Ischemic postconditioning lightening ischemia/reperfusion apoptosis of rats via mitochondria pathway.

OBJECTIVE:   To explore whether ischemic postconditioning will lighten hepatic apoptosis caused by hepatic ischemia/reperfusion injury by inhibiting the mitochondria pathway. MATERIALS AND METHODS: Pathomorphology of hepatic tissues in rats was observed under an optical microscope after hematoxylin-eosin (HE) staining. Hepatic apoptosis was detected using agarose gel electrophoresis (AGE) with DNA fragments and flow cytometry. Changes in morphology structure of mitochondria in hepatocytes of rats were observed under an electron microscope. Changes in mitochondria transmembrane potential of hepatocytes of rats were detected using a laser scanning confocal microscope (LSCM). Western blotting was adopted to detect changes in the expression of caspase-3 and cytochrome C protein in hepatocytes of rats. RESULTS: Compared with that in I/R group, swelling degree of mitochondria in most hepatocytes of rats in ischemic postconditioning (IPOST) group and IPC group was lighter. Changes in expression of caspase-3 and cytochrome C protein in hepatic cells of rats: caspase-3 was lowly expressed and cytochrome C was highly expressed in S group. The expression of caspase-3 was evidently higher in I/R group than that in S group and expression of cytochrome C protein was evidently lower than that in S group (p<0.05). The expression of caspase-3 protein was evidently decreased in IPOST group and IPC group and the expression of cytochrome C protein was evidently increased (p<0.05). CONCLUSIONS: IPOST can reduce hepatic apoptosis caused by hepatic ischemia/reperfusion injury in rats, which may be achieved by inhibiting the mitochondria pathway.

[Time series analysis on the effect of ambient fine particulate matters and temperature interactions on schizophrenia admission in Tongling City of Anhui Province, 2014-2017].

Objective: To explore the effect of ambient fine particulate matters (PM(2.5)) and temperature interaction on schizophrenia admission. Methods: All admission data were retrieved from the Psychiatric Hospital and Municipal Hospital of TongLing from January 1, 2014 to December 31, 2017. Daily air pollution and meteorological data were collected from the Tongling Environmental Protection Agency and Meteorological Bureau, respectively. A distributed lag non-linear model combined with the generalized additive model were applied to explore the effects of PM(2.5), multi-pollutants, and the interaction between temperature and PM(2.5) on schizophrenia admission. The stratification of temperature was divided by three criteria. The low temperature layer was defined as P(95) or >P(90) or >P(80) was defined as the high temperature layer. Results: From 2014 to 2017, 6 642 patients were admitted for schizophrenia in Tongling, and the median of PM(2.5) and temperature were 47.0 µg/m(3) and 17.5 ℃, respectively. The median concentration of PM(2.5) (P(50)) was taken as a reference. When the exposure concentration of PM(2.5) was P(90), the lagged effect appeared in the first day with RR=1.03 (95%CI: 1.00-1.07) and reached the maximum in the fifth day with RR=1.16 (95%CI: 1.13-1.19). In the multi-pollutant models, it was found that the simultaneous inclusion of PM(2.5) and NO(2) had higher risk of schizophrenia admission, with the RR=1.18 (95%CI: 1.15-1.22), P<0.001. The risk of schizophrenia admission caused by PM(2.5) exposure at high temperature was greatest under the three temperature stratification standards, which were 12.1% (8.5%-15.7%), 9.7% (6.9%-12.6%) and 17.1% (11.6%-22.8%), all P values <0.001. Conclusion: With the increase of PM(2.5) concentration, the risk of schizophrenia admission is increased, and the risk effect of PM(2.5) is stronger at high temperature.

Myostatin inhibits porcine intramuscular preadipocyte differentiation in vitro.

This study assessed the effect of myostatin on adipogenesis by porcine intramuscular preadipocytes. Intramuscular preadipocytes were isolated from the longissimus dorsi muscle of newborn pigs. Myostatin inhibited intramuscular preadipocyte differentiation in a dose-dependent manner. Myostatin treatment during preadipocyte differentiation significantly (P < 0.05) inhibited the expression of the adipogenic marker genes CCAAT/enhancer-binding protein ß, CCAAT/enhancer-binding protein α, peroxisome proliferator-activated receptor γ, sterol regulatory element-binding protein-1c, fatty acid-binding protein, and adiponectin. Myostatin also significantly (P < 0.05) reduced the release of glycerol and decreased both adipose triglyceride lipase and hormone-sensitive lipase expression in intramuscular adipocytes. Our study suggests that myostatin acts as an extrinsic regulatory factor in regulating intramuscular adipogenesis.

Organ-specific hemosiderosis and functional correlation in Chinese patients with thalassemia intermedia and hemoglobin H disease.

We performed MRI assessment in 37 adult Chinese patients with thalassemia intermedia and hemoglobin H disease. Despite abnormal ferritin and liver T2*, only 5% of patients had cardiac hemosiderosis. The two patients with reduced ejection fraction had normal cardiac T2*. Half of the cases showed pituitary and pancreatic iron loading. Subclinical endocrine abnormalities (HOMA, insulin growth factor) showed correlation with pancreatic, pituitary, and cardiac MRI values. Prospective data with serial functional and imaging monitoring is needed to verify the utility for chelation to improve cardiac and endocrine function in this group of patients.

Literature Mapping with PubAtlas - extending PubMed with a 'BLASTing interface'.

PubAtlas (www.pubatlas.org) is a web service and standalone program providing literature maps for the biomedical research literature. It accepts user-defined sets of terms (PubMed queries) as input, and permits 'BLASTing' of one set against another: for all terms x and y in these sets, deriving the results of the pairwise intersections x AND y. This all vs. all capability extends PubMed with a literature analysis interface. Correspondingly, the basic form of literature map that PubAtlas provides for exploring associations among sets of terms is an interactive tabular display, in heatmap/microarray format.PubAtlas supports development of specialized lexica -- hierarchies of controlled terminology that can represent sets of related concepts or a 'user-defined query language'. PubAtlas also provides historical perspectives on the literature, with temporal query features that highlight historical patterns. Generally, it is a framework for extending the PubMed interface, and an extensible platform for producing interactive literature maps.

Dietary fiber and coronary artery disease.

Ischemic coronary disease remains the leading cause of death in the United States, and exerts a tremendous cost burden to the health care system. Hypercholesterolemia has been shown to be one of the major risk factors of artherosclerosis, which plays an important role in the pathogenesis of coronary artery disease (CAD). Over the past 3 decades, a variety of epidemiological, animal studies and human (clinical) trials have demonstrated the preventive and therapeutic benefits of dietary fibers on hypercholesterolemia and the reduction of mortality rate from CAD. To review the data, hopefully this article can draw more public attention to dietary fibers given their beneficial effects and relatively low side-effect profile. Diet modification should be the initial approach to the clinical management of hypercholesterolemia.

A medical digital library to support scenario and user-tailored information retrieval.

Current large-scale information sources are designed to support general queries and lack the ability to support scenario-specific information navigation, gathering, and presentation. As a result, users are often unable to obtain desired specific information within a well-defined subject area. Today's information systems do not provide efficient content navigation, incremental appropriate matching, or content correlation. We are developing the following innovative technologies to remedy these problems: 1) scenario-based proxies, enabling the gathering and filtering of information customized for users within a pre-defined domain; 2) context-sensitive navigation and matching, providing approximate matching and similarity links when an exact match to a user's request is unavailable; 3) content correlation of documents, creating semantic links between documents and information sources; and 4) user models for customizing retrieved information and result presentation. A digital medical library is currently being constructed using these technologies to provide customized information for the user. The technologies are general in nature and can provide custom and scenario-specific information in many other domains (e.g., crisis management).

Creating and indexing teaching files from free-text patient reports.

Teaching files based on real patient data can enhance the education of students, staff and other colleagues. Although information retrieval system can index free-text documents using keywords, these systems do not work well where content bearing terms (e.g., anatomy descriptions) frequently appears. This paper describes a system that uses multi-word indexing terms to provide access to free-text patient reports. The utilization of multi-word indexing allows better modeling of the content of medical reports, thus improving retrieval performance. The method used to select indexing terms as well as early evaluation of retrieval performance is discussed.

Term domain distribution analysis: a data mining tool for text databases.

In this paper, we give a case history illustrating the real-world application of a useful technique for data mining of text databases. The technique, which we call Term Domain Distribution Analysis (TDDA), consists of keeping track of term frequencies for specific finite domains and announcing significant differences from standard frequency distributions over these domains as a hypothesis. TDDA is part of a larger framework, the Digital Filter Model, for data mining of text documents. In the case study presented, the domain of terms was the pair {right, left}, over which we expected a uniform distribution. In analyzing term frequencies in a thoracic lung cancer database, the TDDA technique led to the surprising discovery that primary thoracic lung cancer tumors appear in the right lung more often than the left lung, with a ratio of 3:2. Treating the text discovery as a hypothesis, we verified this relationship against the medical literature in which primary lung tumor sites were reported, using a standard chi 2 statistic. We subsequently developed a working theoretical model of lung cancer that may explain the discovery. This discovery and our model may change how oncologists view the mechanisms of primary lung tumor location.

A human prostatic stromal myofibroblast cell line WPMY-1: a model for stromal-epithelial interactions in prostatic neoplasia.

Here we report the characterization of an SV40 large-T antigen-immortalized stromal cell line, WPMY-1, derived from the same prostate as our previously described epithelial cell lines. The WPMY-1 cells were determined to be myofibroblasts on the basis of co-expression of smooth muscle alpha-actin and vimentin. They also show positive staining for androgen receptor, large-T antigen, and positive but heterogeneous staining for p53 and pRb. Their growth is stimulated by the synthetic androgen mibolerone to 145% of control (100%). Platelet-derived growth factor BB, epidermal growth factor and basic fibroblast growth factor, at 10 ng/ml, stimulated growth to 138, 143 and 146% of control, respectively. Transforming growth factor-beta, at 10 ng/ml, inhibited serum-induced growth to 65% of control in the presence of 1% serum, and bFGF-induced growth to 30% of control. A serum-free medium was developed for optimal growth of WPMY-1 cells. They show anchorage-independent growth in soft agar. Studies on paracrine interactions show that myofibroblast-conditioned medium causes a marked inhibition of growth in WPE1-10 cells, while conditioned medium from WPE1-10 prostatic epithelial cells caused only a small increase in the growth of WPMY-1 cells. WPMY-1 cells secrete very low levels of MMP-9 but high levels of MMP-2, markedly higher than the epithelial cells. These epithelial and myofibroblast cell lines, derived from the same prostate, provide novel and useful models for studies on paracrine stromal-epithelial interactions in carcinogenesis, tumor progression, prevention and treatment of prostate cancer and benign prostatic hyperplasia.

A composite regulatory element in the first intron of the estrogen-responsive very low density apolipoprotein II gene.

During periods of egg laying in the chicken, when circulating levels of estrogen are increased, the liver-specific estrogen-dependent very low density apolipoprotein II (apoVLDLII) gene is expressed. This expression takes place primarily at the level of transcription, driven by two estrogen response elements that reside in the promoter. In transient transfection assays, expression is increased fourfold when the first intron is added to the promoter construct, indicating that 75% of the regulation comes from intron A. Using in vitro DNase I footprinting, six protein-binding sites were revealed throughout the first intron. The functional significance of these binding sites was evaluated by mutation and transient transfection. Two of the protein-binding regions were shown to increase transcription. Site-specific mutations introduced at either the +66 to +86 or +112 to +129 sites disrupted trans-factor binding and reduced the estrogen-dependent expression by 45% and 34%, respectively. A plasmid containing both mutations resulted in a 43% decrease in expression, indicating that the contributions of these regions are not additive. Competition with known sequences in electrophoretic mobility shift assays suggested that the +66 to +86 site binds a chicken member of the nuclear receptor transcription factor family.

A multimedia database system for thermal ablation therapy of brain tumors.

A prototype multimedia medical database is described for supporting thermal ablation therapy of brain tumors. Its design is motivated by the major need to manage and access multimedia information on the progress and reaction of tumors to various therapy protocols. The database links images to patient data in a way that permits the use to view and query medical information using alphanumeric, temporal, and feature-based predicates. Visualization programs permit the user to view or annotate the query results in various ways. These results support the wide variety of data types and presentation methods required by neuroradiologists to manage thermal ablation therapy data. The database satisfactorily meets the requirements defined by thermal ablation therapy. A similar approach is being undertaken for supporting different therapies of other types of tumors, thus showing the generality of our approach.

A unified timeline model and user interface for multimedia medical databases.

A multimedia medical database model and prototype is described for supporting a timeline-based presentation of information. The database links image and text data in a way that permits users to look at medical information in a single unified view. Various visualization programs permit the user to view data in various ways, including full image views, graphs, and tables. Our technology is applied for proof-of-concept to two areas: thoracic oncology and thermal tumor ablation therapy of the brain. This effort is part of the multidisciplinary KMeD project in collaboration with medical research and clinical treatment projects at UCLA.

Integrated multimedia timeline of medical images and data for thoracic oncology patients.

A prototype multimedia medical database has been developed to provide image and textual data for thoracic oncology patients undergoing treatment of advanced malignancies. The database integrates image data from the hospital picture archiving and communication system with textual reports from the radiology information system, alphanumeric data contained in the hospital information system, and other electronic medical data. The database presents information in a timeline format and also contains visualization programs that permit the user to view and annotate radiographic measurements in tabular or graphic form. The database provides an efficient and intuitive display of the changing status of oncology patients. The ability to integrate, manage, and access relevant multimedia information may substantially enhance communication among distributed multidisciplinary health care providers and may ensure greater consistency and completeness of patient-related data.

Insulin inhibits the estrogen-dependent expression of the chicken very low density apolipoprotein II gene in Leghorn male hepatoma cells.

Expression of the very low density apolipoprotein II (apoVLDLII) gene in the chicken is absolutely dependent on estrogen. ApoVLDLII mRNA is expressed in the Leghorn male hepatoma (LMH) cell line in response to estrogen in completely defined medium. Addition of serum to these cultures results in a decrease in apoVLDLII mRNA. Data in this report demonstrate that 1 nM insulin has the same inhibitory effect as 10% serum. Insulin inhibits apoVLDLII mRNA in a dose-dependent manner; 100 fM insulin inhibits the estrogen-dependent response by 76%. After transfection of LMH cells with apoVLDLII sequences from an 8.9-kilobase (kb) genomic clone (pApo107) that contains the entire 2.9-kb coding sequence along with approximately 3 kb each of 5'- and 3'-flanking DNA, the estrogen-dependent expression of apoVLDLII mRNA from both the endogenous gene and transfected DNA is reduced by insulin. Furthermore, insulin reduces by more than 90% the estrogen-dependent expression from a chimeric construct, pApoCAT, which contains apoVLDLII sequences -900/+1455 cloned 5' of the bacterial chloramphenicol acetyltransferase (CAT) reporter gene. To determine the specificity of the response, expression of the pApoCAT construct was tested with insulin-like growth factor-I and insulin. Three hundred picomolar insulin inhibits the estrogen-mediated CAT activity by 50%. Insulin-like growth factor-I at this concentration has no effect or slightly increases the estrogen-dependent expression of pApoCAT, suggesting that the observed inhibitory action is mediated by the insulin receptor. Consequently, the LMH cells provide an excellent model system in which to study the molecular mechanism of insulin and estrogen interaction in the regulation of gene expression.