tbuckley/cabot-search huggingface dataset:
Etiological Investigation of Diabetes in Young Adults Presenting With Apparent Type 2 Diabetes
Authors: Katharine R. Owen, Amanda Stride, Sian Ellard, Andrew T. Hattersley
Journal: Diabetes Care (2003)

OBJECTIVE—Young adults with newly diagnosed apparent type 2 diabetes present the clinician with a wide differential diagnosis of possible etiology, including autoimmune and genetic causes as well as young-onset type 2 diabetes (YT2D). The characteristics of these groups have been described, but it is not known in which subjects investigation for etiology may be beneficial. RESEARCH DESIGN AND METHODS—A total of 268 unselected U.K. Caucasian subjects diagnosed at ages 18–45 years and not treated with permanent insulin for ≤6 months were studied. All subjects underwent clinical assessment and screening for GAD antibodies (GADA) and tyrosine phosphatase IA-2 antibodies (IA-2A). Screening for a common mutation in the hepatocyte nuclear factor-1α (HNF-1α) gene and the common mitochondrial mutation was performed in the antibody-negative subjects. Subjects without insulin resistance were selected for sequencing of the HNF-1α gene. RESULTS—A specific etiology was defined in 11.6% of the 268 subjects and in 24.7% of the lean subjects. Twenty-six subjects (9.7%) were positive for a β-cell antibody, one subject had familial partial lipodystrophy and the lamin A/C mutation R482W, and two subjects had the mitochondrial mutation A3243G. Two of 15 selected subjects had HNF-1α mutations, the novel missense mutation A501T, and the previously reported R583Q. CONCLUSIONS—This unselected series shows that there is considerable heterogeneity in apparent YT2D. β-Cell autoantibodies should be performed in all those presenting at ages 18–45 years. Genetic investigations can be targeted to phenotypically defined subjects. The finding of a specific etiology will allow individualization of management and give patients valuable information about their condition.
Analysis of the Reticulon Gene Family Demonstrates the Absence of the Neurite Growth Inhibitor Nogo-A in Fish
Authors: Heike Diekmann, Michael Klinger, Thomas Oertle, Dietmar Heinz, Hans-Martin Pogoda, Martin E. Schwab, Claudia A. O. Stuermer
Journal: Molecular Biology and Evolution (2005)

Reticulons (RTNs) are a family of evolutionary conserved proteins with four RTN paralogs (RTN1, RTN2, RTN3, and RTN4) present in land vertebrates. While the exact functions of RTN1 to RTN3 are unknown, mammalian RTN4-A/Nogo-A was shown to inhibit the regeneration of severed axons in the mammalian central nervous system (CNS). This inhibitory function is exerted via two distinct regions, one within the Nogo-A–specific N-terminus and the other in the conserved reticulon homology domain (RHD). In contrast to mammals, fish are capable of CNS axon regeneration. We performed detailed analyses of the fish rtn gene family to determine whether this regeneration ability correlates with the absence of the neurite growth inhibitory protein Nogo-A. A total of 7 rtn genes were identified in zebrafish, 6 in pufferfish, and 30 in eight additional fish species. Phylogenetic and syntenic relationships indicate that the identified fish rtn genes are orthologs of mammalian RTN1, RTN2, RTN3, and RTN4 and that several paralogous fish genes (e.g., rtn4 and rtn6) resulted from genome duplication events early in actinopterygian evolution. Accordingly, sequences homologous to the conserved RTN4/Nogo RHD are present in two fish genes, rtn4 and rtn6. However, sequences comparable to the first ∼1,000 amino acids of mammalian Nogo-A including a major neurite growth inhibitory region are absent in zebrafish. This result is in accordance with functional data showing that axon growth inhibitory molecules are less prominent in fish oligodendrocytes and CNS myelin compared to mammals.
Auto-Immune Disease and the Chronic Biologic False-Positive Test for Syphilis
Authors: A. McGehee Harvey
Journal: JAMA (1962)

A significant percentage of persons who react positively to serological tests for syphilis (STS) do not have syphilis but are referred to as chronic biologic false-positive (BFP) reactors. The author studied 192 BFP reactors. Most of them were apparently healthy and had submitted to the STS in the course of premarital, prenatal, or preemployment examinations, but others had various diseases, including two cases of systemic lupus erythematosus (SLE). The clinical course of these BFP reactors has been significant, since the group includes 14 who now have SLE and 3 who have since developed Hashimoto's thyroiditis. The marked predominance of women in this series of BFP reactors was not explained by any discernible bias in the sample.
Allergy to millet: another risk for atopic bird keepers
Authors: B. Bohle, W. Hirt, P. Nachbargauer, H. Ebner, C. Ebner
Journal: Allergy (2003)

Background: Millet has been reported to induce not very frequent but severe anaphylactic reactions following ingestion. Seven individuals who all kept cage birds experienced allergic reactions after ingestion of millet‐containing food. Methods: We investigated the immunoglobulin E (IgE)‐reactivity of these individuals to millet employing immunoblotting, RAST and skin prick tests. As the sensitization possibly occurred via the inhalant route we investigated millet‐specific IgE levels of 16 additional sera from bird keepers with proven atopy, in retrospect. Results: All patients who had experienced reactions after ingestion of millet displayed millet‐specific IgE. Sixty‐three percent of the atopic bird keepers possessed millet‐specific IgE. By means of immunoblotting three major allergens in millet extract were detected. Conclusions: Our results indicate that millet plays an important role as inhalant allergen for atopic bird keepers. A sensitization to millet may subsequently also elicit food allergy.
Trying to Lose Weight, Losing Weight, and 9-Year Mortality in Overweight U.S. Adults With Diabetes
Authors: Edward W. Gregg, Robert B. Gerzoff, Theodore J. Thompson, David F. Williamson
Journal: Diabetes Care (2004)

The aim of this study was to examine the relationships between intention to lose weight, actual weight loss, and all-cause mortality among overweight individuals with diabetes.We performed a prospective analysis among 1,401 overweight diabetic adults aged > or =35 years sampled in the National Health Interview Survey. The previous year intention to lose weight and weight change were assessed by self-report. Nine-year mortality rates were examined according to intent to lose weight and weight loss, which were adjusted for age, sex, education, ethnicity, smoking, initial body weight, and diabetes complications.Individuals trying to lose weight had a 23% lower mortality rate (hazard rate ratio [HRR] 0.77, 95% CI 0.61-0.99) than those who reported not trying to lose weight. This association was as strong for those who failed to lose weight (0.72, 0.55-0.96) as for those who succeeded in losing weight (0.83, 0.63-1.08). Trying to lose weight was beneficial for overweight (BMI 25-30 kg/m2) individuals (0.62, 0.46-0.83) but not for obese (BMI>30) individuals (1.17, 0.72-1.92). Overall weight loss, without regard to intent, was associated with an increase of 22% (1.22, 0.99-1.50) in the mortality rate. This increase was largely explained by unintentional weight loss, which was associated with a 58% (1.58, 1.08-2.31) higher mortality rate.Overweight diabetic adults trying to lose weight have a reduced risk of all-cause mortality, independent of whether they lose weight. Actual weight loss is associated with increased mortality only if the weight loss is unintentional.
Wilms' Tumor in Adults: Results of the Society of Pediatric Oncology (SIOP) 93-01/Society for Pediatric Oncology and Hematology (GPOH) Study
Authors: Harald Reinhard, Schahin Aliani, Christian Ruebe, Michael Stöckle, Ivo Leuschner, Norbert Graf
Journal: Journal of Clinical Oncology (2004)

Purpose In the Society of Pediatric Oncology (SIOP) 93-01 study, 30 patients older than 16 years were found to have Wilms' tumor. They were treated according to the pediatric protocol and were analyzed for clinical presentation, stage distribution, and prognosis. Patients and Methods Patient age ranged from 16 to 62 years (median, 25.4 years). Tumor stages were defined according to SIOP, and treatment was risk-adapted according to SIOP 93-01/Society for Pediatric Oncology and Hematology (GPOH) protocol. The patients were evaluated with regard to response, toxicity, and prognosis. Specimens of all tumors were centrally reviewed. Results Ten patients (33%) had metastatic disease at the time of diagnosis (liver, four patients; lung, three patients; liver and lung, three patients). The local stage distribution showed a predominance of higher stages (stage I, eight patients; stage IIN−, three patients; stage IIN+, four patients; stage III, 15 patients). Histologic studies revealed intermediate-risk in 23 of 30 tumors; two tumors were classified as high-risk; and three tumors were clear-cell sarcomas. Two of 30 patients showed a nephroblastoma and a renal cell carcinoma simultaneously in the same kidney. A complete remission was achieved in 24 patients; four patients relapsed after complete remission; and three of them reached a second remission with further treatment. Event-free survival was 57%, with an overall survival of 83% (median observation time, 4 years). Conclusion Adults can be cured in a high percentage by a multimodal treatment according to pediatric protocols. Toxicity is higher than in children, but acceptable in view of the high remission rate.
Clinical and Radiological Recurrence After Childhood Arterial Ischemic Stroke
Authors: Vijeya Ganesan, Mara Prengler, Angela Wade, Fenella J. Kirkham
Journal: Circulation (2006)

Data on rates and risk factors for clinical and radiological recurrence of childhood arterial ischemic stroke (AIS) might inform secondary prevention strategies.Consecutive Great Ormond Street Hospital patients with first AIS were identified retrospectively (1978-1990) and prospectively (1990-2000). Patients underwent repeat neuroimaging at the time of clinical recurrence or, if asymptomatic, at least 1 year after AIS. Cox and logistic regression analyses were used to explore the relationships between risk factors and clinical and radiological recurrence, respectively. A total of 212 patients were identified, of whom 97 had another prior diagnosis. Seventy-nine children had a clinical recurrence (29 strokes, 46 transient ischemic attacks [TIAs], 4 deaths with reinfarction 1 day to 11.5 years (median 267 days) later); after 5 years, 59% (95% confidence interval, 51% to 67%) were recurrence free. Moyamoya on angiography and low birth weight were independently associated with clinical recurrence in the whole group. Genetic thrombophilia was associated with clinical recurrence in previously healthy patients, independent of the presence of moyamoya. Sixty of 179 patients who had repeat neuroimaging had radiological reinfarction, which was clinically silent in 20. Previous TIA, bilateral infarction, prior diagnosis (specifically immunodeficiency), and leukocytosis were independently associated with reinfarction. Previous TIA and leukocytosis were also independently associated with clinically silent reinfarction.Clinical and radiological recurrence are common after childhood AIS. The risk of clinical recurrence is increased in children with moyamoya and, in previously healthy patients, in those with genetic thrombophilia. Preexisting pathology, including immunodeficiency, and persistent leukocytosis are risk factors for radiological recurrence, which suggests a potential role for chronic infection.
Targeted Inhibition of Replication Protein A Reveals Cytotoxic Activity, Synergy with Chemotherapeutic DNA-Damaging Agents, and Insight into Cellular Function
Authors: Sarah C. Shuck, John J. Turchi
Journal: Cancer Research (2010)

Targeting uncontrolled cell proliferation and resistance to DNA-damaging chemotherapeutics with a single agent has significant potential in cancer treatment. Replication protein A (RPA), the eukaryotic ssDNA-binding protein, is essential for genomic maintenance and stability via roles in both DNA replication and repair. We have identified a novel small molecule that inhibits the in vitro and cellular ssDNA-binding activity of RPA, prevents cell cycle progression, induces cytotoxicity, and increases the efficacy of chemotherapeutic DNA-damaging agents. These results provide new insight into the mechanism of RPA-ssDNA interactions in chromosome maintenance and stability. This represents the first molecularly targeted eukaryotic DNA-binding inhibitor and reveals the utility of targeting a protein-DNA interaction as a therapeutic strategy for cancer treatment.
Prosthetic Valve Endocarditis Resulting from Nosocomial Bacteremia: A Prospective, Multicenter Study
Authors: Guodong Fang
Journal: Annals of Internal Medicine (1993)

Objective: To determine the incidence of endocarditis in bacteremic patients with prosthetic heart valves and the risk factors for and the effect of duration of antibiotic therapy on development of endocarditis in such patients. Design: Multicenter, prospective observational study. Setting: Six university teaching hospitals with high-volume cardiothoracic surgery. Participants: One hundred seventy-one consecutive patients with prosthetic heart valves who developed bacteremia during hospitalization. Measurements and Main Results: Patients were evaluated when they were identified as having bacteremia and 1, 2, 6, and 12 months after its occurrence. Of 171 patients, 74 (43%) developed endocarditis: Fifty-six (33%) had prosthetic valve endocarditis at the time bacteremia was discovered (endocarditis at outset), whereas 18 (11%) developed endocarditis a mean of 45 days after bacteremia was discovered (new endocarditis). Mitral valve location and staphylococcal bacteremia (Staphylococcus aureus or S. epidermidis) were significantly associated with the development of new endocarditis. All 18 cases of new endocarditis were nosocomial, and in 6 of these cases (33%) bacteremia was acquired via intravascular devices. Twenty-one patients without evidence of endocarditis at the time of bacteremia received short-term antibiotic therapy (<14 days); 1 patient (5%) developed endocarditis. Eleven of 70 patients (16%) who received long-term antibiotic therapy (>14 days) developed endocarditis (P > 0.2). Conclusions: Bacteremic patients with prosthetic heart valves were at notable risk for developing endocarditis, even when they received antibiotic therapy before endocarditis developed and regardless of the duration of such therapy. Intravascular devices were a common portal of entry.
Traditional and Nontraditional Risk Factors Predict Coronary Heart Disease in Chronic Kidney Disease
Authors: Paul Muntner, Jiang He, Brad C. Astor, Aaron R. Folsom, Josef Coresh
Journal: Journal of the American Society of Nephrology (2005)

Some risk factors for coronary heart disease (CHD) incidence in the general population are not associated with CHD incidence among patients with ESRD but have not been well characterized in chronic kidney disease (CKD). The association of several risk factors with CHD incidence was studied among participants with CKD in the population-based Atherosclerosis Risk in Communities (ARIC) Study. CHD risk factors and estimated GFR using serum creatinine were measured among 807 ARIC participants with CKD (estimated GFR between 15 and 59 ml/min per 1.73 m(2)). The incidence of CHD during 10.5 yr of follow-up was 6.3, 8.5, and 14.4 per 1000 person-years among ARIC participants with an estimated GFR of >/=90, 60 to 89, and 15 to 59 ml/min per 1.73 m(2), respectively. After adjustment for age, race, gender, and ARIC field center, among those with CKD, the relative risk (95% confidence interval) of CHD was 1.65 (1.01 to 2.67) for current smoking, 2.02 (1.27 to 3.22) for hypertension, 3.06 (2.01 to 4.67) for diabetes, and 1.96 (1.14 to 3.36) for anemia. The comparably adjusted relative risks of CHD for each standard deviation higher total and HDL cholesterol were 1.50 (1.25 to 1.71) and 0.79 (0.62 to 1.01), respectively, and 1.38 (1.13 to 1.69), 1.24 (1.06 to 1.46), 0.65 (0.54 to 0.79), and 1.38 (1.19 to 1.59) for waist circumference, leukocyte count, serum albumin, and fibrinogen, respectively. CHD risk factors in the general population remain predictive among patients with CKD. Given the high risk for CHD among patients with CKD, control of these risk factors may have a substantial impact on their excess burden of CHD.
Microarray Analysis Reveals Differences in Gene Expression of Circulating CD8+ T Cells in Melanoma Patients and Healthy Donors
Authors: Tong Xu, Chen-Tsen Shu, Elizabeth Purdom, Demi Dang, Diane Ilsley, Yaqian Guo, Jeffrey Weber, Susan P. Holmes, Peter P. Lee
Journal: Cancer Research (2004)

Abstract Circulating T cells from many cancer patients are known to be dysfunctional and undergo spontaneous apoptosis. We used microarray technology to determine whether gene expression differences exist in T cells from melanoma patients versus healthy subjects, which may underlie these abnormalities. To maximize the resolution of our data, we sort purified CD8+ subsets and amplified the extracted RNA for microarray analysis. These analyses show subtle but statistically significant expression differences for 10 genes in T cells from melanoma patients versus healthy controls, which were additionally confirmed by quantitative real-time PCR analysis. Whereas none of these genes are members of the classical apoptosis pathways, several may be linked to apoptosis. To additionally investigate the significance of these 10 genes, we combined them into a classifier and found that they provide a much better discrimination between melanoma and healthy T cells as compared with a classifier built uniquely with classical apoptosis-related genes. These results suggest the possible engagement of an alternative apoptosis pathway in circulating T cells from cancer patients.
Molecular Phylogenetics, Temporal Diversification, and Principles of Evolution in the Mustard Family (Brassicaceae)
Authors: T. L. P. Couvreur, A. Franzke, I. A. Al-Shehbaz, F. T. Bakker, M. A. Koch, K. Mummenhoff
Journal: Molecular Biology and Evolution (2009)

Brassicaceae is an important family at both the agronomic and scientific level. The family not only includes several model species, but it is also becoming an evolutionary model at the family level. However, resolving the phylogenetic relationships within the family has been problematic, and a large-scale molecular phylogeny in terms of generic sampling and number of genes is still lacking. In particular, the deeper relationships within the family, for example between the three major recognized lineages, prove particularly hard to resolve. Using a slow-evolving mitochondrial marker (nad4 intron 1), we reconstructed a comprehensive phylogeny in generic representation for the family. In addition, and because resolution was very low in previous single marker phylogenies, we adopted a supermatrix approach by concatenating all checked and reliable sequences available on GenBank as well as new sequences for a total 207 currently recognized genera and eight molecular markers representing a comprehensive coverage of all three genomes. The supermatrix was dated under an uncorrelated relaxed molecular clock using a direct fossil calibration approach. Finally, a lineage-through-time-plot and rates of diversification for the family were generated. The resulting tree, the largest in number of genera and markers sampled to date and covering the whole family in a representative way, provides important insights into the evolution of the family on a broad scale. The backbone of the tree remained largely unresolved and is interpreted as the consequence of early rapid radiation within the family. The age of the family was inferred to be 37.6 (24.2-49.4) Ma, which largely agrees with previous studies. The ages of all major lineages and tribes are also reported. Analysis of diversification suggests that Brassicaceae underwent a rapid period of diversification, after the split with the early diverging tribe Aethionemeae. Given the dates found here, the family appears to have originated under a warm and humid climate approximately 37 Ma. We suggest that the rapid radiation detected was caused by a global cooling during the Oligocene coupled with a genome duplication event. This duplication could have allowed the family to rapidly adapt to the changing climate.
Dose Effects of Aspirin on Gastric Prostaglandins and Stomach Mucosal Injury
Authors: Makau Lee
Journal: Annals of Internal Medicine (1994)

Objective: To determine if a dose of aspirin exists that might inhibit thromboxane-dependent platelet function without causing gastric mucosal injury, we studied the effects of a wide range of doses of aspirin (3 mg/d to 2600 mg/d) on gastric juice prostaglandins (PGE2 and PGF2α), on serum thromboxane B2, and on stomach mucosal injury as reflected by gastric juice hemoglobin and DNA concentrations. Design: A randomized, placebo-controlled study. Setting: Research laboratory at a Veterans Affairs medical center. Participants: 16 healthy volunteers (5 men and 11 women). Intervention: In the first part of the study, volunteers received placebo; aspirin, 324 mg/d; 1300 mg/d; or 2600 mg/d for 2 days. In the second part, volunteers received placebo; aspirin, 3 mg/d; 10 mg/d; 30 mg/d; or 81 mg/d for 8 days. Measurements: Gastric juice PGE2 and PGF2α, hemoglobin and DNA concentrations; gastric juice volume and acidity; and serum salicylate and thromboxane B2 concentrations. Results: In the first part, significant and similar (approximately 50%) inhibition of gastric juice prostaglandin output was observed with daily aspirin doses of 324 to 2600 mg. However, a significant increase in gastric juice hemoglobin output occurred only with 2600 mg/d. In the second part, significant inhibition (approximately 50%) of gastric PGE2 output was noted at a daily aspirin dose of 30 mg. Lower aspirin doses did not reduce PGE2 output significantly, although these doses did significantly reduce serum thromboxane B2 in a dose-related manner. Conclusions: Aspirin can significantly reduce serum thromboxane B2 at doses of 3 mg/d or 10 mg/d, which are significantly below the threshold dose for significant gastric prostaglandin inhibition and acute stomach mucosal injury.
The tumor suppressor gene WWOX links the canonical and noncanonical NF-κB pathways in HTLV-I Tax-mediated tumorigenesis
Authors: Jing Fu, Zhaoxia Qu, Pengrong Yan, Chie Ishikawa, Rami I. Aqeilan, Arnold B. Rabson, Gutian Xiao
Journal: Blood (2010)
MicroRNA Regulation of DNA Repair Gene Expression in Hypoxic Stress
Authors: Meredith E. Crosby, Ritu Kulshreshtha, Mircea Ivan, Peter M. Glazer
Journal: Cancer Research (2009)

Genetic instability is a hallmark of cancer; the hypoxic tumor microenvironment has been implicated as a cause of this phenomenon. MicroRNAs (miR) are small nonprotein coding RNAs that can regulate various cellular pathways. We report here that two miRs, miR-210 and miR-373, are up-regulated in a hypoxia-inducible factor-1alpha-dependent manner in hypoxic cells. Bioinformatics analyses suggested that these miRs could regulate factors implicated in DNA repair pathways. Forced expression of miR-210 was found to suppress the levels of RAD52, which is a key factor in homology-dependent repair (HDR); the forced expression of miR-373 led to a reduction in the nucleotide excision repair (NER) protein, RAD23B, as well as in RAD52. Consistent with these results, both RAD52 and RAD23B were found to be down-regulated in hypoxia, but in both cases, the hypoxia-induced down-regulation could be partially reversed by antisense inhibition of miR-210 and miR-373. Importantly, luciferase reporter assays indicated that miR-210 is capable of interacting with the 3' untranslated region (UTR) of RAD52 and that miR-373 can act on the 3' UTR of RAD23B. These results indicate that hypoxia-inducible miR-210 and miR-373 play roles in modulating the expression levels of key proteins involved in the HDR and NER pathways, providing new mechanistic insight into the effect of hypoxia on DNA repair and genetic instability in cancer.