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Biomedical subjects

C Nelson

Publications and source records attributed to C Nelson.

At least 145 records · Page 8Linked to original sources
PubMed1990

Comparisons of female and male early adolescent sex role attitude and behavior development.

This study contrasted female and male early adolescent sex role attitude and behavior development in an ecological context as defined by Bronfenbrenner. Data were the results of a state-wide survey of early adolescents and their parents. Hierarchical multiple regression was used to test both sex role attitude development and behavior development models. Only the models for attitude development were significant. The level of traditionalism of female sex role attitude development was significantly influenced by maternal employment, the level of traditionalism of the father's sex role attitudes in interaction with the amount of time he spent with his daughter, and chronological age. In contrast, the level of traditionalism of male sex role attitude development was significantly influenced by the level of traditionalism of the mother's sex role attitudes in interaction with the level of closeness to the mother that was reported by the son, and both mother's and father's perception of pubertal age. The implications of the findings for human development theory, early adolescence as a stage of development, and sex role theory and research are discussed.

Adolescent↗
PubMed1989

The chymotrypsin enhancer core. Specific factor binding and biological activity.

A 20-base pair (bp) conserved sequence present in the 5'-flanking regions of genes highly expressed in the exocrine pancreas forms part of the enhancers of the rat amylase 2A, chymotrypsin B, and elastase I genes. Factor(s) that interact with the conserved DNA sequence of the rat chymotrypsin B gene in vitro have been detected in extracts from acinar cells but not in three other cell lines tested. Transfection experiments suggest that the acinar cell factor(s) recognizing this enhancer core sequence are transcriptional activators. Multimers of a 28-bp sequence located by DNase I protection are capable of activating heterologous promoters in acinar cells. In vitro competition binding and methylation interference analyses indicate protein-DNA interactions at two distinct sites 10 base pairs apart on the DNA. This interaction is identical in extracts from cultured acinar cells as well as from whole pancreas tissue. The presence of two contiguous binding motifs on the same face of the DNA suggests that two (multiple) factors cooperate in the transcriptional regulation of this gene. We term these factors CACCTG pan-1 and TTTCCC pan-1. A factor with the binding specificity of the adenovirus major late transcription factor (MLTF) cross-reacts with the factor CACCTG pan-1 in vitro. However, the distribution of this factor in the various cells does not correlate with the activity of the enhancer core element in vivo. Further, conversion of the chymotrypsin sequence into a consensus MLTF site by three-point mutations abolished enhancer activity in acinar cells. Thus, the MLTF-like factor cannot substitute functionally for the factor CACCTG pan-1 and may act as an inhibitor of chymotrypsin enhancer function.

Animals↗
PubMed1989

A pituitary POU domain protein, Pit-1, activates both growth hormone and prolactin promoters transcriptionally.

The anterior pituitary gland provides a model for investigating the molecular basis for the appearance of phenotypically distinct cell types within an organ, a central question in development. The rat prolactin and growth hormone genes are expressed selectively in distinct cell types (lactotrophs and somatotrophs, respectively) of the anterior pituitary gland, reflecting differential mechanisms of gene activation or restriction, as a result of the interactions of multiple factors binding to these genes. We find that when the pituitary-specific 33-kD transcription factor Pit-1, expressed normally in both lactotrophs and somatotrophs, is expressed in either the heterologous HeLa cell line or in bacteria, it binds to and activates transcription from both growth hormone and prolactin promoters in vitro at levels even 10-fold lower than those normally present in pituitary cells. This suggests that a single factor, Pit-1, may be capable of activating the expression of two genes that define different anterior pituitary cell phenotypes. Because a putative lactotroph cell line (235-1) that does not express the growth hormone gene, but only the prolactin gene, appears to contain high levels of functional Pit-1, a mechanism selectively preventing growth hormone gene expression may, in part, account for the lactotroph phenotype.

Animals↗
PubMed1989

Maternal age and screening for gestational diabetes: a population-based study.

The American College of Obstetricians and Gynecologists (ACOG) has recommended screening for gestational diabetes, using a 50-g, 1-hour glucose challenge (threshold for further testing 140 mg/dL or higher), for all pregnant women aged 30 or older and for younger women with risk factors. In order to assess these recommendations, we collected demographic and historic data on 6214 pregnant women representing a population of universally screened individuals. Of 125 cases of gestational diabetes diagnosed (ACOG criteria), 70 patients (56%) were under the age of 30. In addition, 44% of gestational diabetics had no risk factors. The cost per case diagnosed would be $190 with the ACOG recommendations, $192 if the age for routine screening were lowered to 25 years or more, and $222 if universal screening were practiced. Using the ACOG recommendations, 35% of gestational diabetes would go undiagnosed, with little cost savings.

Adult↗
PubMed1989

Similar and synergistic inhibition of gap-junctional communication by ras transformation and tumor promoter treatment of mouse primary keratinocytes.

Modulation of gap junctional communication (GJIC) is likely to play an important role in tumorigenesis, as suggested by the action of tumor promoters and certain oncogene products. In this report we examine the effects of ras transformation and TPA (12-O-tetradecanoylphorbol-13-acetate) treatment on GJIC of murine primary keratinocytes. Introduction of the ras oncogene into primary keratinocyte cultures by Harvey Sarcoma virus (HaSV) infection is sufficient to cause a 70-80% reduction in their GJIC as measured by Scrape-Loading/Dye Transfer technique. Furthermore, while a 100% increase in GJIC is observed when normal keratinocyte cultures are induced to differentiate by addition of calcium, no such increase can be detected with their ras transformed counterparts. As with ras, TPA treatment of normal keratinocytes results in a 70-80% reduction of GJIC both under low and high calcium conditions. TPA treatment of keratinocytes already transformed by ras completely abolishes GJIC of these cells, regardless of calcium concentrations. The similar and synergistic effects of ras and TPA on GJIC of primary keratinocytes suggest that inhibition of this function represents an important early step in transformation of these cells.

Animals↗
PubMed1988

Enzyme-linked immunosorbent assays (ELISAs) for the determination of contaminants resulting from the immunoaffinity purification of recombinant proteins.

Two immunoassays have been developed for the quantitation of part-per-million levels of contaminants likely to co-purify with monoclonal antibodies produced in tissue culture and purified by protein A affinity chromatography. These contaminants are bovine IgG originating from the fetal bovine serum used in cell culture, and protein A. Mouse IgG was shown not to interfere in the bovine IgG assay, where contamination levels of 0.2-0.7% bovine IgG were measured in the lots of monoclonal antibody tested. The protein A ELISA was developed with monoclonal antibody included in the standard, and in the preparations of monoclonal antibody tested, 64 parts per million (ppm) or less of protein A were demonstrated. An additional immunoassay was developed to quantitate monoclonal antibody contamination of two recombinant proteins, rHBsAg and rgp 120 from HIV, purified by affinity chromatography with such antibodies. Possible interference of monoclonal antibody quantitation by the respective antigens was examined in this ELISA, and contamination levels of less than 56 ppm of antibody were determined in the purified recombinant proteins. The three immunoassays were shown to be specific for the major protein contaminants in either monoclonal antibodies or the recombinant proteins and were necessary in demonstrating their purity.

Animals↗
PubMed1988

Activation of cell-specific expression of rat growth hormone and prolactin genes by a common transcription factor.

In the anterior pituitary gland, there are five phenotypically distinct cell types, including cells that produce either prolactin (lactotrophs) or growth hormone (somatotrophs). Multiple, related cis-active elements that exhibit synergistic interactions appear to be the critical determinants of the transcriptional activation of the rat prolactin and growth hormone genes. A common positive tissue-specific transcription factor, referred to as Pit-1, appears to bind to all the cell-specific elements in each gene and to be required for the activation of both the prolactin and growth hormone genes. The data suggest that, in the course of development, a single tissue-specific factor activates sets of genes that ultimately exhibit restricted cell-specific expression and define cellular phenotype.

Animals↗
PubMed1988

Differential regulation of the coexpressed calcitonin/alpha-CGRP and beta-CGRP neuroendocrine genes.

The rat calcitonin/alpha-CGRP and beta-CGRP genes are members of a neuroendocrine gene family that are coexpressed in a distinct cell-specific pattern. The alpha- and beta-CGRP gene sequences predict highly related peptides that differ by only a single amino acid. Using rat medullary thyroid carcinoma cells as an in vitro system for testing hormone responsiveness, we have shown that the calcitonin/alpha-CGRP and beta-CGRP genes are differentially regulated. The synthetic glucocorticoid, dexamethasone, caused a 2- to 5-fold increase in calcitonin and alpha-CGRP mRNAs due to an increase in the nuclear transcription rate. In contrast, the levels of beta-CGRP mRNA did not significantly change following dexamethasone treatment. Differential regulation within neuroendocrine gene families might be a common mechanism for generating functionally similar peptides in response to a variety of hormonal signals.

Calcitonin↗
PubMed1988

A single domain of the estrogen receptor confers deoxyribonucleic acid binding and transcriptional activation of the rat prolactin gene.

Binding of ligand to the estrogen receptor, a member of the steroid receptor gene family, rapidly increases PRL gene transcription. A 15 base pair core sequence 5'TTGTCACTATGTCCT-3' greater than 1.5 kilobase upstream from the rat PRL gene transcription start site is necessary for receptor binding, demonstrates interaction with the receptor DNA binding domain, and confers estrogen regulation. Transient cotransfection of expression plasmids encoding mutant estrogen receptors with a luciferase reporter plasmid under regulation of the rat PRL estrogen regulatory element were used to investigate the minimal information necessary and sufficient for activation of gene transcription. These analyses confirmed the absolute requirement for the receptor DNA binding domain in positive regulation of transcription, and revealed that removal of amino-terminal domains reduced, but did not abolish transcriptional effects. In contrast, truncation of the receptor immediately carboxy-terminal to the DNA binding domain resulted in constitutive activation of the receptor. The observations that removal of the steroid binding domain results in a constitutively active transcriptional factor, and that the amino-terminal domains are not required for transcriptional effect provides evidence that for two members of the steroid receptor gene family (the glucocorticoid and estrogen receptors), a relatively short DNA binding domain is sufficient for transcriptional activation. These results are likely to be prototypic for other members of this family of transcriptional factors.

Animals↗
PubMed1987

The influence of food on the oral absorption of bevantolol.

The bioavailability of bevantolol was compared in 12 healthy volunteers given single doses of the drug as the HCl salt after an overnight fast, or 15 minutes before or after a standardized breakfast in a nonblind, randomized crossover design. Bevantolol was rapidly absorbed in all three treatment groups, with maximum concentrations (Cmax) observed at 1.0, 0.9, and 1.8 hours for the fasting, before breakfast, and after breakfast groups, respectively. Time to Cmax was significantly longer than fasting only when bevantolol was given after breakfast. Food ingestion did not significantly affect Cmax, total of absorbed drug, or the drug elimination rate. Since food only slightly decreases the drug absorption rate and has no measurable effect on the extent of drug absorption, the relationship of bevantolol administration to meals is not expected to influence therapeutic efficacy.

Absorption↗
PubMed1987

Frequency and significance of concurrent hepatitis B surface antigen and antibody in acute and chronic hepatitis B.

Of 228 consecutive hepatitis B surface antigen (HBsAg)-positive patients who had simultaneous hepatitis B surface antibody (anti-HBs) determinations, HBsAg and anti-HBs were found concurrently in 73 (32%). Concurrence was found with greater frequency in patients with chronic active hepatitis than in those with acute hepatitis (36/57 vs 13/38, p less than 0.02). Patients with chronic active hepatitis had concurrent markers more commonly than those with chronic persistent hepatitis or asymptomatic carrier state (36/57 vs. 24/133, p less than 0.001). No major risk factors were identified. Hepatitis B e antigen was detected more frequently in patients with concurrence (68% vs. 42%, p less than 0.01). Subtyping was possible in 30 patients with chronic infection, including 18 with chronic active hepatitis, 7 with chronic persistent hepatitis, and 5 with a carrier state. In 25 patients, HBsAg subtype ad was found with antibody to subdeterminant y and in four instances, HBsAg subtype ay was found with antibody to subdeterminant d. Only 1 patient had homotypic HBsAg and anti-HBs. Of 38 patients who had successive determinations, concurrence was constant in 29. In 9 others, anti-HBs was detected intermittently and the heterotypia of the recurrent antibody remained constant. Antibody to hepatitis delta-virus was not detected. We conclude that concurrent HBsAg and anti-HBs are found frequently in acute and chronic hepatitis B. The markers are commonly heterotypic in chronic disease. The presence of heterotypic markers is not associated with specific risk factors or delta-infection. Concurrence is associated with evidence of viral replication and features of active inflammation.

Adolescent↗
PubMed1987

Gout presenting as a popliteal cyst. A case of pseudothrombophlebitis.

A 64-year-old man with progressive swelling and erythema of his right calf preceded by dull aching in the right popliteal fossa was presumed to have deep vein thrombophlebitis. A venogram revealed normal circulation in the right lower leg, and an ultrasound examination of the right popliteal fossa revealed a 2 X 5-cm popliteal cyst. Fluid aspirated from the cyst confirmed the diagnosis of gout. Popliteal cysts associated with gout are rare, and those that rupture, leak, dissect, or enlarge can mimic thrombophlebitis (a phenomenon known as pseudothrombophlebitis). Thus, the primary care physician should consider the diagnosis of popliteal cyst in patients who appear to have deep vein thrombophlebitis.

Diagnosis, Differential↗
PubMed1987

Mutually independent effects of adrenocorticotropin on luteinizing hormone and testosterone secretion.

In this study, we examined the effect of ACTH on the sensitivity of the testes to gonadotropin and determined the role of the testosterone (T) negative feedback system in mediating the inhibitory effect of ACTH on LH secretion in adult male rats. ACTH infusion for 3 days reduced basal levels of serum T and the T response to GnRH, but did not alter basal levels of serum LH (immunoreactive) or the LH response to GnRH. These effects required the presence of the adrenal glands. Infusion of corticosterone (B) at a dose that increased serum B concentrations 9-fold had an effect similar to that of ACTH on basal serum T levels and the serum T response to GnRH. Basal levels of serum LH and the serum LH response to GnRH were not affected by B administration. These data suggest that ACTH administration reduces the sensitivity of the testes to LH, resulting in a lower basal level of T and a reduced T response to GnRH. This effect was independent of basal serum LH levels or the LH response to GnRH. It appears that B mediates the effect of ACTH on testicular sensitivity to gonadotropin. In another experiment, ACTH administration for 4 days did not alter serum LH values, but reduced serum T levels in sham-castrated male rats. In contrast, ACTH treatment blunted the increase in serum LH after castration by day 2 of treatment, despite the absence of detectable levels of serum T within 6 h after castration. These data suggest that T is not essential for the inhibitory effect of ACTH on LH secretion to occur. They do not support the hypothesis that ACTH enhances the sensitivity of the hypothalamus and/or pituitary to the negative feedback effects of T.

Adrenalectomy↗
PubMed1987

Genetic defects of steroidogenesis in premature pubarche.

Twenty three patients (19 girls, 4 boys) presented with typical features of premature pubarche between the ages of 2-7 yr. The patients were studied for the presence of an adrenal steroidogenic defect by ACTH stimulation testing (Cortrosyn, 0.25 mg iv bolus dose). Based on published nomogram standards for serum 17-hydroxyprogesterone (17-OHP), seven patients (30%) were diagnosed as having the nonclassical symptomatic form of 21-hydroxylase deficiency [mean post ACTH 4244 +/- 1113 (SD) ng/dl]. Three patients (13%) were diagnosed to have a mild form of 3 beta-hydroxysteroid dehydrogenase deficiency based upon the response of serum delta 5-17-hydroxypregnenolone (delta 5-17P) and dehydroepiandrosterone, and the ratio of delta 5-17P/17-OHP to ACTH stimulation (delta 5-17P: 1543 +/- 272 ng/dl vs. Tanner stage I control subjects, 350 +/- 197 ng/dl; dehydroepiandrosterone: 675 +/- 190 ng/dl vs. Tanner stage I control subjects, 82 +/- 79 ng/dl; delta 5-17P/17-OHP: 8.1 +/- 2.6 vs. Tanner stage I control subjects, 1.4 +/- 0.6). No enzyme defect could be identified in the remaining 13 patients (57%). Eleven patients with premature pubarche, with and without an adrenal enzymatic defect, underwent dexamethasone suppression. In all patients the measured steroid levels were suppressed. Thus, the dexamethasone suppression test alone did not distinguish the pathogenesis of premature pubarche. In conclusion, premature pubarche is more commonly due to a partial enzyme defect in adrenal steroidogenesis than has been previously recognized.

3-Hydroxysteroid Dehydrogenases↗