tbuckley/cabot-search huggingface dataset:
Intra-Abdominal Fat and Elevated Urine Albumin Excretion in Men With Type 1 Diabetes
Authors: Shalamar D. Sibley, Ian H. de Boer, Michael W. Steffes, John D. Brunzell
Journal: Diabetes Care (2007)

Earlier studies documented associations between central obesity and elevated albumin excretion rate or other renal injury indicators in nondiabetic subjects (1–11). A retrospective study conducted in a Kaiser Permanente mixed diabetic-nondiabetic cohort suggested that obesity increased risk for progression to end-stage renal disease (12). Studies also identified obesity as a risk factor for renal disease in type 1 diabetes (13,14). We previously examined obesity-related factors and albumin excretion within the total Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. Conducted between 1982 and 1993, the DCCT included 1,441 subjects with type 1 diabetes randomized to intensive or conventional diabetes treatment and followed for 6.5 years on average. Details of resources utilized for the DCCT/EDIC (observational follow-up) study designs were previously published (15–18). These studies demonstrate the powerful effect of intensive insulin therapy on preventing and slowing progression of micro- and macrovascular complications and established intensive therapy as the current standard of diabetes care for patients with type 1 diabetes. However, type 1 diabetic subjects, like the general population, are becoming heavier and more at risk for obesity-related complications (19). In our cross-sectional analysis 4 years after the end of the DCCT, waist-to-hip ratio (WHR), a visceral fat surrogate, was associated with elevated albumin excretion (20). In our longitudinal analysis, waist circumference was associated with subsequent development of persistent microalbuminuria (21). For this current analysis, we hypothesized that …
Neuropeptide Y Receptor Selective Ligands in the Treatment of Obesity
Authors: M. M. Kamiji, A. Inui
Journal: Endocrine Reviews (2007)

Obesity is a serious public health problem throughout the world, affecting both developed societies and developing countries. The central nervous system has developed a meticulously interconnected circuitry in order to keep us fed and in an adequate nutritional state. One of these consequences is that an energy-dense environment favors the development of obesity. Neuropeptide Y (NPY) is one of the most abundant and widely distributed peptides in the central nervous system of both rodents and humans and has been implicated in a variety of physiological actions. Within the hypothalamus, NPY plays an essential role in the control of food intake and body weight. Centrally administered NPY causes robust increases in food intake and body weight and, with chronic administration, can eventually produce obesity. NPY activates a population of at least six G protein-coupled Y receptors. NPY analogs exhibit varying degrees of affinity and specificity for these Y receptors. There has been renewed speculation that ligands for Y receptors may be of benefit for the treatment of obesity. This review highlights the therapeutic potential of Y1, Y2, Y4, and Y5 receptor agonists and antagonists as additional intervention to treat human obesity.
Occlusion time dependency of regional noradrenaline release and cardiac arrhythmias during reperfusion of acutely ischaemic heart in the dog in vivo
Authors: N. Yamaguchi, T. Kimura, D. Lamontagne, J. d. Champlain, R. Nadeau
Journal: Cardiovascular Research (1990)

Study objective – The aim was to study the occlusion time dependency of reperfusion induced increases in regional cardiac noradrenaline release from the ischaemic area in relation to the incidence of ventricular arrhythmias. Design – The left anterior descending coronary artery was ligated for 15, 30 and 60 min in three separate groups of dogs (n = 10 per group). Each occlusion period was followed by a 30 min reperfusion period. The coronary sinus and the epicardial vein running in parallel with the left anterior descending coronary artery were canndated for measurement of noradrenaline and lactate. Experimental material – 30 adult mongrel dogs, 22.5(SEM 1.1) kg, were used for the study. The animals were anaesthetised with sodium pentobarbitone. Measurements and main results – During occlusion, epicardial venous blood noradrenaline concentrations remained unchanged up to 30 min, but increased from 0.133(0.027) ng·ml−1 to 0.289(0.069) ng·ml−1 after 60 min of occlusion (p<0.05). However, epicardial venous blood lactate concentrations increased immediately upon occlusion, and remained elevated (p<0.05) during the whole period of occlusion in all groups. Neither noradrenaline nor lactate concentrations in coronary sinus blood increased during occlusion. During reperfusion, nine dogs showed early ventricular fibrillation. The highest incidence of fibrillation (n = 5/10) was found in the 15 min occlusion group, but the difference was not significant between groups. Epicardial venous blood noradrenaline concentrations increased to 0.371(0.076) ng·ml−1, 0.470(0.178) ng·ml−1, and 1.824(0.713) ng·ml−1 upon reperfusion following 15, 30 and 60 min occlusion, respectively (each p<0.05). Maximum increases in epicardial venous blood noradrenaline concentrations during reperfusion were correlated with duration of preceding occlusion (r = 0.60, n = 21, p<0.0l). Maximum increases in mean arrhythmic ratios observed during the first 10 min of reperfusion were proportionally related to mean epicardial venous blood noradrenaline concentrations. The increases in epicardial venous blood noradrenaline concentrations and the incidence of ventricular arrhythmias in the 60 min occlusion group were greater (p<0.05) than in the other two groups. Conclusions – This study shows that noradrenaline is released progressively from the ischaemic area during occlusion for 60 min. The amount of noradrenaline washed out upon reperfusion and the incidence of reperfusion ventricular arrhythmias both appear to be dependent upon duration of preceding occlusion. The results suggest that cardiac noradrenaline released locally from the ischaemic region may contribute to the genesis of reperfusion ventricular arrhythmias, but not to that of reperfusion ventricular fibrillation.
Association of vegetable and fruit intake with gastric cancer risk among Japanese: a pooled analysis of four cohort studies
Authors: T Shimazu, K Wakai, A Tamakoshi, I Tsuji, K Tanaka, K Matsuo, C Nagata, T Mizoue, M Inoue, S Tsugane, S Sasazuki
Journal: Annals of Oncology (2014)
Intentional systems in cognitive ethology: The “Panglossian paradigm” defended
Authors: Daniel C. Dennett
Journal: Behavioral and Brain Sciences (1983)

Abstract Ethologists and others studying animal behavior in a “cognitive” spirit are in need of a descriptive language and method that are neither anachronistically bound by behaviorist scruples nor prematurely committed to particular “information-processing models.” Just such an interim descriptive method can be found in intentional system theory . The use of intentional system theory is illustrated with the case of the apparently communicative behavior of vervet monkeys. A way of using the theory to generate data - including usable, testable “anecdotal” data - is sketched. The underlying assumptions of this approach can be seen to ally it directly with “adaptationist” theorizing in evolutionary biology, which has recently come under attack from Stephen Gould and Richard Lewontin, who castigate it as the “Panglossian paradigm.” Their arguments, which are strongly analogous to B. F, Skinner's arguments against “mentalism,” point to certain pitfalls that attend the careless exercise of such “Panglossian” thinking (and rival varieties of thinking as well), but do not constitute a fundamental objection to either adaptationist theorizing or its cousin, intentional system theory.
Blockade of Transforming Growth Factor-β Signaling Suppresses Progression of Androgen-Independent Human Prostate Cancer in Nude Mice
Authors: Fahao Zhang, Juwon Lee, Shan Lu, Curtis A. Pettaway, Zhongyun Dong
Journal: Clinical Cancer Research (2005)

We investigated the role of transforming growth factor-beta (TGF-beta) signaling in the growth and metastasis of PC-3MM2 human prostate cancer cells. Highly metastatic PC-3MM2 human prostate cancer cells were engineered to constitutively overexpress a dominant-negative type II TGF-beta receptor (DNR). Transfection of DNR had minimal direct effects on cell growth and attenuated TGF-beta-induced cell growth inhibition and TGF-beta1 production. There were no discernable differences in tumorigenicity (tumor incidence) among PC-3MM2 variants when the cells were implanted into the prostates of nude mice. Growth rate and metastatic incidence of DNR-engineered PC-3MM2 cells, however, were significantly reduced. Most cells in the control tumors were positively stained by an antibody to proliferation cell nuclear antigen and very few cells were stained by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL). In sharp contrast, tumors formed by PC-3MM2-DNR cells contained fewer proliferation cell nuclear antigen-positive cells and many more TUNEL-positive cells. Staining with antibody against CD31 showed that control tumors contained more blood vessels than PC-3MM2-DNR tumors. Expression of interleukin-8 (IL-8) in tumors formed by PC-3MM2 cells was significantly reduced as revealed by both Northern blotting and ELISA. Finally, transfection of antisense IL-8 cDNA significantly reduced IL-8 production by PC-3MM2 cells and antisense IL-8-transfected PC-3MM2 cells grew slower in comparison with parental and control vector-transfected cells. Taken together, our data suggest that TGF-beta signaling, by regulating IL-8 expression in tumor cells and hence tumor angiogenesis, is critical for progressive growth of PC-3MM2 cells in the prostate of nude mice.
Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency
Authors: Heiko Krude, Barbara Schütz, Heike Biebermann, Arpad von Moers, Dirk Schnabel, Heidi Neitzel, Holger Tönnies, Dagmar Weise, Antony Lafferty, Siegfried Schwarz, Mario DeFelice, Andreas von Deimling, Frank van Landeghem, Roberto DiLauro, Annette Grüters
Journal: Journal of Clinical Investigation (2002)

The occurrence of neurological symptoms and developmental delay in patients affected by congenital hypothyroidism (CH) has been attributed to the lack of thyroid hormone in the developing CNS. Accordingly, after the introduction of neonatal screening programs for CH, which allowed early and adequate treatment, an almost normal outcome for most CH patients could be achieved. However, a few patients did not reach this favorable outcome despite early and adequate treatment. Here we describe five patients with variable degrees of CH who suffered from choreoathetosis, muscular hypotonia, and pulmonary problems, an association of symptoms that had not been described before this study. Since this clinical picture matched the phenotype of mice targeted for deletion of the transcription factor gene Nkx2-1, we investigated the human NKX2-1 gene in these five patients. We found heterozygous loss of function mutations in each of these five patients, e.g., one complete gene deletion, one missense mutation (G2626T), and three nonsense mutations (2595insGG, C2519A, C1302A). Therefore, the unfavorable outcome in patients with CH, especially those with choreoathetosis and pulmonary symptoms, can be explained by mutations in the NKX2-1 gene rather than by hypothyroidism. Moreover, the association of symptoms in the patients with NKX2-1 mutations points to an important role of human NKX2-1 in the development and function of thyroid, basal ganglia, and lung, as already described for rodents.
Lung Cancer Death Rates in Lifelong Nonsmokers
Authors: Michael J. Thun, S. Jane Henley, David Burns, Ahmedin Jemal, Thomas G. Shanks, Eugenia E. Calle
Journal: JNCI Journal of the National Cancer Institute (2006)

Few studies have directly measured the age-, sex-, and race-specific risks of lung cancer incidence and mortality among never tobacco smokers. Such data are needed to quantify the risks associated with smoking and to understand racial and sex disparities and temporal trends that are due to factors other than active smoking.We measured age-, sex-, and race-specific rates (per 100,000 person-years at risk) of death from lung cancer among more than 940,000 adults who reported no history of smoking at enrollment in either of two large American Cancer Society Cancer Prevention Study cohorts during 1959-1972 (CPS-I) and 1982-2000 (CPS-II). We compared lung cancer death rates between men and women and between African Americans and whites and analyzed temporal trends in lung cancer death rates among never smokers across the two studies by using directly age-standardized rates as well as Poisson and Cox proportional hazards regression analyses. All statistical tests were two-sided.The age-standardized lung cancer death rates among never-smoking men and women in CPS-II were 17.1 and 14.7 per 100,000 person-years, respectively. Men who had never smoked had higher age-standardized lung cancer death rates than women in both studies (CPS-I: hazard ratio [HR] = 1.52, 95% confidence interval [CI] = 1.28 to 1.79; CPS-II: HR = 1.21, 95% CI = 1.09 to 1.36). The rate was higher among African American women than white women in CPS-II (HR = 1.43, CI = 1.11 to 1.85). A small temporal increase (CPS-II versus CPS-I) in lung cancer mortality was seen for white women (HR = 1.25, CI = 1.12 to 1.41) and African American women (HR = 1.22, CI = 0.64 to 2.33), but not for white men (HR = 0.89, CI = 0.74 to 1.08). Among white and African American women combined, the temporal increase was statistically significant only among those aged 70-84 years (P < .001).Contrary to clinical perception, the lung cancer death rate is not higher in female than in male never smokers and shows little evidence of having increased over time in the absence of smoking. Factors that affect the interpretation of lung cancer trends are discussed. Our novel finding that lung cancer mortality is higher among African American than white women never smokers should be confirmed in other studies.
Abstract 3532: Antitumor activity of SR16388 on multiple myeloma targets factors needed for adaptation to bone marrow microenvironment
Authors: Wan-Ru Chao, Dominic H. Dinh, Yihui Shi, Carol Hou, Barbara Sato, Carsten Alt, Nathan Collins, Lidia Sambucetti
Journal: Cancer Research (2011)

Abstract Multiple myeloma (MM) is a B-cell malignancy that is characterized by accumulation of clonal plasma cells in the bone marrow. The bone marrow microenvironment plays a critical role in MM cell pathogenesis and progression. In the bone marrow milieu, MM cells adhere to the bone marrow stromal cells and trigger the secretion of growth factors such as vascular endothelial growth factor (VEGF). VEGF in turn upregulates the secretion of interleukin-6 (IL-6), the major cytokine that mediates MM cell growth and survival in part through the activation of Janus kinase (Jak)/signal transducers and activators of transcription 3 (STAT3). VEGF also stimulates the proliferation of endothelial and stromal cells and induces angiogenesis via its receptors. Thus, targeting both myeloma cells and bone marrow microenvironment is a valid approach for the development of therapeutic agents for MM. At SRI International, we have developed an antiestrogen, SR16388, that binds to ER-α, ER-β and ERR-α with potent antitumor and antiangiogenic properties. We have previously reported that SR16388 inhibited MM cell proliferation in vitro and MM tumors in vivo. In the current study, we are presenting data to show that the inhibitory effect of SR16388 on MM cell proliferation was achieved by inducing apoptosis, and arresting cells at the G2 phase. Furthermore, at nanomolar concentrations SR16388 inhibited IL-6-induced cell proliferation and blocked the activation of STAT3 induced by IL-6 in RPMI-8226 human MM cells. In human endothelial cells, SR16388 inhibited VEGF-induced cell proliferation and VEGF-induced phosphorylation of STAT3. In a RPIM-8226 tumor xenograft model, the microvessel density in the tumor tissue was markedly reduced by treatment with SR16388. We are currently investigating the effect of SR16388 in combination with known therapeutic agents on the growth of MM tumors in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3532. doi:10.1158/1538-7445.AM2011-3532
A multicentre, randomized, controlled study of the efficacy, safety and cost-effectiveness of a combination therapy with amorolfine nail lacquer and oral terbinafine compared with oral terbinafine alone for the treatment of onychomycosis with matrix involvement
Authors: R. Baran, B. Sigurgeirsson, D. de Berker, R. Kaufmann, M. Lecha, J. Faergemann, N. Kerrouche, F. Sidou
Journal: British Journal of Dermatology (2007)

Background Onychomycosis is common, accounting for up to 50% of all nail disorders. Toenail onychomycosis can cause nail deformity, embarrassment, pain and walking difficulties. Some populations, such as individuals with diabetes, are at higher risk for developing secondary complications such as infections. Treatment takes many months and therapeutic choices can increase clinical effectiveness, lower toxicity and minimize healthcare costs. Objectives Based on the results of a previous pilot study, the objective of the present study was to show, in a larger population, the enhanced efficacy of a combination of amorolfine nail lacquer and oral terbinafine in the treatment of onychomycosis with matrix involvement. In addition, a cost-effectiveness analysis was performed. Methods In this multicentre, randomized, open-label, parallel group study, patients were randomized to receive either a combination of amorolfine hydrochloride 5% nail lacquer once weekly for 12 months plus terbinafine 250 mg once daily for 3 months (AT group) or terbinafine alone once daily for 3 months (T group). The study duration was 18 months including a 6-month treatment-free phase following the 12-month active treatment phase for the AT group and a 15-month treatment-free phase following the 3-month active treatment phase for the T group. The primary efficacy criterion was overall response, dichotomized into success or failure, success being the combination of clinical cure and negative mycology at month 18. This criterion was used as the effectiveness measure in the pharmacoeconomic analysis, conducted from a payer perspective. Results In total, 249 patients were included into the study: 120 in the AT group and 129 in the T group. A significantly higher success rate was observed for patients in the AT group relative to those in the T group at 18 months (59·2% vs. 45·0%; P = 0·03). Both treatment regimens were safe and well tolerated. Treatment cost per cured patient was lower for the combination than for terbinafine alone in all countries. Conclusions Study results confirmed that, in the treatment of dermatophytic toenail onychomycosis with matrix involvement, amorolfine nail lacquer in combination with oral terbinafine enhances clinical efficacy and is more cost-effective than terbinafine alone.
P41 Liver disease-specific gene expression profile in hepatocellular carcinoma
Authors: A. Marshall
Journal: Gut (2011)

<h3>Introduction</h3> In the UK, hepatocellular carcinoma (HCC) has the largest increase in cancer mortality of all cancers over the last decade. Although it is well known that the most important risk factor for HCC development is liver cirrhosis, the specific role of liver disease aetiology in promoting cancer development remains under-explored. We hypothesised that different liver diseases might drive HCC development by expression of different sets of genes. Identification of liver disease-specific genes could be applied to developing disease-specific diagnostic markers or therapeutic targets. <h3>Aim</h3> To compare global gene expression profiles from HCC arising in different liver diseases, using our own and publicly available data. <h3>Method</h3> Fresh-frozen liver samples were collected from normal liver (4) and both background liver (7) and HCC (7) from patients with haemochromatosis (HH) undergoing liver transplantation or resection for HCC. RNA was extracted using a phenol-chloroform method, assessed for quality then hybridised to Affymetrix U133Plus2.0 gene expression arrays. Public microarray databases ArrayExpress and Gene Expression Omnibus were mined for liver gene expression data measured using Affymetrix U133Plus2.0 array platform. Annotations for all identified liver samples were curated and relevant samples selected for RMA normalisation. Principal component analysis and differential gene expression analysis were carried out using R Bioconductor. The lists of differentially expressed genes were created by separate comparison of each disease group against normal liver samples. The lists of p value corrected statistically significant genes were further filtered for twofold expression change. Disease specific gene lists were created. Genes identified as highly expressed in HH-related HCC were validated using quantitative RT-PCR. <h3>Results</h3> Public databases yielded gene expression data on normal liver (n=51), HCV/cirrhosis (n=59), HCV-related HCC (n=126), HBV/cirrhosis (n=4), and HBV-related HCC (n=5). Principal component analysis showed clustering of normal, cirrhosis and HCC samples. Using a twofold cut-off, 16 genes were differentially expressed in HH-related HCC compared to normal liver, 502 genes in HBV-related HCC and 29 genes in HCV-related HCC (Abstract P41 figure 1). No differentially-expressed genes were common to all three groups. Genes CD109 and SPP1 were identified as highly expressed in HH-related HCC compared to all other groups (Abstract P41 figure 2) and their expression in normal and HH samples were confirmed with quantitative RT-PCR. <h3>Conclusion</h3> Comparison of global gene expression profiles yielded sets of differentially expressed genes specific to liver disease aetiology in HCC related to HCV, HBV and haemochromatosis. Two genes highly expressed in haemochromatosis-related HCC were identified that might be useful as disease-specific markers.