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Biomedical subjects

C Wilcox

Publications and source records attributed to C Wilcox.

At least 19 recordsLinked to original sources

Effects of amlodipine and valsartan on oxidative stress and plasma methylarginines in end-stage renal disease patients on hemodialysis.

Patients with end-stage renal disease (ESRD) receiving hemodialysis (HD) treatment have a markedly shortened life expectancy in large part owing to cardiovascular disease (CVD), not explained by established risk factors. We tested the hypothesis that therapy with valsartan, an angiotensin receptor blocker and amlodipine, an antioxidant calcium channel blocker will reduce oxidative stress and the plasma levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. We confirmed that compared with age- and gender-matched healthy controls, ESRD patients have excessive oxidative stress and arginine methylation as indexed by elevated plasma levels of oxidation products of lipids (13-hydroxyoctadecadienoic acid (13-HODE)), thiols (oxidized:reduced glutathione, oxidized glutathione (GSSG):GSH), proteins, and nucleic acids, and the methylation products ADMA and symmetric dimethylarginine (SDMA). We undertook a double blind, crossover study of equi-antihypertensive treatment with amlodipine and valsartan for 6 weeks each to test our hypothesis. Both treatments significantly reduced GSSG:GSH, 8-hydroxy 2-deoxyguanosine, ADMA, and SDMA levels and amlodipine reduced 13-HODE. We conclude that hypertensive patients with ESRD receiving HD have evidence of extensive oxidation of lipids, thiols, proteins, and nucleic acids and methylation of arginine that could contribute to CVD. Many of these changes can be reduced by short-term treatment with amlodipine and valsartan.

Adult↗

Cdc25 inhibition and cell cycle arrest by a synthetic thioalkyl vitamin K analogue.

A synthetic vitamin K analogue, 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone or compound 5 (Cpd 5), was found previously to be a potent inhibitor of tumor cell growth. We now demonstrate that Cpd 5 arrested cell cycle progression at both G1 and G2-M. Because of the potential arylating activity of Cpd 5, it might inhibit Cdc25 phosphatases, which contain a cysteine in the catalytic site. To test this hypothesis, we examined the inhibitory activity of Cpd 5 against several cell cycle-relevant protein tyrosine phosphatases and found that Cpd 5 was a potent, selective, and partially competitive inhibitor of Cdc25 phosphatases. Furthermore, Cpd 5 caused time-dependent, irreversible enzyme inhibition, consistent with arylation of the catalytic cysteine in Cdc25. Treatment of cells with Cpd 5 blocked dephosphorylation of the Cdc25C substrate, Cdc2, and its kinase activity. Cpd 5 enhanced tyrosine phosphorylation of both potent regulators of G1 transition, ie., Cdk2 and Cdk4, and decreased the phosphorylation of Rb, an endogenous substrate for Cdk4 kinase. Furthermore, close chemical analogues that lacked in vitro Cdc25 inhibitory activity failed to block cell cycle progression and Cdc2 kinase activity. Cpd 5 did not alter the levels of p53 or the endogenous cyclin-dependent kinase inhibitors, p21 and p16. Our results support the hypothesis that the disruption in cell cycle transition caused by Cpd 5 was attributable to intracellular Cdc25 inhibition. This novel thioalkyl K vitamin analogue could be useful for cell cycle control studies and may provide a valuable pharmacophore for the design of future therapeutics.

Cell Cycle↗

Involvement of rodent prefrontal cortex subregions in strategy switching.

The present study examined whether inactivation of the prelimbic-infralimbic areas or the dorsal anterior cingulate area impairs strategy switching in the cheeseboard task. After implantation of a cannula aimed at either the prelimbic-infralimbic or dorsal anterior cingulate areas, all rats were tested in a spatial and a visual-cued version of the task. Some of the rats received the spatial version first, followed by the visual-cued version. The procedure for the other rats was reversed. Infusions of 2% tetracaine into the prelimbic-infralimbic or dorsal anterior cingulate areas did not impair acquisition of the spatial or visual-cued versions. However, inactivation of the prelimbic-infralimbic areas, but not the dorsal anterior cingulate area, impaired learning when rats were switched from one version to the other. These findings suggest that the prelimbic-infralimbic areas are involved in switching to new behavior-guiding strategies.

Animals↗

Public opinion and policymaking in the states: the case of post-Roe abortion policy.

Whether public opinion should be expected to play a role in the shaping of abortion legislation in the states is a debatable question. Representation is a difficult task, especially if legislators receive mixed cues from the public, activists, and the political parties. In this study, we find that grass-roots activism and public opinion tend to match, and both are reflected in state abortion policy. In addition, more Pro-Life policies are found in states with a tradition of conservative policies in other areas, Republican majorities in the state legislature, more Catholic residents, and fewer women legislators. These patterns hold true for a composite index of abortion policies and for the specific policy area of government funding of abortions. Slightly different patterns occur for parental consent law, though these statutes also tend to reflect general preferences on abortion and interest group activity in a state.

Abortion, Induced↗

Is Bradburn's measure of psychological well-being fair to introverts? A study among 16- to 18-yr.-old students.

A sample of 242 students between the ages of 16 and 18 years, attending schools in the North East of England, completed the Bradburn Balanced Affect Scale together with the abbreviated form of the Revised Eysenck Personality Questionnaire. The findings show that scores on the Bradburn scale (indicating psychological well-being as assessed by balanced affect) are correlated significantly and positively with scores for Extraversion (.25), negatively with Neuroticism (.52) and nonsignificantly with Psychoticism. The implications of these findings are discussed for the assessment of psychological well-being among introverts.

Adolescent↗

Purkinje cell expression of a mutant allele of SCA1 in transgenic mice leads to disparate effects on motor behaviors, followed by a progressive cerebellar dysfunction and histological alterations.

Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurological disorder caused by the expansion of a CAG repeat encoding a polyglutamine tract. Work presented here describes the behavioral and neuropathological course seen in mutant SCA1 transgenic mice. Behavioral tests indicate that at 5 weeks of age mutant mice have an impaired performance on the rotating rod in the absence of deficits in balance and coordination. In contrast, these mutant SCA1 mice have an increased initial exploratory behavior. Thus, expression of the mutant SCA1 allele within cerebellar Purkinje cells has divergent effects on the motor behavior of juvenile animals: a compromise of rotating rod performance and a simultaneous enhancement of initial exploratory activity. With age, these animals develop incoordination with concomitant progressive Purkinje neuron dendritic and somatic atrophy but relatively little cell loss. Therefore, the eventual development of ataxia caused by the expression of a mutant SCA1 allele is not the result of cell death per se, but the result of cellular dysfunction and morphological alterations that occur before neuronal demise.

Alleles↗

Magnitude estimation scaling of annoyance in response to rock music: effects of sex and listeners' preference.

The present study parallels an earlier one Fucci, Petrosino, and Banks in 1994 concerned with sex and listeners' preference effects on magnitude estimation scaling of rock music. The difference between the two studies is that the subjects in 1994 were asked to scale "loudness" while the present subjects were asked to scale "annoyance." The prior results and those of the present study were different, i.e., the women's preference appeared influential in the magnitude estimation scaling of rock music previously but here the men's preference appeared influential. If subjects are instructed to judge the annoyance of an auditory signal, they may respond differently than if asked to judge its loudness. Judgments of annoyance appear to be more context dependent whereas loudness judgments may reflect a perceptual process more closely related to physical aspects of the signal.

Analysis of Variance↗

Magnitude estimation scaling of the loudness of a wide range of auditory stimuli.

The study of the perception of loudness lends itself well to the psychophysical scaling technique of magnitude estimation. This study was designed to extend the range of auditory stimuli used to study the magnitude estimation scaling of loudness. The five stimuli chosen were a 1000-Hz pure tone, narrow band noise (700-1300 Hz band width), broad band noise (100-10,000 Hz band width), rock music, and babble speech, i.e., speech in which meaning is not discernible because several individuals are talking at once. Subjects were 30 normal young women (M = 19 yr.). During the auditory magnitude-estimation task for each of the five stimuli, a subject was instructed to assign numbers to stimulus presented in a randomly ordered series of nine sensation levels (10, 20, 30, 40, 50, 60, 70, 80, and 90 dB SL). Multivariate analysis of variance for repeated measures indicated there were no significant differences in the numerical responses of the subjects for the five stimuli. A possible explanation for these results is the presence of an underlying stabilizing factor (internal scaling mechanism) that allows adults to scale loudness consistently irrespective of the type of auditory stimulus.

Acoustic Stimulation↗

Assessment of structure and function in progressive renal disease.

The incidence and prevalence rates of end-stage renal disease (ESRD) in the United States continue to increase. In 1995, the incidence rate was 262 per million population, with a point prevalence rate of 975 per million population. The exact number of individuals with abnormal renal function but not yet at end stage is difficult to assess. Crude estimates suggest that approximately 0.4% of the U.S. population has serum creatinine values greater than 2.0 mg/dl. In some sub-populations, such as African Americans, the estimate is + as high as 1.0%. The rate of progression, likewise, is difficult to assess. In general, renal manifestations of certain systemic diseases such as diabetes mellitus and systemic lupus erythematosus, and those with significant proteinuria (usually greater that 3.0 g/24 hr) seem to have a more rapid progressive course to end stage. If intervention is expected to be successful in halting or slowing down progression, accurate assessment of the early manifestations of renal disease, structure, and function need to be established. Currently accepted methods of assessment of renal disease include measurement of renal function such as serum creatinine and glomerular filtration rate, measurement of proteinuria, assessment of tubular function, glomerular sieving and permselectivity, radiologic imaging techniques, and evaluation of histo-morphometry. Interventions that have been shown to slow progression include control of hypertension, and treatment modalities that reduce proteinuria, such as, the use of angiotensin converting enzyme inhibitors. Further clinical and basic science studies are needed to accurately define the important predictors of progression, and interventions that are effective in slowing or halting progression.

Animals↗

Alteration of GABAA receptor function following gene transfer of the CLC-2 chloride channel.

The effect of GABAA receptor activation varies from inhibition to excitation depending on the state of the transmembrane anionic concentration gradient (delta anion). delta anion was genetically altered in cultured dorsal root ganglion neurons via adenoviral vector-mediated expression of ClC-2, a Cl- channel postulated to regulate the Cl- concentration in neurons in which GABAA receptor activation is predominantly inhibitory. ClC-2 expression was verified by the presence of the appropriate mRNA, protein, and membrane conductance. CIC-2 expression resulted in a large negative shift in the Cl- equilibrium potential (ECl) that attenuated the GABA-mediated membrane depolarization and prevented GABAA receptor-mediated action potentials. These results establish that gene transfer of transmembrane ion channels to neurons can be used to demonstrate their physiological function, and that delta anion can be genetically manipulated to alter the function of neuronal GABAA receptors in situ.

Adenoviridae↗

The effect of preference for three different types of music on magnitude estimation-scaling behavior in young adults.

The purpose of the present study was to assess the effect of preference for three different types of music on magnitude estimation scaling behavior in young adults. Three groups of college students, 10 who liked rock music, 10 who liked big band music, and 10 who liked classical music were tested. Subjects were instructed to assign numerical values to a random series of nine suprathreshold intensity levels of 10-sec, samples of rock music, big band music, and classical music. Analysis indicated that subjects who liked rock music scaled that stimulus differently from those subjects who liked big band and classical music. Subjects who liked big band music scaled that stimulus differently from those subjects who liked rock music and classical music. All subjects scaled classical music similarly regardless of their musical preferences. Results are discussed in reference to the literature concerned with personality and preference as well as spectrographic analyses of the three different types of music used in this study.

Adolescent↗

Prayer, church attendance, and personality revisited: a study among 16- to 19-yr.-old girls.

A sample of 236 16- to 19-yr.old female A level students studying in the north east of England completed the short form Revised Eysenck Personality Questionnaire together with indices of prayer and church attendance. The data support the view that psychoticism is correlated with self-reported church attendance (r = -.15) and self-reported prayer (r = -.15), while scores on neither extraversion nor neuroticism are correlated with these indices of religiosity.

Adolescent↗

Diagnosis of renal artery stenosis: feasibility of combining MR angiography, MR renography, and gadopentetate-based measurements of glomerular filtration rate.

OBJECTIVE: Our aim was to evaluate the feasibility of combining in a single test (1) structural evaluation of renal arteries with MR angiography, (2) functional evaluation of global glomerular filtration rates calculated on the basis of plasma disappearance of gadopentetate dimeglumine, and (3) renographic analysis of individual kidneys based on the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine. SUBJECTS AND METHODS: We used unenhanced MR angiography to measure patency of the renal arteries in 10 healthy volunteers and in 10 patients with renal artery stenosis. Calculations of global glomerular filtration rate were based on measurements of plasma disappearance of gadopentetate dimeglumine as shown by MR relaxometry. For renography with gadopentetate dimeglumine, we generated curves that showed changes in signal intensity in both kidneys over time; intrarenal kinetics were studied by measuring the time of arrival of gadopentetate dimeglumine in the cortex and outer medulla of the kidney. Conventional angiograms, measurements of global glomerular filtration rate based on plasma disappearance of 99mTc-DTPA, and 99mTc-DTPA renograms were used as reference standards. We compared the two different methods of determining global glomerular filtration rates by computing the correlation coefficient of the linear regression of rates derived from studies with gadopentetate dimeglumine versus rates derived from studies with 99mTc-DTPA. RESULTS: In all volunteers, renal arteries were well visualized, and global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine were normal. In nine of 10 patients, correlation was good between findings on MR angiograms and findings on conventional arteriograms. Finding were discordant in one patient because the patient moved during the MR angiography. For all six patients studied, correlation was good between measurements of global glomerular filtration rates based on plasma clearance of gadopentetate dimeglumine and those based on clearance of 99mTc-DTPA (r = 98%). CONCLUSION: Our results suggest the potential of magnetic resonance for a comprehensive approach for detection of renal artery stenosis. This novel approach provides structural evaluation of renal arteries with unenhanced MR angiography. MR renography is done and global glomerular filtration rates are determined by using MR relaxometry after injection of contrast material. Corticomedullary transit times can be determined on the basis of the dynamic changes in signal intensity that occur after administration of gadopentetate dimeglumine.

Adult↗

Gas-phase infrared spectroscopy for determination of double bond configuration of monounsaturated compounds.

Gas-phase Fourier-transform infrared spectra allow unambiguous determination of the configuration of the double bonds of long-chain unsaturated compounds bearing RCH=CHR' type bonds. Although the infrared absorption at 970-967 cm-1 has been used previously for the identification of trans bonds, the absorption at 3028-3011 cm-1 is conventionally considered to be incapable of distinguishing cis and trans isomers. In this paper, we present a large number of gas-phase spectra of monounsaturated long-chain acetates which demonstrate that an absorption, highly characteristic for the cis configuration, occurs at 3013-3011 cm-1, while trans compounds fail to show any bands in this region. However, if a double bond is present at the C-2 or C-3 carbon atoms, this cis=CH stretch absorption shows a hypsochromic shift to 3029-3028 and 3018-3017 cm-1, respectively. Similarly, if a cis double bond is present at the penultimate carbon atom, this band appears at 3022-3021 cm-1. All the spectra of trans alkenyl acetates showed the expected C-H wag absorption at 968-964 cm-1. In addition, the spectra of (E)-2-alkenyl acetates show a unique three-peak "finger-print" pattern which allows the identification of the position and configuration of this bond. Furthermore, by synthesizing and obtaining spectra of appropriate deuteriated compounds, we have proved that the 3013-3011 cm-1 band is representative of the C-H stretching vibration of cis compounds of RCH=CHR' type.

Alkenes↗

A mock disaster.

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Disaster Planning↗