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Morphological changes induced by extracellular matrix are correlated with maturation of rat small hepatocytes.

Small hepatocytes (SHs), which are known to be hepatic progenitor cells, were isolated from an adult rat liver. SHs in a colony sometimes change their shape from small to large and from flat to rising/piled-up. The aim of the present study is to clarify whether the alteration of cell shape is correlated with the maturation of SHs and whether extracellular matrix (ECM) can induce the morphological changes of SHs. We used liver-enriched transcription factors (LETFs) such as hepatocyte nuclear factor (HNF) 4 alpha, HNF6, CCAAT/enhancer binding proteins (C/EBP) alpha, and C/EBP beta, tryptophan 2,3-dioxygenase (TO), and serine dehydratase (SDH) as markers of hepatic maturation. To enrich the number of SH colonies, the colonies were isolated from dishes and replated. Replated colonies proliferated and the average number of cells per colony was about five times larger at day 9 than at day 1. When the cells were treated with laminin, type IV collagen, a mixture of laminin and type IV collagen, Matrigel or collagen gel (CG), only the cells treated with Matrigel dramatically changed their shape within several days and had reduced growth activity, whereas the cells treated with other ECM did not. HNF4 alpha, HNF6, C/EBP alpha, C/EBP beta, and TO were well expressed in the cells treated with Matrigel. Furthermore, addition of both glucagon and dexamethasone dramatically induced the expression of SDH mRNA and protein in the cells treated with Matrigel. In conclusion, morphological changes of SHs may be correlated with hepatic maturation and basement membrane (BM)-like structure may induce the morphological changes of SHs.

Animals↗

Immortalized rat whisker dermal papilla cells cooperate with mouse immature hair follicle buds to activate type IV procollagenases in collagen matrix coculture: correlation with ability to promote hair follicle development in nude mouse grafts.

An in vivo nude mouse graft model and an in vitro collagen matrix culture system were used to study interactions of immature hair follicle buds from newborn mice with clonally derived AdE1A-12S-immortalized rat whisker dermal papilla cell lines. Of the 19 available dermal papilla cell lines, four consistently supported good hair follicle development and hair growth in grafts. Seven cell lines were clearly negative in this assay, and the remaining eight cell lines yielded poor to moderate hair growth. As a correlate to in vivo extracellular matrix remodeling accompanying hair follicle development, type IV collagenase activity in the medium from cocultures of dermal papilla cells and hair follicle buds was analyzed by gelatin zymography. Hair follicle buds cultured alone secrete primarily the 92-kDa type IV procollagenase. Cocultivation of hair follicle buds with eight of the dermal papilla cell lines resulted in activation of this proenzyme and activation of the 72-kDa and 92-kDa type IV procollagenases produced by the dermal papilla cells. Seven of these eight dermal papilla cell lines support hair growth in the graft system. In the absence of dermal papilla cells, several growth factors induced activation of the 92-kDa procollagenase secreted by hair follicle buds cultured in serum-free medium: epidermal growth factor, transforming growth factor alpha, acidic fibroblast growth factor, and keratinocyte growth factor. The current working hypothesis is that a) hair follicle epithelial cells interact with dermal papilla cells in coculture by mutual induction of growth factors and cytokines that stimulate the release and activation of matrix remodeling proteases; and b) the ability of dermal papilla cells to interact with hair follicle epithelial cells in this way may be crucial for controlled dermal matrix remodelling during HF development.

Animals↗

Matrix metalloproteinases correlate with alveolar-capillary permeability alteration in lung ischemia-reperfusion injury.

BACKGROUND: Matrix metalloproteinases (MMPs) are able to degrade the endothelial basal lamina and increase vascular permeability. METHODS: In a porcine model of isolated-reperfused lung, we studied the alveolar-capillary permeability and the zymographic expression of MMP-9 and MMP-2 in the bronchoalveolar lavage fluid of lungs submitted ex vivo to ischemia in three preservation solutions [modified Euro-Collins (EC), low-potassium-dextran, modified-blood]. Twenty-two pigs were randomly divided into three groups according to the preservation solution used. One lung of each pig was rapidly reperfused and analyzed (control lung) although the other lung was reperfused and analyzed after 8 hr of ischemia (ischemic lung). RESULTS: Alveolar-capillary permeability, evaluated by the transferrin leak index, was increased after 8 hr of ischemia compared with controls in the three groups, but was significantly higher in the modified EC group. In the EC group, after 8 hr of ischemia, both proMMP-9 and MMP-9 increased significantly (8.8- and 22-fold, respectively) compared with controls and this increase correlated with the transferrin leak index. Neither proMMP-9 nor MMP-9 increased with the other two preservation solutions. The MMP-2 increase after ischemia was smaller and was also restricted to the EC group. CONCLUSION: MMP expression is enhanced during lung ischemia-reperfusion, especially in the presence of EC and this phenomenon correlates with the alteration of alveolar-capillary permeability.

Animals↗

Comparative analysis of genetic diversity among Indian populations of Scirpophaga incertulas by ISSR-PCR and RAPD-PCR.

Genetic variation between 28 Indian populations of the rice pest, Scirpophaga incertulas was evaluated using inter-simple sequence repeats (ISSR)-PCR assay. Nine SSR primers gave rise to 79 amplification products of which 67 were polymorphic. A dendrogram constructed from this data indicates that there is no geographical bias to the clustering and that gene flow between populations appears to be relatively unrestricted, substantiating our earlier conclusion based on the RAPD (random amplified polymorphic DNA) data. The dendrograms obtained using each of these marker systems were poorly correlated with each other as determined by Mantel's test for matrix correlation. Estimates of expected heterozygosity and marker index for each of these marker systems suggests that both these marker systems are equally efficient in determining polymorphisms. Matrix correlation analyses suggest that reliable estimates of genetic variation among the S. incertulas pest populations can be obtained by using RAPDs alone or in combination with ISSRs, but ISSRs alone cannot be used for this purpose.

Animals↗

Delay correlation subspace decomposition algorithm and its application in fMRI.

This paper reports a new delay subspace decomposition (DSD) algorithm. Instead of using the canonical zero-delay correlation matrix, the new DSD algorithm introduces a delay into the correlation matrix of the subspace decomposition to suppress noises in the data. The algorithm is applied to functional magnetic resonance imaging (fMRI) to detect the regions of focal activities in the brain. The efficiency is evaluated by comparing with independent component analysis and principal component analysis method of fMRI.

Algorithms↗

Technique for backward particle tracking in a flow field.

A numerical method to determine the history of particle paths is presented and its application for mixing quantification is illustrated. When more than one source exists in a flow field, the current technique can reveal the particle's identity found in any time and place in the field, by backward tracking its origin. Since the particle position at a preceding time is not known, the velocity vector is implicit. To resolve this uncertainty, a three-stage iterative procedure is developed and implemented. The current particle velocity is multiplied by the time increment and the product is used to estimate the previous time increment particle position. Two velocity matrices are generated on a mesh around the estimated position. The first matrix is the Eulerian velocity field interpolated on the mesh. The second matrix contains velocity vectors that point to the current particle position. A correlation matrix is calculated from the two velocity matrices in order to resolve the actual particle position in the previous time increment. Determination of the time increments' size is performed by checking the maximum of the correlation matrix. The new algorithm was validated using a numerical solution of the confined twin-jet flow at low Reynolds number. This flow performs a Hopf bifurcation at a Reynolds number of about 30, therefore chaotic trajectories might exist in the flow. First, the convergence of the backward particle path to the streamlines in steady flow was demonstrated. Convergence of the particle paths for various time increments was achieved also at the unsteady two-dimensional confined twin-jet flow. When the flow has more than one source, the proposed tracking method can be applied to generate complete and ordered particle source images in any desired position and time in the flow field. Maps of particle sources are used to visualize the flow patterns and the stretched interface between the two fluid sources. Those maps are demonstrated as a powerful tool for mixing quantification and can be implemented also for pollution source detection and many other fluid dynamics applications.

Journal Article↗

Modulation of growth factor responsiveness of murine mammary carcinoma cells by cell matrix interactions: correlation of cell proliferation and spreading.

We have examined the role of growth factors and extracellular matrix in the proliferation and cell adhesion of a murine mammary carcinoma, SP1, and a stable highly metastatic variant, SP1-3M. On fibronectin, both cell types proliferated strongly in response to basic fibroblast growth factor (bFGF) and platelet-derived growth factor BB (PDGF-BB) after culture for 24 h and 72 h. In contrast, on collagen type I, SP1 cells proliferated only weakly to PDGF-BB at either time, and SP1-3M cells showed a response to PDGF-BB only at 72 h. The proliferative response to bFGF was also consistently lower when the cells were cultured on collagen than on fibronectin. No significant proliferative responses were detected to epithelial growth factor (EGF), transforming growth factor-beta (TGF-beta), or estrogen on any substratum. The lack of responsiveness to PDGF-BB of cells cultured on collagen type I was not due to differences in numbers or affinity of PDGF receptors. We therefore examined the adhesion and spreading properties of SP1 and SP1-3M cells. Without exogenous growth factors, both cell lines adhered to fibronectin and laminin. SP1-3M cells did not bind to collagen type I, whereas SP1 cells did. Attachment to all three substrata was inhibited by anti-beta 1 integrin IgG, suggesting that the primary adhesion to these substrata is mediated by beta 1 integrins. SP1 and SP1-3M cells showed similar integrin patterns following immunoprecipitation by anti-beta 1 integrin IgG. bFGF stimulated increased adhesion and spreading of both SP1 and SP1-3M cells to collagen type I within 24 h, whereas PDGF-BB was less capable of this effect. Our results suggest that the proliferative response of SP1 and SP1-3M cells to PDGF-BB and bFGF is dependent on the extracellular matrix environment, and imply that modification of extracellular matrix and/or surface integrin receptors may regulate responsiveness to these growth factors in the SP1 tumor model.

Adenocarcinoma↗

Higher-order factor analysis of an instrument with dichotomous data.

This article reports the use of higher-order factor analysis to examine the underlying dimensions of an instrument designed to measure community acceptance of nurse practitioners/physician's assistants. The instrument consisted of both dichotomous and Likert scale items. Use of factor analysis with dichotomous data is controversial. Higher-order factor analysis provides a potential solution to this dilemma. Following initial factor analysis using maximum likelihood extraction with oblique rotation, the factor correlation matrix was factored to obtain second order factors. The second order factors were interpreted using the factor pattern matrix and examining correlations of individual survey items with the second order factors. This procedure provides additional factorial validity of the underlying uni- and multidimensional concepts related to acceptance of NPs and PAs in rural settings: knowledge, competence, access, and trust.

Attitude to Health↗

Longitudinal analysis of symptoms reported by patients with chronic fatigue syndrome.

PURPOSE: To determine the effect of chronic fatigue syndrome (CFS) illness duration and onset type on the likelihood of reporting a symptom during successive follow-up periods.METHODS: In 1997, a two-phase RDD survey in Wichita, Kansas, was conducted to estimate the prevalence of CFS. Phase I identified 56,154 respondents 18-69 years of age and screened for severe fatigue, extreme tiredness or exhaustion lasting for 1 month or longer. In phase II an equal number of fatigued (n = 7,176) and randomly selected non-fatigued subjects were asked about 8 CFS and 13 non-CFS symptoms, as well as the presence of specific medical and psychiatric conditions. Eligible respondents were clinically evaluated to establish CFS diagnosis. Phase II respondents were re-contacted at 12- (n = 4,331) and 24-months (n = 4,266) for additional follow-up and diagnosis. In this study we considered symptoms reported as being present most of the time during each successive observation period. Generalized estimating equations were used to model symptoms over time and to address study questions. Such a model accounts for correlations among repeated symptoms for each subject. We used an auto-regressive structure for the correlation matrix, assuming the correlations between each pair of repeated symptoms should decrease as the time between symptoms increased.RESULTS: There were 74 CFS patients who had been ill for 1 to 20 years (median = 6.3 years). Among these, 46 reported gradual and 28 reported sudden onset. Symptoms fluctuated over the course of illness. However, only stomach pain (non-CFS symptom) was more likely to be reported as duration of illness increased (p < 0.05). There was no association between onset type and the likelihood of reporting a symptom during an interview, except that chills and severe headaches were more likely to be reported by sudden cases.CONCLUSIONS: The likelihood of expressing CFS and non-CFS symptom "most of the time" is the same across years of illness. More analyses are warranted to consider expression of symptoms for >/=6 months and severe symptoms.

Journal Article↗

Cognitive interference is associated with neuronal marker N-acetyl aspartate in the anterior cingulate cortex: an in vivo (1)H-MRS study of the Stroop Color-Word task.

The neurobiology of cognitive interference is unknown. Previous brain imaging studies using the Stroop Color-Word (SCW) task indicate involvement of the cingulate cortex cognitive division. The present study examines interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectroscopy in the right and left anterior cingulate cortex (ACC), dorsolateral prefrontal cortex, orbitofrontal cortex and thalamus) and cognitive interference (as measured by the SCW task) in 15 normal subjects. The results show that brain chemistry depends on cognitive interference levels (high vs low). Reduction of NAA levels was demonstrated in the right ACC (ie, cognitive midsupracallosal division) of high interference subjects, as compared to the low interference group (P < 0.01, two-tailed t-test). Chemical-cognitive relationships were analyzed by calculating correlations between regional NAA levels and the SCW task scores. Cognitive interference was highly correlated with the right anterior cingulate NAA (r = 0.76, P < 0.001), and was unrelated to other studied regional NAA, including the left ACC (P < 0.025; comparing the difference between r values in the right and left ACC). The interrelationships between NAA across brain regions were examined using correlation analysis (square matrix correlation maps), which detected different connectivity patterns between the two groups. These findings provide evidence of ACC involvement in cognitive interference suggesting a possibility of neuronal reorganization in the physiological mechanism of interference (most likely due to genetically predetermined control of the number of neurons, dendrites and receptors, and their function). We conclude that spectroscopic brain mapping of NAA, the marker of neuronal density and function, to the SCW task measures differentiates between high and low interference in normal subjects. This neuroimaging/cognitive tool may be useful for documentation of interference in studying cognitive control mechanisms, and in diagnosis of neuropsychiatric disorders where dysfunction of cingulate cortex is expected.

Adult↗

Does participation in a pain course based on the International Association for the Study of Pain's curricula guidelines change student knowledge about pain?

BACKGROUND: The People in Pain course was set up as a joint initiative of the Departments of Occupational Therapy and Physiotherapy within the School of Health and Rehabilitation Sciences at The University of Queensland. It was instigated in response to the publication of Pain Curricula for Occupational Therapy and Physiotherapy by the International Association for the Study of Pain (IASP) in 1994 (1). The first year it was offered, the "People in Pain" course comprised 14 h of lecture content. It was then expanded to encompass 28 h of lectures and seminar involvement. OBJECTIVES: To evaluate the impact of participation in a university pain course that meets the IASP pain curricula guidelines to increase health professional students' knowledge about pain. METHODS: Students who participated in the People in Pain course over the first three years were invited to complete the Revised Pain Knowledge and Attitudes Questionnaire (R-PKAQ) pre- and postcourse. Data obtained from 22 students in the short course formed a pilot project, and data from 22 students in the longer version of the course were used in the present study. RESULTS: Examination of the correlation matrix indicated substantial correlations between all R-PKAQ subscales except physiological basis of pain and pharmacological management of pain. In both the pilot project during the first year of the course and the expanded course in the following two years, significant improvement was found in the students' knowledge on five of the six subscales of the R-PKAQ: physiological basis of pain, psychological factors of pain perception, assessment and measurement of pain, cognitive-behavioural methods of pain relief, and pharmacological management of pain. Improvements in the developmental aspects of pain perception subscale failed to reach significance. CONCLUSIONS: An integrated pain course developed according to the pain curriculum guidelines developed by the IASP resulted in increased student knowledge regardless of the length of the program attended.

Analysis of Variance↗

[Bacteriological quality of groundwaters in cemeteries].

Groundwater samples collected by piezometers from three cemeteries in geologically distinct areas of S. Paulo and Santos, Brazil, were analysed in order to determine their hygienic and sanitary conditions. Fecal coliformes, fecal streptococci, sulfite reducer clostridia and Salmonella were searched for the purpose of evaluating sanitary conditions, and total coliforms, heterotrophic bacteria, proteolitic and lipolitic microorganisms for evaluating hygienic conditions. In some samples, nitrate levels were also determined. It was discovered that these waters do not present adequate sanitary and hygienic conditions and that, in some cases, nitrate levels were extremely high (75.7 mg/l). In most samples, higher levels of fecal streptococci and sufite reducer clostridia than fecal coliforms were detected, which seems to show that the two former indicators would be more appropriate for evaluating the sanitary conditions of this kind of water. Salmonella were detected in only one of 44 samples analysed and coliphages in none. In the statistical analysis, the correlation matrix showed significant correlations among three fecal pollution indicators, as well as among anaerobic and aerobic heterotrophs and lipolitic bacteria. A direct relationship between the deterioration of water quality and the geological and hydrogeological conditions of the environment studied was observed. When cemeteries are constructed these conditions should, therefore, be taken into consideration.

Clostridium↗

Modularity and integration in the hominoid scapula.

In this paper, several hypotheses of morphological integration within the hominoid (ape) scapula are tested. In particular, whether the scapula represents a set of developmental tissues sharing tight correlations between constituent parts (i.e., highly integrated) or is more modularly organized (i.e., covariation is greater within regions than between) is tested. Whether the patterns of integration in the scapula have changed over phylogenetic time or in response to selective forces is also examined. Results from two different analyses (matrix correlations and edge deviance) indicate traits comprising the blade and acromion, and to a weaker degree the glenoid, correlate highly with each other. The coracoid exhibits more independence from other parts of the scapula, perhaps reflecting its distinct evolutionary developmental history. Overall, similarity in species-specific patterns of correlation was high between all taxa. Correlation matrix similarity was significantly correlated with functional similarity and morphological distance, but not with phylogenetic distance. These results are congruent with other studies of integration that suggest correlation patterns remain stable over evolutionary time. There are changes associated with phylogeny, but the tight link between functional similarity and phylogenetic distance at this level of comparison presents possible challenges to interpretation. Overall similarities in the pattern of integration in all taxa might be better interpreted as relative strengthening or weakening of trait correlations rather than broadscale changes in the pattern of relationship between developmental regions. Larger sample sizes with greater taxonomic/functional breadth, and finer scale analyses of patterns of correlation are needed to test these hypotheses further.

Animals↗

The structure of individual differences in heterogeneous stock mice across problem types and motivational systems.

Sixty Heterogeneous Stock (HS) mice received a battery of six problem-solving tasks and three control procedures. The problem-solving tasks included Hebb-Williams, a place learning task conducted in a plus maze, radial maze, a working memory test following the radial maze, a set of detour problems and a visual non-matching to sample task. The control procedures consisted of land and water activity measures and a light-dark test. The correlation matrix derived from these tasks did not exhibit positive manifold, that is, positive correlations across all problem-solving tasks. Principal components analysis reduced the correlation matrix to four components with eigenvalues exceeding 1.0. Instead of the general factor solution common in the study of human problem-solving, this component structure appeared more congenial to a modular interpretation, with the four components each explaining approximately the same magnitude of matrix variance.

Animals↗

Glomerulosclerosis in mice transgenic for growth hormone. Increased mesangial extracellular matrix is correlated with kidney mRNA levels.

Mice transgenic for growth hormone (GH) develop progressive glomerulosclerosis. The compositions of kidney extracellular matrix (ECM) and ECM mRNA were examined. The glomerulosclerotic areas in GH mice contained types I and IV collagen, laminin, and basement membrane heparan sulfate proteoglycan (HSPG), which increased with age. The type IV collagen, laminin B2, and HSPG mRNA levels in GH mice, measured by a solution hybridization RNase protection assay, were increased over normal littermates. These findings suggest that the accumulation of ECM components in the glomeruli of GH mice is regulated at the transcriptional level and that glomerulosclerosis is, in part, due to the excess production of ECM rather than simply a reduction in its turnover. The glomerular lesions in GH mice resemble diabetic nephropathy and may allow further dissection of the molecular basis of certain forms of glomerulosclerosis.

Aging↗

[Metrical study on teeth and mandible in Macaca fuscata fuscata. 2. Principal component analysis].

Metrical investigation on teeth and mandible together was performed to understand the morphological relationship between these two components in Macaca fuscata fuscata. Measurements are 9 items from the mandible, 2 items from dental arch, and 8 mesiodistal diameters from teeth. Correlation matrix composed of 19 items, in total, was examined in males and females, respectively. Significant correlation coefficients were frequently seen among mandibular measurements and also among tooth measurements, but rarely seen between mandibular and tooth measurements. The only exception was a mesiodistal diameter of P3 which has a few significant correlations with mandibular measurements. Principal component analysis was also carried out based on the correlation matrix of 19 measurements. The first component was a size factor in which factor loadings were all positive. The second component was thought to be a factor of the mandibular size in which factor loadings were highly positive on the mandibular measurements and contrarily low on the dental measurements. It is concluded that there is no obvious correlation between general sizes of the mandible and the teeth in Macaca fuscata fuscata.

Animals↗

Quantification of cross correlations in complex spatiotemporal systems.

We propose a design of the equal time correlation matrix suitable for the analysis of multivariate time series with ill-defined phases. We present the cross-correlation analysis of model data sets taken from coupled stochastic oscillators and compare the concept with the results obtained from a conventional correlation matrix analysis. We show that the concept provides a higher sensitivity combined with a better statistical significance when quantifying weak cross correlations.

Journal Article↗

[Role of tissue factor in the invasion of cultured human colon carcinoma cells and its correlation with matrix metalloproteinases].

OBJECTIVE: To investigate the role of tissue factor expression in the invasive ability of human colon carcinoma cells and to analyze the correlation between tissue factor and MMP-2 and MMP-9. METHODS: HT-29 cells with sense-TFcDNA transfection and LoVo cells with antisense-TFcDNA transfection were implanted subcutaneously into nude mice as well as controls. The expressions of MMP-9 and MMP-2 at the protein and mRNA levels were detected by Western blot and RT-PCR respectively; Gelatin zymography was used for assay of the MMP-9 and MMP-2 activities in the supernatant cultured media of LoVo cells with antisense-TFcDNA transfection and controls. RESULTS: The expressions of MMP-9 and MMP-2 at the protein and mRNA levels in the group of HT-29 cells with sense-TFcDNA were significantly increased with untransfected HT-29 cells. The expression in the group of LoVo cells with antisense-TFcDNA had a significant decrease than that of the controls. The MMP-9 and MMP-2 activities of LoVo cells with antisense-TFcDNA were weakened because of the lower expression of tissue factor by gelatin zymography. The expression of MMP-9 and MMP-2 were closely correlated to the expression of tissue factor. CONCLUSION: Tissue factor can increase the invasive ability of human colon carcinoma cells. The partial mechanism is that TF can upregulate the expressions of MMP-9 and MMP-2. Tissue factor may be an inner agonist in the secretion of MMPs in colon carcinoma cells.

Animals↗