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L Hopp

Publications and source records attributed to L Hopp.

At least 37 records · Page 2Linked to original sources

Acute myocardial infarction in a young boy with nephrotic syndrome: a case report and review of the literature.

A 7-year-old boy with a 5-year history of steroid-unresponsive nephrotic syndrome due to minimal change disease presented with acute myocardial infarction. Angiography was suggestive of a dissected atherosclerotic plaque at the initial and mid portions of the right coronary artery, as well as a lesion in the mid portion of the circumflex artery. The child had a long history of extreme hypercholesterolemia and hypertriglyceridemia, along with apolipoprotein-E 4/3 phenotype. The mother, who also has apolipoprotein-E 4/3 phenotype, has mild hypercholesterolemia. The case suggests that children with long-lasting nephrotic syndrome and even mild familial propensity for hyperlipidemia may be at increased risk for ischemic cardiovascular events. The literature is reviewed regarding the relationship between nephrotic syndrome and the incidence of ischemic heart disease.

Arteriosclerosis↗

Improving results of pediatric renal transplantation.

BACKGROUND: Outcome after renal transplantation in children has been variable. We undertook a retrospective study of our experience over the past five years. STUDY DESIGN: From January 1, 1988, to October 15, 1992, 60 renal transplantations were performed upon 59 children at the Children's Hospital of Pittsburgh. Twenty-eight (47 percent) of the kidneys were from cadaveric donors, and 32 (53 percent) were from living donors. The recipients ranged in age from 0.8 to 17.4 years, with a mean of 9.8 +/- 4.8 years. Forty-six (77 percent) recipients were undergoing a first transplant, while 14 (23 percent) received a second or third transplant. Eight (13 percent) of the patients were sensitized, with a panel reactive antibody of more than 40 percent. Eleven of the 14 patients undergoing retransplantation and seven of the eight patients who were sensitized received kidneys from cadaveric donors. Thirty-three (55 percent) patients received cyclosporine-based immunosuppression, and 27 (45 percent) received FK506 as the primary immunosuppressive agent. RESULTS: The median follow-up period was 36 months, with a range of six to 63 months. The one- and four-year actuarial patient survival rate was 100 and 98 percent. The one- and four-year actuarial graft survival rate was 98 and 83 percent. For living donor recipients, the one- and four-year actuarial patient survival rate was 100 and 100 percent; for cadaveric recipients, it was 100 and 96 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 95 percent for the living donor recipients and 96 and 69 percent for the cadaveric recipients. Patients on cyclosporine had a one- and four-year patient survival rate of 100 and 97 percent, and patients on FK506 had a one- and three-year patient survival rate of 100 and 100 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 85 percent in the cyclosporine group, while one- and three-year actuarial graft survival rates were 96 and 84 percent in the FK506 group. The mean serum creatinine level was 1.24 +/- 0.64 mg per dL; the blood urea nitrogen level was 26 +/- 13 mg per dL. The incidence of rejection was 47 percent; 75 percent of the rejections were steroid-responsive. The incidence of cytomegalovirus was 10 percent. The incidence of post-transplant lymphoproliferative disorder was 8 percent. None of the patients on cyclosporine were able to be taken off prednisone; 56 percent of the patients receiving FK506 were taken off prednisone successfully. Early growth and development data suggest that the patients receiving FK506 off prednisone had significant gains in growth. CONCLUSIONS: These results support the idea that renal transplantation is a successful therapy for end-stage renal disease in children. They also illustrate the potential benefits of a new immunosuppressive agent, FK506.

Adolescent↗

Lipophilic impurity of phenol red is a potent cation transport modulator.

Previously, we described substantial alterations in the Na+ and K+ homeostasis of human skin fibroblasts following removal of fetal bovine serum (FBS). Herein, we report that FBS removal per se does not cause any cellular ionic changes unless a lipophilic impurity of commercial phenol red preparations is present. This substance accelerates 86Rb+ efflux four to seven times, causes a four to eight time increase in cellular Na+, and a 40-70% reduction in cellular K+ contents. FBS (10%) or albumin (0.8%) appears to bind the impurity thus inhibiting its action. The increased cellular Na+ and decreased K+ contents do not return to baseline within 4 hours following the removal of the phenol red extract. However, albumin completely reverses the cellular cationic changes that develop during a 2 hour exposure of the cells to the free substance. The reversibility of its action by albumin suggests that the substance exerts its effect on or within the cell membrane and not intracellularly. Among seven different cell lines tested the 86Rb+ efflux from, and the Na(+)-K+ contents of, COS-7 and Hs68 cells also responded to unpurified phenol red in a way similar to human fibroblasts. The amount of the phenol red contaminant is manufacturer dependent. As little as 0.5 microM phenol red, from one vendor, was sufficient to elicit response in the 86Rb+ efflux. Given that the impurity is unlikely to be more than a small fraction of phenol red, it seems to be a potent ionic transport modulator. Based on these results, the presence of commercial phenol red in serum-free growth or test media, including the increasing variety of chemically defined culture media, should be considered as a potential confounding factor in measurements that depend on intracellular Na(+)-K+ homeostasis. The findings of such earlier studies may need to be reconsidered if the cells were exposed to unbound phenol red. We recommend that, until the manufacturers further refine their product, phenol red be purified by ether extraction before its use. The evaluation of the potential physiologic or pharmacologic relevance of this potent cation transport modulator awaits its isolation.

Albumins↗

Acute noncrescentic poststreptococcal glomerulonephritis presenting with pulmonary hemorrhage.

We report a child with acute poststreptococcal noncrescentic glomerulonephritis and pulmonary hemorrhage. This patient demonstrates that: (1) poststreptococcal noncrescentic glomerulonephritis in children can be associated with pulmonary hemorrhage, (2) an expeditious renal biopsy in patients with acute or rapidly progressive glomerulonephritis and pulmonary hemorrhage can establish an early diagnosis and provide timely guidance for treatment, and (3) although not proven by controlled studies, the intravenous administration of methylprednisolone in our patient may have been effective in the treatment of pulmonary hemorrhage.

Acute Disease↗

A study of early fetal growth patterns in twin pairs.

The relationships of sitting heights and body weights of fetal twin pairs were analyzed in comparison with established growth rate standards of singleton fetuses. The apparent rate of growth of individual twins scattered around the average growth curve in the same manner as singletons. In contrast, members of 12 twin pairs with < 125 mm sitting heights, were closely similar in terms of bodily dimensions. Among the 7 pairs with crown-rump lengths of > 125 mm, 4 were discordant, suggesting a deceleration of growth in one of the twin fetuses, starting after the 18th week of gestation.

Body Height↗

Characterization of Na(+)-K+ homeostasis of cultured human skin fibroblasts in the presence and absence of fetal bovine serum.

Previously, we demonstrated that removal of fetal bovine serum (FBS) from the medium of human skin fibroblasts resulted in an accelerated 86Rb+ washout, decreased cellular K+, and increased Na+ contents. In the present study we examined the mechanism underlying these changes. The efflux rate constant for 86Rb+, and the cellular contents of Na+ and K+ were measured. Verapamil (K1/2 = 15 microM) and chlorpromazine (K1/2 = 1 microM) reduced by approximately 70% the increased 86Rb+ washout evoked by FBS removal. The effect of the two drugs was additive at low, but not high, concentrations. Verapamil and chlorpromazine also attenuated the decrease in cellular K+ content and prevented the increase in cellular Na+ content associated with FBS depletion. Bumetanide (50 microM) was only partially effective in offsetting the enhanced 86Rb+ efflux and was completely without any effect on the cellular Na+ and K+ changes induced by FBS removal. In the presence of FBS, A-23187 produced a slight and transient increase of the 86Rb+ washout. The protein kinase C activator phorbol 12-myristate 13-acetate enhanced the 86Rb+ efflux in FBS-containing medium for a prolonged period but this increase was only a fraction of that caused by serum removal. Cellular Na+ and K+ contents were not changed by the phorbol ester. We conclude that FBS removal raises the cellular Na+ content, and enhances 86Rb+ efflux, through a calmodulin-dependent pathway activated by calcium influx.

Animals↗

IgA nephritis in a patient with Alagille syndrome and a transplanted liver.

Alagille syndrome (arteriohepatic dysplasia) is a major cause of intrahepatic cholestasis in infancy. The present report describes a patient with Alagille syndrome who presented with hematuria and IgA nephritis 7 years after an orthotopic liver transplantation and immunosuppression. This patient suggests that glomerular lipidosis is not an inherent feature of the Alagille syndrome, and that IgA nephritis may develop in spite of ongoing immunosuppressive treatment.

Alagille Syndrome↗

Characterization of murine monoclonal antibodies directed against the core proteins of human immunodeficiency virus types 1 and 2.

Monoclonal antibodies (MAbs) raised against the core proteins of human immunodeficiency virus type 1 (HIV-1; laboratory strain HTLV-IIIB) and HIV-2 (strain ROD) were investigated in a variety of tests, e.g., enzyme-linked immunosorbent assay (ELISA), immunostaining of Western immunoblots, immunofluorescence, immunoprecipitation, and alkaline phosphatase anti-alkaline phosphatase assay. The MAbs were grouped according to their cross-reactions. Seven HIV-1-specific MAbs reacted exclusively with HIV-1, and five showed cross-reactivity with HIV-2 and simian immunodeficiency virus of macaques in ELISA. Four of the 15 MAbs against HIV-2 reacted only with the HIV-2 protein p26. Six showed cross-reactivity with HIV-1, and five showed a broad reaction with all three viruses. Overlapping 30-amino-acid-long peptides derived from the p24 protein sequence of HIV-1 were used in an epitope-mapping system. Three different immunogenic regions (A, B, and C) could be defined. Specific regions where anti-HIV-1 and -HIV-2 MAbs cross-reacted were mapped with shorter oligopeptides.

Amino Acid Sequence↗

[Current trends in perinatal mortality statistics at the New Jersey Obstetric Center].

The study presents an overview of the changes in perinatal mortality rates at the Statewide Perinatal Center of New Jersey during the past decades. According to the data, the increase in the rate of cesarean sections from 4.5 percent to 17 percent, and the comparable reduction of the rates of manipulative intrapartum and extraction procedures, contributed significantly to the decrease of the perinatal mortality rates from 51/1000 to 17/1000 between 1971 and 1983. Of the new technical tools, those utilized for the evaluation of fetal well-being antepartum appeared to be more useful then those used intrapartum. On account of the high prevalence of genital infections in the population, the recent acceptance in the service of the use of invasive intrapartum technology, appears to have impacted unfavorably upon the perinatal mortality trends. The increased rate of births of premature babies, the widespread abuse of habit forming drugs in the community, and the routine use of procedures requiring artificial rupture of the membranes, probably all contributed to the rapid increase of the perinatal mortality rate in the Center from 15/1000 in 1986 to 28/1000 in 1988. It is concluded that perinatal care is a complex medical and social task. The overall result of the relevant efforts depends to a great extent upon the social environment, and the moral standing, educational level and motivation of the recipients.

Humans↗

A higher cellular sodium turnover rate in cultured skin fibroblasts from blacks.

Differences in cellular Na+ and K+ regulation may relate to the pathogenesis of essential hypertension and the predisposition of blacks to this disease. To explore these tenets, we examined several aspects of cellular Na+ homeostasis in serially passed, cultured skin fibroblasts from 30 subjects (15 hypertensive blacks and whites and normotensive subjects matched for sex, age, and race.) Fibroblasts from blacks demonstrated higher cellular Na+ turnover rates than did those from whites. This difference was expressed by accelerated Na+-K+ pump activity (ouabain-sensitive Na+ washout rate, 3.46 +/- 0.216 for blacks vs 1.84 +/- 0.283 mEq/L/min for whites; p = 0.0006) and a higher rate of cellular accumulation of Na+ in the presence of ouabain (0.964 +/- 0.0743 vs 0.562 +/- 0.0440 mEq/L/min for blacks and whites, respectively; p = 0.0045). Associated with these findings, fibroblasts from blacks had higher cellular Na+ concentration than did those from whites (9.78 +/- 0.512 vs 7.50 +/- 0.400 mEq/L; p = 0.0170, as measured by atomic absorption, and 7.84 +/- 0.470 vs 5.03 +/- 0.980 mEq/L; p = 0.0141, as derived from the equilibrium distribution ratio of 22Na+). It is concluded that blacks differ from whites with respect to cellular Na+ turnover rate, which is evidenced by an increased Na+ influx and accelerated Na+-K+ pump activity in their fibroblasts. Our findings support the tenet that innate racial differences in cellular Na+ regulation may underlie the predisposition of blacks to hypertension.

Adult↗

Refined evaluation of the exponential curve parameters and initial exchange rate constant for 22Na+ washout in cultured human skin fibroblasts.

A technique is proposed to evaluate the exponential curve parameters and the initial exchange rate constant (kie) for 22Na+ washout from cultured human skin fibroblasts. After loading with the isotope, the cells were subjected to cold washing and warming steps. A desaturation curve for 22Na+ washout was developed including the activity in the warming medium that corresponded to t = 0 min. Using nonlinear regression analysis, a general three exponential function adequately described the 22Na+ washout in the time interval of 0-70 min. A back extrapolation was performed to estimate the initial time (ti; a negative number) when the total activity was present in the cells. The ti was substituted into the first derivative function of the three exponents to yield the kie. Calculated from the equilibrium distribution of 22Na+ and the specific activity of the medium, the concentration of Na+ (in mM; mean +/- SD) for fibroblasts of two individuals were 13.3 +/- 2.3, n = 3, and 19.0 +/- 5.2, n = 4. This indicates that the washout originated mainly or exclusively from the cellular milieu. Therefore, the kie represents the equilibrium exchange rate constant for Na+ washout from an inhomogeneous cell-related space. Multiple experiments demonstrated that the kie value for the two subjects were significantly higher than the initial slopes of the washout curves (kA), a commonly used parameter to characterize Na+ washout, and significantly lower than the slopes of the fastest exponential components (k3): kie = 0.531 +/- 0.017, kA = 0.502 +/- 0.019, and k3 = 0.557 +/- 0.017 min-1 (n = 3) for one subject, and kie = 0.567 +/- 0.065, kA = 0.479 +/- 0.031, and k3 = 0.667 +/- 0.094 min-1 (n = 6) for the other subject. The respective equilibrium exchange rates for these cells, namely the products of kie and cellular Na+ contents, were 1.10 +/- 0.16 and 1.19 +/- 0.24 nmole/10(5) cells. Using the exponential curve parameters, analytical solutions of a serial model and a parallel model with three compartments were performed. According to these analyses the major portion of the cellular Na+ comprises a fast exchangeable cellular compartment. The relative size of this compartment (expressed as a fraction of total cellular Na+ content) for fibroblasts of the two subjects was 96.2 and 89.2% for the serial model and 96.1 and 89.3% according to the parallel model.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

Angiotensin II effect on 22Na+ transport in vascular smooth muscle cells.

It is well established that angiotensin II (AII) rapidly increases free cytosolic Ca2+ in vascular smooth muscle cells (VSMCs). Several studies have indicated that the hormone also plays a role in Na+-K+ regulation of these cells. In this study, we explored the mechanism of AII effect on 22Na+ transport in cultured rat VSMCs. The 22Na+ washout from these cells was described by three exponents with exponential factors k1 greater than k2 greater than k3. In 1.8 mM Ca2+ medium, AII (10(-9)-10(-6) M) increased (in a dose response manner) the k1 value, and consequently the initial washout rate constant (kei) for the isotope. AII had no effect on kei in Ca2+-deficient medium or in the presence of ouabain. Amiloride (10(-3) M) and verapamil (10(-5) M) abolished the AII induced increase in kei. These findings are consistent with angiotensin II stimulation of an amiloride-sensitive Na+ transport, which is likely to represent the Na+/H+ antiport. In cultured VSMCs, the sustained stimulation by AII of this transport system requires the presence of extracellular Ca2+ and its influx into these cells.

Amiloride↗

Viral myocarditis.

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Critical Care↗

Effect of acute serum depletion on Na+-K+ homeostasis in cultured human skin fibroblasts.

In order to elucidate changes in cell transport behavior of cultured human skin fibroblasts in response to acute serum depletion, we performed uptake and washout of 22Na+ and 86Rb+ as well as measurements of the intracellular Na+ and K+ levels in the presence and absence of ouabain. Pronounced and lasting increase in cellular Na+ and decrease in K+ were observed after removal of fetal bovine serum (FBS) from the medium. The sum of the Na+ and K+ contents (nEq/10(5) cells) was lower in FBS-free medium (mean +/- SD; 17.3 +/- 2.2) than in FBS-containing medium (26.2 +/- 3.8; P less than .02). Simultaneously, a decrease in cellular water volume was detected in the FBS-free medium. The cation uptake and washout data suggest that FBS removal primarily renders the cells more permeable to Na+ and K+ with a secondary stimulation of the ouabain-sensitive Na+ extrusion mechanism. FBS at a concentration of 0.2% prevented approximately 50% of the maximal increase in the 86Rb+ washout rate constant associated with FBS depletion. Ouabain (2 microM) produced an increase in the 86Rb+ washout rate constant. This effect was substantially larger in cells subjected to medium without FBS (from 0.0303 to 0.2500 min-1) than in fibroblasts incubated in medium with FBS (from 0.0107 to 0.0487 min-1). The cellular K+ content was drastically reduced by ouabain to a level not different in medium with or without FBS (33.9 +/- 4.5 to 1.75 +/- 0.38 and 16.7 +/- 1.4 to 1.4 +/- 0.13 nEq/10(5) cells, respectively). The 22Na+ washout data exhibited a three-exponential pattern. Analytical solutions of the washout data by means of two models (serial and parallel) with three compartments showed that FBS depletion resulted in increase of the size of all three compartments. It is concluded that in cultured human skin fibroblasts, FBS is essential to the maintenance of a normal Na+ and K+ homeostasis. The removal of FBS results in dramatic permutation of this homeostasis that develops within minutes and lasts for hours.

Adult↗

Sodium 22+ washout from cultured rat cells.

The washout of Na+ isotopes from tissues and cells is quite complex and not well defined. To further gain insight into this process, we have studied 22Na+ washout from cultured Wistar rat skin fibroblasts and vascular smooth muscle cells (VSMCs). In these preparations, 22Na+ washout is described by a general three-exponential function. The exponential factor of the fastest component (k1) and the initial exchange rate constant (kie) of cultured fibroblasts decrease in magnitude in response to incubation in K+-deficient medium or in the presence of ouabain and increase in magnitude when the cells are incubated in a Ca++-deficient medium. As the magnitude of the kie declines (in the presence of ouabain) to the level of the exponential factor of the middle component (k2), 22Na+ washout is adequately described by a two-exponential function. When the kie is further diminished (in the presence of both ouabain and phloretin) to the range of the exponential factor of the slowest component (k3), the washout of 22Na+ is apparently monoexponential. Calculations of the cellular Na+ concentrations, based on the 22Na+ activity in the cells at the initiation of the washout experiments, and the medium specific activity agree with atomic absorption spectrometry measurements of the cellular concentration of this ion. Thus, all three components of 22Na+ washout from cultured rat cells are of cellular origin. Using the exponential parameters, compartmental analyses of two models (in parallel and in series) with three cellular Na+ pools were performed. The results indicate that, independent of the model chosen, the relative size of the largest Na+ pool is 92-93% in fibroblasts and approximately 96% in VSMCs. This pool is most likely to represent the cytosol.

Amiloride↗