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PubMed2001

Functional correlates of central arterial geometric phenotypes.

We have assessed the functional correlates of common carotid artery (CCA) arterial geometry, derived by combining a measure of vascular mass (VM) with the wall-to-lumen (W/L) ratio in both untreated hypertensive (HT) and normotensive (NT; blood pressure <140/90 mm Hg) subjects of a broad age span (30 to 79 years) of both genders. Brachial systolic, diastolic, and pulse (SBP, DBP, PP) pressures; CCA SBP and PP; CCA diameter (D); intima-media thickness (IMT); relative distensibility; circumferential wall stress (MBPxW/L); fluid shear stress (FSS); strain; augmentation index (AGIh); and aortic pulse wave velocity (PWV) were measured in 680 NT and 635 untreated HT Taiwanese men and women. Carotid geometric phenotypes (CGPs) were derived from ultrasonographic measures of VM and W/L ratio. A normal CGP (CGP1) was defined as that within the 95th NT percentile of age- and gender-specific VM and W/L means. Three "deviant" CGPs were defined as follows: CGP2 or remodeling, ie, a normal VM coupled with an increased W/L; CGP3 or hypertrophy, ie, an increase in both VM and W/L; and CGP4 or hypertrophy with dilation, ie, an increased VM with normal W/L. The prevalence of specific CGPs in the total sample was 83.4% for CGP1, 5.5% for CGP2, 2.2% for CGP3, and 8.9% for CGP4. Compared with CGP1, all deviant CGPs had increased carotid resistance, had higher CCA circumferential wall stress, and varied in blood flow velocity. Compared with CGP1, CGP2 subjects were more likely to be women (69.3% versus 45.9%), were on average 10 years older, and had similar central and brachial BP levels, PWV, and AGIh but had increased strain, higher distensibility, lower flow, and a higher FSS. CGP3 subjects did not differ in age or gender but had a higher prevalence of HT; higher circumferential stress, PWV, and distensibility; and lower flow, as well as a trend toward higher SBP, PP, and AGIh and lower FSS. CGP4 subjects did not differ in age or gender but exhibited higher AGIh and aortic PWV, lower distensibility and FSS, and unchanged strain and flow. CGP4 was the only deviant CGP in which the average brachial or central arterial pressures were significantly increased. CGP4 subjects also had the highest prevalence of HT among all the CGPs (77.8% versus 45% in CGP1). CGPs exhibit some common mechanical or functional properties but each also exhibits a unique profile. Although differing quantitatively in NT and HT and at young and older age, the characteristic functional profile of a given CGP is preserved, regardless of age or BP status. A normal CGP is characterized by a low circumferential wall stress and high FSS. Each deviant CGP is characterized by a unique combination of increased circumferential wall stress, with variable FSS, strain, distensibility, central BP, and late pressure augmentation. The interplay among these factors, particularly circumferential wall and FSS, likely determines the CGP; conversely, the resultant CGP may modulate the FSS and wall stress for a given pressure and flow.

Adult↗
PubMed1992

Determinants of left ventricular filling dynamics: alteration in the Doppler-derived transmitral filling profile with progressive impairment of cardiac function in a dog preparation.

To clarify the factors determining transmitral filling, left ventricular and atrial pressures (LVP and LAP) and Doppler-derived diastolic indices were analysed in six anaesthetized dogs at various right atrial pacing rates during dextran infusion. The relationship of the late to early diastolic peak velocity ratio (A/E ratio) to end-diastolic LVP (LVEDP) showed a quadratic curve concave to the LVEDP axis in five animals (r2 = 0.320-0.588). An elevation in LVEDP up to 25 mmHg accompanied an increase in A/E ratio (ascending limb), and further LVEDP elevation caused its inverse decline (descending limb). Multiple regression analysis indicated that A/E ratio correlated positively with maximal LVP, a-wave LAP and heart rate, and negatively with v-wave LAP in both limbs. The time constant of isovolumic LVP decline, which was prolonged as LVEDP was elevated, was a positive correlate of A/E ratio in the ascending limb, but lost its influence on A/E ratio in the descending limb. An elevation in v-wave LAP must have masked the expected effect of left ventricular relaxation abnormality on A/E ratio in this limb. Thus, the transmitral filling profile did not alter unidirectionally, but returned to that seen before volume loading, with a simultaneous progressive impairment of cardiac function.

Animals↗
PubMedDate not supplied

Analysis of vessel absorption profiles in retinal oximetry.

The optical densities of vessel absorption features in small bandwidth fundus photographs have been used by many people for finding the oxygenation of the blood in retinal vessels. The purpose of this article is to show that the information found in this way can be made more accurate, and more information can be found by considering the details of the absorption profile (intensity as a function of distance across the vessel). The "wings" of the profile are primarily determined by the line-spread function of the video camera or film. A four-parameter curve fitting procedure using the line-spread function and an "ideal" vessel profile can be used to eliminate the effects both of the line-spread function and of any central reflection (vessel reflex) that may be present, yielding estimates of the vessel diameter and central absorption. The conclusions concerning the reflection are supported by studies of reflections from capillary tubes and wires in a model eye.

Biophysical Phenomena↗
PubMed2000

Functional discovery via a compendium of expression profiles.

Ascertaining the impact of uncharacterized perturbations on the cell is a fundamental problem in biology. Here, we describe how a single assay can be used to monitor hundreds of different cellular functions simultaneously. We constructed a reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae, and we show that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles. The utility of this approach is validated by examining profiles caused by deletions of uncharacterized genes: we identify and experimentally confirm that eight uncharacterized open reading frames encode proteins required for sterol metabolism, cell wall function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbations by identifying a novel target of the commonly used drug dyclonine.

Cell Wall↗
PubMed2004

Combining evolutionary and structural information for local protein structure prediction.

We study the effects of various factors in representing and combining evolutionary and structural information for local protein structural prediction based on fragment selection. We prepare databases of fragments from a set of non-redundant protein domains. For each fragment, evolutionary information is derived from homologous sequences and represented as estimated effective counts and frequencies of amino acids (evolutionary frequencies) at each position. Position-specific amino acid preferences called structural frequencies are derived from statistical analysis of discrete local structural environments in database structures. Our method for local structure prediction is based on ranking and selecting database fragments that are most similar to a target fragment. Using secondary structure type as a local structural property, we test our method in a number of settings. The major findings are: (1) the COMPASS-type scoring function for fragment similarity comparison gives better prediction accuracy than three other tested scoring functions for profile-profile comparison. We show that the COMPASS-type scoring function can be derived both in the probabilistic framework and in the framework of statistical potentials. (2) Using the evolutionary frequencies of database fragments gives better prediction accuracy than using structural frequencies. (3) Finer definition of local environments, such as including more side-chain solvent accessibility classes and considering the backbone conformations of neighboring residues, gives increasingly better prediction accuracy using structural frequencies. (4) Combining evolutionary and structural frequencies of database fragments, either in a linear fashion or using a pseudocount mixture formula, results in improvement of prediction accuracy. Combination at the log-odds score level is not as effective as combination at the frequency level. This suggests that there might be better ways of combining sequence and structural information than the commonly used linear combination of log-odds scores. Our method of fragment selection and frequency combination gives reasonable results of secondary structure prediction tested on 56 CASP5 targets (average SOV score 0.77), suggesting that it is a valid method for local protein structure prediction. Mixture of predicted structural frequencies and evolutionary frequencies improve the quality of local profile-to-profile alignment by COMPASS.

Algorithms↗
PubMed1987

Maximizing productivity in an immobilized cell reactor.

A vertical immobilized cell reactor employing Saccharomyces cerevisiae cross-linked to a gelatin support with glutaraldehyde has proven to be an effective system to achieve high cell concentrations and high dilution rates. The reactor is very stable over long periods of time, during which the cell concentration increases continuously without achieving steady state. Therefore, periodic regeneration by gas purging is required to remove excess biomass from the interstitial spaces. The glucose concentrations along the reactor follow an exponential profile when plotted as a function of the true residence time. Such profiles are a function of the initial glucose concentration fed to the system. The overall productivity of the reactor is a function of the flow rate and the inlet glucose concentration. For a 99% conversion, the maximum overall productivity is obtained at a substrate concentration of between 15% and 20%. Theoretical cell profiles were obtained and they indicate that mass transfer is promoted at high substrate concentrations and flow rates. The performance of a variety of packing materials having different shapes and materials of construction were compared in a vertical packed bed immobilized cell reactor. With other parameters being constant, the performance of the reactor is dominated by the quantity of cells present. The packing that has the highest surface area per volume of bed yields the most extensive monolayer and gives faster reactor start-up. Packing materials having high biomass loading rates are desirable at prolonged operating periods when growth beyond the monolayer occurs. Ultimately, the packing with the highest initial porosity would be capable of loading the highest cell volume, provided that sufficient interstitial spaces were provided for cell entrapment. When the immobilized cell reactor is operated in the horizontal position, CO2 holdup is decreased, as is evidenced by an increase in liquid holdup. However, the horizontal and vertical reactors showed almost identical substrate profiles at constant cell densities. In addition, under prolonged operation, the performance of the horizontal reactor decayed after several days, while the vertical reactor remained stable for over 40 days. The improved operation of this type of column in the vertical position is attributed to the necessary promotion of mass transfer with CO2 evolution and better liquid distribution. The addition of fatty acids to the media for an ICR results in limiting growth and increasing productivity. Overgrowth can be minimized, thus allowing longer periods of operation without regeneration.(ABSTRACT TRUNCATED AT 400 WORDS)

Biotechnology↗
PubMed1990

[Study of the quality of measurement by the Sickness Impact Profile. Assessment of the reliability of a method to determine the functional level of psychiatric patients].

The Sickness Impact Profile (SIP) is a questionnaire method of assessing the functional level within 12 fields which together provide a generalized measurement of the level of health in agreement with the definition of health by WHO. In the present investigation, the method was employed for the first time occasion for 58 suitable psychiatric patients and the result of Rasch's item-analysis of the replies to the individual questions showed altogether scales of good measurement quality. A single question, however, appeared to be unsuitable. The item-analysis is a demanding measurement for the internal validity and homogeneity and it supplements foreign investigations of the criteria-related validity of SIP.

Adolescent↗
PubMed2005

Inference of protein function from protein structure.

Structural genomics has brought us three-dimensional structures of proteins with unknown functions. To shed light on such structures, we have developed ProKnow (http://www.doe-mbi.ucla.edu/Services/ProKnow/), which annotates proteins with Gene Ontology functional terms. The method extracts features from the protein such as 3D fold, sequence, motif, and functional linkages and relates them to function via the ProKnow knowledgebase of features, which links features to annotated functions via annotation profiles. Bayes' theorem is used to compute weights of the functions assigned, using likelihoods based on the extracted features. The description level of the assigned function is quantified by the ontology depth (from 1 = general to 9 = specific). Jackknife tests show approximately 89% correct assignments at ontology depth 1 and 40% at depth 9, with 93% coverage of 1507 distinct folded proteins. Overall, about 70% of the assignments were inferred correctly. This level of performance suggests that ProKnow is a useful resource in functional assessments of novel proteins.

Amino Acid Motifs↗
PubMedDate not supplied

Personality predictors of dimensions of psychosocial adjustment after surgery.

OBJECTIVE: Although many studies have examined the relationship between personality factors and adjustment after surgery, most of them have had very short follow-up periods. The present prospective study examines whether preoperative psychodynamic assessment of personality traits enhances prediction of various areas of psychosocial adjustment assessed at least 1 year after surgery. METHODS: In 53 patients undergoing pelvic pouch surgery for ulcerative colitis, we examined the relationship between personality traits measured before surgery, and postoperative psychosocial adjustment assessed at a median of 17 months postoperatively, controlling for the effect of surgical functional outcome. Personality traits were assessed with the Karolinska Psychodynamic Profile (KAPP). Surgical functional outcome scales and the Psychosocial Adjustment to Illness Scale (PAIS) were used. RESULTS: Problems with sexual satisfaction, perfectionistic body ideals, lack of alexithymia, and poor frustration tolerance predicted poor postoperative adjustment in various areas, beyond what was predicted by surgical functional outcome alone. Moreover, moderate preoperative levels of alexithymia were beneficial to postoperative adjustment in the area of psychological distress. CONCLUSIONS: The findings suggest that the preoperative assessment of the patient's long-term sexual functioning and satisfaction, the importance attached to his or her appearance, level of alexithymia, and general capacity to tolerate frustration and set-backs in life, might alert both the surgeon and the patient to potential risk factors for poor postsurgical adjustment.

Activities of Daily Living↗
PubMedDate not supplied

The influence of the size of the grid used for dose calculation on the accuracy of dose estimation.

The standard presentation of a dose distribution as an isodose map is based on interpolation between dose values calculated on a matrix of equally spaced points. We explored the question of how the spacing of the grid used for the dose matrix affects the error due to interpolating the dose at any point. We defined two types of errors: the dose error, which is the difference between the interpolated and true dose at a given point; and the position error, which is the distance between the point of interest and the nearest point which has, in fact, the dose value estimated for the point of interest. We examine the problem using both an analytical beam profile (a Fermi function) and measured 60Co, x-ray and proton beam profiles. Our analysis showed that the interpolation errors are proportional to the curvature of the dose distribution and are relatively high in regions on either side of, but not including, the steepest part of the penumbra. Our results showed how big an interpolation error one should expect for a given size of the calculation grid. The specification of accuracy should be cast in the form of a pair of requirements, one for dose and the other for position. At a given point, only one of the two requirements needs to be satisfied. The position requirement is almost always the less demanding in clinical practice and permits the use of a larger grid spacing than if only a dose requirement is applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Cobalt Radioisotopes↗
PubMed2004

Comparison of systemic responses of radiofrequency ablation, cryotherapy, and surgical resection in a porcine liver model.

BACKGROUND: The degree of systemic response after hepatic radiofrequency ablation (RFA) has not been well investigated. METHODS: An in vivo study was conducted on 23 domestic swine. Different hepatic procedures (RFA, cryotherapy, hepatic pedicle ligation, and hepatectomy) were performed on the medial lobe of the liver (30% of the liver volume). Systemic responses in terms of systemic inflammatory marker changes and end-organ functions were determined. RESULTS: During the early postoperative period, the systemic inflammatory marker concentrations (tumor necrosis factor-alpha and interleukin-1beta) in the RFA group were significantly lower than in the cryotherapy group but significantly higher than in the control group. The corresponding concentrations in the hepatectomy group remained similar to those in the control group. The pattern of changes of serum inflammatory marker concentrations in the pedicle ligation group followed the pattern in the RFA group. The serum intracellular content concentrations (lactate dehydrogenase and urate) of the cryotherapy group peaked at 6 hours after operation, which was significantly later than in the other groups. Liver function, renal function, and coagulation profiles remained normal in the RFA group. However, the renal function deteriorated in the cryotherapy group on day 1. Both platelet count and activated clotting time showed significant derangement in the cryotherapy group compared with the control group. There was more severe interstitial pneumonitic change of the porcine lung after cryotherapy than after RFA. CONCLUSIONS: The systemic responses of RFA were significantly less severe than those of cryotherapy in this porcine model. However, the increase in serum inflammatory markers and pneumonitis after RFA was substantial when compared with hepatectomy.

Animals↗
PubMed1999

Effects of graft-versus-host reaction on intrahepatic islet transplants.

The use of donor-specific bone marrow transplantation might represent a valuable approach for the induction of hyporesponsiveness to concurrent allogeneic organ and tissue grafts. In this setting, the occurrence of subclinical forms of graft-versus-host reaction (GVHR) can seldom be formally ruled out. When systemic administration of donor-specific bone marrow is performed together with intraportal transplantation of islets of Langerhans, GVHR might damage the implanted islets through an innocent bystander mechanism. The liver is, in fact, a prominent target of GVHR, and islets are sensitive to the noxious effects of proinflammatory mediators, including selected cytokines produced during GVHR. A parent (Lewis) to F1 (Lewis x Brown Norway) splenocyte transfer model was used to induce GVHR in rats. Islets were also obtained from Lewis donors and implanted into F1 recipients to examine the effects of GVHR on islet function in the absence of rejection. Selected doses of splenocytes were infused in F1 recipients to induce GVHR. When 150 x 10(6) cells were administered, all recipients developed clinical lethal GVHR. When 100 x 10(6) or 80 x 10(6) cells were given, lethal GVHR was observed in 40 and 20% of the F1 animals, respectively. A transient clinical syndrome occurred in the remaining animals and spontaneously subsided; histological findings consistent with persistent low-grade GVHR were observed in these animals at the time of death several months after splenocyte inoculation. When simultaneous splenocyte infusions and islet grafts were performed in chemically diabetic animals, no adverse effect of either clinical or subclinical GVHR was observed on islet function. Blood glucose profiles were normal, as were intravenous glucose tolerance test profiles. In conclusion, GVHR does not seem to adversely influence function of islets of Langerhans implanted intrahepatically in this parent to F1 experimental model.

Animals↗
PubMed2006

Combining gene expression profiles and protein-protein interaction data to infer gene functions.

The ever-increasing flow of gene expression profiles and protein-protein interactions has catalyzed many computational approaches for inference of gene functions. Despite all the efforts, there is still room for improvement, for the information enriched in each biological data source has not been exploited to its fullness. A composite method is proposed for classifying unannotated genes based on expression data and protein-protein interaction (PPI) data, which extracts information from both data sources in novel ways. With the noise nature of expression data taken into consideration, importance is attached to the consensus expression patterns of gene classes instead of the actual expression profiles of individual genes, thus characterizing the composite method with enhanced robustness against microarray data variation. With regard to the PPI network, the traditional clear-cut binary attitude towards inter- and intra-functional interactions is abandoned, whereas a more objective perspective into the PPI network structure is formed through incorporating the varied function-function interaction probabilities into the algorithm. The composite method was implemented in two numerical experiments, where its improvement over single-data-source based methods was observed and the superiority of the novel data handling operations was discussed.

Algorithms↗
PubMed2005

Visual working memory for simple and complex features: an fMRI study.

Visual working memory (VWM) allows us to hold visual information briefly in our minds after its disappearance. It is important for bridging the present to the immediate past. Previous neuroscience studies on VWM have shown that several parietal, frontal, and occipitotemporal brain regions subserve this function. Those studies, however, have often focused on VWM for a single property, such as color. Yet, in behavior, the capacity of VWM is sensitive to the complexity of to-be-remembered visual features. How do different brain areas represent VWM for visual features of different complexity and for combination of features? To address this question, we used functional MRI to study the response profile of several brain regions in three VWM tasks. In all tasks, subjects saw 1 to 7 colored polygons and had to remember their color (a simple feature), shape (a complex feature), or both color and shape. Behavioral performance showed that VWM reached capacity limit at about 3 colors, 2 shapes, and 2 compound objects. In the fMRI data, we found different functional profiles for frontal, parietal, and occipitotemporal regions. Specifically, the posterior parietal cortex was sensitive to both featural and VWM load manipulations. The prefrontal regions were sensitive to VWM load manipulation but relatively insensitive to featural differences. The occipitotemporal regions were sensitive to featural differences, but not to VWM load manipulation. We propose that the response properties of these regions can jointly account for several findings in human VWM behavior.

Adolescent↗
PubMed2006

Similar gene expression profiles do not imply similar tissue functions.

Although similarities in gene expression among tissues are commonly inferred to reflect functional constraints, this has never been formally tested. Furthermore, it is unclear which evolutionary processes are responsible for the observed similarities. When examining genome-wide expression data in mouse, we found that patterns of expression similarity between tissues extend to genes that are unlikely to function in the tissues. Thus, ectopic expression can seem coordinated across tissues. This indicates that knowledge of gene expression patterns per se is insufficient to infer gene function. Ectopic expression is possibly explained as expression leakage, caused by spreading of chromatin modifications or the transcription apparatus into neighboring genes.

Animals↗
PubMed1997

Assessing the responsiveness of a functional status measure: the Sickness Impact Profile versus the SIP68.

In this study, the Sickness Impact Profile (SIP) and the SIP68 are studied for their ability to detect changes in health-related behavioral status. Methodological approaches toward responsiveness are invented and discussed. Next, literature findings on the responsiveness of the SIP are presented and judged for their validity. The SIP appeared to be able to demonstrate changes in the expected direction and in accordance with changes detected by other instruments. Using data from seven different longitudinal projects in populations with different diagnoses, the responsiveness of both the SIP136 and the SIP68 are subsequently studied and compared. In all populations, changes in functional status were indicated by both instruments. In terms of effect sizes, the SIP136 and the SIP68 do not differ significantly in their responsiveness. Moreover, changes detected by both SIPs appear to be valid representations of changes in health-related functional status.

Activities of Daily Living↗
PubMed1982

[The cardiovascular risk profile of long-term diabetics and its relation to kidney function].

Of 250 diabetics with a duration of the disease between 15 and 54 years the relations between the renal function and the cardiovascular risk profile were examined. The clearly increased serum creatinine values the frequency of persons with overweight was lower than in diabetics with very favourable creatinine levels. The increasing concentration of the serum led to an increase of the frequency of hyperuricaemia, whereas the frequencies of hypertension hypertriglyceridaemia and hypercholesterolaemia did not show any significant changes. The habits of smoking of long-term diabetics with and without renal insufficiency did not differ from each other qualitatively. Particularly after the 50th year of age long-term diabetics more frequently had diabetic blood-relatives than newly detected diabetic patients of the same age. Patients with familial occurrence of diabetes (relatives of 1st degree) in comparison to diabetics without known diabetic relatives showed an identical cardiovascular risk profile, so that there is no influence of the heredity of diabetes on the formation of the non-diabetic sizes of influence of the metabolic syndrome.

Adolescent↗
PubMedDate not supplied

[Structural and physico-chemical properties of amino acids of functionally important regions of proteins].

A correlation of the localization of functionally important regions with places having low and high values on twelve profiles built on a basis of amino acid sequences was analysed using a broad set of proteins. The profiles of hydrophilicity, resemblance to the sequences of human proteins, flexibility, mutability and others were considered. The resemblance profile was plotted by the program fixing short similar fragments in the testing protein and 92 human ones. The active centres were shown to be located in the primary structure regions having relatively low values on the resemblance profiles. Similar effect was observed in the mutability and alpha-helicity profiles. The potential functionally important sites of the human leukocyte interferon and interleukin-2 isolated on the basis of the analysis of this profiles were in accord with the available literary data.

Amino Acids↗