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Biomedical subjects

D M Wilson

Publications and source records attributed to D M Wilson.

At least 253 records · Page 14Linked to original sources

Computed tomographic findings in septo-optic dysplasia: discordance between clinical and radiological findings.

The clinical and radiological findings in four children with septo-optic dysplasia are reported. All four had growth retardation associated with growth hormone deficiency, as well as varying degrees of ophthalmologic dysfunction. The CT scan findings spanned a spectrum from normal to the expected abnormalities involving the ventricular system and orbits. Only two of the four had an absent septum pellucidum. A third patient had normal CT scans except for optic nerve hypoplasia, while the fourth had entirely normal CT scans of both the brain and orbits. Because the anatomic defects of septo-optic dysplasia may be subtle, an apparently normal CT scan does not invalidate the clinical diagnosis of septo-optic dysplasia.

Brain↗

Prospective clinical trial of human growth hormone in short children without growth hormone deficiency.

Ten unselected, apparently healthy short children who were capable of normal growth hormone secretion were given human growth hormone (0.1 U/kg 1M thrice weekly) for 6 months to determine whether such treatment might lead to an increase in growth velocity. During treatment, all patients increased their growth rate (from 4.3 +/- 0.3 cm/yr to 7.4 +/- 0.5 cm/yr P less than 0.001). No adverse effects were detected. During the four-day IGF generation test, IGF I and IGF II levels rose significantly from 0.32 +/- 0.04 U/ml to 0.62 +/- 0.13 U/ml and from 279 +/- 36 ng/ml to 434 +/- 49 ng/ml, respectively. However, the growth response was not predicted by either the acute rise in IGF I or that in IGF II. Human growth hormone in standard doses may be capable of inducing accelerated growth in some short children without growth hormone deficiency. Measurements of IGF I and II cannot be used to predict which children will respond.

Blood Glucose↗

Viable fungi in corn dust.

Numbers of viable fungal propagules in corn dusts in southern Georgia were estimated during various farm and grain elevator operations in 1979, 1980, and 1982. A six-stage Andersen sampler for viable microbial particles was used to sample the dusts with various agar media. The most abundant fungi in corn dusts were species of yeasts: Aspergillus, Penicillium, Cladosporium, Alternaria. Helminthosporium, and Fusarium. However, the relative abundance of these fungi differed between years. There was a greater incidence of the Aspergillus flavus group in the hot, dry year of 1980 compared with the cooler, wetter years of 1979 and 1982. Fungi in the corn dusts sampled numbered between 10(4) and 10(9) viable propagules per m3 of air. By contrast, outdoor air often contained fewer than 10(4) viable fungal propagules per m3. Most A. flavus propagules were deposited at stages three and four of the Andersen sampler, with correspond to the trachea, primary bronchi, and secondary bronchi in the human respiratory system. In an assessment of the air spores by exposing sterile petri dishes, more large-spored fungi, like Alternaria tenuis, and fewer small-spored fungi, such as A. flavus, were detected when compared with colony counts from petri dishes exposed to air in the Anderson sampler.

Air Microbiology↗

Characterization of high affinity receptors for insulin-like growth factors I and II on rat anterior pituitary cells.

Primary cultures of rat anterior pituitary cells were assessed for the presence of specific receptors for insulin and for the somatomedin peptides, insulin-like growth factors I and II (IGF-I and IGF-II). Specific binding per 100,000 pituitary cells averaged 9.45 +/- 1.69% (mean +/- SD) for [125I]IGF-II, 0.83 +/- 0.06% for [125I]IGF-I, and only 0.11% for [125I]insulin, IGF-II was twice as potent as IGF-I in displacing [125I]IGF-II, while insulin was totally nonreactive, IGF-I was 5-fold more potent than IGF-II at displacing [125I]IGF-I and 1000-fold more potent than insulin. Scatchard analysis of [125I]IGF-II binding revealed a curvilinear plot, which could be resolved into a high affinity receptor with a Ka of 7.0 X 10(8) M-1 and 120,000 receptor sites/cell, and a low affinity receptor with a Ka of 1.1 X 10(8) M-1 and 720,000 receptor sites/cell. The existence of abundant high affinity somatomedin receptors (especially for IGF-II) on rat anterior pituitary cells is consistent with a potential role for these peptides in the regulation of GH secretion.

Animals↗

Acromegaly and Zollinger-Ellison syndrome secondary to an islet cell tumor: characterization and quantification of plasma and tumor human growth hormone-releasing factor.

A young woman with acromegaly and Zollinger-Ellison syndrome associated with a GH-releasing factor (GRF)- and gastrin-secreting metastatic islet cell carcinoma was studied by means of specific antisera which recognize various regions of the GRF molecule. Using specific immunohistochemical techniques, the tumor cells were shown to contain GRF, gastrin, and gastrin-releasing peptide, but not GH. During a 4-h period, plasma GRF levels averaged 5.6 +/- 1.4 ng/ml (+/- SD), while GH levels averaged 148 +/- 71 ng/ml. GH secretion was pulsatile and increased after TRH administration. GRF RIAs may be useful in establishing the diagnosis of acromegaly secondary to the ectopic secretion of GRF.

Acromegaly↗

The stone clinic effect in patients with idiopathic calcium urolithiasis.

The "stone clinic effect" refers to the effect of encouraging a high intake of fluid and avoiding dietary excesses on stone formation and growth in patients with urolithiasis. To determine the extent of this effect we reviewed the clinical courses of 108 patients with idiopathic calcium urolithiasis and indeterminant metabolic activity. There was no evidence of stone growth or new stone formation (metabolic inactivity) after a mean followup of 62.6 months in 63 of the 108 patients (58.3 per cent), including 12 of 17 (70.6 per cent) with hypercalciuria and 7 of 15 (46.7 per cent) with hyperuricosuria. Comparison of initial and followup 24-hour urine volumes demonstrated a significant increase in patients who were metabolically inactive at followup (p less than 0.0005), while no increase was detected in patients who were metabolically active at followup. We recommend that specific drug therapy should not be given to patients with idiopathic calcium urolithiasis until the stone clinic effect has been evaluated.

Adolescent↗

Somatomedins in adolescence: a cross-sectional study of the effect of puberty on plasma insulin-like growth factor I and II levels.

To explore the effect of puberty on the somatomedins (SMs), a group of insulin-like peptides which mediate the action of GH on skeletal tissue, we measured SM-C/insulin-like growth factor-I (SM-C/IGF-I) and IGF-II by specific RIAs in 110 adolescents between the ages of 10 and 18 yr. All subjects were in good health and between the 5th and 95th percentiles for height. In both females and males, SM-C/IGF-I levels rose during puberty to a peak approximately 3-fold higher than the average adult level. The rise in SM-C/IGF-I levels corresponded better with the Tanner stage of the adolescents than with their chronological age. IGF-II levels did not rise during puberty and were slightly below adult levels. The dramatic rise in SM-C/IGF-I levels during puberty suggests a role for this SM peptide in the adolescent growth spurt. Furthermore, these data indicate that proper interpretation of SM-C/IGF-I levels during adolescence must include a knowledge of the patient's pubertal development.

Adolescent↗

Levels of insulin-like growth factors I and II in human cord blood.

Levels of insulin-like growth factors I and II (IGF-I and IGF-II) and somatomedin peptide content (SMPC) were measured in 32 normal term and 11 preterm infants. After acid chromatography to remove somatomedin-binding protein, SMPC was measured by placental membrane radioreceptor assay, while plasma IGF-I and II concentrations were measured by specific RIAs. SMPC levels in term infants were significantly below normal adult levels [0.49 +/- 0.13 (+/- SD) U/ml for infants compared to 1.30 +/- 0.25 U/ml for adult males]. IGF-I levels in term infants were also low, averaging 113 +/- 35 ng/ml for infants; the normal adult levels is 184 +/- 32 ng/ml. The IGF-II level was 282 +/- 84 ng/ml for infants and 687 +/- 169 ng/ml for adults. Both IGF-I and II levels in preterm infants were lower than those in term infants. IGF-I, and IGF-II, and SMPC levels showed a positive correlation with birth weight in term infants. Both IGF-I and IGF-II levels showed a strong positive correlation with gestational age in all infants.

Adult↗

Effect of renal function on plasma levels of bone Gla-protein.

Plasma bone Gla-protein (BGP) is a sensitive and specific marker for metabolic bone disease. Because BGP is removed from the circulation mainly by kidney clearance, increased plasma BGP in subjects with impaired renal function could be due to decreased renal clearance, increased bone metabolism, or both. These factors were evaluated in 62 patients with various degrees of renal failure in whom we measured plasma BGP, [125I]iothalamate clearance [a measure of glomerular filtration rate (GFR)], and [131I]o-iodohippurate clearance (a measure of effective renal plasma flow). In all patients with GFR greater than 30 ml/min X 1.73 m2, plasma BGP was within the normal range for age- and sex-comparable control subjects, and large increases in plasma BGP did not occur until GFR was below 20 ml/min X 1.73 m2. Nonlinear regression analysis showed that the variation in plasma BGP was substantially accounted for using the exponential of GFR. Similarly, plasma BGP was normal for values of effective renal plasma flow above 150 ml/min X 1.73 m2. Thus, for normal subjects and patients with mild to moderate renal failure, plasma elevations of BGP reflect increased bone turnover rather than decreased renal filtration.

Adult↗

Biosynthetic methionyl human growth hormones is biologically active in adult man.

The acute effects of synthetic methionyl human growth hormone produced by recombinant DNA technology were compared with those of pituitary human growth hormone in 22 healthy male volunteers. Both caused increases in somatomedin and triglycerides and decreases in blood urea nitrogen and cholesterol. By all indices measured, synthetic methionyl human growth hormone was equipotent with pituitary human growth hormone. The ability to make biologically active synthetic human growth hormone creates an essentially unlimited supply of growth hormone for the treatment of hypopituitarism and for the study of additional therapeutic indications.

Blood Urea Nitrogen↗

Serum free thyroxine values in term, premature, and sick infants.

Free thyroxine concentrations were determined by radioimmunoassay in 96 infants within an intensive care nursery and in 32 healthy term infants. Sera for free T4 levels were drawn simultaneously with the filter paper specimens for T4 obtained to screen these infants for congenital hypothyroidism. The mean free T4 level in 20 adults was 1.38 +/- 0.03 ng/dl (mean +/- SEM). The mean in the ICN infants was 3.48 +/- 0.18 ng/dl and in healthy term infants, 4.24 +/- 0.23 ng/dl. Like T4, free T4 correlated positively with increasing gestational age and birth weight, and was lower in infants with RDS. Although 66% of the ICN infants had T4 levels below the statistically selected screening level (fifth percentile), all of these infants had free T4 levels greater than 0.8 ng/dl. Two additional infants with untreated congenital hypothyroidism has free T4 levels of 0.3 and 0.4 ng/dl. The measurement of free T4 appears to be an accurate indicator of thyroid function in these infants.

Adult↗

Synergism between immunosuppressive agents and uremia?

The susceptibility of uremic patients to infectious disease has been widely reported, but the host immune factors associated with the increased incidence of infection have not been clearly defined. In this study, the possibility of synergism between biologically active components that accumulate in uremia and immunosuppressive drugs used in the course of management was investigated. An animal model of chronic stable uremia was used in these experiments to assess the effect of cyclophosphamide, methotrexate, and azathioprine on antibody response in the uremic host. Chronic uremia did not affect the immunosuppressive activity of cyclophosphamide, methotrexate, or azathioprine, and synergism between these agents and uremic components is unlikely to complicate further the immune status of the host in renal failure.

Animals↗

Both human pituitary growth hormone and recombinant DNA-derived human growth hormone cause insulin resistance at a postreceptor site.

We have investigated the effects on carbohydrate metabolism of human GH produced by recombinant DNA technology (methionyl-hGH) compared with pituitary hGH. Twelve normal adult male subjects received four daily im injections of either methionyl-hGH or pituitary hGH in a double blind, crossover study. Oral glucose tolerance tests and assays of insulin binding to peripheral monocytes were performed before th initial administration and 12 h after the fourth injection of both hGH preparations. Both methionyl-hGH and pituitary hGH resulted in significant carbohydrate intolerance, with a rise in fasting plasma glucose from 96.6 +/- 2.9 to 105.9 +/- 3.0 mg/ml (mean +/- SEM) after pituitary hGH and from 96.2 +/- 1.5 to 107.5 +/- 3.3 mg/dl after methionyl-hGH (P less than 0.01). The area under the glucose tolerance curve increased by 34% after pituitary hGH and by 37% after methionyl-hGH. With both hGH preparations, carbohydrate intolerance was associated with marked hyperinsulinemia, with a rise in fasting plasma insulin levels from 9.4 +/- 1.2 to 33.2 +/- 7.8 microU/ml after pituitary hGH and from 7.4 +/- 1.1 to 45.8 +/- 11.1 microU/ml after methionyl-hGH (P less than 0.01). The integrated plasma insulin levels during the oral glucose tolerance test tripled after both hGH preparations. The pronounced insulin resistance could not be attributed to an alteration in insulin receptor concentrations. Both hGH preparations were associated with small reductions in insulin binding to monocytes at tracer concentrations, but the decline in binding was not statistically significant. The calculated binding sites per cell and Ke were not significantly altered by hGH administration. We conclude that methionyl-hGH and pituitary hGH are indistinguishable in their ability to induce insulin-resistant carbohydrate intolerance. This decrease in insulin sensitivity cannot be attributed to an alteration in insulin binding, and presumably represents a postreceptor defect in insulin action.

Adult↗

Somatomedins in pregnancy: a cross-sectional study of insulin-like growth factors I and II and somatomedin peptide content in normal human pregnancies.

To explore the role of the somatomedins (SM) during human pregnancy, we have measured plasma levels of insulin-like growth factor I (IGF-I), IGF-II, and SM peptide content (SMPC) in 79 women in various stages of normal pregnancies. IGF-I and IGF-II were measured by specific RIAs, and SMPC was measured by a radioreceptor assay using human placental membranes. IGF-I and SMPC rose during pregnancy, showing a significant positive correlation with the length of gestation. Plasma levels of IGF-I in the third trimester averaged 324 ng/ml, a 33% increase over the first trimester average of 243 ng/ml (P less than 0.05). Although IGF-II did not correlate with the length of gestation, the third trimester average was significantly higher than the first trimester average (780 vs. 630 ng/ml; P less than 0.05). After delivery, both IGF-I and IGF-II levels rapidly dropped to levels significantly below those seen in the third trimester. The gestational rise in SMPC and plasma levels of both IGF-I and IGF-II supports the hypothesis that SM play a role in the regulation of fetal growth.

Adolescent↗

Incidence of gamma-globulin banding in a healthy population by high-resolution electrophoresis.

We report the incidence of electrophoretically homogeneous protein bands occurring in the gamma-globulin region in serum samples from 600 healthy adults, as determined with a high-resolution electrophoretic system. One or more electrophoretically homogeneous protein bands of various intensities were detected in the gamma-globulin region of 30 specimens when we used an improved agarose electrophoretic system, and in two specimens when we used a cellulose acetate electrophoretic system. Improvement of the agarose gel electrophoretic system thus enhanced its sensitivity in defining homogeneous protein bands in the gamma-globulin region. The incidence of these bands in a healthy population is approximately 5%.

Adult↗

Beta 2-microglobulin determined by radioimmunoassay with monoclonal antibody.

In this sensitive radioimmunoassay for beta 2-microglobulin (beta 2-M) involving a commercially available monoclonal antibody, we used a second monoclonal antibody, produced in our laboratory, for affinity-chromatographic purification of beta 2-M. Both monoclonal antibodies bound to all of the charge isomers of beta 2-M identified by two-dimensional gel electrophoresis. Polyethylene glycol was used to separate the phases after incubation for 3 h at room temperature. Sensitivity was 0.25 ng of beta 2-M. Within-assay CVs were less than 5.4%, between-assay CVs less than 7.3%. Analytical recovery was 95-102%. The reference interval was 1.2-2.2 mg/L for 49 healthy subjects. The correlation coefficient for comparison with a polyclonal antibody assay was 0.997 for 44 patients. In a study correlating serum beta 2-M and creatinine concentrations with glomerular filtration rate for 50 patients, correlation coefficients for log-log transformed data were -0.94 and- 0.95, respectively. Concentrations of beta 2-M were increased in serum of patients with imparied renal function and also in patients with normal renal function who had disorders involving the immunologic response. We found no clear-cut advantage of measuring serum beta 2-M over serum creatinine in the estimation of glomerular filtration rate.

Adult↗

Aflatoxicol and aflatoxins B1 and M1 in the tissues of pigs receiving aflatoxin.

Aflatoxicol (AFL) and aflatoxins B1 and M1 were found in tissues (kidney, liver, and muscle) of feeder pigs given an estimated LD50 oral dose of B1 (1.0 mg/kg body weight) provided as a rice culture of Aspergillus flavus and of market-weight pigs fed a naturally contaminated feed, containing aflatoxin B1 at a level of 400 ng/g from corn, for 14 days. The residues in all tissues decreased with time after treatment in both groups, with no detectable residues (approximate detection limits, ng/g, B1 0.03, M1 0.05, AFL 0.01) in pig tissues from the feeding experiment 24 h after withdrawal of aflatoxin-contaminated feed. B1 and M1, when found in the feeding experiment, were at about the same levels in all tissues except the kidney, in which M1 was the dominant aflatoxin. The level of AFL, when detected, was about 10% of the B1 level.

Aflatoxin B1↗