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PubMed2005

Coordinated activation of metabolic pathways for antioxidants and defence compounds by jasmonates and their roles in stress tolerance in Arabidopsis.

Jasmonic acid (JA) and methyl jasmonate (MeJA), collectively termed jasmonates, are ubiquitous plant signalling compounds. Several types of stress conditions, such as wounding and pathogen infection, cause endogenous JA accumulation and the expression of jasmonate-responsive genes. Although jasmonates are important signalling components for the stress response in plants, the mechanism by which jasmonate signalling contributes to stress tolerance has not been clearly defined. A comprehensive analysis of jasmonate-regulated metabolic pathways in Arabidopsis was performed using cDNA macroarrays containing 13516 expressed sequence tags (ESTs) covering 8384 loci. The results showed that jasmonates activate the coordinated gene expression of factors involved in nine metabolic pathways belonging to two functionally related groups: (i) ascorbate and glutathione metabolic pathways, which are important in defence responses to oxidative stress, and (ii) biosynthesis of indole glucosinolate, which is a defence compound occurring in the Brassicaceae family. We confirmed that JA induces the accumulation of ascorbate, glutathione and cysteine and increases the activity of dehydroascorbate reductase, an enzyme in the ascorbate recycling pathway. These antioxidant metabolic pathways are known to be activated under oxidative stress conditions. Ozone (O3) exposure, a representative oxidative stress, is known to cause activation of antioxidant metabolism. We showed that O3 exposure caused the induction of several genes involved in antioxidant metabolism in the wild type. However, in jasmonate-deficient Arabidopsis 12-oxophytodienoate reductase 3 (opr3) mutants, the induction of antioxidant genes was abolished. Compared with the wild type, opr3 mutants were more sensitive to O3 exposure. These results suggest that the coordinated activation of the metabolic pathways mediated by jasmonates provides resistance to environmental stresses.

Acetates↗
PubMed1992

Diagnostic criteria for human diffuse malignant mesothelioma.

Diffuse malignant mesothelioma is a rare tumor in the general population, yet is unique in that it is caused almost exclusively by exposure to asbestos with long-term latency (15 years and over). Pathologists are required to provide a reliable diagnosis of the tumor for clinicians who are responsible for the treatment of affected patients. Pathological diagnosis of diffuse malignant mesothelioma is not always easy; however, it has improved over the last few decades. Currently, comprehensive analysis, including gross appearance, histology, histochemistry, immunocytochemistry and electron microscopy is recommended as the best approach to an accurate diagnosis of diffuse malignant mesothelioma.

Carcinoembryonic Antigen↗
PubMed2003

The pattern of ocular dominance columns in cat primary visual cortex: intra- and interindividual variability of column spacing and its dependence on genetic background.

We present a comprehensive analysis of the intrinsic variability of the periodicity of ocular dominance columns in cat primary visual cortex (area 17) and its relationship to genetic background and visual experience. We characterized the intra-areal and interindividual variability of column spacing in a large set (n = 49) of ocular dominance patterns adapting a recently developed technique for the two-dimensional analysis of orientation column patterns. Patterns were obtained from three different cat colonies (termed F, M and D), the cats having either normal visual experience or experimentally induced strabismus. Two-dimensional maps of local column spacing were calculated for every pattern. In individual cortices, local column spacings varied by > 50% with the majority of column spacings ranging between 0.6 and 1.5 mm in different animals. In animals from colonies F and M (n = 29), the mean column spacing ranged between 1.03 and 1.27 mm and exhibited no significant differences, either between the two breeds or between strabismic and normal animals. The mean spacing was moderately clustered in the left and right brain hemisphere of individual animals but not in littermates. In animals from colony D (n = 2), average column spacing ranged between 0.73 and 0.95 mm, and was thus significantly different from the distribution of spacings in animals from breeds F and M, suggesting an influence of genetic factors on the layout of ocular dominance columns. Local column spacing exhibited a considerable systematic intra-areal variation, with largest spacings along the representation of the horizontal meridian and smallest spacings along the peripheral representation of the vertical meridian. The total variability of ocular dominance column spacing comprised 24% systematic intra-areal variation, 18% interindividual differences of mean column spacing and 58% nonsystematic intra-areal variability.

Animals↗
PubMed2006

Transpulmonary thermodilution hemodynamic monitoring for pheochromocytoma surgery in a child with complex congenital heart disease.

Hemodynamic alterations related to pheochromocytoma surgery may lead to decompensation with an associated cardiac malformation. Moreover, they are incompletely described in children because of potential hazards of invasive monitoring. We report transpulmonary thermodilution hemodynamic monitoring during pheochromocytoma surgery in a child with a complex congenital heart malformation. Comprehensive analysis of hemodynamic events was obtained that guided therapeutic decisions. Cardiac function was preserved and no complication occurred.

Adolescent↗
PubMed1997

Development of a dietary supplement database.

Data describing the composition of dietary supplements are not readily available to the public health community. As a result, intake from dietary supplements is generally not considered in most dietary surveys and, hence, little is known about the significance of supplement intake in relation to total diet or disease risk. To enable a more comprehensive analysis of dietary data, a database of the composition of various dietary supplements has been compiled. Active ingredients of all dietary supplements sold in Australia are included in the Australian Register of Therapeutic Goods (ARTG), maintained by the Therapeutic Goods Administration. Products included in the database were restricted to those vitamin, mineral and other supplements identified in dietary data collected from studies conducted in southeast Queensland and New South Wales (850 supplements). Conversion factors from ingredients compounds to active elements were compiled from standard sources. No account has been made for bioavailability, consistent with current practice for food composition databases. The database can be queried by ARTG identification number, brand, product title, or a variety of other fields. Expected future developments include development of standard formulations for use when supplements are incompletely specified, and expansion of products included for more widespread use.

Australia↗
PubMed2006

Whose interests are they, anyway?

This review both praises Richard Miller's book--a thoughtful, judicious, and comprehensive analysis of bioethics for the pediatric age group, notably the first effort worthy of the name--and points out the work still to be done in this area, work firmly based in and illuminated by Miller's ground-breaking thesis. Specifically, the book rightly compels us to recognize obligations of beneficence as primary and to refocus on the child's basic interests, rather than putative "best" interests. There remains much to be done in defining and discerning basic interests and in distinguishing whose interests are on the table when decisions are being made for seriously ill and dying children.

Beneficence↗
PubMed2005

Differential connexin expression in preglomerular and postglomerular vasculature: accentuation during diabetes.

BACKGROUND: Gap junctions may play an important role in regulating renal blood flow and glomerular responses. We have therefore made a comprehensive analysis of connexin expression in the renal vasculature of control and diabetic mice since elevated glucose has been reported to down-regulate connexin 43 in vascular cells in vitro. METHODS: Connexin distribution was determined with immunohistochemistry using subtype-specific and cell type-specific antibodies. Diabetes was induced with streptozotocin (120/80 mg/kg, intraperitoneally) in C57BL/6 mice. RESULTS: Connexins 37, 40, and 43 were expressed in endothelial cells of the renal, lobar, arcuate, and interlobular arteries and afferent arterioles, although connexin 43 was weak in the renal and arcuate arteries. Connexin 37 was detected in the media of arcuate, interlobular arteries and afferent arterioles and connexins 37 and 40 were found in renin-secreting cells. Both connexins 37 and 40 were expressed in extraglomerular mesangial cells, connexin 40 was abundantly expressed in intraglomerular mesangial cells, but connexin 37 was limited to mesangial cells at the vascular pole. In contrast, only connexin 43 was detected in endothelial cells of efferent arterioles and there was no connexin staining in the media. In diabetes, connexin 40 was expressed in smooth muscle cells along afferent arterioles, glomerular connexin staining was more extensive and connexin 43 was detected in renin-secreting cells. In contrast connexin 43 expression in endothelial cells of efferent arterioles was markedly reduced. CONCLUSION: The renal vasculature and mesangial cells are well coupled on the preglomerular side but there is little evidence that the coupling extends into the efferent arteriole. This pattern of cell coupling is accentuated during diabetes.

Animals↗
PubMed1988

Fundamental considerations in pacing of the diaphragm for chronic ventilatory insufficiency: a multi-center study.

Records were reviewed of 477 patients who had diaphragm pacemakers implanted for treatment of chronic hypoventilation. Three groups were established for comparison. (1) Center group: 165 patients operated on in six medical centers participating in a cooperative study; (2) Noncenter group, sufficient data available: 203 patients operated on by surgeons with experience limited to a few cases; (3) Nonstudy group, minimal data available: 109 patients operated on as in group 2; vital statistics only were contributed. The protocol for data gathering was comprised of 154 major variables. Basic data on age, sex, diagnosis and etiology were analyzed for homogenicity of data among the groups. A comprehensive analysis of the pacing methods, complication and results from the Center group yielded information on the early experience with diaphragm pacing important to its future application.

Diaphragm↗
PubMed1994

Toward an organizational-relational model of open adoption.

Clinicians and social scientists have attempted to demonstrate the advisability of open versus closed adoption (communication and/or contact vs. no communication and/or contact between biological and adoptive parents) from a variety of theoretical perspectives. In our article, we seek a conceptual framework that will (a) elaborate how such divergent conclusions about openness versus confidentiality have heretofore been drawn, and (b) provide a comprehensive analysis of the behavior and experiences of all members of the adoption triad (birthparents, adoptive parents, adoptees). Employing structural aspects of organismic-developmental theory (Werner, 1957) and dynamic aspects of self-in-relation theory (Miller, 1976), we propose an organizational-relational approach to open adoption. Preliminary research findings are also provided.

Adaptation, Psychological↗
PubMed2000

Health systems and maternal and child survival in Central Asian Republics.

PURPOSE: To describe the status of health care systems in five Central Asian Republics (CAR): Kyrgzstan, Kazakhstan, Uzbekistan, Turkmenistan, and Tajikistan, with particular attention to women's and children's health. ORGANIZING CONSTRUCT: Changing mortality profiles are investigated using the "protracted-polarized" model of epidemiologic transition. SOURCES: Empirical evidence was drawn from the World Health Organization (WHO) database for the region, along with additional evidence presented at a maternal-child health conference held in Bishkek, Kyrgyzstan, on November 11-14, 1998. The conference was sponsored by the Albert Schweitzer Institute and the Soros Foundation. This evidence is evaluated for completeness, validity, and reliability. Trends are identified using the 1998 and 1999 World Health Reports and 1999/2000 World Bank Development Report. FINDINGS: Incomplete data prohibited comprehensive analysis. Available data indicated high but variable rates of maternal and child mortality and overall declines in health status and the health care infrastructure in the 1990s. CONCLUSIONS: Data collection and analysis from this part of the world are often incomplete and unreliable. Future research should focus on improving maternal and child health indicators by enhancing resource sharing and opportunities for international collaboration.

Asia, Central↗
PubMedDate not supplied

The non-photosynthetic plastid in malarial parasites and other apicomplexans is derived from outside the green plastid lineage.

The discovery of a non-photosynthetic plastid genome in Plasmodium falciparum and other apicomplexans has provided a new drug target, but the evolutionary origin of the plastid has been muddled by the lack of characters, that typically define major plastid lineages. To clarify the ancestry of the plastid, we undertook a comprehensive analysis of all genomic characters shared by completely sequenced plastid genomes. Cladistic analysis of the pattern of plastid gene loss and gene rearrangements suggests that the apicomplexan plastid is derived from an ancestor outside of the green plastid lineage. Phylogenetic analysis of primary sequence data (DNA and amino acid characters) produces results that are generally independent of the analytical method, but similar genes (i.e., rpoB and rpoC) give similar topologies. The conflicting phylogenies in primary sequence data sets make it difficult to determine the the exact origin of the apicomplexan plastid and the apparent artifactual association of apicomplexan and euglenoid sequences suggests that DNA sequence data may be an inappropriate set of characters to address this phylogenetic question. At present we cannot reject our null hypothesis that the apicomplexan plastid is derived from a shared common ancestor between apicomplexans and dinoflagellates. During the analysis, we noticed that the Plasmodium tRNA-Met is probably tRNA-fMet and the tRNA-fMet is probably tRNA-Ile. We suggest that P. falciparum has lost the elongator type tRNA-Met and that similar to metazoan mitochondria there is only one species of methionine tRNA. In P. falciparum, this has been accomplished by recruiting the fMet-type tRNA to dually function in initiation and elongation. The tRNA-Ile has an unusual stem-loop in the variable region. The insertion in this region appears to have occurred after the primary origin of the plastid and further supports the monophyletic ancestory of plastids.

Animals↗
PubMed2006

Contribution of OCTN variants within the IBD5 locus to pediatric onset Crohn's disease.

BACKGROUND & AIMS: The IBD5 locus on chromosome 5q31 is a confirmed Crohn's disease (CD) susceptibility locus in adults. Recently, two polymorphisms in the organic cation transporter (OCTN) gene cluster within the IBD5 locus have been found to be associated with CD. Although the original report of significant linkage to IBD5 was in families with at least one case of early age at onset CD, there are no published reports on the role of OCTN genes in pediatric onset CD. We performed a comprehensive analysis of OCTN variants in an independent, exclusively pediatric onset CD cohort and examined the genotype/phenotype correlations. METHODS: 264 Caucasian CD children (172 of them were trios) were genotyped along with 527 controls for OCTN1 (SLC22A4 C1672T), OCTN2 (SLC22A5 G-207C), and two haplotype-tagging SNPs (IGR2230 and IGR2198). RESULTS: TDT confirmed the association of SLC22A4 and SLC22A5. Case-control analysis of the SLC22A4 1672T, SLC22A5-207C diplotype showed significant association (p=0.04) with CD susceptibility compared with controls. Little correlation was seen with regard to clinical phenotype and the SLC22A4/SLC22A5 diplotype. There was no significant interaction between the SLC22A4/SLC22A5 diplotype and the three CD-associated CARD15 SNPs. CONCLUSIONS: We confirm the association of the OCTN variants (SLC22A4 and SLC22A5) in pediatric onset CD as seen in adult CD cohorts. However, when an extended IBD5 haplotype was examined, no independent association between OCTN variants and pediatric onset CD can be demonstrated. Compared with adults, a relatively weak association of the OCTN variants was observed in our CD cohort. No definitive genotype-phenotype correlation or gene-gene interactions with CARD15 were observed. Although the IBD5 locus is associated with pediatric onset CD, no definitive conclusions can be drawn about OCTN variants as causative genes in pediatric CD at this point.

Child↗
PubMed2006

Insights into the role of gp63-like proteins in lower trypanosomatids.

Any actual understanding of trypanosomatids in general requires a comprehensive analysis of the less-specialized species as thorough as our knowledge of the more specialized Leishmania and Trypanosoma. In this context, we have shown by antibody cross-reactivity that purified extracellular metallopeptidases from Phytomonas françai, Crithidia deanei (cured strain) and Crithidia guilhermei share common epitopes with the leishmanial gp63. Flow cytometry and fluorescence microscopy analyses indicated the presence of gp63-like molecules on the cell surface of these lower trypanosomatids. Binding assays with explanted guts of Aedes aegypti incubated with purified gp63 and the pretreatment of trypanosomatids with anti-gp63 antibodies indicated that the gp63-like molecules are involved in the adhesive process of these trypanosomatids to the A. aegypti gut wall. In addition, our results indicate for the first time that the gp63-like molecule binds to a polypeptide of 50 kDa on the A. aegypti gut epithelium extract.

Aedes↗
PubMed1999

Identification of genetic aberrations in cell lines from oral squamous cell carcinomas by comparative genomic hybridization.

We detected genetic alterations in 14 cell lines established from 14 human oral squamous cell carcinomas (OSCCs) using comparative genomic hybridization (CGH), which allows a comprehensive analysis of chromosomal imbalances and identification of nonrandom genetic aberrations specific to OSCCs. All cell lines showed gains and losses of DNA copy number. DNA losses were detected for chromosomes 18q (10/14) and 4q (9/14) with minimal overlapping regions of 18q12-32 and 4q31-qter, respectively. In contrast, the common sites for increased copy number were chromosomes 5p (12/14), 8q23-ter (11/14), 20p (8/14), 20q (8/14), and 3q25-ter (7/14). These results suggest that losses of 18q12-22 and 4q31-ter and gains of 5p and 8q23-ter play important roles in the development and/or progression of OSCC.

Aged↗
PubMed2005

Physical activity and stroke risk.

Stroke represents a leading cause of morbidity and mortality especially among the elderly people, and therefore the need for effective preventive strategies is imperative. The value of physical activity for stroke prevention is not as well established as for other cardiovascular diseases. Despite some conflicting results, the majority of published studies have demonstrated a negative association between physical activity and stroke risk. In this article, we provide a concise overview of the epidemiological studies that investigate this association as well as a comprehensive analysis of the most relevant underlying pathophysiological mechanisms.

Aged↗
PubMed2006

Impact of the native-state stability of human lysozyme variants on protein secretion by Pichia pastoris.

We report the secreted expression by Pichia pastoris of two human lysozyme variants F57I and W64R, associated with systemic amyloid disease, and describe their characterization by biophysical methods. Both variants have a substantially decreased thermostability compared with wild-type human lysozyme, a finding that suggests an explanation for their increased propensity to form fibrillar aggregates and generate disease. The secreted yields of the F57I and W64R variants from P. pastoris are 200- and 30-fold lower, respectively, than that of wild-type human lysozyme. More comprehensive analysis of the secretion levels of 10 lysozyme variants shows that the low yields of these secreted proteins, under controlled conditions, can be directly correlated with a reduction in the thermostability of their native states. Analysis of mRNA levels in this selection of variants suggests that the lower levels of secretion are due to post-transcriptional processes, and that the reduction in secreted protein is a result of degradation of partially folded or misfolded protein via the yeast quality control system. Importantly, our results show that the human disease-associated mutations do not have levels of expression that are out of line with destabilizing mutations at other sites. These findings indicate that a complex interplay between reduced native-state stability, lower secretion levels, and protein aggregation propensity influences the types of mutation that give rise to familial forms of amyloid disease.

Amyloidosis↗
PubMed1997

Does dietary fat influence insulin action?

What is clear from the research thus far is that dietary fat intake does influence insulin action. However, whether the effect is good, bad, or indifferent is strongly related to the fatty acid profile of that dietary fat. The evidence has taken many forms, including in vitro evidence of differences in insulin binding and glucose transport in cells grown with different types of fat in the incubation medium, in vivo results in animals fed different fats, relationships demonstrated between the membrane structural lipid fatty acid profile and insulin resistance in humans, and finally epidemiological evidence linking particularly high saturated fat intake with hyperinsulinemia and increased risk of diabetes. This contrasts with the lack of relationship, or even possible protective effect, of polyunsaturated fats. In particular, habitual increased n-3 polyunsaturated dietary fat intake (as fish fats) would appear to be protective against the development of glucose intolerance. It is reassuring that the patterns of dietary fatty acids that appear beneficial for insulin action and energy balance are also the patterns that would seem appropriate in the fight against thrombosis and cardiovascular disease. Mechanisms, though, still need to be defined. However, there are strong indicators that defining the ways in which changes in the fatty acid profile of membrane structural lipids are achieved, and in turn influence relevant transport events, plus understanding the processes that control accumulation and availability of storage lipid in muscle may be fruitful avenues for future research. One of the problems of moving the knowledge gained from research at the cellular level through to the individual and on to populations is the need for more accommodating research designs. In vitro studies may provide in-depth insights into intricate mechanisms, but they do not give the "big picture" for practical recommendations. On the other hand, correlational studies tend to be fairly blunt instruments, requiring large numbers that are very often not feasible if a greater depth of understanding of the biological processes is to be incorporated. There may be benefit in turning to the clinical case study as a framework for a more comprehensive analysis of the links between dietary fats and insulin action. The real challenge is to keep the depth of analysis rigorous enough to be able to explain and accommodate individual variation (i.e., the diversity of both environmental and genetic backgrounds) while at the same time satisfying the cultural need to provide appropriate overall dietary guidelines. Finally, David Kritchevsky brought to our attention a delightful quote from Mark Twain: "There is something fascinating about science. One gets such a wholesale return of conjecture for such a trifling investment of fact." In the field of dietary fats and the Metabolic Syndrome, this quotation is, unfortunately, apt. Much more research is necessary to define how dietary fats really work to affect insulin action. Well designed, long-term studies in "free range" humans must be undertaken if dietary guidelines for the Metabolic Syndrome are to be based on anything more than a "trifling" amount of "fact."

Animals↗
PubMed1999

Socioeconomic status and health: what we know and what we don't.

In the past 15 years, we have seen a marked increase in research on socioeconomic status (SES) and health. Research in the first part of this era examined the nature of the relationship of SES and health, revealing a graded association; SES is important to health not only for those in poverty, but at all levels of SES. On average, the more advantaged individuals are, the better their health. In this paper we examine the data regarding the SES-health gradient, addressing causal direction, generalizability across populations and diseases, and associations with health for different indicators of SES. In the most recent era, researchers are increasingly exploring the mechanisms by which SES exerts an influence on health. There are multiple pathways by which SES determines health; a comprehensive analysis must include macroeconomic contexts and social factors as well as more immediate social environments, individual psychological and behavioral factors, and biological predispositions and processes.

Causality↗