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Biomedical subjects

C E Martin

Publications and source records attributed to C E Martin.

At least 19 recordsLinked to original sources
PubMed1992

Specificity of unsaturated fatty acid-regulated expression of the Saccharomyces cerevisiae OLE1 gene.

The Saccharomyces cerevisiae OLE1 gene encodes the delta-9 fatty acid desaturase, an enzyme which forms the monounsaturated palmitoleic (16:1) and oleic (18:1) fatty acids from palmitoyl (16:0) or stearoyl (18:0) CoA. Previous studies demonstrated that OLE1 mRNA levels and desaturase enzyme activity are repressed when either 16:1 delta-9 and 18:1 delta-9 are added to the growth medium (1). The polyunsaturate, linoleic acid (18:2, delta-9,12), which is not a product of the enzyme, is also a strong repressor. The specificity of the OLE1 transcriptional regulatory sensor was examined by testing the response of OLE1 promoter-lacZ fusion reporter genes to fatty acids that differ in chain length, degree of unsaturation and double bond positions. Monounsaturated and polyunsaturated fatty acids that contain a delta-9 double bond are strong repressors of reporter gene activity and native OLE1 mRNA levels. Monounsaturated fatty acids containing double bonds in the delta-10, delta-11, or delta-5 positions showed no repression of reporter enzyme levels although they were rapidly incorporated into membrane lipids and some supported growth of an OLE1 gene disrupted strain. Although 17:1 delta-10 does not repress OLE1 transcription, lipid analysis showed that it replaces almost all of the endogenous 16:1 delta-9 and 18:1 delta-9 in cellular lipids and OLE1 mRNA levels are strongly repressed. This suggests that additional systems regulate desaturase activity by post-transcriptional mechanisms that differ from the transcriptional sensor in their responses to specific fatty acids.

Fatty Acid Desaturases↗
PubMed1991

Triazolam fails to induce sleep in suprachiasmatic nucleus-lesioned rats.

Rats with suprachiasmatic nuclei (SCN) lesions did not show increased sleep after triazolam (TRZ) injections at any dose from 0.2 to 1.6 mg/kg, whereas 0.4 mg/kg TRZ given intact rats in the middle of their activity phase significantly increased sleep. Across SCN-lesioned and intact rats, the amount of sleep before and after TRZ 0.4 mg/kg was negatively correlated. SCN-lesioned rats did not have a circadian activity-dominant period and so did not accumulate a biological sleep debt. Their lack of response to TRZ may have resulted from the absence of a sleep debt compared to intact rats injected in the middle of their activity phase. These data support our hypothesis that the homeostatic process controlling sleep gates benzodiazepine hypnotic efficacy.

Animals↗
PubMed1991

Influence of running wheel activity on free-running sleep/wake and drinking circadian rhythms in mice.

Previous studies have indicated that manipulation of activity levels can modify characteristics of sleep/wake and activity rhythms. The generality of these observations was evaluated by simultaneously measuring drinking and sleep/wake rhythms while mice had free or no access to a running wheel in constant conditions (DD). Robust circadian rhythms in all parameters were observed in the "wheel free" (unrestricted) condition. When wheels were locked, the peak amplitude of the sleep/wake circadian rhythm decreased by approximately 50% without affecting the amplitude of the drinking rhythm. Total wake time decreased 11% per circadian day when wheels were locked with increases in both NREM and REM sleep. Whereas the amplitude of the drinking waveform was unaffected, wheel restriction caused an equivalent increase in period length (tau) for both rhythms. These results indicate that, unlike the generalized effects of activity on tau, activity restriction influences on rhythm amplitude do not generalize to all behavioral and/or physiological variables. This work also supports the notion that activity influences on sleep/wake rhythm amplitude reflect behavioral "masking" rather than a fundamental change in the direct coupling mechanisms of the biological clock.

Animals↗
PubMed1991

Activity feedback to the mammalian circadian pacemaker: influence on observed measures of rhythm period length.

In the mouse, activity is precisely timed by the circadian clock and is normally most intense in the early subjective night. Since vigorous activity (e.g., wheel running) is thought to induce phase shifts in rodents, the temporal placement of daily exercise/activity could be a determinant of observed circadian rhythm period. The relationship between spontaneous running-wheel activity and the circadian period of free-running rhythms was studied to assess this possibility. With ad libitum access to a running wheel, mice exhibited a free-running period (tau) of 23.43 +/- 0.08 hr (mean +/- SEM). When running wheels were locked, tau increased (23.88 +/- 0.04 hr, p less than 0.03), and restoration of ad libitum wheel running again produced a shorter period (tau = 23.56 +/- 0.06 hr, p less than 0.05). A survey of free-running activity patterns in a population of 100 mice revealed a significant correlation between the observed circadian period and the time of day in which spontaneous wheel running occurred (r = 0.7314, p less than 0.0001). Significantly shorter periods were observed when running was concentrated at the beginning of the subjective night (tau = 23.23 +/- 0.04), and longer periods were observed if mice ran late in the subjective night (tau = 23.89 +/- 0.04), F (1, 99) = 34.96, p less than 0.0001. It was previously believed that the period of the circadian clock was primarily responsive to externally imposed tonic or phasic events. Systematic influences of spontaneous exercise on tau demonstrate that physiological and/or behavioral determinants of circadian timekeeping exist as well.

Animals↗
PubMed1990

The OLE1 gene of Saccharomyces cerevisiae encodes the delta 9 fatty acid desaturase and can be functionally replaced by the rat stearoyl-CoA desaturase gene.

Strains of Saccharomyces cerevisiae bearing the ole1 mutation are defective in unsaturated fatty acid (UFA) synthesis and require UFAs for growth. A previously isolated yeast genomic fragment complementing the ole1 mutation has been sequenced and determined to encode the delta 9 fatty acid desaturase enzyme by comparison of primary amino acid sequence to the rat liver stearoyl-CoA desaturase. The OLE1 structural gene encodes a protein of 510 amino acids (251 hydrophobic) having an approximate molecular mass of 57.4 kDa. A 257-amino acid internal region of the yeast open reading frame aligns with and shows 36% identity and 60% similarity to the rat liver stearoyl-CoA desaturase protein. This comparison disclosed three short regions of high consecutive amino acid identity (greater than 70%) including one 11 of 12 perfect residue match. The predicted yeast enzyme contains at least four potential membrane-spanning regions and several shorter hydrophobic regions that align exactly with similar sequences in the rat liver protein. An ole1 gene-disrupted yeast strain was transformed with a yeast-rat chimeric gene consisting of the promoter region and N-terminal 27 codons of OLE1 fused to the rat desaturase coding sequence. Fusion gene transformants displayed near equivalent growth rates and modest lipid composition changes relative to wild type yeast control implying a significant conservation of delta 9 desaturase tertiary structure and efficient interaction between the rat desaturase and yeast cytochrome b5.

Amino Acid Sequence↗
PubMed1990

The nursing shortage: dynamics and solutions. A response from an educational perspective.

The dynamics underlying the current shortage of nurses are complex and embedded in a historical heritage of relative deprivation in terms of status, decision making, and resource allocation. Within this context the work of nurses has been largely invisible and lightly regarded. Challenging the status quo and proactively striving to create opportunities that empower nurses for greater risk taking, flexibility, and tolerance for differences will enhance nursing. Nursing education has a unique responsibility to provide socialization experiences that promote collegiality and self-confidence. Educational opportunities need to be planned to attract potential students who are currently underrepresented in nursing. The future of nursing is unlimited in its potential for nurses themselves and the people for whom we care, provided the professional maturity that supports full collegial partnership in the delivery of health care is achieved.

Curriculum↗
PubMed1989

Isolation and characterization of OLE1, a gene affecting fatty acid desaturation from Saccharomyces cerevisiae.

The unsaturated fatty acid (ufa) requiring ole1 mutant of Saccharomyces cerevisiae appears to produce a defective delta-9 fatty acid desaturase. This enzyme catalyzes double bond formation between carbons 9 and 10 of palmitoyl and stearoyl coenzyme A. A DNA fragment isolated by complementation of an ole1 strain repairs the ufa requirement in mutant cells. Genetic analysis of the cloned DNA fragment indicates that it is allelic to the OLE1 gene. Disruption of a single copy of the wild type gene in a diploid strain produces both wild type and nonreverting ufa-requiring haploid progeny upon sporulation. Membrane lipids of the disrupted haploid strains contain only ufas supplied in the growth medium. The recovery of activity in both wild type and disrupted segregants was examined after removal of ufas from the growth medium. Following ufa deprivation disruptant cells grew normally for about three generations and then at a slower rate for at least 0.6 generations. During that time cellular ufas dropped from 63 to 7.3 mol % of the total fatty acids. No production of the 16:1 and 18:1 products of the desaturase was observed in disruptant cells, whereas desaturation in wild type control cells was evident 2 h after deprivation. These results indicate that 1) the OLE1 gene is essential for production of monounsaturated fatty acids and is probably the structural gene for the delta-9 desaturase enzyme. 2) A large part of membrane ufas present under normal culture conditions are not essential for growth and cell division.

DNA, Fungal↗
PubMed1989

Nutritional regulation of yeast delta-9 fatty acid desaturase activity.

The addition of unsaturated fatty acids to cultures of Saccharomyces cerevisiae significantly altered the microsomal lipid composition. Supplementation with either of the naturally occurring palmitoleic (16:1) or oleic (18:1) acids caused increased levels in membrane phospholipids and reduced levels of the complementary acid. Growth in the presence of equimolar quantities of 16:1 and 18:1 acids, however, produced a fatty acid composition similar to that found in unsupplemented cell membranes. Linoleic acid (18:2) was not found in S. cerevisiae grown under normal conditions. It was preferentially internalized and incorporated into microsomes, however, at levels exceeding 50% of the total fatty acid species. This resulted in an almost total loss of 16:1 and a reduction of 18:1 to 25% of its normal level. The delta-9 fatty acid desaturase, a microsomal enzyme that forms 16:1 and 18:1 from saturated acyl coenzyme A precursors, was affected by the presence of exogenous fatty acids. Enzyme activity toward the 16:0 coenzyme A substrate was elevated in microsomes from saturated-fatty-acid-supplemented cultures and sharply repressed following the addition of unsaturated fatty acids, including 18:2. Northern (RNA blot) and slot-blot analyses of mRNA encoded by the OLE1 gene, which appears to be the structural gene for the delta-9 desaturase, indicated that it was sharply reduced in unsaturated-fatty-acid-fed cells. These data suggest that a significant part of the regulation involves modulation of available transcripts.

Blotting, Northern↗
PubMed1989

Adult support and the exploratory behavior of children with learning disabilities.

Low- and moderate-exploratory children with learning disabilities engaged in exploratory behavior independently and with an adult who communicated support in one of two nonintrusive ways. Consistent with a developmental motivation perspective, low- and moderate-exploratory children showed higher levels of exploration under both kinds of supportive conditions.

Child↗
PubMed1989

Alternatives for students with life experiences: reconceptualizing nursing education.

A future that happens for nursing will be created only if visionary nurses provide the necessary leadership. The experienced student is potentially part of the solution to our need for professional nurses, in terms of both quantity and quality. There is an obvious connection between recognizing the needs and potentials of students with life experience and the ideals of the curriculum revolution. In fact, it is possible that the student with life experience could be considered one of the motivating forces that drives the curriculum revolution toward its eventual victory.

Age Factors↗
PubMed1987

The effect of vitreous humour on prostaglandin production by cultured rabbit chorioretinal fibroblasts.

Factors in vitreous humour which regulate prostaglandin production were investigated using cultured rabbit chorioretinal fibroblasts. These cells produced predominantly prostaglandin E2, 6-ketoprostaglandin F1 alpha, a compound likely to be a metabolite of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid. The synthesis of 6-ketoprostaglandin F1 alpha was nearly completely inhibited by the cyclooxygenase inhibitor aspirin and partially inhibited by 10(-6) M dexamethasone (49%) and 10(-5) M forskolin (68%). Addition of 10% rabbit vitreous humour to subconfluent cells maintained in Dulbecco's modified Eagle's medium plus 1% fetal bovine serum resulted in stimulation of 6-ketoprostaglandin F1 alpha production by as much as 246% as measured by radioimmunoassay. Chorioretinal fibroblasts labelled by [3H]arachidonic acid incorporation into cellular phospholipids synthesised greater amounts of all labelled arachidonic acid metabolites in response to vitreous humour. It was concluded, therefore, that there are factors present in vitreous humour of molecular weight above 10 kDa which are capable of stimulating cellular cyclooxygenase activity. Confluent cells also responded to a factor(s) present in vitreous humour. The fraction of less than 10 kDa inhibited 6-ketoprostaglandin F1 alpha production by 50% when used at a concentration of 10%. Furthermore, 6-ketoprostaglandin F1 alpha production in confluent cells (but not subconfluent cells) was inhibited to 40% of control levels by vitamin C at a concentration of 1 mg/100 ml. The latter result points to an inhibitory role for vitamin C in vitreous humour. We conclude, therefore, that vitreous humour contains factors important for the regulation of prostaglandin metabolism in the eye.

Animals↗
PubMed1985

Human anti-luteinizing hormone-releasing hormone antibodies in patients treated with synthetic luteinizing hormone-releasing hormone.

One hundred sixty-three patients who were given synthetic LH-RH therapeutically underwent monitoring of serum IgG anti-LH-RH antibodies. Five of the patients showed specific binding to antibodies. Development of anti-LH-RH antibodies was not limited to those patients with a congenital deficiency of LH-RH. Urticarial responses occurred in four patients, only one of whom had IgG antibodies. Patients who had IgG antibodies or an urticarial response underwent monitoring of their serum IgE anti-LH-RH antibodies, but none had a positive binding response. The refractory state which has been reported in patients in whom similar antibodies to LH-RH develop was not invariably observed among these patients.

Adult↗
PubMed1985

Taxol for the treatment of proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) results in retinal detachment and visual impairment due to fibroblastic proliferation in the vitreous and subsequent cellular contraction. The authors have used an in vitro model for PVR to evaluate the action of the antineoplastic drug, taxol, on chorioretinal fibroblast proliferation and contractility. Dose response curves obtained show taxol to be a potent inhibitor of both cellular events. Fifty percent inhibition of contraction and proliferation occurred at 2 X 10(-8)M and 3 X 10(-9)M, respectively. On the basis of this pharmacodynamic data, three dosage regimes were chosen to evaluate possible prevention of PVR in an animal model based on the intravitreal injection of cultured fibroblasts. These animals trials show that a single intravitreal dose of either 35 micrograms or 0.5 microgram taxol significantly reduces incidence and extent of PVR. The average grade of vitreoretinal traction at 28 days for 35 micrograms taxol and 250,000 cells was 0.4 (control 1.8); for 35 micrograms taxol and 700,000 cells, 1.0 (control 2.2); and for 0.5 microgram taxol and 250,000 cells, 1.0 (control 2.3). Delayed optic nerve damage was noted with the highest dose used, but a good therapeutic margin may exist. Long-term clinical histopathologic and electrophysiologic studies will be required. The authors conclude from these preliminary studies that taxol holds definite promise for the relief of traction retinal detachment and PVR.

Alkaloids↗
PubMed1984

Effect of cyclic AMP on cellular contractility and DNA synthesis in chorioretinal fibroblasts maintained in collagen matrices.

Dibutyryl cyclic AMP (db-cAMP), theophylline and forskolin were found to be potent inhibitors of DNA synthesis and cell contractility in chorioretinal fibroblasts maintained in 3-dimensional collagen matrices. Dose-response curves were constructed for the inhibitory action of these agents on both cellular parameters and their interrelationship examined by regression analysis. The results obtained indicate that these parameters were equally inhibited by cAMP with the exception of high concentrations of db-cAMP (greater than 10(-3) M) where a greater effect on DNA synthesis than cell contractility was observed which was attributed to additional inhibition of DNA synthesis by db-cAMP degradation products. It is proposed from the present results and those of other investigators that cAMP regulates non-transformed fibroblast proliferation and contraction through a common regulatory mechanism possibly involving cAMP-dependent protein kinases and calcium ions.

Animals↗