tbuckley/cabot-search huggingface dataset:
Networks of Gene Sharing among 329 Proteobacterial Genomes Reveal Differences in Lateral Gene Transfer Frequency at Different Phylogenetic Depths
Authors: T. Kloesges, O. Popa, W. Martin, T. Dagan
Journal: Molecular Biology and Evolution (2010)

Lateral gene transfer (LGT) is an important mechanism of natural variation among prokaryotes. Over the full course of evolution, most or all of the genes resident in a given prokaryotic genome have been affected by LGT, yet the frequency of LGT can vary greatly across genes and across prokaryotic groups. The proteobacteria are among the most diverse of prokaryotic taxa. The prevalence of LGT in their genome evolution calls for the application of network-based methods instead of tree-based methods to investigate the relationships among these species. Here, we report networks that capture both vertical and horizontal components of evolutionary history among 1,207,272 proteins distributed across 329 sequenced proteobacterial genomes. The network of shared proteins reveals modularity structure that does not correspond to current classification schemes. On the basis of shared protein-coding genes, the five classes of proteobacteria fall into two main modules, one including the alpha-, delta-, and epsilonproteobacteria and the other including beta- and gammaproteobacteria. The first module is stable over different protein identity thresholds. The second shows more plasticity with regard to the sequence conservation of proteins sampled, with the gammaproteobacteria showing the most chameleon-like evolutionary characteristics within the present sample. Using a minimal lateral network approach, we compared LGT rates at different phylogenetic depths. In general, gene evolution by LGT within proteobacteria is very common. At least one LGT event was inferred to have occurred in at least 75% of the protein families. The average LGT rate at the species and class depth is about one LGT event per protein family, the rate doubling at the phylum level to an average of two LGT events per protein family. Hence, our results indicate that the rate of gene acquisition per protein family is similar at the level of species (by recombination) and at the level of classes (by LGT). The frequency of LGT per genome strongly depends on the species lifestyle, with endosymbionts showing far lower LGT frequencies than free-living species. Moreover, the nature of the transferred genes suggests that gene transfer in proteobacteria is frequently mediated by conjugation.
Repertoires of T cells directed against a large protein antigen, beta-galactosidase. II. Only certain T helper or T suppressor cells are relevant in particular regulatory interactions.
Authors: U Krzych, A V Fowler, E E Sercarz
Journal: The Journal of Experimental Medicine (1985)

11 cyanogen bromide (CB) peptides, comprising 70% of the large protein, Escherichia coli beta-galactosidase (GZ), were studied for their ability to induce T suppressor (Ts) cells capable of strongly suppressing the in vitro anti-fluorescein (FITC) response to GZ-FITC. Only CB-2 (amino acid residues 3-92) and CB-3 (residues 93-187) were found to bear such Ts-inducing epitopes. In examining the specificity of T helper cell (Th) targets susceptible to CB-2 and CB-3-specific Ts, it appeared that only nearly Th targets could be suppressed. Thus, CB-10-primed Th were not suppressed by either Ts; even CB-3-primed Ts did not suppress CB-2-specific Th, although CB-2-specific Ts were effective. Furthermore, analysis of the suppression pattern revealed a hierarchical use of potential epitopes on native GZ in triggering functional regulatory T cells. A dominant Th epitope near the amino terminus of GZ tops a hierarchy of potential Th, most of which are never engaged. The dominant determinant seems to exist on the peptide CB-2-3 (residues 3-187), and presumably is destroyed by its cleavage at Met 92; the Th cells that it induces are suppressible by each of the Ts-inducing peptides. In the GZ system, where the native antigen is quite large, the interactions between Th and Ts are highly circumscribed. This may be attributable to the topology of antigen fragments produced during processing; any relevant fragment must bear at least a Ts- and Th-reactive determinant to permit intercellular regulation. A final implication of these results is that, not only does the existence of a Th-inducing determinant depend on its being an appropriate distance from a B cell epitope, but the existence of Ts-inducing determinants likewise depends on the existence of a neighboring Th-B cell association.
Classification of Distinct Baseline Insulin Infusion Patterns in Children and Adolescents With Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion Therapy
Authors: Paul-Martin Holterhus, Rainer Odendahl, Sandra Oesingmann, Rudolf Lepler, Verena Wagner, Olaf Hiort, Reinhard Holl
Journal: Diabetes Care (2007)

We hypothesized systematic differences in the patterns of programmed basal insulin infusion rates in children and adolescents with type 1 diabetes on continuous subcutaneous insulin infusion (CSII). We aimed at classification of basal insulin infusion rate regimens and comparing patients' underlying clinical characteristics.The German/Austrian diabetes data acquisition system for prospective surveillance database for quality control and scientific surveys in pediatric diabetology served as the primary data source. Latest (September 2004) basal insulin infusion rates of all 1,248 patients with type 1 diabetes on CSII (0.38-18 years) were analyzed (dataset 1). Basal insulin infusion rates per hour were expressed relative to mean basal insulin infusion rates per 24 h. Unsupervised clustering was used to classify basal insulin infusion rate patterns. Clinical characteristics of patients falling into distinct basal insulin infusion rate clusters were compared by Kruskal-Wallis test. Changes of basal insulin infusion rates in 64 patients were followed from initial settings before CSII to latest programming in an independent dataset 2.Seven different basal insulin infusion rate patterns occurred in dataset 1. A dawn-dusk pattern was used in 708 patients (14.9 +/- 2.4 years) with the peak basal insulin infusion rate at 5 a.m. Additional patterns showed only one basal insulin infusion rate oscillation per 24 h with a backshift of peak basal insulin infusion rates in younger children (P < 0.000001) (1 A.M.: n = 152, 12.4 years and 9 P.M.: n = 117, 8.9 years). All but two patients in dataset 2 were initially set on dawn-dusk patterns but showed a comparable diversification of basal insulin infusion rates during follow-up with backshift of peak basal insulin infusion rates in younger children (P < 0.01).Pediatric diabetologists shape distinct basal insulin infusion rate profiles during treatment of CSII patients, mainly reflecting differences in age. Our data strongly suggest that age-dependent endocrine changes during childhood (e.g., puberty) affect circadian distribution of insulin needs in CSII, which should be kept in mind when considering basal insulin infusion rate strategies in children and adolescents.
The cupped disc
Authors: David S Greenfield, R.Michael Siatkowski, Joel S Glaser, Norman J Schatz, Richard K Parrish
Journal: Ophthalmology (1998)

To determine the incidence of positive neuroradiologic studies in consecutive patients with glaucoma associated with normal intraocular pressure and to compare the psychophysical and clinical characteristics of these eyes with eyes with disc cupping associated with intracranial masses.Retrospective case-controlled study.Fifty-two eyes of 29 patients with glaucoma associated with normal intraocular pressure and 44 eyes of 28 control patients with compressive lesions were reviewed.The medical records of consecutive glaucoma patients with normal intraocular pressure who underwent brain magnetic resonance imaging or computed tomography scanning as part of a diagnostic evaluation between January 1, 1985, and July 1, 1995, were reviewed. A masked reading of optic nerve photographs and visual fields was performed by one observer. A similar analysis was performed on a control group of consecutive patients with nonglaucomatous optic nerve cupping with known intracranial mass lesions.The neuroradiologic findings, clinical characteristics, optic nerve head appearance, and patterns of visual field loss were compared between groups.None of the patients diagnosed with glaucoma had neuroradiologic evidence of a mass lesion involving the anterior visual pathway. Compared to control subjects, patients with glaucoma were older (P = 0.0001), had better visual acuity (P = 0.002), greater vertical loss of neuroretinal rim tissue (P = 0.0001), more frequent optic disc hemorrhages (P = 0.01), less neuroretinal rim pallor (P = 0.0001), and more nerve fiber bundle visual field defects aligned at the horizontal midline (P = 0.0001). Visual acuity less than 20/40, vertically aligned visual field defects, optic nerve pallor in excess of cupping, and age younger than 50 years were 77%, 81%, 90%, and 93% specific for nonglaucomatous cupping associated with compressive lesions, respectively.Anterior visual pathway compression is an uncommon finding in the neuroradiologic evaluation of patients with a presumptive diagnosis of normal-tension glaucoma. Younger age, lower levels of visual acuity, vertically aligned visual field defects, and neuroretinal rim pallor may increase the likelihood of identifying an intracranial mass lesion.
Relationship between leptin and lung function in young healthy children
Authors: Jacobien B. Eising, Cuno S.P.M. Uiterwaal, Annemieke M.V. Evelein, Frank L.J. Visseren, Cornelis K. van der Ent
Journal: European Respiratory Journal (2013)

possibly be due to the variability that characterises asthma.Nevertheless, we believe that this study provides proof of concept for the use of an experimental virus infection model in the study of chronic asthmatics whose disease requires the use of ICS.
Neuropeptide Y Is an Essential In Vivo Developmental Regulator of Cardiac <i>I</i> <sub>Ca,L</sub>
Authors: Lev Protas, Andrea Barbuti, Jihong Qu, Vitalyi O. Rybin, Richard D. Palmiter, Susan F. Steinberg, Richard B. Robinson
Journal: Circulation Research (2003)

Cell culture studies demonstrate an increase in cardiac L-type Ca2+ current (ICa,L) density on sympathetic innervation in vitro and suggest the effect depends on neurally released neuropeptide Y (NPY). To determine if a similar mechanism contributes to the postnatal increase in ICa,L in vivo, we prepared isolated ventricular myocytes from neonatal and adult mice with targeted deletion of the NPY gene (Npy-/-) and matched controls (Npy+/+). Whole-cell voltage clamp demonstrates ICa,L density increases postnatally in Npy+/+ (by 56%), but is unchanged in Npy-/-. Both ICa,L density and action potential duration are significantly greater in adult Npy+/+ than Npy-/- myocytes, whereas ICa,L density is equivalent in neonatal Npy+/+ and Npy-/- myocytes. These data indicate NPY does not influence ICa,L prenatally, but the postnatal increase in ICa,L density is entirely NPY-dependent. In contrast, there is a similar postnatal negative voltage shift in the I-V relation in Npy+/+ and Npy-/-, indicating NPY does not influence the developmental change in ICa,L voltage-dependence. Immunoblot analyses and measurements of maximally activated ICa,L (in presence of forskolin or BayK 8644) show that the differences in current density between Npy+/+ and Npy-/- cannot be attributed to altered Ca2+ channel alpha1C subunit protein expression. Rather, these results suggest that the in vivo NPY-dependent postnatal increase in ICa,L density in cardiac myocytes results from regulation ICa,L properties by NPY.
Subcutaneous Unfractionated Heparin vs Low-Molecular-Weight Heparin for Acute Thromboembolic Disease
Authors: Jeffrey L. Carson
Journal: JAMA (2006)

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Puerto Rican Spiritualists View Mental Illness: The Faith Healer as a Paraprofessional
Authors: ISAAC LUBCHANSKY, GLADYS EGRI, JANET STOKES
Journal: American Journal of Psychiatry (1970)

The authors examined the attitudes and beliefs about mental illness of 20 faith healers in the Puerto Rican community of New York City; these were compared with data collected earlier from samples of Spanish-speaking community leaders and a cross-section of Puerto Rican household heads. Spiritualists appear to be an idiosyncratic group differentiated within their culture for the purpose of healing. The authors emphasize the lack of professional acknowledgment of the role native healers play in this and other minorities and present two case studies that may help to explain this lack of acknowledgment.
Impaired IgA response to Giardia heat shock antigen in children with persistent diarrhoea and giardiasis.
Authors: S Char, A M Cevallos, P Yamson, P B Sullivan, G Neale, M J Farthing
Journal: Gut (1993)

The serum antibody response in Gambian children with persistent diarrhoea and giardiasis has been studied. Total serum IgG, IgA, and IgM concentrations were increased in these patients as compared with controls from the same area. Determination of the concentrations of Giardia specific antibodies by enzyme linked immuno adsorbent assay (ELISA), however, revealed that only IgM was raised while those of IgA and IgG were similar to the controls. Analysis of the antigenic determinants of the IgG and IgA responses by immunoblotting showed that patients with chronic infection unlike those who clear the infection have no IgA response to a 57 kDa Giardia heat shock antigen. The association of high concentrations of Giardia specific IgM, low concentrations of Giardia specific IgA and IgG and inability to clear the infection suggests that the switch from an IgM to an IgG or IgA response is inefficient.
Effects of MK-0941, a Novel Glucokinase Activator, on Glycemic Control in Insulin-Treated Patients With Type 2 Diabetes
Authors: Gary E. Meininger, Russell Scott, Maria Alba, Yue Shentu, Edmund Luo, Himal Amin, Michael J. Davies, Keith D. Kaufman, Barry J. Goldstein
Journal: Diabetes Care (2011)

To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes.In this double-blind study, 587 patients taking stable-dose insulin glargine (±metformin ≥1,500 mg/day) were randomized (1:1:1:1:1) to MK-0941 10, 20, 30, or 40 mg or matching placebo t.i.d. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by a 40-week treatment phase during which patients were to be uptitrated as tolerated to 40 mg (or placebo) t.i.d. a.c. The primary efficacy end point was change from baseline in A1C at Week 14.At Week 14, A1C and 2-h postmeal glucose (PMG) improved significantly versus placebo with all MK-0941 doses. Maximal placebo-adjusted least squares mean changes from baseline in A1C (baseline A1C 9.0%) and 2-h PMG were -0.8% and -37 mg/dL (-2 mmol/L), respectively. No significant effects on fasting plasma glucose were observed at any dose versus placebo. By 30 weeks, the initial glycemic responses noted at 14 weeks were not sustained. MK-0941 at one or more doses was associated with significant increases in the incidence of hypoglycemia, triglycerides, systolic blood pressure, and proportion of patients meeting criteria for predefined limits of change for increased diastolic blood pressure.In patients receiving stable-dose insulin glargine, the GKA MK-0941 led to improvements in glycemic control that were not sustained. MK-0941 was associated with an increased incidence of hypoglycemia and elevations in triglycerides and blood pressure.
MyD88 inhibition amplifies dendritic cell capacity to promote pancreatic carcinogenesis via Th2 cells
Authors: Atsuo Ochi, Andrew H. Nguyen, Andrea S. Bedrosian, Harry M. Mushlin, Saman Zarbakhsh, Rocky Barilla, Constantinos P. Zambirinis, Nina C. Fallon, Adeel Rehman, Yuliya Pylayeva-Gupta, Sana Badar, Cristina H. Hajdu, Alan B. Frey, Dafna Bar-Sagi, George Miller
Journal: The Journal of Experimental Medicine (2012)

The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen-restricted Th2-deviated CD4(+) T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC-Th2 axis.
Psychosocial Predictors of Survival in Metastatic Melanoma
Authors: Phyllis N. Butow, Alan S. Coates, Stewart M. Dunn
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Research interest in psychosocial predictors of the onset and course of cancer has been active since the 1950s. However, results have been contradictory and the literature is noted for methodologic weaknesses. In this prospective study, we aimed to systematically obtain data on psychosocial factors associated with human response to illness. PATIENTS AND METHODS: One hundred twenty-five patients with metastatic melanoma completed questionnaires measuring cognitive appraisal of threat, coping, psychologic adjustment, perceived aim of treatment, social support, and quality of life (QOL). Questionnaires were completed, where possible, every 3 months for 2 years after diagnosis. Survival was measured from date of study entry to date of death or was censored at the date of last follow-up for surviving patients. RESULTS: In a multivariate Cox regression analysis of baseline data, which controlled for demographic and disease predictors, the psychologic variables of perceived aim of treatment (P &lt; .001), minimization (P &lt; .05), and anger (P &lt; .05) were independently predictive of survival. Patients who were married (P &lt; .01) and who reported a better QOL (P &lt; .05) also survived longer. CONCLUSION: The prognostic significance of psychologic and QOL scores remained after allowance for conventional prognostic factors. If these associations reflect an early perception by the patient or doctor of disease progression, then measures are at least valuable early indicators of such progression. If psychologic processes have a more direct influence on the course of the underlying illness, then it may be possible to manipulate them for therapeutic effect. We are now conducting a randomized controlled trial of a psychologic intervention to further elucidate these issues.
Stress Echocardiography for Risk Stratification of Diabetic Patients With Known or Suspected Coronary Artery Disease
Authors: Riccardo Bigi, Alessandro Desideri, Lauro Cortigiani, Jeroen J. Bax, Leopoldo Celegon, Cesare Fiorentini
Journal: Diabetes Care (2001)

Coronary artery disease (CAD) is a leading cause of mortality and morbidity in diabetic patients; therefore, their risk stratification is a relevant issue. Because exercise tolerance is frequently impaired in these patients, pharmacological stress echocardiography (SE) has been suggested as a valuable alternative. Our aim was to evaluate the prognostic value of this technique in diabetic patients with known or suspected CAD.A total of 259 consecutive diabetic patients underwent pharmacological SE (dobutamine in 108 patients and dipyridamole in 151 patients) and follow-up for 24 +/- 22 months. A comparison between the prognostic value of SE and exercise electrocardiography (ECG) was made in a subgroup of 120 subjects.A total of 13 cardiac deaths and 13 nonfatal infarctions occurred during follow-up, and 58 patients were revascularized. Univariate predictors of outcome were known CAD, positive SE, rest and peak wall motion score index (WMSI), and peak/rest WMSI variation. Peak WMSI was the only significant and independent prognostic indicator (odds ratio 11; 95% CI 4-29, P < 0.0001) on multivariate Cox's analysis. After adjustment for the most predictive clinical and exercise ECG variables, SE provided 43% additional prognostic information (gain in X(2) = 7, P < 0.01). Moreover, positive SE was associated with a significantly lower event-free survival.SE effectively predicts cardiac events in diabetic patients with known or suspected CAD and adds additional prognostic information as compared with exercise ECG.