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At least 1,261 records · Page 70Linked to original sources
PubMed2001

Gene targeting in Arabidopsis.

Precise modification by gene targeting (GT) provides an important tool for studies of gene function in vivo. Although routine with many organisms, only isolated examples of GT events have been reported for flowering plants. These were at low frequencies precluding reliable estimation of targeting efficiency and evaluation of GT mechanisms. Here we present an unambiguous and straightforward system for detection of GT events in Arabidopsis using an endogenous nuclear gene encoding protoporphyrinogen oxidase (PPO), involved in chlorophyll and heme syntheses. Inhibition of PPO by the herbicide Butafenacil results in rapid plant death. However, the combination of two particular mutations renders PPO highly resistant to Butafenacil. We exploited this feature for selection of GT events by introducing the mutations into the PPO gene by homologous recombination. We have estimated the basal GT frequency to be 2.4 x 10(-3). Approximately one-third of events were true GT (TGT) leading to the anticipated modification of the chromosomal PPO copy. The remaining events could be classified as ectopic GT (EGT) arising by modification of vector DNA by the chromosomal template and its random integration into the Arabidopsis genome. Thus the TGT frequency in our experimental setup is 0.72 x 10(-3). In view of the high efficiency of Arabidopsis transformation, GT experiments of a reasonable size followed by a PCR screen for GT events should also allow for modification of non-selectable targets. Moreover, the system presented here should contribute significantly to future improvement of GT technology in plants.

Arabidopsis↗
PubMed1995

Differentiation between adenomyoma and leiomyoma with transvaginal ultrasonography.

The clinical utility of transvaginal ultrasonography in the differentiation of adenomyoma from leiomyoma was evaluated in 147 patients who had been scheduled for surgery due to symptomatic uterine masses. In all subjects, ultrasonographic images obtained preoperatively were correlated postoperatively with surgicopathological findings. Pathological findings showed that 110 patients proved to have fibroids, while 30 had adenomyomata. For the diagnosis of adenomyoma, transvaginal ultrasonography attained a sensitivity of 80%, a specificity of 94.3%, a positive predictive value of 85.7% and a negative predictive value of 90.9%, compared with a sensitivity of 94.3%, a specificity of 80%, a positive predictive value of 90.9% and a negative predictive value of 85.7% for leiomyoma diagnosis. Further to assess which characteristic used in ultrasonography was useful in the differential diagnosis, five characteristics were analyzed and compared by chi 2 test. These were position, number, margin and echogenicity of the uterine masses and the presence or absence of hypoechoic spaces (lacunae). Margin, echogenicity, mass number and lacunae were significantly different between both conditions. A stepwise logistic regression procedure revealed that margin, lacunae and echogenicity were good parameters for differentiating adenomyoma from leiomyoma. If we selected the features of distinct margin and absence of hypoechoic lacunae within the masses for analysis, leiomyoma could be correctly predicted in 97% of patients.

Adenomyoma↗
PubMedDate not supplied

Expression of the insulin-like growth factor-I receptor in primary breast cancer and lymph node metastases: correlations with estrogen receptors alpha and beta.

Numerous laboratory studies and some epidemiological data have suggested the involvement of the insulin-like growth factor-I receptor (IGF-IR) in breast cancer development and progression. However, data on IGF-IR expression in human tissues, including breast cancer sections, are limited and often inconsistent. We therefore examined by immunohistochemistry the expression of IGF-IR in primary tumors and breast cancer metastases to lymph nodes, and correlated IGF-IR positivity with estrogen receptor (ER) status and selected clinicopathological features. We found that 1) IGF-IR was expressed in primary tumors as well as in lymph node metastases, but the expression in primary tumors was more frequent (56 % vs. 44.4 %); 2) IGF-IR expression in primary tumors was associated with negative node status (p < 0.033); 3) in node-negative primary tumors, IGF-IR positively correlated with ERbeta (p < 0.008; r = 0.538), but not with ERalpha, tumor size or grade; 4) both IGF-IR-positive and IGF-IR-negative primary tumors were found to produce IGF-IR-positive as well as IGF-IR-negative metastases; 5) in metastases, IGF-IR expression did not associate with ERalpha, ERbeta or any of the studied pathobiological markers. The results suggest that IGF-IR could become a viable pharmaceutical target in breast cancer therapy, but such therapy should be based on IGF-IR assessment in primary tumor and metastasis in each potential patient.

Breast Neoplasms↗
PubMed1975

Clinical importance of lymphoblasts with T markers in childhood acute leukemia.

Of 48 children with acute lymphocytic leukemia 11 had blast cells with receptors for sheep erythrocytes in their initial bone-marrow aspirates and 37 did not. A comparison of selected clinical features indicated striking differences between the two groups. Leukemia with the receptors was associated with a high proportion of older children, predominantly boys, a thymic mass, and a high white-cell count at diagnosis. In contrast, the 37 children with leukemia without the receptors were generally less than five years of age, with a nearly equal distribution of boys and girls; all but one had normal chest roentgenograms, and only one had a white-cell count greater than 100,000. Thus, the presence or absence of lymphoblasts with sheep erythrocyte receptors--a T-cell marker--distinguishes two forms of childhood acute lymphocytic leukemia, each with a distinct distribution of age and sex as well as other characteristic clinical features.

Adolescent↗
PubMed1997

Fixation patterns made during brief examination of two-dimensional images.

Measurements were carried out of saccadic eye movements made during brief (3 s) examination of images which the observer was asked to identify. Each image was identified in three forms: low-pass filtered, high-pass filtered, and unfiltered. The analysis of the eye-movement patterns was based on the locations of fixations made during examination of the images, for which purpose a least-squares measures of similarity between two sets of locations was introduced. It is shown that there is a high degree of similarity between fixations made by the same observer to the different versions of a given image and that for a given image there is a high degree of similarity between fixations made by the eighteen observers who participated in the experiments. The similarities are greater for the initial 1.5 s than for the full viewing period of 3 s. The similarity between the locations of fixations and those of selected image features such as local contrast, high-spatial-frequency content, and edge density was also examined. It is shown that there is only weak similarity between the locations of fixations and those of any given local image feature, and the tendency of observers to fixate centrally on the image is identified as the principal reason for the low similarity values. It is shown that if the nonuniform distribution of eye movements is taken into account, significant similarities are found between the locations of fixations and those of certain image features, such as edge density.

Adult↗
PubMed2005

Predisposing factors for inner ear hearing loss association with chronic otitis media.

The aim of the present study was to investigate the consequences of chronic otitis media on inner ear function. Retrospective analysis of conventional pure-tone audiometry tests was carried out on 344 patients who were scheduled for surgical treatment of unilateral chronic otitis media without other risk factors for sensorineural hearing loss. Bone conduction thresholds of diseased ears were compared with those of contralateral, non-diseased ears. Selected clinical features were assessed among diseased ears to examine possible influences on inner ear function. Mean bone conduction threshold differences varied from 0.6 dB at 0.5 kHz to 3.7 dB at 4 kHz. These differences augmented with increasing duration of middle ear disease. Impaired hearing by bone conduction thresholds of diseased ears correlated with increased age at every frequency and with an interruption of the ossicular chain only at higher frequencies. The severity of sensorineural hearing loss correlated with longer duration of middle ear disease. Thus, surgical treatment of dry and apparently stable tympanic membrane perforation is warranted.

Adult↗
PubMed2026

BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans↗
PubMed2001

Topographical and physicochemical modification of material surface to enable patterning of living cells.

Precise control of the architecture of multiple cells in culture and in vivo via precise engineering of the material surface properties is described as cell patterning. Substrate patterning by control of the surface physicochemical and topographic features enables selective localization and phenotypic and genotypic control of living cells. In culture, control over spatial and temporal dynamics of cells and heterotypic interactions draws inspiration from in vivo embryogenesis and haptotaxis. Patterned arrays of single or multiple cell types in culture serve as model systems for exploration of cell-cell and cell-matrix interactions. More recently, the patterned arrays and assemblies of tissues have found practical applications in the fields of Biosensors and cell-based assays for Drug Discovery. Although the field of cell patterning has its origins early in this century, an improved understanding of cell-substrate interactions and the use of microfabrication techniques borrowed from the microelectronics industry have enabled significant recent progress. This review presents the important early discoveries and emphasizes results of recent state-of-the-art cell patterning methods. The review concludes by illustrating the growing impact of cell patterning in the areas of bioelectronic devices and cell-based assays for drug discovery.

Animals↗
PubMed2000

BAFF mediates survival of peripheral immature B lymphocytes.

B cell maturation is a very selective process that requires finely tuned differentiation and survival signals. B cell activation factor from the TNF family (BAFF) is a TNF family member that binds to B cells and potentiates B cell receptor (BCR)-mediated proliferation. A role for BAFF in B cell survival was suggested by the observation of reduced peripheral B cell numbers in mice treated with reagents blocking BAFF, and high Bcl-2 levels detected in B cells from BAFF transgenic (Tg) mice. We tested in vitro the survival effect of BAFF on lymphocytes derived from primary and secondary lymphoid organs. BAFF induced survival of a subset of splenic immature B cells, referred to as transitional type 2 (T2) B cells. BAFF treatment allowed T2 B cells to survive and differentiate into mature B cells in response to signals through the BCR. The T2 and the marginal zone (MZ) B cell compartments were particularly enlarged in BAFF Tg mice. Immature transitional B cells are targets for negative selection, a feature thought to promote self-tolerance. These findings support a model in which excessive BAFF-mediated survival of peripheral immature B cells contributes to the emergence and maturation of autoreactive B cells, skewed towards the MZ compartment. This work provides new clues on mechanisms regulating B cell maturation and tolerance.

Animals↗
PubMed2005

Genetic evidence for a distinct subtype of schizophrenia characterized by pervasive cognitive deficit.

A novel phenotyping strategy in schizophrenia, targeting different neurocognitive domains, neurobehavioral features, and selected personality traits, has allowed us to identify a homogeneous familial subtype of the disease, characterized by pervasive neurocognitive deficit. Our genome scan data indicate that this subtype, which accounts for up to 50% of our sample, has a distinct genetic basis and explains linkage to chromosome 6p24 reported previously. If representative of other populations, the ratio of schizophrenia subtypes observed in our families could have a profound impact on sample heterogeneity and on the power of genetic studies to detect linkage and association. Our proposed abbreviated battery of tests should facilitate phenotype characterization for future genetic analyses and allow a focus on a crisply defined schizophrenia subtype, thus promoting a more informed search for susceptibility genes.

Attention↗
PubMed2005

The changing face of fungal infections in health care settings.

As strategies to prevent invasive fungal infections among both hospitalized and nonhospitalized patients have evolved, the epidemiology of these infections has changed. Several unique features of select Candida species and molds have facilitated the emergence of these pathogens as more-common causes of infection than in previous years. In this context, the changing pathogen profiles, unique antifungal susceptibilities, and approaches to treatment are outlined.

Antifungal Agents↗
PubMed2003

Time course of cortical hemorrhages after closed traumatic brain injury: statistical analysis of posttraumatic histomorphological alterations.

We examined 305 autopsied brains for histomorphological alterations to determine the time course of reactions in cortical hemorrhages following traumatic closed brain injury. Eighteen morphological criteria were considered: red blood cells (RBCs), polymorphonuclear leukocytes (PMNs), macrophages (Ms), RBC-containing Ms, hemosiderin, hematoidin, lipid-containing Ms, fibroblasts, endothelial cells, collagenous fibres, gemistocytic astrocytes, fibrillary gliosis, hemosiderin-containing astrocytes, neuronal damage, neuronophagy, axonal swelling (beta-amyloid precursor protein: beta-APP), axonal bulbs (van Gieson stain), and mineralisation of neurons. The interval between the time of brain injury and death ranged from 1 min to 58 years. Following routine staining and immunohistochemical staining of microglia (CD68), astrocytes (GFAP) and injured axons (beta-APP), paraffin sections were examined by light microscopy for the presence of the selected histomorphological features. For each cytomorphological phenomenon, the time at which it could be demonstrated for the first time and for the last time (observation period) was determined. The relative frequency of each criterion was established for each observation period. The limits of confidence for the respective relative frequencies were estimated with a reliability of 95% according to Clopper and Pearson. An apparent correlation was found between the frequency of a given histomorphological phenomenon and the length of the posttraumatic interval. To check for accuracy of prediction, half of the cases (group 1; n = 153) were used to develop a multistage evaluation model; half (group 2; n = 152) were used to evaluate the validity of the data of group 1. Applying this model, 117 of the 152 control group cases (76.97%) could be correctly classified and further 26 cases (17.11%) being assigned to an interval close to the correct interval. Thus, this model allows classification of the correct posttraumatic interval or an interval close to the correct posttraumatic interval in about 95% of cases. We developed a software program that allows the estimation of survival time of TBI based on the relative frequency of the 18 morphological features. Applying this software will help to estimate the posttraumatic interval of cortical hemorrhages following TBI of unknown survival time.

Adolescent↗
PubMed1990

Morphologic diversity in malignant melanomas.

A review was conducted of 335 malignant melanomas to identify variant morphologic patterns that might be confused with other tumors. In all, 27 predominantly amelanotic neoplasms with unusual histologic features were selected for additional study. These included nine with an adenoid or pseudopapillary pattern, seven small cell neoplasms, five with prominent myxoid stroma, four with a hemangiopericytoma-like appearance, and two composed of neoplastic cells with a signet-ring configuration. A diagnosis of melanoma was confirmed in all cases by Fontana-Masson strains for melanin pigment, electron microscopic examination, or the results of immunohistochemical analyses for cytokeratin, vimentin, S-100 protein, and the HMB-45 antigen. One tumor was associated with a congenital hairy melanocytic nevus, five were vulvovaginal lesions, four arose in the sinonasal tract, and one occurred in the rectum. Four of the specified microscopic patterns were observed in both primary and secondary neoplasms; the two signet-ring cell melanomas were recurrent lesions. The authors conclude that malignant melanomas may assume the histologic guise of adenocarcinomas, small cell carcinomas, and sarcomas, in a variety of tissue sites. Special studies designed to detect melanocytic differentiation are therefore appropriate in diverse differential diagnostic settings.

Adolescent↗
PubMed2004

Data mining in bioinformatics using Weka.

UNLABELLED: The Weka machine learning workbench provides a general-purpose environment for automatic classification, regression, clustering and feature selection-common data mining problems in bioinformatics research. It contains an extensive collection of machine learning algorithms and data pre-processing methods complemented by graphical user interfaces for data exploration and the experimental comparison of different machine learning techniques on the same problem. Weka can process data given in the form of a single relational table. Its main objectives are to (a) assist users in extracting useful information from data and (b) enable them to easily identify a suitable algorithm for generating an accurate predictive model from it. AVAILABILITY: http://www.cs.waikato.ac.nz/ml/weka.

Algorithms↗