PubMed Health⌕ Search

Biomedical subjects

S Stadler

Publications and source records attributed to S Stadler.

18 recordsLinked to original sources
PubMed2006

Tracer test with As(V) under variable redox conditions controlling arsenic transport in the presence of elevated ferrous iron concentrations.

To study transport and reactions of arsenic under field conditions, a small-scale tracer test was performed in an anoxic, iron-reducing zone of a sandy aquifer at the USGS research site on Cape Cod, Massachusetts, USA. For four weeks, a stream of groundwater with added As(V) (6.7 muM) and bromide (1.6 mM), was injected in order to observe the reduction of As(V) to As(III). Breakthrough of bromide (Br(-)), As(V), and As(III) as well as additional parameters characterizing the geochemical conditions was observed at various locations downstream of the injection well over a period of 104 days. After a short lag period, nitrate and dissolved oxygen from the injectate oxidized ferrous iron and As(V) became bound to the freshly formed hydrous iron oxides. Approximately one week after terminating the injection, anoxic conditions had been reestablished and increases in As(III) concentrations were observed within 1 m of the injection. During the observation period, As(III) and As(V) were transported to a distance of 4.5 m downgradient indicating significant retardation by sorption processes for both species. Sediment assays as well as elevated concentrations of hydrogen reflected the presence of As(V) reducing microorganisms. Thus, microbial As(V) reduction was thought to be one major process driving the release of As(III) during the tracer test in the Cape Cod aquifer.

Arsenic↗
PubMed2001

Monoclonal anti-acid-labile subunit oligopeptide antibodies and their use in a two-site immunoassay for ALS measurement in humans.

Quantification of the acid-labile subunit (ALS) has to date been restricted to immunoassays utilizing polyclonal antibodies. By immunization with N-terminal and C-terminal specific ALS oligopeptides, we generated monoclonal antibodies (mAbs) that target ALS-specific sequences outside the nonspecific leucine-rich repeats in the ALS molecule. For mAb selection, a special screening method was developed. Monoclonal antibody 5C9, which targets the N-terminus of ALS, is immobilized and the anti-ALS mAb 7H3, directed against the C-terminus, is biotinylated and used as tracer Ab. Due to the extreme pH-lability of ALS, changes in immunorecognition of ALS were investigated after acidification for protein unfolding in different pH ranges and in a time-dependent manner. It was determined that acidification of the serum samples to pH 2.7 for 30 min, followed by neutralization and dilution to 1:100 was the optimal acid-neutralization method. For standardization purposes, a serum pool derived from healthy volunteers was assigned the value 1 U/ml ALS. The sandwich assay has a working range with a linear dose-response curve in a log/log system between 0.005 and 10 U/ml. ALS levels in seven acromegalic patients ranged from 2.0 to 4.2 U/ml, and in 12 untreated growth hormone deficient patients from 0.036 to 0.986 U/ml (mean=0.45 U/ml). After 12 months of growth hormone therapy, ALS levels increased significantly to 1.18+/-0.45 U/ml (mean+/-SD; p<0.0006). The increase ranged from 0.48 to 1.4 U/ml. The change in ALS with growth hormone (GH) therapy correlated closer with the change in IGF-I (r=0.798, p=0.0057; Spearman rank correlation) than with the change in insulin-like growth factor binding protein (IGFBP3; r=0.549, p=0.057). This specific sandwich assay for the measurement of ALS provides a potentially valuable indicator of growth hormone secretory status. With this mAb-based immunofluorometric assay, the nonspecific detection of other proteins containing leucine-rich repeat sequences can be excluded.

Acromegaly↗
PubMed2001

Detection of neonatal argininosuccinate lyase deficiency by serum tandem mass spectrometry.

Argininosuccinate lyase (ASL) deficiency (McKusick 207900) is an inborn error of the urea cycle. The leading symptom is progressive hyperammonaemia, which is a life-threatening condition, particularly in patients with a neonatal onset. Early diagnosis and treatment of the hyperammonaemia are necessary to improve survival and the long-term outcome of ASL-deficient patients. Currently, the diagnosis of ASL deficiency is based on the measurement of urea cycle intermediates and amino acids by automated quantitative ion exchange chromatography in plasma and urine. Here, we report a newborn presenting with coma and severe hyperammonaemia. ASL deficiency was suspected on the basis of an adapted tandem mass spectrometric (MS-MS) procedure which allows determination of argininosuccinate in addition to the amino acids in serum samples. MS-MS measurements revealed a characteristic increase of argininosuccinate, a moderate increase of citrulline, and lowered levels of arginine and ornithine in the serum of the patient. The diagnosis was confirmed by the detection of a novel homozygous frameshift mutation in exon 14 of the argininosuccinate lyase gene. We propose MS-MS as a diagnostic tool suitable for the rapid detection of specific alterations in the amino acid spectra caused by ASL deficiency.

Amino Acid Sequence↗
PubMed1995

Hemorrheologic effects of metabolites of pentoxifylline (Trental).

Pentoxifylline (Trental) is metabolized by red blood cells and the liver into seven metabolites. Metabolites I and V have significant hemorrheologic effects. They are both similar to pentoxifylline in their activity on red blood cell membrane fluidity. Metabolite I is more active than pentoxifylline in inhibiting ADP-induced platelet aggregation. Metabolite V is more active than pentoxifylline in inhibiting epinephrine-induced platelet aggregation.

Adenosine Diphosphate↗
PubMed1994

Potentiation of thrombolytic therapy by enzyme combinations and with aspirin or pentoxifylline.

Radioactively labeled human fibrin clots were placed into veins of Macaca arctoides monkeys. Thrombolysis was recorded by the disappearance of radioactivity and by angiography. Streptokinase (SK) and urokinase (UK) induced thrombolysis was potentiated by low dose aspirin (ASA) and pentoxifylline (PE). Studies on the mechanisms of action revealed that PE inhibits platelet aggregation, releases tissue plasminogen activator (t-PA) from the endothelium, increases red cell deformability and inhibits white cell adhesion. Thrombolysis by pro-urokinase (pro-UK) was potentiated by low dose SK probably because of streptokinase-plasmin activation of pro-UK to UK. Platelet aggregation inhibitory effects, disaggregation of platelet aggregate inducing effects, and the t-PA releasing activity of PE was demonstrated in patients with obstructive cardiovascular disease. Pharmacodynamic studies suggested that PE metabolites one and five are most effective from this point of view. These metabolites are currently studied in combination with thrombolytic enzymes.

Animals↗
PubMed1993

Risks of peritoneal membrane failure in children undergoing long-term peritoneal dialysis.

Children undergoing long-term peritoneal dialysis are at risk for membrane injury, necessitating conversion to hemodialysis. We analyzed the incidence and risk factors for membrane failure (inadequate ultrafiltration with or without peritoneal adhesions and decreased peritoneal surface area) in 68 children maintained with peritoneal dialysis for more than 3 months at our institution. The overall incidence of membrane failure was 16.2% (11/68). Kaplan-Meier estimates of peritoneal membrane survival were 88% at 24 months, 72% at 36 months, 65% at 48 months, and 52% at 60 months. Logistic regression analysis demonstrated that the risk of membrane failure increased with the number of episodes of peritonitis (odds ratio 1.61). The rate of peritonitis was 1 per 7.02 patient months in children who developed membrane failure compared with 1 per 9.18 patient months in children without membrane failures but the rate of peritonitis was not predictive of membrane failure (P = 0.09). Multiple logistic regression analysis demonstrated that peritonitis caused by Pseudomonas aeruginosa or alpha streptococcal organisms were independent predictors of membrane failure. We conclude that peritoneal membrane survival declines substantially with time on peritoneal dialysis and that membrane failure is associated with peritonitis, particularly peritonitis caused by Pseudomonas aeruginosa and alpha streptococcal organisms. The mechanism(s) of membrane injury are unknown but may be related to the inflammatory response initiated during peritonitis.

Adolescent↗
PubMed1992

Studies on tumor induced angiogenesis.

Methods were developed to test angiogenic response to human tumor implants and various biologic agents in the cornea of rabbits and non-human primates (Macaca arctoides). Crude PDGF preparations were found to have significant angiogenic effect. Purified, recombinant PDGF preparations were also effective inhibitors (e.g. pentoxifylline (Px) (which also were found to release PgI2 and t-PA) inhibited human tumor implant induced angiogenesis and reduced spontaneous metastases in 3 transplantable murine tumors (Furth-Columbia Wilms' tumor in Furth-Wistar rats, C-1300 neuroblastoma in A/J mice and HM-Kim mammary carcinoma in Wistar rats) but not in the NIH adenocarcinoma in Balb/c mice. Sodium diethyldithiocarbamate (DDTC), a metal complexing agent with special affinity to copper and anti-thyroid as well as, immune stimulating activity was shown to be anti-angiogenic and to potentiate the effect of Px. The anti-fibrinolytic agents epsilon amino caproic acid (EACA) and tranaxamic acid (t-AMCHA) were anti-angiogenic. DDTC and Px were synergistic from this point of view.

Adenocarcinoma↗
PubMed1992

Increased prostaglandin E2 and cAMP phosphodiesterase levels in Kaposi's sarcoma--a virus against host defense mechanism.

In Kaposi's sarcoma tissue, prostaglandin E2 (PgE2) levels and cAMP phosphodiesterase levels were found to be higher than in surrounding normal tissue. We have shown earlier that PgE2 suppresses interferon (IFN) alpha production. High levels of cAMP phosphodiesterases result in low cAMP levels. Thus, this phenomenon may be involved in altered immunologic resistance, growth and differentiation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Hemorheologic effects of Meclomen including effect in malignant melanoma.

Sodium Meclofenamate, (Meclomen) (M) is a non-steroidal anti-inflammatory drug, which inhibits both cyclooxygenases and lipooxygenases of the arachidonic acid cascade (AA). (M) inhibited adenosine diphosphosphate (ADP) induced platelet aggregation, arachidonic acid (AA) induced platelet aggregation and collagen induced platelet aggregation. (M) inhibited platelet factor 3 availability when measured by Stypven clotting time. Red cells from patients with advanced malignancies and normal red cells stored in blood banks exhibited loss of deformability. (M) enhanced red cell deformability in these blood samples.

Arachidonic Acid↗
PubMed1990

Dose-response effects of pentoxifylline on erythrocyte filterability: clinical and animal model studies.

Ten patients with chronic occlusive arteriosclerosis received single oral doses of 100, 200, 400, 800, and 1200 mg pentoxifylline in a single-blind, placebo-controlled study. Blood samples were drawn at baseline and at 2 hour intervals for 6 hours. Drug and metabolite levels, as well as red cell filterability (deformability), were determined on all blood samples. Statistically significant dose-response increases of red cell filterability were found 4 and 6 hours after oral medication with the dosages of 200 to 1200 mg pentoxifylline. These changes were proportional to the plasma levels of pentoxifylline and metabolites 1 and 5 of this agent. Attempts were made to develop a suitable animal-screening method for agents with similar activity and to determine whether red blood cells in the absence of disease-related abnormalities may respond to this type of therapy. Five healthy Macaca arctoides monkeys were given 24 mg/kg pentoxifylline intravenously, and measurable but lesser increases in red cell deformability were recorded than in the patients.

Animals↗
PubMed1990

Effect of meclomen on production and action of human interferon alpha.

Meclomen (sodium meclofenamate) is a nonsteroidal anti-inflammatory drug (NSAID) with dual inhibition of both cyclooxygenase and lipooxygenase enzymes involved in arachidonic acid metabolism. Meclomen at nontoxic levels (10(-5) to 10(-8) mol/l) caused a 2-6 fold increase in interferon (IFN) production in lymphocytes induced by Sendai virus. This enhancement was observed in the case of all blood donors tested. Meclomen at the same concentration range had no effect on the antiviral activity of human IFN alpha. However, meclomen did show some enhancement of antiproliferative activity of human IFN alpha against human adenocarcinoma lung cells. Meclomen (10(-5) mol/l) inhibited intracellular levles of prostaglandin E2 by over 90% within the first four hours. The results presented here strongly suggest that inhibition of intracellular levels of PGE2 has no adverse influence upon the antiviral and antiproliferative activities of human IFN alpha.

Cell Division↗
PubMed1988

Studies on the vasoocclusive crisis of sickle cell disease IV. Mechanism of action of pentoxifylline (Trental).

Pentoxifylline was shown to prevent sickling induced by deoxygenation of SS-genotype blood from sickle cell disease patients. It also prevents development of cell stiffness, based on decreased membrane fluidity. This effect is related to increased red cell ATP content, decreased potassium loss during sickling and decreased attachment of hemoglobin to the red cell membrane during sickling. There was no effect on osmotic fragility or mean corpuscular volume. There was some increase in pH of blood from patients in vasoocclusive crisis of sickle cell disease under the effect of pentoxifylline. The consideration is discussed that pentoxifylline may prevent vasoocclusive crisis, but may not abort an existing process.

Adenosine Triphosphate↗
PubMed1987

Studies on the vasoocclusive crisis of sickle cell disease. III. In vitro and in vivo effect of the pyrimido-pyrimidine derivative, RA-233: studies on its mechanism of action.

Red cell deformability was found to be impaired in SS- and SC-genotype and to a lesser extent SA-genotype red blood cells as compared with those of AA-genotype. RA-233 in vitro improved deformability according to a bell-shaped dose-response curve. RA-233 also prevented experimental vasoocclusive crisis in Macaca arctoides. Deoxygenation of SS-genotype red cells resulted in sickle shape transformation, ATP depletion, potassium efflux, and attachment of hemoglobin molecules to the membrane. These changes were prevented by RA-233. Suspending SS-genotype red blood cells in potassium rich tris-buffer also prevented potassium efflux during deoxygenation and also decreased cellular deformability. RA-233 had no effect on osmotic fragility of SS-genotype red blood cells.

Adult↗