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Biomedical subjects

I Clark

Publications and source records attributed to I Clark.

At least 19 recordsLinked to original sources
PubMed2004

Ground-level solar spectral irradiance in Glasgow: an inter-comparison of two sites.

BACKGROUND: Solar spectral radiometry presents significant challenges to produce accurate and reproducible data. To investigate the reliability of the measurements, several inter-comparisons have been set up. Although these are useful, their main drawback is that equipment must be dismantled and transported to a common site and re-calibrated. METHODS: In this study, an inter-comparison has been performed of two spectroradiometers that are located 3 miles apart some 30 m above sea level. These two systems have operated using different calibration techniques. Data were compared on clear days, to minimise actual differences in ultraviolet irradiation. RESULTS: There were substantial differences at some individual wavelength points, but overall the mean difference of results at 5 nm intervals on an individual scan from the two systems agreed to within 11%. If the data were used to compute the erythemal irradiance, the differences were reduced to 4%. CONCLUSION: This study demonstrates both the limitations and the level of reliability that might be expected from these systems operating under careful scientific supervision.

Geography↗
PubMed2003

Response to different environmental stress conditions of industrial and laboratory Saccharomyces cerevisiae strains.

Two sets of Saccharomyces cerevisiae strains were compared for their physiological responses to different stress conditions. One group is composed of three strains adapted to controlled laboratory conditions (CEN.PK, LR88 and RS58), whereas the other consisted of five industrial strains (IND1101, SuperStart, LO24, LO41 and Azteca). Most industrial strains showed higher tolerance to heat shock and to an oxidative environment than laboratory strains. Excluding CEN.PK, a similar behavior was observed regarding ethanol production in high sugar concentrations (180 g/l glucose). Addition of acetate (10 g/l) or furfural (2 g/l), in concentrations similar to those found in sugar cane bagasse hydrolysates, decreased cell mass formation and growth rate in almost all strains. CEN.PK and SuperStart showed the highest sensitivity when grown in furfural-containing medium. Acetic acid treatment severely affected cell mass formation and reduced growth rate in all strains; CEN.PK and LO24 were the most resistant. The specific ethanol production rate was not affected by furfural addition. However, specific ethanol production rates decreased in response to acetic acid in four industrial strains, and increased in all laboratory strains and in LO24. No significant correlation was found between the stress tolerance of the strains tested and the transcript accumulation of genes selected by their involvement in the response to each of the stressful environments applied.

Acetic Acid↗
PubMed2002

Temozolomide and whole brain irradiation in melanoma metastatic to the brain: a phase II trial of the Cytokine Working Group.

PURPOSE: To evaluate the antitumor effects and toxicities of whole brain irradiation (WBI) with temozolomide (TMZ) administered by prolonged oral dosing in patients with melanoma metastatic to the brain. BACKGROUND: Patients with melanoma metastatic to the central nervous system (CNS) have an extremely poor prognosis and appear to benefit little from WBI. TMZ is an alkylating agent chemically similar to dacarbazine (DTIC) with good oral bioavailability and CNS penetration. TMZ has broad preclinical antitumor activity which in melanoma is comparable to that of DTIC. The combination of TMZ and WBI may provide enhanced antitumor activity against CNS metastasis from melanoma. PATIENTS AND METHODS: Patients with measurable CNS metastases with or without systemic disease were treated with WBI, 30 Gray over ten fractions (days 1-5 and 8-12). TMZ, 75 mg small middle dotm(2 small middle dot)day, was started on day 1, continued daily for 6 weeks and repeated every 10 weeks. RESULTS: Thirty-one patients were treated. There was one CNS complete response of 4.5 months and two CNS partial responses of 2 months and 7 months duration; the latter patient also had a 4-month complete remission of systemic metastases. Toxicities were limited to a single episode of grade 3 transaminase elevation and two episodes of grade 3 neutropenia, one complicated by fatal sepsis. The median progression-free interval for both CNS and extracranial sites was 2 months (range 1 week-11 months), and median survival 6 months (range 2-12 months). CONCLUSIONS: WBI has lower than expected activity in CNS metastasis of malignant melanoma. Although TMZ can be safely administered with WBI, the combination has limited anti-tumor activity.

Administration, Oral↗
PubMed2002

Protecting against promiscuity: the regulatory role of insulators.

Eukaryotic genomes contain transcriptional regulatory elements that alter promoter activity through long-range interactions. Many control elements show a broad range of promoter interactions, suggesting that these elements are capable of inappropriate transcription. The identification of a novel class of directing regulatory elements, called insulators, has provided clues into mechanisms used in eukaryotic genomes to maintain transcription fidelity. Insulators contribute to the organization of independent domains of gene function by restricting enhancer and silencer function. This review describes the properties of insulators and related elements that have been isolated from several eukaryotic genomes. Two classes of models of insulator function are considered. These models provide insights into possible mechanisms used by these diverse elements to provide regulatory autonomy.

Animals↗
PubMed2001

Salicylates, nitric oxide, malaria, and Reye's syndrome.

Reye's syndrome virtually disappeared from much of the world after the use of salicylate in febrile children was successfully discouraged. This severe sepsis-like disease was thought to be caused by a hypersensitivity to salicylates in children with mild viral infections, although no mechanism consistent with this proposal was ever established. Salicylate toxicity in African children has been noted to have many clinical features in common with severe falciparum malaria, including acidosis, altered consciousness, convulsions, and hypoglycaemia. Salicylates are widely available in various formulations in many African countries, and are commonly used for initial treatment of the symptoms that malaria shares with other diseases. There is now experimental evidence that salicylate increases and prolongs the activity of key elements along the signalling pathway through which interferon gamma generates inducible nitric oxide synthase (iNOS), and we have shown that iNOS is strongly expressed in fatal malaria and other acute fevers in African children. We further propose that, in areas where salicyaltes are still used to treat the symptoms of febrile illnesses in children, this mechanism could exacerbate potentially serious infectious diseases, including falciparum malaria. In contrast, the absence of salicylate use in children in some Pacific islands could contribute to the milder outcome of falciparum malaria than is observed in Africa. Widespread expression of iNOS has also been seen in the tissues of a patient with fatal clinically defined Reye's syndrome. This finding suggests that Reye's syndrome can be mediated through salicylate enhancement of iNOS expression, the initial trigger in this instance usually being a viral infection.

Africa↗
PubMed1999

NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase.

We have recently cloned and characterized a unique sodium bicarbonate cotransporter, NBC3, which unlike other members of the NBC family, is ethylisopropylamiloride (EIPA) inhibitable, DIDS insensitive, and electroneutral (A. Pushkin, N. Abuladze, I. Lee, D. Newman, J. Hwang, and I. Kurtz. J. Biol. Chem. 274: 16569-16575, 1999). In the present study, a specific polyclonal antipeptide COOH-terminal antibody, NBC3-C1, was generated and used to determine the pattern of NBC3 protein expression in rabbit kidney. A major band of approximately 200 kDa was detected on immunoblots of rabbit kidney. Immunocytochemistry of rabbit kidney frozen sections revealed specific staining of the apical membrane of intercalated cells in both the cortical and outer medullary collecting ducts. The pattern of NBC3 protein expression in the collecting duct was nearly identical to the same sections stained with an antibody against the vacuolar H+-ATPase 31-kDa subunit. In addition, the NBC3-C1 antibody coimmunoprecipitated the vacuolar H+-ATPase 31-kDa subunit. Functional studies in outer medullary collecting ducts (inner stripe) showed that type A intercalated cells have an apical Na+-dependent base transporter that is EIPA inhibitable and DIDS insensitive. The data suggest that NBC3 participates in H+/base transport in the collecting duct. The close association of NBC3 and the vacuolar H+-ATPase in type A intercalated cells suggests a potential structural/functional interaction between the two transporters.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1997

Reparametrization of autoregressive models with coefficients depending on covariables: application to EEG spectrum maturation.

To describe the spectral characteristics of the EGG development through autoregressive (AR) time series models it is necessary to perform regression analysis of the AR parameters with regards to the age of the subject. A major difficulty in this approach is the very complex nature of the admissible region of the AR coefficients, which impedes the straight use of regression techniques. The present paper overcomes this difficulty by first applying the Barndoff-Nielsen and Schou reparametrization of AR models, followed by Fisher's transformation and then carrying out age regression analysis of the transformed parameters. We apply this approach to real EEG data obtained from a normative sample of subjects in the age range from 5 to 95 years.

Adolescent↗
PubMed1997

UV protection by clothing: an intercomparison of measurements and methods.

In an attempt to reduce the incidence of skin cancer, cancer foundations have run educational campaigns which encourage the general population to limit their solar UVR exposures. An important part of these campaigns, in particular in Australia, but also more recently in Europe and the U.S., has been the adoption of protective measures such as sunscreens, hats, sunglasses and clothing. The protective properties of fabrics and clothing against ultraviolet radiation (UVR) have been known for some time, but recently there has been considerable interest in quantifying the degree of protection. This has been generated, in part, by the requirements for occupational protection for outdoor workers as well as the provision of UVR protection for the recreational market. The quantification of UVR protection has been laboratory based using in vitro test methods. Development of a standard test method has become an important part of the testing process, and this paper presents results from an intercomparison involving five independent testing laboratories. Agreement is good, in particular for samples with protection factors below 50. Technical difficulties and sources of errors associated with the measurements are discussed.

Australia↗
PubMed1996

Incorporation of the Arden Syntax within the reimplementation of a closed-loop decision support system.

The initial implementation of a clinical decision support system, although extremely successful and popular with users, suffered from response time and operational support difficulties. As part of the redesign of the system, which uses closed-loop rules to propose laboratory and other investigations, the decision was taken to move to Arden Syntax for the expression of such rules, although in some areas the current standard was felt to be either inadequate or inelegant. Such limitations have been overcome by the development of local extensions to the Arden Syntax, which are described and where appropriate proposed as possible enhancements of the standard. The use of common UNIX tools in the creation of a compiler which converts Arden Medical Logic Modules to M (MUMPS) code is also discussed.

Decision Making, Computer-Assisted↗
PubMed1995

Isotopomer study of lipogenesis in human hepatoma cells in culture: contribution of carbon and hydrogen atoms from glucose.

Recent developments in the application of stable isotopes and mass spectrometry have permitted the estimation of precursor enrichment and fractional synthesis of the product through mass isotopomer analysis. Thus, the application of isotopomer analysis in studies with 2H- and 13C-labeled glucose may potentially overcome the limitations of traditional methods which can only estimate the fractional use of carbon and hydrogen from glucose for lipogenesis. To illustrate this approach, isotope incorporation and mass isotopomer distribution were determined in fatty acids and cholesterol from a hepatoma cell line (Hep G2) grown in media containing specific (C1 or C6) 2H- or 13C-labeled glucose. Using the binomial model, the respective precursor enrichment, and fractional synthesis of palmitate, stearate and cholesterol were determined using mass isotopomer distribution analysis. In 1 week, 80% of palmitate, 65.5% of stearate, and 50% of cholesterol molecules in the cell extract were derived from de novo synthesis. Under serum-free condition, glucose contributed about 80% of the carbon of the newly synthesized lipids. Using the relative isotope yield of [1-13C] and [6-13C]glucose and a standard formula, the contribution of the pentose pathway to glucose catabolism was calculated to be 4.7%. Fractional syntheses of palmitate, stearate, and cholesterol determined using [1-2H]glucose agreed well with values determined using 13C-labeled glucose. After correcting for the contribution of deuterium label from the glycolytic pathway, the deuterium from [1-2H]glucose contributed 4.7% of the total reducing equivalents for lipogenesis. Unlike radioisotope studies, the stable isotope approach provides information from the perspective of the product and insight into the economy of acetyl units and reducing equivalents which were otherwise not available.

Carbon Isotopes↗
PubMed1995

Multiresolution decomposition of non-stationary EEG signals: a preliminary study.

Wavelet representation is a recent development in the analysis of non-stationary signals. Its possibilities for use in the description of time-frequency characteristics of both transients in spontaneous EEG and time-varying rhythms in event related brain activity are explored here. By way of illustration, multiresolution decompositions of a wide variety of EEG transients are carried out in this work, including spike-and-waves, single spikes, sharp waves, blink artifacts, frontal intermittent rhythmic delta activity (FIRDA) and paroxysmal delta activity. Also, the application of the wavelet representation to study related spectra perturbations is illustrated with data from psychophysical experiments on the perception of image motion. The results demonstrate the capabilities of the wavelet transform, as an alternative to the Fourier transform, for the representation and analysis of non-stationary EEG signals.

Artifacts↗
PubMed1995

Maximum a posteriori estimation of change points in the EEG.

A new approach for EEG segmentation is introduced. This is based on a methodology for optimal segmentation of non-stationary signals derived from the maximum a posteriori estimation principle. It is a model-based, not sequential approach that allows for segmentation at different resolution levels. The features of the methodology are illustrated by its application to EEG recordings containing several types of spectral changes due to normal and pathological variations of spontaneous brain rhythmic activities, as well as physiological artifacts.

Algorithms↗
PubMed1995

Immunoblotting in the diagnosis of culture negative endocarditis caused by streptococci and enterococci.

AIM: To improve the diagnosis of culture negative endocarditis by diagnosing cases due to streptococci and enterococci. METHODS: Serum samples were immunoblotted against extracts of the commonest streptococci and enterococci. They were selected from patients with a cardiac murmur, persistent pyrexia and at least three negative blood cultures. The presence of patterns of endocarditis species specific antigenic bands was measured and correlated with clinical outcome. RESULTS: Negative serology was found in 28 patients where the diagnosis of endocarditis was rejected or, if proved, staphylococcal, yeast, Gram negative, systemic lupus erythematosus, due to Q fever or Chlamydia psittaci or nonbacterial thrombotic. Positive serology was found in 27 of the 34 patients where the response to antibiotics suggested streptococcal or enterococcal infection. In 22 of these there was objective evidence of endocarditis. Positive serology was also found in three of four further patients with vegetations at necropsy. CONCLUSION: The identification of patterns of antibody response on immunoblotting can be used to make a specific diagnosis of streptococcal or enterococcal endocarditis in the absence of positive blood cultures.

Antibodies, Bacterial↗
PubMed1994

Transient posterior localization of a kinesin fusion protein reflects anteroposterior polarity of the Drosophila oocyte.

BACKGROUND: During oogenesis in Drosophila, determinants that will dictate abdomen and germline formation are localized to the 'polar plasm' in the posterior of the oocyte. Assembly of the polar plasm involves the sequential localization of several messenger RNAs and proteins to the posterior of the oocyte, beginning with the localization of oskar mRNA and Staufen protein during stages 8 and 9 of oogenesis. The mechanism by which these two early components accumulate at the posterior is not known. We have investigated whether directed transport along microtubules could be used to accomplish this localization. RESULTS: We have made a fusion protein composed of the bacterial beta-galactosidase enzyme as a reporter, joined to part of the plus-end-directed microtubule motor, kinesin, and have found that the fusion protein transiently localizes to the posterior of the oocyte during stages 8 and 9 of oogenesis. Treatment with the microtubule-depolymerizing agent colchicine prevents both the localization of the fusion protein and the posterior transport of oskar mRNA and Staufen protein. Furthermore, the fusion protein localizes normally in oocytes mutant for either oskar and staufen, but not in other mutants in which oskar mRNA and Staufen protein are mislocalized. CONCLUSIONS: Association with a plus-end-directed microtubule motor can promote posterior localization of a reporter protein during oogenesis. The genetic requirements for this localization and its sensitivity to colchicine, both of which are shared with the posterior transport of oskar mRNA and Staufen protein, suggest that similar mechanism may function in both processes.

Adenosine Triphosphate↗
PubMed1994

Cerebrospinal fluid concentrations of the complement MAC inhibitor CD59 in multiple sclerosis and patients with other neurological disorders.

Rodent oligodendrocytes have a unique susceptibility among glia to the lytic effects of complement, due in part to a deficiency in CD59 (protectin), a key surface inhibitor of the complement membrane attack complex (MAC). The possibility that shedding of CD59 by human oligodendrocytes contributes to complement-mediated oligodendrocyte injury in inflammatory demyelinating disease has been investigated by estimating levels of CD59 in cerebrospinal fluid samples from 12 patients with demyelinating disease of the central nervous system and 13 with other neurological diseases. No significant differences were found between patients and controls, or between patients with active and those with clinically inactive demyelinating disease, providing no direct support for oligodendrocyte shedding of CD59 in multiple sclerosis.

Antigens, CD↗
PubMed1994

High resolution quantitative EEG analysis.

High resolution spectral methods are explored as an alternative to broad band spectral parameters (BBSP) in quantitative EEG analysis. In a previous paper (Valdes et al. 1990b) regression equations ("Developmental surfaces") were introduced to characterize the age-frequency distribution of the mean and standard deviation of the log spectral EEG power in a normative sample. These normative surfaces allow the calculation of z transformed spectra for all derivations of the 10/20 system and z maps for each frequency. Clinical material is presented that illustrates how these procedures may pinpoint frequencies of abnormal brain activity and their topographic distribution, avoiding the frequency and spatial "smearing" that may occur using BBSP. The increased diagnostic accuracy of high resolution spectral methods is demonstrated by means of receiver operator characteristic (ROC) curve analysis. Procedures are introduced to avoid type I error inflation due to the use of more variables in this type of procedure.

Adolescent↗
PubMed1994

A global scale factor in brain topography.

In this paper statistical resampling techniques are used to support the presence of an equiangular first principal component in EEG log spectra and therefore the existence of a global scale factor in EEG recordings. the Log transformed spectra from a normal sample (n = 211, age 5-97) were analyzed. To reach this conclusion a method for estimating the scale factor is introduced. It is also shown that this factor remains constant in each individual for all derivations and frequencies and across functional states. The contribution of this scale factor to the overall variance of the normal EEG reaches 42% of the total variance of age corrected data. Part of the variance of the scale factor exhibits age dependency. Scale factor correction of EEG spectra data improves the diagnostic accuracy for detecting pathological EEG spectra from an almost random level (Area under the ROC curve = .6) to .84.

Adolescent↗