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PubMed2004

Oesophageal and gastric bile exposure after gastroduodenal surgery with Henley's interposition or a Roux-en-Y loop.

BACKGROUND: The degree which the various reconstruction techniques prevent bile reflux after gastroduodenal surgery has been poorly studied. METHODS: Bile exposure in the intestinal tract just proximal to the jejunal loop was measured with the Bilitec 2000 device for 24 h after gastroduodenal surgery in three groups of patients. Group 1 comprised 24 patients with a 60-cm Henley's loop after total gastrectomy. Group 2 included 31 patients with a 60-cm Roux-en-Y loop after total (22 patients) or subtotal (nine) gastrectomy. Group 3 contained 21 patients with a 60-cm Roux-en-Y loop anastomosed to the proximal duodenum as part of a duodenal switch operation for pathological transpyloric duodenogastric reflux. Bile exposure, measured as the percentage time with bile absorbance greater than 0.25, was classified as nil, within the range of a control population of healthy subjects, or pathological (above the 95th percentile for the control population). Reflux symptoms were scored and all patients had upper gastrointestinal endoscopy. RESULTS: Bile was detected in the intestine proximal to the loop in none of 24 patients in group 1, eight of 31 in group 2 and 12 of 21 in group 3 (P < 0.001). The mean reflux symptom score increased with the degree of bile exposure, and the proportion of patients with oesophagitis or gastritis correlated well with the extent of bile exposure (P < 0.001). CONCLUSION: A long Henley's loop was more effective in preventing bile reflux than a long Roux-en-Y loop. Bilitec data correlated well with the severity of reflux symptoms and the presence of mucosal lesions.

Adolescent↗
PubMed2005

Ultrasonic velocities, densities, viscosities, electrical conductivities, Raman spectra, and molecular dynamics simulations of aqueous solutions of Mg(OAc)2 and Mg(NO3)2: Hofmeister effects and ion pair formation.

The ultrasonic velocities, densities, viscosities, and electrical conductivities of aqueous solutions of magnesium nitrate and magnesium acetate have been measured from dilute to saturation concentrations at 0 < or = t/degrees C < or = 50. The temperature derivative of the isentropic compressibility, kappa(s), became zero at 2.28 and 2.90 mol kg(-1) for Mg(OAc)2 and Mg(NO3)2 solutions, respectively, at 25 degrees C. The total hydration numbers of the dissolved ions were estimated to be, respectively, 24.3 and 19.2 at these concentrations. Differences in kappa(s) for various M2+ salts, using the present and literature data, correlated with reported M2+-OH2 bond lengths and to a lesser extent with cationic charge densities (ionic radii). The influence of anions on kappa(s) appears to follow the Hofmeister series and also correlates approximately with the anionic charge density. Substantial differences between Mg(OAc)2(aq) and Mg(NO3)2(aq) occur with respect to their structural relaxation times (derived from compressibility and viscosity data) and their electrical conductivities. These differences were attributed to a much greater ion association in Mg(OAc)2 solutions. Raman spectra recorded at 28 degrees C confirmed the presence of various types of contact ion pairs including mono- and bidentate complexes in Mg(OAc)2(aq). In Mg(NO3)2(aq), only noncontact ion pairs appear to be formed even at high concentrations. The experimental results are supported by molecular dynamics simulations, which also reveal the much stronger tendency of OAc- compared to NO3- to associate with Mg2+ in aqueous solutions. The simulations also allow an evaluation of the ion-ion and ion-water radial distribution functions and cumulative sums and provide a molecular picture of ion hydration in Mg(OAc)2(aq) and Mg(NO3)2(aq) at varying concentrations.

Journal Article↗
PubMed2004

Quantitative high-throughput analysis of transcription factor binding specificities.

We present a general high-throughput approach to accurately quantify DNA-protein interactions, which can facilitate the identification of functional genetic polymorphisms. The method tested here on two structurally distinct transcription factors (TFs), NF-kappaB and OCT-1, comprises three steps: (i) optimized selection of DNA variants to be tested experimentally, which we show is superior to selecting variants at random; (ii) a quantitative protein-DNA binding assay using microarray and surface plasmon resonance technologies; (iii) prediction of binding affinity for all DNA variants in the consensus space using a statistical model based on principal coordinates analysis. For the protein-DNA binding assay, we identified a polyacrylamide/ester glass activation chemistry which formed exclusive covalent bonds with 5'-amino-modified DNA duplexes and hindered non-specific electrostatic attachment of DNA. Full accessibility of the DNA duplexes attached to polyacrylamide-modified slides was confirmed by the high degree of data correlation with the electromobility shift assay (correlation coefficient 93%). This approach offers the potential for high-throughput determination of TF binding profiles and predicting the effects of single nucleotide polymorphisms on TF binding affinity. New DNA binding data for OCT-1 are presented.

Acrylic Resins↗
PubMed2003

Microarrays bring new insights into understanding of breast cancer metastasis to bone.

Using a microarray approach, Kang and colleagues identified several genes involved in the generation of breast cancer metastasis in bone and demonstrated their roles in bone colonization in vivo. Their findings and interpretations are reviewed in the context of recent array studies that compared gene expression in primary tumors and metastases. RNA expression array results have already demonstrated value in predicting whether metastases will develop in patients. They have also shown that expression patterns are similar in primary tumors and metastases. The latter data have invited re-examination of long-held notions related to mechanisms of metastasis. While the arrays show promise for improving diagnostic capability in breast cancers, ascribing mechanistic interpretations to correlative data should be done with extreme caution. Kang and colleagues' paper in Cancer Cell elegantly reinforces the concepts that efficiency of the metastatic process is dependent on the coordinated expression of multiple genes and that the expression of metastasis-associated genes is sometimes dependent on the microenvironment in which cells find themselves.

Bone Neoplasms↗
PubMed1993

Longitudinal study of relations between human salivary antimicrobial proteins and measures of dental plaque accumulation and composition.

Many studies have attempted to relate levels of antimicrobial proteins in saliva to oral health; results have been inconsistent, and one reason might be inconsistency of measures of plaque and saliva within subjects. This study investigated associations between plaque and salivary variables in longitudinal data. Whole saliva, and 8-h plaque pooled from buccal first permanent molars, was obtained from 32 dental students on Tuesdays from 3:00-6:00 p.m. over 4 weeks. Salivary flow rate was determined, and samples were assayed for lysozyme, lactoferrin, total peroxidase, myeloperoxidase, OSCN-, sIgA and total protein. Colonies on mitis-salivarius agar were assigned to Streptococcus sanguis, Strep. mutans or Strep. salivarius on the basis of morphology, supplemented by the API Rapid Strep identification system. Consistency of values within subjects across weeks was evaluated by repeat-measures analysis of variance and intraclass correlation; data were transformed to reduce skewness. Pearson's r was used to determine associations between plaque and salivary variables. Significant intraclass correlations (alpha = 0.05) were found for all salivary variables except myeloperoxidase, and for total flora, total streptococci, Strep. sanguis and Strep. sanguis as a proportion of total streptococci. Significant Pearson correlations with Strep. sanguis as a proportion of total streptococci were found for total protein (r = -0.24), sIgA (r = -0.22), lactoferrin (r = -0.19) and OSCN- (r = 0.20) when data from all weeks were pooled (n = 128). Strep. sanguis proportions tended to be low in subjects with high values for salivary proteins; the range of proportions was wider in subjects with low salivary values. These findings suggest some consistency of weekly values for many plaque and salivary variables. They also support previous cross-sectional data which suggested that salivary antimicrobial proteins may have some effect on plaque composition. This study was made before recent revisions in streptococcal taxonomy, and further research is needed to clarify interactions of salivary proteins with currently defined species.

Bacteria↗
PubMed1999

GEECAT and GEEGOR: computer programs for the analysis of correlated categorical response data.

GEECAT and GEEGOR are two user-friendly SAS macros for the analysis of clustered, correlated categorical response data. Both programs implement methodology which extend the generalized estimating equation (GEE) approach of Liang and Zeger (Biometrika 73 (1986) 13-22). GEECAT and GEEGOR both use a first set of estimating equations to model the marginal response. With GEECAT, either correlated nominal or ordered categorical response data can be analyzed. The program GEEGOR employs a second set of estimating equations to model the association of ordered categorical responses within a cluster using the global odds ratio as a measure of association. The programs run on both mainframe computers and microcomputers. Examples are provided to illustrate the features of both programs.

Antirheumatic Agents↗
PubMed2005

Simple strategies for reducing sample loads in in vitro metabolic stability high-throughput screening experiments: a comparison between traditional, two-time-point and pooled sample analyses.

Higher-throughput ADME programs in early drug discovery are becoming common throughout the pharmaceutical industry as companies strive to reduce their compound attrition in later-stage development. Many of the ADME assays developed into higher-throughput formats rely on LC/MS analyses. Since the biological aspects of the assay are amenable to parallel processes using dense plate formats, the number of samples generated from these assays produce a large analysis load for serial LC/MS. Presented in this report are two novel strategies, including a sample pooling method and a two time-point method, that could be used in drug discovery to reduce the number of samples generated during multiple time-point in-vitro ADME assays. One hundred and sixty-three compounds were subjected to human microsomal incubations with full time-point method samples taken at t = 0, 5, 15, 30, and 45 min. The ER data correlation (R(2)) between the full time-point method and the pooling method and two time-point methods were 0.98 and 0.97, respectively. Both methods have the potential to: 1. produce data of similar quality to traditional high throughput ADME assays, 2. be easily implemented, 3. shorten analytical run times, and 4. be reproducible and robust.

Algorithms↗
PubMed2005

Discriminating between point and non-point sources of atrazine contamination of a sandy aquifer.

This study analyses the sources of atrazine contamination in the Brusselian sandy aquifer of central Belgium. Atrazine has in the past been used for both agricultural and non-agricultural applications, but it is difficult to distinguish the contamination originating from these two sources. The spatial and temporal covariance of atrazine concentrations was studied by fitting semi-variogram models to monitoring data. Correlation ranges were found to be 600 m and 600-700 days, respectively. The results were used to apply a declustering algorithm before examining the distribution of atrazine concentrations measured in groundwater. Monitoring data appeared to follow a pseudo-lognormal distribution, as a lognormality test was negative. An inflexion point on the cumulative density function was thought to indicate the two different pollution processes, i.e., agricultural and non-agricultural contamination sources. A non-parametric one-way analysis of variance suggested that the vast majority of atrazine in groundwater was from non-agricultural, point sources. This was supported by the strong relationship between mean concentrations and land use, whilst other environmental variables, such as soil organic matter or groundwater depth, produced less meaningful results.

Analysis of Variance↗
PubMed2006

Clinical assessment of pathological personality traits.

OBJECTIVE: Research has raised questions about the ability of clinicians to make reliable diagnostic judgments about personality. The aim of this study was to assess the reliability and validity of the dimensional diagnosis of pathological personality traits with the Shedler-Westen Assessment Procedure-200 (SWAP-200) Q sort. METHOD: Two clinician/judges independently described 24 outpatients using the SWAP-200, based on a systematic clinical interview. Treating clinicians described the patients using the SWAP-200 based on their knowledge of the patients over the course of treatment while they were blind to interview data. RESULTS: Interrater reliability was high. Convergent and discriminant validity between interviewers and clinicians was also strong. A procedure recently developed for providing precise estimates of construct validity with contrast analysis applied to correlational data documented strong evidence of validity. CONCLUSIONS: Clinicians and independent interviewers can reliably assess complex personality traits associated with personality pathology using the SWAP-200.

Adult↗
PubMed2000

Combined magnetic resonance imaging- and positron emission tomography-guided stereotactic biopsy in brainstem mass lesions: diagnostic yield in a series of 30 patients.

OBJECT: In the management of brainstem lesions, the place of stereotactic biopsy sampling remains debatable. The authors compared the results of magnetic resonance (MR) imaging, positron emission tomography (PET) scanning, and histological studies obtained in 30 patients who underwent MR imaging- and PET-guided stereotactic biopsy procedures for a brainstem mass lesion. METHODS: Between July 1991 and December 1998, 30 patients harboring brainstem mass lesions underwent a stereotactic procedure in which combined MR imaging and PET scanning guidance were used. Positron emission tomography scanning was performed using [18F]fluorodeoxyglucose in 16 patients, methionine in two patients, and both tracers in 12 patients. Definite diagnosis was established on histological examination of the biopsy samples. Interpretation of MR imaging findings only or PET findings only was in agreement with the histological diagnosis in 63% and 73% of cases, respectively. Magnetic resonance imaging and PET findings were concordant in 19 of the 30 cases; in those cases, imaging data correlated with histological findings in 79%. Treatment based on information derived from MR imaging was concordant with therapy based on histological findings in only 17 patients (57%). Combining MR imaging and PET scanning data, the concordance between the neuroimaging-based treatment and treatments based on histological findings increased to 19 patients (63%). In seven patients who underwent biopsy procedures with one PET-defined and one MR imaging-defined trajectory, at histological examination the PET-guided samples were more representative of the tumor's nature and grade than the MR imaging-guided samples in four cases (57%). In 18 patients PET scanning was used to define a biopsy target and provided a diagnostic yield in 100% of the cases. CONCLUSIONS: Although the use of combined PET and MR imaging improves radiological interpretation of a mass lesion in the brainstem, it does not accurately replace histological diagnosis that is provided by a stereotactically obtained biopsy sample. Combining information provided by MR imaging and PET scanning in stereotactic conditions improves the accuracy of targeting and the diagnostic yield of the biopsy sample; an MR imaging- and PET-guided stereotactic biopsy procedure is a safe and efficient modality for the management of mass lesions of the brainstem.

Adolescent↗
PubMed1995

Alcohol dehydrogenase of class I: kiwi liver enzyme, parallel evolution in separate vertebrate lines, and correlation with 12S rRNA patterns.

Alcohol dehydrogenase class I from kiwi liver has been purified, analyzed, and compared with that of other alcohol dehydrogenases. The results show that several avian and mammalian forms of the enzyme exhibit parallel evolutionary patterns in two independent lineages of a single protein, establishing a pattern in common. Furthermore, the data correlate the enzyme evolutionary pattern with that of 12S rRNA. Biologically, the patterns complement those on ratite and other avian relationships. Functionally, the enzyme has a low Km with ethanol and a branched-chain residue at position 141, like the mammalian enzymes but in contrast to the other characterized ratite enzyme (with Ala-141 and a higher Km). This pattern of natural variability suggests a frequent but not fully complete correlation between a large residue size at position 141 and tight ethanol binding.

Alcohol Dehydrogenase↗
PubMed1990

[Length of the kidney and length of the foot. Correlative study during the fetal period].

The renal length growth was studied in 240 specimens taken from 120 staged human fetuses (74 males and 46 females). The gestational age of the fetuses ranged between 10 and 36 weeks postconception. The kidneys were measured for greatest length and the data correlated to fetal foot length by using the allometric method (Y = bXk). Equations and growth curves for males, females and whole sample are presented. The renal length grows with greater velocity in early gestation. These was no growth difference between left and right kidneys. During the third trimester, males fetuses presented renal length significantly greater than females. This study has practical utility in the quantitative determination of renal anomalies.

Age Factors↗
PubMed2003

Reference values for second trimester fetal and neonatal organ weights and measurements.

To establish accurate reference ranges for the entire second trimester, we documented organ weights, body weight, and linear measurements for 597 fetuses and neonates with gestational ages ranging from 12 to 26 wk. We determined the mean and standard deviation for weights and measurements at each week of gestation using the StatView trade mark SE + Graphics statistical program. The analyses revealed a linear correlation between the gestational age and, respectively, the toe-heel length, crown-rump length, and crown-heel length. Body and organ weights increase at varying rates throughout the second trimester. The data correlate well with weights and measurements previously published for the latter half of the second trimester, and extend these reference ranges to encompass the entire second trimester.

Crown-Rump Length↗
PubMed1999

CT assessment of cerebral perfusion: experimental validation and initial clinical experience.

PURPOSE: To validate a dynamic single-section computed tomographic (CT) method to measure cerebral blood volume (CBV) and cerebral blood flow (CBF) by using a noncarotid artery as the input and to demonstrate the feasibility of this method in a pilot series of patients. MATERIALS AND METHODS: Twelve dynamic contrast material-enhanced CT studies were performed in beagles. CBV, CBF, and mean transit time (MTT) values were calculated by using an internal carotid artery (ICA) and a noncarotid artery as the input artery to the brain. Patient studies with use of the radial artery as the input were performed (a) repetitively in two patients after subarachnoid hemorrhage, (b) in a patient with a symptomatic ICA occlusion before and after the intravenous injection of 1 g of acetazolamide, and (c) in a patient with a malignant brain tumor. RESULTS: Linear regression analyses revealed highly significant correlations (P < .001) between CBV (r, 0.98; slope, 0.96), CBF (r, 0.89; slope, 0.87), and MTT (r, 0.80; slope, 0.76) values calculated with the ICA and the noncarotid inputs. The CT-derived patient data correlated well with ancillary clinical and neuroradiologic findings. CONCLUSION: Dynamic single-section CT scanning to measure CBV and CBF on the basis of a noncarotid input is a highly accessible and cost-effective blood flow measurement technique.

Animals↗
PubMed2000

Inhibition of the mitogen activated protein kinase pathway potentiates radiation-induced cell killing via cell cycle arrest at the G2/M transition and independently of increased signaling by the JNK/c-Jun pathway.

The ability of low dose ionizing radiation (2 Gy) to modulate the activities of the mitogen activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK1) cascades in human monocytic leukemia (U937/pREP4) cells and in cells over-expressing dominant negative c-Jun (TAM67) (U937/TAM67) was investigated. Radiation exposure caused prolonged ( approximately 1 h) MAPK activations in U937 cells. In contrast, low dose irradiation weakly modulated JNK1 activity in these cells. Inhibition of the MAPK pathway by use of the specific MEK1/2 inhibitor (10 microM PD98059) in both U937/pREP4 and U937/TAM67 cells prior to radiation exposure permitted strong prolonged radiation-induced activations of JNK1. Expression of TAM67 decreased the ability of radiation to cause apoptosis compared to control transfected cells. However, combined MEK1/2 inhibition and radiation exposure in both cell types caused a large decrease in suspension culture growth and a large increase in apoptosis, when compared to either treatment alone. Reduced proliferation after combined irradiation and PD98059 treatment in both cell types correlated with prolonged cell cycle arrest in G2/M phase. Prolonged growth arrest was abolished when MEK1/2 inhibitor was removed 6 h following irradiation, which was associated with a reduction in apoptosis. The ability of MEK1/2 inhibition to cause prolonged G2/M growth arrest was reduced in U937 cells stably transfected with a p21Cip-1/WAF1 antisense construct (U937/p21AS). This data correlated with an enhancement of radiation-induced apoptosis and a reduced ability of MEK1/2 inhibition to potentiate apoptosis. Collectively our data demonstrate that inhibition of MEK1/2 function increases the radiation sensitivity of U937 cells, independently of c-Jun function, and decreases the ability of these cells to recover from the radiation-induced G2/M cell cycle checkpoint arrest. In addition, our data also demonstrate that the ability of MEK1/2 inhibition to potentiate radiation-induced cell death in U937 cells in part requires an ability of cells to express low levels of p21Cip-1/WAF1.

Apoptosis↗
PubMed1987

Transformation modes in computerized human thalamic brain mapping.

An exact transfer of data intraoperatively gathered in thalamic nuclei to an anatomical atlas requires an efficient mathematical transformation mode. Three different kinds of transformation modes were analyzed: First, the AC PC distance was used as a parameter to correlate data with the atlas coordinate system. Second, the influence of the patients 3rd ventricle widths on the transformation procedure. Third, a transformation mode was performed based on "noise"-data, registered when the electrode penetrated patient's thalamus. This method was also used to combine the atlas and CT images.

Brain Mapping↗
PubMed2005

Identification of genes involved in Ca2+ ionophore A23187-mediated apoptosis and demonstration of a high susceptibility for transcriptional repression of cell cycle genes in B lymphoblasts from a patient with Scott syndrome.

BACKGROUND: In contrast to other agents able to induce apoptosis of cultured cells, Ca2+ ionophore A23187 was shown to elicit direct activation of intracellular signal(s). The phenotype of the cells derived from patients having the hemorrhagic disease Scott syndrome, is associated with an abnormally high proportion of apoptotic cells, both in basal culture medium and upon addition of low ionophore concentrations in long-term cultures. These features are presumably related to the mutation also responsible for the defective procoagulant plasma membrane remodeling. We analyzed the specific transcriptional re-programming induced by A23187 to get insights into the effect of this agent on gene expression and a defective gene regulation in Scott cells. RESULTS: The changes in gene expression upon 48 hours treatment with 200 nM A23187 were measured in Scott B lymphoblasts compared to B lymphoblasts derived from the patient's daughter or unrelated individuals using Affymetrix microarrays. In a similar manner in all of the B cell lines, results showed up-regulation of 55 genes, out of 12,000 represented sequences, involved in various pathways of the cell metabolism. In contrast, a group of 54 down-regulated genes, coding for histones and proteins involved in the cell cycle progression, was more significantly repressed in Scott B lymphoblasts than in the other cell lines. These data correlated with the alterations of the cell cycle phases in treated cells and suggested that the potent effect of A23187 in Scott B lymphoblasts may be the consequence of the underlying molecular defect. CONCLUSION: The data illustrate that the ionophore A23187 exerts its pro-apoptotic effect by promoting a complex pattern of genetic changes. These results also suggest that a subset of genes participating in various steps of the cell cycle progress can be transcriptionally regulated in a coordinated fashion. Furthermore, this research brings a new insight into the defect in cultured Scott B lymphoblasts, leading to hypothesize that a mutated gene plays a role not only in membrane remodeling but also in signal transduction pathway(s) leading to altered transcriptional regulation of cell cycle genes.

Apoptosis↗
PubMed2006

Two-dimensional correlation study of uniaxially drawn poly(ethylene terephthalate) films by using attenuated total reflection based dynamic compression modulation step-scan fourier transform infrared in combination with spectral simulation analysis by density functional theory.

Attenuated total reflection (ATR) based dynamic compression modulation two-dimensional (2D) correlation studies of uniaxially drawn poly(ethylene terephthalate) (PET) films have been performed in combination with spectral simulation analysis by density functional theory (DFT). The dynamic 2D infrared (IR) correlation spectra in the region of the CCO stretching mode vibrations show four distinct correlation peaks located around 1290, 1265, 1248, and 1234 cm(-1). These bands can be clearly assigned to the combination bands or coupling modes of the CH in-plane bend of the benzene ring or the CH(2) deformation of the ethylene glycol unit, as well as CCO stretching vibrations, which are gauche conformer's characteristic bands, by DFT analysis. The sequential analysis of 2D correlation data shows that, upon applying the dynamic compression, the response of the side chain regions (ester groups) occurs first, followed by that of the backbone regions (benzene rings). The ATR based dynamic compression modulation 2D correlation spectroscopy in combination with DFT analysis can be a powerful tool for various polymer characterizations.

Algorithms↗