tbuckley/cabot-search huggingface dataset:
GAD65 Autoantibody Responses in Japanese Latent Autoimmune Diabetes in Adult Patients
Authors: Taro Maruyama, Shilpa Oak, Akira Shimada, Christiane S. Hampe
Journal: Diabetes Care (2008)

OBJECTIVE—To determine whether development of insulin requirement in patients with latent autoimmune diabetes in adults (LADA) is accompanied with the emergence of a type 1 diabetes–like autoimmune response. RESEARCH DESIGN AND METHODS—We correlated β-cell–specific autoimmunity reflected in autoantibodies to the 65-kDa isoform of GAD (GAD65) with insulin requirement. We determined GAD65Ab epitope specificities in type 1 diabetic patients, LADA patients without insulin requirement (nonprogressed), and LADA patients that had developed insulin requirement (progressed). RESULTS—Recognition of a type 1 diabetes–specific GAD65Ab epitope was more pronounced in type 1 diabetic patients than in nonprogressed (P &amp;lt; 0.001) or progressed (P &amp;lt; 0.01) LADA patients, with no significant differences between the two LADA cohorts. These differences were particularly pronounced in samples with GAD65Ab titers &amp;lt;1,000 units/ml, with no differences in epitope specificities in samples with higher GAD65Ab titers. Disease duration (initial diabetes diagnosis until sample collection or development of insulin requirement) in nonprogressed and progressed LADA patients, respectively, was not correlated with epitope specificity, suggesting lack of epitope maturation. This was supported by epitope analyses of longitudinal samples from LADA patients during progression to insulin requirement. CONCLUSIONS—First, the GAD65Ab-specific autoimmune reaction in type 1 diabetic patients with low and moderate GAD65Ab titers differs from that in LADA patients, irrespective of insulin requirement. Second, the GAD65Ab-specific autoimmune response in LADA patients does not change after their initial diabetes diagnosis. Finally, LADA patients with high GAD65Ab titers resemble type 1 diabetic patients in their GAD65Ab epitope specificity.
Long-term treatment of alpha1-antitrypsin deficiency-related pulmonary emphysema with human alpha1-antitrypsin. Wissenschaftliche Arbeitsgemeinschaft zur Therapie von Lungenerkrankungen (WATL)-alpha1-AT-study group
Authors: M Wencker, N Banik, R Buhl, R Seidel, N Konietzko
Journal: European Respiratory Journal (1998)

Alpha1-antitrypsin (alpha1-AT) deficiency is a genetic disorder characterized by low serum levels of alpha1-AT and a high risk of pulmonary emphysema at a young age. The resulting surplus of proteases, mainly of neutrophil elastase, can be balanced by i.v. augmentation with alpha1-AT. However, it is not clear if affected patients benefit from long-term augmentation therapy and no long-term safety data are available. We examined 443 patients with severe alpha1-AT deficiency and pulmonary emphysema receiving weekly i.v. infusions of 60 mg x kg body weight(-1) alpha1-AT in addition to their regular medication. The progression of the disease was assessed by repeated lung function measurements, particularly the decline in forced expiratory volume in one second (deltaFEV1). Four hundred and forty three patients with alpha1-AT deficiency tolerated augmentation therapy well with few adverse reactions. The deltaFEV1 in 287 patients with available follow-up data was 57.1+/-31.1 mL x yr(-1). Stratified for baseline FEV1, the decline was 35.6+/-21.3 mL in the 108 patients with an initial FEV1 &lt;30% and 64.0+/-26.4 mL in the 164 with FEV1 30-65% of predicted normal (p=0.0008). The remaining 15 patients had an initial FEV1 &gt;65% pred. Long-term treatment with i.v. alpha1-antitrypsin in patients with severe alpha1-antitrypsin deficiency is feasible and safe. The decline in forced expiratory volume in one second is related to the initial forced expiratory volume in one second as in alpha1-antitrypsin deficient patients not receiving augmentation therapy.
Immunoglobulin heavy-chain gene rearrangement in adult acute lymphoblastic leukemia reveals preferential usage of JH-proximal variable gene segments
Authors: Forida Y. Mortuza, Ilidia M. Moreira, Maria Papaioannou, Paula Gameiro, Luke A. Coyle, Clair S. Gricks, Peter Amlot, Hugh Grant Prentice, Alejandro Madrigal, Alan Victor Hoffbrand, Letizia Foroni
Journal: Blood (2001)
Studies on human thyroxine-binding globulin (TBG)
Authors: James S. Marshall, Jack Pensky
Journal: Journal of Clinical Investigation (1969)

A method for obtaining highly purified thyroxine-binding globulin (TBG) from whole human serum is presented. The method employs relatively simple procedures of step-wise ammonium sulfate precipitation followed by column chromatography on DEAE cellulose and DEAE Sephadex. The final product produces a single protein band on disc electrophoresis. The sedimentation constant of the TBG thus purified is 3.91 and its calculated mol wt is 54,000. An antiserum to the highly purified TBG produced a single arc on immunoelectrophoresis. When the antiserum was reacted against normal human serum or against serum from subjects deficient in TBG, each produced two arcs-one identical with that produced by the antigen alone. The second arc is probably the result of a contaminating protein in the antigen, present in too low a concentration to be detectable by disc gel electrophoresis. It is concluded that some persons with TBG "deficiency" have a circulating protein, immunologically indistinguishable from TBG, which is defective in its ability to bind thyroxine.
Accumulation of p53 and Reductions in XIAP Abundance Promote the Apoptosis of Prostate Cancer Cells
Authors: Subhra Mohapatra, Baoky Chu, Xiuhua Zhao, W.J. Pledger
Journal: Cancer Research (2005)

Abstract Toward the goal of developing effective treatments for prostate cancers, we examined the effects of cyclin-dependent kinase inhibitors on the survival of prostate cancer cells. We show that roscovitine, R-roscovitine, and CGP74514A (collectively referred to as CKIs) induce the apoptosis of LNCaP and LNCaP-Rf cells, both of which express wild-type p53. Apoptosis required caspase-9 and caspase-3 activity, and cytochrome c accumulated in the cytosol of CKI-treated cells. Amounts of p53 increased substantially in CKI-treated cells, whereas amounts of the endogenous caspase inhibitor XIAP decreased. CKIs did not appreciably induce the apoptosis of LNCaP cells treated with pifithrin-α, which prevents p53 accumulation, or of prostate cancer cells that lack p53 function (PC3 and DU145). Ectopic expression of p53 in PC3 cells for 44 hours did not reduce XIAP abundance or induce apoptosis. However, p53-expressing PC3 cells readily apoptosed when exposed to CKIs or when depleted of XIAP by RNA interference. These findings show that CKIs induce the mitochondria-mediated apoptosis of prostate cancer cells by a dual mechanism: p53 accumulation and XIAP depletion. They suggest that these events in combination may prove useful in the treatment of advanced prostate cancers.
Paternal Age and Schizophrenia: Further Support for an Association
Authors: Christina Dalman, Peter Allebeck
Journal: American Journal of Psychiatry (2002)

Advanced paternal age has been proposed as a risk factor for later development of schizophrenia in offspring, although studies are not conclusive. De novo mutations arising in paternal germ cells have been suggested as the underlying mechanism.The hypothesized association was investigated in a population-based case-control study comprising 524 subjects with schizophrenia and 1,043 matched comparison subjects selected from registers. Birth records with data on parental age were retrieved manually. Odds ratios were computed, with controls for maternal age, parity, marital status, socioeconomic status, maternal psychotic illness, and obstetric complications.The odds of schizophrenia in offspring of fathers 45 years old or older were 2.8 times as great as in offspring of fathers aged 20-24 years.These findings confirm previous reports of a higher risk for schizophrenia associated with advanced paternal age. They may be of interest for further studies on the genetic mechanisms behind schizophrenia.
Effects of nutrition, growth hormone disturbances, training, altitude and sleep on lung volumes
Authors: C Gaultier, R Crapo
Journal: European Respiratory Journal (1997)

Various modulating factors have been shown to affect postnatal lung growth and development in humans and other mammalian species.Therefore, normative pulmonary function data should ideally indicate the environmental conditions of life.This paper will review current knowledge on the effects of nutrition, growth hormone disturbances, training and altitude on lung volumes in children and adults.Furthermore, the impact of sleep states on lung volumes is considered.The present review is a background paper of a consensus document on measurements of lung volumes in humans.
Antiapoptotic Effect of Serum and Glucocorticoid-Inducible Protein Kinase Is Mediated by Novel Mechanism Activating IκB Kinase
Authors: Liping Zhang, Ruwen Cui, Xiaodong Cheng, Jie Du
Journal: Cancer Research (2005)

Abstract Serum and glucocorticoid inducible protein kinase (SGK) plays a crucial role in promoting cell survival, but the mechanisms for this response are not clear. We show that SGK is involved in the regulation of apoptosis in breast cancer cells by modulating the transcriptional activity of nuclear transcription factor κB (NF-κB). High levels of SGK expression were observed in human breast cancer samples. When SGK was reduced the apoptotic rate increased, and increased SGK activity prevents serum withdrawal–induced apoptosis. SGK-induced cell survival was abolished by a dominant-negative form of IκB kinase β (IKKβ, K44A) or a null mutation of IKKβ in mouse embryonic fibroblast cells indicating involvement of the NF-κB pathway. Serum-induced SGK or increased expression of SGK activated NF-κB transcriptional activity, whereas small interference RNA to SGK blocked NF-κB activity. Coexpression of SGK and IKKβ significantly increased the activation of NF-κB (versus expression of IKKβ alone). Expression of dominant-negative IKKβ K44A, IκBα AA, and kinase-dead SGK (127KM) blocked the ability of SGK to stimulate NF-κB activity, suggesting that IKKβ is a target of SGK. We also show that SGK enhances the ability of IKKβ to phosphorylate endogenous IκBα in cells or recombinant glutathione S-transferase-IκBα in vitro and increases IκBα degradation; SGK physically associates with and activates IKKβ in MDA231 cells via phosphorylation of Ser181 in IKKβ. Taken together, we conclude that SGK acts as an oncogene in breast cancer cells through activation of the IKK-NF-κB pathway, thereby preventing apoptosis. Blocking SGK expression/activity represents a potential therapeutic approach for breast cancer treatment.
Asbestos, Simian virus 40 and malignant mesothelioma
Authors: S. C. Stenton
Journal: Thorax (1997)

Background.DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small t antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany.SV40 is not normally infective in man though it can transform human cells in tissue culture.A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the incidence of mesothelioma in the United States, Britain and Europe.The present study investigated the presence of SV40LTAg DNA in recently diagnosed cases of mesothelioma in Britain and the feasibility of detecting the SV40 DNA in archival tissue for retrospective analysis of cases in the peri-vaccination period.Methods.DNA was extracted from fresh frozen and/or rehydrated formalin fixed, paraffin embedded tissue sections from nine recently diagnosed cases of mesothelioma, nine cases of pulmonary adenocarcinoma, and three reactive pleurae, and amplified by the polymerase chain reaction (PCR) using the primer pairs used previously on fresh frozen tissues -namely, the SV primer set directed at the LTAg gene sequence unique to SV40 and the PYV primer set directed at a sequence shared by SV40 and papovavirus strains BK and JC, respectively.Results.PCR positivity with the SV primer set was restricted to four of the nine cases of mesothelioma.In contrast, six of the nine mesotheliomas, two of the nine adenocarcinomas, and one of the three reactive pleurae showed positivity with the PYV primers.The fresh frozen and corresponding formalin fixed, paraffin embedded tissue results concorded well with each other.Conclusions.Our data provide evidence for the association of SV40LTAg primer specific DNA with human pulmonary mesothelioma in the British population.
Synergistic Induction of <i>DOC-2/DAB2</i> Gene Expression in Transitional Cell Carcinoma in the Presence of GATA6 and Histone Deacetylase Inhibitor
Authors: Jian Zhou, Gina Hernandez, Szu-wei Tu, Jessica Scholes, Hong Chen, Ching-Ping Tseng, Jer-Tsong Hsieh
Journal: Cancer Research (2005)

Abstract The down-regulation of DOC-2/DAB2 gene, which encodes a unique phosphoprotein modulating signal pathways elicited by exogenous stimuli, is often associated with several cancer types; however, the underlying mechanism is still unknown. Dramatically different expression levels of DOC-2/DAB2 mRNA and protein are observed among several human transitional cell carcinoma (TCC) cell lines, suggesting that transcriptional regulation may play a role in these cells. In this study, we have shown that the histone acetylation status associated with the 5′ upstream regulatory sequence of DOC-2/DAB2 gene is one of the key determinants for its gene expression. In addition, GATA6 but not other GATA family members, such as GATA2 and GATA4, can specifically induce DOC-2/DAB2 promoter activity, although GATA transcription factors share a very similar DNA-binding sequence. We also show that increased histone acetylation and the presence of GATA6 have a synergistic effect on DOC-2/DAB2 promoter activity, which results in the elevation of DOC-2/DAB2 protein expression. Thus, we conclude that transcriptional regulation of DOC-2/DAB2 gene in human TCC is determined by histone acetylation and a specific transcription factor (i.e., GATA6), which underlie the reduced DOC-2/DAB2 protein expression in TCC cells.
Relationship of Metabolic Control and Body Weight to Hypercholesterolemia in NIDDM Patients With Apolipoprotein E4
Authors: Masaaki Eto, Kiyoshi Watanabe, Isao Makino
Journal: Diabetes Care (1991)

Objective We previously reported that non-insulindependent diabetes mellitus (NIDDM) patients with apolipoprotein E4 (apoE4) are more susceptible to hypercholesterolemia. The purpose of this study was to clarify whether metabolic control or body weight is related to hypercholesterolemia in NIDDM patients with apoE4. Research Design and Methods Two hundred forty NIDDM patients with apoE4 or apoE3/3 who had either hypercholesterolemia or normolipidemia were studied. ApoE phenotypes were determined by isoelectric focusing method. Results The apoE4- carrying NIDDM patients with hypercholesterolemia (n = 39) showed significantly higher fasting plasma glucose (8.4 vs. 7.2 mM, P &amp;lt; 0.05), HbA, (9.3 vs. 8.1%, P &amp;lt; 0.05), and percentage of ideal body weight values (116 vs. 102%, P &amp;lt; 0.01) than the apoE4-carrying NIDDM patients with normolipidemia (n – 26), whereas there was no significant difference in their levels between the apoE3/3-carrying NIDDM patients with hypercholesterolemia (n = 47) and normolipidemia (n = 128). Conclusions In addition to our previous finding, this study indicates that hypercholesterolemia in apoE4-carrying NIDDM patients may be more closely related to poor metabolic control and increased percentage of ideal body weight.
Stereotactic ablative radiotherapy (SABR) in non-surgical non small cell lung cancer: Effects on respiratory function
Authors: Cinzia Ferrero, Matteo Giaj Levra, Simonetta Rapetti, Francesco Moretto, Umberto Ricardi, Andrea Filippi, Claudio Ciacco, Marco Guglielmo, Luana Focaraccio, Silvia Novello, Roberto Torchio
Journal: European Respiratory Journal (2014)

AIM:To study lung function and treatment-related radiological and clinical toxicity in a cohort of patients with non-small cell lung cancer (NSCLC) who underwent Stereotactic Ablative Radiotherapy (SABR).  METHODS:31 patients with NSCLC stage IA-IB unfit/refusing surgery were treated with single Volumetric Modulated Arc Therapy with fractionation schedule depending on tumor location. Follow-up was performed at 45, 135, 225, 315 days (T45, T135.. by means of body plethysmography, diffusion capacity for CO (D L CO) and blood gas analysis.  RESULTS: preliminary analysis was performed on 31/31 patients at T45, 25/31 at T135, 22/31 at T225 and 13/31 at T315. Total lung capacity (TLC) decreased significantly,without changes in forced expiratory volume in 1s /vital capacity ratio, from 6.02±1.30 liters to 5.54±1.33 at T225 (p L CO (but not ratio between D L CO and dilution alveolar volume D L CO/VA) decreases significantly since T45. Arterial oxygen tension (PaO2) was slightly reduced only until T135 (75.2±8.4 vs 71.9±8.5 mmHg, p L CO reduction (p  CONCLUSIONS:Preliminary data suggest good tolerability for SABR with slight persistent lung volume and D L CO reduction but only transient PaO2 reduction over time.
Gelatin Sheet Incorporating Basic Fibroblast Growth Factor Enhances Healing of Devascularized Sternum in Diabetic Rats
Authors: A Iwakura, Y Tabata, N Tamura, K Doi, K Nishimura, T Nakamura, Y Shimizu, M Fujita, M Komeda
Journal: Circulation (2001)

Poor healing of the sternum often limits the use of bilateral internal thoracic arteries (BITAs) after coronary bypass surgery in diabetic patients. We have reported that a gelatin sheet that incorporates basic fibroblast growth factor (bFGF) accelerates sternal healing after BITA removal in normal rats. This study evaluated the effects of the above method for sternal healing in diabetic animals.Diabetic Wistar rats with blood glucose levels >400 mg/dL and body-weight loss >20 g were established by a single intravenous injection of streptozotocin (55 mg/kg). After median sternotomy and BITA removal, 16 diabetic rats received either a gelatin sheet that incorporated bFGF (100 microg/sheet) on the posterior table of the sternum (FGF group, n=9) or no gelatin sheet (control, n=7). Peristernal blood flow, as measured by a noncontact laser Doppler 4 weeks after surgery in the FGF group, recovered to the preoperative level (106+/-10% versus 82+/-9%, P<0.01), and marked angiogenesis was also observed around the sternum in the FGF group (30.5+/-3.2 versus 15.8+/-2.7 vessels/unit area, P<0.01). Deep sternal wound complications developed in 5 control rats but only in 1 rat in the FGF group (P<0.05). In the FGF group, histological examination showed improved sternal healing (excellent in 6 rats and slow/poor healing in 3). Bone mineral content as assessed by dual-energy x-ray absorptometry was greater in the FGF group (75.9+/-18.1 versus 48.9+/-10.7 mg, P<0.05). Bone mineral density of the sternum was similar between the 2 groups.A gelatin sheet that incorporates bFGF may offset sternal ischemia and accelerate sternal bone regeneration and healing, even in diabetic patients.
Metabolic syndrome and incidence of asthma in adults: the HUNT study
Authors: Ben Michael Brumpton, Carlos Arturo Camargo, Pål Richard Romundstad, Arnulf Langhammer, Yue Chen, Xiao-Mei Mai
Journal: European Respiratory Journal (2013)

Obesity is a risk factor for incident asthma in adults, and obesity is a major component of metabolic syndrome. This study aimed to explore the associations of metabolic syndrome and its components with the cumulative incidence of asthma in adults. We conducted a prospective cohort study of participants who were asthma-free at baseline (n = 23 191) in the Nord-Trøndelag Health Study from 1995 to 2008. Baseline metabolic syndrome was categorised using the definition of the Joint Interim Statement from several international organisations. Incident asthma was self-reported at follow-up, which averaged 11 years. Metabolic syndrome was a risk factor for incident asthma (adjusted OR 1.57, 95% CI 1.31–1.87). This association was consistent in sensitivity analyses using a stricter asthma definition (adjusted OR 1.42, 95% CI 1.13–1.79). Among the components of metabolic syndrome, two remained associated with incident asthma after mutual adjustment for the other metabolic components: high waist circumference (adjusted OR 1.62, 95% CI 1.36–1.94) and elevated glucose or diabetes (adjusted OR 1.43, 95% CI 1.01–2.04). Metabolic syndrome and two of its components (high waist circumference and elevated glucose or diabetes) were associated with an increased risk of incident asthma in adults.
Synopsis of the National Institute for Health and Clinical Excellence Guideline for Prevention of Delirium
Authors: Rachel O'Mahony
Journal: Annals of Internal Medicine (2011)

Description: Delirium is common, is often underrecognized, and is associated with poor outcomes and high costs. In July 2010, the National Institute for Health and Clinical Excellence released a guideline that addressed diagnosis, prevention, and management of delirium. This synopsis focuses on the main recommendations about prevention of delirium. Methods: The National Clinical Guideline Centre developed these guidelines by using standard methodology of the National Institute for Health and Clinical Excellence. A multidisciplinary guideline development group posed review questions, discussed evidence, and formulated the recommendations. To underpin the guideline, a technical team from the National Clinical Guideline Centre systematically reviewed and graded pertinent evidence identified from literature searches of studies published in English to August 2009 and performed health economic modeling. Stakeholder and public comment informed guideline development and modifications. Recommendations: Considering prevention a feasible and cost-effective health strategy, the guideline development group made 13 specific recommendations that addressed the stability of the care environment (both the care team and location) and the provision of a multicomponent intervention package tailored for persons at risk for delirium. The multicomponent intervention package included assessment and modification of key clinical factors that may precipitate delirium, including cognitive impairment or disorientation, dehydration or constipation, hypoxia, infection, immobility or limited mobility, several medications, pain, poor nutrition, sensory impairment, and sleep disturbance.