tbuckley/cabot-search huggingface dataset:
2009 Presidential Address: Mentoring … Touching the Future
Authors: R. Paul Robertson
Journal: Diabetes Care (2009)

Mentoring may be the most important thing we do on a daily basis. It produces some of our greatest experiments and successes, our mentees themselves. Ironically, although we are fond of publishing data from diabetes research, we never publish the results of our mentoring in contemporary literature. We must turn to oral and written history to even define the word “mentoring.” What exactly is it?

### A modestly revised version of Greek mythology

The word “mentor” evolved from Homer's opus, The Odyssey . Odysseus (or Ulysses, his other name) was a graduate of Cornell University and became King of Ithaca. He was very conflicted about fighting the Trojan War. To avoid going to battle, he pretended to be crazy by plowing his field with salt. However, the Greek military was suspicious and tested Odysseus by putting his newly born son, Telemachus, in front of his plow. Odysseus stopped plowing to save his son. Having thus demonstrated his sanity and blown his cover, Odysseus joined the army and sailed up the wine-dark Aegean Sea to Troy where he entered graduate school in the Greek War College. His research project was to ascertain the effect of wooden horses on warfare. Before leaving Ithaca, Odysseus had asked an elderly friend named Mentor to provide advice to Telemachus, as well as to his lovely wife Penelope.

After fighting the Trojans for 10 years and defeating them, Odysseus received his first patent for inventing the Trojan horse and in many other ways distinguished himself in wisdom and leadership. He received his phd in Creative Combat and then started out on his victorious trip home, sailing south and seeing the sights in the Aegean Sea. However, he encountered storms, took several wrong turns, and wound up traveling around the southern Mediterranean, Tyrrhenian, and Ionian seas for 10 more years. This became his first postdoctoral …
Dual SPECT Imaging of Löffler’s Endomyocarditis in the Acute Phase
Authors: Tomoyuki Yamaguchi, Yoshio Yasumura, Satoshi Nakatani, Noritoshi Nagaya, Hatsue Ishibashi-Ueda, Masayuki Inubushi, Yoshio Ishida, Masakazu Yamagishi
Journal: Circulation (2000)
Development of a logically devised line drawing atlas for grading of knee osteoarthritis
Authors: Y. Nagaosa
Journal: Annals of the Rheumatic Diseases (2000)

<h3>OBJECTIVES</h3> To (<i>a</i>) develop an atlas of line drawings for the assessment and grading of narrowing and osteophyte (that is, changes of osteoarthritis) on knee radiographs, and (<i>b</i>) compare the performance of this atlas with that of the standard Osteoarthritis Research Society (OARS) photographic atlas of radiographs. <h3>METHODS</h3> Normal joint space widths (grade 0) for the medial and lateral tibiofemoral and medial and lateral patellofemoral compartments were obtained from a previous community study. Grades 1–3 narrowing in each compartment was calculated separately for men and women, grade 3 being bone on bone, grades 1 and 2 being two thirds and one third the value of grade 0. Maximum osteophyte size (grade 3) for each of eight sites was determined from 715 bilateral knee<i>x</i> ray films obtained in a knee osteoarthritis (OA) hospital clinic; grades 1–2 were calculated as two thirds and one third reductions in the area of grade 3. Drawings for narrowing and osteophyte were presented separately. 50 sets of bilateral knee <i>x</i> ray radiographs (standing, extended anteroposterior; flexed skyline) showing a spectrum of OA grades were scored by three observers, twice using the OARS atlas and twice using the drawn atlas. <h3>RESULTS</h3> Intraobserver and interobserver reproducibility was similar and generally good with both atlases, though varied according to site. All three observers preferred the line drawing atlas for ease and convenience of use. Higher scores for patellofemoral narrowing and lower scores for osteophyte, especially medial femoral osteophyte, were seen using the line drawing atlas, showing that the two atlases are not equivalent instruments. <h3>CONCLUSION</h3> A logically derived line drawing atlas for grading of narrowing and osteophyte at the knee has been produced. The atlas showed comparable reproducibility with the OARS atlas, but was discordant in several aspects of grading. Such a system has several theoretical and practical advantages and should be considered for use in knee OA studies.
Granulocyte/macrophage colony-stimulating factor and interleukin 3 release from human peripheral blood eosinophils and neutrophils.
Authors: H Kita, T Ohnishi, Y Okubo, D Weiler, J S Abrams, G J Gleich
Journal: The Journal of Experimental Medicine (1991)

Human peripheral blood eosinophils released eosinophil survival-enhancing activity when stimulated with the calcium ionophore, ionomycin. The release of activity was detected as early as 3 h after stimulation and was inhibited by an immunomodulating agent, cyclosporin A. The survival-enhancing activity was completely abolished by treatment with anti-interleukin 3 (IL-3) and anti-granulocyte/macrophage colony-stimulating factor (GM-CSF) monoclonal antibodies. Moreover, IL-3 and GM-CSF were measurable in ionomycin-stimulated eosinophil supernatants by immunoassay. Eosinophils produced approximately one-half as much IL-3 and one-fifth as much GM-CSF as ionomycin-stimulated mononuclear cells. Neutrophils also produced IL-3 and GM-CSF, but the amounts were less than those produced by eosinophils. These observations suggest a novel role for eosinophils in pathophysiology of allergic inflammation and host defense mechanisms.
HIV Infection and the Risk of Acute Myocardial Infarction
Authors: Matthew S. Freiberg, Chung-Chou H. Chang, Lewis H. Kuller, Melissa Skanderson, Elliott Lowy, Kevin L. Kraemer, Adeel A. Butt, Matthew Bidwell Goetz, David Leaf, Kris Ann Oursler, David Rimland, Maria Rodriguez Barradas, Sheldon Brown, Cynthia Gibert, Kathy McGinnis, Kristina Crothers, Jason Sico, Heidi Crane, Alberta Warner, Stephen Gottlieb, John Gottdiener, Russell P. Tracy, Matthew Budoff, Courtney Watson, Kaku A. Armah, Donna Doebler, Kendall Bryant, Amy C. Justice
Journal: JAMA Internal Medicine (2013)

Importance: Whether people infected with human immunodeficiency virus (HIV) are at an increased risk of acute myocardial infarction (AMI) compared with uninfected people is not clear.Without demographically and behaviorally similar uninfected comparators and without uniformly measured clinical data on risk factors and fatal and nonfatal AMI events, any potential association between HIV status and AMI may be confounded.Objective: To investigate whether HIV is associated with an increased risk of AMI after adjustment for all standard Framingham risk factors among a large cohort of HIV-positive and demographically and behaviorally similar (ie, similar prevalence of smoking, alcohol, and cocaine use) uninfected veterans in care.Design and Setting: Participants in the Veterans Aging Cohort Study Virtual Cohort from April 1, 2003, through December 31, 2009.Participants: After eliminating those with baseline cardiovascular disease, we analyzed data on HIV status, age, sex, race/ethnicity, hypertension, diabetes mellitus, dyslipidemia, smoking, hepatitis C infection, body mass index, renal disease, anemia, substance use, CD4 cell count, HIV-1 RNA, antiretroviral therapy, and incidence of AMI.Main Outcome Measure: Acute myocardial infarction.Results: We analyzed data on 82 459 participants.During a median follow-up of 5.9 years, there were 871 AMI events.Across 3 decades of age, the mean (95% CI) AMI events per 1000 person-years was consistently and significantly higher for HIV-positive compared with uninfected veterans: for those aged 40 to 49 years, 2.0 (1.6-2.4)vs 1.5 (1.3-1.7); for those aged 50 to 59 years, 3.9 (3.3-4.5)vs 2.2 (1.9-2.5); and for those aged 60 to 69 years, 5.0 (3.8-6.7)vs 3.3 (2.6-4.2) (P Ͻ.05 for all).After adjusting for Framingham risk factors, comorbidities, and substance use, HIV-positive veterans had an increased risk of incident AMI compared with uninfected veterans (hazard ratio, 1.48; 95% CI, 1.27-1.72).An excess risk remained among those achieving an HIV-1 RNA level less than 500 copies/mL compared with uninfected veterans in time-updated analyses (hazard ratio, 1.39; 95% CI, 1.17-1.66).Conclusions and Relevance: Infection with HIV is associated with a 50% increased risk of AMI beyond that explained by recognized risk factors.
Therapeutic angiogenesis. A single intraarterial bolus of vascular endothelial growth factor augments revascularization in a rabbit ischemic hind limb model.
Authors: S Takeshita, L P Zheng, E Brogi, M Kearney, L Q Pu, S Bunting, N Ferrara, J F Symes, J M Isner
Journal: Journal of Clinical Investigation (1994)

Vascular endothelial growth factor (VEGF) is a heparin-binding, endothelial cell-specific mitogen. Previous studies have suggested that VEGF is a regulator of naturally occurring physiologic and pathologic angiogenesis. In this study we investigated the hypothesis that the angiogenic potential of VEGF is sufficient to constitute a therapeutic effect. The soluble 165-amino acid isoform of VEGF was administered as a single intra-arterial bolus to the internal iliac artery of rabbits in which the ipsilateral femoral artery was excised to induce severe, unilateral hind limb ischemia. Doses of 500-1,000 micrograms of VEGF produced statistically significant augmentation of collateral vessel development by angiography as well as the number of capillaries by histology; consequent amelioration of the hemodynamic deficit in the ischemic limb was significantly greater in animals receiving VEGF than in nontreated controls (calf blood pressure ratio, 0.75 +/- 0.14 vs. 0.48 +/- 0.19, P < 0.05). Serial angiograms disclosed progressive linear extension of the collateral artery of origin (stem artery) to the distal point of parent vessel (reentry artery) reconstitution in seven of nine VEGF-treated animals. These findings establish proof of principle for the concept that the angiogenic activity of VEGF is sufficiently potent to achieve therapeutic benefit. Such a strategy might ultimately be applicable to patients with severe limb ischemia secondary to arterial occlusive disease.
Identification of Promoter Variants in Baboon Endothelial Lipase That Regulate High-Density Lipoprotein Cholesterol Levels
Authors: Laura A. Cox, Shifra Birnbaum, Michael C. Mahaney, David L. Rainwater, Jeff T. Williams, John L. VandeBerg
Journal: Circulation (2007)

High-density lipoprotein cholesterol (HDL) levels are a major risk factor for cardiovascular disease. Previously we identified a quantitative trait locus on baboon chromosome 18 that regulates HDL. From positional cloning studies and expression studies, we identified the endothelial lipase gene (LIPG) as the primary candidate gene for the quantitative trait locus. The mechanism by which LIPG variation influences HDL levels has not been determined.We identified 164 LIPG polymorphisms in a panel of sibling baboons discordant for HDL1 and genotyped putative regulatory polymorphisms in a population of 951 pedigreed baboons. With the use of quantitative trait nucleotide analysis we identified 3 polymorphisms in the LIPG promoter associated with variation in serum HDL1 levels. In addition, we demonstrated that these 3 polymorphisms affect LIPG promoter activity in vitro. In silico analysis was used to identify putative transcription factors that differentially bind the functional promoter polymorphisms.These results reveal LIPG variants that specifically contribute to HDL1 levels and demonstrate mechanisms by which these polymorphisms may regulate LIPG promoter activity. Results from the present study provide a mechanism, namely variation in LIPG promoter activity possibly caused by altered transcription factor binding, by which LIPG variation affects HDL levels.
Metabolic Control in Non-Insulin-Dependent Diabetes Mellitus: Factors Associated With Patient Outcomes
Authors: Patrick J O'connor, Regina Fragneto, John Coulehan, Benjamin F Crabtree
Journal: Diabetes Care (1987)

We conducted a cross-sectional study to assess the association of various demographic and medical-care variables with metabolic outcomes in non-insulin-dependent diabetic subjects. The study population was representative of the diagnosed care-seeking diabetic population of a defined geographic community on the Navajo reservation in Arizona. The dependent variable metabolic control was measured as the mean of all random plasma glucose values obtained only at scheduled diabetes clinic visits over 2yr. Multivariate analysis of the data showed that better metabolic control was most strongly associated with compliance with scheduled appointments. Mode of treatment was also associated with metabolic control. Other variables tested, including source of care, age, sex, duration of diabetes, presence of complications, and weight change, were not associated with metabolic control. The strongest analysis of covariance model with demographic and medical-care variables accounted for 39% of the variance in metabolic control. The analysis suggests that other variables, possibly including several psychosocial variables, need to be assessed for their contribution to metabolic control.
Effect of transjugular intrahepatic portosystemic shunt (TIPS) on renal function and vasoactive systems in hepatorenal syndrome (SHR)
Authors: M Guevara, P Ginès, P Sort, JC Bandi, W Jiménez, R Gilabert, J Bosch, V Arroyo, J Rodés
Journal: Journal of Hepatology (1998)
Hepatic progenitor cells from adult human livers for cell transplantation
Authors: T S Weiss, M Lichtenauer, S Kirchner, P Stock, H Aurich, B Christ, G Brockhoff, L A Kunz-Schughart, K-W Jauch, H-J Schlitt, W E Thasler
Journal: Gut (2008)

<h3>Objective:</h3> Liver regeneration is mainly based on cellular self-renewal including progenitor cells. Efforts have been made to harness this potential for cell transplantation, but shortage of hepatocytes and premature differentiated progenitor cells from extra-hepatic organs are limiting factors. Histological studies implied that resident cells in adult liver can proliferate, have bipotential character and may be a suitable source for cell transplantation. <h3>Methods:</h3> Particular cell populations were isolated after adequate tissue dissociation. Single cell suspensions were purified by Thy-1 positivity selection, characterised in vitro and transplanted in immunodeficient Pfp/Rag2 mice. <h3>Results:</h3> Thy-1<sup>+</sup> cells that are mainly found in the portal tract and the surrounding parenchyma, were isolated from surgical liver tissue with high yields from specimens with histological signs of regeneration. Thy-1<sup>+</sup> cell populations were positive for progenitor (CD34, c-kit, CK14, M2PK, OV6), biliary (CK19) and hepatic (HepPar1) markers revealing their progenitor as well as hepatic and biliary nature. The potential of Thy-1<sup>+</sup> cells for differentiation in vitro was demonstrated by increased mRNA and protein expression for hepatic (CK18, HepPar1) and biliary (CK7) markers during culture while progenitor markers CK14, chromogranin A and nestin were reduced. After transplantation of Thy-1<sup>+</sup> cells into livers of immunodeficient mice, engraftment was predominantly seen in the periportal portion of the liver lobule. Analysis of in situ material revealed that transplanted cells express human hepatic markers HepPar1 and albumin, indicating functional engraftment. <h3>Conclusion:</h3> Bipotential progenitor cells from human adult livers can be isolated using Thy-1 and might be a potential candidate for cell treatment in liver diseases.
Individual allergens as risk factors for asthma and bronchial hyperresponsiveness in Chinese children
Authors: G.W.K. Wong, S.T. Li, D.S.C. Hui, T.F. Fok, N.S. Zhong, Y.Z. Chen, C.K.W. Lai
Journal: European Respiratory Journal (2002)

The role of allergen sensitization in the development of asthma in the Chinese is not clear. This study aims to determine the relationship of sensitization to individual allergens, and the development of asthma and bronchial hyperresponsiveness (BHR) in schoolchildren from three Chinese cities: Hong Kong, Beijing and Guangzhou. Community-based random samples of 10-yr-old schoolchildren from three Chinese cities were recruited for study using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Subjects were studied by parental questionnaires (n=10,902), skin-prick tests (n=3,479), and methacholine challenge tests (n=608). The prevalence rates of wheeze in the past 12 months (Hong Kong, 5.8%; Beijing, 3.8%; Guangzhou, 3.4%) and atopy (Hong Kong, 41.2%; Beijing, 23.9%; Guangzhou, 30.8%) were highest in schoolchildren from Hong Kong. Multivariate logistic regression analyses revealed that sensitization to Dermatophagoides pteronyssinus (odds ratio (OR)=4.48; 95% confidence interval (CI): 3.02–6.66), cat (2.59; 1.67–4.03), Dermatophagoides farinae (2.41; 1.65–3.51) and mixed grass pollen (2.85; 1.24–6.50) were significantly associated with current wheeze. Atopy, defined as having ⩾1 positive skin-prick tests, was not an independent risk factor for current wheeze in children from any of the three cities. Furthermore, atopy (OR=2.53; 95% CI: 1.07–5.97), sensitization to cat (3.01; 1.39–6.52) and D. farinae (3.67; 1.93–6.97) were significantly associated with BHR. The authors confirmed that sensitization to house dust mite and cat was significantly associated with current wheeze and bronchial hyperresponsiveness in Chinese schoolchildren. However, the difference in the prevalence rate of atopic sensitization cannot explain the higher prevalence of childhood asthma in Hong Kong, when compared with those children from Beijing and Guangzhou.
Hemostatic molecular markers before the onset of disseminated intravascular coagulation
Authors: Hideo Wada, Nobuo Sakuragawa, Yositaka Mori, Mikio Takagi, Takahiro Nakasaki, Minori Shimura, Kazuyo Hiyoyama, Masakatu Nisikawa, Esteban C. Gabazza, Katsumi Deguchi, Mutuyoshi Kazama, Hiroshi Shiku
Journal: American Journal of Hematology (1999)

We retrospectively measured various hemostatic markers in 240 patients with disseminated intravascular coagulation (DIC) before the onset of DIC and in 110 non-DIC patients, and examined their usefulness for the diagnosis of pre-DIC. Changes in prothrombin time ratio and fibrinogen levels were not significant before the onset of DIC. The plasma levels of fibrinogen and fibrin degradation products before the onset of DIC were increased and the platelet count was gradually reduced in nonleukemic patients; these changes were already significant in the non-DIC state. The plasma levels of thrombin–antithrombin complex (TAT), plasmin–plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were increased before the onset of DIC. In leukemic patients, the plasma levels of sFM on day 5, those of TAT on day 3, and D-dimer on day 1, were significantly increased before the onset of DIC. The levels of most hemostatic markers 7 days before the onset of DIC were not different from those observed in the non-DIC state. In nonleukemic patients, only D-dimer, sFM, and TAT levels were significantly increased 7 days before the onset of DIC compared with values in the non-DIC state. The positive rate of hemostatic markers for the diagnosis of DIC, TAT, and PPIC were high during the pre-DIC and non-DIC groups. The plasma levels of sFM and D-dimer were low in non-DIC and increased gradually during the pre-DIC state. These findings suggest that hemostatic molecular markers such as sFM, D-dimer, and TAT are useful for the diagnosis of pre-DIC, although their cutoff values were different among various diseases. Am. J. Hematol. 60:273–278, 1999. © 1999 Wiley-Liss, Inc.
Hypersensitivity of Tumor Cell Lines with Microsatellite Instability to DNA Double Strand Break Producing Chemotherapeutic Agent Bleomycin
Authors: Hai-Ri Li, Elena I. Shagisultanova, Kentaro Yamashita, Zhe Piao, Manuel Perucho, Sergei R. Malkhosyan
Journal: Cancer Research (2004)

Abstract Genetic or epigenetic inactivation of DNA mismatch repair genes results in a strong mutator phenotype, known as the microsatellite mutator phenotype or microsatellite instability (MSI). This mutator phenotype causes mutations in genes responsible for the regulation of cell growth and survival/death and thus promotes the development and progression of tumors. In addition to such tumorigenic lesions, mutations in genes of other types of DNA repair, for example, DNA double-strand break (DNA DSB) repair, are found in tumor cells with MSI. We report here that the majority of MSI-positive tumor cell lines of different tissue origins (endometrial, ovarian, prostate, and colorectal carcinomas) are hypersensitive to bleomycin, a DNA DSB producing chemotherapeutic drug. We suggest that this hypersensitivity may be a result of inactivation of the DNA DSB repair activity by concomitant mutations of different DNA DSB repair genes. To provide experimental support to this hypothesis, we show that the subclones of the MSI-positive colorectal cancer cell line HCT-8 that bear heterozygous frameshift mutations in the DNA DSB repair gene DNA-PKCS are more sensitive to a combined treatment with bleomycin and the DNA protein kinase inhibitor LY294002 than the original HCT-8 cells, which are wild type for this gene. These results may be useful in designing therapies for MSI-positive cancer.
A Comparison of Rates, Risk Factors, and Outcomes of Gestational Diabetes Between Aboriginal and Non-Aboriginal Women in the Saskatoon Health District
Authors: Roland Dyck, Helena Klomp, Leonard K. Tan, Roger W. Turnell, Makram A. Boctor
Journal: Diabetes Care (2002)

OBJECTIVE—To determine possible differences in gestational diabetes mellitus (GDM) between aboriginal and non-aboriginal people in the Saskatoon Health District. RESEARCH DESIGN AND METHODS—This was a prospective survey of all women admitted for childbirth to the Saskatoon Royal University Hospital between January and July 1998. We compared prevalence rates, risk factors, and outcomes of GDM between aboriginal and non-aboriginal women. RESULTS—Information was obtained from 2,006 women, of whom 252 aboriginal and 1,360 non-aboriginal subjects had been tested for GDM. The overall rates of GDM were 3.5% for women in the general population and 11.5% for aboriginal women. For those living within the Saskatoon Health District, GDM rates were 3.7 and 6.4%, respectively. Multivariate analysis demonstrated that aboriginal ethnicity, most notably when combined with obesity, was an independent predictor for GDM. Pregravid BMI ≥27 kg/m2 and maternal age ≥33 years were the most important risk factors for GDM in aboriginal women, whereas previous GDM, family history of diabetes, and maternal age ≥38 years were the strongest predictors for GDM in non-aboriginal women. CONCLUSIONS—There may be fundamental differences in GDM between aboriginal and non-aboriginal people. Because GDM contributes to an increased risk for type 2 diabetes in aboriginal women and their offspring, the impact of prevention and optimal treatment of GDM on the type 2 diabetes epidemic in susceptible populations are important areas for further investigation.