tbuckley/cabot-search huggingface dataset:
Abnormal Development of Intestinal Intraepithelial Lymphocytes and Peripheral Natural Killer Cells in Mice Lacking the IL-2 Receptor β Chain
Authors: Haruhiko Suzuki, Gordon S. Duncan, Hiroaki Takimoto, Tak W. Mak
Journal: The Journal of Experimental Medicine (1997)

The interleukin-2 receptor β chain (IL-2Rβ) is expressed on a variety of hematopoietic cell types, including natural killer (NK) cells and nonconventional T lymphocyte subsets such as intestinal intraepithelial lymphocytes (IEL). However, the importance of IL-2Rβ-mediated signaling in the growth and development of these cells has yet to be clearly established. We have investigated IEL and NK cells in mice deficient for IL-2Rβ and describe here striking defects in the development of these cells. IL-2Rβ−/− mice exhibited an abnormal IEL cell population, characterized by a dramatic reduction in T cell receptor αβ CD8αα and T cell receptor γδ lymphocytes. This selective decrease indicates that IEL can be classified into those whose development and/or differentiation is dependent on IL-2Rβ function and those for which IL-2Rβ–mediated signaling is not essential. NK cell development was also found to be disrupted in IL-2Rβ–deficient mice, characterized by a reduction in NK1.1+CD3− cells in the peripheral circulation and an absence of NK cytotoxic activity in vitro. The dependence of NK cells and certain subclasses of IEL cells on IL-2Rβ expression points to an essential role for signaling through this receptor, presumably by IL-2 and/or IL-15, in the development of lymphocyte subsets of extrathymic origin.
Long-Term Trends in Cardiorespiratory Fitness and the Incidence of Type 2 Diabetes
Authors: Susumu S. Sawada, I.-Min Lee, Hisashi Naito, Jun Noguchi, Koji Tsukamoto, Takashi Muto, Yasuki Higaki, Hiroaki Tanaka, Steven N. Blair
Journal: Diabetes Care (2010)

Whereas single assessments of cardiorespiratory fitness have been shown to predict lower incidence of type 2 diabetes, there are no data on long-term trends in fitness and risk. We investigated the relationship between long-term trends in fitness and the incidence of type 2 diabetes.A cohort of 4,187 Japanese men free of diabetes completed annual health checkups and fitness tests for estimated maximal oxygen uptake at least four times over 7 years (1979-1985). We modeled the trend in fitness over 7 years for each man using simple linear regression. Men were then divided into quartiles based on the regression coefficient (slope) from the model. During the follow-up period (1985-1999), 274 men developed diabetes. Hazard ratios (HRs) and 95% CIs for the incidence of diabetes were obtained using the Cox proportional hazards model.Men in the lowest quartile of the distribution decreased in fitness over the 7 years (median slope -1.25 ml/kg/min), whereas men in the highest quartile increased in fitness (median slope 1.33 ml/kg/min). With adjustment for age, initial fitness level, BMI, systolic blood pressure, cigarette smoking, alcohol intake, and a family history of diabetes and use of the lowest quartile, the HRs (95% CI) for the second through fourth quartiles were 0.64 (0.46-0.89), 0.40 (0.27-0.58), and 0.33 (0.21-0.50), respectively (P(trend) < 0.001).These results indicate that the long-term trend in fitness is a strong predictor of the incidence of type 2 diabetes in Japanese men.
Results of a case-detection programme for 1-antitrypsin deficiency in COPD patients
Authors: C. de la Roza
Journal: European Respiratory Journal (2005)

α<sub>1</sub>-Antitrypsin (α<sub>1</sub>-AT) deficiency is an underdiagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The present authors have conducted a nationwide case detection programme of α<sub>1</sub>-AT deficiency in unselected patients with COPD using dried blood spots. The first phase analysed samples from 971 patients by determining α<sub>1</sub>-AT concentrations and identifying the deficient Z allele by genotyping using rapid real-time PCR. The second phase analysed 1,166 samples with α<sub>1</sub>-AT concentrations and identified both the S and the Z allele, but only in samples with low α<sub>1</sub>-AT concentrations. A total of eight (0.37%) individuals with the severe deficiency PiZZ were detected. In addition, three patients were identified with the PiSZ genotype in the second phase (0.3%). The global cost of the programme was \#8364;41,512, which represents \#8364;19.42 per sample and \#8364;5,189 per PiZZ detected. A sensitivity analysis demonstrated that performing Z genotype to all samples would have resulted in increased costs of \#8364;28 per sample and \#8364;7,479.5 per PiZZ case identified. In conclusion, a case detection programme of α<sub>1</sub>-antitrypsin deficiency in patients with chronic obstructive pulmonary disease using dried blood spots is feasible and at a reasonable cost per case detected. Diagnostic yield and costs depend largely on inclusion criteria and the protocol for processing of samples.
Haem oxygenase-1 plays a central role in NNK-mediated lung carcinogenesis
Authors: M-Y. Li, J. Yip, M. K. Y. Hsin, T. S. K. Mok, Y. Wu, M. J. Underwood, G. G. Chen
Journal: European Respiratory Journal (2008)

The tobacco-specific nitrosamine, 4-( N -methyl- N -nitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent lung cancer inducer. However, how NNK induces lung cancer is still largely unknown. Haem oxygenase (HO)-1 was evaluated in 30 pairs of lung cancer tumour samples and matched nontumour tissues from patients with a history of cigarette smoking. Expression of HO-1, p21 Cip1/Waf1/Cid1 (p21), B-cell lymphoma (Bcl)-2 family members, mitogen-activated protein kinase and nuclear factor (NF)-κB was also studied in lung cancer cells treated with NNK. The levels of HO-1 and p21 were significantly increased in lung tumour tissues. There was a positive relationship between these two proteins in the tumour. NNK stimulated lung cell proliferation and elevated the levels of HO-1, p21, inhibitor of apoptosis protein (c-IAP)2 and Bcl-2, but downregulated Bad. These effects of NNK were blocked by zinc protoporphyrin-XII, an HO-1 inhibitor. The NNK-mediated expression of HO-1 was governed by NF-κB and extracellular signal-regulated kinase 1/2, since blocking either of these prevented the stimulatory effect of NNK on HO-1, as well as molecules downstream of HO-1, such as p21, c-IAP2, Bcl-2 and Bad. In conclusion, haem oxygenase-1 plays a central role in NNK-mediated cell proliferation by promoting the expression of p21 Cip1/Waf1/Cid1 , inhibitor of apoptosis protein 2 and B-cell lymphoma-2 but inhibiting the activity of Bad. Nuclear factor-κB and extracellular signal-regulated kinase 1/2 function upstream of haem oxygenase-1. Therefore, haem oxygenase-1 is likely to be a potential target in the treatment of smoking-related lung cancer.
Parasympathetic response in chick myocytes and mouse heart is controlled by SREBP
Authors: Ho-Jin Park, Serban P. Georgescu, Chuang Du, Christopher Madias, Mark J. Aronovitz, C. Michael Welzig, Bo Wang, Ulrike Begley, Yali Zhang, Robert O. Blaustein, Richard D. Patten, Richard H. Karas, Herbert H. Van Tol, Timothy F. Osborne, Hitoshi Shimano, Ronglih Liao, Mark S. Link, Jonas B. Galper
Journal: Journal of Clinical Investigation (2008)

Parasympathetic stimulation of the heart, which provides protection from arrhythmias and sudden death, involves activation of the G protein–coupled inward rectifying K+ channel GIRK1/4 and results in an acetylcholine-sensitive K+ current, IKACh. We describe a unique relationship between lipid homeostasis, the lipid-sensitive transcription factor SREBP-1, regulation of the cardiac parasympathetic response, and the development of ventricular arrhythmia. In embryonic chick atrial myocytes, lipid lowering by culture in lipoprotein-depleted serum increased SREBP-1 levels, GIRK1 expression, and IKACh activation. Regulation of the GIRK1 promoter by SREBP-1 and lipid lowering was dependent on interaction with 2 tandem sterol response elements and an upstream E-box motif. Expression of dominant negative SREBP-1 (DN–SREBP-1) reversed the effect of lipid lowering on IKACh and GIRK1. In SREBP-1 knockout mice, both the response of the heart to parasympathetic stimulation and the expression of GIRK1 were reduced compared with WT. IKACh, attenuated in atrial myocytes from SREBP-1 knockout mice, was stimulated by SREBP-1 expression. Following myocardial infarction, SREBP-1 knockout mice were twice as likely as WT mice to develop ventricular tachycardia in response to programmed ventricular stimulation. These results demonstrate a relationship between lipid metabolism and parasympathetic response that may play a role in arrhythmogenesis.
Contrary to Rat-Type, Human-Type Na,K-ATPase Is Phosphorylated at the Same Amino Acid by Hormones that Produce Opposite Effects on Enzyme Activity
Authors: Riad Efendiev, Carlos H. Pedemonte
Journal: Journal of the American Society of Nephrology (2005)

Renal sodium homeostasis is a major determinant of BP and is regulated by several natriuretic and antinatriuretic hormones. These hormones, acting through intracellular secondary messengers, either activate or inhibit proximal tubule Na,K-ATPase. It was shown previously that phorbol esters and angiotensin II and serotonin induce the phosphorylation of both Ser-11 and Ser-18 of the Na,K-ATPase alpha-subunit. This results in the recruitment of Na,K-ATPase molecules to the plasma membrane and an increased capacity to transport sodium ions. Treatment of the same cells with dopamine leads to phosphorylation of the Na,K-ATPase alpha-subunit Ser-18. The subsequent internalization of Na,K-ATPase molecules results in a reduced capacity to transport sodium ions. These effects are observed in cells that express the rat-type Na,K-ATPase. However, the Na,K-ATPase alpha1-subunit of several species, such as human, pig, and mouse, does not have a Ser-18 in their N-terminal region. Therefore, the possibility exists that, in those species, the Na,K-ATPase is not regulated by the hormones that regulate natriuresis. This study presents evidence that in cells that express the human-type Na,K-ATPase, dopamine inhibits and phorbol esters activate the Na,K-ATPase-mediated transport. These opposite effects are mediated by the phosphorylation of the same amino acid residue, Ser-11 of Na,K-ATPase alpha1, and the presence of alpha1 Ser-18 is not essential for the hormonal regulation of Na,K-ATPase activity in LLCPK1 cells. It was observed that, whereas the regulatory stimulation of Na,K-ATPase is mediated by protein kinase Cbeta, the regulatory inhibition is mediated by protein kinase Czeta. This is similar to what was demonstrated previously in cells that express the rat-type Na,K-ATPase.
Multicenter, Randomized Controlled Trial of Yoga for Sleep Quality Among Cancer Survivors
Authors: Karen M. Mustian, Lisa K. Sprod, Michelle Janelsins, Luke J. Peppone, Oxana G. Palesh, Kavita Chandwani, Pavan S. Reddy, Marianne K. Melnik, Charles Heckler, Gary R. Morrow
Journal: Journal of Clinical Oncology (2013)

Purpose Thirty percent to 90% of cancer survivors report impaired sleep quality post-treatment, which can be severe enough to increase morbidity and mortality. Lifestyle interventions, such as exercise, are recommended in conjunction with drugs and cognitive behavioral therapy for the treatment of impaired sleep. Preliminary evidence indicates that yoga—a mind-body practice and form of exercise—may improve sleep among cancer survivors. The primary aim of this randomized, controlled clinical trial was to determine the efficacy of a standardized yoga intervention compared with standard care for improving global sleep quality (primary outcome) among post-treatment cancer survivors. Patients and Methods In all, 410 survivors suffering from moderate or greater sleep disruption between 2 and 24 months after surgery, chemotherapy, and/or radiation therapy were randomly assigned to standard care or standard care plus the 4-week yoga intervention. The yoga intervention used the Yoga for Cancer Survivors (YOCAS) program consisting of pranayama (breathing exercises), 16 Gentle Hatha and Restorative yoga asanas (postures), and meditation. Participants attended two 75-minute sessions per week. Sleep quality was assessed by using the Pittsburgh Sleep Quality Index and actigraphy pre- and postintervention. Results In all, 410 survivors were accrued (96% female; mean age, 54 years; 75% had breast cancer). Yoga participants demonstrated greater improvements in global sleep quality and, secondarily, subjective sleep quality, daytime dysfunction, wake after sleep onset, sleep efficiency, and medication use at postintervention (all P ≤ .05) compared with standard care participants. Conclusion Yoga, specifically the YOCAS program, is a useful treatment for improving sleep quality and reducing sleep medication use among cancer survivors.
Promoter Methylation of Genes in and around the Candidate Lung Cancer Susceptibility Locus <i>6q23-25</i>
Authors: Mathewos Tessema, Randy Willink, Kieu Do, Yang Y. Yu, Wayne Yu, Emi O. Machida, Malcolm Brock, Leander Van Neste, Christine A. Stidley, Stephen B. Baylin, Steven A. Belinsky
Journal: Cancer Research (2008)

Abstract Chromosomal aberrations associated with lung cancer are frequently observed in the long arm of chromosome 6. A candidate susceptibility locus at 6q23-25 for lung cancer was recently identified; however, no tumor suppressor genes inactivated by mutation have been identified in this locus. Genetic, epigenetic, gene expression, and in silico screening approaches were used to select 43 genes located in 6q12-27 for characterization of methylation status. Twelve (28%) genes were methylated in at least one lung cancer cell line, and methylation of 8 genes was specific to lung cancer cell lines. Five of the 8 genes with the highest prevalence for methylation in cell lines (TCF21, SYNE1, AKAP12, IL20RA, and ACAT2) were examined in primary lung adenocarcinoma samples from smokers (n = 100) and never smokers (n = 75). The prevalence for methylation of these genes was 81%, 50%, 39%, 26%, and 14%, respectively, and did not differ by smoking status or age at diagnosis. Transcription of SYNE1, AKAP12, and IL20RA was completely silenced by hypermethylation and could be restored after treatment with 5-aza-2-deoxycytidine. Significant associations were found between methylation of SYNE1 and TCF21, SYNE1 and AKAP12, and AKAP12 and IL20RA, indicating a coordinated inactivation of these genes in tumors. A higher prevalence for methylation of these genes was not associated with early-onset lung cancer cases, most likely precluding their involvement in familial susceptibility to this disease. Together, our results indicate that frequent inactivation of multiple candidate tumor suppressor genes within chromosome 6q likely contributes to development of sporadic lung cancer. [Cancer Res 2008;68(6):1707–14]
Gout and neurological abnormalities associated with cardiomyopathy in a young man.
Authors: M E Mavrikakis, P P Sfikakis, D A Kontoyannis, L G Antoniades, C Tsakanikas
Journal: Annals of the Rheumatic Diseases (1990)

A 21 year old man with a family history of gout and neurological deficits, developed severe idiopathic congestive cardiomyopathy after a long history of typical gouty attacks and neurological abnormalities. Clinical and laboratory evaluations showed borderline mental retardation, ataxia, sensorineural deafness, marked hyperuricaemia, and excessive uric acid excretion in the presence of impaired renal function. None of the known causes of cardiomyopathy was found. Even though red cell hypoxanthine guanine phosphoribosyltransferase enzyme activity was normal, this case probably represents an inborn error of purine metabolism. The association of cardiomyopathy with gout is very unusual. Previously it has been only once described in a single case.
Clear differences in adiponectin level and glutathione redox status revealed in obese and normal-weight patients with psoriasis
Authors: S. Kaur, K. Zilmer, C. Kairane, M. Kals, M. Zilmer
Journal: British Journal of Dermatology (2008)

Several studies have shown increased prevalence of obesity in patients with psoriasis.To characterize both inflammatory- and oxidative stress-related differences between obese patients with psoriasis (OPP) and normal-weight patients with psoriasis (NWPP).The plasma concentrations of adiponectin and interleukin (IL)-6 were analysed by quantitative sandwich enzyme immunoassay technique in 10 patients with a body mass index (BMI)<25 and 12 patients with a BMI>30. Total glutathione and oxidized glutathione levels were measured spectrophotometrically.Plasma concentration of adiponectin in NWPP was more than twice the level in healthy normal-weight controls (P<0.001), while such an elevation did not occur in OPP. OPP were characterized by a significantly increased IL-6 level, which correlated negatively with the adiponectin level (r=-0.85, P<0.001). The glutathione redox status, which was also inversely correlated with the adiponectin level (r=-0.63, P<0.05), was associated with significantly increased oxidative stress in the OPP compared with the NWPP or controls.Obesity in patients with psoriasis is associated with both decreased plasma levels of protective adiponectin compared with NWPP, and enhanced systemic inflammation and oxidative stress. These findings are in concordance with high prevalence of diseases related to lower adiponectin levels among psoriasis patients.
Increased brain uptake and oxidation of acetate in heavy drinkers
Authors: Lihong Jiang, Barbara Irene Gulanski, Henk M. De Feyter, Stuart A. Weinzimer, Brian Pittman, Elizabeth Guidone, Julia Koretski, Susan Harman, Ismene L. Petrakis, John H. Krystal, Graeme F. Mason
Journal: Journal of Clinical Investigation (2013)

When a person consumes ethanol, the body quickly begins to convert it to acetic acid, which circulates in the blood and can serve as a source of energy for the brain and other organs. This study used 13C magnetic resonance spectroscopy to test whether chronic heavy drinking is associated with greater brain uptake and oxidation of acetic acid, providing a potential metabolic reward or adenosinergic effect as a consequence of drinking. Seven heavy drinkers, who regularly consumed at least 8 drinks per week and at least 4 drinks per day at least once per week, and 7 light drinkers, who consumed fewer than 2 drinks per week were recruited. The subjects were administered [2-13C]acetate for 2 hours and scanned throughout that time with magnetic resonance spectroscopy of the brain to observe natural 13C abundance of N-acetylaspartate (NAA) and the appearance of 13C-labeled glutamate, glutamine, and acetate. Heavy drinkers had approximately 2-fold more brain acetate relative to blood and twice as much labeled glutamate and glutamine. The results show that acetate transport and oxidation are faster in heavy drinkers compared with that in light drinkers. Our finding suggests that a new therapeutic approach to supply acetate during alcohol detoxification may be beneficial.
Heterogeneous Atrial Denervation Creates Substrate for Sustained Atrial Fibrillation
Authors: Jeffrey E. Olgin, Haris J. Sih, Steven Hanish, J. Vijay Jayachandran, Jiashin Wu, Qi Huang Zheng, Wendy Winkle, G. Keith Mulholland, Douglas P. Zipes, Gary Hutchins
Journal: Circulation (1998)

Background —Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF. Methods and Results —After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation. Dogs then underwent PET imaging with either a sympathetic ([ 11 C]hydroxyephedrine, HED) or parasympathetic (5-[ 11 C]methoxybenzovesamicol, MOBV) nerve label. None of the animals had sustained AF (&gt;60 minutes) at baseline. None of the sham dogs and 14 of 15 phenol dogs had sustained AF at follow-up. Sites to which phenol was applied had a significantly shorter ERP (136±17.6 ms) than those same sites in the sham controls (156±19.1 ms) ( P =0.01). Although there was no difference in the ERP change with either vagal or sympathetic stimulation alone between phenol and nonphenol sites, the percent decrease in ERP with simultaneous vagal/sympathetic stimulation was greater in the phenol sites (17±8%) than in the nonphenol sites (9±9%) ( P =0.01). There was a significantly increased dispersion of refractoriness (21±6.4 ms in the sham versus 58±14 ms in the phenol dogs, P =0.01) as well as dispersion of AF cycle length (49±10 ms in the sham versus 105±12 ms in the phenol dogs, P =0.0001). PET images demonstrated defects of HED uptake in the areas of phenol application, with no defect of MOBV uptake. Conclusions —Heterogeneous sympathetic atrial denervation with phenol facilitates sustained AF.
Prelinguistic evolution in early hominins: Whence motherese?
Authors: Dean Falk
Journal: Behavioral and Brain Sciences (2004)

In order to formulate hypotheses about the evolutionary underpinnings that preceded the first glimmerings of language, mother-infant gestural and vocal interactions are compared in chimpanzees and humans and used to model those of early hominins. These data, along with paleoanthropological evidence, suggest that prelinguistic vocal substrates for protolanguage that had prosodic features similar to contemporary motherese evolved as the trend for enlarging brains in late australopithecines/early Homo progressively increased the difficulty of parturition, thus causing a selective shift toward females that gave birth to relatively undeveloped neonates. It is hypothesized that hominin mothers adopted new foraging strategies that entailed maternal silencing, reassuring, and controlling of the behaviors of physically removed infants (i.e., that shared human babies' inability to cling to their mothers' bodies). As mothers increasingly used prosodic and gestural markings to encourage juveniles to behave and to follow, the meanings of certain utterances (words) became conventionalized. This hypothesis is based on the premises that hominin mothers that attended vigilantly to infants were strongly selected for, and that such mothers had genetically based potentials for consciously modifying vocalizations and gestures to control infants, both of which receive support from the literature.