tbuckley/cabot-search huggingface dataset:
Risk Factors for Pulmonary Mycobacterial Disease in South African Gold Miners
Authors: ELIZABETH L. CORBETT, GAVIN J. CHURCHYARD, TIM CLAYTON, PHILIP HERSELMAN, BRIAN WILLIAMS, RICHARD HAYES, DAAN MULDER, KEVIN M. DE COCK
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Pulmonary mycobacterial disease is common in miners. Risk factors for nontuberculous pulmonary mycobacterial (NTM) disease and tuberculosis (TB) in gold miners were identified in a retrospective case-control study that included 206 NTM patients and 381 TB patients of known human immunodeficiency virus (HIV) status diagnosed between 1993 and 1996. A total of 180 HIV-tested trauma/surgical inpatients were selected as control patients. Both HIV infection (odds ratio [OR] 3.6 for NTM and 4.5 for TB patients) and higher grades of silicosis (OR 5.0 for NTM and 4.9 for TB patients) were significantly more common in NTM and TB patients than in control patients. HIV prevalence rose in the control and both case groups during the study period. The overall HIV prevalence was 13.1% in NTM patients, 14.2% in TB patients, and 5.6% in control patients. Previous TB (OR 9.6), premorbid focal radiological scarring (OR 7.4) and a dusty job at diagnosis (OR 2.4) were additional significant risk factors for NTM disease. These findings suggest that the historically high incidence of NTM disease in miners is largely attributable to chronic chest disease from silica dust inhalation and prior TB. HIV infection has recently become an additional risk factor for mycobacterial disease in miners and is likely to become increasingly important as the HIV epidemic progresses.
Lack of Allelic Exclusion in B Cell Chronic Lymphocytic Leukemia
Authors: Laura Z. Rassenti, Thomas J. Kipps
Journal: The Journal of Experimental Medicine (1997)

We determined the immunoglobulin (Ig) VH subgroup expressed by the leukemia cells of 108 patients with B cell chronic lymphocytic leukemia (CLL). Surprisingly, we found that six samples (5%) each expressed Ig of more than one VH subgroup. Southern blot analysis demonstrated that these samples each had rearrangements involving both Ig heavy chain alleles. Nucleic acid sequence analyses of the Ig cDNA revealed each to express two functional Ig VH genes: VH3-33 and VH4-39; VH3-7 and VH4-39; VH3-23 and VH4-61; VH2-70 and VH3-30.3; or VH3-30 and VH4-b (DP67). One sample expressed three Ig VH genes: VH2-70, VH3-7, and VH4-59. Despite having more than one Ig heavy chain transcript, each sample was found to express only one functional Ig light chain. From the primary sequence, we deduced that the Ig of some of these CLL samples should react with Lc1, a monoclonal antibody (mAb) reactive with a supratypic cross-reactive idiotype present on Ig encoded by a subgroup of Ig VH4 genes (namely, VH4-39, VH4-b [DP-67], VH4-59, or VH4-61), and B6, an mAb that reacts with Ig encoded by certain Ig VH3 genes (namely, VH3-23, VH3-30, or VH3-30.3), and/or modified staphylococcal protein A (SpA), a 45-kilodalton bacterial “superantigen” that reacts with most Ig of the VH3 subgroup. Flow cytometric analyses revealed that such samples did in fact react with Lc1 and B6 and/or SpA, but not with control mAbs of irrelevant specificity. This study demonstrates that a subset of CLL patients have leukemic B cells that express more than one functional Ig heavy chain.
Use of Framingham risk score and new biomarkers to predict cardiovascular mortality in older people: population based observational cohort study
Authors: W. de Ruijter, R. G J Westendorp, W. J J Assendelft, W. P J den Elzen, A. J M de Craen, S. le Cessie, J. Gussekloo
Journal: BMJ (2009)

<b>Objectives</b> To investigate the performance of classic risk factors, and of some new biomarkers, in predicting cardiovascular mortality in very old people from the general population with no history of cardiovascular disease. <b>Design</b> The Leiden 85-plus Study (1997-2004) is an observational prospective cohort study with 5 years of follow-up. <b>Setting</b> General population of the city of Leiden, the Netherlands. <b>Participants</b> Population based sample of participants aged 85 years (215 women and 87 men) with no history of cardiovascular disease; no other exclusion criteria. <b>Main measurements</b> Cause specific mortality was registered during follow-up. All classic risk factors included in the Framingham risk score (sex, systolic blood pressure, total and high density lipoprotein cholesterol, diabetes mellitus, smoking and electrocardiogram based left ventricular hypertrophy), as well as plasma concentrations of the new biomarkers homocysteine, folic acid, C reactive protein, and interleukin 6, were assessed at baseline. <b>Results</b> During follow-up, 108 of the 302 participants died; 32% (35/108) of deaths were from cardiovascular causes. Classic risk factors did not predict cardiovascular mortality when used in the Framingham risk score (area under receiver operating characteristic curve 0.53, 95% confidence interval 0.42 to 0.63) or in a newly calibrated model (0.53, 0.43 to 0.64). Of the new biomarkers studied, homocysteine had most predictive power (0.65, 0.55 to 0.75). Entering any additional risk factor or combination of factors into the homocysteine prediction model did not increase its discriminative power. <b>Conclusions</b> In very old people from the general population with no history of cardiovascular disease, concentrations of homocysteine alone can accurately identify those at high risk of cardiovascular mortality, whereas classic risk factors included in the Framingham risk score do not. These preliminary findings warrant validation in a separate cohort.
Pharmacology of the Lower Urinary Tract
Authors: William C de Groat, Naoki Yoshimura
Journal: The Annual Review of Pharmacology and Toxicology (2001)

The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the urinary bladder, urethra, and external urethral sphincter. This activity is in turn controlled by neural circuits in the brain, spinal cord, and peripheral ganglia. Various neurotransmitters, including acetylcholine, norepinephrine, dopamine, serotonin, excitatory and inhibitory amino acids, adenosine triphosphate, nitric oxide, and neuropeptides, have been implicated in the neural regulation of the lower urinary tract. Injuries or diseases of the nervous system, as well as drugs and disorders of the peripheral organs, can produce voiding dysfunctions such as urinary frequency, urgency, and incontinence or inefficient voiding and urinary retention. This chapter will review recent advances in our understanding of the pathophysiology of voiding disorders and the targets for drug therapy.
Growth in Very Young Children Undergoing Chronic Peritoneal Dialysis
Authors: Lesley Rees, Marta Azocar, Dagmara Borzych, Alan R. Watson, Anja Büscher, Alberto Edefonti, Ilmay Bilge, David Askenazi, Giovanna Leozappa, Claudia Gonzales, Koen van Hoeck, Donna Secker, Aleksandra Zurowska, Kai Rönnholm, Antonia H. M. Bouts, Heather Stewart, Gema Ariceta, Bruno Ranchin, Bradley A. Warady, Franz Schaefer
Journal: Journal of the American Society of Nephrology (2011)

Very young children with chronic kidney disease often have difficulty maintaining adequate nutrition, which contributes to the high prevalence of short stature in this population. Characteristics of the dialysis prescription and supplemental feeding via a nasogastric (NG) tube or gastrostomy may improve growth, but this is not well understood. Here, we analyzed data from 153 children in 18 countries who commenced chronic peritoneal dialysis at <24 months of age. From diagnosis to last observation, 57 patients were fed on demand, 54 by NG tube, and 10 by gastrostomy; 26 switched from NG to gastrostomy; and 6 returned from NG to demand feeding. North American and European centers accounted for nearly all feeding by gastrostomy. Standardized body mass index (BMI) uniformly decreased during periods of demand feeding and increased during NG and gastrostomy feeding. Changes in BMI demonstrated significant regional variation: 26% of North American children were obese and 50% of Turkish children were malnourished at last observation (P < 0.005). Body length decreased sharply during the first 6 to 12 months of life and then tended to stabilize. Time fed by gastrostomy significantly associated with higher lengths over time (P < 0.001), but adjustment for baseline length attenuated this effect. In addition, the use of biocompatible peritoneal dialysate and administration of growth hormone independently associated with improved length, even after adjusting for regional factors. In summary, growth and nutritional status vary regionally in very young children treated with chronic peritoneal dialysis. The use of gastrostomy feeding, biocompatible dialysis fluid, and growth hormone therapy associate with improved linear growth.
Ischemic Cerebrovascular Complications of Cardiac Procedures
Authors: Harold P. Adams
Journal: Circulation (2010)

T he interactions between heart disease and stroke are close and well known.Advances in therapeutics are leading to the development of a broad gamut of interventions, including medical, surgical, and endovascular procedures that are aimed at improving outcomes in persons with severe heart disease.In particular, innovative surgical and endovascular procedures are being used to treat patients who otherwise could not be treated.Unfortunately, these procedures may be accompanied by neurological complications that result in considerable morbidity or even death.Stroke and neuropsychological impairments are well-recognized complications of cardiovascular operations. 1,2In addition, cerebrovascular events may follow endovascular procedures, especially those that involve catheterization of the left side of the heart. 3lthough these complications are relatively uncommon, they do have a negative impact on outcomes and survival. 4The patterns of brain injury include global brain ischemia secondary to hypotension or hypoxia that may cause coma or an encephalopathy; localized brain ischemia secondary to hypoperfusion that appears in a watershed (border zone) or that primarily affects the posterior cerebral hemispheres and leads to visual loss and cognitive deficits; neurotoxicity secondary to contrast agents; intracranial hemorrhage resulting from an idiopathic coagulopathy or from antithrombotic medications; and acute ischemic stroke secondary to embolization of thrombi, air, debris or pieces of atherosclerotic plaque. 5esides overt strokes, patients undergoing cardiovascular procedures may have long-term neuropsychological sequelae, including memory loss or impaired executive functioning. 5,6n addition, brain imaging performed after procedures also may detect clinically silent or subtle ischemic strokes. 5,7
The Effect of Nonsurgical Periodontal Therapy on Hemoglobin A<sub>1c</sub>Levels in Persons With Type 2 Diabetes and Chronic Periodontitis
Authors: Steven P. Engebretson, Leslie G. Hyman, Bryan S. Michalowicz, Elinor R. Schoenfeld, Marie C. Gelato, Wei Hou, Elizabeth R. Seaquist, Michael S. Reddy, Cora E. Lewis, Thomas W. Oates, Devjit Tripathy, James A. Katancik, Philip R. Orlander, David W. Paquette, Naomi Q. Hanson, Michael Y. Tsai
Journal: JAMA (2013)

Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control.To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis.The Diabetes and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter, randomized clinical trial. Participants had type 2 diabetes, were taking stable doses of medications, had HbA1c levels between 7% and less than 9%, and untreated chronic periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers.The treatment group (n = 257) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months. The control group (n = 257) received no treatment for 6 months.Difference in change in HbA1c level from baseline between groups at 6 months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score.Enrollment was stopped early because of futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, -0.05% [95% CI, -0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all).Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c.clinicaltrials.gov Identifier: NCT00997178.
USP18 inhibits NF-κB and NFAT activation during Th17 differentiation by deubiquitinating the TAK1–TAB1 complex
Authors: Xikui Liu, Hongxiu Li, Bo Zhong, Marzenna Blonska, Sara Gorjestani, Ming Yan, Qiang Tian, Dong-Er Zhang, Xin Lin, Chen Dong
Journal: The Journal of Experimental Medicine (2013)

Reversible ubiquitin modification of cell signaling molecules has emerged as a critical mechanism by which cells respond to extracellular stimuli. Although ubiquitination of TGF-β-activated kinase 1 (TAK1) is critical for NF-κB activation in T cells, the regulation of its deubiquitination is unclear. We show that USP18, which was previously reported to be important in regulating type I interferon signaling in innate immunity, regulates T cell activation and T helper 17 (Th17) cell differentiation by deubiquitinating the TAK1-TAB1 complex. USP18-deficient T cells are defective in Th17 differentiation and Usp18(-/-) mice are resistant to experimental autoimmune encephalomyelitis (EAE). In response to T cell receptor engagement, USP18-deficient T cells exhibit hyperactivation of NF-κB and NFAT and produce increased levels of IL-2 compared with the wild-type controls. Importantly, USP18 is associated with and deubiquitinates the TAK1-TAB1 complex, thereby restricting expression of IL-2. Our findings thus demonstrate a previously uncharacterized negative regulation of TAK1 activity during Th17 differentiation, suggesting that USP18 may be targeted to treat autoimmune diseases.
Enzalutamide: A Novel Antiandrogen for Patients with Castrate-Resistant Prostate Cancer
Authors: Jean Hoffman-Censits, Wm. Kevin Kelly
Journal: Clinical Cancer Research (2013)

Abstract Enzalutamide (MDV3100, Xtandi, Medivation\Astellas) is an oral inhibitor of androgen receptor signaling that blocks androgen receptor interaction, inhibits translocation of the androgen receptor to the nucleus, impairs androgen receptor binding to DNA, and inhibits coactivator recruitment and receptor-mediated DNA transcription. In a phase III randomized study comparing enzalutamide with placebo in men with progressive castration-resistant prostate cancer (CRPC) who were previously treated with docetaxel, enzalutamide showed an improvement in overall survival (18.4 vs. 13.6 months, HR, 0.63; P &amp;lt; 0.001). In addition, all secondary endpoints including proportion of patients with prostate-specific antigen (PSA) decline, soft-tissue response, quality-of-life response, time to PSA progression, radiographic progression-free survival, and the time to the first radiographic skeletal event all significantly favored patients treated with enzalutamide. Fatigue, diarrhea, and hot flashes were common in patients treated with enzalutamide, with seizures reported in 5 (0.6%) of the patients. Enzalutamide is a novel therapy that very potently blocks the androgen signaling pathway, which is unregulated during the development of CRPC. The preclinical studies along with the pivotal trials that led to its approval by the U.S. Food and Drug Administration (FDA) in September 2012 will be reviewed. Clin Cancer Res; 19(6); 1335–9. ©2012 AACR.
Deoxyhaemoglobin concentrations in the detection of central cyanosis.
Authors: H L Snider, T M Roy
Journal: Thorax (1988)

Deoxylaelobin conentratiom in te detection of central cyano_s SIR,-Although not explicitly stated in their article, Dr Geraldine Goss and her associates (March 1988;43:212-3) appear to share with others' the misconception that Lunds- gaard and Van Slyke2 believed cyanosis first could be detected when 5 g/dl reduced haemoglobin was present in the arterial blood.Lundsgaard and Van Slyke wrote, "About 5 grams ofreduced haemoglobin per 100 c.c. ofcapillary blood appear necessary to cause cyanosis.. . 2 They calculated mean capillary unsaturation by averaging the arterial and venous unsaturations.The difference between mean capillary unsaturation and arterial unsaturation would depend on the haemoglobin affinity for oxygen, perfusion ofthe tissue being viewed, and oxygen utilisation by that particular tissue.Since these factors were not reported by Dr Goss and colleagues, their data cannot be used to determine the correctness or incorrectness of the original conclusion of Lundsgaard and Van Slyke.Admittedly, one should have reservations about that early assertion after considering the fact that Lunds- gaard and Van Slyke did not report analyses ofarterial blood specimens on patients-only free flowing peripheral venous specimens had been analysed.It is interesting that reanalysis of Stadie's data from 1919,3 which did involve arterial blood sampling, would lead one to much the same conclusion as was reached by Dr Goss and her associates.None of his five patients without cyanosis had more than 1-3 g/dl arterial unsaturation while 4/27 with cyanosis had values less than 15 g/dl arterial unsaturation.
GADD45 Deregulation in Cancer: Frequently Methylated Tumor Suppressors and Potential Therapeutic Targets
Authors: Luiz F. Zerbini, Towia A. Libermann
Journal: Clinical Cancer Research (2005)

In this issue of Clinical Cancer Research , Ying et al. ([1][1]) have investigated the hypothesis that GADD45γ , a member of the GADD45 family originally identified as a growth arrest– and DNA damage–inducible gene, could serve as a functional tumor suppressor gene, and moreover, as a
Hypothalamo-pituitary-adrenal function in intrinsic non-atopic asthma.
Authors: J V Collins, D Bellamy, M G Britton, J Townsend, D J Brown
Journal: Thorax (1975)

Sixteen patients with intrinsic non-atopic asthma with persistent wheezing who had never been treated with corticosteroids showed normal adrenocortical responses to prolonged stimulation with Tetracosactin Depot. In a subgroup of six patients the hypothalamo-pituitary-adrenal (HPA) response to a standard insulin stress test was normal. It is concluded that impaired responsiveness of the HPA axis is unlikely to be a common factor in initiating or maintaining airways obstruction in patients with intrinsic asthma.
Evaluation of Coronary Artery Disease by Computed Tomography Angiography in Patients Treated for Childhood Hodgkin's Lymphoma
Authors: Serhan Küpeli, Tuncay Hazırolan, Ali Varan, Deniz Akata, Dursun Alehan, Mutlu Hayran, Aytekin Besim, Münevver Büyükpamukçu
Journal: Journal of Clinical Oncology (2009)

PURPOSE To detect pathologies in coronary arteries by computed tomography angiography (CTA) in survivors of childhood Hodgkin's lymphoma who have been treated with radiotherapy and/or cardiotoxic agents. PATIENTS AND METHODS Patients with HL who have been in remission for at least 2 years after completion of therapy were included. CBC, lipid profile, urine analysis, brain natriuretic peptide, troponin-T, creatinine kinase-myocardial band, ECG, telecardiography, echocardiography, and CTA of the patients were performed. Cardiac vascular abnormalities were noted. Results A total of 119 patients were included in the study. In 19 patients (16%), we found coronary artery abnormalities. There was a significant difference between the patients who received mediastinal radiotherapy and those who did not (P = .02). By multivariate analysis, in patients receiving mediastinal radiotherapy the risk of developing a coronary artery abnormality was found to increase 6.8 times compared with patients who did not receive mediastinal radiotherapy (P = .009). Stent implantation was performed in a 28-year-old patient because of critical stenosis in right coronary. In two patients some irregularities were detected both in CTA and conventional angiography, and they remained in close follow-up. A 22-year-old patient whose CTA showed critical stenosis in his left anterior descending artery refused the conventional angiography. CONCLUSION To our knowledge, this is the first large study using CTA for detection of coronary abnormalities in patients treated for HL in pediatric age group. Coronary CTA is a minimally invasive tool for early diagnosis of coronary artery disease in patients who were treated with mediastinal radiotherapy and/or cardiotoxic chemotherapy.
Downregulation of Ca2+ and Mg2+ Transport Proteins in the Kidney Explains Tacrolimus (FK506)-Induced Hypercalciuria and Hypomagnesemia
Authors: Tom Nijenhuis, Joost G.J. Hoenderop, René J.M. Bindels
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. FK506 (tacrolimus) and dexamethasone are potent immunosuppressants known to induce significant side effects on mineral homeostasis, including hypercalciuria and hypomagnesemia. However, the underlying molecular mechanisms remain unknown. The present study investigated the effects of FK506 and dexamethasone on the expression of proteins involved in active Ca2+ reabsorption: the epithelial Ca2+ channel TRPV5 and the cytosolic Ca2+-binding protein calbindin-D28K. In addition, the renal expression of the putative Mg2+ channel TRPM6, suggested to be involved in transcellular Mg2+ reabsorption, was determined. Administration of FK506 to rats by daily oral gavage during 7 d significantly enhanced the urinary excretion of Ca2+ and Mg2+ and induced a significant hypomagnesemia. FK506 significantly decreased the renal mRNA expression of TRPV5 (62 ± 7% relative to controls), calbindin-D28K (9 ± 1%), and TRPM6 (52 ± 8%), as determined by real-time quantitative PCR analysis. Furthermore, semiquantitative immunohistochemistry showed reduced renal protein abundance of TRPV5 (24 ± 5%) and calbindin-D28K (29 ± 4%), altogether suggesting that downregulation of these transport proteins is responsible for the FK506-induced Ca2+ and Mg2+ wasting. In contrast, dexamethasone significantly enhanced renal TRPV5 (150 ± 15%), calbindin-D28K (177 ± 23%), and TRPM6 (156 ± 20%) mRNA levels along with TRPV5 (211 ± 8%) and calbindin-D28K (176 ± 5%) protein abundance in the presence of significantly increased Ca2+ and Mg2+ excretion. This indicated that these proteins are directly or indirectly regulated by dexamethasone. In conclusion, FK506 and dexamethasone induce renal Ca2+ and Mg2+ wasting, albeit by different mechanisms. Downregulation of specific Ca2+ and Mg2+ transport proteins provides a molecular mechanism for FK506-induced hypercalciuria and hypomagnesemia, whereas dexamethasone positively regulates these proteins.