Search PubMed⌕ Search

Biomedical subjects

S L Goldstein

Publications and source records attributed to S L Goldstein.

35 records · Page 2Linked to original sources
PubMed1999

Serial estimation of glomerular filtration rate in children after renal transplant.

Evaluation of serial monthly estimated glomerular filtration rate (eGFR) may be useful for studying pediatric renal allograft outcome. To determine the validity of this approach, we reviewed our single-center experience in pediatric renal transplant recipients to determine the effect of risk factors for renal allograft failure on eGFR. Clinical parameters recorded monthly through 5 years post transplant allowed serial assessment of eGFR. Monthly clinical data included height, weight, serum creatinine, cumulative number of acute rejection episodes, cyclosporine dose, and cyclosporine trough levels. From these data, eGFR was calculated monthly for each patient using the Schwartz formula. Time post transplant was grouped in 6-month intervals and plotted against mean eGFR to compare eGFR in patients grouped by demographic and clinical factors; 1,786 monthly data sets from 6 months post transplant (n=76 patients) to 5 years post transplant (n=25 patients) were analyzed. Overall mean eGFR from 6 months to 1 year was 75 ml/min per 1.73 m(2) and from 4. 5 to 5 years 46 ml/min per 1.73 m(2). eGFR was lower at all time intervals for recipients of cadaver versus living-related donor grafts, and patients with >/=1 versus 0 acute rejections (P<0.01). After 1 year, eGFR was lower in black patients compared with white or Hispanic patients (P<0.01). Cyclosporine dose greater than 5 mg/kg per day was associated with better early and worse late graft function. These results are similar to those reported in multi-center studies using the outcome variable of graft failure and suggest that serial eGFR may be valid as an outcome variable to study chronic renal allograft dysfunction in children.

Adolescent↗
PubMed1999

Evaluation and prediction of urea rebound and equilibrated Kt/V in the pediatric hemodialysis population.

The posthemodialysis blood urea nitrogen (BUN) concentration rebounds for 30 to 60 minutes after hemodialysis in adults. Timing of the posttreatment BUN sample has a significant impact on the calculation of Kt/V. Urea rebound and its effect on Kt/V have not been extensively studied in children and adolescents. We evaluated posthemodialysis urea rebound after 46 treatments in 18 pediatric patients with end-stage renal disease. BUN levels were drawn at 30 seconds and 5 and 15 minutes posttreatment. From these values, a logarithmic regression curve was derived that defined percentage of urea rebound (%UR) = -0.254 + 10.9*log(t), (r = 0.79). Using this equation, we estimated BUN, %UR, and Kt/V at equilibration (50 minutes) for each treatment. Estimated mean %UR was 18.7%. Single-pool Kt/V (spKt/V) and estimated double-pool Kt/V (estKt/V) values were significantly different (P < 0.0001). %UR and percentage of difference between spKt/V and estKt/V did not vary as a function of dry weight, body surface area, or K/V. To test the validity of logarithmic extrapolation, additional BUN levels were drawn at 30 seconds and every 10 minutes for 1 hour postdialysis in six patients. Percentage of difference between estKt/V and measured equilibrated Kt/V was 3.6% +/- 1.7%. Our results show %UR has a significant impact on the calculation of Kt/V in children, does not vary with patient size, and is similar to that seen in adults. We have devised an easy and accurate method to predict equilibrated BUN and calculate double-pool Kt/V in children, which requires only an additional 15-minute posttreatment BUN sample.

Adult↗
PubMed1999

Natural logarithmic estimates of Kt/V in the pediatric hemodialysis population.

The natural logarithm formula for Kt/V proposed by Daugirdas is recognized as a valid and simple alternative to formal urea kinetic modeling (UKM) in adults receiving hemodialysis. No data have been published to validate the use of this formula in infants, children, and adolescents. We compared Kt/V derived by formal UKM with the natural logarithmic formula for 103 treatments in 21 pediatric end-stage renal disease patients receiving chronic hemodialysis. Values for Kt/V derived by formal UKM ranged from 0.65 to 2.06. Patients ranged in age from 1.8 to 22.5 years and in dry weight from 10.2 to 82.5 kg. The largest percent error between the two methods for any data point was less than 6%. The total error (absolute value percent error + 2 SD) was less than 6% across the entire range of dry weights. Our data show excellent agreement between formal UKM and the natural logarithm formula for Kt/V in pediatric hemodialysis patients, even those weighing less than 30 kg. These results support the use of the natural logarithm formula as a valid alternative to formal UKM in children. The simplicity of this formula should allow for the use of Kt/V as the best measure to study the relationship between delivered dialysis dose and outcomes in children.

Adolescent↗
PubMed1999

(Alpha)3(beta)1 integrin regulates epithelial cytoskeletal organization.

Epithelial cell morphology and cytoskeletal organization are determined by interactions, with both adjacent cells and the extracellular matrix, which are mediated by integrins and cadherins. Little is known, however, of the relative contributions of integrins and cadherins to maintaining the sub-cortical cytoskeleton characteristic of epithelial cells. Since most studies that utilize integrin-blocking antibodies result in a loss of both cell-cell adhesion and sub-cortical cytoskeletal organization, it has been difficult to distinguish whether integrins and cadherins both mediate cytoskeletal assembly in epithelial cells. Therefore, cells derived from kidney collecting ducts of (alpha)3(beta)1 integrin-deficient mice were used to examine the role of integrins in epithelial cell morphology and cytoskeletal organization. In primary cell culture, (alpha)3(beta)1 integrin-deficient kidney collecting duct cells maintain cadherin-mediated cell-cell adhesions but fail to form the sub-cortical cytoskeleton that is characteristic of epithelial cells, and instead assemble actin stress fibers. Moreover, the cell-cell junctions in mutant cells were irregular, rather than being uniformly oriented perpendicular to the culture substrate. These results demonstrated that integrins have an primary and essential function in establishing and maintaining the sub-cortical cytoskeleton that is characteristic of epithelial cells. To further study the role of (alpha)3(beta)1 integrin in establishing and maintaining cytoskeletal organization in tubular epithelial cells, we derived immortalized cell lines from wild-type and (alpha)3(beta)1 integrin-deficient kidney collecting ducts that duplicated the cytoskeletal and cadherin organization observed in primary cells. E-cadherin and (alpha)- and (beta)-catenin were complexed together in equal amounts in membranes of wild-type and (alpha)3(beta)1 integrin-deficient cells. However, association of the cadherin:catenin complex with (alpha)-actinin was greatly decreased in mutant cells, indicating that integrin-mediated assembly of the sub-cortical cytoskeleton is essential for subsequent association of the cytoskeleton with the cadherin:catenin complex. These results present direct evidence for integrin:cadherin cross-regulation in which cadherin function is dependent on the presence of an integrin.

Animals↗
PubMed1998

cDNA encoding a single-chain antibody to HIV p17 with cytoplasmic or nuclear retention signals inhibits HIV-1 replication.

HIV-1 gag p17 protein is an attractive target for molecular intervention, because it is involved in the viral replication cycle at both the pre- and postintegration levels. In the present experiments, we targeted p17 by intracellularly expressing a cDNA encoding an Ab to p17. cDNA from a hybridoma-secreting Ab to p17 was cloned, sequenced, reconstructed as a single-chain Ab fragment (scFv), and expressed in the cytoplasm or nucleus with appropriate retention signals. The expressed scFvs had no effect on T cell growth or CD4 expression and bound specifically to HIV-1 p17. Human CD4+ Jurkat T cells that expressed scFvs and were infected with HIV-1 showed a marked reduction in virus replication compared with cells expressing vector alone. The inhibition of virus replication was more pronounced when scFvs were expressed in the cytoplasm rather than the nucleus. From these studies, we conclude that the intracellular expression of a single-chain Ab to p17 inhibits HIV replication; in addition, the degree of inhibition is related to the intracellular targeting site.

Amino Acid Sequence↗
PubMed1997

Hemodialysis catheter survival and complications in children and adolescents.

Venous catheters have become an indispensable form of hemodialysis access. We evaluated catheter performance as temporary and long-term access in children with end-stage renal disease (ESRD). We assessed the survival rates and causes of catheter failure in 78 catheters used for hemodialysis access in 23 pediatric patients (aged 10 months to 22 years) with ESRD over a 5-year period. Median survival was 31 days for 56 uncuffed catheters. One- and 2-month actuarial survival was 69% and 48%, respectively. Reasons for removal were: elective (39%), kinking (36%), trauma (11%), infection (7%), and other (5%). Smaller catheters (7 or 9 French) were more likely to be removed for kinking (P = 0.003). One-year actuarial survival for 22 cuffed catheters was 27%. Cuffed catheters were removed due to: infection (36%), kinking (14%), elective (9%), trauma (9%) and other (9%). Twelve catheters were removed for infection. Infection rates leading to removal were 0.58 and 0.71 per patient-year for uncuffed and cuffed catheters, respectively. Staphylococcus species were cultured most commonly. We conclude that uncuffed catheters function well for short-term hemodialysis access of up to 2 months' duration and cuffed catheters are successful for long-term access in children and adolescents with ESRD.

Adolescent↗
PubMed1996

Determination of isotope enrichments of magnesium in microwave-digested biological samples by thermal ionization mass spectrometry using a direct loading technique.

The isotope ratios of magnesium were determined in isotopically normal and 26 Mg-enriched samples of human blood, blood plasma, urine and faeces and bovine muscle. The measurements were made with a magnetic sector, thermal ionization mass spectrometer (TIMS) equipped with a multiple ion collector system for simultaneous detection of the ion currents. The samples were decomposed using microwave digestion with HNO3 and HCI. Without further chemical treatment, the mineralized samples were deposited together with silica gel and boric acid on rhenium filaments, which served as thermal ionization source filaments. This method, called the direct loading technique (DLT), results in stable ion signals of the magnesium isotopes with isotope ratios indistinguishable from those of natural Mg standards within experimental error. Fractionation-corrected 26 Mg/24 Mg ratios of natural Mg standards were determined with a relative external precision of 0.02%. The magnesium recoveries for all of the analysed matrices were > or = 97%; 26 Mg was added to calibrated sample solutions to produce isotopic enrichments within a range typically appearing in samples of human tracer studies. Linear regression analysis of measured versus expected per 1000 (/1000) enrichments yields y = 0.998x + 0.79. The DLT described here is a simpler and quicker method than other methods reported hitherto. It has the advantage of avoiding magnesium separation and purification steps prior to TIMS analysis for all of the analysed biological samples and thus reduces contamination and guarantees optimum magnesium recovery. The reported method improves the applicability of stable isotopes of magnesium in human tracer studies.

Animals↗
PubMed1996

Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis.

A mutation was targeted to the murine alpha3 integrin gene. Homozygous mutant mice survived to birth, but died during the neonatal period. The mutation caused abnormal kidney and lung development. Mutant kidneys displayed decreased branching of the medullary collecting ducts, although the number of nephrons was not altered. Proximal tubules exhibited two distinct subsets of abnormalities, with the epithelial cells either containing excess lysosomes or becoming microcystic. In addition, glomerular development was markedly affected. In mutant kidneys, the extent of branching of glomerular capillary loops was decreased, with capillary lumina being wider than normal. The glomerular basement membrane was disorganized and glomerular podocytes were unable to form mature foot processes. Branching of the bronchi in lungs of mutant mice was also decreased and the large bronchi extended to the periphery. These results indicate a role for integrin receptors in basement membrane organization and branching morphogenesis.

Animals↗
PubMed1994

Sm-Nd dating of Fig Tree clay minerals of the Barberton greenstone belt, South Africa.

Sm-Nd isotopic data from carbonate-derived clay minerals of the 3.22-3.25 Ga Fig Tree Group, Barberton greenstone belt, South Africa, form a linear array corresponding to an age of 3102 +/- 64 Ma, making these minerals the oldest dated clays on Earth. The obtained age is 120-160 m.y. younger than the depositional age determined by zircon geochronology. Nd model ages for the clays range from approximately 3.39 to 3.44 Ga and almost cover the age variation of the Barberton greenstone belt rocks, consistent with independent evidence that the clay minerals are derived from material of the belt. The combined isotopic and mineralogical data provide evidence for a cryptic thermal overprint in the sediments of the belt. However, the highest temperature reached by the samples since the time of clay-mineral formation was <300 degrees C, lower than virtually any known early Archean supracrustal sequence.

Aluminum Silicates↗
PubMed1983

Metabolite distribution and rate of residue clearance in turkeys fed a diet containing aflatoxin B1.

The retention of aflatoxin residues in tissues of turkey poults fed a diet containing aflatoxin B1 (500 ppb) for 18 days was determined. Free and conjugated aflatoxin metabolites were quantified using high-pressure liquid chromatography. Aflatoxin residue levels were greater in liver than muscle tissues, although all levels were low (range 0.01-1.19 ng/g tissue). Free and conjugated aflatoxins B1 and M1, a metabolite of B1, were the principal tissue residues. Other metabolites investigated included aflatoxicol, which was detected in certain samples, and aflatoxin Q1 which was not detected. Conjugated aflatoxins, hydrolysed and extracted from the aqueous tissue fractions, comprised 55-91% of the total detected aflatoxin residues. All aflatoxin residues were rapidly cleared following discontinuation of the dietary aflatoxin B1 (half-life 1.4 days for total aflatoxin clearance from liver). These results provide further evidence that tissues from animals maintained on diets containing aflatoxins do not provide a major source of aflatoxins when consumed by man.

Aflatoxin B1↗
PubMed1975

Investigations concerning the mode of action of 3,4-dihydroxybutyl-1-phosphonate on Escherichia coli.

Experiments were performed to evaluate the ability of the enzymes of Escherichia coli involved in glycerol 3-phosphate metabolism to recognize phosphonic acid analogues of the natural substrate. Neither the catabolic membrane-bound glycerol-3-phosphate dehydrogenase nor the acyl coenzyme A: glycerol-3-phosphate acyltransferase can use 3,4-dihydroxybutyl-1-phosphnate or 2,3-dihydroxypropyl-1-phosphonate are inhibitors of the reduction of dihydroxyactone phosphate as substrates. The 4-carbon phosphonic acid analogue does not exhibit inhibitory activity for either of these enzymes. While the 3-carbon phosphonic acid analogue has no inhibitory effect upon the catabolic dehydrogenase, it does appear to have a slight but reproducible inhibitory effect on the acyltransferase. Glycerol 3-phosphate and 3,4-dihydroxybutyl-1-phosphonate by glycerol 3-phosphate:NAD (P) oxidoreductase. rac-2,3-Dihydroxypropyl-1-phosphonate does not appear to be recognized by this enzyme. The apparent K-i for snglycerol 3-phosphate is 19 muM and for D-3,4-dihydroxybutyl-1-phosphonate it is 42 muM. In addition the glycerol 3-phosphate:NAD(P) oxidoreductase catalyzes the reduction of 4-hydroxy-3-oxobutyl-1-phosphonate (apparent K-m of 182 muM), a phosphonic acid analogue of dihydroxyacetone phosphate. 3,4-Dihydroxybutyl-1-phosphonate is both a competitive inhibitor (apparent Ki of 740 muM) and a substrate (apparent K-m of 450 muM) for the CDP-diglyceride: glycerol 3 phosphate phosphatidyltransferase but it has no effect upon CDP-diglyceride:L-serine phosphatidyltransferase. The relationship ofthese in vitro studies to in vivo investigations is discussed.

Acyltransferases↗