tbuckley/cabot-search huggingface dataset:
Genome-Wide Analyses of Recombination Suggest That Giardia intestinalis Assemblages Represent Different Species
Authors: F. Xu, J. Jerlstrom-Hultqvist, J. O. Andersson
Journal: Molecular Biology and Evolution (2012)

Giardia intestinalis is a major cause of waterborne enteric disease in humans. The species is divided into eight assemblages suggested to represent separate Giardia species based on host specificities and the genetic divergence of marker genes. We have investigated whether genome-wide recombination occurs between assemblages using the three available G. intestinalis genomes. First, the relative nonsynonymous substitution rates of the homologs were compared for 4,009 positional homologs. The vast majority of these comparisons indicate genetic isolation without interassemblage recombinations. Only a region of 6 kbp suggests genetic exchange between assemblages A and E, followed by gene conversion events. Second, recombination-detecting software fails to identify within-gene recombination between the different assemblages for most of the homologs. Our results indicate very low frequency of recombination between the syntenic core genes, suggesting that G. intestinalis assemblages are genetically isolated lineages and thus should be viewed as separated Giardia species.
pH dependence of acid secretion and gastrin release in normal and ulcer subjects.
Authors: J H Walsh, C T Richardson, J S Fordtran
Journal: Journal of Clinical Investigation (1975)

By use of a recently described method, which estimates the rate of gastric acid secretion by measuring the rate of sodium bicarbonate infusion needed to keep intragastric pH constant, gastric acid secretion rates and changes in serum gastrin were measured in five normal subjects while gastric pH was kept at 5.5, 4.0, 3.0, or 2.5. Preliminary experiments revealed that the method did not accurately measure acid secretion at a pH lower than 2.5. Stimulation of acid secretion was produced by gastric instillation of a solution of amino acids and cornstarch. The secretion rate with the amino acid meal was highest at pH 5.5 and was 60% of that produced by a steak meal at the same pH. As the pH of the amino acid meal was decreased, there was a stepwise reduction in acid secretion so that at pH 2.5 the rate was only half as great as at pH 5.5. The amino acid meal produced increases in serum gastrin that were also less marked than those produced by a steak meal. With amino acid stimulation, serum gastrin responses were similar at pH 5.5, 4.0, and 3.0, but no increase in gastrin could be measured when the meal was maintained at pH 2.5. A group of six patients with duodenal ulcers was compared with seven normal subjects at pH 5.5 and 2.5. Ulcer patients released more gastrin and secreted more acid at each time period at both pH values. More important, the degree of inhibition at pH 2.5 was significantly less in ulcer patients. For example, during the 2nd h after stimulation acid secretion was inhibited by only 30% in ulcer patients compared with 70% in normal subjects. These findings suggest a defect in autoregulation of gastrin release and gastric acid secretion at low pH in ulcer patients which may play a role in pathogenesis of this disease.
A mutation in the gene encoding the α2 chain of the fibril-associated collagen IX, COL9A2, causes multiple epiphyseal dysplasia (EDM2)
Authors: Yasuteru Muragaki, Edwin C.M. Mariman, Sylvia E.C. van Beersum, Merja Perälä, Jan B.A. van Mourik, Matthew L. Warman, Bjorn R. Olsen, Ben C.J. Hamel
Journal: Nature Genetics (1996)
Protein biomarkers in cystic fibrosis research: where next?
Authors: Sally H Pattison, J Stuart Elborn
Journal: Genome Medicine (2010)

Cystic fibrosis is one of the most common life-limiting inherited disorders. Its clinical impact manifests chiefly in the lung, pancreas, gastrointestinal tract and sweat glands, with lung disease typically being most detrimental to health. The median age for survival has increased dramatically over the past decades, largely thanks to advances in understanding of the mechanisms and consequences of disease, leading to the development of better therapies and treatment regimes. The discovery of dysregulated protein biomarkers linked to cystic fibrosis has contributed considerably to this end. This article outlines clinical trials targeting known protein biomarkers, and the current and future contributions of proteomic techniques to cystic fibrosis research. The treatments described range from those designed to provide functional copies of the mutant protein responsible for cystic fibrosis, to others addressing the associated symptoms of chronic inflammation. Preclinical research has employed proteomics to help elucidate pathways and processes implicated in disease that might present opportunities for therapy or prognosis. Global analyses of cystic fibrosis have detected the differential expression of proteins involved in inflammation, proteolytic activity and oxidative stress, which are recognized symptoms of the cystic fibrosis phenotype. The dysregulation of other processes, such as the complement and mitochondrial systems, has also been implicated. A number of studies have focused specifically on proteins that interact with the cystic fibrosis protein, with the goal of restoring its normal proteostasis. Consequently, proteins involved in synthesis, folding, degradation, translocation and localization of the protein have been identified as potential therapeutic targets. Cystic fibrosis patients are prone to lung infections that are thought to contribute to chronic inflammation, and thus proteomic studies have also searched for microbiological biomarkers to use in early infection diagnosis or as indicators of virulence. The review concludes by proposing a future role for proteomics in the high-throughput validation of protein biomarkers under consideration as outcome measures for use in clinical trials and routine disease monitoring.
Risk analysis of severe myelotoxicity with temozolomide: The effects of clinical and genetic factors
Authors: Terri S. Armstrong, Yumei Cao, Michael E. Scheurer, Elizabeth Vera-Bolaños, Rochelle Manning, Mehmet F. Okcu, Melissa Bondy, Renke Zhou, Mark R. Gilbert
Journal: Neuro-Oncology (2009)

A benefit of temozolomide (TMZ) is that myelotoxicity is uncommon. Recently, several small series have reported significant myelotoxicity resulting in treatment delays or death. The ability to predict risk of myelotoxicity may influence patient care. We retrospectively reviewed 680 malignant glioma patients and developed a clinical risk formula for myelotoxicity for each gender by logistic regression. The variables that remained were assigned a score of 1 and added together for a final risk score. Women experienced more myelotoxicity than did men (p = 0.015). For males, risk factors included body surface area (BSA) > or = 2 m(2) (odds ratio [OR] = 2.712, p = 0.04), not on steroids (OR = 2.214, p = 0.06), and on bowel medication (OR = 3.955, p = 0.008). For females, final factors included no prior chemotherapy (OR = 3.727, p = 0.001), creatinine > or = 1 mg/dl (OR = 6.08, p = 0.002), platelets < 270,000/mm(3) (OR = 2.438, p = 0.03), BSA < 2 m(2) (OR = 4.178, p = 0.04), not on medication for gastroesophageal reflux disease (OR = 2.942, p = 0.01), and on analgesics (OR = 2.169, p = 0.05). Age was included because of observable trends. Risk of developing myelotoxicity ranged from 0% to 33% (male) and from 0% to 100% (females). Polymorphisms in NQO1 (NAD(P)H dehydrogenase, quinone 1), MGMT (O(6)-methylguanine-DNA methyltransferase), and GSTP1 (glutathione S-transferase pi 1) were related to risk of developing myelotoxicity in a subset of patients. Myelotoxicity with TMZ is a significant clinical issue for those at risk. Use of a clinical model to predict risk and evaluation of identified genetic polymorphisms related to myelotoxicity may allow for individualized dosing, optimizing patient management.
Doppler-derived rate of left ventricular pressure rise. Its correlation with the postoperative left ventricular function in mitral regurgitation.
Authors: R G Pai, R C Bansal, P M Shah
Journal: Circulation (1990)

A new Doppler-derived index of the rate of left ventricular (LV) pressure rise (delta P/delta t) was evaluated for the prognostic stratification of patients with chronic mitral regurgitation. The index is derived from the continuous wave Doppler mitral regurgitation signal by dividing magnitude of LV-left atrial pressure gradient rise (delta p) between 1 and 3 m/sec of the mitral regurgitation velocity signal by the time taken (delta t) for this change. We studied the LV delta P/delta t and other echocardiographic indexes of LV function before and after mitral valve surgery in 25 patients with chronic, severe mitral regurgitation in the absence of significant coronary artery disease. There was a good correlation between postoperative ejection fraction (EF) and the derived LV delta P/delta t (r = 0.75, p less than 0.001). The other echocardiographic parameters that correlated with postoperative EF were LV end-systolic dimension (r = -0.7, p less than 0.001), end-systolic volume (r = -0.69, p less than 0.001), end-diastolic dimension (r = -0.58, p less than 0.01), end-diastolic volume (r = -0.57, p less than 0.01), preoperative EF (r = 0.69, p less than 0.001), end-systolic wall stress (r = -0.61, p less than 0.01), and end-systolic wall stress normalized for end-systolic volume index (r = -0.45, p less than 0.05). With multiple regression, the LV delta P/delta t and LV end-systolic dimension (ESD) were shown to be independent predictors of postoperative EF. The postoperative EF could defined by the equation: 43 + 0.8 square root delta P/delta t--0.53 ESD (mm) (r = 0.86).(ABSTRACT TRUNCATED AT 250 WORDS)
Recommended Guidelines for Uniform Reporting of Pediatric Advanced Life Support: The Pediatric Utstein Style
Authors: Arno Zaritsky, Vinay Nadkarni, Mary Fran Hazinski, George Foltin, Linda Quan, Jean Wright, Debra Fiser, David Zideman, Patricia O’Malley, Leon Chameides, Richard O. Cummins
Journal: Circulation (1995)

This consensus document is an attempt to provide an organized method of reporting pediatric ALS data in out-of-hospital, emergency department, and in-hospital settings. For this methodology to gain wide acceptance, the task force encourages development of a common data set for both adult and pediatric ALS interventions. In addition, every effort should be made to ensure that consistent definitions are used in all age groups. As health care changes, we will all be challenged to document the effectiveness of what we currently do and show how new interventions or methods of treatment improve outcome and/or reduce cost. Only through collaborative research will we obtain the necessary data. For these reasons, and to improve the quality of care and patient outcomes, it is the hope of the task force that clinical researchers will follow the recommendations in this document. It is recognized that further refinements of this statement will be needed; these recommendations will improve only when researchers, clinicians, and EMS personnel use them, work with them, and modify them. Suggestions, recommendations, and other comments aimed at improving the reporting of pediatric resuscitation should be sent to Arno Zaritsky, MD, Eastern Virginia Medical School, Children's Hospital of The King's Daughter, Division of Critical Care Medicine, 601 Children's Lane, Norfolk, VA 23507.
STUDIES OF DIABETES IN A COMMUNITY POPULATION
Authors: Elliott P. Joslin
Journal: JAMA (1962)

In 1946-1947, Wilkerson and Krall<sup>1</sup>of the U.S. Public Health Service carried out the first sizable community study of the prevalence of diabetes as manifested by blood and urine sugar studies. The original survey found that while there were 40 known cases of diabetes in the 3,516 persons studied from the entire 4,983 inhabitants in Oxford, Mass., there were also 30 newly discovered cases. This indicated a prevalence of 2.0 per cent of those tested, or a projected 1.7 per cent of the entire population of the town, and was one of the factors that suggested the probability of "1,000,000 unknown diabetics" in the United States. The serial observations and comprehensive physical examinations have continued through the years, and the most recent report (fourth of the series) published in this issue ofThe Journal(p. 652) indicates that 36 of the original 70 have now died. Thirty-two of these
Patterns of Reproductive Isolation in<i>Eucalyptus—</i>A Phylogenetic Perspective
Authors: Matthew J. Larcombe, Barbara Holland, Dorothy A. Steane, Rebecca C. Jones, Dean Nicolle, René E. Vaillancourt, Brad M. Potts
Journal: Molecular Biology and Evolution (2015)

We assess phylogenetic patterns of hybridization in the speciose, ecologically and economically important genus Eucalyptus, in order to better understand the evolution of reproductive isolation. Eucalyptus globulus pollen was applied to 99 eucalypt species, mainly from the large commercially important subgenus, Symphyomyrtus. In the 64 species that produce seeds, hybrid compatibility was assessed at two stages, hybrid-production (at approximately 1 month) and hybrid-survival (at 9 months), and compared with phylogenies based on 8,350 genome-wide DArT (diversity arrays technology) markers. Model fitting was used to assess the relationship between compatibility and genetic distance, and whether or not the strength of incompatibility "snowballs" with divergence. There was a decline in compatibility with increasing genetic distance between species. Hybridization was common within two closely related clades (one including E. globulus), but rare between E. globulus and species in two phylogenetically distant clades. Of three alternative models tested (linear, slowdown, and snowball), we found consistent support for a snowball model, indicating that the strength of incompatibility accelerates relative to genetic distance. Although we can only speculate about the genetic basis of this pattern, it is consistent with a Dobzhansky-Muller-model prediction that incompatibilities should snowball with divergence due to negative epistasis. Different rates of compatibility decline in the hybrid-production and hybrid-survival measures suggest that early-acting postmating barriers developed first and are stronger than later-acting barriers. We estimated that complete reproductive isolation can take up to 21-31 My in Eucalyptus. Practical implications for hybrid eucalypt breeding and genetic risk assessment in Australia are discussed.
THE PRODUCTION OF CHRONIC GLOMERULONEPHRITIS IN RATS BY THE INJECTION OF RABBIT ANTI-RAT-PLACENTA SERUM
Authors: Beatrice Carrier Seegal, Emily Nichols Loeb
Journal: The Journal of Experimental Medicine (1946)

1. The injection of rabbit anti-rat-placenta serums in young adult rats produced chronic glomerulonephritis in 18 of 32 animals. 2. The course of the nephritis and the renal lesions were indistinguishable from those obtained in 11 of 13 animals injected with rabbit anti-rat-kidney serum. 3. Six instances of similar renal lesions occurred among 99 control animals. In 2 the rats had been injected with rabbit anti-rat-erythrocyte serum, in 2 with rabbit anti-rat-serum serum, while in 2 others the lesions were found among normal stock.
Methods of separation and in-vitro culture of pre-antral follicles from mammalian ovaries
Authors: S. Roy
Journal: Human Reproduction Update (1996)

A variety of procedures to isolate intact pre-antral follicles have been developed in our laboratories based on different concentrations of collagenase and DNase in a simple salt solution containing glucose as an energy substrate. The enzyme mixture effectively separates follicles of different sizes derived from ovaries of hamster, mouse, rat, pig and human. While no damage of the basal lamina is apparent for the hamster and human follicles, some loss is present in the other species. Follicles were classified into several stages or classes based on their diameter, the number of granulosa cell layers and the presence of an antral cavity. Pre-antral hamster and human follicles cultured in the presence of follicle stimulating hormone for up to 168 h developed an antral cavity with intact germinal vesicle oocytes.
Phase I Trial Design for Solid Tumor Studies of Targeted, Non-Cytotoxic Agents: Theory and Practice
Authors: W. R. Parulekar, E. A. Eisenhauer
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: New targeted, non-cytotoxic anticancer agents, such as small-molecule kinase inhibitors, pose challenges to the current phase I paradigm of dose selection based on toxicity. Moreover, increasing the drug dose to toxicity may be unnecessary for drug effect, making the use of maximum tolerated dose as a surrogate of effective dose inappropriate in the phase I setting. Because little is known about the optimal methods of recommended phase II dose selection of targeted, non-cytotoxic therapies, we reviewed the strategies that were used in completed phase I studies of these drugs. Methods: We retrieved 60 publications of phase I studies involving 31 single agents representative of the most common targets of interest in the oncology literature. For each publication, we abstracted data regarding patient population, starting dose, methods of dose escalation and determination of recommended phase II dose, and inclusion of correlative studies in study conduct. Results: Of the 60 completed phase I studies, 36 used toxicity and eight used pharmacokinetic data as endpoints for selection of the recommended phase II dose. Nontraditional endpoints, such as measures of molecular drug effects in tumor or surrogate tissue or functional imaging studies, were not routinely incorporated into the study design and rarely formed the primary basis for dose selection. Conclusions: To date, phase I studies of targeted anticancer agents have generally used traditional endpoints for selection of the recommended phase II dose. More research is needed to define suitable molecular measures of drug effect and the means to incorporate them in the early drug development process.
Effects of air pollution on the respiratory health of asthmatic children living in Mexico City.
Authors: I Romieu, F Meneses, S Ruiz, J J Sienra, J Huerta, M C White, R A Etzel
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The relation between air pollution and the exacerbation of childhood asthma was studied in a panel of 71 children (aged 5 to 7 yr) with mild asthma who resided in the northern part of mexico City. During the follow-up, ambient measures of particulate matter less than 10 microns (PM10, 24-h average) and ozone (1-h maximum) frequently exceeded the Mexican standards for these contaminants. The peak expiratory flow rate (PEFR) was strongly associated with PM10 levels and marginally with ozone levels. Respiratory symptoms (coughing, phlegm production, wheezing, and difficulty breathing) were associated with both PM10 and ozone levels. An increase of 20 micrograms/m3 of PM10 was related to an 8% increase in lower respiratory illness (LRI) among children on the same day (95% confidence interval [CI] = 1.04-1.15), and an increase of 10 micrograms/m3 in the weekly mean of particulate matter less than 2.5 microns (PM2.5) was related to a 21% increase in LRI (95% CI = 1.08-1.35). A 50 parts per billion (ppb) increase in ozone was associated with a 9% increase in LRI (95% CI = 1.03-1.15) on the same day. We concluded that children with mild asthma are affected by the high ambient levels of particulate matter and ozone observed in the northern part of Mexico City.
Antifibrotic Effect of Tamoxifen in a Model of Progressive Renal Disease
Authors: Humberto Dellê, José Roberto C. Rocha, Rita C. Cavaglieri, José Mauro Vieira, Denise M.A.C. Malheiros, Irene L. Noronha
Journal: Journal of the American Society of Nephrology (2011)

Tamoxifen, a selective estrogen receptor modulator, has antifibrotic properties; however, whether it can attenuate renal fibrosis is unknown. In this study, we tested the effects of tamoxifen in a model of hypertensive nephrosclerosis (chronic inhibition of nitric oxide synthesis with L-NAME). After 30 days, treated rats had significantly lower levels of albuminuria as well as lower histologic scores for glomerulosclerosis and interstitial fibrosis than untreated controls. Tamoxifen was renoprotective despite having no effect on the sustained, severe hypertension induced by L-NAME. Tamoxifen prevented the accumulation of extracellular matrix by decreasing the expression of collagen I, collagen III, and fibronectin mRNA and protein. These renoprotective effects associated with inhibition of TGF-β1 and plasminogen activator inhibitor-1, and with a significant reduction in α-smooth muscle actin-positive cells in the renal interstitium. Furthermore, tamoxifen abrogated IL-1β- and angiotensin-II-induced proliferation of fibroblasts from both kidney explants and from the NRK-49F cell line. Tamoxifen also inhibited the expression of extracellular matrix components and the production and release of TGF-β1 into the supernatant of these cells. In summary, tamoxifen exhibits antifibrotic effects in the L-NAME model of hypertensive nephrosclerosis, likely through the inhibition of TGF-β1, suggesting that it may have therapeutic use in CKD treatment.
Effect of abiraterone acetate on fatigue in patients with metastatic castration-resistant prostate cancer after docetaxel chemotherapy
Authors: C.N. Sternberg, A. Molina, S. North, P. Mainwaring, K. Fizazi, Y. Hao, M. Rothman, D.D. Gagnon, T. Kheoh, C.M. Haqq, C. Cleeland, J.S. de Bono, H.I. Scher
Journal: Annals of Oncology (2012)
Role of Fructose-Containing Sugars in the Epidemics of Obesity and Metabolic Syndrome
Authors: Kimber L. Stanhope
Journal: Annual Review of Medicine (2011)

There is controversy concerning the role of sugar in the epidemics of obesity and metabolic syndrome. There is less controversy concerning the effects of fructose on components of metabolic syndrome; consumption of fructose has been shown to increase visceral adipose deposition and de novo lipogenesis (DNL), produce dyslipidemia, and decrease insulin sensitivity in older, overweight/obese subjects. This review examines the potential mechanisms of these effects of fructose and considers whether these mechanisms are relevant to the effects of consuming sucrose or high-fructose corn syrup. Evidence demonstrating that the commonly consumed sugars increase visceral adipose deposition, DNL, and insulin insensitivity is limited or inconclusive. Evidence that sugar consumption promotes development of an unfavorable lipid profile is strong and suggests that the upper added sugar consumption limit of 25% of energy or less, suggested in the Report of the Dietary Guidelines Advisory Committee on the Dietary Guidelines for Americans 2010, may merit re-evaluation.
The effect of anti-mu suppression of gammaM and gammaG on the production of gammaE.
Authors: J M Dwyer, J T Rosenbaum, S Lewis
Journal: The Journal of Experimental Medicine (1976)

Newbonr mice were treated from the day of birth with either bovine gamma globulin or anti-mu chain sera. The latter was administered using a protocol known to produce suppression of gammaM, gammaG, and gammaA production. Subsequent immunization with ovalbumin (OA) in alum was attempted to see if suppression of gammaM, gammaG, and gammaA classes of antibody would also be accompanied by suppression of gammaE-producing capacity. gammaG and gammaM antibody to OA and mercaptoethanol-resistant (gammaG) antibody to OA were measured by passive hemagglutination; gammaG and gammaE anti-OA antibodies were measured by passive cutaneous anaphylaxis. Anti-mu suppression was achieved with significant reduction in gammaM and gammaG antibodies. gammaE antibodies were not affected, suggesting an ontogenetic development for gammaE-bearing lymphocytes independent of the previously described gammaM to gammaG to gammaA ontogenetic sequence.