Biomedical subjects

D M Wilson

Publications and source records attributed to D M Wilson.

At least 199 records · Page 11Linked to original sources

PubMed1989

Role of the clinical laboratory in the diagnosis and management of malignant melanoma.

The biosynthesis of melanin from tyrosine is reviewed as the basis for assessment of laboratory tests that might potentially aid in the diagnosis and management of patients with malignant melanoma. These tests include qualitative and quantitative assays for the intermediates in metabolism of melanin and catecholamines, enzyme assays, metal ion analyses, and, most recently, immunoassays. Although currently no role exists for the clinical laboratory in the early diagnosis of malignant melanoma, serial quantitative analyses of total or individual melanogens or of catecholamine metabolites in urine or plasma specimens may be of value in the management of patients with this disorder. Immunologically based methods for the diagnosis and management of malignant melanoma hold some promise for the future.

Antigen-Antibody Complex↗

PubMed1989

Natriuretic response to volume expansion in polycystic kidney disease.

Hypertension is an early manifestation of autosomal dominant polycystic kidney disease (ADPKD). Whether polycystic kidneys have an intrinsic abnormality that leads to sodium retention, volume expansion, and hypertension is uncertain. We studied the natriuretic response to a 4-hour infusion of physiologic saline at a rate of 6.5 ml/kg per hour in 10 patients with ADPKD who had normal renal function and 10 gender- and age-matched control subjects. Baseline 24-hour urinary excretions of sodium and potassium were similar in both groups. The baseline filtration fraction was significantly higher in the patients with ADPKD than in the control subjects. During the infusion of saline, no significant changes in blood pressure, clearance of inulin, or clearance of p-aminohippuric acid were detected. The increase in fractional excretion of sodium over baseline was significantly higher in the patients with ADPKD than in the control subjects. The pressure-natriuresis regression line was significantly shifted to the right in patients with ADPKD who had hypertension. The fractional excretion of potassium was significantly lower in patients with ADPKD than in control subjects. No significant differences in plasma renin activity, aldosterone, or atrial natriuretic factor were detected between the two groups. These observations suggest the presence of subtle abnormalities in the management of renal sodium that might contribute to the development and maintenance of hypertension in patients with ADPKD.

Adult↗

PubMed1989

Prorenin and vascular complications of diabetes.

A high plasma prorenin is a marker of microvascular complications of diabetes. We have followed 56 adults and 120 children with uncomplicated insulin-dependent (type 1) diabetes. When plasma prorenin rises above the normal range in an adolescent or adult with type 1 diabetes, signs of nephropathy, retinopathy, or neuropathy follow within one to two years. The earliest sign may be intermittent microalbuminuria, which can often be abolished by improved control of hyperglycemia. The association between increased plasma prorenin and complications of noninsulin-dependent (type 2) diabetes is less reliable in patients with hypertension and in those receiving medication that affects plasma prorenin. The oral hypoglycemic agent, glipizide, lowers plasma prorenin, but its effect on prognosis is unknown. Plasma prorenin and renin decline as blood pressure rises, whereas the prevalence of micro- and macroalbuminuria increases. Many drugs used to control hypertension affect the level of prorenin. In the majority of our patients with type 2 diabetes who are hypertensive or are taking a medication that affects plasma prorenin, microalbuminuria may prove to be a more reliable warning of vascular complications.

Albuminuria↗

PubMed1989

Transformation of diploid human fibroblasts by transfection of N-ras-oncogenes.

To determine if diploid human fibroblasts can be transformed by the N-ras oncogene found in human tumors, early passage cell lines were transfected with an N-ras oncogene from human leukemia cell line 8402 cloned into a high expression plasmid (pSV N-ras), with the N-ras oncogene from human fibrosarcoma cell line HT1080 cloned into pNR-MG1, or with pSV2neo as a control. Each plasmid carries the neo gene coding for Geneticin resistance, but in pSV N-ras, the endogenous promoter of the N-ras gene has been eliminated, and the gene has been inserted between the viral long-terminal repeat (LTR) and the neo gene so that transcription initiated from the LTR must transcribe the N-ras gene before transcribing neo. In pNR-MG1, transcription of the N-ras gene is driven from its endogenous promoter, and the neo gene is transcribed from an SV40 viral promoter, as in pSV2neo. When the transfectants were selected for Geneticin resistance, 70% of the colonies formed with pSV N-ras consisted of morphologically altered cells. Less than 5% of the drug resistant colonies formed with pNR-MG1 had cells with altered morphology, and the change in morphology was much less distinct than with pSV N-ras. No colonies of morphologically-transformed cells were found with pSVneo. If the transfected populations were not selected in Geneticin, but were simply allowed to grow to confluence, very distinct foci composed of morphologically-altered cells could be seen against a contact-inhibited monolayer with pSV N-ras. Foci formed by the pNR-MG1 population were subtle and much less distinct. No foci were found with pSV2neo. Representative colonies and foci of morphologically-transformed cells were isolated. Those from pNR-MG1 transfection reverted to a normal morphology after 5-10 population doublings. Most of those from pSV N-ras transfection either reverted or senesced after 5-10 population doublings. However, progeny of two colonies expressed stable morphological transformation throughout a normal life span equal to that of age-matched pSV2neo controls. Both of these stably transformed cell strains exhibited anchorage independence and formed distinct foci. Immunoprecipitation analysis showed that these cells produced much larger amounts of N-ras protein than did pSV2neo-transfected control cells. However, these two cell strains did not exhibit an infinite life span in culture and were unable to form tumors in athymic mice.

Cell Line↗

PubMed1989

Structural characterization and immunohistochemical localization of receptors for insulin-like growth factor II in the rat pituitary gland.

Insulin-like growth factor II (IGF-II) receptors were detected, localized, and structurally characterized in rat pituitary tissue sections and cultures of dispersed pituitary cells by immunohistochemistry, and affinity labeling with gel electrophoresis. Using highly specific antisera against IGF-II receptors (type 2 IGF receptors) and somatotropin (GH), intense type 2 receptor immunoreactivity was detected in both anterior and intermediate pituitary lobes. In anterior pituitary sections and cultures, type 2 receptor immunoreactivity colocalized to most GH-immunoreactive cells (somatotropes), as well as cells which did not contain GH. Intermediate lobe immunoreactivity was uniformly distributed throughout the parenchyma. In both anterior and intermediate pituitary lobes, type 2 receptor immunoreactivity was predominately localized to the plasma membrane of labeled cells, with little or no cytoplasmic labeling. GH immunoreactivity, on the other hand, was intracellular. Affinity labeling of microsomal membranes from anterior and neurointermediate pituitary tissues with 125I-IGF-II disclosed classical 230k type 2 receptors. The magnitude of affinity cross-linking from both lobes was similar to that of rat liver, indicating pituitary tissues, like liver tissue, are rich sources of type 2 receptors. These results suggest possible roles for IGF-II and the type 2 receptor in the regulation of synthesis or secretion of pituitary trophic hormones, including GH and pro-opiomelanocortin gene products.

Animals↗

PubMed1989

Bilateral pelviureteric junction obstruction causing renal failure in two elderly patients.

Two elderly patients presented with renal failure due to pelviureteric junction (PUJ) obstruction. After dialysis, obstruction was relieved by percutaneous nephrostomy and the diagnosis was established radiologically. Differential renal function was assessed by direct measurement or isotope scanning. Surgical correction resulted in both patients remaining free of dialysis at follow-up 2 years later. PUJ obstruction is an uncommon cause of renal failure, particularly in the elderly, but is potentially correctable.

Acute Kidney Injury↗

PubMed1989

Characterization of insulin-like growth factor binding proteins from human breast cancer cells.

The insulin-like growth factor binding proteins (IGF-BPs) are structurally and immunologically distinct from the IGF type 1 or type 2 receptors and are characterized by two major forms: a large, GH-dependent BP found in human plasma (Mr = 150 k) and a small GH-independent BP (Mr = 28-42 k) present in human plasma, amniotic fluid, and HEP G2 cells. Using affinity cross-linking techniques, we have identified several binding proteins secreted by human breast cancer cell lines (Hs578T, MDA-231, T-47D, and MCF-7). Under nonreducing conditions these proteins migrated at an apparent Mr = 35, 28, 27, and 24 k, while reducing conditions revealed bands of apparent Mr = 35, 32, 27, and 24 k. Competitive binding studies in T-47D-conditioned media demonstrated that these BPs bound more IGF-II than IGF-I, and that IGF-II potently inhibited binding of either IGF-I or -II. Immunological studies using a polyclonal antibody against the HEP G2 small BP revealed no immunoreactive BP in conditioned media from MCF-7 and T-47D and only slight immunoreactivity in conditioned media from Hs578T and MDA 231. Analysis by Northern blot, using a probe from the cDNA sequence of the HEP G2 BP, demonstrated that Hs578T and MDA-231 cell lines contained small amounts of the 1.65 kilobase mRNA characteristic of the HEP G2 BP, while MCF-7 and T-47D tested negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Blotting, Northern↗

PubMed1989

Smoking cessation in primary care. A randomized controlled trial of nicotine-bearing chewing gum.

The results are reported from a multicentered, randomized clinical trial of a physician-delivered smoking cessation intervention package. All physicians attended a four-hour training session during which the rationales for the different aspects of the intervention were discussed, including a detailed description of the proper use of nicotine-bearing chewing gum. Patients were randomized to receive an offer of a prescription of 2 mg of nicotine chewing gum in addition to the basic intervention (n = 111) or the basic intervention alone (n = 112). The basic intervention included advice, setting a date for quitting, self-help materials, and the offer of supportive follow-up visits. Receptionists were instructed to recruit the first two smokers attending the practice each day. One-year smoking cessation was validated by cotinine saliva analysis. The validated three-month sustained abstinence rates at one year were 8.1 percent and 9.8 percent in the gum and no-gum groups, respectively. The 95 percent confidence interval about this difference was -9.3 percent to 6.4 percent. There is no evidence from this study that the offer of 2 mg of nicotine-bearing gum enhances smoking cessation rates when added to a comprehensive intervention offered to all smokers in primary care. Until larger trials are completed, however, the possibility that this dose of nicotine gum may produce small beneficial effects cannot be excluded.

Chewing Gum↗

PubMed1989

Effect of a high affinity aluminosilicate sorbent on prevention of aflatoxicosis in growing pigs.

Adding 0.5% hydrated sodium calcium aluminosilicate to diets formulated with aflatoxin-contaminated corn significantly reduced the detrimental effects of the mycotoxin on live weight gains and feed intake. Hepatocellular changes normally associated with aflatoxin consumption could not be detected histopathologically in liver sections from pigs fed contaminated diets plus the aluminosilicate sorbent.

Aluminum Silicates↗

PubMed1989

The role of neural and vasoactive mediators in the regulation of the pulmonary circulation during cardiopulmonary preservation.

The autoperfused working heart-lung preparation has been used for extended cardiopulmonary preservation for transplantation. However, acute lung injury and failure of the preparation can result from pulmonary hypertension, which previous investigators have linked to denervation. We studied the neural and vasoactive mediators of pulmonary vasoconstriction during normothermic autoperfusion of the heart and lungs from 13 calves. Pulmonary vascular resistance was quantitated by multipoint pulmonary artery pressure/flow plots generated by incremental reduction in venous return at three times: A, after sternotomy but before autoperfusion (control); B, during in situ autoperfusion (innervated heart-lung preparation); and C, after explanation (denervated heart-lung preparation). During hemodynamic measurements, left atrial blood samples were obtained for measurement of thromboxane B2, 6-keto-prostaglandin-F1 alpha, and complement activation products C3a and C5a. Results show that pulmonary hypertension in the autoperfused working heart-lung preparation begins during autoperfusion before denervation and may be related to complement activation and to increased levels of circulating thromboxane B2 and 6-keto-prostaglandin F1 alpha (both the absolute levels and the ratio of thromboxane B2 to 6-keto-prostaglandin F1 alpha). After denervation, both prostaglandin intermediates were markedly increased, but their ratio was not significantly affected. These data suggest that there is an initial stage of pulmonary vasoconstriction at the onset of autoperfusion that is accompanied by increased circulating levels of vasoactive mediators and that denervation further contributes to this response.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Competitive enzyme-linked immunosorbent assay (ELISA) for the quantitation of apolipoprotein A-I using a monoclonal antibody.

A semi-automated competitive enzyme-linked immunosorbent assay for human plasma apolipoprotein (Apo) A-I has been developed which utilizes nondelipidated samples, microtiter plates, commercially available monoclonal antibodies and alkaline phosphatase conjugated second antibody. The working range of the assay is 5-100 ng of Apo A-I. The range of plasma concentrations for plasma Apo A-I was 1.21 +/- 0.34 g/l for a random sample of 40 healthy adults. Intra- and inter-assay coefficients of variation (CV) were 4 and 7%, respectively. There was a good correlation between this assay and a radial immunodiffusion assay (r = 0.96). The assay is suitable for measurement of apolipoprotein A-I in either normal or pathological plasma, lipoprotein density classes, and for cell biological and molecular biological investigations.

Antibodies, Monoclonal↗

PubMed1988

The lactose carrier of Klebsiella pneumoniae M5a1; the physiology of transport and the nucleotide sequence of the lacY gene.

A comparison has been made between the physiology and amino acid sequence of the lactose carriers of Klebsiella pneumoniae M5a1 and Escherichia coli K-12. The membrane transport of lactose was much weaker in Klebsiella than in E. coli. On the other hand o-nitrophenylgalactoside uptake by Klebsiella was distinctly greater than with E. coli. In spite of the differences in sugar transport between the two organisms, the amino acid sequences of the respective lactose carriers were remarkably similar (60% of the amino acids are identical).

Amino Acid Sequence↗

PubMed1988

A randomized trial of a family physician intervention for smoking cessation.

We assessed the impact of three conditions on one-year smoking cessation rates. Physicians in 70 community general practices were randomly allocated by practice to one of three groups: In the usual care group, smoking patients were to receive the care they normally would receive. In the gum only group, physicians were asked to speak to patients about smoking cessation and offer nicotine gum. In the gum plus group, physicians were trained in the experimental intervention. This intervention involved advice to stop smoking, the setting of a quit date, the offer of nicotine gum, and four follow-up visits. Smoking cessation was measured by self-report after one year and validated using saliva cotinine measures. Using a criterion of at least three months of abstinence, 8.8% of the patients of the trained physicians had stopped smoking at the one-year follow-up compared with 4.4% and 6.1% of the patients in the usual care and gum only groups, respectively.

Adolescent↗

PubMed1988

Demonstration of insulin-like growth factor (IGF-I and -II) receptors and binding protein in human breast cancer cell lines.

The insulin like growth factors (IGFs), potent mitogens for a variety of normal and transformed cells, have been reported to be secreted by several human breast cancer cell lines (BC). We have investigated the binding characteristics of IGF-I and -II in four human BC: MCF-7, T-47D, MDA 231 and Hs578T. Binding studies in microsomal membrane preparations detected high specific binding for both IGF in all four BC studied. Cross-linking with 125I-IGF-I, followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) under reduced conditions, revealed the presence of an alpha subunit of apparent Mr = 130,000 in MCF-7, T-47D and MDA 213 cells. When 125I-IGF-II was cross-linked, a major band of apparent Mr = 260,000 was seen in all BC. This band was inhibited by IGF-II, but not by insulin. Cross-linking of 125I-IGF-I to conditioned media from BC demonstrated the presence of three binding proteins of apparent Mr = 45,000, 36,000 and 29,000 in all BC but T-47D, in which the 36,000 band was not seen. These data demonstrate that BC possess classical receptors for both IGF-I and -II and, furthermore, that BC produce specific binding proteins for these growth factors.

Breast Neoplasms↗

PubMed1988

Effects of testosterone therapy for pubertal delay.

We reviewed the effects of a brief course of testosterone enanthate (four intramuscular injections of 200 mg at three-week intervals) on pubertal advancement and final adult height in 50 male patients with delayed puberty. Although those treated with testosterone were slightly older than a group of 38 untreated subjects, the two groups had similar baseline mean bone age delays, height z scores, Tanner stages, predicted adult heights, growth rates, and midparental heights. Four months after baseline, the treated group had a significantly greater mean increase in the height z score and sexual maturation index. At 12 months, the mean increase in the sexual maturation index remained greater in the treated group. Among treated and untreated subjects older than 17 years, there was no significant difference in the absolute height z score. Over 95% of treated subjects were satisfied with the effects of therapy.

Adolescent↗

PubMed1988

Plasma prorenin and renin in childhood and adolescence.

We studied 108 subjects (age range, 4 to 76 years) to determine the effect of age on prorenin (inactive renin), active renin, and plasma renin activity in normal children, adolescents, and adults. Children and adolescents had lower prorenin concentrations and higher plasma renin activity and active renin concentrations than did adults. Prorenin concentrations were positively correlated with age over the range of 4 to 76 years, while plasma renin activity and active renin concentration were negatively correlated with age. Plasma prorenin and active renin concentrations from umbilical cord blood samples obtained from 11 newborns and arterial samples obtained from five infants were higher than those in samples obtained from children or adults.

Adolescent↗

PubMed1988

Carbohydrate and lipid metabolism in Turner syndrome: effect of therapy with growth hormone, oxandrolone, and a combination of both.

To evaluate the effects of growth-promoting therapy on carbohydrate metabolism in girls with Turner syndrome, we determined glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) at baseline and after 5 days, 2 months, and 12 months of treatment with growth hormone (GH), oxandrolone, or a combination of GH and oxandrolone, or after the same intervals with no therapy. Before therapy, subjects had a significantly greater glucose response during OGTT than published normal control values. There were no significant changes in mean fasting glucose, cholesterol, or triglyceride concentrations in any of the treatment groups. The integrated glucose concentrations rose significantly over baseline values in the oxandrolone group at 2 and 12 months and in the combination group at 5 days. There were significant increases in the mean integrated insulin concentrations at 2 and 12 months for the group receiving oxandrolone alone and at all three times for the group receiving combination therapy. Thus oxandrolone, alone or in combination with GH, had significant effects on carbohydrate metabolism in subjects with Turner syndrome, whereas GH alone did not.

Blood Glucose↗

PubMed1988

A randomized, placebo-controlled trial of effects of dexamethasone on hypothalamic-pituitary-adrenal axis in preterm infants.

As part of a blinded, randomized, placebo-controlled study of dexamethasone therapy in 27 preterm infants with bronchopulmonary dysplasia, we investigated the effect of 7 days of high-dose glucocorticoid therapy on the hypothalamic-pituitary-adrenal axis. Before therapy the median basal cortisol concentration in all infants was 8.2 micrograms/dl (226 nmol/L). After stimulation with 1-24 ACTH, the serum cortisol concentration rose in all infants to a median concentration of 23.5 micrograms/dl (649 nmol/L), resulting in a median rise of 13.4 micrograms/dl (37 nmol/L). Immediately after 7 days of glucocorticoid therapy basal and peak cortisol concentrations were significantly decreased in the dexamethasone group. The rise in serum cortisol following 1-24 ACTH, however, remained equivalent in both groups. Ten days after the end of therapy basal and peak cortisol concentrations in the dexamethasone group had returned to levels equivalent to those seen in the placebo group. Weight gain was markedly diminished while the infants were receiving dexamethasone. Weight gains were, however, equivalent 10 days after the end of treatment. These data indicate that 7 days of dexamethasone therapy has significant but short-term effects on cortisol secretion and possibly on weight gain.

Bronchopulmonary Dysplasia↗