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Biomedical subjects

C R Angle

Publications and source records attributed to C R Angle.

At least 37 records · Page 2Linked to original sources
PubMed1987

Childhood lead toxicity and impaired release of thyrotropin-stimulating hormone.

Decreased stature of children is epidemiologically associated with increased blood lead independent of multiple socioeconomic and nutritional variables. Since endocrine dysfunction occurs in adult lead workers, we studied two girls, 2 years of age, before and after calcium disodium edetate chelation for blood leads (PbB) of 19-72 micrograms/dl. The height of both children had crossed from the 50th to below the 10th percentile during the course of chronic lead toxicity. Basal free T4, T4, T3, cortisol, somatomedin C, and sex steroids were normal. A decrease in the growth hormone response and elevation of basal prolactin and gonadotropins were noted in one. Both children demonstrated blunted thyrotropin-stimulating hormone (TSH) responses to thyrotropin-releasing hormone (TRH) in six of seven challenges. This prompted in vitro studies of cultured cells from rat pituitaries. After incubation of pituitary cells with 0.1-10 microM Pb2+ for 2 hr, followed by the addition of TRH, there was a dose-dependent inhibition of TSH release. Lead did not interfere with the assay of TSH. To investigate the interaction of lead and calcium, 45Ca2+ kinetic analyses were done on rat pituitary slices after 1 hr incubation with 1.0 microM lead. The impaired late efflux was consistent with a decrease in the size and exchangeability of the tightly bound pool of intracellular microsomal or mitochondrial calcium. The rat pituitary cell model provides a model for the decreased TSH release of lead poisoning, supports the biological plausibility of a neuroendocrine effect on growth, and suggests that interference with calcium-mediated intracellular responses is a basic mechanism of lead toxicity.

Animals↗
PubMed1987

Nephropathy-gonadal dysgenesis, type 2: renal failure in three siblings with XY dysgenesis in one.

The nephropathy-XY gonadal dysgenesis syndrome in a 17-year-old phenotypical female with focal glomerulosclerosis was associated with renal failure in two sisters, one with crescentic glomerulonephritis at 27 months, and one with membranoproliferative glomerulonephritis at 10 years. Neither the propositus or the siblings had the distinctive mesangial sclerosis of nephropathy-XY dysgenesis, type 1 (Drash syndrome). The association of nephropathy-XY dysgenesis with familial nephritis of heterogeneous pathology suggests that nephropathy-XY dysgenesis, type 2, may relate to separate genetic loci for XY dysgenesis and glomerulopathy or reflect a loss of protection against familial renal disease when the Y chromosome is absent or defective.

Adolescent↗
PubMed1987

Erythrocyte membrane microviscosity and phospholipid composition in lead workers.

The microviscosity and fluidity of erythrocyte ghost membranes from lead workers and control subjects was measured by fluorescence polarisation using the fluorophore, 1,6-diphenyl-1,3,5-hexatriene (DPH). Increased lead was associated with a significant decrease in the average microviscosity of resealed and unsealed erythrocyte membranes. Since DPH fluorescence reflects the organisation of lipids in the central core of the membrane, two aspects of phospholipid metabolism were investigated. Phospholipids were extracted from red blood cell ghost membranes and identified by high performance liquid chromatography. The ratio of phosphatidyl choline to phosphatidyl ethanolamine, an established correlate of membrane fluidity, was significantly increased in lead workers. This is attributed to the known increases in red blood cell cholesterol in lead workers and the structural incompatibility of phosphatidyl ethanolamine and cholesterol, which result in a compensatory increase of phosphatidyl choline. Erythrocyte ghost membranes from control subjects were resealed with the intermediates in phospholipid synthesis that increase with a lead inhibited decrease in red blood cell pyrimidine 5'-nucleotidase. Membrane fluidity was not modified by incubation with cytidine triphosphate, uridine triphosphate, cytidine diphosphate choline, or cytidine diphosphate ethanolamine. Alterations in the microviscosity of the lipid regions of the hydrophobic core of the erythrocyte membrane bilayer and in the phospholipid composition of the membrane may be defects which contribute to the clinical and biochemical instability of the red blood cell on exposure to lead.

Adult↗
PubMed1986

Erythrocyte arginase, pyrimidine 5'-nucleotidase (P5N), and deoxypyrimidine 5'-nucleotidase (dP5N) as indices of lead exposure.

The activities of three erythrocyte (rbc) enzymes, arginase, pyrimidine 5'-nucleotidase (P5N), and deoxypyrimidine 5'-nucleotidase (dP5N), were compared in 16 lead workers and 14 age matched controls as correlates of blood lead (PbB) and unextracted zinc protoporphyrin (EP) concentrations. Subjects with PbB of 0.9-2.5 microM (19-52 micrograms/dl) had 6.5 +/- 0.6 IU of P5N activity with uridine monophosphate (UMP) as substrate, significantly less (p less than 0.001) than the 12.0 +/- 0.7 IU activity of controls with PbB 0.3-0.6 microM (6-12 micrograms/dl). The mean activity of rbc dP5N with either deoxyuridine monophosphate (dUMP) or thymidine monophosphate as substrate, and of rbc arginase, did not differentiate the two groups. The correlation coefficients of ln PbB with the selected substrates for P5N and dP5N were: UMP, r = -0.75; dUMP, r = -0.61; TMP, r = -0.23. The correlation coefficient of ln PbB and arginase activity was -0.03. Rbc P5N (UMPase) is a significant correlate of PbB, equivalent to rbc protoporphyrin. HPLC assay of rbc UMPase activity is a sensitive and rapid assay that appears to meet criteria for a reliable clinical laboratory index of blood lead concentrations.

5'-Nucleotidase↗
PubMed1986

Laxative phosphate poisoning: pharmacokinetics of serum phosphorus.

Despite the frequency of acute poisoning in normal children by oral or rectal phosphosoda laxatives, the rate of clearance of the resultant high level of phosphorus and the rationale for therapy are defined incompletely. Pharmacokinetic analysis has been made of plasma inorganic phosphate (Pi) in an infant after ingestion of phosphosoda laxative and of data reported for four comparable poisonings in healthy infants to provide a nomogram which predicts the decline in Pi in paediatric phosphate poisoning. Clearance of Pi is exponential; it directly correlates with and approaches the glomerular filtration rate. After single oral or rectal overdoses, plasma Pi at diagnosis is 4-20 mmol/l and has a half-life of 5-11 h that appears independent of therapy. The time for plasma Pi to return to normal can be calculated from the initial Pi as t = (ln 5/Pi)/0.1292. Neuromuscular and cardiac abnormalities relate to the low serum calcium; the increase of total serum calcium during recovery from phosphate poisoning is linear but is accelerated by intravenous (i.v.) calcium salt. Continued i.v. calcium therapy may be required since restoration of plasma calcium is often delayed.

Calcium↗
PubMed1986

Circulating immune complexes in cystic fibrosis and their correlation to clinical parameters.

Circulating immune complexes (CIC) have been found to be elevated in individuals with cystic fibrosis (CF). Previous investigators, using a variety of assays, have reported high levels of CIC in as many as 86% of these patients. Our study followed the progress of 25 patients with CF over a period of 10 months to determine which, if any, clinical parameters correlated with the occurrence and/or concentration of CIC. Immune complex determinations were performed using a coprecipitation method with equine rheumatoid-complement complex. One hundred percent of the CF patients had CIC elevated above normal levels, however, levels of CIC did not correlate with the severity of an individual's acute exacerbation. Clinical parameters including pulmonary function tests, vital signs, total serum IgG levels, and other laboratory studies, were obtained on each individual and analyzed with respect to their relationship to CIC. Only four of 38 parameters examined had p less than 0.05. Factors that showed significant correlation to elevated CIC's in the highly elevated portion of our CIC population were poor NIH score, increased patient age, low peak expiratory flow rate, and elevated total serum IgG. These clinical values are associated more with the measurement of chronic disease. These data suggest that CICs cannot be used as an indication of short-term prognosis or as a monitor to follow the course of acute severe lung infections in the CF patient. Of interest was the observation that all patients who died during the course of the investigation had CIC levels greater than 80 micrograms/ml.

Adolescent↗
PubMed1985

Abnormal erythrocyte pyrimidine nucleotides in uremic subjects.

Uremia causes major increases in the erythrocyte (RBC) purine nucleotides, presumably secondary to phosphate retention, but no previous study has been made of the pyrimidine nucleotides, normally absent from RBC. This investigation was prompted by demonstration of the abnormal presence of RBC pyrimidine nucleotides, primarily cytidine triphosphate (CTP) plus cytidine diphosphate-choline (CDP-C) and cytidine diphosphate-ethanolamine (CDP-E), in two types of congenital hemolytic anemia as well as in lead poisoning. These observations suggested an analogy to the RBC membrane dysfunction of uremia. This is a report of the identification of CDP-C and CDP-E as the predominant abnormal pyrimidine nucleotides in the RBC hemolysates of uremic subjects. High-performance liquid chromatography of hemolysates from uremic adults showed a 50% increase in purine nucleotides and the abnormal presence of pyrimidine nucleotides and diesters at approximately 10% of the concentration of the purine nucleotides. By means of UV spectra and 31P nuclear magnetic resonance, these were identified as CDP-C and CDP-E. The increased purine and abnormal pyrimidine nucleotides of uremic RBC were unrelated to the pre- or posthemodialysis state, allopurinol, levels of blood lead, copper and zinc, or RBC pyrimidine 5'-nucleotidase, the cytosolic enzyme that specifically dephosphorylates the pyrimidine nucleotides. Although the accumulation of CTP, CDP-C and CDP-E may be an epiphenomenon of phosphate retention, it also suggests a common pathway to the accelerated hemolysis of chronic renal insufficiency.

5'-Nucleotidase↗
PubMed1984

Omaha childhood blood lead and environmental lead: a linear total exposure model.

The majority of experimental and population studies of blood lead (PbB) and environmental lead, including the Omaha study, have utilized the Goldsmith-Hexter log-log or power function model. Comparison was made of the log-log model and a linear model of total exposure to describe the Omaha Study of 1074 PbBs from children ages 1-18 years as related to air (PbA), soil (PbS), and housedust (PbHD) lead. The data fit of the linear model was statistically equivalent to the power model and the predicted curves were biologically more plausible. The linear model avoids the mathematical limitations of the power model which predicts PbB zero at PbA zero. From the Omaha data, this model, ln PbB = ln (beta 0 + B1 PbA + B2 PbS + beta 3 PbHD) predicts that PbB increases 1.92 micrograms/dl as PbA increases 1.0 microgram/m3. Since PbS and PbHD increase with PbA, however, the increases in total exposure predict a PbB increase of 4-5 micrograms/dl as PbA increases 1.0 microgram/m3.

Adolescent↗
PubMed1984

Identification of cytidine diphosphodiesters in erythrocytes from a patient with pyrimidine nucleotidase deficiency.

Pyrimidine 5'-nucleotidase deficient (PND) erythrocytes contain elevated levels of pyrimidine nucleotides and relatively normal purine nucleotide levels. The composition of this nucleotide pool has been examined by others, but not all of the abnormal red cell metabolites in this disorder were identified. We have isolated and positively confirmed the identity of cytidine diphosphate (CDP)-choline and CDP-ethanolamine from PND red cells using methods including proton FT-NMR, spectroscopy, and comparative mass spectrometry. The concentrations of these and other pyrimidine nucleotidase-deficient erythrocyte nucleotides were determined using anion-exchange high performance liquid chromatography and ultraviolet (u.v.) detection. The pyrimidine diphosphodiesters appear to be the most prominent abnormal pyrimidine nucleotides in PND red cells, accounting for 55% of the total red cell pyrimidine nucleotides in this disorder. It is proposed that these abnormal phosphodiesters may be related to the accelerated hemolysis in PND.

5'-Nucleotidase↗
PubMed1984

The adolescent overdose. Evaluation and referral.

Guidelines are provided for distinguishing between an accidental overdose, a suicidal gesture, and an attempted suicide. Emergency physicians are the primary contacts for overdosed adolescents and are responsible for both the acute medical care and the initial psychosocial evaluation. The physician must refer the patient to the appropriate acute and long-term support programs that facilitate the process of maturation.

Adolescent↗
PubMed1983

31P NMR study of erythrocytes from a patient with hereditary pyrimidine-5'-nucleotidase deficiency.

The composition of phosphate metabolites and the intracellular pH in erythrocytes from a patient with hereditary pyrimidine-5'-nucleotidase deficiency were examined using 31P NMR spectroscopy. Several resonances were identified in spectra from intact cells and from extracts. The 2,3-bisphosphoglycerate line intensities were normal but the NTP resonances were about twice normal due to the presence of millimolar quantities of pyrimidine phosphates. Several intense resonances were also observed in the diphosphodiester region of the spectrum. One compound contributing to these lines has been identified as cytidine diphosphocholine. The resonances of NTPs were in a position indicating that the additional triphosphates were also bound by Mg2+. Direct measurement shows that there is a nearly proportional increase in total cell Mg2+ in the patient's cells, in agreement with the interpretation of the spectra. The intracellular pH was about 0.2 unit lower in the patient's erythrocytes. This lower pH is due to the elevation in intracellular fixed negative charges and the shift in permeable anions consequent to the Donnan equilibrium. We suggest that the lower intracellular pH may explain the lower oxygen affinity of these cells in the presence of otherwise normal 2,3-bisphosphoglycerate levels and the increased Mg2+ triphosphates level, because the Mg2+ form of NTPs is known not to alter the oxygen affinity of hemoglobin under physiologic conditions. Furthermore, the lower intracellular pH can also explain the abnormalities in glycolytic intermediates observed for these cells.

5'-Nucleotidase↗
PubMed1983

Adolescent self-poisoning: a nine-year followup.

A 9-year followup was made of 47 adolescents initially hospitalized at ages 12 to 18 years in a psychiatric facility because of severe psychosocial dysfunction associated with an intentional self-poisoning. No deaths were disclosed as determined by an extensive telephone interview (15 subjects), report by the family (9 subjects), or death certificate search. The 15 subjects interviewed (14 females, 1 male) reported a total of 47 suicide gestures with a peak frequency at ages 14 to 15. There was a sharp decline after age 18, supporting the concept that self-poisoning is an age-related mode of expression. All subjects considered themselves better adjusted, with greater life satisfaction and improved interpersonal relationships; 80% had completed high school, and 93% were capable of stable employment. Functional adaptation was independent to the number of repeat poisonings or of the initial psychiatric diagnosis. All subjects attributed benefits to multiple support systems, particularly a strong relationship with at least one emotionally mature person, a more favorable environment--usually accomplished by moving out of their parents' house--achievement of education and employment skills, and economic independence.

Adaptation, Psychological↗
PubMed1983

Partial purification and zinc dependence of human red cell pyrimidine-5'-nucleotidase.

Human red cell pyrimidine-5'-nucleotidase (EC 3.1.3.5) was partially purified from the blood of normal subjects by ion-exchange and affinity chromatography. Red cells were lysed in 50 mmol/l Tris-Cl buffer at pH 7.5 containing 1.0 mmol/l dithiothreitol and 0.5 mmol/l EDTA. The lysate was centrifuged and introduced onto a column of Sephadex A-50. After washing, the pyrimidine-5'-nucleotidase activity was eluted from the column with a NaCl gradient from 0 to 200 mmol/l in Tris buffer at pH 7.5. The pyrimidine-5'-nucleotidase was then desalted on Sephadex G-25 and introduced onto a UDP agarose column with a Tris buffer at pH 6.5 containing 150 mmol/l NaCl. This partial purification resulted in an approximately 80,000-fold increase in enzyme concentration. The Km for the partially purified enzyme was 0.32 mmol/l for UMP, 0.16 mmol/l for CMP and 0.11 mmol/l for OMP with a pH maximum of 7.5. This partially purified pyrimidine-5'-nucleotidase was then dialyzed in 50 mmol/l Tris-Cl buffer at pH 7.5 with 0.01 mmol/l CaCl2 and NaCl against 2 X 10(-3) mol/l 1,10-phenanthroline for 24 h at 4 degrees C. This incubation resulted in 73% decrease in enzyme activity which could be restored by the addition of zinc into the mixture, but not by the addition of other divalent metal ions.

5'-Nucleotidase↗
PubMed1982

Glutathione S-transferase activity in liver, lung and intestinal mucosa of aging female mice.

1. Changes in the activity of glutathione S-transferase (GST) in liver, lungs and intestinal mucosa of female Swiss-Webster mice with age were determined. 2. GST activity increased with age from 1 to 9 months, reached a maximum activity at 9 months and decreased thereafter with advanced age in all three tissues. 3. GST activity decreased by approximately 75% in liver between 9 and 18 months, with decreases of 65 and 64% occurring over the same time period for lung and intestinal mucosa, respectively.

Aging↗
PubMed1982

Erythrocyte nucleotides in children--increased blood lead and cytidine triphosphate.

The erythrocyte nucleotides of 25 children, 1-5 years old, with normal and increased blood leads, were assayed by anion-exchange high-performance liquid chromatography. Red blood cells of the 12 children with blood lead (PbB) below 30 micrograms/dl (20.3 +/- 6 micrograms/dl, mean +/- S.D.) had normal levels of activity of pyrimidine 5'-nucleotidase (P5N) and their erythrocytes were virtually free of pyrimidine nucleotides except for small amounts of UMP and UDP. The purine nucleotides, predominantly ATP and GTP, were present at values similar to adults. In the 13 children with PbB 30-72 micrograms/dl (45.3 +/- 14.3 micrograms/dl), total cytidine phosphates (CMP, CDP, CTP) were significantly (P less than 0.001) increased from trace values to 8.31 +/- 6.21 nmoles/10(10) erythrocytes. The purine nucleotides were unchanged. P5N activity was 143.3 +/- 22.0 units/g hemoglobin in children with PbB less than 30 micrograms/dl and 75.4 +/- 24.2 units (P less than 0.001) in the high lead subjects. There was a logarithmic correlation of erythrocyte cytidine phosphates with PbB (r = 0.89, P less than 0.001) and an inverse correlation of cytidine phosphates with ln P5N activity (r = 0.59, P less than 0.001), of ln P5N with PbB (r = 0.64, P less than 0.001) and of ln P5N with ln erythrocyte zinc protoporphyrin (Protoporphyrin IX) (r = 0.57, P less than 0.001).

Child, Preschool↗
PubMed1982

Effect of lead chelation therapy with EDTA in children on erythrocyte pyrimidine 5'-nucleotidase and with cytidine triphosphate levels.

Children with elevated whole blood lead levels were treated for 4 days with EDTA. Changes in whole blood lead concentrations, erythrocyte zinc protoporphyrin concentrations, red cell pyrimidine 5'-nucleotidase activities, and erythrocyte cytidine triphosphate (CTP) levels were measured during the course of the EDTA therapy. EDTA treatment decreased blood lead levels by approximately 50% after 4 days. An inverse relationship existed between blood lead levels and erythrocyte pyrimidine 5'-nucleotidase activity. Despite reactivation of pyrimidine 5'-nucleotidase enzyme activity by EDTA, there was no decrease in erythrocyte cytidine triphosphate or in zinc protoporphyrin concentrations. The lack of change in these two parameters during EDTA treatment supports the concept that pyrimidine 5'-nucleotidase inhibition by lead in the reticulocyte cytidine phosphate accumulation in moderate lead poisoning may reflect chronic lead overburden analogous to prolonged elevation of erythrocyte zinc protoporphyrins.

5'-Nucleotidase↗