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Biomedical subjects

S J Soldin

Publications and source records attributed to S J Soldin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Serial lecithin/sphingomyelin ratios and surfactant/albumin ratios in tracheal aspirates from term infants with respiratory failure receiving extracorporeal membrane oxygenation.

Serial tracheal aspirate samples were obtained for determination of lecithin/sphingomyelin (L/S) ratios from 47 term infants in respiratory failure. Phospholipids were extracted with Folch solution (chloroform:methanol, 2:1 by vol) and analyzed by HPLC with use of silica column and a mobile phase of acetonitrile:methanol:water (48:31:21, by vol). Surfactant/albumin (S/A) ratios were determined with the TDx Fetal Lung Maturity Assay (Abbott Labs). L/S ratios increased significantly over time in all patients (F = 19.42, P < 0.0001). The S/A ratio correlated with the L/S ratio (r = 0.554, P < 0.001). This study suggests that postnatal surfactant deficiency in term newborns with respiratory failure is a component of the newborn's lung injury.

Albumins↗
PubMed1994

Identification of a 14 kDa FK-506/rapamycin binding immunophilin from calf thymus.

Specific binding proteins (immunophilins, 12-17 kDa) have been described in the cytosol for the immunosuppressant drugs cyclosporine, FK-506, and rapamycin. We describe the identification of a low abundant minor immunophilin (14 kDa) from calf thymus. Saturation experiments using dihydro[3H]-FK-506 gave a Kd of 2 nM and the Bmax of 72 nmol/mg protein. At saturation, 71.3 nmol of FK-506 is bound per mg of the 14 kDa protein (71 nmol) giving a drug/protein ratio of 1.0. Competition experiments using 3H-dihydro FK-506 and rapamycin showed displacement of rapamycin, with Kd in the range of 40 nM. The 14 kDa immunophilin does not have peptidyl-prolyl cis-trans isomerase activity with any of the four substrates investigated. Initial amino acid analysis and protein sequencing data indicate that the immunophilin is different from both the 12 kDa FK-506 binding protein and any other known protein.

Amino Acid Isomerases↗
PubMed1994

Partial characterization of a 52 kDa CsA/FK506/rapamycin binding protein.

Identification and characterization of the cellular proteins that specifically bind to the immunosuppressive drugs, cyclosporine (CsA), FK506, and rapamycin is necessary to understand their mechanism of action. We have isolated and partially characterized a 52 kDa binding protein (BP) from calf thymus. Using 12 peptide substrates we observed very low or no cis-trans peptidyl prolyl isomerase activity. We further tested the protein for catalytic activity including kinase activity, phosphatase activity, protein kinase C regulation, and LCK tyrosine kinase regulation. The 52 kDa BP was capable of blocking the cyclic AMP dependent, protein kinase mediated, phosphorylation of histones and casein. The protein did not demonstrate kinase activity, nor did it affect the activity of protein kinase C or LCK tyrosine kinase. Microsequencing of the 52 kDa BP was performed. A comparison of known sequences indicated that the protein is unique and has not been previously characterized.

Amino Acid Isomerases↗
PubMed1994

Neurologic manifestations of cocaine exposure in childhood.

OBJECTIVE: To describe the neurologic manifestations of cocaine exposure in children and adolescents as the neurologic effects of cocaine have been described in adults and neonates. METHODS: During 1-year period, 41 children between the ages of 2 months and 18 years who had been exposed to cocaine, were examined in the emergency department at the Children's National Medical Center. Cocaine exposure was documented on urine samples; all were confirmed by urine gas chromatographic/mass spectrometric analysis. RESULTS: Nineteen (46%) of 41 had neurologic abnormalities, including seizures (7), obtundation (6), delirium (4), dizziness (1), drooling (1), and ataxia (1). In 14 others, the neurologic effects of cocaine were difficult to determine because of other concomitant medical conditions, including head injuries and severe abdominal or chest trauma. Two major age-related patterns were seen: (a) in each child < 5 years of age, seizures and obtundation; and (b) in 11 older children, delirium (3), dizziness (1), drooling (2), and lethargy (4). Seizures, occurring at ages 12 months to 8 years, were focal with secondary generalization in three and generalized in four. They were associated with fever in two children. Six children had no further seizures, and one developed a mixed-seizure disorder. Passive intoxication while being in a room in which "crack" was smoked was the most likely cause of exposure for young victims. Multiple drug abuse was not documented in any child with neurologic impairment. CONCLUSIONS: 1) Cocaine exposure is common in children in our urban setting; 2) neurologic manifestations frequently occur; 3) in children 8 years of age or younger, "passive" ingestion/inhalation is associated with focal and generalized seizures without evidence of structural brain injury; 4) cocaine may lower seizure threshold in children predisposed to seizures; 5) in children > 8 years of age, manifestations are similar to those in adults; 6) trauma and motor vehicle accidents were seen in the adolescent age group exposed to cocaine; and 7) urine toxicological study in cocaine exposure is recommended in all first-time seizures as well as first-time febrile seizures.

Adolescent↗
PubMed1993

Immunophilin receptors for immunosuppressive drugs.

The major immunophilins that bind cyclosporine (cyclophilin) and FK-506/rapamycin (FK-BP 12) have been well characterized. They possess rotamase activity, which is inhibited by the immunosuppressant that binds to them. The immunosuppressive action does not appear to be coupled to rotamase activity. The literature is reviewed on some possible mechanisms of immunosuppression. Minor immunophilins of 14, 36, and 52 kDa have also been isolated and partially characterized. Receptor assays employing immunophilins have been developed.

Animals↗
PubMed1993

Vitamin B12 and folate. Pediatric reference ranges.

Pediatric reference ranges were obtained for vitamin B12 and folate (Quantaphase radioimmunoassay, BioRad, Hercules, Calif) using a large hospital population. Data were analyzed employing the Hoffman approach, which was computer adapted. For folic acid, the range for subjects aged 1 to 12 years averaged 5.7 to 31.3 nmol/L for female subjects and 4.5 to 27.0 nmol/L for male subjects. There was a significant decrease in folic acid concentrations after 13 years, the upper limit being 16.5 nmol/L in female subjects and 19.9 nmol/L in male subjects. For vitamin B12, the values in the 0- to 1-year age group were nearly double those in the 13- to 18-year age group. For female subjects, the values in the 0- to 1-year age group were 168 to 1116 pmol/L and in male subjects were 216 to 891 pmol/L. At 13 to 18 years, for female subjects the values were 158 to 637 pmol/L and for male subjects, 134 to 605 pmol/L.

Adolescent↗
PubMed1993

Cyclosporin G and metabolite binding to cyclophilin and a 50-kDa binding protein related to in vitro immunosuppression.

Seven purified metabolites of cyclosporin G (CsG) were studied for binding to cyclophilin and a 50-kDa binding protein (50-kDa BP). The ratios of the metabolite dissociation constants with respect to CsG were compared with in vitro immunosuppression by using the primary mixed lymphocyte suppression assay. The immunosuppressive potency ratio of the parent compounds, both cyclosporin A (CsA) and CsG, compared favorably with the drug dissociation constants for cyclophilin and the 50-kDa BP. Three of the seven metabolites had comparable binding and potency ratios for the 50-kDa BP. In contrast, none of the seven metabolites appreciably bound to cyclophilin in the concentration range tested.

Amino Acid Isomerases↗
PubMed1992

Bentiromide test using liquid-chromatographic measurement of p-aminobenzoic acid and its metabolites for diagnosing pancreatic insufficiency in childhood.

We assessed the diagnostic capability of the bentiromide test using a high-pressure liquid-chromatography method to analyze p-aminobenzoic acid and its metabolites in plasma as an indirect measure of exocrine pancreatic function. Mean total amine concentration in pancreatic-insufficient subjects was significantly lower than in control subjects. There were 3 of 15 false-negative results and no false-positive results. We conclude that this chromatographic method is an effective means of analyzing p-aminobenzoic acid and its metabolites after ingestion of bentiromide.

4-Aminobenzoic Acid↗
PubMed1992

Development of a radioreceptor assay to measure glucocorticoids.

We have developed a radioreceptor assay to measure glucocorticoids. The assay employs the partially purified 95-kDa receptor isolated from human liver and purified by size fractionation on high-performance liquid chromatography (HPLC). In the assay [3H]prednisolone competes with steroids (endogenous and exogenous) for binding to the receptor. Bound and free are separated by treatment with charcoal. The between-day precision [% coefficient of variation (CV)] at concentrations of 9.4, 18.7, and 69.9 micrograms/L prednisolone is 16.6, 9.3 and 4.5%, respectively. Specificity studies revealed that hydrocortisone, deoxycorticosterone, 4-pregnene-17 alpha,21-diol-3,20-dione, 17 alpha-hydroxyprogesterone, corticosterone and beta-hydroxyprogesterone all compete with [3H]prednisolone for binding to the receptor. Prednisone and 6 alpha-methyl prednisolone displace [3H]prednisolone to only a minor degree. The assay has been used to assess "glucocorticoid activity" in children with rheumatic diseases treated with prednisolone.

Charcoal↗
PubMed1992

Use of a radioreceptor assay in the assessment of cushingoid features in patients with juvenile rheumatic diseases.

A marked variation has been observed in severity of cushingoid appearance in patients with rheumatic diseases (RD) following steroid administration. We studied ten children with RD to determine if a relationship exists between cushingoid features and an individual's steroid activity as measured by prednisolone equivalents using a radioreceptor assay. Cushingoid features were clinically assessed by a "cushing score" according to the method of Bergrem. Patients were assigned to either the cushingoid (C) or noncushingoid (NC) group at study entry according to their cushing score. Blood was drawn prior to prednisone ingestion and then at 30, 60, 90, 120, 240, and 360 minutes and each sample was assessed for prednisolone equivalents and also for free and total cortisol. Group comparisons of dose-adjusted area under curve (AUC) and peak response are reported. Cushingoid patients had higher plasma prednisolone equivalents (PE) than noncushingoid patients as measured by peak PE and AUC. The PE.6 h/L average AUC for C patients was 248 micrograms PE.6 h/L versus 134 micrograms PE.6 h/L for NC patients. This nearly twofold difference was also noted between mean peak values (C 82 micrograms/L vs. NC 44 micrograms/L). Spearman correlations of Cushing scores with these two parameters indicated significant (p less than 0.05) relationships. A patient's Cushing score correlated best with peak response (rs = 0.78) and also with AUC (rs = 0.72). Measurement of plasma peak PE or AUC could be valuable for individualizing steroid dosing in children with RD.

Adolescent↗
PubMed1992

Preliminary studies on the in vitro and in vivo effect of salicylate on sperm motility.

We have studied the in vitro effect of different concentrations of salicylic acid on the motility of normal human spermatozoa. Sperm motility was evaluated over 48 h at 0, 50, 100, and 200 mg/L of salicylate concentrations. Results are reported as the mean % motility, where 100% motility at each time interval was taken to be the motility of the control (0 mg/L of salicylate). At 48 h, the mean % motility (n = 12) was 61, 43, and 33% at 50, 100, and 200 mg/L of salicylate. Twenty-four-hour values (n = 17) were 75, 65, and 48%. Eosin supravital staining demonstrated that the decrease in sperm motility was caused by direct inhibition of motility rather than by spermatozoal death. Four healthy males (17-51 years of age) gave a semen specimen prior to taking 650 mg of salicylate four times daily, followed by a second semen specimen 72 h later. Each individual, therefore, served as his own control. The mean % motility in the postdrug sample at 2, 24, and 48 h was 49, 53, and 47% of the motility found in the predrug sample (n = 4). We conclude that salicylate significantly decreases sperm motility in vitro and in vivo.

Adolescent↗
PubMed1992

Organic acids interfere in the measurement of carbon dioxide concentration by the Kodak Ektachem 700.

A significant discrepancy was noted in our laboratory between the total plasma carbon dioxide concentration measured by the Kodak Ektachem 700 and the bicarbonate concentration derived from the Corning 170 pH/Blood Gas analyser in an 8-day-old patient. The concentration of total carbon dioxide was 18 mmol/L while the derived bicarbonate was 13 mmol/L. The patient was eventually diagnosed as maple syrup urine disease. This finding led us to examine the effect of various organic acids on the measurement of carbon dioxide by the Ektachem 700. Several interfered significantly. Clinicians should be aware that when organic acid concentrations are increased, the Ektachem 700 total carbon dioxide result may be falsely raised.

Blood Gas Analysis↗
PubMed1992

Radioreceptor assay for quantifying FK-506 immunosuppressant in whole blood.

We describe a quantitative radioreceptor assay (RRA) for quantifying FK-506 in whole blood. FK-506 extracted from whole blood with a cyclohexyl-sorbent column competes with [3H]dihydro-FK-506 for binding to a partially purified preparation of FK-506 binding protein (FK-BP). Free and protein-bound FK-506 are separated on LH 20 Sephadex chromatographic columns. We compared the results of this method with those of an enzyme immunoassay that uses a monoclonal antibody: r = 0.97, Sy/x = 0.039. Between-day precisions (CV) at FK-506 concentrations of 8 and 17 micrograms/L were 9.2% and 8.2%, respectively. Within-run precisions were 5.9%, 8.1%, and 9.4%, respectively, at 4, 8, and 15 micrograms/L. Analytical recovery, evaluated at 5, 10, 15, 20, and 25 micrograms/L for FK-506 added to whole blood, ranged from 98% to 103%. The assay can reliably quantify FK-506 blood concentrations between 1.0 and 25 micrograms/L.

Chromatography, High Pressure Liquid↗
PubMed1991

Purification and characterization of cyclosporine and FK-506 binding proteins from a human T-helper cell line.

Cytosolic proteins that specifically bind cyclosporine A and FK-506 were isolated and purified from the JURKAT human T-helper cell line. These binding proteins were purified by affinity, molecular weight exclusion and weak cation exchange column chromatography. Radiolabeled cyclosporine A specifically bound to a approximately 17 kDa molecule which is cyclophilin and also bound to a approximately 50 kDa protein(s). Radiolabeled FK-506 did not bind to the approximately 17 kDa molecular weight protein, but specifically bound to soluble approximately 10 kDa and approximately 50 kDa proteins.

Amino Acid Isomerases↗
PubMed1991

Correlation of cyclosporine and metabolite binding to cyclophilin and a 50 kDa binding protein with in vitro immunosuppression: a preliminary report.

Seven purified cyclosporine (CsA) metabolites were analyzed for binding to cyclophilin and to a 50 kDa protein purified from a JURKAT cell line. In addition, the potency of the seven metabolites, relative to CsA, was obtained using a primary mixed lymphocyte culture (MLC) suppression assay. CsA, M1, 17, and 21 were found to be immunosuppressive in the concentration range used (0-500 ng/mL). These results were then compared to protein binding. CsA and metabolite 17 (M17) bound to both proteins. Conversely, M1, 13, 21, and 26 bound only to cyclophilin, while M8 and M18 bound only to the 50 kDa protein.

Amino Acid Isomerases↗