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Biomedical subjects

C Fisher

Publications and source records attributed to C Fisher.

At least 253 records · Page 14Linked to original sources
PubMed1995

Nurses' sensitivity to the ethical aspects of clinical practice.

The purpose of this study was to describe the extent to which nurses perceive the ethical dimensions of clinical practice situations involving patients, families and health care professionals. Using the composite theory of basic moral principles and the professional standard of care established by legal custom as a framework, situations involving ethical dilemmas were gleaned from the nursing literature. They were reviewed for content validity, clarity and representativeness in a two-stage process by expert panels. The situations were presented in a written format to a convenience sample of nurses (n = 125), who were primarily staff nurses (65.6%). Respondents' judgements about whether the main issue of each situation concerned ethics ranged from a low of 0.8% to a high of 40%. From analyses of the categories into which the majority of subjects placed each situation, it was concluded that these nurses generally perceived ethics as the main issue in situations that directly involve patients' autonomy. Analysis yielded unanticipated findings about the themes in ethical situations to which nurses in practice may respond.

Adult↗
PubMed1995

Retinoid receptors and keratinocytes.

In 1987, a tremendous boost in our understanding of the action of dietary vitamin A occurred with the discovery and characterization of nuclear receptors for retinoic acid, the active form of the vitamin, in the laboratories of P. Chambon and R. Evans. They have shown that the nuclear receptors are ligand-activated transcription factors capable of specific gene regulation. Since that discovery, it has been determined that there are at least six retinoic acid receptors belonging to two families, RARs and RXRs, that they are differentially expressed in various mammalian tissues, and that they act as homo- and heterodimers interacting with other ligand-activated nuclear receptors. The domain structure of the receptors has been described, and their DNA-binding, ligand-binding, dimerization, and transcriptional activation regions characterized. Among the most important retinoid-regulated genes are the homeobox proteins, regulatory transcription factors which are responsible for body axis formation, patterning, limb formation, and other crucial processes during development. Retinoic acid and its receptors also regulate many differentiation markers which are particularly important in stratified epithelia, such as skin and oral epithelia. Our increased understanding led to improved therapy of a large number of skin disorders, ranging from acne to wrinkles and including epidermal and oral carcinomas.

Animals↗
PubMed1995

Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens.

The aromatase enzyme complex catalyzes the conversion of androgens to estrogens in a wide variety of tissues, including the ovary, testis, placenta, brain, and adipose tissue. Only a single human gene encoding aromatase P450 (CYP19) has been isolated; tissue-specific regulation is controlled in part by alternative promoters in a tissue-specific manner. We report a novel mutation in the CYP19 gene in a sister and brother. The 28-yr-old XX proband, followed since infancy, exhibited the cardinal features of the aromatase deficiency syndrome as recently defined. She had nonadrenal female pseudohermaphrodism at birth and underwent repair of the external genitalia, including a clitorectomy. At the age of puberty, she developed progressive signs of virilization, pubertal failure with no signs of estrogen action, hypergonadotropic hypogonadism, polycystic ovaries on pelvic sonography, and tall stature. The basal concentrations of plasma testosterone, androstenedione, and 17-hydroxyprogesterone were elevated, whereas plasma estradiol was low. Cyst fluid from the polycystic ovaries had a strikingly abnormal ratio of androstenedione and testosterone to estradiol and estrone. Hormone replacement therapy led to breast development, menses, resolution of ovarian cysts, and suppression of the elevated FSH and LH values. Her adult height is 177.6 cm (+2.5 SD). Her only sibling, an XY male, was studied at 24 yr of age. During both pregnancies, the mother exhibited signs of progressive virilization that regressed postpartum. The height of the brother was 204 cm (+3.7 SD) with eunuchoid skeletal proportions, and the weight was 135.1 kg (+2.1 SD). He was sexually fully mature and had macroorchidism. The plasma concentrations of testosterone (2015 ng/dL), 5 alpha-dihydrotestosterone (125 ng/dL), and androstenedione (335 ng/dL) were elevated; estradiol and estrone levels were less than 7 pg/mL. Plasma FSH and LH concentrations were more than 3 times the mean value. Plasma PRL was low; serum insulin-like growth factor I and GH-binding protein were normal. The bone age was 14 yr at a chronological age of 24 3/12 yr. Striking osteopenia was noted at the wrist. Bone mineral densitometric indexes of the lumbar spine (cancellous bone) and distal radius (cortical bone) were consistent with osteoporosis; the distal radius was -4.7 SD below the mean value for age- and sex-matched normal men; indexes of bone turnover were increased. Hyperinsulinemia, increased serum total and low density lipoprotein cholesterol, and triglycerides and decreased high density lipoprotein cholesterol were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Adaptive modification of oculomotor pursuit influences manual tracking responses.

We have addressed the question of whether adaptively modifying the oculomotor response to a visual pursuit stimulus has an influence on a related manual tracking response. Subjects used their unseen right hand to track targets moving at constant velocities while visually fixating a stationary LED. Manual tracking performance was compared before and after a 20 min period during which smooth pursuit eye movements alone were adaptively enhanced by adding 50% of the instantaneous eye position signal to target position. Compared with the preadaptation trials, hand gain was markedly increased during the postadaptation period. These results imply that the adaptation occurred at a level common to both motor systems, probably in CNS structures concerned with visual motion processing.

Adaptation, Physiological↗
PubMed1994

Amplification and overexpression of cyclin D1 in breast cancer detected by immunohistochemical staining.

Immunohistochemical staining with a monoclonal antibody against human cyclin D1 can be used to identify breast cancers that have an amplification of the q13 region of chromosome 11. In general, the intensity of staining is directly proportional to the degree of DNA amplification. In two unusual tumors, in which the CCND1 locus is highly amplified but staining is relatively weak, it appears that the DNA has undergone rearrangement and that the amplified/rearranged CCND1 allele may have reduced transcriptional activity. More significantly, the immunohistochemical technique identifies additional tumors in which the cyclin D1 gene is overexpressed with only marginal or undetectable increases in copy number, implying that other mechanisms can lead to deregulated expression. These results suggest that the frequency of overexpression is much higher than previously concluded from DNA-based analyses and that more than one-third of human breast cancers may contain excessive levels of cyclin D1. The technique we describe should facilitate the detection of this abnormality in a clinical setting and clarify its prognostic significance.

Alleles↗
PubMed1994

Real-time DNA binding measurements of the ETS1 recombinant oncoproteins reveal significant kinetic differences between the p42 and p51 isoforms.

The sequence-specific DNA binding of recombinant p42 and p51 ETS1 oncoprotein was examined quantitatively to determine whether the loss of the Exon VII phosphorylation domain in p42 ETS1 or the phosphorylation of expressed Exon VII in p51 ETS1 had an effect on DNA binding activity. The kinetics of sequence-specific DNA binding was measured using real-time changes in surface plasmon resonance with BIAcore (registered trademark, Pharmacia Biosensor) technology. The real-time binding of p42 and p51 ETS1 displayed significant differences in kinetic behavior. p51 ETS1 is characterized by a fast initial binding and conversion to a stable complex, whereas p42 ETS1 exhibits a slow initial binding and conversion to a stable complex. All of the p51 ETS1 DNA binding states are characterized by rapid turnover, whereas the p42 ETS1 DNA binding states are 4-20 times more stable. A model describing these kinetic steps is presented. Stoichiometric titrations of either p42 or p51 ETS1 with specific oligonucleotides show 1:1 complex formation. The DNA sequence specificity of the p42 and p51 ETS1 as determined by mutational analysis was similar. The in vitro phosphorylation of p51 ETS1 by CAM kinase II obliterates its binding to specific DNA, suggesting that the regulation of p51 ETS1 sequence-specific DNA binding occurs through phosphorylation by a calcium-dependent second messenger. The p42 ETS1 lacks this regulatory domain (Exon VII), and binding to its specific DNA sequence is not sensitive to calcium signaling.

Base Sequence↗
PubMed1994

Interstitial collagenase is required for angiogenesis in vitro.

Human umbilical vein endothelial cells (HUVECs) invade collagen gels and establish vascular-like structures within the gel following stimulation with phorbol esters. This process was quantitated by measuring release of radioactivity from gels composed of [3H]collagen. Collagen was steadily degraded over the period of several weeks by phorbol ester-treated cells while little collagenolysis by cells not receiving phorbol ester was noted. Examination of matrix metalloproteinases (MMPs) secreted by HUVECs revealed a prominent induction of interstitial collagenase. Production of the mature forms of gelatinase A was also stimulated, as was the secretion of gelatinase B. Stromelysin was not detected. Two inhibitors of MMPs, the naturally occurring tissue inhibitor of metalloproteinases (TIMP; 10 micrograms/ml) and the synthetic, peptide inhibitor BB-94 (1 microM) were both effective at blocking HUVEC-mediated collagen degradation. Morphological examination of control, PMA-treated HUVECs, as well as PMA-treated HUVECs receiving TIMP or BB-94, revealed that MMP inhibition resulted in a block to invasion and tubule formation within the collagen gels. Similar results for MMP expression and inhibition of tubule formation in vitro were obtained with human dermal microvascular endothelial cells. Examination of collagen proteolytic fragments revealed that both BB-94 and TIMP blocked cleavage of the alpha 1 and alpha 2 chains of type I collagen and the appearance of tropocollagen fragments A and B, demonstrating that the inhibitors were acting directly upon interstitial collagenase. Our results demonstrate that interstitial collagenase is required for angiogenesis in vitro.

Amino Acid Sequence↗