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Biomedical subjects

D M Wilson

Publications and source records attributed to D M Wilson.

At least 163 records · Page 9Linked to original sources
PubMed1992

Prolactin message in brain and pituitary of adult male rats is identical: PCR cloning and sequencing of hypothalamic prolactin cDNA from intact and hypophysectomized adult male rats.

Prolactin (PRL), or a PRL-like molecule has been identified in the central nervous system and other tissues by numerous investigators. The previous finding of PRL in brain persisting for weeks following hypophysectomy led us, and others, to conclude the brain and central nervous system PRL is synthesized locally. Also, our previous results showing PRL mRNA in hypothalamic and extra-hypothalamic brain regions using reverse transcription-polymerase chain reaction (RT-PCR) techniques, along with this report that the sequence of the PRL message in the brain is identical to that found in the anterior pituitary solidifies our, and others, hypothesis that PRL is synthesized in many locations other than the traditional one (anterior pituitary). The actual sequencing of hypothalamic PRL cDNA produced from RT-PCR of mRNA from intact or hypophysectomized rats demonstrates unequivocally that brain PRL mRNA is identical to anterior pituitary prolactin mRNA.

Amino Acid Sequence↗
PubMed1992

Insulin-like growth factor binding protein-3 in normal pubertal girls.

IGFBP-3 concentrations rise in the second decade of life. To test the hypothesis that the stage of pubertal development, independent of chronological age, was associated with these increases we measured serum IGFBP-3 concentrations by radioimmunoassay in 324 sixth and seventh grade girls (12.3 +/- 0.7 years) at the beginning of a multisite school-based health curriculum. The mean (+/- SD) serum IGFBP-3 among the 242 girls with complete data was 4.0 +/- 0.7 mg/l. Pubertal stage was significantly associated with IGFBP-3 (p less than 0.0001, ANOVA). Mean concentrations rose from 3.5 +/- 0.7 mg/l among those with the earliest pubertal stages to 4.2 +/- 0.7 mg/l among the mature girls. IGF-I and IGFBP-3 concentrations were significantly correlated (Spearman's r = 0.43, p less than 0.0001). After controlling for the association between pubertal development and IGFBP-3 concentrations, only the waist/hip ratio, among the various measures of body composition, was significantly associated with IGFBP-3 concentration (Spearman's r = -0.23, p = 0.0002). Likewise, none of the measures of nutrition: intake of total calories, protein, fat and carbohydrate; serum iron; red cell mean corpuscular volume; or cholesterol; were significantly associated with IGFBP-3 concentrations. There was, however, a small, but significant association between IGFBP-3 concentrations and both serum transferrin and blood hemoglobin concentrations. Pubertal stage has a significant impact on IGFBP-3 concentrations and those attempting to utilize IGFBP-3 concentrations during adolescence should be cognizant of the subject's pubertal stage.

Adolescent↗
PubMed1992

Effects of insulin-like growth factors (IGFs) and IGF receptor antibodies on the proliferation of human breast cancer cells.

It has been shown previously that MCF-7 cells proliferate in response to nanomolar concentrations of IGF-I and IGF-II. It has also been reported that the actions of both peptides are mediated through the IGF-I receptor. To further characterize these observations, we used MCF-7 and Hs578T cell lines in the serum-free/phenol red-free system developed by Ogasawara and Sibarsku, 1988. Cell proliferation was studied in the presence of insulin, IGF-I and -II and a series of growth factor receptor antibodies. No effect was observed on Hs578T cell proliferation with any of the growth factors. However, MCF-7 cells were stimulated 4-5 fold with IGF-I and insulin, while IGF-II was only slightly less potent. alpha IR3, a monoclonal antibody directed against the IGF-I receptor, was stimulatory when added alone. However, alpha IR3 blocked approximately 50% of the IGF-I response, only 5% of the insulin response, and did not block the IGF-II effect on cell proliferation. These data suggest that alpha IR3 and IGF-I are acting as agonists through the IGF-I receptor, but that insulin and IGF-II are acting through other receptors. Two different IGF-II/M-6-P receptor antibodies and an insulin receptor antibody failed to significantly block IGF-II actions. All three antibodies were stimulatory when added alone. beta-gal inhibited 27% of the IGF-II response and had no effect when added alone. Since beta-gal decreases the binding affinity of the IGF-II/M-6-P receptor for IGF-II and does not bind to the IGF-I or insulin receptor, these data suggest the possibility that IGF-II mitogenic action is mediated through the IGF-II/M-6-P receptor. In summary, these data indicate that nanomolar concentration of insulin, IGF-I and IGF-II are potent mitogens in MCF-7 cells and can potentially stimulate cell proliferation through all three receptors.

Analysis of Variance↗
PubMed1992

Two-dimensional electrophoresis of urine specimens from patients with renal disease.

In an effort to develop non-invasive markers capable of characterizing renal disease with greater sensitivity and specificity than those currently available, urinary proteins were studied by high-resolution two-dimensional electrophoresis in order to catalog those proteins which appeared to be most affected by a variety of renal diseases. Urine specimens were prepared by high-pressure liquid chromatography and subjected to two-dimensional gel electrophoresis. Proteins were visualized with silver stain. Gels from 17 patients were analyzed in detail and compared to standard maps of human urinary proteins and plasma. The two-dimensional gels displayed approximately 100 times the number of proteins demonstrated by high resolution agarose electrophoresis. We have identified 34 proteins whose urinary concentrations were most affected by renal disease. Twenty seven were of plasma origin, based upon comigration with plasma samples (17 of unknown identity and function). Seven proteins were observed in normal urine but not present in plasma. These proteins, which may represent kidney tissue proteins, were not apparent in the urine of patients with proteinuria, most likely due to dilutional effects.

Biomarkers↗
PubMed1992

Clinical actions of growth hormone.

Although biotechnology has provided physicians with essentially unlimited supplies of growth hormone (GH), there are currently only a few clear-cut indications for exogenous GH therapy. Data now support the use of GH in the treatment of children with GH deficiency and short girls with Turner syndrome. Tantalizing preliminary data suggest that GH therapy has a role in the management of short, poorly growing children with other causes for their growth failure. Recent studies have examined the utility of GH therapy in GH-deficient adults, whereas other studies suggest that GH improves the clinical status of GH-sufficient older adults. This article explores the recent data underlying these claims.

Adult↗
PubMed1991

Standardized percentile curves of body-mass index for children and adolescents.

Weight-for-height indexes are often used in the clinical assessment of obesity in children and adolescents. The direct measurement of adiposity, using hydrostatic weighing and other techniques, is not feasible in studies involving young children or with large numbers of older subjects. Ratios of weight relative to height, such as the body-mass index (weight/height), may be used as indirect measures of obesity and correlate with more direct measures of adiposity. Using data from the First National Health and Nutrition Examination Study, 1971 to 1974, standardized percentile curves of body-mass index for white children and adolescents were developed. These curves may be used to monitor the body-mass index of white children and adolescents longitudinally and for comparing an individual with others of the same sex and age.

Adolescent↗
PubMed1991

Growth hormone therapy in hypophosphatemic rickets.

The effects of growth hormone therapy on the biochemical measures of bone metabolism were studied in 11 children aged 3.5 to 17 years who had familial hypophosphatemic rickets; five were male. Subjects were maintained on a regimen of stable doses of conventional therapy (calcitriol and phosphate). Subjects were studied at baseline receiving conventional therapy and during three sequential treatment periods: no therapy (4 weeks), growth hormone only (0.05 mg/kg per day for 4 weeks), and conventional therapy plus growth hormone (2 weeks). The nine youngest subjects were continued on a regimen of triple therapy for an additional 24 weeks. Serum phosphate averaged 0.93 +/- 0.13 mmol/L (mean +/- SD) at entry and decreased when the subjects were not receiving any therapy. During the 4 weeks of growth hormone only treatment, phosphate rose in all 11 subjects (0.70 +/- 0.08 mmol/L to 0.83 +/- 0.08 mmol/L). With triple therapy, phosphate remained higher than with no therapy. Calcitriol, osteocalcin, and parathyroid hormone increased as the subjects received growth hormone alone. Insulinlike growth factor I z scores rose significantly in response to growth hormone therapy alone. All nine subjects receiving 6 months of triple therapy increased their growth rate z scores. Exogenous growth hormone therapy may be useful in familial hypophosphatemic rickets.

Adolescent↗
PubMed1991

Examination of potential mechanisms of carcinogenicity of 1,4-dioxane in rat nasal epithelial cells and hepatocytes.

Several long-term studies with 1,4-dioxane (dioxane) have shown it to induce liver tumors in mice, and nasal and liver tumors in rats when administered in amounts from 0.5 to 1.8% in the drinking water (Argus et al. 1965; Kociba et al. 1974; National Cancer Institute, 1978). In order to examine potential mechanisms of action, chemically-induced DNA repair (as an indicator of DNA reactivity) and cell proliferation (as an indicator of promotional activity) were examined in nasal turbinate epithelial cells and hepatocytes of male Fischer-344 rats treated with dioxane. Neither dioxane nor 1,4-dioxane-2-one, one of the proposed metabolites, exhibited activity in the in vitro primary rat hepatocyte DNA repair assay, even from cells that had been isolated from animals given either 1 or 2% dioxane in the drinking water for 1 week to induce enzymes that might be responsible for producing genotoxic metabolites. No activity was seen in the in vivo hepatocyte DNA repair assay in animals given a single dose of up to 1000 mg/kg dioxane or up to 2% dioxane in the drinking water for 1 week. Treatment of rats with 1.0% dioxane in the drinking water for 5 days yielded no increase in liver/body weight nor induction of palmitoyl CoA oxidase, indicating that dioxane does not fit into the class of peroxisomal proliferating carcinogens. The percentage of cells in DNA synthesis phase (S-phase) was determined by administration of 3H-thymidine and subsequent quantitative histoautoradiography. The hepatic labeling index (LI) did not increase at either 24 or 48 h following a single dose of 1000 mg/kg dioxane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Eosinophiluria in atheroembolic renal disease.

PURPOSE AND PATIENTS: Eosinophiluria has been reported in acute interstitial nephritis and other renal diseases, but its presence in atheroembolic renal disease (AERD) has not been previously established. AERD has been identified as a cause of acute and chronic renal failure, particularly in elderly patients with advanced atherosclerosis and in those patients who have undergone manipulation or intervention of the abdominal aorta, renal artery, or coronary artery. The definitive diagnosis is made by renal biopsy. However, many patients are too acutely ill to tolerate renal biopsy and, in recent years, peripheral eosinophilia, hypocomplementemia, and thrombocytopenia have been recognized in association with AERD. Previous studies have reported that AERD is associated with an inactive renal sediment and an absence of urine eosinophils. We reviewed our experience over a 4-year period with 24 patients with renal biopsy-proven AERD. RESULTS: Urine eosinophils were evaluated in nine patients to help determine the cause of their renal deterioration. Seven of these patients presented with evidence of vascular disease. Three patients had procedures involving manipulation of the abdominal aorta. Physical examination revealed findings of atheroembolism in three of nine patients. Overall, eight of nine patients had a positive Hansel's stain for eosinophiluria. Six of eight patients had more than 5% of their urinary white cell count as eosinophils. The reason for failure of previous studies to detect eosinophiluria in AERD is unclear but may have been related to the use of Wright's stain instead of Hansel's stain. CONCLUSION: In the evaluation of acute renal insufficiency, eosinophiluria may indicate AERD in addition to the other known causes for this finding.

Acute Kidney Injury↗
PubMed1991

Improving feedback on student papers: a quantitative method which aids marking and gives valid feedback.

A quantifying method of marking was developed to aid in consistent and thorough marking of student papers and to improve the manner and validity of feedback. This feedback is on common technical writing skills. Giving feedback on technical writing skills, as opposed to concentrating on critical thinking skills, is defended. The benefits and purposes of this marking method are further developed. Implementation of the method is outlined, and a completed Quantitative Feedback form is demonstrated. Through evaluation, the method has been found effective for aiding marking and for clearly identifying strengths and weaknesses in writing.

Education, Nursing↗
PubMed1991

Impact of pubertal development on body fat distribution among white, Hispanic, and Asian female adolescents.

Variation in the waist/hip ratio (WHR) may be related to changes in hormonal secretion associated with pubertal maturation. We therefore studied the effects of race, pubertal development, and body fatness on WHR during adolescence in a multiethnic population. A total of 688 white, Asian, and Hispanic female adolescents (mean (+/- SD) 12.4 +/- 0.7 years), participating in the evaluation of a multisite school-based health education program, were included in these analyses. Self-assessed stage of puberty and measurements of height, weight, waist circumference, and hip circumference were obtained from each participant. The WHR and age-adjusted body mass index were calculated. Analysis of covariance demonstrated that puberty significantly affects hip circumference and WHR but not waist circumference among female adolescents. Age and fatness, as reflected by age-adjusted body mass index, contributed significantly to both circumferences and to the WHR. There was a significant effect of ethnicity on hip circumference but not on waist circumference or the WHR. These results confirm that pubertal stage exerts a significant effect on the hip circumference and WHR in female adolescents, even after the effects of fatness and age are controlled. Studies of body fat distribution during late childhood and adolescence should include assessments of pubertal maturation.

Adipose Tissue↗
PubMed1991

Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease.

We compared the tubular transport of sodium and the erythrocyte sodium-lithium countertransport activity in hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) and in normotensive control subjects. In addition, we assessed the effects of inhibition of converting enzyme on renal hemodynamics and sodium excretion in hypertensive patients with ADPKD to provide information on mechanisms responsible for the increased renal vascular resistance and filtration fraction and the adjustment of the pressure-natriuresis relationship during saline expansion, observed in patients with ADPKD, hypertension, and preserved renal function. In comparison with normotensive control subjects, the hypertensive patients with ADPKD had lower renal plasma flows, higher renal vascular resistances and filtration fractions, and similar proximal and distal fractional reabsorptions of sodium. The administration of enalapril resulted in significant increases in the renal plasma flow and significant reductions in mean arterial pressure, renal vascular resistance, and filtration fraction, but the glomerular filtration rate remained unchanged. Despite the significant reduction in mean arterial pressure during inhibition of converting enzyme, the distal fractional reabsorption of sodium decreased while the total fractional excretion of sodium remained unchanged or increased slightly. No significant differences were detected between the normotensive control subjects and the hypertensive patients with ADPKD in erythrocyte sodium-lithium countertransport activity, plasma renin activity, plasma aldosterone concentration, or atrial natriuretic factor. These results suggest that the renal renin-angiotensin system plays a central role in the alterations in renal hemodynamics and sodium management associated with the development of hypertension in ADPKD.

Adult↗
PubMed1991

Insulin-like growth factors are mitogenic for human keratinocytes and a squamous cell carcinoma.

Normal adult human keratinocytes in monolayer culture and SCL-1, a skin-derived squamous-cell carcinoma cell line, were investigated for the expression of receptors for insulin-like growth factors (IGF) and insulin. As demonstrated by affinity crosslinking, radiolabeled IGF-1, IGF-2, and insulin bound specifically to both cell types. Each cell expressed type I IGF receptors, with affinity for IGF-1 greater than IGF-2 much greater than insulin. Insulin receptors, with highest affinity for insulin, were also present on both cells. However, keratinocytes and SCL-1 cells differed in 125I-IGF-2 binding. 125I-IGF-2-bound to both type I and type II IGF receptors in normal keratinocytes, but bound predominantly to membrane-associated IGF binding proteins in SCL-1. IGF-1 was slightly more potent than IGF-2 in stimulating growth of both keratinocytes and SCL-1 cells. In keratinocytes, concentrations of IGF-1 ranging from 5-100 ng/ml, and of IGF-2 from 50-100 ng/ml, resulted in a significant increase in cell number. At the maximum dose of 100 ng/ml, either IGF-1 or IGF-2 caused a 2.3-times increase in cell number. In SCL-1 cells, IGF-1 was more potent than IGF-2 or insulin at lower concentrations, but either IGF-1 or IGF-2 at the maximal concentration of 333 ng/ml stimulated a 4.7-times increase in thymidine incorporation. The stimulatory effect of insulin in SCL-1 was 10-50 times less potent than that of the IGF. The effect of either IGF on SCL-1 was completely inhibited by the type I IGF receptor antibody alpha IR-3, suggesting that both IGFs are mitogenic through the type I IGF receptor. Insulin action was partially blocked by alpha IR-3, suggesting that insulin can act through both the insulin and type I IGF receptors. It thus appears that IGF-1 and IGF-2 are mitogens for normal and transformed human keratinocytes and that their actions are primarily mediated through the type I IGF receptor, whereas insulin is a mitogen through both the IGF-1 receptor and the insulin receptor.

Carcinoma, Squamous Cell↗
PubMed1991

Insulin-like growth factors I and II and their binding proteins in rat milk.

IGF-I and -II are peptide growth factors that may be important contributors to the growth-promoting properties associated with milk. IGF in extracellular fluids, including serum and milk, are carried by specific high-affinity binding proteins (IGFBP). In this study, the levels of IGF-I and -II in rat serum and milk were quantified by specific RIA, and the IGFBP were characterized using Western ligand blotting and autoradiography throughout lactation. The levels of IGF-I in both milk and maternal serum decreased during lactation. Serum IGF-I decreased from 743 +/- 187 micrograms/L on d 1 to 391 +/- 106 (mean +/- SD) on d 21 of lactation, and milk IGF-I levels fell from 30 +/- 10 to 13 +/- 8 micrograms/L. Levels of IGF-II in serum and milk were much lower than IGF-I, and were unaffected by lactation. In maternal serum, several IGFBP were identified: IGFBP-3, which migrates as four glycosylated bands with apparent Mr from 38 to 42 kD and one to two nonglycosylated bands with apparent Mr of 28 to 29 kD, and an IGFBP with an apparent Mr of 24 kD. In milk, IGFBP-3, the 24-kD binding protein, and a third IGFBP with an apparent Mr of 29 kD were identified. Treatment of milk and serum with Endoglycosidase F reduced the four glycosylated IGFBP-3 bands (38-42 kD) to two bands with apparent Mr of 35 and 32 kD. In rat milk, but not adult rat serum, the IGFBP with an apparent Mr of 29 kD was immunoprecipitable by an antibody that recognizes IGFBP-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Differential regulation of the insulin-like growth factors (IGF-I and -II) and IGF binding proteins during malnutrition in the neonatal rat.

Insulin-like growth factor (IGF)-I and -II are known to play a major role in fetal and early postnatal growth. The IGF binding proteins (IGFBPs) are thought to be important in modulating the actions of the IGFs. In this paper, the effect of malnutrition in the neonatal rat on serum IGFs and IGFBPs and hepatic IGFBP messenger (m) RNA was examined. Control (C) dams (n = 9) were allowed ad libitum intake, whereas restricted (R) dams (n = 9) were limited to 50% of ad libitum intake throughout lactation, which results in decreased milk production and malnutrition of pups suckling on restricted dams. A subset of pups were cross-fostered from the R-dams to the C-dams from days 15-19 postpartum (PP) to investigate the effect of nutritional repletion (refed). Pups were killed on days 8, 12, 15, and 19 PP and liver and blood collected. Serum IGF-I and -II concentrations were measured by RIA after acid-chromatography to remove IGFBPs. Serum IGFBPs were characterized by Western ligand blot. Hepatic mRNA for IGFBP-1, -2, and -3 were determined by northern analysis. Body weight (BW) of R-pups was significantly less than C-pups by day 10 PP (P less than or equal to 0.05), and mean BW at day 19 was 56% of the C-pups. Refeeding from days 15-19 resulted in a significantly greater rate of growth vs. R-pups (3.2 vs. 0.9 g/day), and mean BW of refed pups at day 19 PP was 75% of C-pups. Malnutrition caused a significant reduction in both serum IGF-I and -II after day 12 PP, while causing an elevation in serum IGFBP-2. IGFBP-1 and IGFBP-2 mRNA expression were not significantly affected at days 8 and 12, but were elevated in livers of day 15 and 19 pups. Malnutrition caused a delay in the development shift from IGFBP-2 to IGFBP-3, which normally occurs between day 15 and 19 in the rat. Refeeding raised serum IGF-I and -II levels to those found in the C-pups and a trend toward normalization of IGFBP profiles. In conclusion, IGFs and IGFBPs are differentially regulated during neonatal malnutrition. The decrease in IGF peptide and induction of IGFBP-1 and -2 may provide protective mechanisms by inhibiting growth during malnutrition.

Animals↗
PubMed1991

Insulin-like growth factor-I as a reflection of body composition, nutrition, and puberty in sixth and seventh grade girls.

Large variations in nutritional intake have profound effects on the GH-insulin-like growth factor-I (IGF-I) axis in children and adults, but the effect of normal variations in nutrition on IGF-I concentrations is largely unstudied, particularly during puberty. We measured serum IGF-I concentrations in 325 sixth and seventh grade girls (12.4 +/- 0.7 yr) at the beginning of a multisite school-based health curriculum. The mean serum IGF-I level among the 243 girls with complete data was 573 +/- 244 micrograms/L. Pubertal stage was significantly associated with IGF-I (P less than 0.0001, by analysis of variance). Mean concentrations rose from 427 +/- 198 micrograms/L among those at the earliest pubertal stages to 639 +/- 219 micrograms/L among the mature girls. After adjusting for the association with the stage of pubertal development, serum IGF-I was not significantly associated with measures of body composition (body mass index, triceps skin fold thickness, waist/hip ratio, height, and weight). Additionally, IGF-I concentrations were not associated with nutritional intake (total calories, total protein, total fat, and total carbohydrate) or such measures of nutrition as serum iron, hemoglobin, red cell mean corpuscular volume, white cell count, and cholesterol. IGF-I concentrations, however, were significantly correlated with transferrin concentrations, another possible index of nutritional status (r = 0.29; P less than 0.0001). IGF-I is not a clinically useful index of nutritional status among normal pubertal girls.

Adolescent↗
PubMed1991

Modified enzyme-based colorimetric assay of urinary and plasma oxalate with improved sensitivity and no ascorbate interference: reference values and sample handling procedures.

The measurement of oxalate in urine and plasma continues to be difficult, particularly in the presence of ascorbate. We have modified and validated a colorimetric assay involving the use of oxalate oxidase (EC 1.2.3.4). Modification of an HPLC spectrophotometric detector improved sensitivity (to as much as 1000-fold that of conventional spectrophotometers) and allowed measurement of oxalate concentrations less than 1 mumol/L. This provided more than enough sensitivity for measurement of normal concentrations of plasma oxalate. We established reference values for oxalate concentrations in urine and plasma, studied sample handling, and established conditions to avoid ascorbate interference in urine and plasma measurements. Mean analytical recovery of [14C]oxalate from plasma to the filtrate was 86 (SD 10)%; recovery of unlabeled oxalate from filtrate was 87 (SD 9)%. Urinary oxalate excretion rates in apparently healthy controls were 0.11-0.46 mmol/24 h. Plasma concentrations in control subjects were 2.5 (SD 0.7) mumol/L, similar to concentrations determined by recent gas chromatographic and isotope dilution methods. Frozen and acidified urine samples showed no interference from ascorbate when excess ascorbate was avoided. Ingestion of 2 g of ascorbate daily did not increase urinary oxalate in healthy control subjects, but during storage ascorbate was converted to oxalate in all conditions tested.

Adult↗