tbuckley/cabot-search huggingface dataset:
Linkage of a Gene Causing Familial Membranoproliferative Glomerulonephritis Type III to Chromosome 1
Authors: John J. Neary, Peter J. Conlon, David Croke, Anthony Dorman, Mary Keogan, Feng Yu Zhang, Jeffery M. Vance, Margaret A. Pericak-Vance, William K. Scott, Michelle P. Winn
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. Membranoproliferative glomerulonephritis (MPGN) type III is a chronic progressive renal disease of unknown cause. The diagnosis is based on renal pathologic features (specifically immunofluorescence staining patterns and ultrastructural appearance). Mesangial cell proliferation and subendothelial and subepithelial deposits characterize the renal disease. Although the actual prevalence of this disease is not known, the disease is rare and usually sporadic. The clinical features of MPGN include the nephrotic syndrome and hematuria, with renal dysfunction occurring in approximately 50% of patients. Progression to end-stage renal disease is variable, and some patients exhibit stabilization or even improvement. Here is presented an Irish family in which there are eight affected members in four generations, suggesting autosomal dominant inheritance. This is the only reported family with an inherited form of MPGN type III. To evaluate the disease in this family, a genome-wide scan was performed with a panel of 402 polymorphic microsatellite markers, defining a grid with an average resolution of 10 cM (centimorgans). Significant evidence for linkage was observed on chromosome 1q31–32, with a maximal logarithm of the odds score of 3.86 at θ = 0.00 for microsatellite marker GATA135F02. Recombination events among affected individuals, as detected by haplotype analysis, established a 22-cM minimal candidate region flanked by markers D1S3470 and GATA124F08. The data provide evidence for a gene for familial MPGN on chromosome 1q.
Structural bases for the chemical regulation of Connexin43 channels
Authors: M Delmar
Journal: Cardiovascular Research (2004)

Connexins proteins associate with a variety of catalytic and non-catalytic molecules. Also, different domains of connexin can bind to each other, providing a mechanism for channel regulation. Here, we review some of these associations, placing particular emphasis on the intramolecular interactions that regulate Connexin43 (Cx43). We also describe some novel methods that allow for the characterization of protein–protein interactions such as those observed in the cardiac gap junction protein Connexin43. Overall, intra- and inter-molecular interactions may regulate gap junctions to filter the passage of molecular messages between cells at the appropriate time and between the appropriate cells. As a potential area for future investigations, we also speculate as to whether some of the inter-molecular interactions involving connexins lead to modifications in the function of the associated protein, rather than on the function of connexin itself.
Cost-Effectiveness of Screening for Pre-Diabetes Among Overweight and Obese U.S. Adults
Authors: Thomas J. Hoerger, Katherine A. Hicks, Stephen W. Sorensen, William H. Herman, Robert E. Ratner, Ronald T. Ackermann, Ping Zhang, Michael M. Engelgau
Journal: Diabetes Care (2007)

To estimate the cost-effectiveness of screening overweight and obese individuals for pre-diabetes and then modifying their lifestyle based on the Diabetes Prevention Program (DPP).A Markov simulation model was used to estimate disease progression, costs, and quality of life. Cost-effectiveness was evaluated from a health care system perspective. We considered two screening/treatment strategies for pre-diabetes. Strategy 1 included screening overweight subjects and giving them the lifestyle intervention included in the DPP if they were diagnosed with both impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Strategy 2 included screening followed by lifestyle intervention for subjects diagnosed with either IGT or IFG or both. Each strategy was compared with a program of no screening.Screening for pre-diabetes and treating those identified as having both IGT and IFG with the DPP lifestyle intervention had a cost-effectiveness ratio of $8,181 per quality-adjusted life-year (QALY) relative to no screening. If treatment was also provided to subjects with only IGT or only IFG (strategy 2), the cost-effectiveness ratio increased to $9,511 per QALY. Changes in screening-related parameters had small effects on the cost-effectiveness ratios; the results were more sensitive to changes in intervention-related parameters.Screening for pre-diabetes in the overweight and obese U.S. population followed by the DPP lifestyle intervention has a relatively attractive cost-effectiveness ratio.
Intrahepatic regulatory T cells in autoimmune hepatitis are associated with treatment response and depleted with current therapies
Authors: Richard Taubert, Matthias Hardtke-Wolenski, Fatih Noyan, Artur Wilms, Anna K. Baumann, Jerome Schlue, Sven Olek, Christine S. Falk, Michael P. Manns, Elmar Jaeckel
Journal: Journal of Hepatology (2014)
Clinical and ultrastructural studies in duodenal pseudomelanosis.
Authors: J Y Kang, A Y Wu, J L Chia, A Wee, I H Sutherland, R Hori
Journal: Gut (1987)

Nine patients with duodenal pseudomelanosis are described: seven had endstage renal failure while one other patient had undergone renal transplantation. Eight of the nine had been on oral iron supplements. The pigment stained positively with Perls' stain for iron in five patients, positively with the Masson-Fontana method normally used to identify melanin in one, and positively with both methods in three. Electron probe x-ray analysis of the pigment on samples from six patients showed iron to be present in all six, while sulphur was present in five. Varying sulphur content of the pigment in different patients could account for differences in histochemical characteristics. Iron was also shown in the duodenal biopsies of 34 of 48 uraemic patients on oral iron supplements, but was present in only 22 of 120 patients endoscoped for miscellaneous conditions (p less than 0.001). We postulate that the pigment of duodenal pseudomelanosis is derived from iron absorbed from the lumen.
Educational differences in smoking: international comparison
Authors: A E J M Cavelaars
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To investigate international variations in smoking associated with educational level. <b>Design:</b> International comparison of national health, or similar, surveys. <b>Subjects:</b> Men and women aged 20 to 44 years and 45 to 74years. <b>Setting:</b> 12 European countries, around 1990. <b>Main outcome measures:</b> Relative differences (odds ratios) and absolute differences in the prevalence of ever smoking and current smoking for men and women in each age group by educational level. <b>Results:</b> In the 45 to 74 year age group, higher rates of current and ever smoking among lower educated subjects were found in some countries only. Among women this was found in Great Britain, Norway, and Sweden, whereas an opposite pattern, with higher educated women smoking more, was found in southern Europe. Among men a similar north-south pattern was found but it was less noticeable than among women. In the 20 to 44 year age group, educational differences in smoking were generally greater than in the older age group, and smoking rates were higher among lower educated people in most countries. Among younger women, a similar north-south pattern was found as among older women. Among younger men, large educational differences in smoking were found for northern European as well as for southern European countries, except for Portugal. <b>Conclusions:</b> These international variations in social gradients in smoking, which are likely to be related to differences between countries in their stage of the smoking epidemic, may have contributed to the socioeconomic differences in mortality from ischaemic heart disease being greater in northern European countries. The observed age patterns suggest that socioeconomic differences in diseases related to smoking will increase in the coming decades in many European countries.
Effect of inhaled steroids on airway hyperresponsiveness, sputum eosinophils, and exhaled nitric oxide levels in patients with asthma
Authors: E. L J van Rensen, K. C M Straathof, M. A Veselic-Charvat, A. H Zwinderman, E. H Bel, P. J Sterk
Journal: Thorax (1999)

<h3>BACKGROUND</h3> Airway hyperresponsiveness, induced sputum eosinophils, and exhaled nitric oxide (NO) levels have all been proposed as non-invasive markers for monitoring airway inflammation in patients with asthma. The aim of this study was to compare the changes in each of these markers following treatment with inhaled glucocorticosteroids in a single study. <h3>METHODS</h3> In a randomised, double blind, placebo controlled, parallel study 25 patients with mild asthma (19–34 years, forced expiratory volume in one second (FEV<sub>1</sub>) &gt;75% predicted, concentration of histamine provoking a fall in FEV<sub>1</sub> of 20% or more (PC<sub>20</sub>) &lt;4 mg/ml) inhaled fluticasone propionate (500 μg twice daily) for four weeks. PC<sub>20</sub> to histamine, sputum eosinophil numbers, and exhaled NO levels were determined at weeks 0, 2, and 4, and two weeks after completing treatment. Sputum was induced by inhalation of hypertonic (4.5%) saline and eosinophil counts were expressed as percentage non-squamous cells. Exhaled NO levels (ppb) were measured by chemiluminescence. <h3>RESULTS</h3> In the steroid treated group there was a significant increase in PC<sub>20</sub>, decrease in sputum eosinophils, and decrease in exhaled NO levels compared with baseline at weeks 2 and 4 of treatment. Subsequently, each of these variables showed significant worsening during the two week washout period compared with week 4. These changes were significantly different from those in the placebo group, except for the changes in sputum eosinophils and exhaled NO levels during the washout period. There were no significant correlations between the changes in the three markers in either group at any time. <h3>CONCLUSIONS</h3> Treatment of asthmatic subjects with inhaled steroids for four weeks leads to improvements in airway hyperresponsiveness to histamine, eosinophil counts in induced sputum, and exhaled nitric oxide levels. The results suggest that these markers may provide different information when monitoring anti-inflammatory treatment in asthma.
Myocardial microvascular permeability, interstitial oedema, and compromised cardiac function
Authors: Ranjeet M. Dongaonkar, Randolph H. Stewart, Hans J. Geissler, Glen A. Laine
Journal: Cardiovascular Research (2010)

The heart, perhaps more than any other organ, is exquisitely sensitive to increases in microvascular permeability and the accumulation of myocardial interstitial oedema fluid. Whereas some organs can cope with profound increases in the interstitial fluid volume or oedema formation without a compromise in function, heart function is significantly compromised with only a few percent increase in the interstitial fluid volume. This would be of little consequence if myocardial oedema were an uncommon pathology. On the contrary, myocardial oedema forms in response to many disease states as well as clinical interventions such as cardiopulmonary bypass and cardioplegic arrest common to many cardiothoracic surgical procedures. The heart's inability to function effectively in the presence of myocardial oedema is further confounded by the perplexing fact that the resolution of myocardial oedema does not restore normal cardiac function. We will attempt to provide some insight as to how microvascular permeability and myocardial oedema formation compromise cardiac function and discuss the acute changes that might take place in the myocardium to perpetuate compromised cardiac function following oedema resolution. We will also discuss compensatory changes in the interstitial matrix of the heart in response to chronic myocardial oedema and the role they play to optimize myocardial function during chronic oedemagenic disease.
Porphyromonas gingivalis Resistance to Polymyxin B Is Determined by the Lipid A 4′‐Phosphatase, PGN_0524
Authors: Stephen R Coats, Thao T To, Sumita Jain, Pamela H Braham, Richard P Darveau
Journal: International Journal of Oral Science (2009)

To elucidate the genetic basis for the pronounced resistance that the oral pathogen, Porphyromonas gingivalis (P. gingivalis), exhibits towards the cationic antimicrobial peptide, polymyxin B.A genetic screen of P. gingivalis clones generated by a Tn4400'-based random insertion mutagenesis strategy was performed to identify bacteria harboring novel genetic mutations that render P. gingivalis susceptible to killing by the cationic antimicrobial peptide, polymyxin B (PMB, 50 microg x mL(-1)).P. gingivalis (ATCC 33277) is unusually resistant to the cationic antimicrobial peptide, PMB at relatively high concentrations (200 microg x mL(-1)). Approximately 2,700 independent Tn4400'-derived mutants of P. gingivalis were examined for increased sensitivity to PMB killing at a relatively low dose (50 microg x mL(-1)). A single PMB-sensitive mutant was obtained in this phenotypic screen. We determined that the Tn4400' transposon was integrated into the gene encoding the lipid A 4'-phosphatase, PGN_0524, demonstrating that this insertion event was responsible for its increased susceptibility of this clone to PMB-dependent killing. The resulting mutant strain, designated 0524-Tn4400', was highly sensitive to PMB killing relative to wild-type P. gingivalis, and exhibited the same sensitivity as the previously characterized strain, 0524KO, which bears a genetically engineered deletion in the PGN_0524 locus. Positive ion mass spectrometric structural (MALDI-TOF MS) analyses revealed that lipid A isolates from 0524-Tn4400' and 0524KO strains displayed strikingly similar MALDI-TOF MS spectra that were substantially different from the wildtype P. gingivalis lipid A spectrum. Finally, intact 0524-Tn4400' and 0524KO mutant bacteria, as well as their corresponding LPS isolates, were significantly more potent in stimulating Toll-like receptor 4 (TLR4)-dependent E-selectin expression in human endothelial cells relative to intact wild-type P. gingivalis or its corresponding LPS isolate.The combined molecular evidence provided in this report suggests that PGN_0524, a lipid A 4'-phosphatase, is the sole genetic element conferring the ability of the periodontopathogen, P. gingivalis, to evade the killing activity of cationic antimicrobial peptides, such as PMB. These data strongly implicate PGN_0524 as a critical virulence factor for the ability of P. gingivalis to evade front-line host innate defenses that are dependent upon cationic antimicrobial peptide activity and TLR 4 sensing.
Relational processing in conceptual combination and analogy
Authors: Zachary Estes, Lara L. Jones
Journal: Behavioral and Brain Sciences (2008)

Abstract We evaluate whether evidence from conceptual combination supports the relational priming model of analogy. Representing relations implicitly as patterns of activation distributed across the semantic network provides a natural and parsimonious explanation of several key phenomena observed in conceptual combination. Although an additional mechanism for role resolution may be required, relational priming offers a promising approach to analogy.
Human resources in health research institutions in sub-Saharan African countries: results of a questionnaire-based survey
Authors: Derege Kebede, Chris Zielinski, Peter Ebongue Mbondji, Issa Sanou, Wenceslas Kouvividila, Paul-Samson Lusamba-Dikassa
Journal: Journal of the Royal Society of Medicine (2014)

Objective To describe human capacity and staff movement in national health research institutions in 42 sub-Saharan African countries. Design A structured questionnaire was used to solicit information on governance and stewardship from health research institutions. Setting Eight hundred and forty-seven health research institutions in 42 sub-Saharan African countries. Participants Key informants from 847 health research institutions. Main outcome measures The availability, mix and quality of human resources in health research institutions. Results On average, there were 122 females employed per respondent health research institution, compared with 159 males. For researchers, the equivalent figures were nine females to 17 males. The average annual gross salary of researchers varied between US$ 12,260 for staff with 5–10 years of experience and US$ 14,772 for the institution head. Of those researchers who had joined the institution in the previous 12 months, 55% were employed on a full-time basis. Of the researchers who left the institutions in the same period, 71% had a full-time contract. Among all those who left, those who left to a non-research sector and to another country accounted for two-thirds. Conclusions The study revealed significant gaps in the area of human capacity development for research in Africa. The results showed a serious shortage of qualified staff engaged in health research, with a dearth of staff that held at least a master’s degree or doctoral degree. Major efforts will be required to strengthen human resource capacity, including addressing the lack of motivation or time for research on the part of existing capable staff.
Immediate Early and Early Lytic Cycle Proteins Are Frequent Targets of the Epstein-Barr Virus–induced Cytotoxic T Cell Response
Authors: N.M. Steven, N.E. Annels, A. Kumar, A.M. Leese, M.G. Kurilla, A.B. Rickinson
Journal: The Journal of Experimental Medicine (1997)

Epstein-Barr virus (EBV), a human gamma-herpesvirus, can establish both nonproductive (latent) and productive (lytic) infections. Although the CD8+ cytotoxic T lymphocyte (CTL) response to latently infected cells is well characterized, very little is known about T cell controls over lytic infection; this imbalance in our understanding belies the importance of virus-replicative lesions in several aspects of EBV disease pathogenesis. The present work shows that the primary CD8+ CTL response to EBV in infectious mononucleosis patients contains multiple lytic antigen-specific reactivities at levels at least as high as those seen against latent antigens; similar reactivities are also detectable in CTL memory. Clonal analysis revealed individual responses to the two immediate early proteins BZLF1 and BRLF1, and to three (BMLF1, BMRF1, and BALF2) of the six early proteins tested. In several cases, the peptide epitope and HLA-restricting determinant recognized by these CTLs has been defined, one unusual feature being the number of responses restricted through HLA-C alleles. The work strongly suggests that EBV-replicative lesions are subject to direct CTL control in vivo and that immediate early and early proteins are frequently the immunodominant targets. This contrasts with findings in alpha- and beta-herpesvirus systems (herpes simplex, cytomegalovirus) where viral interference with the antigen-processing pathway during lytic infection renders immediate early and early proteins much less immunogenic. The unique capacity of gamma-herpesvirus to amplify the viral load in vivo through a latent growth-transforming infection may have rendered these agents less dependent upon viral replication as a means of successfully colonizing their hosts.
Sodium Chloride Intake
Authors: Hiddo Lambers Heerspink, Eberhard Ritz
Journal: Journal of the American Society of Nephrology (2012)

Current treatment of kidney disease is not completely satisfactory, particularly when initiated in the late stages of renal progression. There is an urgent need for additional interventions, especially reduction of salt intake, which is rather high in the Western world. In this commentary we provide a critical assessment of post hoc analyses of recent interventional and observational studies on the effect of salt intake on renal and cardiovascular outcomes. To evaluate the mechanisms and safety of reduced salt intake, studies specifically designed to assess salt intake as an endpoint are needed. This approach will have implications for health care policies and labeling of the salt content of purchased foods.
Increased Diabetes Incidence in Greek and Italian Migrants to Australia
Authors: Allison M. Hodge, Dallas R. English, Kerin O’Dea, Graham G. Giles
Journal: Diabetes Care (2004)

OBJECTIVE—The aims of the study were to determine whether Greek or Italian migrants to Australia have an elevated incidence of type 2 diabetes compared with Australian-born individuals and to what extent any differences can be explained by known risk factors. RESEARCH DESIGN AND METHODS—This was a prospective study of 34,097 men and women aged 40–69 years born in Greece, Italy, Australia, or New Zealand who were free from diabetes at baseline. For all self-reported cases of diabetes at the 4-year follow-up, a confirmation of diagnosis was sought from medical practitioners. Of these, anyone for whom there was no evidence against a diagnosis of type 2 diabetes was considered a case subject. RESULTS—Follow-up was completed by 29,331 (86%) participants, and 334 case subjects were identified. The cumulative incidence of type 2 diabetes among Greek (2.6%) and Italian (2.4%) migrants was more than three times that in Australian-born (0.7%) individuals. After adjusting for age only, the odds ratios (ORs) for being of Greek and Italian origin compared with Australian origin were 3.8 (95% CI 2.9–5.0) and 3.3 (2.6–4.3), respectively. The only known risk factor for type 2 diabetes that materially affected these ORs was BMI. After adjusting for BMI and age, the ORs for being of Greek and Italian origin, respectively, were 2.4 (1.8–3.2) and 2.0 (1.5–2.6). CONCLUSIONS—Greek and Italian migrants to Australia have a more than three times greater incidence of type 2 diabetes than Australian-born individuals, and this is only partly explained by BMI. Although weight control will remain important for these high-risk groups, identification of other risk factors is required.
Geographic Concentration of Poverty and Arteriovenous Fistula Use among ESRD Patients
Authors: William M. McClellan, Haimanot Wasse, Ann C. McClellan, James Holt, Jenna Krisher, Lance A. Waller
Journal: Journal of the American Society of Nephrology (2010)

There is substantial geographic variability in both incident and prevalent arteriovenous fistula (AVF) use among patients with ESRD. This study examined the degree to which these variations associate with poverty in the county of a patient's treatment center. We performed a cross-sectional study including 28,135 patients treated by 1127 hemodialysis centers in five ESRD networks (16 states) between June 1, 2005 and May 31, 2006. We used the 2000 U.S. Census to categorize county-level poverty and ascertained incident AVF use from the Medicare CMS 2728 form. We calculated the 30-month slope of change in AVF prevalence from monthly facility reports collected between 2003 and 2005. More than 33% of treatment centers were located in high-poverty counties. County poverty inversely associated with incident AVF use (P for trend = 0.001). In contrast, substantial increases in prevalent AVF rates from 30.9 to 38.6% (P < 0.001) among treatment centers did not associate with county poverty (P = 0.9519). In conclusion, the concentration of poverty in the county where a treatment is located associates with incident AVF use by patients with ESRD but not with subsequent improvement in AVF use among prevalent patients. These results suggest that the Medicare ESRD program may mitigate poverty effects on AVF use.