tbuckley/cabot-search huggingface dataset:
Population-Based Analysis of Prognostic Factors and Survival in Familial Melanoma
Authors: Scott R. Florell, Kenneth M. Boucher, Gilda Garibotti, John Astle, Richard Kerber, Geraldine Mineau, Charles Wiggins, R. Dirk Noyes, Alexander Tsodikov, Lisa A. Cannon-Albright, John J. Zone, Wolfram E. Samlowski, Sancy A. Leachman
Journal: Journal of Clinical Oncology (2005)

Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma.This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk.Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2).These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.
The Role of Surgery in Resectable, Nonresectable, and Metastatic Neuroblastoma
Authors: C. Everett Koop
Journal: JAMA (1968)

The neuroblastoma is a unique tumor not only because of its apparent ability to change from a clinically and pathologically malignant tumor to one of a benign nature (ganglioneuroma) but also because of the remarkable gradient in histology exhibited by this tumor, the variable response according to the age of the patient, a prognosis definitely associated with the anatomical site of the tumor, and finally and perhaps most important to this discussion, what frequently appears to be a lack of correlation between the survival of the patient and the mode of surgical therapy.<sup>18-23</sup> Because the prognosis is so much more favorable in children under the age of 1 year, surgery without adjuvant therapy is considered by many to be sufficient treatment. (Only 28% of our survivors were over 1 year of age at the time of diagnosis.) The site of origin of the tumor has a definite effect upon
Oestrogen and the sexual dimorphism of pulmonary arterial hypertension: a translational challenge
Authors: Jessica K. Paulus, Kari E. Roberts
Journal: European Respiratory Journal (2013)

The striking female predominance in idiopathic and familial pulmonary arterial hypertension (PAH) has been well documented since the publication of the National Institutes of Health (NIH) registry in 1987 [1]. In the majority of PAH registries, females are at least twice as likely to be represented as males, with female to male ratios as high as four to one [2–6]. Notably, these sex differences are not fully explained by a differential distribution of known risk factors for PAH by sex, such as autoimmune disease or anorexigen exposure. Taken together, these epidemiological data suggest that other sex-associated factors, including sex hormones, may influence PAH pathogenesis.

Endogenous and exogenous sex hormone exposures represent a biologically plausible potential risk factor for PAH. Sex hormones determine in utero organ development, drive tissue-specific changes in early life and exert an evolving influence across the life span as their absolute and relative concentrations shift [7]. There can be no doubt that sex hormones, with their ability to modulate vascular tone, inflammation and remodelling, play a fundamental role in determining cardiovascular phenotypes [8]. Emerging data on the importance of sex hormones in animal models of pulmonary hypertension provide tantalising evidence that the pulmonary vascular phenotype of an organism is dependent upon these pleiotropic signalling molecules [9, 10].

In this issue of the European Respiratory Journal , Yuan et al. [11] demonstrate that monocrotaline (MCT) creates an oestrogen-deficient state in rats characterised by low plasma oestradiol (E2) and altered pulmonary expression of oestrogen receptors and enzymes responsible for E2 anabolism (reduced) and catabolism (increased). In the absence of sufficient endogenous ( i.e. post-ovariectomy) or exogenous oestradiol, a pro-proliferative, anti-apoptotic and vasoconstrictive phenotype emerges that is mediated in part via reduced nitric oxide and prostacyclin, and increased endothelin. Rescue of the …
Effect of dietary supplementation with fish oil lipids on mild asthma.
Authors: J P Arm, C E Horton, J M Mencia-Huerta, F House, N M Eiser, T J Clark, B W Spur, T H Lee
Journal: Thorax (1988)

Recruitment of inflammatory leucocytes to the airways may play a part in the pathogenesis of asthma. As dietary enrichment with fish oil lipids can suppress leucocyte function, the effect of these lipids on asthma control and neutrophil function was studied in 20 subjects with mild asthma. Twelve subjects received capsules containing 3.2 g of eicosapentaenoic acid and 2.2 g of docosahexaenoic acid daily and eight subjects received placebo capsules containing olive oil for 10 weeks in a double blind fashion. Baseline specific airways conductance, airways responsiveness to histamine and exercise, diurnal peak expiratory flow, symptom scores, and bronchodilator use were measured. Neutrophil fatty acid composition was evaluated by gas chromatography, calcium ionophore induced neutrophil leukotriene (LT)B4 and LTB5 generation were measured by reverse phase high performance liquid chromatography and radioimmunoassay, and neutrophil chemotactic responses to formyl-methionyl-leucyl-phenylalanine (FMLP) and LTB4 were assessed by a microchemotaxis technique. Although the fish oil supplemented diet produced a greater than 10 fold increase in the eicosapentaenoic acid content of neutrophil phospholipids, there was no significant change in airways responsiveness to histamine or any change in any of the clinical measurements. After dietary supplementation with fish oil there was a 50% inhibition of total LTB (LTB4 + LTB5) generation by ionophore stimulated neutrophils and neutrophil chemotaxis was substantially suppressed. Neutrophil function remained unchanged in the placebo group. It is concluded that in subjects with mild asthma a fish oil enriched diet attenuates neutrophil function without changing the severity of asthma.
Association of interleukin 1B gene polymorphism and gastric cancers in high and low prevalence regions in China
Authors: Z-R Zeng
Journal: Gut (2003)

Our aim was to study the relationship between interleukin 1B (IL-1B) polymorphism, Helicobacter pylori infection, and gastric cancer in high prevalent (Shanxi) and low prevalent (Guangdong) regions in China.Genomic DNA was extracted from peripheral blood of 192 healthy volunteers, 84 gastric cancer patients from Guangdong and 169 healthy volunteers, and 86 gastric cancer patients from Shanxi. Polymorphisms in IL-1B that encodes IL-1beta and IL-1RN that encodes IL-1 receptor antagonist were analysed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). These polymorphic sites include promoter regions of IL-1B at positions +3954, -511 (C-T transition), and -31 (T-C transition), and IL-1RN variable tandem repeats.In the low prevalence region, the frequencies of the IL-1B +3954 T/T and IL-1RN *2/*2 genotypes were similar. IL-1B -511T/T genotype frequency was significantly higher among patients with gastric cancer (25.0%) than control subjects (12.5%) (chi2=6.7, p=0.01). In the high prevalence region, the frequencies of the IL-1B +3954T/T and -511T/T genotypes and the IL-1RN *2/*2 genotype in the cancer and control groups were similar. IL-1B -31C/C genotype frequency was significantly higher among patients with gastric cancer (90.0%) than controls (78.0%) (chi2=5.0, p=0.025). Compared with the low prevalence region, control subjects from the high prevalence region had a higher frequency of the IL-1B -511T/T genotype (23.0% v 12.5%; chi2=7.0, p<0.008). While H pylori infection alone had only a modest effect on the risk of gastric cancer development (odds ratio (OR) 5.0 (95% confidence interval (CI) 1.5-16.3)), combined with the IL-1B -511T/T genotype the risk was markedly elevated (OR 17.1, 95% CI 3.8-76.4).IL-1B -511T/T genotypes are associated with gastric cancer in China. The effect of IL-1B polymorphism is less obvious in areas of high prevalence for gastric cancer.
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Authors: Christopher P. Cannon, Eugene Braunwald, Carolyn H. McCabe, Daniel J. Rader, Jean L. Rouleau, Rene Belder, Steven V. Joyal, Karen A. Hill, Marc A. Pfeffer, Allan M. Skene
Journal: New England Journal of Medicine (2004)

Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear.We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24).The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan-Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen.Among patients who have recently had an acute coronary syndrome, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.
III. TOLERANCE FOR MERCURY POISONING INCREASED BY FREQUENT HEMOGLOBIN INJECTIONS
Authors: William H. Havill, John A. Lichty, George H. Whipple
Journal: The Journal of Experimental Medicine (1932)

Frequent injections of superthreshold amounts of dog hemoglobin will cause deposits of pigment material in the renal tubular epithelium. When this has happened this dog will survive minimal lethal doses of mercuric chloride with little evidence of renal injury. In fact some dogs will tolerate twice the minimal lethal dose without severe reaction. There is no evidence that continued injections of dog hemoglobin in these amounts will cause any injury or functional disability of the kidney. Rest periods will effect a disappearance of this pigment in the renal tubules.
A study of pulmonary dust deposits using the electron microscope in conjunction with the electron sound analyser
Authors: R. Pariente, J. P. Berry, P. Galle, E. Cayrol, G. Brouet
Journal: Thorax (1972)

Castaing's electronic microsound method has been used to locate mineral particles in lung tissue. Silicon and other minerals were found in the interstitial elastic-type fibres in the lungs of patients with pulmonary fibrosis.
Influence of Adiponectin Gene Polymorphisms on Adiponectin Level and Insulin Resistance Index in Response to Dietary Intervention in Overweight-Obese Patients With Impaired Fasting Glucose or Newly Diagnosed Type 2 Diabetes
Authors: Hye Kyung Chung, Jey Sook Chae, Yae Jung Hyun, Jean Kyung Paik, Ji Young Kim, Yangsoo Jang, Hyuck Moon Kwon, Young Duk Song, Hyun Chul Lee, Jong Ho Lee
Journal: Diabetes Care (2009)

OBJECTIVE The aim of this study was to determine the effect of common adiponectin gene polymorphisms on dietary intervention-mediated changes in adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) indexes. RESEARCH DESIGN AND METHODS A total of 363 subjects with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes followed a dietary intervention (replacement of cooked refined rice with whole grains and an increase in vegetable intake) and regular walking for 12 weeks without any medication. Adiponectin gene single nucleotide polymorphisms (SNPs) (45, 276, and −11377) were examined in these subjects. RESULTS After this dietary intervention, fasting glucose levels decreased in all three SNP 45T&amp;gt;G genotype groups. Subjects with the SNP 45TT genotype showed increased adiponectin levels and decreased HOMA-IR indexes. Haplotype analysis revealed that homozygous carriers of the TG haplotype (45TT and 276GG) and heterozygous carriers of the TG haplotype (TG/X) showed a reduction in the HOMA-IR index after adjustment for baseline levels. Significant differences were observed in changes in HOMA-IR indexes and adiponectin concentrations according to the 45-276 TG haplotype in overweight-obese, but not in normal-weight subjects: the greatest decrease in HOMA-IR indexes and the greatest increase in adiponectin levels were shown in overweight-obese subjects with the TG/TG haplotype. CONCLUSIONS ADIPOQ genetic variants can affect circulating adiponectin levels and insulin resistance indexes in subjects with IFG or newly diagnosed type 2 diabetes in response to dietary intervention.
The Ethos and Ethics of Translational Research
Authors: Jane Maienschein, Mary Sunderland, Rachel A. Ankeny, Jason Scott Robert
Journal: The American Journal of Bioethics (2008)

Abstract Calls for the "translation" of research from bench to bedside are increasingly demanding. What is translation, and why does it matter? We sketch the recent history of outcome-oriented translational research in the United States, with a particular focus on the Roadmap Initiative of the National Institutes of Health (Bethesda, MD). Our main example of contemporary translational research is stem cell research, which has superseded genomics as the translational object of choice. We explore the nature of and obstacles to translational research and assess the ethical and biomedical challenges of embracing a translational ethos. Keywords: Translational sciencehistoryNational Institutes of Healthstem cell research
Myocardial perfusion and function of the systemic right ventricle in patients after atrial switch procedure for complete transposition: long-term follow-up
Authors: Barbara Lubiszewska, Elzbieta Gosiewska, Piotr Hoffman, Anna Teresińska, Jacek Różański, Walerian Piotrowski, Wanda Rydlewska-Sadowska, Krystyna Kubicka, Witold Rużyłło
Journal: Journal of the American College of Cardiology (2000)
T5 The KCa3.1 K+ channel mediates wound healing in human myofibroblasts
Authors: K. M. Roach, W. Coward, C. Feghali-Bostwick, S. M. Duffy, P. Bradding
Journal: Thorax (2011)

Idiopathic pulmonary fibrosis (IPF) is a common progressive interstitial lung disease and current treatments are ineffective. The Ca<sup>2+</sup>-activated K<sup>+</sup> channel K<sub>Ca</sub>3.1 modulates the activity of several structural and inflammatory cells which play important roles in model diseases characterised by tissue remodelling and fibrosis. We hypothesise that K<sub>Ca</sub>3.1-dependent cell processes are a common denominator in IPF. We have therefore examined K<sub>Ca</sub>3.1 expression and function in human myofibroblasts derived from patients with IPF and non-fibrotic controls (NFC). IPF tissue was obtained from diagnostic lung biopsies, and NFC tissue from healthy lung removed at surgery for carcinoma. Myofibroblasts grown in vitro were characterised by Western blot, immunofluorescence and RT-PCR to determine K<sub>Ca</sub>3.1 channel expression. Patch clamp electrophysiology was used to demonstrate functional K<sub>Ca</sub>3.1 channels. Wound healing and proliferation assays were performed using two specific K<sub>Ca</sub>3.1 blockers (TRAM-34, ICA-17043 [Senicapoc]). Both NFC and IPF myofibroblasts expressed K<sub>Ca</sub>3.1 channel mRNA and protein. Using the K<sub>Ca</sub>3.1 channel opener 1-EBIO, K<sub>Ca</sub>3.1 ion currents were elicited in 59% of NFC and 77% of IPF myofibroblasts tested (p=0.0411). These currents were blocked by TRAM-34 (200 nM). The 1-EBIO-induced currents were significantly larger in IPF cells compared to NFC cells (p=0.0124). Basic fibroblast growth factor (bFGF) (10 ng/ml) significantly increased the frequency of K<sub>Ca</sub>3.1 currents across groups (p=0.0046). Similarly bFGF stimulation significantly increased myofibroblast wound healing (p=0.002). Following K<sub>Ca</sub>3.1 blockade bFGF-stimulated wound healing was attenuated dose-dependently. Thus at the 48 h time-point wound healing was reduced by 22.2±11.1% and 27.3±9.5% for TRAM-34, 20 nM and 200 nM respectively (p=0.0467 across groups), and reduced by 16.9±8.1% and 24.4±6.6% for ICA-17043, 10 nM and 100 nM respectively (p=0.0076 across groups). K<sub>Ca</sub>3.1 blockade had no effect on myofibroblast proliferation. We show for the first time that human lung myofibroblasts express the K<sub>Ca</sub>3.1 K<sup>+</sup> channel. K<sub>Ca</sub>3.1 currents are larger and more frequently present in cells from patients with IPF, and functional channel expression is increased by pro-fibrotic growth factors. K<sub>Ca</sub>3.1 inhibition attenuates bFGF stimulated myofibroblast wound healing. These findings raise the possibility that blocking the K<sub>Ca</sub>3.1 channel will inhibit pathological myofibroblast function in IPF, and thus offer a novel approach to IPF therapy.
Glucocorticoids induce beta2-adrenergic receptor function in human nasal mucosa.
Authors: J N Baraniuk, M Ali, D Brody, J Maniscalco, E Gaumond, T Fitzgerald, G Wong, A Yuta, J C Mak, P J Barnes, R Bascom, T Troost
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Glucocorticoids are hypothesized to induce beta2-adrenergic receptors (beta2-R) and their functions. The ability of dexamethasone (DEX) in vitro and beclomethasone dipropionate (BDP) in vivo to induce beta2-R messenger RNA (mRNA) and function was investigated in human nasal mucosa. In this tissue, albuterol does not stimulate exocytosis either in vivo or in vitro (Mullol and coworkers, 1992). Therefore, induction of beta2-R-mediated glandular exocytosis by glucocorticoids was proposed as an unambiguous outcome measure. Human nasal mucosa was cultured for 3 d with and without 1 microM DEX, then challenged with media or 100 microM albuterol. Culture supernatants were collected for measurement of exocytosed glandular products. Explant mRNA was extracted for reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ hybridization of beta2-R mRNA performed. In vivo, normal subjects received saline or BDP for 3 d before albuterol nasal provocation. Concentrations of exocytosed products were measured in nasal secretions. RNA was extracted from nasal epithelial scrapings for RT-PCR. In vitro, DEX treatment induced albuterol-mediated glandular exocytosis (p < 0.04), and increased the steady-state beta2-R/beta-actin mRNA ratio (p < 0.05), and expression of beta2-R mRNA in glands. In vivo, BDP increased the beta2-R/beta-actin mRNA ratio in epithelial scrapings (p < 0.04), but did not induce albuterol-mediated glandular secretion. We conclude that glucocorticoids increase steady-state beta2-R mRNA levels in vivo and in vitro, and can induce beta2-R function as assessed by submucosal gland exocytosis in vitro. While topical BDP induced epithelial beta2-R mRNA, it did not modulate exocytosis from the deeper submucosal glands.
Vesico-Vaginal and Recto-Vaginal Fistulae
Authors: J Kelly
Journal: Journal of the Royal Society of Medicine (1992)

A personal series of 716 patients with vesico-vaginal and/or recto-vaginal fistulae is presented. Five hundred and seventy-eight patients were managed in Africa, mainly at the Addis Ababa Fistula Hospital, while 138 were kindly referred to me from various parts of Britain. The main cause of such fistulae in the developing world is pressure necrosis from obstructed labour. In the developed world the aetiology is surgery, malignancy, radiotherapy or a combination of these. Other causes include neglected foreign bodies, coital injury and local treatment by an unqualified practitioner. A vesico-vaginal fistula alone was present in 78.8%, a recto-vaginal fistula alone in 4.3%, while 16.9% of patients had both a vesico-vaginal and a recto-vaginal fistula. Six hundred and six (84.6%) patients were cured at the first attempt at repair, 45 (6.3%) failed and 65 (9.1%) had stress incontinence.
A Pluralistic Account of Homology: Adapting the Models to the Data
Authors: Leanne S. Haggerty, Pierre-Alain Jachiet, William P. Hanage, David A. Fitzpatrick, Philippe Lopez, Mary J. O’Connell, Davide Pisani, Mark Wilkinson, Eric Bapteste, James O. McInerney
Journal: Molecular Biology and Evolution (2013)

Defining homologous genes is important in many evolutionary studies but raises obvious issues. Some of these issues are conceptual and stem from our assumptions of how a gene evolves, others are practical, and depend on the algorithmic decisions implemented in existing software. Therefore, to make progress in the study of homology, both ontological and epistemological questions must be considered. In particular, defining homologous genes cannot be solely addressed under the classic assumptions of strong tree thinking, according to which genes evolve in a strictly tree-like fashion of vertical descent and divergence and the problems of homology detection are primarily methodological. Gene homology could also be considered under a different perspective where genes evolve as "public goods," subjected to various introgressive processes. In this latter case, defining homologous genes becomes a matter of designing models suited to the actual complexity of the data and how such complexity arises, rather than trying to fit genetic data to some a priori tree-like evolutionary model, a practice that inevitably results in the loss of much information. Here we show how important aspects of the problems raised by homology detection methods can be overcome when even more fundamental roots of these problems are addressed by analyzing public goods thinking evolutionary processes through which genes have frequently originated. This kind of thinking acknowledges distinct types of homologs, characterized by distinct patterns, in phylogenetic and nonphylogenetic unrooted or multirooted networks. In addition, we define "family resemblances" to include genes that are related through intermediate relatives, thereby placing notions of homology in the broader context of evolutionary relationships. We conclude by presenting some payoffs of adopting such a pluralistic account of homology and family relationship, which expands the scope of evolutionary analyses beyond the traditional, yet relatively narrow focus allowed by a strong tree-thinking view on gene evolution.