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PubMed2004

[Identification and origin of Brazilian journals related to public or collective health issues, published from 1998 to 2003].

The diversity of contents regarding Brazilian scientific journals related to public or collective health reflects peculiar aspects of this field's reach and its interfaces with several other fields. A bibliometric survey was conducted with five databases, including catalogs and sites, aimed at identifying journals related to the public/collective health field and published from 1998 to 2003, while identifying the geographic location of the respective institutions. A total of 118 titles were initially identified, subsequently reduced to 83 journals when indicators of these bases were confronted and matched, 66 of which were published in the last five years. Some 57.6% of the institutions responsible for these journals are located in the Southeast of Brazil; 16.7% in the South; 13.6% in the Central West; 10.6% in the Northeast; and 1.5% in the North. The results are displayed in a summary chart according to journal title, ISSN, name of the institution in charge, and respective regional location.

Bibliometrics↗
PubMedDate not supplied

[Prognostic value of lymphatic vessel and neural invasion in colorectal carcinoma].

OBJECTIVES: The paradoxical evolution of approximately one third of patients with colorectal cancer cataloged in Dukes stages B and C demonstrates the necessity of make useful other prognostic criteria. The presence of neural and lymphatic invasion of tumor cells was correlated with the prognosis of patients submitted to radical operation. METHODS: We performed a retrospective study on 320 patients with colo-rectal carcinoma, with mean age 58 years and 199 (62.2%) females. Neural invasion was assessed as positive if cancer cells infiltration into the perineurium or neural fasciculus was detected at the leading point. Lymphatic invasion was defined by cancer cells infiltration into a space limited by endothelium without muscular or elastic fibers. Those variable were associated to the original classification of Dukes. RESULTS: Lymphatic and neural invasion was demonstrated in 14.1% and 15% of 320 operation specimens respectively. The most frequent site of lymphatic and neural invasion was the rectum. The overall survival was 25% in the presence of neural invasion and 64% without neural invasion (p<.01). At the presence of lymphatic invasion, the overall survivals were 26.7% and 63.3%, respectively (p <0.01). The overall survival was always worse in the presence of the invasion neural, independently of the compromising or not of the lymphonodes. In patients of free lymphonodes, the lymphatic invasion identified sub-groups of sick with worse prognosis. The presence of these variable it identified in patients with tumors Dukes B, sub-group of worse prognosis. CONCLUSION: Neural and lymphatic invasion are important ways of spread of colorectal cancer and the presence of both is associated with worse prognosis.

Adenocarcinoma↗
PubMed2005

Parameters of LRP5 from a structural and molecular perspective.

LRP5, along with LRP6 and their Drosophila homolog, Arrow, constitute a novel subclass of the LDL receptor superfamily. The arrangement of structural motifs in these receptors is different from the other members of the superfamily, and only recently have we begun to understand the functional importance of human LRP5 (and LRP6). Whole genome positional cloning studies have identified a number of mutations in LRP5 that underlie inherited human diseases/phenotypes, particularly those involving the skeleton and the eye. A number of studies have illustrated the importance of Lrp5/6/Arrow as a co-receptor with Frizzled for the Wnt proteins and their critical role in the regulation of the Wnt/beta-catenin signaling pathway. The cataloging of these human mutations, in combination with engineered mutations in mice and other studies involving gene/protein modifications, has led to a better understanding of the function of the various domains in LRP5/6. In this review, we discuss a number of studies that have revealed a wide variety of protein-protein interactions that occur with the various structural motifs in the Lrp5 protein. Ultimately, these interactions regulate the activity of the Wnt/beta-catenin signaling pathway and the role it plays in processes such as bone mass accrual and vision.

Amino Acid Sequence↗
PubMed2001

MicroSAGE analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages.

Mesenchymal stem cells (MSCs) isolated from the bone marrow of adult organisms are capable of differentiating into adipocytes, chondrocytes, myoblasts, osteoblasts, and hematopoiesis-supporting stroma. We recently demonstrated that MSCs also adopt glial cell fates when transplanted into the developing central nervous system and hence can produce tissue elements derived from a separate embryonic layer. Despite these remarkable properties, it has been difficult to establish specific criteria to characterize MSCs. Using a modified protocol for micro-serial analysis of gene expression, we cataloged 2,353 unique genes expressed by a single cell-derived colony of undifferentiated human MSCs. This analysis revealed that the MSC colony simultaneously expressed transcripts characteristic of various mesenchymal cell lineages including chondrocytes, myoblasts, osteoblasts, and hematopoiesis-supporting stroma. Therefore, the profile of expressed transcripts reflects the developmental potential of the cells. Additionally, the MSC colony expressed mRNAs characteristic of endothelial, epithelial and neuronal cell lineages, a combination that provides a unique molecular signature for the cells. Other expressed transcripts included various products involved in wound repair as well as several neurotrophic factors. A total of 268 novel transcripts were also identified, one of which is the most abundantly expressed mRNA in MSCs. This study represents the first extensive gene expression analysis of MSCs and as such reveals new insight into the biology, ontogeny, and in vivo function of the cells.

Base Sequence↗
PubMed2005

Biological activities encoded by the murine mesenchymal stem cell transcriptome provide a basis for their developmental potential and broad therapeutic efficacy.

We used serial analysis of gene expression to catalog the transcriptome of murine mesenchymal stem cells (MSCs) enriched from bone marrow by immunodepletion. Interrogation of this database, results of which are delineated in the appended databases, revealed that immunodepleted murine MSCs (IDmMSCs) highly express transcripts encoding connective tissue proteins and factors modulating T-cell proliferation, inflammation, and bone turnover. Categorizing the transcriptome based on gene ontologies revealed the cells also expressed mRNAs encoding proteins that regulate mesoderm development or that are characteristic of determined mesenchymal cell lineages, thereby reflecting both their stem cell nature and differentiation potential. Additionally, IDmMSCs also expressed transcripts encoding proteins regulating angiogenesis, cell motility and communication, hematopoiesis, immunity and defense as well as neural activities. Immunostaining and fluorescence-activated cell sorting analysis revealed that expression of various regulatory proteins was restricted to distinct subpopulations of IDmMSCs. Moreover, in some cases, these proteins were absent or expressed at reduced levels in other murine MSC preparations or cell lines. Lastly, by comparing their transcriptome to that of 17 other murine cell types, we also identified 43 IDmMSC-specific transcripts, the nature of which reflects their varied functions in bone and marrow. Collectively, these results demonstrate that IDmMSC express a diverse repertoire of regulatory proteins, which likely accounts for their demonstrated efficacy in treating a wide variety of diseases. The restricted expression pattern of these proteins within populations suggests that the cellular composition of marrow stroma and its associated functions are more complex than previously envisioned.

Animals↗
PubMed2006

Reverse serial analysis of gene expression (SAGE) characterization of orphan SAGE tags from human embryonic stem cells identifies the presence of novel transcripts and antisense transcription of key pluripotency genes.

Serial analysis of gene expression (SAGE) is a powerful technique for the analysis of gene expression. A significant portion of SAGE tags, designated as orphan tags, however, cannot be reliably assigned to known transcripts. We used an improved reverse SAGE (rSAGE) strategy to convert human embryonic stem cell (hESC)-specific orphan SAGE tags into longer 3' cDNAs. We show that the systematic analysis of these 3' cDNAs permitted the discovery of hESC-specific novel transcripts and cis-natural antisense transcripts (cis-NATs) and improved the assignment of SAGE tags that resulted from splice variants, insertion/deletion, and single-nucleotide polymorphisms. More importantly, this is the first description of cis-NATs for several key pluripotency markers in hESCs and mouse embryonic stem cells, suggesting that the formation of short interfering RNA could be an important regulatory mechanism. A systematic large-scale analysis of the remaining orphan SAGE tags in the hESC SAGE libraries by rSAGE or other 3' cDNA extension strategies should unravel additional novel transcripts and cis-NATs that are specifically expressed in hESCs. Besides contributing to the complete catalog of human transcripts, many of them should prove to be a valuable resource for the elucidation of the molecular pathways involved in the self-renewal and lineage commitment of hESCs.

Cells, Cultured↗
PubMed2003

The gene expression profiling of sporadic pheochromocytoma and novel full-length cDNAs cloning.

Pheochromocytoma is a chromaffin cell neoplasm that typically causes symptoms and signs of episodic catecholamine release. Pheochromocytoma can be divided into two types: familial and sporadic. The molecular mechanisms involved in familial pheochromocytoma have been unraveled, but the detailed molecular mechanism of sporadic pheochromocytoma remains unknown. The present study thus aimed at characterization of gene expression profiling of sporadic pheochromocytoma using expressed sequence tags (ESTs), and established a preliminary catalog of genes expressed in the tumor. In total, 4115 ESTs were generated from the tumor library. The gene expression profilings of the pheochromocytoma and the normal adrenal gland were compared, and 341 genes were identified to be significantly expressed differently between the two libraries. Interestingly, 16 known genes participating in cell division or apoptosis were notably differently expressed between the tumor and the normal adrenal gland. Twenty-four novel full-length cDNAs were cloned from the tumor library and five of them were significantly up-regulated in the tumor. Some of them may be involved in the tumorigenesis of pheochromocytoma. The sequence data of ESTs and novel full-length cDNAs described in this paper have been submitted to the GeneBank library.

Adrenal Gland Neoplasms↗
PubMed2003

Expression profile of mRNAs from human pancreatic islet tumors.

In order to understand the tIssue specificity of the endocrine pancreas, it is important to clarify the expression profile of mRNAs in various states of the tIssue. A total of approximately 9000 non-redundant expressed genes from human pancreatic islets and insulinoma have so far been determined as expressed sequence tags (ESTs) and deposited in public databases. In the present study towards the identification of a complete set of genes expressed in human pancreatic islets, we have determined 3'-ESTs of 21267 clones randomly selected from a cDNA library of human pancreatic islet tumors. Clustering analysis generated 6157 non-redundant sequences comprising 2323 groups and 3834 singletons. Nucleotide and peptide database searches show that 3103 of them represent known human sequences or homologs of genes identified in other species and 58 are new members of structurally related families. The sequences were classified on the basis of the putative protein functions encoded, and were assigned to the respective chromosome by database analysis. The sequences were also compared with the EST databases (dbEST and EPConDB) including ESTs from normal pancreatic islet, insulinoma, and fetal pancreas. Since 3384 genes were newly found to be expressed in human pancreatic islets and 587 of them were unique to the islets, this study has considerably expanded the catalog of genes expressed in the endocrine pancreas. The larger collection of pancreatic islet-related ESTs should provide a better genome source for molecular studies of differentiation, tIssue-specific functions, and tumorigenesis of the endocrine pancreas as well as for genetic studies of diabetes mellitus.

Cloning, Molecular↗
PubMedDate not supplied

Framework for pharmacy services quality improvement--a bridge to cross the quality chasm. Part I. The opportunity and the tool.

OBJECTIVE: To review the literature on the subject of quality improvement principles and methods applied to pharmacy services and to describe a framework for current and future efforts in pharmacy services quality improvement and effective drug therapy management. BACKGROUND: The Academy of Managed Care Pharmacy produced the Catalog of Pharmacy Quality Indicators in 1997, followed by the Summary of National Pharmacy Quality Measures in February 1999. In April 2002, AMCP introduced Pharmacy's Framework for Drug Therapy Management in the 21st Century. The Framework documents include a self-assessment tool that details more than 250 specific "components" that describe tasks, behaviors, skills, functions, duties, and responsibilities that contribute to meeting customer expectations for effective drug therapy management. FINDINGS: There are many opportunities for quality improvement in clinical, service, and cost outcomes related to drug therapy management. These may include patient safety; incidence of medical errors; adverse drug events; patient adherence to therapy; attainment of target goals of blood pressure, glucose, and lipid levels; risk reduction for adverse cardiac events and osteoporotic-related fractures; patient satisfaction; risk of hospitalization or mortality; and cost of care. Health care practitioners can measure improvements in health care quality in several ways including (a) a better patient outcome at the same cost, (b) the same patient outcome at lower cost, (c) a better patient outcome at lower cost, or (d) a significantly better patient outcome at moderately higher cost. Measurement makes effective management possible. A framework of component factors (e.g., tasks) is necessary to facilitate changes in the key processes and critical factors that will help individual practitioners and health care systems meet customer expectations in regard to drug therapy, thus improving these outcomes. CONCLUSIONS: Quality improvement in health care services in the United States will be made in incremental changes that rely on a structure-process-outcome model. The structure is provided by evidence created from controlled randomized trials and other studies of care and system outcomes that are based on the scientific method. The process portion is created by the application of evidence in the form of clinical practice guidelines, clinical practice models, and self-assessment tools such as Pharmacy's Framework for Drug Therapy Management. Incremental changes in structure and process will result in the desirable outcome of meeting customer needs for more effective drug therapy and disease management.

Guidelines as Topic↗
PubMed2006

Identification of compounds associated with testosterone depressions in fish exposed to bleached kraft pulp and paper mill chemical recovery condensates.

In previous experiments, bleached kraft chemical recovery condensates generated during softwood pulp production have been identified as a primary source of substances causing testosterone depressions in mummichog (Fundulus heteroclitus). Recent toxicity identification evaluations have encountered inconsistencies in the potential of condensates and fractions to reduce steroid concentrations between three repeated exposures. To assess the sources of these inconsistencies, temporal assessments of condensate extractives and analytical methodologies were evaluated. Condensates were collected during a six-month period, extracted by solid-phase extraction (SPE), and analyzed by gas chromatography-mass spectrometry and gas chromatography-flame photometric detection. All unique extractives were cataloged by mass spectra, peak area, and gas chromatographic retention time, and nine were confirmed and quantified against authentic standards. Confirmed components included phenolic guaiacyl-based lignin degradation products, sulfur (S9), three diterpenoids, and a dimethoxy stilbene. Concentrations of confirmed condensate extractives were consistent in all samples collected. Spiking experiments of confirmed extractives revealed substantial losses following high-pressure liquid chromatographic fractionation and three different methods of fraction preparation. In an effort to propose chemical classes associated with biological activity, all unique condensate extractives in previously established bioactive and inactive fractions were classified based on their potential to depress testosterone in mummichog. Of 39 unique components in bioactive SPE extracts of condensates, six were associated with hormonal activity. Mass spectral interpretation indicated hydroxylated diterpenoids, sesquiterpenoids, and a lignin-derived stilbene as classes of chemicals associated with steroid depressions.

Animals↗
PubMed2006

The Genetic Basis of Type 2 Diabetes.

Type 2 Diabetes results from a complex physiologic process that includes the pancreatic beta cells, peripheral glucose uptake in muscle, the secretion of multiple cytokines and hormone-like molecules from adipocytes, hepatic glucose production, and likely the central nervous system. Consistent with the complex web of physiologic defects, the emerging picture of the genetics will involve a large number of risk susceptibility genes, each individually with relatively small effect (odds ratios below 1.2 in most cases). The challenge for the future will include cataloging and confirming the genetic risk factors, and understanding how these risk factors interact with each other and with the known environmental and lifestyle risk factors that increase the propensity to type 2 diabetes.

Journal Article↗
PubMed1984

The sleeping giant: Reinforcement schedules.

Schedule research has been the core of operant conditioning, but it is no longer an active area, at least with respect to its traditional focus of describing and explaining moment-to-moment behavior. Yet schedules are central in psychology: Not only do they establish lawful behavior, but they also play a major role in determining the effects of other variables. The reason for the decline appears to be primarily theoretical, in that the work seems not to have led to meaningful integration. The search for controlling variables brought into play by schedule specification has proven unsuccessful, and a catalog of all possible schedule effects is of limited interest. The paper reviews the reasons for the contemporary state of affairs. One prediction about future developments is that instead of revealing component variables and their modes of interaction, schedule effects will be treated as basic empirical laws. Theory will take the form of abstract statements that integrate these separate laws by reference to higher-order principles rather than by reduction to supposedly simpler component variables.

Journal Article↗
PubMed2006

Lasers in periodontics: a review of the literature.

BACKGROUND: Despite the large number of publications, there is still controversy among clinicians regarding the application of dental lasers to the treatment of chronic periodontitis. The purpose of this review is to analyze the peer-reviewed research literature to determine the state of the science concerning the application of lasers to common oral soft tissue problems, root surface detoxification, and the treatment of chronic periodontitis. METHODS: A comprehensive computer-based search combined the following databases into one search: Medline, Current Contents, and the Cumulated Index of Nursing and Allied Health. This search also used key words. In addition, hand searches were done for several journals not cataloged in the databases, and the reference lists from published articles were checked. All articles were considered individually to eliminate non-peer-reviewed articles, those dealing with commercial laser technology, and those considered by the author to be purely opinion articles, leaving 278 possible articles. RESULTS: There is a considerable conflict in results for both laboratory studies and clinical trials, even when using the same laser wavelength. A meaningful comparison between various clinical studies or between laser and conventional therapy is difficult at best and likely impossible at the present. Reasons for this dilemma are several, such as different laser wavelengths; wide variations in laser parameters; insufficient reporting of parameters that, in turn, does not allow calculation of energy density; differences in experimental design, lack of proper controls, and differences in severity of disease and treatment protocols; and measurement of different clinical endpoints. CONCLUSIONS: Based on this review of the literature, there is a great need to develop an evidence-based approach to the use of lasers for the treatment of chronic periodontitis. Simply put, there is insufficient evidence to suggest that any specific wavelength of laser is superior to the traditional modalities of therapy. Current evidence does suggest that use of the Nd:YAG or Er:YAG wavelengths for treatment of chronic periodontitis may be equivalent to scaling and root planing (SRP) with respect to reduction in probing depth and subgingival bacterial populations. However, if gain in clinical attachment level is considered the gold standard for non-surgical periodontal therapy, then the evidence supporting laser-mediated periodontal treatment over traditional therapy is minimal at best. Lastly, there is limited evidence suggesting that lasers used in an adjunctive capacity to SRP may provide some additional benefit.

Chronic Disease↗
PubMed2026

Emerging genes implicated in human congenital heart disease: a 2023-2025 scoping review.

BACKGROUND: Congenital heart disease (CHD) is the most common major congenital anomaly and a leading cause of infant morbidity and mortality. The rapid expansion of genomic technologies has accelerated the discovery of rare genetic variants implicated in CHD pathogenesis. However, most individuals with CHD still lack an identifiable molecular etiology. The purpose of this scoping review is to systematically characterize genes reported in the recent literature as candidate CHD-associated genes and contextualize these findings within the stages of cardiac morphogenesis. METHODS: PubMed was searched using predefined terms related to CHD and genetic variants, supplemented by a prospectively maintained internal database. We included human studies published between January 2023 and December 2025 that identified pathogenic, likely pathogenic, or uncertain monogenic variants in at least one patient with CHD. Animal-only studies, chromosomal abnormalities, copy number variants, multigenic associations, transcriptomic/proteomic analyses, reviews, and maternal-only genetic studies were excluded. Gene-disease validity classifications were assigned using the Clinical Genome Resource (ClinGen) CHD Gene Curation Expert Panel framework. RESULTS: Of 2,834 screened articles, 391 studies met inclusion criteria, identifying 912 unique genes reported as candidate CHD-associated genes. Frequently reported genes included PTPN11, NOTCH1, GATA4, JAG1, MYH6, GATA6, and LZTR1. Identified genes spanned all major stages of cardiogenesis, including developmental priming, cardiac progenitor specification, left-right axis formation, neural crest migration, outflow tract development, septation, and postnatal structural remodeling. Studies increasingly implicated ciliary dysfunction, transcriptional regulation, ribosomal biology, and multigenic inheritance in CHD pathogenesis. Emerging methodologies included stem cell-derived cardiac models, machine learning-based gene prioritization, and epigenetic analyses. CONCLUSIONS: Recent literature substantially expands the catalog of candidate genes that may be associated with CHD and highlights the biologic complexity underlying cardiac morphogenesis. Integration of genomic, developmental, and functional approaches will be essential to improve mechanistic understanding, refine genetic counseling, and support future precision medicine strategies for CHD.

Cardiac development↗
PubMed2004

PathoGene: a pathogen coding sequence discovery and analysis resource.

PathoGene is a web-based resource that streamlines the process of predicting genes in microorganisms and designs PCR primers for amplification to facilitate sequence analysis and experimentation. PathoGene currently supports primer design for every complete microbial, viral, and fungal genome as cataloged in GenBank by the National Center for Biotechnology Information (NCBI; http://www.ncbi.nlm.nih.gov/). The resulting primers can then be subjected to a stand-alone Basic Local Alignment Search Tool (BLAST) system called PathoBLAST in which the predicted PCR product and/or primers can be compared against the genome of interest or a similar genome to find related genes or estimate primer quality.

Bacillus anthracis↗
PubMed2026

The Association of Allergic Rhinitis with Chronic Adenotonsillar Diseases and Chronic Rhinosinusitis: A Mendelian Randomization Study.

INTRODUCTION: Allergic rhinitis (AR) has long been considered to be associated with chronic adenotonsillar disease (CATD). However, their causal relationship remains unclear. This study aims to investigate the causal relationship between AR and CATD and to examine the mediating role of chronic rhinosinusitis (CRS) in this association. METHODS: This study employed a two-sample Mendelian randomization (MR) design using genetic instrumental variable analysis. Data for allergic rhinitis (AR) were obtained from the MRC IEU OpenGWAS data infrastructure, data for chronic adenotonsillar disease (CATD) from the FinnGen biobank, and data for chronic rhinosinusitis (CRS) from the GWAS Catalog. Several MR methods were applied. In addition, a two-step MR approach was used to investigate the mediating role of CRS in the relationship between AR and CATD. RESULTS: MR analysis identified a positive correlation between AR and CATD. IVW and weighted median analyses showed significant causal effects (beta = 0.55, 95% CI: 0.26 to 0.84); p <0.001). No causal association was found between CATD and AR. AR and CRS showed a positive correlation (beta = 1.38, 95% CI: 0.78 to 1.98; p = 6.5 &#xd7; 10-6). CRS had a beta value of 0.15 (95% CI: 0.06 to 0.24; p = 0.001) for CATD. CRS mediates 37.6% of the AR to CATD pathway (mediation effect = 0.20, 95% CI: 0.04 to 0.37; p = 0.013). DISCUSSION: These findings indicate that AR may contribute to CATD risk through CRS, highlighting the need for further research to explore underlying biological mechanisms and validate these findings. CONCLUSIONS: This study suggests a positive causal relationship between AR and CATD, with CRS acting as a mediator.

Mendelian Randomization Analysis↗
PubMed2004

Functional consequences of immune cell adhesion to endothelial cells.

Research regarding the interactions between the endothelium and immune cells has undergone a significant expansion during the past decade. Major shifts of emphasis have been the norm, from the production of a detail catalog of the cell surface receptors and counter-receptors acting at the interface between the vascular endothelium and circulating cells to a more mechanistic account of leukocyte/endothelium interactions. The past five years has seen new, groundbreaking developments in the field, with exiting studies aimed at understanding the functional consequences of the direct contact of endothelial cells and leukocytes. Based on early work to be discussed below, new data on local chemokine production and cell-to-cell contacts, attempt to clarify the physiopathological significance of these events. The exceptional anatomical arrangement of endothelial cells insures a permanent contact of the endothelium with leukocytes, an event likely to result in cellular signals originating from direct cell contact or through the action of soluble factors produced by endothelial cells or immune cells. As we will discuss, current evidence supports the idea that endothelial cells present at vascular endothelium as well as at specialized high endothelial venules, play not only a critical role in the homing and recruitment of immune cells but that it can also influence the outcome of the immune response. Additionally, new evidence clearly corroborates the idea that B and T lymphocytes as well as NK cells can modulate endothelial cell function.

Animals↗
PubMed2005

A comprehensive listing of bioactivation pathways of organic functional groups.

The occurrence of idiosyncratic adverse drug reactions during late clinical trials or after a drug has been released can lead to a severe restriction in its use and even in its withdrawal. Metabolic activation of relatively inert functional groups to reactive electrophilic intermediates is considered to be an obligatory event in the etiology of many drug-induced adverse reactions. Therefore, a thorough examination of the biochemical reactivity of functional groups/structural motifs in all new drug candidates is essential from a safety standpoint. A major theme attempted in this review is the comprehensive cataloging of all of the known bioactivation pathways of functional groups or structural motifs commonly utilized in drug design efforts. Potential strategies in the detection of reactive intermediates in biochemical systems are also discussed. The intention of this review is not to "black list" functional groups or to immediately discard compounds based on their potential to form reactive metabolites, but rather to serve as a resource describing the structural diversity of these functionalities as well as experimental approaches that could be taken to evaluate whether a "structural alert" in a new drug candidate undergoes bioactivation to reactive metabolites.

Animals↗