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At least 433 records · Page 24Linked to original sources

PubMed2005

Characterization of a metal-chelating substance in coffee.

A metal-chelating substance in brewed coffee was separated and characterized by its chemical structure. This substance was a brown polymer. The contents of sugars, amino acids and phenolics in the substance were evaluated. This polymer contained small amounts of sugars and amino acids in its partial structure. After being decomposed by alkaline fusion, the decomposition products were identified by HPLC and GC-MS. Several phenolics were detected in the decomposed products. To characterize this substance, various types of model compounds were prepared by roasting chlorogenic acid, sucrose, and (or) protein with cellulose powder. Among these model compounds, the polymer-forming ability was highest in the model prepared from all four of materials, but the metal-chelating ability was the highest in the model prepared from chlorogenic acid and cellulose. These results suggest that this metal-chelating substance was a melanoidin-like polymer formed by the decomposition and polymerization of sugars, amino acids and phenolics.

Chelating Agents↗

PubMed1998

Clinical administration procedures in the Read Thesaurus: extending the ENV 1828 model to support regional terminology requirements.

Documentation of the administrative aspects of clinical practice (fee claims, referrals, visits etc.) is essential and a controlled terminology for the electronic health care record needs to support this requirement. The Read Codes--used in the United Kingdom for over 10 years--include a chapter of administration terms for this purpose. The latest version, the Read Thesaurus, adopts a partially compositional approach to concept representation. We describe an extension of the ENV 1828 surgical procedure scheme developed as a provisional model to represent administrative procedures. Applicable concept fields, semantic links and modifiers are identified and compared. A compositional approach appears to provide a flexible and manageable method of representing administrative procedures, and readily accommodates regional variations.

Delivery of Health Care↗

PubMed2002

Contextual social-cognitive mediators and child outcome: a test of the theoretical model in the Coping Power program.

This study tests the contextual social-cognitive model, which has served as the basis for the Coping Power program, an indicated preventive intervention with at-risk preadolescent boys at the time of transition from elementary to middle school. The contextual social-cognitive model assumes that aggressive children have distortions in their social-cognitive appraisals and deficiencies in their social problem solving skills and that their parents have deficiencies in their parenting behaviors. To test this model, boys were identified as being at risk on the basis of fourth grade and fifth grade teachers' ratings of children's aggressive and disruptive behaviors, and interventions were delivered at the end of elementary school and the beginning of middle school. The intervention effect on delinquency, substance use, and school behavior outcomes was at least partially mediated through intervention-produced changes in child and parent variables that were targets for the intervention. These analyses provided unique support for the assumptions in the contextual social-cognitive model that changes in these mediating processes, even among high-risk boys, can have a meaningful impact on later negative outcomes.

Adaptation, Psychological↗

PubMed2006

Significance of ectodomain cysteine boxes 2 and 3 for the activation mechanism of the thyroid-stimulating hormone receptor.

Recently, we identified constitutively activating mutations at positions Asp-403, Glu-404, and Asn-406 in the third extracellular cysteine box (C-b3) of the thyroid-stimulating hormone receptor. We hypothesized that this region could act as a molecular interface between the extracellular and serpentine domain. In this study we present a model for properties of potential interaction partners for this region. Moreover, we show that Pro-400 and Pro-407 adjacent to this epitope are also important for stabilizing the partially active, basal conformation of the wild-type (WT) thyroid-stimulating hormone receptor. Furthermore, the mutation K291A in the second extracellular cysteine box (C-b2) was identified as a new constitutively activating mutation that releases the basal conformation of the WT receptor like the known tryptic cleavage in its close vicinity. Taken together, we provide an activation scenario at the C-b2/C-b3 unit. Three anchor fragments (anchors I-III) most likely constrain the basal conformation. The three anchor fragments are tightly packed. A disulfide bridge holds the C-b2/C-b3 portions in close positions. Independent of the type of conformational interference such as side chain modifications, tryptic cleavage, or hormone stimulation that act on the constrained C-b2/C-b3 WT conformation, it will always release one of the anchor fragments. Subsequently, this results in a conformational displacement of the C-b2/C-b3 portions relative to each other, inducing receptor activation.

Animals↗

PubMed1986

Iconic memory, location information, and partial report.

It has been suggested that the systematic decline of partial report as the delay of the partial-report cue increases is due to a time-related loss of location information. Moreover, the backward masking effect is said to be precipitated by the disruption of location information before and after identification. Results from three experiments do not support these claims when new indices of location information and of item information are used. Instead, it was found that the systematic decline in partial report was due to a time-related loss of item information, and location information was affected neither by the delay of the partial-report cue nor by the delay of backward masking. Subjects adopted the "select-then-identify" mode of processing.

Cues↗

PubMed1986

[Optimization of conditions for detecting density variations in focal activity in SPECT using the rotating gamma camera. Model calculations, phantom measurements and clinical applications].

The signal to noise ratio (quotient of contrast and mean noise) is a quality parameter for identifying activity gaps during single photon emission computed tomography (SPECT). Contrast and mean noise level are site-dependent on the reconstruction plane which is influenced in a complex manner by absorption conditions (strong or weak absorption), modes of rotation (full angle or partial angle imaging), interdependencies of opposing partial projections (arithmetic or geometric mean), magnitude of defect (relative to the resolution of the imaging system), geometry of the object to be measured, and scatter. In the present study the authors performed analysis and graphical representation of the SPECT imaging properties on the basis of model calculations illustrated by phantom measurements. The optimal conditions of examination or evaluation and the diagnostic criteria in SPECT of the heart, liver, brain and pelvis are discussed by comparative calculation of signal to noise ratios in defect identification.

Brain↗

PubMed2005

A Caenorhabditis elegans Parkin mutant with altered solubility couples alpha-synuclein aggregation to proteotoxic stress.

Mutations in the human parkin gene encoding an E3 ubiquitin ligase have been associated with early-onset recessive forms of Parkinson's disease (PD). However, the molecular mechanisms by which mutations in the parkin gene cause PD are still under debate. Here, we identified and characterized the Caenorhabditis elegans parkin homolog, pdr-1. PDR-1 protein physically associates and cooperates with a conserved degradation machinery to mediate ubiquitin conjugation. Strikingly, in contrast to pdr-1 loss-of-function mutants, an in-frame deletion variant with altered solubility and intracellular localization properties is hypersensitive toward different proteotoxic stress conditions. Both endoplasmic reticulum-derived folding stress and cytosolic stress conferred by expression of mutant human alpha-synuclein resulted in severe developmental defects and lethality in pdr-1(lg103) mutant background. Furthermore, we show that the corresponding truncated protein PDR-1(Deltaaa24-247) aggregates in cell culture, but still interacts with its ubiquitylation co-enzymes. Thus, it might block the cellular degradation/detoxification machinery and therefore renders worms highly vulnerable to protein folding stress. In contrast to other complete gene knockouts or RNAi models of Parkin function, this C. elegans model recapitulates Parkin insolubility and aggregation similar to several autosomal recessive juvenile parkinsonism (AR-JP)-linked Parkin mutations. We suggest that such Parkin variants that either confer a neomorphic function or a partial loss-of-function may help to further elucidate the biological function of Parkin in vivo and the pathogenic mechanisms resulting in AR-JP. Due to high-throughput capacity of C. elegans, this model is particularly well suited to identify genetic and chemical modifiers of toxicity.

Amino Acid Sequence↗

PubMed2005

Evidence for macrophage-mediated myelin disruption in an animal model for Charcot-Marie-Tooth neuropathy type 1A.

Charcot-Marie-Tooth neuropathy type 1A (CMT 1 A) is the most common inherited neuropathy in humans and is mostly caused by a 1.5-Mb tandem duplication of chromosome 17 comprising the gene for the peripheral myelin protein 22-kDa (PMP 22). Although there are numerous studies on the functional role of PMP 22, the mechanisms of myelin degeneration under PMP 22-overexpression conditions have not yet been fully understood. We have shown previously that in mouse mutants hetero- or homozygously deficient for two other myelin components, P0 and C x 32, respectively, immune cells contribute to the demyelinating neuropathy. To test this possibility for PMP 22 overexpression, we investigated a putative mouse model for CMT 1 A, i.e., the mouse strain C 6 1 mildly overexpressing human PMP 22 in peripheral nerves. Electron microscopic and electrophysiologic investigations revealed that this mouse strain develops pathologic features similar to those found in CMT 1 A patients. A novel finding, however, was the upregulation of CD8- and F4/80-positive lymphocytes and macrophages, respectively, in peripheral nerves. The observation that macrophages enter endoneurial tubes of the mutants and obviously phagocytose morphologically normal myelin strongly suggests that the myelin degeneration is mediated at least partially by these phagocytic cells. By gene array technology and quantitative RT-PCR of peripheral nerve homogenates from PMP 22 mutants, monocyte chemoattractant protein-1 (MCP-1; cc l2) could be identified as a putative factor to attract or activate macrophages that attack myelin sheaths in this model of CMT 1 A.

Aging↗

PubMed1990

Protective efficacy of a cloned Brugia malayi antigen in a mouse model of microfilaremia.

Immunization of mice with irradiated Brugia larvae or parasite extracts has been shown to induce partial resistance to microfilaremia and enhance clearance of infective larvae. We recently reported the cloning of a 548 amino acid 62-kDa Brugia malayi Ag identified on the basis of reactivity with antisera to a subset of protective microfilarial Ag. Our study describes the protective efficacy against microfilaremia in mice, immunogenicity, and parasite stage-specificity of this candidate vaccine molecule. Immunization of Swiss or BALB/c mice with 1 to 3 micrograms of a 92-kDa trpE fusion protein encoding amino acids 1-479 reduced the intensity of microfilaremia by 40 to 60% compared to control animals given buffer or bacterial trpE (p less than 0.01 to 0.001). Mice immunized with the 92-kDa fusion protein developed delayed-type hypersensitivity reactivity to B. malayi as assessed by enhanced footpad swelling 24 and 48 h after intradermal injection of adult worm extract and in vitro lymph node mononuclear cell proliferation (3H-thymidine uptake) in response to the fusion protein (mean +/- SD stimulation index 4.7 +/- 0.8 vs 2.0 +/- 1.4 for trpE, p less than 0.05). Proliferative responses of lymph node cells coincubated with three other fusion proteins corresponding to the filarial protein truncated from its carboxyl-terminus suggest that dominant T cell epitopes of the 62-kDa Ag are encompassed by amino acids 437-479. Rabbit antibody to the 92-kDa trpE fusion protein immunoprecipitated a 62-kDa polypeptide from [35S] methionine biosynthetically labeled B. malayi microfilariae, adult female, and adult male worms. These data indicate that a recombinant Ag expressed in several developmental stages of B. malayi is capable of inducing partial resistance against microfilariae and Ag-specific T cell responses in mice.

Animals↗

PubMed2005

Genetic and ecological dynamics of species replacement in an arid-land river system.

Museum records indicate that Hybognathus placitus was introduced into the Pecos River, New Mexico during the early 1960s. Approximately 10 years later, a congener, Hybognathus amarus, was extirpated from the system. We used microsatellite and mtDNA data, ecological data and modelling, and a computer simulation approach to reconstruct the history of invasion and species replacement. To identify the potential role of hybridization and introgression, we genetically screened H. amarus (n = 389) from the Rio Grande, New Mexico, and H. placitus (n = 424) from the Pecos River, New Mexico using four nuclear microsatellites and a partial fragment of the mtDNA ND4 gene. Assignment tests excluded hybridization as a primary factor in species replacement and suggested a role for interspecific competition. Genetic analyses showed that H. placitus were introduced into the Pecos River from at least two genetically distinct source populations in the Canadian and Red rivers, Oklahoma. Lotka-Volterra models of interspecific competition indicated that the number of founding individuals could have been as few as 20 for H. placitus to have competitively displaced H. amarus in the Pecos River in 10 to 15 generations. Observed differences of allele frequencies between source and founder populations indicated that between 32 and 115 H. placitus individuals founded the Pecos River. Genetic and ecological data suggest that interspecific competition could have led to species replacement in this arid-land river system.

Animals↗

PubMed1998

10 years of Genomics, chromosome 21, and Down syndrome.

During the first 10 years of Genomics (1987-1997), the molecular structure of human chromosome 21 (HC21) has been intensively investigated. Due to its small size and involvement in Down syndrome, it continues to serve as a model in the development of "genomics technologies." Increasingly more detailed genetic, radiation hybrid, physical, and transcription maps, in addition to NotI restriction and chromosomal breakpoint maps, of HC21 have been developed, and approximately 10% of its genes have been cloned. These maps have been vital in the localization of loci for 15 monogenic disorders to HC21, and 10 of these genes have been identified and characterized. The genetic maps have aided in the detailed elucidation of the origin of the supernumerary HC21 in trisomy 21 from investigations of recombination and nondisjunction events. Mouse models of Down syndrome, with partial trisomy 16, the mouse chromosome principally syntenic to HC21, have been created and initially characterized. A substantial number of the above studies related to the molecular mapping, gene cloning, and infrastructure of HC21 were published in Genomics (e.g., approximately 30% of papers describing HC21 maps were published here). The future goals of genomic analysis of HC21 will be the determination of its complete nucleotide sequence and the identification and functional analysis of all of its genes. These advances will help to provide a molecular explanation of the pathophysiology of Down syndrome and aid in the identification of genes for monogenic and polygenic disorders that map on this chromosome. Novel therapeutic interventions for Down syndrome and the monogenic and polygenic disorders that map to HC21 will be designed and tried based on the knowledge of the disease pathogenesis resulting from the genomic analysis.

Animals↗

PubMed2005

Constitutive activity of endogenous receptors by inducible Gq overexpression.

We have developed an inducible cell line that transiently expresses Gq alpha G protein subunits in response to doxycycline. HEK293/Tet-On pBI(Gq alpha) cells worked consistently, achieving high and tightly regulated levels of Gq alpha overexpression (38-fold increase compared with non-induced cells). We investigated the possibility of using an inducible system to increase the proportion of constitutively active endogenously expressed G protein-coupled receptors (GPCRs) by overexpressing Gq alpha. Not only did we observe an increase in basal activity following doxycycline treatment, but also increased intrinsic activity of agonists such as carbachol, endothelin, lysophosphatidic acid (LPA), and bradykinin. Furthermore, carbachol and LPA potency increased following Gq alpha overexpression, as did the intrinsic activity of the partial agonist pilocarpine, observations indicative of constitutive activity. An inducible cell line, transiently expressing G proteins, can therefore be employed to induce constitutive activity of endogenously expressed GPCRs. This model system could be used to identify clinically important inverse agonists.

Animals↗

PubMed1989

Localization of the fourth membrane spanning domain as a ligand binding site in the human platelet alpha 2-adrenergic receptor.

The human platelet alpha 2-adrenergic receptor is an integral membrane protein which binds epinephrine. The gene for this receptor has been cloned, and the primary structure is thus known [Kobilka et al. (1987) Science 238, 650-656]. A model of its secondary structure predicts that the receptor has seven transmembrane spanning domains. By covalent labeling and peptide mapping, we have identified a region of the receptor that is directly involved with ligand binding. Partially purified preparations of the receptor were covalently radiolabeled with either of two specific photoaffinity ligands: [3H]SKF 102229 (an antagonist) or p-azido[3H]clonidine (an agonist). The radiolabeled receptors were then digested with specific endopeptidases, and peptides containing the covalently bound radioligands were identified. Lysylendopeptidase treatment of [3H]SKF 102229 labeled receptor yielded one peptide of Mr 2400 as the product of a complete digest. Endopeptidase Arg-C gave a labeled peptide of Mr 4000, which was further digested to the Mr 2400 peptide by additional treatment with lysylendopeptidase. Using p-azido[3H]clonidine-labeled receptor, a similar Mr 2400 peptide was obtained by lysylendopeptidase cleavage. This Mr 2400 peptide corresponds to the fourth transmembrane spanning domain of the receptor. These data suggest that this region forms part of the ligand binding domain of the human platelet alpha 2-adrenergic receptor.

Affinity Labels↗

PubMed2003

Allelic variation of MHC structure alters peptide ligands to induce atypical partial agonistic CD8+ T cell function.

T cell receptors recognize small changes in peptide ligands leading to different T cell responses. Here, we analyzed a panel of HLA-A2-Tax11-19 reactive T cell clones to examine how small allelic variations of MHC molecules could alter the functional outcome of antigen recognition. Similar to the effects induced by antigenic altered peptide ligands, weak or partial agonistic T cell functions were identified in individual T cell clones with the recognition of MHC-altered peptide ligands (MAPLs). Interestingly, one subtype of HLA-A2 molecules induced an unusual type of partial agonistic function; proliferation without cytotoxicity. Modeling of crystallographic data indicated that polymorphic amino acids in the HLA-A2 peptide binding groove, especially the D-pocket, were responsible for this partial agonism. Reciprocal mutations of the Tax peptide side chain engaging the D-pocket indeed restored the agonist functions of the MHC-peptide complex. Whereas early intracellular signaling events were not efficiently induced by these MAPLs, phosphorylated c-Jun slowly accumulated with sustained long-term expression. These data indicate that MAPLs can induce atypical partial agonistic T cell function through structural and biochemical mechanisms similar to altered peptide ligands.

Alleles↗

PubMed2004

Activation, isolation, identification and in vitro proliferation of oval cells from adult rat livers.

Oval cells, putative hepatic stem cells, could potentially provide a novel solution to the severe shortage of donor livers, because of their ability to proliferate and differentiate into functional hepatocytes. We have previously demonstrated that oval cells can be induced to differentiate into cells with morphologic, phenotypic, and functional characteristics of mature hepatocytes. In this study, we have established a new model combining ethionine treatment with partial hepatectomy to activate oval cells, then developed a procedure utilizing selective enzymatic digestion and density gradient centrifugation to isolate and purify such cells from heterogeneous liver cell population. We identified oval cells by their morphological characteristics and phenotypic properties, thereby providing definitive evidence of the presence of hepatic stem-like cells in adult rat livers. Viewed by transmission electron microscopy, they were small cells with ovoid nuclei, a high nucleus/cytoplasm ratio and few organelles, including mitochondria and endoplasmic reticulum. Flow cytometric assay showed that these cells highly expressed OV-6, cytokeratin-19 (CK-19) and albumin. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis displayed that the freshly isolated cells co-expressed albumin, cytokeratin-7 (CK-7) and CK-19 mRNA, indicating that they were essentially bipotential hepatic stem-like cells. Furthermore, we set up a culture system containing growth factors and a fibroblast feeder layer, to provide nourishment to these cells. Thus, we were able to culture them in vitro for more than 3 months, with the number of cells doubling 100 times. Gene expressions of albumin, CK-7 and CK-19 in the cells derived from the expanding colonies at day 95 were confirmed by RT-PCR analysis. These data suggested that the hepatic oval cells derived from adult rat livers possess a high potential to proliferate in vitro with a large increase in number, while maintaining the bipotential nature of hepatic stem cells.

Albumins↗

PubMed2002

Toxicological evaluation of complex mixtures by pattern recognition: correlating chemical fingerprints to mutagenicity.

We describe the use of pattern recognition and multivariate regression in the assessment of complex mixtures by correlating chemical fingerprints to the mutagenicity of the mixtures. Mixtures were 20 organic extracts of exhaust particles, each containing 102-170 individual compounds such as polycyclic aromatic hydrocarbons (PAHs), nitro-PAHs, oxy-PAHs, and saturated hydrocarbons. Mixtures were characterized by full-scan GC-MS (gas chromatography-mass spectrometry). Data were resolved into peaks and spectra for individual compounds by an automated curve resolution procedure. Resolved chromatograms were integrated, resulting in a predictor matrix that was used as input to a principal component analysis to evaluate similarities between mixtures (i.e., classification). Furthermore, partial least-squares projections to latent structures were used to correlate the GC-MS data to mutagenicity, as measured in the Ames Salmonella assay (i.e., calibration). The best model (high r2 and Q2) identifies the variables that co-vary with the observed mutagenicity. These variables may subsequently be identified in more detail. Furthermore, the regression model can be used to predict mutagenicity from GC-MS chromatograms of other organic extracts. We emphasize that both chemical fingerprints as well as detailed data on composition can be used in pattern recognition.

Animals↗

PubMed1979

The effect of platinum analogues and combination chemotherapy on murine bladder cancer.

Cis-diamminedichloroplatinum II currently is the most effective chemotherapeutic agent in advanced bladder cancer. However, most of the objective responses are partial and/or of limited duration (average 6 months). In an effort to identify a more effective compound with less toxicity platinum analogues have been synthesized. Since results in the carcinogen-induced murine bladder cancer model have correlated with activity of drugs in man this model was used to evaluate 4 of these analogues. Although not as effective as the parent compound, cis-diamminedichloroplatinum, they exhibited significant antitumor activity in the poorly differentiated transplanted tumor. However, they were not able to reduce the incidence or size of primary tumors. Another approach to enhance tumor cell kill is combination chemotherapy. The addition of cyclophosphamide or cyclophosphamide and doxorubicin hydrochloride to cis-diamminedichloroplatinum produced a greater tumor inhibition than cis-diamminedichloroplatinum alone in experiments with the transplanted and the primary tumor models. It is hoped that these studies will continue to provide background information for the design of disease oriented phase I and II clinical trials.

Animals↗

PubMedDate not supplied

Electronic apex locator: a useful tool for root canal treatment in the primary dentition.

The purpose of this study was to test the ability of an electronic apex locator, Root ZX to measure the root canal length in primary teeth with partial resorption. Twenty extracted primary molars were embedded in an alginate model imitating in vivo conditions. Root ZX and radiographic measurements were compared in dry and wet environments to the actual tooth length. Root ZX identified the tooth length at the most coronal portion of the resorption. The content of the root canal did not influence the results. No statistical differences were found between electronic, radiographic and actual tooth length measurements, although the radiographic measurements were longer than the electronic ones. It is suggested that Root ZX is a preferable auxiliary device to measure root canal length in the primary dentition.

Child↗