tbuckley/cabot-search huggingface dataset:
Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus*
Authors: Holbrooke S. Seltzer, E. William Allen, Arthur L. Herron, Mildred T. Brennan
Journal: Journal of Clinical Investigation (1967)

Insulin secretory responses to paired intravenous and oral glucose loads were determined in 38 nonobese individuals classified as normal (nondiabetic) subjects, "mild" diabetics (fasting blood glucose below 105 mg per 100 ml), or "moderate" diabetics (fasting glucose below 192 mg per 100 ml). Studies were also performed in 29 obese persons who were similarly grouped. The intravenous load was given to assess the alacrity of hormonal release after glycemic stimulus, and the oral glucose to determine how the speed of initial insulinogenesis modifies the disposition of ingested carbohydrate. In the nonobese group, normal subjects responded to massive hyperglycemia after rapid injection of glucose with immediate and maximal outpouring of insulin, in contrast to a desultory insulinogenic response in patients with mild diabetes, and no initial response at all in moderate diabetics. During oral glucose tolerance tests, the much faster clearance of blood sugar in nondiabetic subjects was actually associated with lower absolute insulin output than was found in mildly diabetic patients, since the latter exhibited delayed hyperinsulinemia in concert with prolonged hyperglycemia. Moderate diabetics never showed excessive insulin release despite even greater hyperglycemia. An empirical "insulinogenic index," the ratio relating enhancement of circulating insulin to magnitude of corresponding glycemic stimulus, was used to compare the secretory capacities of respective groups. Despite the higher absolute hormonal output after oral glucose in mild diabetics, the index revealed that insulin release in normal subjects was proportionally more than twice as great. This relatively greater normal secretory response declared itself shortly after the administration of glucose by either route, and was maintained throughout both tests. In the 29 obese individuals, differences among groups were essentially the same as in persons of normal weight. Obese nondiabetics did show much larger absolute insulinogenic responses during both tests than did nonobese controls. Since corresponding glucose tolerance curves were also higher, the mean insulinogenic indexes for obese subjects were not statistically greater. Moreover, when comparable glucose curves of obese and nonobese controls
Rationality, logic, and fast and frugal heuristics
Authors: José Luis Bermúdez
Journal: Behavioral and Brain Sciences (2000)

Gigerenzer and his co-workers make some bold and striking claims about the relation between the fast and frugal heuristics discussed in their book and the traditional norms of rationality provided by deductive logic and probability theory. We are told, for example, that fast and frugal heuristics such as “Take the Best” replace “the multiple coherence criteria stemming from the laws of logic and probability with multiple correspondence criteria relating to real-world decision performance.” This commentary explores just how we should interpret this proposed replacement of logic and probability theory by fast and frugal heuristics.
Ghost Management: How Much of the Medical Literature Is Shaped Behind the Scenes by the Pharmaceutical Industry?
Authors: Sergio Sismondo
Journal: PLoS Medicine (2007)

There are many reports of medical journal articles being researched and written by or on behalf of pharmaceutical companies, and then published under the name of academics who had played little role earlier in the research and writing process [2–14]. In extreme cases, drug companies pay for trials by contract research organizations (CROs), analyze the data in-house, have professionals write manuscripts, ask academics to serve as authors of those manuscripts, and pay communication companies to shepherd them through publication in the best journals. The resulting articles affect the conclusions found in the medical literature, and are used in promoting drugs to doctors.For example, as reported in
Why are doctors so unhappy?
Authors: R. Smith
Journal: BMJ (2001)

There are probably many causes, some of them deep See editorial p 1078 News pp 1082, 1083 Doctors are unhappy. They are not all unhappy all the time, but when doctors gather, their conversation turns to misery and talk of early retirement. The unhappiness has been illustrated in a plethora of surveys and manifests itself in talk of a mass resignation by general practitioners from the NHS.1 The British government is rattled by the unhappiness of doctors, recognising that a health service staffed by demoralised doctors cannot flourish. It has responded by trying to hand more control of the service to frontline staff. 2 3 But is this the right treatment? Treatment must, of course, follow diagnosis, and the causes of doctors' unhappiness may be many and deep. #### Doctors and patients: redrafting a bogus contract ##### The bogus contract: the patient's view ##### The bogus contract: the doctor's view
Cytokine expression in the diaphragm of rats breathing against subacute hypoxic conditions
Authors: M. Dominguez, S. Pascual, M. Sabaté, F. Sánchez, C. Casadevall, E. Barreiro, J. Gea
Journal: European Respiratory Journal (2011)

COPD patients show muscle damage and an increase in the expression of local cytokines in their diaphragms. The paracrine role of these cytokines still remains controversial.   Objective:  To analyze the effects of subacute hypoxia on the diaphragm muscle.   Methods:  Wistar rats (n=8/group) were exposed to: (1) hypoxia (FIO2 0.10) +placebo, (2) normoxia +placebo, (3) hypoxia +Infliximab [monoclonal antibody that results in the blockade of TNF-α receptors], and (4) normoxia +Infliximab for 2 weeks in all cases. At the end of the study period diaphragm and gastrocnemius muscles as well as blood samples were obtained. Molecular and cellular indices of muscle damage, oxidative stress, cytokine expression and activation of regeneration pathways were obtained using morphometry, Western-blot, spectrophotometry, ELISA, luminometry and RT-PCR.   Results:  Although rats exposed to hypoxia showed higher levels of expression of different cytokines (TNF-α, IL-6, INF-g) in their diaphragms than the control animals (normoxia), no differences were observed in muscle damage, oxidative stress and biomarkers of muscle regeneration. Inhibition of TNF-α action in hypoxic animals resulted in an even higher expression of local cytokines with no relevant changes in the other variables when compared with hypoxic animals receiving placebo. No changes were observed in either limb muscle or blood in any of the groups.   Conclusions:  Hypoxia induces local inflammation in respiratory muscles of hypoxic rats. This effect appears to be selective for respiratory muscles and can be related to changes in their mechanical loading and its mismatching with the oxygen delivery to the muscle.  Funded: SAF07-62719, CIBERES, SEPAR & SOCAP.
Sphingosine 1-Phosphate Receptor-1 Enhances Mitochondrial Function and Reduces Cisplatin-Induced Tubule Injury
Authors: Amandeep Bajwa, Diane L. Rosin, Piotr Chroscicki, Sangju Lee, Krishna Dondeti, Hong Ye, Gilbert R. Kinsey, Brian K. Stevens, Katarzyna Jobin, Brandon M. Kenwood, Kyle L. Hoehn, Kevin R. Lynch, Mark D. Okusa
Journal: Journal of the American Society of Nephrology (2014)

Sphingosine 1-phosphate (S1P), the natural sphingolipid ligand for a family of five G protein– coupled receptors (S1P1–S1P5Rs), regulates cell survival and lymphocyte circulation. We have shown that the pan-S1PR agonist, FTY720, attenuates kidney ischemia-reperfusion injury by directly activating S1P1 on proximal tubule (PT) cells, independent of the canonical lymphopenic effects of S1P1 activation on B and T cells. FTY720 also reduces cisplatin-induced AKI. Therefore, in this study, we used conditional PT-S1P1-null (PepckCreS1pr1fl/fl) and control (PepckCreS1pr1w/wt) mice to determine whether the protective effect of FTY720 in AKI is mediated by PT-S1P1. Cisplatin induced more renal injury in PT-S1P1-null mice than in controls. Although FTY720 produced lymphopenia in both control and PT-S1P1-null mice, it reduced injury only in control mice. Furthermore, the increase in proinflammatory cytokine (CXCL1, MCP-1, TNF-α, and IL-6) expression and infiltration of neutrophils and macrophages induced by cisplatin treatment was attenuated by FTY720 in control mice but not in PT-S1P1-null mice. Similarly, S1P1 deletion rendered cultured PT cells more susceptible to cisplatin-induced injury, whereas S1P1 overexpression protected PT cells from injury and preserved mitochondrial function. We conclude that S1P1 may have an important role in stabilizing mitochondrial function and that FTY720 administration represents a novel strategy in the prevention of cisplatin-induced AKI.
Association Between Parental Preference and Head Computed Tomography in Children With Minor Blunt Head Trauma
Authors: Yasushi Ishida, Atsushi Manabe, Aya Oizumi, Norio Otani, Michio Hirata, Kevin Urayama, Yukihisa Saida, Isao Kusakawa, Tsuguya Fukui
Journal: JAMA Pediatrics (2013)
Adriamycin-Induced Early Changes in Myocardial Antioxidant Enzymes and Their Modulation by Probucol
Authors: Timao Li, Pawan K. Singal
Journal: Circulation (2000)

The clinical usefulness of adriamycin is restricted by the development of congestive heart failure. It has been suggested that probucol, a strong antioxidant, completely prevents adriamycin-induced cardiomyopathy without interfering with its antitumor properties. The present study investigated the effects of adriamycin and probucol on myocardial antioxidant enzyme activities and immunoreactive protein levels in rats.Activities and protein levels of glutathione peroxidase (GSHPx) were significantly decreased from 2 to 24 hours, and those of manganese superoxide dismutase were decreased at 1 and 2 hours after adriamycin treatment. These changes were prevented by probucol. Catalase activity was increased from 2 to 24 hours after adriamycin treatment, but its protein levels were not significantly changed. Copper zinc superoxide dismutase activity and protein level were not changed at any time. Myocardial lipid peroxidation was found to be significantly higher at all time points, and this change was also prevented by probucol. Treatment with probucol alone increased GSHPx activity at 2 weeks, and in these hearts, lipid peroxidation was lower than the control value. Within 24 hours, there was no mortality in any of the groups.It is suggested that an early and persistent decrease in GSHPx activity and protein may play an important role in the pathogenesis of adriamycin-induced cardiomyopathy, worsening heart failure and mortality.
Working memory and the identification of facial expression in patients with left frontal glioma
Authors: Y.-G. Mu, L.-J. Huang, S.-Y. Li, C. Ke, Y. Chen, Y. Jin, Z.-P. Chen
Journal: Neuro-Oncology (2012)

Patients with brain tumors may have cognitive dysfunctions including memory deterioration, such as working memory, that affect quality of life. This study was to explore the presence of defects in working memory and the identification of facial expressions in patients with left frontal glioma. This case-control study recruited 11 matched pairs of patients and healthy control subjects (mean age ± standard deviation, 37.00 ± 10.96 years vs 36.73 ± 11.20 years; 7 male and 4 female) from March through December 2011. The psychological tests contained tests that estimate verbal/visual-spatial working memory, executive function, and the identification of facial expressions. According to the paired samples analysis, there were no differences in the anxiety and depression scores or in the intelligence quotients between the 2 groups (P > .05). All indices of the Digit Span Test were significantly worse in patients than in control subjects (P < .05), but the Tapping Test scores did not differ between patient and control groups. Of all 7 Wisconsin Card Sorting Test (WCST) indexes, only the Preservative Response was significantly different between patients and control subjects (P < .05). Patients were significantly less accurate in detecting angry facial expressions than were control subjects (30.3% vs 57.6%; P < .05) but showed no deficits in the identification of other expressions. The backward indexes of the Digit Span Test were associated with emotion scores and tumor size and grade (P < .05). Patients with left frontal glioma had deficits in verbal working memory and the ability to identify anger. These may have resulted from damage to functional frontal cortex regions, in which roles in these 2 capabilities have not been confirmed. However, verbal working memory performance might be affected by emotional and tumor-related factors.
Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice.
Authors: D C Bullard, E J Kunkel, H Kubo, M J Hicks, I Lorenzo, N A Doyle, C M Doerschuk, K Ley, A L Beaudet
Journal: The Journal of Experimental Medicine (1996)

During the initial phase of the inflammatory response, leukocytes marginate and roll along the endothelial surface, a process mediated largely by the selectins and their ligands. Mice with mutations in individual selectins show no spontaneous disease and have mild or negligible deficiencies of inflammatory responses. In contrast, we find that mice with null mutations in both endothelial selectins (P and E) develop a phenotype of leukocyte adhesion deficiency characterized by mucocutaneous infections, plasma cell proliferation, hypergammaglobulinemia, severe deficiencies of leukocyte rolling in cremaster venules with or without addition of TNF-alpha, and an absence of neutrophil emigration at 4 h in response to intraperitoneal Streptococcus pneumoniae peritonitis. These mice provide strong evidence for the functional importance of selectins in vivo.
The lipid composition of sebaceous glands as a reflection of gland size*
Authors: R. SUMMERLY, H.J. YARDLEY, MARJORIE RAYMOND, ANNE TABIOWO, ELIZABETH ILDERTON
Journal: British Journal of Dermatology (1976)

Following 4 h incubation in vitro, the patterns of incorporation of [I-14C] acetate into the lipid classes of human sebaceous glands which were dissected from small skin biopsies have been established for glands of different size. It has been shown that in the larger sebaceous glands proportionately more of the labelled acetate is incorporated into squalene at the expense of triglycerides. Experiments are presented as a result of which we conclude that this in vitro phenomenon, observed with [I-14C] acetate incorporation, does reflect parallel changes in the proportions of these lipids actually present in glands of different size. It is suggested that the larger sebaceous glands of the acne patient elaborate sebum which has an enhanced potential for inducing comedo formation by virtue of an increased concentration of squalene. This work also demonstrates that, in the interpretation of in vitro studies of sebaceous gland lipogenesis utilizing labelled precursors, the size of the sebaceous glands must be carefully considered whenever patterns of incorporation are being compared.
THE USE OF BACTERIAL LIPOPOLYSACCHARIDES TO SHOW THAT TWO SIGNALS ARE REQUIRED FOR THE INDUCTION OF ANTIBODY SYNTHESIS
Authors: James Watson, Ekkhart Trenkner, Melvin Cohn
Journal: The Journal of Experimental Medicine (1973)

Evidence is presented that antigen-sensitive cells require two signals for induction. Normally these two signals are delivered to the cell via the recognition of two determinants on the immunogen: the first the receptor on the antigen-sensitive cell, and the second by the cooperating cell system. The special experimental situation described here depends upon the observation that bacterial lipopolysaccharides (LPS) render immunogenic a variety of haptens. When monovalent haptens (TNP-amino acids) are added to spleen cultures, specific antihapten responses are induced in the presence of LPS. After analyzing competing interpretations of this phenomenon, we propose that the antigenic signal is delivered as the consequence of a conformational change in the receptor upon interacting with antigen, and the second signal is delivered directly via the interaction of LPS with the membrane on the antigen-sensitive cell receiving the antigenic signal, or indirectly via the interaction of LPS with the cooperating cell population. These data imply LPS is not itself a mitogen, but merely completes an inductive stimulus to B cells. The experimental results from these and other studies indicate how these two signals may participate in inductive, suppressive, and paralytic stimuli to antigen-sensitive cells.
Infectious diseases are spreading more rapidly than ever before, WHO warns
Authors: Adrian O'Dowd
Journal: BMJ (2007)

Infectious diseases are spreading around the world faster than ever, says the World Health Organization, and new diseases are emerging at the unprecedented rate of one a year.

WHO has appealed in its annual world health report for international cooperation to tackle infectious diseases, which it says are a serious threat to public health worldwide. The disease situation is “anything but stable,” the report says.

Several factors have helped accelerate the spread of diseases around the world: the increasing ease of international travel (each year airlines carry more than two billion passengers), population growth, resistance …
Radon and leukaemia
Authors: R.H Mole, S.H.U Bowie, FredaE Alexander, PatriciaA Mckinney, RaymondA Cartwright, A.G Prentice, J.A Copplestone, K.F Baverstock, B.K Butland, C.R Muirhead, G.J Draper, DenisL Henshaw, JonathanP Eatough, RichardB Richardson, Gideon Rechavi, Isaac Ben-Bassat, Miriam Berkowicz, Yoram Neumann, Bracha Ramot
Journal: The Lancet (1990)
Identification of metabolites with anticancer properties by computational metabolomics
Authors: Adrian K Arakaki, Roman Mezencev, Nathan J Bowen, Ying Huang, John F McDonald, Jeffrey Skolnick
Journal: Molecular Cancer (2008)

Abstract Background Certain endogenous metabolites can influence the rate of cancer cell growth. For example, diacylglycerol, ceramides and sphingosine, NAD + and arginine exert this effect by acting as signaling molecules, while carrying out other important cellular functions. Metabolites can also be involved in the control of cell proliferation by directly regulating gene expression in ways that are signaling pathway-independent, e.g. by direct activation of transcription factors or by inducing epigenetic processes. The fact that metabolites can affect the cancer process on so many levels suggests that the change in concentration of some metabolites that occurs in cancer cells could have an active role in the progress of the disease. Results CoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: Up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression . All nine metabolites predicted to be lowered in Jurkat cells with respect to lymphoblasts that were examined (riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, α-hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole), exhibited antiproliferative activity that has not been reported before, while only two (bilirubin and androsterone) of the eleven tested metabolites predicted to be increased or unchanged in Jurkat cells displayed significant antiproliferative activity. Conclusion These results: a) demonstrate that CoMet is a valuable method to identify potential compounds for experimental validation, b) indicate that cancer cell metabolism may be regulated to reduce the intracellular concentration of certain antiproliferative metabolites, leading to uninhibited cellular growth and c) suggest that many other endogenous metabolites with important roles in carcinogenesis are awaiting discovery.
The tryptophan pathway genes of the Sargasso Sea metagenome: new operon structures and the prevalence of non-operon organization
Authors: Juliana Kagan, Itai Sharon, Oded Beja, Jonathan C Kuhn
Journal: Genome biology (2008)

The enormous database of microbial DNA generated from the Sargasso Sea metagenome provides a unique opportunity to locate genes participating in different biosynthetic pathways and to attempt to understand the relationship and evolution of those genes. In this article, an analysis of the Sargasso Sea metagenome is made with respect to the seven genes of the tryptophan pathway.At least 5% of all the genes that are related to amino acid biosynthesis are tryptophan (trp) genes. Many contigs and scaffolds contain whole or split operons that are similar to previously analyzed trp gene organizations. Only two scaffolds discovered in this analysis possess a different operon organization of tryptophan pathway genes than those previously known. Many marine organisms lack an operon-type organization of these genes or have mini-operons containing only two trp genes. In addition, the trpB genes from this search reveal that the dichotomous division between trpB_1 and trpB_2 also occurs in organisms from the Sargasso Sea. One cluster was found to contain trpB sequences that were closely related to each other but distinct from most known trpB sequences.The data show that trp genes are widely dispersed within this metagenome. The novel organization of these genes and an unusual group of trpB_1 sequences that were found among some of these Sargasso Sea bacteria indicate that there is much to be discovered about both the reason for certain gene orders and the regulation of tryptophan biosynthesis in marine bacteria.
Estimating Divergence Times in the Presence of an Overdispersed Molecular Clock
Authors: David J. Cutler
Journal: Molecular Biology and Evolution (2000)

Molecular loci that fail relative-rate tests are said to be "overdispersed." Traditional molecular-clock approaches to estimating divergence times do not take this into account. In this study, a method was developed to estimate divergence times using loci that may be overdispersed. The approach was to replace the traditional Poisson process assumption with a more general stationary process assumption. A probability model was developed, and an accompanying computer program was written to find maximum-likelihood estimates of divergence times under both the Poisson process and the stationary process assumptions. In simulation, it was shown that confidence intervals under the traditional Poisson assumptions often vastly underestimate the true confidence limits for overdispersed loci. Both models were applied to two data sets: one from land plants, the other from the higher metazoans. In both cases, the traditional Poisson process model could be rejected with high confidence. Maximum-likelihood analysis of the metazoan data set under the more general stationary process suggested that their radiation occurred well over a billion years ago, but confidence intervals were extremely wide. It was also shown that a model consistent with a Cambrian (or nearly Cambrian) origination of the animal phyla, although significantly less likely than a much older divergence, fitted the data well. It is argued that without an a priori understanding of the variance in the time between substitutions, molecular data sets may be incapable of ever establishing the age of the metazoan radiation.