tbuckley/cabot-search huggingface dataset:
Major Depressive Disorder in Youths With IDDM: A controlled prospective study of course and outcome
Authors: Maria Kovacs, D Scott Obrosky, David Goldston, Allan Drash
Journal: Diabetes Care (1997)

OBJECTIVE To determine whether IDDM affects the course of major depressive disorder (MDD) in youths. RESEARCH DESIGN AND METHODS The study samples include 24 youths with IDDM (of a group of 92) who developed MDD during a longitudinal follow-up of 10 years, on average, since onset of the medical condition, and 30 depressed psychiatric control subjects, matched on relevant variables. Both groups were repeatedly assessed by semistructured interviews and diagnosed by operational criteria. RESULTS In diabetic subjects, median time to recovery from the first episode of MDD was 6.4 months; by 12 months from onset, 69% of the youths will have recovered. Within 2 years of recovery, 32% were at risk for a new episode; by 6.5 years, altogether 47% are estimated to have a recurrence. Only 37.5% of diabetic subjects received treatment for the first episode of depression, and 50% received treatment for the second episode. Overall rates of recovery and recurrence were indistinguishable in the diabetic and psychiatric control groups. However, young women with diabetes were at nine times greater risk for recurrent depression than their male counterparts, and diabetic subjects eventually spent more time being depressed than the control subjects. CONCLUSIONS The course characteristics of MDD in young diabetic subjects and psychiatric control subjects appear to be similar in several regards. However, the eventual propensity of diabetic youths for more protracted depressions and the higher risk of recurrence among young diabetic women suggest that the mental health of patients with IDDM should be closely monitored. The findings confirm that depression is undertreated among patients in the primary health care sector.
Chemical Characterization and Bioactivity of Polycyclic Aromatic Hydrocarbons from Non-Oxidative Thermal Treatment of Pyrene-Contaminated Soil at 250-1,000 degrees C
Authors: Henning Richter, Veronique Risoul, Arthur L. Lafleur, Elaine F. Plummer, Jack B. Howard, William A. Peters
Journal: Environmental Health Perspectives (2000)

In this paper we report yields, identities, and mutagenicities ofproducts from heating a polyyclic aromatic hydrocarbon (PAH)-contaminated, Superfimd-related synthetic soil matrix without exogenous oxygen.We heated batch samples of soil pretreated with 5.08 wt%o (by weight) pyrene in a tubular furnace under a constant flow of helium gas at 250, 500, 750, and 1,000 * 20°C.Dichlorometdane (DCM) extracts of cooled residues of heated soil and of volatiles condensed on a cold finger after 1 sec residence time at furnace temperature were assayed graimetricaly and analyzed for PAH by HPLC, HPLC coupled to mass spectrometry, and gas chromatography coU- pled to rms spectrometry.AUt four temperatures volatilized pyrene and generated other PAHs, including alkylated pyrenes.We detected bioactive PAHs in the product volatiles: cydopenta[cadpyrene (CPP) at 750 and 1,0000C and benzo[a]pyrene (BaP) at 1,000°C.We found a dean soil residue, i.e., no pyrene or other DCM extracts, only at 750C.Control experi- ments with uncontaminated soil, pyrene, and Ottawa sand plus 4.89 wt% pyrene revealed no CPP or BaP production from soil itself, but these experiments imply that pyrene interactions with soil, e.g., soil-bound silica, stimulate CPP and BaP production.We detected mutagenicty to human diploid lymphoblasts (in vitro) in volatiles from 1,000C heating of soil plus pyrene and sand plus pyrene, and in the residue from 500°C heating of soil plus pyrene.Three plausible pathways for pyrene conversion to other PAHs are a) a reaton with light gas species, e.g., soil-or pyrene-derived acetylene; b) loss of C2-units followed by reaction with a PAH; and ) dimerization with firther molecular weight growth via cydodehydrogenation.This study shows that thermal treatment of PAH-polluted soil may generate toxic by-products that require fiuther deanup by oxi- dation or other measures.
Safety and efficacy of adefovir dipivoxil in patients infected with lamivudine-resistant hepatitis B and HIV-1
Authors: Yves Benhamou, Vincent Thibault, Pamela Vig, Vincent Calvez, Anne-Genevieve Marcelin, Marie-Hélène Fievet, Graeme Currie, Chuy G. Chang, Lu Biao, Shelly Xiong, Carol Brosgart, Thierry Poynard
Journal: Journal of Hepatology (2005)
Abstract 2763: Utility of clinical biomarkers for detecting protein kinase CK2 inhibition: A report from the phase I trial of CX-4945
Authors: John K.C. Lim, Claire S. Padgett, Robert F. Marschke, Donald W. Northfelt, Eleni Andreopoulou, Daniel D. Von Hoff, Kenna Anderes, Ta Kung Chen, Sean E. O'Brien
Journal: Cancer Research (2010)

Abstract Introduction: CX-4945 is a first-in-class, orally administered small molecule that potently and selectively inhibits protein kinase CK2, a previously unexploited molecular target with well documented roles in many cancers. In vitro, CX-4945 selectively kills cancer cells by modulating key survival pathways, resulting in cell cycle arrest, inhibition of cell proliferation, and promotion of apoptosis. CK2 hyperactivation of the PI3K/Akt pathway promotes the phosphorylation of several proteins which we have exploited as biomarkers for CX-4945 activity. A validated laser scanning cytometry method has been developed to quantify the phosphorylation of p21 and Akt in cells, and this has been employed to characterize these substrates in circulating blood cells collected from patients in the phase I clinical trial of CX-4945. Procedures: Eligible patients with advanced solid tumors with progressive disease, or for whom there are no available standard therapies, were administered CX-4945 in successive dose cohorts using a standard 3×3 design at: 90, 160, 300, 460, and 700 mg per dose. Oral doses were administered twice daily for twenty-one consecutive days of a four week cycle. Serial plasma samples were collected for pharmacokinetic analysis on the first and final dosing days of Cycle 1 (i.e., Day 1 and Day 21). In addition, whole blood samples were collected at pre-treatment, 4 hours and 8 hours following the first dose of CX-4945 on Day 1 and Day 21, and peripheral blood mononuclear cells (PBMCs) were isolated for pharmacodynamic biomarker evaluations (specifically, total and phosphorylated forms of p21 and Akt). Plasma samples were also collected at these time points for quantification of plasma IL-6. Results: Seventeen patients with advanced solid tumors from five separate dose cohorts have received oral doses of CX-4945 to date, and all patients in the study participated in the collection of PBMCs. Biomarkers from patients in Cohorts 3 and 4 demonstrated changes in their profile consistent with the inhibition of CK2. CX-4945 displays general linearity in PK parameters between the dose cohorts, with a terminal half life of approximately 25 hours at steady state. Conclusions: To date, no DLTs have yet been observed, and the MTD remains to be defined in this Phase I study. Early signals suggest a modulation of the biomarker profile consistent with CK2 inhibition. Patient enrollment will continue, to further characterize CX-4945's safety, tolerance, pharmacokinetics and pharmacodynamic effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2763.
Web Resources for Microbial Data
Authors: Qinglan Sun, Li Liu, Linhuan Wu, Wei Li, Quanhe Liu, Jianyuan Zhang, Di Liu, Juncai Ma
Journal: Genomics Proteomics & Bioinformatics (2015)

Abstract There are multitudes of web resources that are quite useful for the microbial scientific research community. Here, we provide a brief introduction on some of the most notable microbial web resources and an evaluation of them based upon our own user experience.
SESTAMIBI BREAST IMAGING OF NON-PALPABLE MAMMOGRAPHICALLY SUSPICIOUS BREAST LESIONS
Authors: J. A. Cutrone, I. Khalkhali, I. Mena, L. Diggles, R. Venegas, M. P. Vargas, H. I. Vargas
Journal: Clinical Nuclear Medicine (1994)

Cutrone, J. A.; Khalkhali, I.; Mena, I.; Diggles, L.; Venegas, R.; Vargas, M. P.; Vargas, H. I. Author Information
Abstract 1712: Ki67 index is an independent prognostic factor in pleural mesothelioma
Authors: Bahil Ghanim, Szilvia Torok, Mir Hoda, Martin Filipits, Gyula Ostoros, Ulrike Setinek, Janos Fillinger, Balazs Dome, Walter Klepetko, Walter Berger, Balazs Hegedus
Journal: Cancer Research (2012)

Abstract Aims: Malignant pleural mesothelioma is a devastating cancer with increasing incidence. Despite the fact that for establishing the diagnosis a number of immunohistochemical markers are needed, there is only one pathological prognosticator accepted and utilized, namely the histological subtype. Accordingly, we have investigated the prognostic significance of the Ki76 labeling index in malignant pleural mesothelioma. Patients and Methods: Ki67 index has been determined by assessing the labeled nuclei per high power field and correlated in a retrospective manner with patients’ clinical history and outcome. The prognostic power of the routine proliferation marker Ki67 was first determined in a test cohort (TC) of paraffin-embedded tissue samples from 55 patients. The independence of prognostic power against basic clinicopathological characteristics has been determined by multivariate analysis. Next, we measured the prognostic power in an independent validation cohort (VC) of 42 patients from another center. Results: Median Ki67 index was found to be 10 for both the test and validation. Patients whose tumor sample was categorized by low Ki67 index (≥ 10) had significantly longer survival times than those with higher Ki76 indices (in the test cohort: hazard ratio [HR] 2.49, 95% confidence interval [CI] 1.30-4.79, p&amp;lt;0.01; in the validation cohort: HR 2.54, CI 1.26-5.13, p&amp;lt;0.01). In the multivariate analyses of the test cohort (n=54), we could prove the prognostic power of Ki67, independent from gender, age, treatment, stage and histology. Treatment (HR 4.02, CI 1.82-8.90, p&amp;lt;0.01) and Ki67 index (HR 2.19, CI 1.07-4.47, p=0.03) were the remaining independent significant prognosticators in the multivariate Cox regression model, whereas biphasic histology showed a clear tendency to worse prognosis when compared to the epitheloid subtype (HR 1.96, CI 0.94-4.07, p=0.07). Conclusion: Our study identifies Ki67 index as an independent, reproducible prognostic factor in malignant pleural mesothelioma and warrants its further investigation and clinical application in patients with this malignancy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1712. doi:1538-7445.AM2012-1712
Childhood Metabolic Syndrome
Authors: Ram Weiss
Journal: Diabetes Care (2011)

The metabolic syndrome, also known as “syndrome X,” describes a cluster of cardiovascular risk factors that have been shown to predict the development of cardiovascular disease and type 2 diabetes (1). Some suggest that the cluster is driven by the consequences of peripheral insulin resistance (2), whereas others believe that obesity-related inflammation is the culprit (3). Many putative molecular mechanisms can provide excellent explanations for both theories regarding the primary driving mechanism of the clustering of cardiovascular risk factors (4) and how each one accelerates atherogenesis (5). Yet teasing inflammation and peripheral insulin resistance apart in individual patients or even in large cohorts is difficult because of their coexistence and possible vicious exacerbation of each other. The general paradigm regarding the evolvement of the syndrome is that adipocyte dysfunction in some obese individuals who are genetically prone or exposed to specific environmental signals leads to peripheral insulin resistance and subclinical inflammation culminating in accelerated atherosclerosis and overt clinical manifestations (6). The clinical utility of defining this syndrome in children and adolescents has been debated, since some propose that from a clinical standpoint, addressing each component of the cluster individually has comparable clinical and predictive outcomes, whereas others suggest such definitions are inappropriate for the pediatric age group. This debate has important implications from an epidemiological and public health standpoint. Yet it is imperative to indicate that the underlying pathophysiology that leads to the typical metabolic milieu characteristic of individuals with obesity-driven peripheral insulin resistance and/or subclinical inflammation has common features in all ages and is postulated to be the “driving force” of the development of accelerated atherogenesis and altered glucose metabolism in susceptible individuals.

Several definitions of the metabolic syndrome in children have been proposed by various research groups (7,8) and expert consensus (9), and the use of …
Overnight urinary 11-hydroxycorticosteroid estimations in diagnosis of Cushing's syndrome.
Authors: D Mattingly, C Tyler
Journal: BMJ (1976)

Overnight specimens of urine were collected from control, obese, and hirsute women and from 11 women with Cushing's syndrome. Urinary 11-hydroxycorticosteroid levels in the group with Cushing's syndrome were significantly higher than in the other three groups. This simple test has proved invaluable when screening for Cushing's syndrome in a busy outpatient clinic.
The Use of a Helium-Oxygen Mixture during Maximum Expiratory Flow to Demonstrate Obstruction in Small Airways in Smokers
Authors: James Dosman, Frederick Bode, John Urbanetti, Richard Martin, Peter T. Macklem
Journal: Journal of Clinical Investigation (1975)

We measured the response to breathing a mixture of 80% helium and 20% oxygen (He) during a maximum expiratory flow-volume (MEFV) maneuver in 66 nonsmokers and 48 smokers, aged 17-67. All of the subjects studied had (forced expiratory volume in 1 s/forced vital capacity [FEV1.0/FVC]) × 100 of greater than 70%. While the flow rates of the smokers were within ±2 SD of those of the nonsmokers at 50% VC (V̇max50), both groups showed a reduction in flow with age (nonsmokers: r=-0.34, P<0.01; smokers r=-0.52, P<0.001). Nonsmokers showed no significant reduction with age in response to breathing He, while smokers showed a marked reduction with age (r=-0.63, P<0.001 at V̇max50). We also measured the lung volume at which maximum expiratory flow (V̇max) while the subject was breathing He became equal to V̇max while he was breathing air, and expressed it as a percent of the VC. This was the most sensitive method of separating smokers from nonsmokers. These results indicate that the use of He during an MEFV maneuver affords sufficient sensitivity to enable detection of functional abnormalities in smokers at a stage when V̇max while they are breathing air is normal.
Single delayed rectifier channels in the membrane of rabbit ventricular myocytes.
Authors: M W Veldkamp, A C van Ginneken, L N Bouman
Journal: Circulation Research (1993)

In rabbit ventricular cells, the delayed rectifier current (IK) has not been extensively studied, and properties of single IK channels still need to be determined. In this study, we present data on a voltage-dependent channel in rabbit ventricular cells; the properties indicate that it is an IK channel. Patch-clamp experiments were carried out on cell-attached and inside-out patches of rabbit ventricular cells. Single-channel currents were recorded at negative potentials as inward currents with 150 mM K+ in the pipette. Voltage-dependent channel activity was only present after the return from a depolarizing test pulse, indicating activation on depolarization. Single-channel conductance calculated from the current-voltage relation was 13.1 pS (pooled data, n = 8). The shift in reversal potential of the unitary currents, determined at 150 and 300 mM K+ at the intracellular side of the membrane, showed that the channels were highly permeable to potassium ions. Increase of the duration or the amplitude of the depolarizing test pulse increased channel activity. The time constant for activation at +30 mV was 187 msec (pooled data, n = 4). Half-activation potential was -4.9 +/- 3.8 mV (mean +/- SD), and the slope factor was 7.2 +/- 3.7 mV (mean +/- SD). Current tails, reconstructed from averaged single-channel currents, revealed that the time course of deactivation decreased from 694 +/- 73 msec at -80 mV to 136 +/- 39 msec at -110 mV. Additional evidence that the channel was indeed an IK channel was provided by the observation that the channel was blocked by 10(-7) M E-4031, a class III antiarrhythmic agent that has been shown to block a component of the macroscopic IK in guinea pig heart.
The pressures of pregnancy
Authors: T. Groves
Journal: BMJ (2014)

In most developed countries except, notably, the United States, women are delaying parenthood for longer and longer. In England and Wales the latest data show that the mean age of a mother giving birth was at an all time high of 29.8 years in 2012 and that women aged 40 or over had the fastest rising fertility rate. Against this backdrop Kate Bramham and colleagues have explored a surprisingly under-researched area: the risks of pregnancy for women with chronic hypertension (doi:10.1136/bmj.g2301).

Their systematic review found that women who were hypertensive before or at the start of pregnancy had high pooled average incidences of all adverse outcomes of pregnancy. The findings withstood subgroup analyses by factors such as gross national income per capita and prevalence of …
Abnormal Sleep/Wake Cycles and the Effect of Environmental Noise on Sleep Disruption in the Intensive Care Unit
Authors: NEIL S. FREEDMAN, JOOST GAZENDAM, LACHELLE LEVAN, ALLAN I. PACK, RICHARD J. SCHWAB
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Little is known about sleep/wake abnormalities in intensive care and less is known about the mechanisms responsible for these abnormalities. We studied 22 (20 mechanically ventilated) medical intensive care unit (ICU) patients with continuous polysomnography (PSG) and environmental noise measurements for 24–48 h to characterize sleep–wake patterns and objectively determine the effect of environmental noise on sleep disruption. All 22 patients demonstrated sleep–wake cycle abnormalities. There were large variations in total sleep time (TST) with the mean total sleep time per 24-h study period of 8.8 ± 5.0 h. Sleep–wake cycles were fragmented and nonconsolidated with a mean of 57 ± 18% and 43 ± 18% of the TST occurring during the day and night, respectively. Environmental noise was responsible for 11.5 and 17% of the overall arousals and awakenings from sleep, respectively. The mean noise arousal index was 1.9 ± 2.1 arousals/h sleep. Conclusions: (1) ICU patients are qualitatively, but not necessarily quantitatively, sleep deprived; and (2) although environmental noise is in part responsible for sleep–wake abnormalities, it is not responsible for the majority of the sleep fragmentation and may therefore not be as disruptive to sleep as the previous literature suggests.
Delivering change is a "brutally exposing business," GP commissioners are warned
Authors: M. Limb
Journal: BMJ (2012)

Doctors were ambitious to radically transform health services in London but could “easily be crushed” by the weight of expectation and bureaucracy, a leading NHS manager has said.

Ruth Carnall, chief executive of the NHS London strategic health authority, said that GPs and their colleagues on clinical commissioning groups would find that delivering change was a “brutally exposing business.”

She said this was being shown by current attempts to reconfigure services in northwest London, where a proposal that nine emergency departments be reduced to five has met fierce opposition.

“Clinicians trying to lead change can be put under enormous scrutiny and pressure,” she said. She said that they could become stressed and disillusioned by the tendency of politicians who oppose the closure of local services “to reduce complex, finely balanced arguments to a soundbite” but should resist compromising …
Major histocompatibility complex class II-expressing endothelial cells induce allospecific nonresponsiveness in naive T cells.
Authors: F M Marelli-Berg, R E Hargreaves, P Carmichael, A Dorling, G Lombardi, R I Lechler
Journal: The Journal of Experimental Medicine (1996)

The role of endothelial cells (EC) in initiating a primary T cell response is of importance in clinical transplantation and autoimmunity since EC are the first allogeneic target encountered by the recipient's immune system and may display tissue-specific autoantigens in the context of an inflammatory response. In this study, we have investigated the antigen-presenting cell function of human umbilical vein-derived EC (HUVEC), depleted of constitutively major histocompatibility complex class II+ cells and induced to express class II molecules by interferon-gamma. The results show that HUVEC do not express B7 but can support proliferation by antigen-specific T cell clones. In contrast, they were unable to initiate a primary alloresponse using three independent HUVEC cultures and MHC class II-mismatched CD4+ T cells from eight donors. The response to HUVEC was reconstituted by trans-costimulation provided by DAP.3 transfectants expressing human B7.1. Coculture of peripheral blood T cells with EC expressing allogeneic DR molecules had markedly different effects on CD45RO+ and RA+ subsets. Subsequent reactivity of the RO+ T cells was unaffected by exposure to EC, indicating a neutral encounter. In contrast, culture with DR+ EC induced allospecific nonresponsiveness in RA+ T cells.
Colchicine clearance is impaired in alcoholic cirrhosis
Authors: Jonathan A. Leighton, Michael K. Bay, Alma L. Maldonado, Steven Schenker, K. Vincent Speeg
Journal: Hepatology (1991)

Colchicine may have benefit in primary biliary cirrhosis and alcoholic liver disease. It is currently used in patients with impaired liver function, yet little is known about its elimination in such patients. Colchicine clearance in the rat is significantly impaired in various models of liver disease. To study this in human beings, colchicine pharmacokinetics were compared in normal subjects and patients with alcoholic cirrhosis. Colchicine clearance was impaired in the cirrhotic patients. Normal subjects had a mean clearance of 10.65 +/- 1.82 ml/min.kg, whereas cirrhotic patients had a mean clearance of 4.22 +/- 0.45 ml/min.kg (p less than 0.01). The half-life was 57.4 +/- 14.2 min in control subjects vs. 114.4 +/- 19.7 min in cirrhotic patients (p = 0.054). Volume of distribution was not different in the two groups (0.718 +/- 0.1 L/kg in control subjects; 0.716 +/- 0.158 L/kg in cirrhotic patients, p greater than 0.99). No correlation was seen between colchicine clearance and bilirubin, albumin, prothrombin time or Child-Pugh classification, but this may be the result of the small number of patients studied. Based on the values measured, it is estimated that colchicine steady state would change from an average 1.12 ng/ml in normal individuals to 2.82 ng/ml in the cirrhotic patients if 0.6 mg were taken every 12 hr. It is unknown whether this change would be clinically significant. These data show that cirrhosis impairs colchicine clearance and demonstrates that the liver is a major route of colchicine elimination.
Transplantation of mesenchymal stem cells within a poly(lactide‐<i>co</i>‐ɛ‐caprolactone) scaffold improves cardiac function in a rat myocardial infarction model
Authors: Jiyong Jin, Sung In Jeong, Young Min Shin, Kwang Suk Lim, Heung soo Shin, Young Moo Lee, Hyun Chul Koh, Kyung‐Soo Kim
Journal: European Journal of Heart Failure (2009)