal antibody that binds to the alpha chain of IL-2R without interrupting the cell machinery of mitogen-induced IL production. Fluorescein-tagged goat anti-rabbit IgG1* was used for subsequent cell staining, and cells were counted by FACS. Net numbers of PHA-activated IL-2R carrier cells were derived by subtracting appropriate background controls. The average number of these cells relative to numbers of total T cell population in uremic PBMC was statistically not different from healthy controls. Several defects in cellular activation associated with IL-2 mechanisms could be envisaged to account for the impaired proliferative response to PHA, manifested by uremic T cells.

Adult↗

Induction of suppressor cell activity by cyclosporin A and/or uremic serum in normal versus uremic peripheral blood mononuclear cells.

We investigated induction of suppressor cell activity in peripheral blood mononuclear cells (PBMC) from normal or uremic subjects. The cells were primed with cyclosporin A (CS-A), uremic serum, or both and subsequently cocultured with fresh phytohemagglutinin-stimulated normal allogeneic responders. CS-A-primed normal as well as uremic PBMC significantly suppressed responder cell thymidine incorporation. Uremic serum primed normal, but not the uremic, PBMC exerted a significant suppression on responder cell proliferation. No significant additive suppressive effect was detected following coculture of responders with PBMC primed by CS-A and uremic serum together. Exclusion of a distinct suppressor cell subset by panning, using anti-Leu-2b monoclonal antibody, did not result in blunting suppressive activity of the CS-A or uremic serum pretreated cells. On the other hand, adherent cell depletion of primed PBMC completely abolished their subsequent suppressive effect on responder cell proliferation.

Adult↗

Induction of suppressor cell activity in normal peripheral blood mononuclear cells by sera from predialytic uremic patients.

Normal peripheral blood mononuclear cells (PBMC) were primed with sera from 22 predialytic uremic patients, normal sera, concanavalin A, or both. Their suppressive activity was subsequently tested on fresh phytohemagglutinin-stimulated allogeneic responders (i.e., genetically unrelated to either primed cell or sera donors). Uremic serum induced suppressor cell activity in the normal PBMC. No correlation was found between serum urea/creatinine levels and their effects on suppressor cell activity. The induced activity, expressed as percent suppression, was similar to that induced by concanavalin A. In PBMC primed with both concanavalin A and uremic serum, an additive suppressive effect was evident. The suppressor subset(s) induced by uremic serum proved to belong to adherent cell population. Addition of indomethacin or catalase to responder systems did not abolish the suppressive effects, thus suggesting a mechanism of action other than prostaglandin or hydrogen peroxide release.

Adult↗

Dual challenge for glomerular damage in mice: uninephrectomy and repetitive pregnancies.

We examined the effects of unilateral nephrectomy (UNx) and repetitive pregnancies (RP) on glomerular damage and blood pressure in mice. Four groups of 10 female mice, 7 weeks old, underwent sham nephrectomy (SV) alone, sham nephrectomy and six pregnancies (SP), right nephrectomy alone (NV) and right nephrectomy followed by six repetitive pregnancies (NP). UNx resulted in a significant elevation of serum creatinine up to 11 weeks. In all animals pregnancy was associated with a temporary decrease in serum creatinine except at termination of the 6th pregnancy in group NP. UNx and RP did not result in an increase in protein excretion. UNx in both virgin and pregnant mice resulted in blood pressure elevation without any renal histological abnormalities by the end of the 6th pregnancy. We conclude that at least up to the end of the 3rd pregnancy, gestation was associated with augmentation in function of a single kidney. This effect was lost by the end of the 6th pregnancy. Multiple repetitive pregnancies in uninephrectomized animals entailed renal functional deterioration and a rise in blood pressure without renal histological abnormalities on light microscopy.

Animals↗

Increased concanavalin A-induced suppressor cell activity in humans with occupational lead exposure.

E-rosette-forming cells (E-RFC), mitogen-induced blast transformation, OKT4+, OKT8+ cells, and their ratio were found to be normal in 10 subjects chronically exposed to lead with blood levels of 40-51 micrograms%. However, concanavalin A (Con A)-induced suppressor cell activity (SCA) in these subjects was significantly greater than in normal matched controls. The clinical relevance of this observation is not clear, but it may have some bearing on the various immunologic defects described in lead exposure.

Adult↗

Uninephrectomy and repetitive pregnancies in mice: a combined stimulus for renal hypertrophy.

Three hundred 7-week-old Beit Dagan female mice underwent right nephrectomy or sham operation, and either remained virgin or were exposed to six repetitive pregnancies. Fractional kidney weight, dry weight and protein content were determined at ages 9, 10, 11, 17 and 26 weeks corresponding to the ends of the first, second and third trimester of the first pregnancy and completion of the third and sixth pregnancies respectively. In addition histological sections were evaluated morphologically and morphometrically. Renal dry weight and protein content per kidney increased abruptly to maximal values a week after nephrectomy and remained stable thereafter. Repetitive pregnancies were associated with progressive increments in both parameters. The effects of unilateral nephrectomy and repetitive pregnancy were additive. Following unilateral nephrectomy or pregnancy the number of glomeruli per field, as well as fractional glomerular area, increased more rapidly than in sham-operated virgin controls. However, the maximal glomerular number or fractional area attained did not differ from control values. We conclude that (a) in 8-week-old mice pregnancy is associated with renal cell hypertrophy; (b) repetitive pregnancies in these animals produce progressive augmentation in both renal dry weight and protein content; (c) the effects of repetitive pregnancy and unilateral nephrectomy on renal cell hypertrophy are additive; (d) this would indicate that neither manoeuvre exhausts maximal renal capacity for cell hypertrophy, and would suggest some possibilities for the underlying mechanisms.

Animals↗

The effect of exogenous lymphokines on immunoglobulin production and lymphocyte proliferation in renal transplant patients.

Peripheral blood mononuclear cells from stable long-term kidney transplant patients were activated in vitro by Staphylococcus Aureus Cowan I (SAC) (a B cell mitogen). The effect of exogenous interleukin 2 and/or B cell growth factor (BCGF) on these cells was measured by 3H-thymidine incorporation and immunoglobulin production. Both proliferation and Ig production were lower in SAC-activated cells from transplanted patients compared to controls (P less than 0.01). BCGF significantly enhanced blastogenesis (P less than 0.01) and Ig production (P less than 0.01) in SAC-treated cells from either patients or controls; however, the SAC- and BCGF-treated cells of transplant patients did not reach normal proliferation or immunoglobulin production values (P less than 0.001, P less than 0.01, respectively). The addition of IL-2 to SAC-activated cells also increased proliferation and Ig production both in controls (P less than 0.05) and patients (P less than 0.005). However, cells from transplant patients treated with SAC and IL-2 did not reach the normal levels of proliferation or immunoglobulin production (P less than 0.05 for both). IL-2 did not enhance the increase of immunoglobulin production brought about by BCGF. SAC-activated B cells from transplant patients do not proliferate normally and do not produce normal amounts of Ig. The addition of IL-2 and BCGF results in a partial but subnormal improvement in both proliferation and Ig production. We conclude that the B cell abnormality in transplant patients may be due to lack of T cell lymphokines and an intrinsic B cell defect. These results suggest that the administration of exogenous lymphokines to transplant patients with B cell dysfunction may be clinically useful.

Adult↗

Rhabdomyolysis and acute renal failure induced by paraphenylenediamine.

1. We present a 40-year-old healthy man who developed a typical clinical picture of rhabdomyolysis following the administration of paraphenylenediamine by a witchdoctor as a pain killer. 2. Two groups of 15 mice were given paraphenylenediamine 70 mg/kg and 35 mg/kg respectively. Biochemical and histological findings of rhabdomyolysis developed in both groups, without kidney damage. 3. Paraphenylenediamine may cause rhabdomyolysis resulting in acute renal failure in humans. In mice, however, it produces rhabdomyolysis, but the kidneys are not affected.

Acute Kidney Injury↗

Changes in peritoneal membrane transport rates in patients on long term CAPD.

Peritoneal equilibration tests (PET's) are a simple means of monitoring peritoneal membrane function in C.A.P.D. patients. Findings on initial testing have been proposed as having prognostic value for a patient's course on peritoneal dialysis. 177 serial P.E.T.'s were performed in 49 patients at six monthly intervals using a 2 litre 4.25% dextrose exchange and a four hour dwell and equilibration ratios were calculated for urea (D/P U), creatinine (D/P C) and glucose (D/Do G). Alterations in equilibration ratios with time were not significant in the group as a whole. However, a subgroup of 12 patients was identified in whom there were significant increases in D/P U (p .02) and in D/P C (p .003) and decreases in D/Do G (p .025) between zero and 18 months. A subgroup of five patients in whom D/P U decreased significantly (p .05) was also identified. These subgroups did not differ significantly in clinical characteristics although peritonitis was more frequent in the group with increasing transport. As results of P.E.T.'s alter with time in many patients prognostication based on initial values only may not be valid.

Adolescent↗