tbuckley/cabot-search huggingface dataset:
Molecular phylogeny of plethodonine salamanders and hylid frogs: statistical analysis of protein comparisons.
Authors: R Highton
Journal: Molecular Biology and Evolution (1991)

The bootstrapping method of determining confidence in the topology of phylogenetic trees has been applied to electrophoretic protein data for two groups of amphibians: salamanders of two North American genera (Aneides and Plethodon) of the tribe Plethodontini and Holarctic hylid frogs. Some current methods of phylogenetic reconstruction for electrophoretic protein data have been evaluated by comparing the trees obtained from molecular data sets with available morphological data. Molecular data on the phylogenetic relationships of Aneides and Plethodon, data obtained from electrophoretic and immunological studies, indicate that Aneides probably was derived from western Plethodon subsequent to the separation of eastern and western Plethodon. Thus Plethodon very likely is a paraphyletic genus. The extremely low rate of morphological evolution in Plethodon compared with that in Aneides causes difficulty in indicating their evolutionary relationships taxonomically because there are no synapomorphic morphological characters that define either eastern or western Plethodon, whereas there are several for the genus Aneides. Thus molecular data alone probably indicate the evolutionary relationships of the species in these genera. Highton and Larson's (1979) arrangement of species of Plethodon into eight species groups is supported. The topologies of the unweighted pair-group method using arithmetic means (UPGMA) and distance Wagner trees were compared with independent morphological and molecular data on the relationships of the 28 plethodonine species. It was found that UPGMA trees indicate relationships that are more in agreement with other information than are those provided by distance Wagner trees. The use of the bootstrap technique indicates that the topologies of UPGMA trees are better supported statistically than are the topologies of distance Wagner trees. Moreover, different addition criteria produce a variety of distance Wagner trees with different topologies, each with several groupings that are not supported statistically. It is concluded that considerable caution should be used in interpreting the topology of distance Wagner trees. Very similar results were obtained with a second data set on 30 taxa of Holarctic hylid frogs. Trees obtained by the neighbor-joining method are more in agreement with UPGMA phenograms and other data, so this method of phylogenetic reconstruction may be useful to systematists not willing to assume constant rates of evolution.(ABSTRACT TRUNCATED AT 400 WORDS)
Increased expression of activation markers and adhesion molecules on lung T-cells compared with blood in the normal rat
Authors: T. Tschernig, F. Fliegert, J. Westermann, R. Pabst
Journal: European Respiratory Journal (1999)

Bleomycin-induced lung injury has been extensively used as a model of interstitial pneumonia and pulmonary fibrosis. Intercellular adhesion molecule (ICAM)-1 is a ligand for lymphocyte function-associated antigen (LFA)-1alpha and has been shown to be required for leukocyte migration into inflamed areas. The purpose of this report was to investigate the role of the ICAM-1/LFA-1alpha pathway in a murine model of bleomycin-induced lung injury. Animals received 75 mg x kg(-1) bleomycin (BLM) i.v. followed by treatment with phosphate-buffered saline (BLM group), anti-ICAM-1 and LFA-1alpha monoclonal antibodies (mAb) (BLM+mAb group). Inflammatory cell counts of bronchoalveolar lavage (BAL) fluid, hydroxyproline content and histological findings were compared between these groups. In the BLM group, significant increases in total cell count, macrophage count and neutrophil count of BAL fluid were observed on days 7 and 14. In the BLM+mAb group, bleomycin-induced accumulation of neutrophils was significantly reduced on days 7 and 14 (p&lt;0.01). However, the administration of mAb to ICAM-1 and LFA-1alpha did not decrease the lung hydroxyproline content or the histopathological fibrosis grading score, indicating that the antagonism of ICAM-I and LFA-1alpha did not attenuate bleomycin-induced pulmonary fibrosis. This study suggests that the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1alpha pathway mediates the accumulation of inflammatory cells in the injured lung caused by bleomycin; however, other mechanisms are important for the subsequent development of pulmonary fibrosis.
Antibody Targeting of Cell-Bound MUC1 SEA Domain Kills Tumor Cells
Authors: Edward Pichinuk, Itai Benhar, Oded Jacobi, Michael Chalik, Lotem Weiss, Ravit Ziv, Carolyn Sympson, Amolkumar Karwa, Nechama I. Smorodinsky, Daniel B. Rubinstein, Daniel H. Wreschner
Journal: Cancer Research (2012)

The cell-surface glycoprotein MUC1 is a particularly appealing target for antibody targeting, being selectively overexpressed in many types of cancers and a high proportion of cancer stem-like cells. However the occurrence of MUC1 cleavage, which leads to the release of the extracellular α subunit into the circulation where it can sequester many anti-MUC1 antibodies, renders the target problematic to some degree. To address this issue, we generated a set of unique MUC1 monoclonal antibodies that target a region termed the SEA domain that remains tethered to the cell surface after MUC1 cleavage. In breast cancer cell populations, these antibodies bound the cancer cells with high picomolar affinity. Starting with a partially humanized antibody, DMB5F3, we created a recombinant chimeric antibody that bound a panel of MUC1+ cancer cells with higher affinities relative to cetuximab (anti-EGFR1) or tratuzumab (anti-erbB2) control antibodies. DMB5F3 internalization from the cell surface occurred in an efficient temperature-dependent manner. Linkage to toxin rendered these DMB5F3 antibodies to be cytotoxic against MUC1+ cancer cells at low picomolar concentrations. Our findings show that high-affinity antibodies to cell-bound MUC1 SEA domain exert specific cytotoxicity against cancer cells, and they point to the SEA domain as a potential immunogen to generate MUC1 vaccines.
Older Women With Diabetes Have a Higher Risk of Falls
Authors: Ann V. Schwartz, Teresa A. Hillier, Deborah E. Sellmeyer, Helaine E. Resnick, Edward Gregg, Kristine E. Ensrud, Pamela J. Schreiner, Karen L. Margolis, Jane A. Cauley, Michael C. Nevitt, Dennis M. Black, Steven R. Cummings
Journal: Diabetes Care (2002)

OBJECTIVE—To determine whether older women with diabetes have an increased risk of falls and whether known risk factors for falls account for any increased risk. RESEARCH DESIGN AND METHODS—This prospective cohort study included 9,249 women ≥67 years of age enrolled in the Study of Osteoporotic Fractures. Diabetes was determined by questionnaire at baseline. Physical performance was measured at the second examination. Subsequently, falls were ascertained every 4 months by postcard. RESULTS—A total of 629 (6.8%) women had diabetes, including 99 who used insulin. During an average of 7.2 years, 1,640 women (18%) fell more than once a year. Diabetes, stratified by insulin use, was associated with an increased risk of falling more than once a year (age-adjusted odds ratio [OR] 1.68 [95% CI 1.37–2.07] for non–insulin-treated diabetes; age-adjusted OR 2.78 [1.82–4.24] for insulin-treated diabetes). In the first 2 years of follow-up, women with diabetes were not more likely to fall than women without diabetes (44 vs. 42%; P = 0.26), but they had more falls (3.1 vs. 2.4; P &amp;lt; 0.01). Women with diabetes were more likely to have other risk factors for falls, which appeared to account for the increased risk of falls associated with non–insulin-treated diabetes (adjusted OR 1.18 [0.87–1.60]) but not insulin-treated diabetes (adjusted OR 2.76 [1.52–5.01]). CONCLUSIONS—Older women with diabetes have an increased risk of falling, partly because of the increased rates of known fall risk factors, and may benefit from interventions to prevent falls. Further research is needed to determine whether diabetes treatment reduces fall risk.
CSF-induced and HIV-1–mediated Distinct Regulation of Hck and C/EBPβ Represent a Heterogeneous Susceptibility of Monocyte-derived Macrophages to M-tropic HIV-1 Infection
Authors: Iwao Komuro, Yasuko Yokota, Sachiko Yasuda, Aikichi Iwamoto, Kiyoko S. Kagawa
Journal: The Journal of Experimental Medicine (2003)

Granulocyte/macrophage colony-stimulating factor (GM-CSF)–induced monocyte-derived macrophages (GM-MΦ) are permissive to M-tropic HIV-1 entry, but inhibit viral replication at posttranscriptional and translational levels, whereas M-CSF-induced macrophages (M-MΦ) produce a large amount of HIV-1. M-MΦ express a high level of Hck and a large isoform of C/EBPβ, and HIV-1 infection increases the expression of Hck but not of C/EBPβ. GM-MΦ express a high level of C/EBPβ and a low level of Hck, and HIV-1 infection drastically increases the expression of a short isoform of C/EBPβ but decreases that of Hck. Treatment of M-MΦ with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPβ and inhibits the viral replication. Treatment of GM-MΦ with a moderate amount of AS-C/EBPβ not only inhibits the expression of the small isoform of C/EBPβ preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate. These results suggest that CSF-induced and HIV-1–mediated distinct regulation of Hck and small isoform of C/EBPβ represent the heterogeneous susceptibility of tissue MΦ to HIV-1 infection, and the regulation of Hck and C/EBPβ are closely related and these two molecules affect one another.
Regional Variation in Out-of-Hospital Cardiac Arrest Incidence and Outcome
Authors: Graham Nichol, Elizabeth Thomas, Clifton W. Callaway, Jerris Hedges, Judy L. Powell, Tom P. Aufderheide, Tom Rea, Robert Lowe, Todd Brown, John Dreyer, Dan Davis, Ahamed Idris, Ian Stiell
Journal: JAMA (2008)

ContextThe health and policy implications of regional variation in incidence and outcome of out-of-hospital cardiac arrest remain to be determined.Objective To evaluate whether cardiac arrest incidence and outcome differ across geographic regions.Design, Setting, and Patients Prospective observational study (the Resuscitation Outcomes Consortium) of all out-of-hospital cardiac arrests in 10 North American sites (8 US and 2 Canadian) from May 1, 2006, to April 30, 2007, followed up to hospital discharge, and including data available as of June 28, 2008.Cases (aged 0-108 years) were assessed by organized emergency medical services (EMS) personnel, did not have traumatic injury, and received attempts at external defibrillation or chest compressions or resuscitation was not attempted.Census data were used to determine rates adjusted for age and sex. Main Outcome MeasuresIncidence rate, mortality rate, case-fatality rate, and survival to discharge for patients assessed or treated by EMS personnel or with an initial rhythm of ventricular fibrillation. ResultsAmong the 10 sites, the total catchment population was 21.4 million, and there were 20 520 cardiac arrests.A total of 11 898 (58.0%) had resuscitation attempted; 2729 (22.9% of treated) had initial rhythm of ventricular fibrillation or ventricular tachycardia or rhythms that were shockable by an automated external defibrillator; and 954 (4.6% of total) were discharged alive.The median incidence of EMS-treated cardiac arrest across sites was 52.1 (interquartile range [IQR], 48.0-70.1)per 100 000 population; survival ranged from 3.0% to 16.3%, with a median of 8.4% (IQR, 5.4%-10.4%).Median ventricular fibrillation incidence was 12.6 (IQR, 10.6-5.2) per 100 000 population; survival ranged from 7.7% to 39.9%, with a median of 22.0% (IQR, 15.0%-24.4%),with significant differences across sites for incidence and survival (PϽ.001). ConclusionIn this study involving 10 geographic regions in North America, there were significant and important regional differences in out-of-hospital cardiac arrest incidence and outcome.
Protective Role of Increased Myocardial Glycogen Stores in Cardiac Anoxia in the Rat
Authors: JAMES SCHEUER, S. William STEZOSKI
Journal: Circulation Research (1970)

To determine whether increased glycogen stores might protect the heart against anoxia, experiments were performed in the isolated perfused rat heart. Marked differences in cardiac glycogen were produced by comparing hearts from rats previously treated with reserpine with hearts from control rats. Lesser differences in cardiac glycogen were produced in hearts by perfusing them for 15 minutes without glucose (0 mM glucose) or with 20 mM glucose. Both groups were then studied during a 5-minute anoxic cycle with 5 mM glucose as the exogenous substrate. Hearts from the reserpine-treated rats had higher left ventricular pressures, maximal rate of left ventricular pressure rise, and lactate output after 2 minutes of anoxia than the hearts from control rats. Similar but less marked mechanical differences were observed between 0 mM glucose and 20 mM glucose hearts. The mechanical differences during anoxia between the two groups were not abolished by simultaneous L-norepinephrine administration. Hearts with greater initial glycogen stores had higher glycogenolytic rates, and proportionately more lactate was produced from glycogen than from glucose. Thus, anaerobic ATP production per mole of hexose was greater in hearts with higher glycogen stores. Calculated ATP production was also greater in hearts from the reserpine-treated rats than in those from control animals. These studies demonstrate that both marked and minor elevations in cardiac glycogen are associated with greater glycolytic reserve and improved mechanical resistance to anoxia. This appears to be mainly due to enhanced glycogenolysis and anaerobic ATP production.
Termination of aquired and natural immunological tolerance with specific complexes.
Authors: G S Habicht, J M Chiller, W O Weigle
Journal: The Journal of Experimental Medicine (1975)

It was possible to terminate the induced unresponsive state to bovine serum albumin (BSA) and the natural unresponsive state to autologous thyroglobulin in rabbits (RTg) by immunization with complexes composed of heterologous cross-reacting antibody and the tolerated antigens. The unresponsive state was terminated in rabbits made unresponsive by neonatal injections of BSA and then 3 mo later injected with complexes composed of BSA and guinea pig antihuman serum albumin. This termination was manifested by the presence of anti-BSA plaque-forming cells. Similarly, the natural unresponsive state was terminated in adult rabbits injected with complexes between RTg and guinea pig antibovine thyroglobulin (BTg) in that thyroid lesions and circulating anti-RTg were produced. The results can be best explained by the presence of unresponsive T cells and competent B cells, where the guinea pig gamma globulin (antibody) activates T cells specific for the guinea pig gamma globulin portion of the complexes and thus permits stimulation of B cells competent to the exposed determinants of the tolerated (BSA or RTg) portion of the complexes. The detailed mechanism for the activation of B cells in tolerant animals is discussed.
Familial Malignant Melanoma
Authors: Alfred W. Kopf
Journal: JAMA (1986)

Characteristics associated with familial compared with nonfamilial malignant melanoma were assessed. These data were obtained from consecutive prospectively completed questionnaires on 1169 cases of cutaneous malignant melanoma. Of these, 69 patients indicated a positive family history for this cancer. Among the various clinical and histological variables compared, those that significantly correlated with the familial occurrence of malignant melanoma include younger age at first diagnosis, smaller diameter of the lesion, lower Clark level, decreased frequency of nonmelanoma skin cancer, and reduced prevalence of noncutaneous cancer. Increased awareness of malignant melanoma among family members could account for some of these observations. Identification of the familial variety of malignant melanoma has practical implications concerning early detection and prompt intervention. (<i>JAMA</i>1986;256:1915-1919)
Triglyceride–to–HDL Cholesterol Ratio in the Dyslipidemic Classification of Type 2 Diabetes
Authors: Ana María Wägner, Antonio Pérez, Jose Luis Sánchez-Quesada, Jordi Ordóñez-Llanos
Journal: Diabetes Care (2005)

Although LDL cholesterol is the main target in the treatment of diabetic dyslipidemia, it does not fully account for the cardiovascular risk associated with diabetes, neither alone nor in combination with triglycerides and HDL cholesterol. On the other hand, diabetic dyslipidemia also includes an overall increase in atherogenic particles identifiable, by measuring apolipoprotein B (apoB), and a predominance of small, dense LDL particles (phenotype B). The latter, although associated with increased cardiovascular risk, is not routinely assessed because its measurement is not available to most clinical laboratories. Therefore, easily measurable predictors of LDL size, such as triglycerides or LDL cholesterol/apoB and triglyceride–to–HDL cholesterol ratios, have been proposed, with the latter being suggested as the best surrogate (1,2,3). However, no study has been conducted that compares all of these predictors.

The aim of the present study is to evaluate the triglyceride–to–HDL cholesterol ratio, non-HDL cholesterol, and apoB to predict LDL phenotype and to assess them in the risk classification of patients with type 2 diabetes.

A total of 107 type 2 diabetic patients (68% male, age 59 ± 10 years [means ± SD], time since diagnosis 8.5 years [range 0–37], HbA1c 7.35% [3.7–16]) were consecutively included in the study. None of the patients were taking drugs or were in situations (not related to diabetes) known to affect lipoprotein metabolism.

Total cholesterol and triglycerides were measured by enzymatic methods and HDL cholesterol by a direct method (Roche Diagnostics, Basel, Switzerland). Hypertriglyceridemia was defined by triglycerides >2.25 mmol/l (4, …
DNA microarrays for comparison of gene expression profiles between diagnosis and relapse in precursor-B acute lymphoblastic leukemia: choice of technique and purification influence the identification of potential diagnostic markers
Authors: F J T Staal, M van der Burg, L F A Wessels, B H Barendregt, M R M Baert, C M M van den Burg, C Van Huffel, A W Langerak, V H J van der Velden, M J T Reinders, J J M van Dongen
Journal: Leukemia (2003)
Prediction of Survival by [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial
Authors: Mitchell Machtay, Fenghai Duan, Barry A. Siegel, Bradley S. Snyder, Jeremy J. Gorelick, Janet S. Reddin, Reginald Munden, Douglas W. Johnson, Larry H. Wilf, Albert DeNittis, Nancy Sherwin, Kwan Ho Cho, Seok-ki Kim, Gregory Videtic, Donald R. Neumann, Ritsuko Komaki, Homer Macapinlac, Jeffrey D. Bradley, Abass Alavi
Journal: Journal of Clinical Oncology (2013)

In this prospective National Cancer Institute-funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non-small-cell lung cancer (NSCLC).Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models.Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak.Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.
Repression of SPI2 transcription by nitric oxide-producing, IFNγ-activated macrophages promotes maturation of<i>Salmonella</i>phagosomes
Authors: Bruce D. McCollister, Travis J. Bourret, Ronald Gill, Jessica Jones-Carson, Andrés Vázquez-Torres
Journal: The Journal of Experimental Medicine (2005)

By remodeling the phagosomal membrane, the type III secretion system encoded within the Salmonella pathogenicity island-2 (SPI2) helps Salmonella thrive within professional phagocytes. We report here that nitric oxide (NO) generated by IFNγ-activated macrophages abrogates the intracellular survival advantage associated with a functional SPI2 type III secretion system. NO congeners inhibit overall expression of SPI2 effectors encoded both inside and outside the SPI2 gene cluster, reflecting a reduced transcript level of the sensor kinase SsrA that governs overall SPI2 transcription. Down-regulation of SPI2 expression in IFNγ-treated macrophages does not seem to be the result of global NO cytotoxicity, because transcription of the housekeeping rpoD sigma factor remains unchanged, whereas the expression of the hmpA-encoded, NO-metabolizing flavohemoprotein is stimulated. Because of the reduced SPI2 expression, Salmonella-containing vacuoles interact more efficiently with compartments of the late endosomal/lysosomal system in NO-producing, IFNγ-treated macrophages. These findings demonstrate that inhibition of intracellular SPI2 transcription by NO promotes the interaction of Salmonella phagosomes with the degradative compartments required for enhanced antimicrobial activity. Transcriptional repression of a type III secretion system that blocks phagolysosome biogenesis represents a novel mechanism by which NO mediates resistance of IFNγ-activated phagocytes to an intracellular pathogen.