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At least 217 records · Page 12Linked to original sources
PubMed1997

Confocal microscopy of cataracts from animal model systems: relevance to human nuclear cataract.

A recent study demonstrated that cytosolic lipid membrane structures, independent of the plasma membrane, preferentially occurred in human cataractous lenses. Animal model systems of cataractogenesis (selenite treated rats: galactose fed rats; buthionine-sulfoxime treated mice; Emory mice) were screened for possible relevant structures using the lipid membrane probe DiI and confocal microscopy. Well delineated plasma membranes of lens fiber cells with independent cytosolic staining structures were only observed in the selenite model system. These cytosolic structures were not observed in aged matched control lenses or within the transparent cortical regions of selenite treated animals with intense nuclear opacification. These results suggested that the morphological changes in DiI staining structures seen in the nucleus of the human cataractous lens were best approximated by those seen in the selenite model system.

Animals↗
PubMed2005

The zebrafish (Danio rerio): a model system for cranial suture patterning.

The zebrafish (Danio rerio) is an alluring model system currently used to study early embryonic development, organogenesis and gene functional analysis. However, few studies have been devoted to post-embryonic development. We have explored the possibility of using this organism to analyze how cranial suture patterning occurs. This study reports on the establishment of the zebrafish skull vault anatomy, calvarial osteogenesis, and cranial suture morphology. Our results demonstrate that the anatomy of the zebrafish cranial vault and cranial sutures is very similar to that of mammalian organisms. Indeed, the zebrafish represents a versatile and valuable model system for the study of the biogenesis of cranial sutures.

Animals↗
PubMed2004

Inference of S-system models of genetic networks using a cooperative coevolutionary algorithm.

MOTIVATION: To resolve the high-dimensionality of the genetic network inference problem in the S-system model, a problem decomposition strategy has been proposed. While this strategy certainly shows promise, it cannot provide a model readily applicable to the computational simulation of the genetic network when the given time-series data contain measurement noise. This is a significant limitation of the problem decomposition, given that our analysis and understanding of the genetic network depend on the computational simulation. RESULTS: We propose a new method for inferring S-system models of large-scale genetic networks. The proposed method is based on the problem decomposition strategy and a cooperative coevolutionary algorithm. As the subproblems divided by the problem decomposition strategy are solved simultaneously using the cooperative coevolutionary algorithm, the proposed method can be used to infer any S-system model ready for computational simulation. To verify the effectiveness of the proposed method, we apply it to two artificial genetic network inference problems. Finally, the proposed method is used to analyze the actual DNA microarray data.

Algorithms↗
PubMed1993

Import of firefly luciferase into peroxisomes of permeabilized Chinese hamster ovary cells: a model system to study peroxisomal protein import in vitro.

A model system for the study of in vitro peroxisomal protein import is described. Chinese hamster ovary (CHO) cells were permeabilized by the bacterial toxin streptolysin O (SLO) and their peroxisomes thus became accessible for a model import protein. Firefly luciferase (FL), which was previously shown to be imported into mammalian peroxisomes in vivo, was used as the reporter protein. When SLO-permeabilized CHO cells were incubated with FL in the presence of an ATP-regenerating system, import of FL could be documented by immunofluorescence staining of the cells with monospecific anti-FL antiserum. FL import increased with time and was dependent on temperature and the presence of hydrolysable ATP, which could not be replaced by GTP. The model system functioned reproducibly and should be of use for investigating fundamental questions on the mechanism of peroxisomal protein import.

Adenosine Triphosphate↗
PubMedDate not supplied

T-lymphocyte immunophenotyping blind proficiency testing: a model system for CD4+ T-cells.

OBJECTIVE: To develop and evaluate methods and results for blind proficiency testing for CD4+ T-cells by T-lymphocyte immunophenotyping. DESIGN: A model system was developed to submit duplicate specimens for T-lymphocyte immunophenotyping as if they were routine patient specimens rather than proficiency specimens. Testing results were compared both interlaboratory and intralaboratory. The model system was designed to gather information on not just the analysis, but other segments of the total testing process. SETTING: Research facilities at the Graduate School of Public Health, San Diego State University, San Diego CA. PARTICIPANTS: 1) A healthy adult volunteer donating one pint of blood. 2) Laboratories offering T-lymphocyte immunophenotyping. MAIN OUTCOME MEASURES: 1) Feasibility of blind proficiency so that PT specimens are received, analyzed, and reported by laboratories without being identified as 'proficiency specimens.' 2) The ease and cost of such a system. 3) The comparability of results and report content among laboratories. RESULTS: A total of twenty-two laboratories received blind proficiency specimens. The model developed to submit specimens and receive results proved feasible. The interlaboratory coefficient of variation for CD4+ count for the four survey years ranged from 10% to 66% and for the CD4+ percent ranged from 4% to 15%. The per specimen cost in this blind proficiency testing was $437.65, approximately seven and a half times the cost for nonblinded proficiency testing or performance evaluations. CONCLUSIONS: Blind proficiency as a tool to compare laboratory test results for T-lymphocyte immunophenotyping is feasible but adds costs. The model system is useful to examine more of the laboratory total testing process than the analysis segment.

Blood Specimen Collection↗
PubMed1995

Model systems for the study of the role of PADPRP in essential biological processes.

The nuclear enzyme poly(ADP-ribose) polymerase (PADPRP) is implicated in a number of cellular processes, including DNA repair, replication, and differentiation. We have been using several model systems to examine these potential roles of PADPRP. A human keratinocyte model system has been developed in which stable lines of epidermal cells contain an inducible construct harboring the antisense cDNA to PADPRP. When PADPRP antisense RNA is induced in culture, endogenous PADPRP mRNA, protein, and enzymatic activity is lowered, and the pattern of poly(ADP) ribosylation in response to alkylating agents is altered. When keratinocyte clones containing the antisense construct or empty vector alone were grafted onto nude mice, they formed histologically normal human skin. The PADPRP antisense construct was also inducible in vivo by the topical application of dexamethasone to the reconstituted epidermis, as determined by in situ hybridization. In addition, poly(ADP-ribose) polymer could be induced and detected in vivo following the topical application of a DNA alkylating agent to the grafted transfected skin layers. Thus, a model system has been developed in which the levels of PADPRP can be selectively manipulated in human keratinocytes in cell culture, and potentially in reconstituted epidermis as these keratinocyte lines can be grafted to nude mice, whereupon they form a histologically and immunocytochemically normal human epidermis. Another system that we have been utilizing to examine the role of PADPRP in proliferation and differentiation is stable lines of mouse preadipocytes that contain an inducible antisense PADPRP RNA. Similar to the keratinocyte system, these cells can inducibly express antisense PADPRP RNA, and subsequently lower levels of endogenous PADPRP.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed2005

A mouse model system for genetic analysis of sociability: C57BL/6J versus BALB/cJ inbred mouse strains.

BACKGROUND: Impairments in social behaviors are highly disabling symptoms of autism, schizophrenia, and other psychiatric disorders. Mouse model systems are useful for identifying the many genes and environmental factors likely to affect complex behaviors, such as sociability (the tendency to seek social interaction). To progress toward developing such a model system, we tested the hypothesis that C57BL/6J inbred mice show higher levels of sociability than BALB/cJ inbred mice. METHODS: Mice tested for sociability were 4- and 9-week-old, male and female C57BL/6J and BALB/cJ mice. On 2 consecutive days, the sociability of each test mouse toward an unfamiliar 4-week-old DBA/2J stimulus mouse was assessed with a social choice paradigm conducted in a three-chambered apparatus. Measures of sociability included the time that the test mouse spent near versus far from the stimulus mouse, the time spent directly sniffing the stimulus mouse, and the time spent in contact between test and stimulus mice in a free interaction. RESULTS: C57BL/6J mice showed higher levels of sociability than BALB/cJ mice overall in each of these measures. CONCLUSIONS: We propose that C57BL/6J and BALB/cJ mice will be a useful mouse model system for future genetic and neurobiological studies of sociability.

Aggression↗
PubMed2004

Operational atmospheric modeling system CARIS for effective emergency response associated with hazardous chemical releases in Korea.

The Chemical Accidents Response Information System (CARIS) was developed at the Center for Chemical Safety Management in South Korea in order to track and predict the dispersion of hazardous chemicals in the case of an accident or terrorist attack involving chemical companies. The main objective of CARIS is to facilitate an efficient emergency response to hazardous chemical accidents by rapidly providing key information in the decision-making process. In particular, the atmospheric modeling system implemented in CARIS, which is composed of a real-time numerical weather forecasting model and an air pollution dispersion model, can be used as a tool to forecast concentrations and to provide a wide range of assessments associated with various hazardous chemicals in real time. This article introduces the components of CARIS and describes its operational modeling system. Some examples of the operational modeling system and its use for emergency preparedness are presented and discussed. Finally, this article evaluates the current numerical weather prediction model for Korea.

Accidents, Occupational↗
PubMed1994

Mechanism and kinetics of transcellular transport of a new beta-lactam antibiotic loracarbef across an intestinal epithelial membrane model system (Caco-2).

Various processes involved in the transcellular transport (TT) of loracarbef (LOR) were studied in the Caco-2 cell monolayer, a cell culture model of the small intestinal epithelium. The results provide support for presence of two AP to BL peptide TT pathways in the intestinal epithelial cell monolayer (Caco-2). The H+ gradient-dependent pathway (Km = 0.789 mM, and Jmax = 163 pmol/min per cm2) is relatively "high affinity" and "low capacity" compared to H+ gradient-independent pathway (Km = 8.28 mM, and Jmax = 316 pmol/min per cm2). In addition, TT of LOR in the presence of a H+ gradient was inhibited 77% to 88% (p < 0.05) by 10 mM of cephalexin, enalapril, Gly-Pro and Phe-Pro, while TT of LOR in the absence of a H+ gradient was only inhibited 42% to 48% (p < 0.05) by 10 mM of Gly-Pro and Phe-Pro. Since AP uptake is H+ gradient-dependent and saturable while the BL efflux is mostly nonsaturable and not driven by a H+ gradient, these two transmembrane transport processes must be different, which could be the result of two different peptide carriers. In vivo, these two transport processes must have worked in concert to produce transcellular flux of loracarbef. To explain the differences between kinetic characteristics of AP uptake and TT transport, a cellular pharmacokinetic (PK) model was developed and the results indicate that the PK model appropriately described the kinetics of LOR TT. The use of this PK model may provide an additional advantage to the use of the cell culture model because kinetic parameters at both sides of the intestinal epithelial membrane may be obtained using the same preparation. Taken together, the Caco-2 model system represents an excellent model system for the study of carrier-mediated processes involved in the TT of peptides and peptide-like drugs.

Amino Acid Sequence↗
PubMed2001

Altered TNF-alpha, glucose, insulin, and amino acids in islets of Langerhans cultured in a microgravity model system.

The present studies were designed to determine effects of a microgravity model system upon lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) activity and indexes of insulin and fuel homeostasis of pancreatic islets of Langerhans. Islets (1,726 +/- 117, 150 islet equivalent units) from Wistar-Furth rats were treated as 1) high aspect ratio vessel (HARV) cell culture, 2) HARV plus LPS, 3) static culture, and 4) static culture plus LPS. TNF-alpha (L929 cytotoxicity assay) was significantly increased in LPS-induced HARV and static cultures; yet the increase was more pronounced in the static culture group (P < 0.05). A decrease in insulin concentration was demonstrated in the LPS-stimulated HARV culture (P < 0.05). We observed a greater glucose concentration and increased disappearance of arginine in islets cultured in HARVs. Although nitrogenous compound analysis indicated a ubiquitous reliance on glutamine in all experimental groups, arginine was converted to ornithine at a twofold greater rate in the islets cultured in the HARV microgravity model system (P < 0.05). These studies demonstrate alterations in LPS-induced TNF-alpha production of pancreatic islets of Langerhans, favoring a lesser TNF activity in the HARV. These alterations in fuel homeostasis may be promulgated by gravity-averaged cell culture methods or by three-dimensional cell assembly.

Amino Acids↗
PubMed2003

Using a human visual system model to optimize soft-copy mammography display: influence of MTF compensation.

RATIONALE AND OBJECTIVES: The investigators developed an efficient method for optimizing cathode ray tube (CRT) monitor performance for digital mammography, based on the correlation between the performance of human observers and the performance of a mathematical computer model of the human visual system. The investigators examined observer performance on soft-copy display of mammographic images that were either unprocessed or processed to compensate for modulation transfer function (MTF) deficiencies in the CRT display. The results were used to validate the human visual system model. MATERIALS AND METHODS: Six radiologists viewed a series of 250 mammographic images with microcalcification clusters with different contrast levels on a CRT monitor. The images were viewed twice: once without image processing and once with processing designed to compensate for MTF deficiencies in the CRT monitor. The images were analyzed with the JNDmetrix Visual Discrimination Model, which is based on the principles of just-noticeable difference measurement and frequency-channel vision modeling. Receiver operating characteristic (ROC) curves were generated for the human observers and compared statistically with the model observers' performance. RESULTS: Both human and model performance was better overall with the MTF-compensated images, especially for microcalcifications in the midlevel contrast range. There was a very high correlation between human and model observers. CONCLUSION: The use of image-processing methods to compensate for limitations in the MTF of CRT monitors can improve the detection performance of radiologists searching for microcalcifications in mammographic images, and a model based on characteristics of the human visual system can be used to predict human observer results accurately.

Computer Simulation↗
PubMed1995

Defining the relationship of oxygen delivery and consumption: use of biologic system models.

To determine the most appropriate mathematical description of the relationship between oxygen consumption and oxygen delivery, we compared the statistical validity of a piecewise linear model to two different biologic system models--Michaelis-Menten (MM) kinetics (used for enzyme systems) and the exponential dose-response relationship (used to describe drug administration and induced response). Nine rabbits underwent five incremental steps of normovolemic hemodilution to progressively decrease DO2. VO2 was measured concurrently by a metabolic gas monitor. All three models (piecewise linear, Michaelis-Menten, and exponential) provided a very close population curve fit to the data points (r2 = 0.88, 0.91, and 0.92). However, there were significant differences in maximum predicted VO2 (VO2max)--6.8, 9.9, 7.2 ml O2.kg-1.min-1 (P < 0.0002)--and a wide range in the model-specific parameters for individual rabbits (critical DO2 6.5-11.8 ml O2.kg-1.min-1, Km 4.2-11.4 ml O2.kg-1.min-1, and kappa 0.12-0.23 ml O2-1.kg.min). In the curvilinear models, average and population parameters were not significantly different. However, in the piecewise linear model, population critical DO2 (10.9 ml O2.kg-1.min-1) was 30% more than the average critical DO2 (8.4 ml O2.kg-1.min-1) for the nine rabbits (P < 0.005). VO2max values predicted by the piecewise linear and exponential dose-response model were more consistent with those in previous publications than was the higher VO2max predicted by the MM model. The difference in the average versus population critical DO2 in the piecewise linear model meant that population modeling was inaccurate because it yielded a critical DO2 higher than that demonstrated by eight of nine individual rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Selecting a model system for neurobiological studies of learning and memory.

This article discusses the logic underlying the use of invertebrate model systems for investigating the neurobiological basis of learning and memory, the kinds of questions which can be asked of these systems as well as their limitations. A model system selected to answer specific questions about learning and memory is most useful if its selection is based on strategy rather than chance.

Animals↗
PubMed1980

Model system studies on N-nitrosamine formation in relation to cured meat: the non-polar phase and S-nitroso peptides.

In view of recent findings that N-nitrosamine formation occurs principally in the adipose tissue of frying bacon, an heterogeneous protein-based model system has been developed which incorporates a 20% decane phase. The N-nitrosation reactions of a series of secondary amines, of varying lipophilicity, have been studied at 37 degrees C, pH 5.25, in the model system, formulated with and without the non-polar phase. In the presence of decane, a 20-fold enhancement in the formation of N-nitrosodihexylamine was observed, whereas no increase was found for N-nitrosopyrrolidine. Ascorbic acid enhanced the N-nitrosation of lipophilic amines in the presence of decane, but did not affect the yield of N-nitrosopyrrolidine under the same conditions. Ascorbyl palmitate had little influence on the N-nitrosation reactions in the presence or absence of decane. The results are discussed in relation to N-nitrosamine formation in the lean and adipose components of fried bacon. The degree of N-nitrosation afforded by S-nitroso amino acids and peptides has been investigated as a function of the size of the 'peptide' molecule in aqueous solution. The reactions of N-methylaniline with sodium nitrite, S-nitrosocysteine, S-nitrosoglutathione and S-nitrosoglutathione bound to a polysaccharide gel have been examined at 37 degrees C, pH 5.5. The rates of N-nitrosamine formation were found to be higher for S-nitrosocysteine than for the peptide systems, although the rate for the polysaccharide model system was dependent upon the local S-nitroso concentration on the gel. The results are discussed in relation to N-nitrosamine formation in cured meats and in the digestive tract.

Amino Acids↗
PubMed1981

Enzyme-incorporated erythrocyte ghosts: a new model system for quantitative enzyme cytochemistry.

The preparation and properties of a new microscopic model system for quantitative enzyme cytochemistry are described. The enzyme to be studied is entrapped in human erythrocyte ghosts by a simple hypotonic procedure. After fixation in suspension the ghosts can be analyzed both biochemically and cytochemically. The system has been tested with alkaline phosphatase. It is demonstrated that an azo method that uses naphthol AS-MX phosphate as substrate and 4-aminodiphenylamine diazonium salt as coupling agent can detect very low levels of enzymic activity. The biochemical activity determinations of alkaline phosphatase loaded erythrocyte ghosts were found to correlate linearly with cytophotometric activity determinations. The possible use of the erythrocyte ghost model system for other cytochemical applications is briefly discussed.

Alkaline Phosphatase↗
PubMed1990

Model systems to study immunomodulation in domestic food animals.

Development of immunomodulators for use in food producing animals is an active area of research. This research has generally incorporated aspects of immunosuppression in model systems. This methodology is appropriate because most of the research has been aimed at developing immunomodulators for certain economically significant diseases in which immunosuppression is believed to be an important component of their pathogenesis. The primary focus has been on stress-associated diseases (especially bovine respiratory disease), infectious diseases in young animals, and mastitis. The model systems used have limitations, but they have demonstrated that immunomodulators are capable of significantly increasing resistance to these important infectious disease syndromes. As our understanding of molecular immunology increases and as more potential immunomodulators become available, the use of relevant model systems should greatly aid advancement in the field of immunomodulation.

Animals↗
PubMed1996

A Konowledge-based Protein Modeling System and Its Evaluation III. A Sensitive Method for Evaluation Protein Model.

A new scoring table of compatibilities of residues with environments in a protein has been derived from environment-dependent amino acid substitution tables. The environments of the residues in the 3D structure are described by: (1) the secondary structure; (2) the solvent accessibility; (3) the hydrogen bonding. On the basis of the scoring table, an assessment method of protein models is proposed. Compared with the famous software Profile-3D, The method not only shows a more effective test of the accuracy of a 3D protein model, but also exhibits a higher sensitivity to the local misfolding. It is an important module in our protein modeling system PMODELING.

Journal Article↗
PubMed1989

Sound propagation in the ear canal and coupling to the eardrum, with measurements on model systems.

A theoretical model of sound propagation in the ear canal is described, which takes into account both the complicated geometry of real ear canals and the distributed acoustical load presented by the eardrum. The geometry of the ear canal enters the theory in the form of a cross-sectional area function relative to a curved axis that follows the center of the ear canal. The tympanic membrane forms part of the ear canal wall and absorbs acoustical energy over its surface. Its motion leads to a driving term that must be added to the horn equation describing the pressure distribution in the ear canal. The sound field within the canal is assumed to be effectively one dimensional, depending only on longitudinal position along the canal. Experiments using model ear canals of uniform cross section were performed to test the ability of the theory to handle distributed loads. Sound-pressure distributions within each model canal were measured using a probe microphone. The behavior of the eardrum was simulated using either a distributed, locally reacting impedance or a mechanically driven piston. The agreement between theory and experiment is good up to a nominal upper frequency limit at which the ratio of canal width to wavelength is 0.25. It is estimated that the theory is applicable in ear canals of cats for frequencies at least as high as 25 kHz and in human ear canals to at least 15 kHz.

Acoustic Stimulation↗