tbuckley/cabot-search huggingface dataset:
IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes
Authors: Märit Wallander, Anna Norhammar, Klas Malmberg, John Öhrvik, Lars Rydén, Kerstin Brismar
Journal: Diabetes Care (2007)

There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGF-binding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes.The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available.During a median follow-up period of 2.2 years, 131 (23%) patients died from all-cause mortality and 102 (18%) from CVD, whereas 175 patients (30%) suffered from at least one cardiovascular event. The independent predictors for cardiovascular death in the Cox regression model were (as hazard ratio [HR] [95% CI]): ln updated mean blood glucose (12.2 [5.8-25.7]), age (+5 years) (1.5 [1.4-1.7]), ln IGFBP-1 (1.4 [1.1-1.8]), and ln serum creatinine at admission (2.4 [1.3-4.2]). The model predicting cardiovascular events contained the same variables (ln IGFBP-1 at admission, 1.2 [1.0-1.4]).High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI.
Risk Factors for Mortality in a Diverse Cohort of Patients With Childhood-Onset Diabetes in Chicago
Authors: Deborah L. Burnet, Andrew J. Cooper, Melinda L. Drum, Rebecca B. Lipton
Journal: Diabetes Care (2007)

We sought to determine whether risk of death differed by demographic or other characteristics in a population-based cohort of patients with childhood-onset diabetes.The Chicago Childhood Diabetes Registry is an ethnically diverse cohort of patients with diabetes onset between ages 0 and 17 years. Cases that accumulated from 1 January 1985 to 31 December 2000 (n = 1,238) were assessed for vital status using death certificates, family reports, and two large administrative databases (Social Security Death Index and National Death Index). Mortality was compared between subgroups using Poisson and Cox proportional hazards regression.Thirty subjects died, with a mean follow-up time of 7.75 years, yielding a crude case fatality rate of 2.4%. Six subjects died of diabetic ketoacidosis (DKA) at initial presentation. Onset age was the predominant risk factor, driven by a substantially higher fatality rate among those diagnosed at age 17 years (13.36/1,000 person-years) than among other ages and by moderately higher rates for those diagnosed in early adolescence (ages 10-13 years) (3.49/1,000 person-years), compared with children diagnosed before age 10 years (0.89/1,000 person-years) or at ages 14-16 years (0.81/1,000 person-years). Mortality did not differ significantly by other factors examined; data for whites were insufficient to allow comparisons with that group. In addition to diabetes, frequent causes of death were trauma, infectious disease, and cardiovascular disease.This study provides short- to medium-term follow-up in a diverse cohort of patients. DKA remains a significant cause of death in young people with diabetes. Young people diagnosed at the threshold of adulthood are at increased risk for mortality.
Internal Diversification of Mitochondrial Haplogroup R0a Reveals Post-Last Glacial Maximum Demographic Expansions in South Arabia
Authors: V. Cerny, C. J. Mulligan, V. Fernandes, N. M. Silva, F. Alshamali, A. Non, N. Harich, L. Cherni, A. B. A. El Gaaied, A. Al-Meeri, L. Pereira
Journal: Molecular Biology and Evolution (2010)

Widespread interest in the first successful Out of Africa dispersal of modern humans ∼60-80 thousand years ago via a southern migration route has overshadowed the study of later periods of South Arabian prehistory. In this work, we show that the post-Last Glacial Maximum period of the past 20,000 years, during which climatic conditions were becoming more hospitable, has been a significant time in the formation of the extant genetic composition and population structure of this region. This conclusion is supported by the internal diversification displayed in the highly resolved phylogenetic tree of 89 whole mitochondrial genomes (71 being newly presented here) for haplogroup R0a-the most frequent and widespread haplogroup in Arabia. Additionally, two geographically specific clades (R0a1a1a and R0a2f1) have been identified in non-Arabic speaking peoples such as the Soqotri and Mahri living in the southern part of the Arabian Peninsula where a past refugium was identified by independent archaeological studies. Estimates of time to the most recent common ancestor of these lineages match the earliest archaeological evidence for seafaring activity in the peninsula in the sixth millennium BC.
Nedd4-2 Modulates Renal Na+-Cl− Cotransporter via the Aldosterone-SGK1-Nedd4-2 Pathway
Authors: Juan Pablo Arroyo, Dagmara Lagnaz, Caroline Ronzaud, Norma Vázquez, Benjamin S. Ko, Lauren Moddes, Dorothée Ruffieux-Daidié, Pierrette Hausel, Robert Koesters, Baoli Yang, John B. Stokes, Robert S. Hoover, Gerardo Gamba, Olivier Staub
Journal: Journal of the American Society of Nephrology (2011)

Regulation of renal Na(+) transport is essential for controlling blood pressure, as well as Na(+) and K(+) homeostasis. Aldosterone stimulates Na(+) reabsorption by the Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule (DCT) and by the epithelial Na(+) channel (ENaC) in the late DCT, connecting tubule, and collecting duct. Aldosterone increases ENaC expression by inhibiting the channel's ubiquitylation and degradation; aldosterone promotes serum-glucocorticoid-regulated kinase SGK1-mediated phosphorylation of the ubiquitin-protein ligase Nedd4-2 on serine 328, which prevents the Nedd4-2/ENaC interaction. It is important to note that aldosterone increases NCC protein expression by an unknown post-translational mechanism. Here, we present evidence that Nedd4-2 coimmunoprecipitated with NCC and stimulated NCC ubiquitylation at the surface of transfected HEK293 cells. In Xenopus laevis oocytes, coexpression of NCC with wild-type Nedd4-2, but not its catalytically inactive mutant, strongly decreased NCC activity and surface expression. SGK1 prevented this inhibition in a kinase-dependent manner. Furthermore, deficiency of Nedd4-2 in the renal tubules of mice and in cultured mDCT(15) cells upregulated NCC. In contrast to ENaC, Nedd4-2-mediated inhibition of NCC did not require the PY-like motif of NCC. Moreover, the mutation of Nedd4-2 at either serine 328 or 222 did not affect SGK1 action, and mutation at both sites enhanced Nedd4-2 activity and abolished SGK1-dependent inhibition. Taken together, these results suggest that aldosterone modulates NCC protein expression via a pathway involving SGK1 and Nedd4-2 and provides an explanation for the well-known aldosterone-induced increase in NCC protein expression.
The European Sleep Apnoea Database (ESADA): report from 22 European sleep laboratories
Authors: J. Hedner, L. Grote, M. Bonsignore, W. McNicholas, P. Lavie, G. Parati, P. Sliwinski, F. Barbé, W. De Backer, P. Escourrou, I. Fietze, J.A. Kvamme, C. Lombardi, O. Marrone, J.F. Masa, J.M. Montserrat, T. Penzel, M. Pretl, R. Riha, D. Rodenstein, T. Saaresranta, R. Schulz, R. Tkacova, G. Varoneckas, A. Vitols, H. Vrints, J. Zielinski
Journal: European Respiratory Journal (2011)

The European Sleep Apnoea Database (ESADA) reflects a network of 22 sleep disorder centres in Europe enabled by a COST action B26 programme. This ongoing project aims to describe differences in standard clinical care of patients with obstructive sleep apnoea (OSA) and to establish a resource for genetic research in this disorder. Patients with suspected OSA are consecutively included and followed up according to local clinical standards. Anthropometrics, medical history, medication, daytime symptoms and sleep data (polysomnography or cardiorespiratory polygraphy) are recorded in a structured web-based report form. 5,103 patients (1,426 females, mean± sd age 51.8±12.6 yrs, 79.4% with apnoea/hypopnoea index (AHI) ≥5 events·h −1 ) were included from March 15, 2007 to August 1, 2009. Morbid obesity (body mass index ≥35 kg·m −2 ) was present in 21.1% of males and 28.6% of females. Cardiovascular, metabolic and pulmonary comorbidities were frequent (49.1%, 32.9% and 14.2%, respectively). Patients investigated with a polygraphic method had a lower AHI than those undergoing polysomnography (23.2±23.5 versus 29.1±26.3 events·h −1 , p&lt;0.0001). The ESADA is a rapidly growing multicentre patient cohort that enables unique outcome research opportunities and genotyping. The first cross-sectional analysis reveals a high prevalence of cardiovascular and metabolic morbidity in patients investigated for OSA.
Tumour necrosis factor-α gene promoter polymorphism in chronic obstructive pulmonary disease
Authors: M.A. Higham, N.B. Pride, A. Alikhan, N.W. Morrell
Journal: European Respiratory Journal (2000)

Tumour necrosis factor(TNF)-alpha levels are elevated in airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to its pathogenesis. A guanine to adenine substitution at position -308 of the TNF-alpha gene promoter (TNF1/2) has been associated with chronic bronchitis of various aetiologies in a Taiwanese population. The authors performed a study investigating association of the polymorphism with smoking-related COPD in Caucasians. Frequencies of TNF1/2 alleles in 86 Caucasians (52 males) with COPD were compared with 63 (52 males) asymptomatic smoker/exsmoker control subjects and a population control of 199 (99 males) blood donors. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic deoxyribonucleic acid (DNA) obtained from peripheral blood. There were no significant differences in TNF1/2 allele frequencies between groups: 0.85/0.15 in COPD, 0.85/0.15 in smoker control subjects, 0.83/0.17 in population control subjects. Within the COPD group there was no association of TNF1/2 alleles with indices of airflow obstruction (% predicted forced expiratory volume in one second (FEV1) and % predicted FEV1/vital capacity ratio) nor gas transfer (% predicted carbon monoxide transfer coefficient and % predicted carbon monoxide diffusing capacity of the lung). It is concluded that: 1) the tumour necrosis factor gene promoter allele does not influence the risk of developing chronic obstructive pulmonary disease in a Caucasian population of smokers; and 2) there is no association of the tumour necrosis factor gene promoter genotype with severity of airflow obstruction nor degree of emphysema in chronic obstructive pulmonary disease.
Development of model equations for selecting optimum parameters for dry process of shea butter extraction
Authors: A. M. Olaniyan, K. Oje
Journal: Journal of Clinical Oncology (2011)

Shea butter is the fat content of the kernel of shea nut (Vitellaria paradoxa) which grows naturally from the wild and uncultivated state in most parts of Africa. The fat is used as edible oil and for raw material in the production of soaps, pomade, drugs and medicinal ointments. Wet extraction process is the method used in shea butter processing industry among women in African rural and urban communities. Apart from the low yield (below 20%), this wet extraction process is associated with environmental polluting effluents as by products. Experiments on dry extraction of shea butter from shea kernel were carried out using an instrumented piston-cylinder rig in conjunction with the TESTOMETRIC Universal Testing Machine (Model M500–50 KN). Shea butter was mechanically expressed when pressures of 1.5, 2.9, 5.8 and 8.8 MPa were applied at the rate of 2.50, 5.00, 7.50 and 10.00 mm/min on crushed shea kernel heated at 50, 70, 90 and 110°C. Measurements were made of oil yield, oil recovery efficiency and process loss during the mechanical expression process. The measured effects of heating temperature, applied pressure and loading speed on oil yield, oil recovery efficiency and process loss were examined using a 43 factorial experiment in randomized complete block design. Model equations were developed by employing multiple regression analysis using SPSS 11.0 package. Further analysis by optimization process revealed optimum heating temperature, applied pressure and loading rate of 82.24°C, 9.69 MPa and 2.50 mm min-1 respectively. These combinations gave 35.39% oil yield, 58.62% oil recovery efficiency and 2.83% process loss. This information provides useful data for developing a process line for dry extraction of shea butter from shea kernel.

	 

	Key words: Shea butter, dry extraction, model equations, optimization, oil yield.
TV: The psychokiller strikes again
Authors: R. M. Condren
Journal: BMJ (2000)

ER , Channel 4, Wednesday 19 April at 9 pm

E R (Emergency Room) , the US television drama of high adrenaline medical heroics, has blazed its way into a sixth series. It has undoubtedly captured the public imagination, with its strong characters, uneasy tensions, and frenetic trauma calls. It presents highly positive images of healthcare professionals, which is perhaps why the BMJ and Nursing Times put two ER characters on the cover of their recent joint issue. The programme reaches the masses. This year, in the week starting 18 January, it was watched in 21 million out of a possible99.4 million US households.

In Britain Channel 4 screened two extraordinary episodes on 19 April, which caused much public excitement, sadness, and even grief. The country watched in horror the double stabbing of medical student Lucy and resident Dr Carter.

In the first episode we saw Lucy working up the case of a young married man, Paul, who had presented with headaches. Carter offers minimal supervision. When the man becomes disoriented she …
Early treatment with aspirin plus extended-release dipyridamole for transient ischaemic attack or ischaemic stroke within 24 h of symptom onset (EARLY trial): a randomised, open-label, blinded-endpoint trial
Authors: Reinhard Dengler, Hans-Christoph Diener, Andreas Schwartz, Martin Grond, Helmut Schumacher, Thomas Machnig, Christoph Cyrill Eschenfelder, Joachim Leonard, Karin Weissenborn, Andreas Kastrup, Roman Haberl
Journal: The Lancet Neurology (2010)
Alexithymic Characteristics and Somatic Illness
Authors: Astrid N&oslash;klebye Heiberg
Journal: Psychotherapy and Psychosomatics (1980)

As part of a study on stress, the author investigated 183 women, the majority of whom were dental patients. A highly significant correlation between a high score of alexithymic characteristics and many reported somatic diseases was found in the subjects who were 40 years of age or older.
Spatial Inhomogeneity of Sympathetic Nerve Function in Hibernating Myocardium
Authors: Andrew J. Luisi, James A. Fallavollita, Gen Suzuki, John M. Canty
Journal: Circulation (2002)

Background— Although humans and swine with hibernating myocardium have an increased risk of sudden death, the contribution of chronic alterations in sympathetic nerve function is unknown. Acute transmural ischemia causes inhomogeneity in sympathetic innervation that may lead to lethal arrhythmias, but it is unclear whether similar abnormalities develop in response to chronic reversible ischemia. Methods and Results— Swine were chronically instrumented with a left anterior descending coronary artery (LAD) stenosis that produced hibernating myocardium after 3 months. Resting subendocardial flow (LAD 0.75±0.14 versus 1.19±0.14 mL · min −1 · g −1 , P &lt;0.05) and wall thickening (LAD 15±3% versus 40±2%, P &lt;0.05) were reduced compared with normal remote regions, without triphenyltetrazolium chloride evidence of necrosis. 131 I-meta-iodobenzylguanidine (MIBG) was used to assess integrity of the norepinephrine uptake-1 mechanism, and the spatial and transmural distributions were quantified by ex vivo counting. In hibernating myocardium, MIBG deposition was decreased in each layer, with the greatest reduction in the subendocardium (LAD subendocardium 0.28±0.02 versus 0.42±0.04 mL · g −1 · min −1 in normal, P &lt;0.05; LAD subepicardium 0.31±0.03 versus 0.38±0.04 mL · g −1 · min −1 in normal, P &lt;0.05). In contrast, there were no spatial alterations of MIBG deposition in sham-instrumented animals. Conclusions— The sympathetic norepinephrine uptake-1 mechanism is impaired in hibernating myocardium. These findings raise the possibility that chronic alterations in sympathetic innervation contribute to the excess mortality seen in the setting of hibernating myocardium.
Basophil histamine release in insect venom allergy
Authors: T. Engel, J. H. Heinig, E. R. Weeke, B. Schwartz, L. Ingemann
Journal: Allergy (1988)

The aim of the present study was to investigate venom-related and venom-non-related immunological reactions in patients stung by bee or wasp. Sixteen consecutive patients (7 with local and 9 with systemic reactions) were tested with skin tests, RAST and basophil histamine release (BHR) test immediately after the insect sting and 2, 4, and 16 weeks later. No test was useful immediately after the insect sting, the "anergic period". In agreement with earlier findings, the SPT was the only allergy test that showed statistically significant differences between patients with local and systemic reactions, although a great overlap was found. Release of histamine from basophils after incubation with anti-IgE also showed statistically significant differences between local and systemic reactions. Further studies are needed, especially measurement of BHR after incubation with anti-IgE before insect stings.
Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity
Authors: Amie S. Corbin, Anupriya Agarwal, Marc Loriaux, Jorge Cortes, Michael W. Deininger, Brian J. Druker
Journal: Journal of Clinical Investigation (2010)

Imatinib therapy, which targets the oncogene product BCR-ABL, has transformed chronic myeloid leukemia (CML) from a life-threatening disease into a chronic condition. Most patients, however, harbor residual leukemia cells, and disease recurrence usually occurs when imatinib is discontinued. Although various mechanisms to explain leukemia cell persistence have been proposed, the critical question from a therapeutic standpoint--whether disease persistence is BCR-ABL dependent or independent--has not been answered. Here, we report that human CML stem cells do not depend on BCR-ABL activity for survival and are thus not eliminated by imatinib therapy. Imatinib inhibited BCR-ABL activity to the same degree in all stem (CD34+CD38-, CD133+) and progenitor (CD34+CD38+) cells and in quiescent and cycling progenitors from newly diagnosed CML patients. Although short-term in vitro imatinib treatment reduced the expansion of CML stem/progenitors, cytokine support permitted growth and survival in the absence of BCR-ABL activity that was comparable to that of normal stem/progenitor counterparts. Our findings suggest that primitive CML cells are not oncogene addicted and that therapies that biochemically target BCR-ABL will not eliminate CML stem cells.
Non–High-Density Lipoprotein Cholesterol as a Biomarker for Nonalcoholic Steatohepatitis
Authors: Kathleen E. Corey, Michelle Lai, Louis G. Gelrud, Joseph Misdraji, Lydia L. Barlow, Hui Zheng, Karin L. Andersson, Michael Thiim, Daniel S. Pratt, Raymond T. Chung
Journal: Clinical Gastroenterology and Hepatology (2012)
A Gene With Major Effect on Susceptibility To Induced Lung Tumors in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Joyce L. Bloom, D. S. Falconer
Journal: JNCI Journal of the National Cancer Institute (1964)

Analyses of the F1 crosses between 6 inbred strains of mice, A/Fa, C57BL/Fa, CBA/Fa, RIII/Fa, JU/Fa, and KL, are presented and discussed. The C57BL strain, which had the lowest susceptibility of all the strains, behaved differently from the other strains in crosses. It did not give F1's with intermediate susceptibilities, but behaved as a “recessive” in all the crosses. This suggested the presence of a single recessive major gene conferring low susceptibility, and the hypothesis was tested experimentally by standard mendelian methods and fully confirmed. The recessive major gene has provisionally been named “pulmonary tumor resistance” (ptr). This gene accounts for three quarters of the difference in susceptibility between the C57BL and A strains. The remaining difference is attributable to minor genes.
Loss of ΔNp63α Promotes Invasion of Urothelial Carcinomas via N-Cadherin/Src Homology and Collagen/Extracellular Signal-Regulated Kinase Pathway
Authors: Hiroshi Fukushima, Fumitaka Koga, Satoru Kawakami, Yasuhisa Fujii, Soichiro Yoshida, Edward Ratovitski, Barry Trink, Kazunori Kihara
Journal: Cancer Research (2009)

p63 plays a critical role in normal development and maintenance of stratified epithelia, including the urothelium. In the normal urothelium, urothelial cells in the basal layers abundantly express the predominant p63 isoform DeltaNp63alpha. We previously showed that (a) DeltaNp63alpha expression at the similar level to the normal urothelium is retained in most low-grade papillary noninvasive (LPN) tumors, whereas frequently lost in high-grade invasive carcinomas, and that (b) loss of DeltaNp63alpha is associated with poor prognosis of invasive bladder urothelial carcinoma patients. However, a functional role of DeltaNp63alpha in progression of urothelial carcinomas remains to be elucidated. Here, we show that loss of DeltaNp63alpha expression promotes invasion of urothelial carcinoma cells. In 5637 cells substantially expressing only DeltaNp63alpha isoform at the protein level, knockdown of endogenous p63 upregulated N-cadherin, which recruited more Src homology and collagen to N-cadherin and activated extracellular signal-regulated kinase (ERK) signaling, and consequently potentiated cell motility, excretion of matrix metalloproteinase-9, and invasion. In T24 cells originally lacking endogenous DeltaNp63alpha expression, exogenous expression of DeltaNp63alpha attenuated invasion by downregulating N-cadherin expression and ERK activity, confirming an invasion-suppressive role of DeltaNp63alpha in urothelial carcinoma cells. We further documented loss of DeltaNp63 expression accompanied by N-cadherin upregulation during muscle-invasive recurrence in patients whose bladder cancer had progressed from LPN tumors to muscle-invasive disease. These results suggest that loss of DeltaNp63alpha and subsequent upregulation of N-cadherin is one of the mechanisms underlying progression of bladder cancer.