tbuckley/cabot-search huggingface dataset:
Impact of Hysterectomy on Endometrial Carcinoma Rates in the United States
Authors: Mark E. Sherman, Joseph D. Carreon, James V. Lacey, Susan S. Devesa
Journal: JNCI Journal of the National Cancer Institute (2005)

In the United States, endometrial carcinoma incidence rates, uncorrected for hysterectomy prevalence, are higher among white women than black women. We estimated corrected endometrial carcinoma rates by racial/ethnic groups and age (30-74 years) for 1992-2000 using data from the Surveillance, Epidemiology, and End Results program and the Behavioral Risk Factor Surveillance Survey. Hysterectomy prevalence was higher among black women than among Hispanic and white non-Hispanic women. Correcting for hysterectomy prevalence increased age-adjusted endometrial carcinoma rates per 10(5) woman-years from 29.2 to 48.7 (66.8% increase) overall, from 14.6 to 28.5 (95.3% increase) in blacks, from 18.8 to 29.6 (57.6% increase) in Hispanics, and from 33.2 to 54.9 (65.1%) in white non-Hispanics. This correction reduced the rate ratio for white non-Hispanics compared with blacks from 2.27 to 1.93. Among blacks but not Hispanics or white non-Hispanics, the endometrial carcinoma risk factors of obesity and diabetes were more prevalent among hysterectomized than nonhysterectomized women. Failure to correct for hysterectomy prevalence may lead to underestimates of endometrial carcinoma risk, especially among blacks. The high prevalence of hysterectomy among blacks with strong endometrial cancer risk factors may partly account for lower cancer rates in this group.
2,4,6-Trihydroxybenzoic Acid in the Treatment of Rheumatic Fever
Authors: E. B. D. Hamilton, E. G. L. Bywaters
Journal: Annals of the Rheumatic Diseases (1960)

Clarke, Clarke, and Mosher (1958) have recently reported on the therapeutic action of 2,3,6-and 2,4,6-trihydroxybenzoic acid (THB) in twelve patients with rheumatic fever and eleven others.The latter compound, usually in a dosage of 1 to 1 33 g./24 hrs, was believed to have a clinical anti- rheumatic potency six to eight times that of salicylic acid and no toxicity.We have found it to have no anti-rheumatic potency in classical rheumatic fever, judged by pain and temperature response in three patients receiving doses varying from 1 to 8 g./24 hrs, whereas calcium aspirin (Disprin) in a dosage of about 4 g./24 hrs was dramatically effective in the same three patients (Figure).
High-Dose Versus Standard Chemotherapy in Metastatic Breast Cancer: Comparison of Cancer and Leukemia Group B Trials With Data From the Autologous Blood and Marrow Transplant Registry
Authors: Donald A. Berry, Gloria Broadwater, John P. Klein, Karen Antman, Joseph Aisner, Jacob Bitran, Mary E. Costanza, Cesar O. Freytes, Edward Stadtmauer, Robert Peter Gale, I. Craig Henderson, Hillard M. Lazarus, Philip L. McCarthy Jr., Larry Norton, Howard Parnes, Andrew Pecora, Michael C. Perry, Philip Rowlings, Gary Spitzer, Mary M. Horowitz
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess survival of patients with metastatic breast cancer treated with high-dose chemotherapy (HDC) versus standard-dose chemotherapy (SDC). PATIENTS AND METHODS: SDC in four Cancer and Leukemia Group B (CALGB) trials was compared with hematopoietic stem-cell support in patients from the Autologous Blood and Marrow Transplant Registry. Cox proportional hazard regression incorporated potentially confounding effects. A total of 1,509 women were enrolled onto CALGB trials, and 1,188 women received HDC. No significant survival differences existed by CALGB trial or HDC regimen. Consideration was restricted to candidates for both SDC and HDC. The resulting sample included 635 SDC and 441 HDC patients. The outcome of interest was overall survival. RESULTS: The HDC group displayed better performance status. The SDC group had slightly better survival in first year after treatment. The HDC group had lower hazard of death from years 1 to 4 and had somewhat higher probability of 5-year survival (adjusted probabilities [95% confidence intervals], 23% [17% to 29%] v 15% [11% to 19%], P = .03). CONCLUSION: After controlling for known prognostic factors in this nonrandomized analysis of two large independent data sets, women receiving HDC versus SDC for metastatic breast cancer have a similar short-term probability of survival, and might have a modestly higher long-term probability of survival.
The Effect of Inotropic Drugs on Filling of the Isolated Right Ventricle of the Dog Heart
Authors: N. M. BUCKLEY, ERIC OGDEN, R. C. McPHERSON
Journal: Circulation Research (1955)

Selected inotropic drugs were studied in an isolated right ventricle preparation in which the work load and heart rate could be controlled. Records of ventricular pressure and volume were made. Rate of ventricular relaxation was estimated, and mechanical impedance to inflow was calculated as the ratio of intraventricular pressure to inflow. The negatively inotropic drugs slowed relaxation and increased impedance. Strophanthin-K reversed these effects. Adrenalin decreased impedance. It is concluded that, during the filling period, inotropic drugs alter those physical properties of ventricle wall which contribute to mechanical impedance.
Letter in response to Tashkin<i>et al</i>: limited generalisability of uplift findings to clinical practice
Authors: Steven Walker, James Fingleton, Mark Weatherall, Richard Beasley
Journal: Thorax (2013)

We appreciate the comments made by Tashkin et al 1 regarding the limited generalisability of the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) findings.2 In response, the sample we studied was not designed to be representative of the general chronic obstructive pulmonary disease (COPD) population, but rather the subgroup of patients with severe COPD who are likely to be at greatest risk of serious cardiovascular events. Second, the derived data presented from the …
Abdominal Adiposity Is a Stronger Predictor of Insulin Resistance Than Fitness Among 50–95 Year Olds
Authors: Susan B. Racette, Ellen M. Evans, Edward P. Weiss, James M. Hagberg, John O. Holloszy
Journal: Diabetes Care (2006)

OBJECTIVE—Physical inactivity and increased adiposity contribute to insulin resistance; less is known, however, about the relative contributions of these factors in older adults. The aim of this study was to determine whether cardiovascular fitness, whole-body adiposity, or abdominal adiposity is the strongest predictor of insulin resistance into old age. RESEARCH DESIGN AND METHODS—Subjects included 407 men and women aged 50–95 years (means ± SD 69 ± 11 years). Insulin resistance was estimated using the insulin sensitivity index (ISI) of Matsuda and DeFronzo [ISI = 10,000/square root of (fasting glucose × fasting insulin) × (mean glucose × mean insulin during an oral glucose tolerance test); lower ISI = greater insulin resistance]. Fitness was determined with a treadmill maximal oxygen consumption (Vo2max) test. Whole-body adiposity measures included BMI and percent fat by dual-energy X-ray absorptiometry or hydrodensitometry; abdominal adiposity was estimated by waist circumference. RESULTS—Waist circumference was the strongest independent correlate of ISI (r = −0.52, P &amp;lt; 0.0001), explaining 28% of the variance when controlling for sex, BMI, percent fat, and Vo2max. BMI (r = −0.45), percent fat (r = −0.40), and Vo2max (r = 0.22) independently predicted ISI (all P &amp;lt; 0.0001); however, after controlling for waist circumference, only Vo2max remained significant (r = 0.13, P = 0.009). CONCLUSIONS—Adiposity and fitness continue to be significant predictors of insulin sensitivity into old age, with abdominal obesity being the most important single factor. These findings support the measurement of waist circumference to assess health risk among older adults.
THE FATE OF BACTERIA WITHIN PHAGOCYTIC CELLS
Authors: Zanvil A. Cohn
Journal: The Journal of Experimental Medicine (1963)

The intraleucocytic fate of a variety of P32- and C14-labeled bacteria has been studied in both polymorphonuclear leucocytes and macrophages. Both cell types brought about extensive degradation of bacterial lipids, nucleic acids, and proteins. Intracellular breakdown was primarily dependant upon the composition of the ingested particle rather than on the type or source of the phagocyte. Evidence is presented for the reincorporation of bacterial constituents into leucocyte lipid. More than 50 per cent of the acid-soluble degradation products of P32-labeled bacteria appear as inorganic phosphate. Bacterial RNA is degraded more readily than DNA. Following phagocytosis, labeled bacteria lose their pool of small molecular weight intermediates. This is followed by the degradation of acid-insoluble constituents. The majority of bacterial breakdown products are then excreted by the leucocyte and appear in the medium. Heat-killed bacteria were more readily broken down than viable organisms. Only small amounts of C14-labeled bacteria were completely oxidized by leucocytic enzymes to C14O2. Acid extracts of polymorphonuclear leucocyte granules, which were highly bactericidal, liberated the acid-soluble constituents of labeled bacteria but did not significantly degrade bacterial macromolecules.
Melanocytic nevi excised during B-Raf proto-oncogene (BRAF) inhibitor therapy: A study of 19 lesions from 10 patients
Authors: Mark C. Mochel, Marc R. Hammond, Dennie T. Frederick, Maria B. Alora-Palli, Adriano Piris, Keith T. Flaherty, Mai P. Hoang
Journal: Journal of the American Academy of Dermatology (2015)
A patient-derived and patient-reported outcome measure for assessing psoriatic arthritis: elaboration and preliminary validation of the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, a 13-country EULAR initiative
Authors: Laure Gossec, Maarten de Wit, Uta Kiltz, Juergen Braun, Umut Kalyoncu, Rossana Scrivo, Mara Maccarone, Laurence Carton, Kati Otsa, Imre Sooäär, Turid Heiberg, Heidi Bertheussen, Juan D Cañete, Anselm Sánchez Lombarte, Andra Balanescu, Alina Dinte, Kurt de Vlam, Josef S Smolen, Tanja Stamm, Dora Niedermayer, Gabor Békés, Douglas Veale, Philip Helliwell, Andrew Parkinson, Thomas Luger, Tore K Kvien
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Introduction</h3> The objective was to develop a questionnaire that can be used to calculate a score reflecting the impact of psoriatic arthritis (PsA) from the patients' perspective: the PsA Impact of Disease (PsAID) questionnaire. <h3>Methods</h3> Twelve patient research partners identified important domains (areas of health); 139 patients prioritised them according to importance. Numeric rating scale (NRS) questions were developed, one for each domain. To combine the domains into a single score, relative weights were determined based on the relative importance given by 474 patients with PsA. An international cross-sectional and longitudinal validation study was performed in 13 countries to examine correlations of the PsAID score with other PsA or generic disease measures. Test–retest reliability and responsiveness (3 months after a treatment change) were examined in two subsets of patients. <h3>Results</h3> Two PsAID questionnaires were developed with both physical and psychological domains: one for clinical practice (12 domains of health) and one for clinical trials (nine domains). Pain, fatigue and skin problems had the highest relative importance. The PsAID scores correlated well with patient global assessment (N=474, Spearman r=0.82–0.84), reliability was high in stable patients (N=88, intraclass correlation coefficient=0.94–0.95), and sensitivity to change was also acceptable (N=71, standardised response mean=0.90–0.91). <h3>Conclusions</h3> A questionnaire to assess the impact of PsA on patients' lives has been developed and validated. Two versions of the questionnaire are available, one for clinical practice (PsAID-12) and one for clinical trials (PsAID-9). The PsAID questionnaires should allow better assessment of the patient9s perspective in PsA. Further validation is needed.
A Phase I Trial of LY2510924, a CXCR4 Peptide Antagonist, in Patients with Advanced Cancer
Authors: Matthew D. Galsky, Nicholas J. Vogelzang, Paul Conkling, Eyas Raddad, John Polzer, Stephanie Roberson, John R. Stille, Mansoor Saleh, Donald Thornton
Journal: Clinical Cancer Research (2014)

Overexpression of C-X-C motif receptor 4 (CXCR4) is implicated in tumor progression. LY2510924 is a peptide antagonist, which blocks stromal cell-derived factor-1 (SDF1) from CXCR4 binding.This phase I study included two parts: a 3+3 dose escalation (part A) and dose confirmation (part B). LY2510924 was administered as a daily subcutaneous injection on a 28-day cycle. The primary objective was to determine the recommended phase II dose. Secondary objectives included safety, pharmacokinetics, efficacy, and pharmacodynamic response, including mobilization of CD34(+) hematopoietic stem cells into the peripheral blood.Forty-five patients were enrolled, 25 in part A and 20 in part B. Patients were administered increasing doses of LY2510924: 1.0, 2.5, 5.0, 10, 20, and 30 mg/day for part A and 2.5 or 20 mg/day for part B. Two patients (30-mg/day cohort) experienced dose-limiting toxicities of grade 3 increased neutrophil count. The maximum tolerated dose (MTD) was 20 mg/day. The most common drug-related treatment-emergent adverse events were fatigue (9%), injection-site reaction (9%), injection site pruritus (7%), and nausea (7%). The best response was stable disease for nine patients (20%). At the end of cycle 1, mean peak LY2510924 plasma concentration and the 24-hour area under the plasma concentration versus time curve increased slightly more than dose proportionally. LY2510924 dose dependently increased CD34(+) cell counts in peripheral blood up to 18-fold.LY2510924 demonstrated CD34(+) cell mobilization at doses ≥2.5 mg/day with a tolerable safety profile up to an MTD of 20 mg/day.
Treating Rheumatoid Arthritis to Target: multinational recommendations assessment questionnaire
Authors: B. Haraoui, J. S. Smolen, D. Aletaha, F. C. Breedveld, G. Burmester, C. Codreanu, J. P. Da Silva, M. de Wit, M. Dougados, P. Durez, P. Emery, J. E. Fonseca, A. Gibofsky, J. Gomez-Reino, W. Graninger, V. Hamuryudan, M. J. Jannaut Pe{eta with perispomeni}a, J. Kalden, T. K. Kvien, I. Laurindo, E. Martin-Mola, C. Montecucco, P. Santos Moreno, K. Pavelka, G. Poor, M. H. Cardiel, E. Stanislawska-Biernat, T. Takeuchi, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Aim</h3> To measure the level of agreement and application of 10 international recommendations for treating rheumatoid arthritis (RA) to a target of remission/low disease activity. <h3>Methods</h3> A 10-point Likert scale (1=fully disagree, 10=fully agree) measured the level of agreement with each of 10 recommendations. A 4-point Likert scale (never, not very often, very often, always) assessed the degree to which each recommendation was being applied in current daily practice. If respondents answered 'never' or 'not very often', they were asked whether they would change their practice according to the particular recommendation. <h3>Results</h3> A total of 1901 physicians representing 34 countries participated. Both agreement with and application of recommendations was high. With regard to application of recommendations in daily practice, the majority of responses were 'always' and 'very often'. A significant percentage of participants who were currently not applying these recommendations in clinical practice were willing to change their practice according to the recommendations. <h3>Conclusion</h3> The results of this survey demonstrated great support of 'Treating RA to Target' recommendations among the international rheumatology community. Additional efforts may be needed to encourage application of the recommendations among certain clinicians who are resistant to changing their practice.
Isolation and characterization of senile amyloid--related antigenic substance (SASSAM) from mouse serum. Apo SASSAM is a low molecular weight apoprotein of high density lipoprotein.
Authors: K Higuchi, A Matsumura, K Hashimoto, A Honma, S Takeshita, M Hosokawa, K Yasuhira, T Takeda
Journal: The Journal of Experimental Medicine (1983)

Sera obtained from senescence-accelerated mouse (SAM) and normal mice contained a substance that reacted with antiserum raised against ASSAM, a novel senile amyloid fibril protein isolated from the liver of SAM. This physiological substance, termed "SASSAM" (serum ASSAM-related antigenic substance), migrated to the albumin/prealbumin region in immunoelectrophoresis and the precipitation line formed with anti-ASSAM antiserum was stained positively with both Amide Black 10 B and Oil Red O/Fat Red 7B solutions, thereby suggesting that SASSAM is an alpha lipoprotein. Using Sephadex G-200 gel chromatography, SASSAM was eluted as a high mol wt form of approximately 200,000 daltons. Fractionation of lipoprotein from normal mouse serum by preparative ultra-centrifugation disclosed that SASSAM was found mainly in high density lipoprotein, HDL (the density is between 1.063 and 1.21 g/cm3). The largest amount of SASSAM was found in the HDL2 fraction (the density is between 1.063 and 1.125) and in this fraction SAA was not detected. Furthermore, ASSAM immunoreactivity appeared in the low mol wt proteins (below 10,000 daltons) of apo HDL separated in the buffer containing 8 M urea through Sephadex G-200. In 8 M urea sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), the major components of apolipoproteins in this position, possibly corresponding to apo C proteins, have the same molecular weight, 5,200 daltons, as ASSAM and this component was labeled by anti-ASSAM antiserum after transfer to nitrocellulose paper.
Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats.
Authors: L Rossetti, G I Shulman, W Zawalich, R A DeFronzo
Journal: Journal of Clinical Investigation (1987)

We have examined the effect of chronic (4 wk) hyperglycemia on insulin secretion in vivo in an awake, unstressed rat model. Three groups of animals were examined: control, partial (90%) pancreatectomy, and partial pancreatectomy plus phlorizin, in order to normalize plasma glucose levels. Insulin secretion in response to arginine (2 mM), hyperglycemia (+100 mg/dl), and arginine plus hyperglycemia was evaluated. In diabetic compared with control animals three specific alterations were observed: (a) a deficient insulin response, in both first and second phases, to hyperglycemia; (b) an augmented insulin response to the potentiating effect of arginine under basal glycemic conditions; and (c) an inability of hyperglycemia to augment the potentiating effect of arginine above that observed under basal glycemic conditions. Normalization of the plasma glucose profile by phlorizin treatment in diabetic rats completely corrected all three beta cell abnormalities. These results indicate that chronic hyperglycemia can lead to a defect in in vivo insulin secretion which is reversible when normoglycemia is restored.
Diacylglycerol synthesis de novo from glucose by pancreatic islets isolated from rats and humans.
Authors: B A Wolf, R A Easom, M L McDaniel, J Turk
Journal: Journal of Clinical Investigation (1990)

Recent evidence has suggested that pancreatic islets isolated from rats synthesize 1,2-diacyl-sn-glycerol (DAG) de novo from glucose and that this process may constitute the long-sought link between the metabolism of glucose and the induction of insulin secretion. The cell-permeant diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol (200 microM) has been found here to amplify both the first and second phases of insulin secretion from perifused human islets. Measurements of the mass of endogenous DAG in human pancreatic islets by enzymatic and by mass spectrometric methods indicate that levels of 200 microM may be achieved under physiologic conditions. Conversion of [14C]glucose to [14C]DAG has been demonstrated here to occur within 60 s of exposure of rat and human islets to stimulatory concentrations of glucose. This process has been found to be a quantitatively minor contributor to the total islet DAG mass after acute stimulation with glucose, however, and glucose has been found not to induce a rise in total islet DAG content within 20 min of induction of insulin secretion. In contrast to the case with rodent islets, two pharmacologic inhibitors of DAG-induced activation of protein kinase C (staurosporine and sphingosine) have been found not to influence glucose-induced insulin secretion from isolated human islets. These findings indicate that de novo synthesis of DAG from glucose does not participate in acute signal-response coupling in islets.
A Nonsynonymous Mutation in the Transcriptional Regulator lbh Is Associated with Cichlid Craniofacial Adaptation and Neural Crest Cell Development
Authors: Kara E. Powder, Hélène Cousin, Gretchen P. McLinden, R. Craig Albertson
Journal: Molecular Biology and Evolution (2014)

Since the time of Darwin, biologists have sought to understand the origins and maintenance of life's diversity of form. However, the nature of the exact DNA mutations and molecular mechanisms that result in morphological differences between species remains unclear. Here, we characterize a nonsynonymous mutation in a transcriptional coactivator, limb bud and heart homolog (lbh), which is associated with adaptive variation in the lower jaw of cichlid fishes. Using both zebrafish and Xenopus, we demonstrate that lbh mediates migration of cranial neural crest cells, the cellular source of the craniofacial skeleton. A single amino acid change that is alternatively fixed in cichlids with differing facial morphologies results in discrete shifts in migration patterns of this multipotent cell type that are consistent with both embryological and adult craniofacial phenotypes. Among animals, this polymorphism in lbh represents a rare example of a coding change that is associated with continuous morphological variation. This work offers novel insights into the development and evolution of the craniofacial skeleton, underscores the evolutionary potential of neural crest cells, and extends our understanding of the genetic nature of mutations that underlie divergence in complex phenotypes.
Current clinical development of PI3K pathway inhibitors in glioblastoma
Authors: P. Y. Wen, E. Q. Lee, D. A. Reardon, K. L. Ligon, W. K. Alfred Yung
Journal: Neuro-Oncology (2012)

Glioblastoma (GBM) is the most common and lethal primary malignant tumor of the central nervous system, and effective therapeutic options are lacking. The phosphatidylinositol 3-kinase (PI3K) pathway is frequently dysregulated in many human cancers, including GBM. Agents inhibiting PI3K and its effectors have demonstrated preliminary activity in various tumor types and have the potential to change the clinical treatment landscape of patients with solid tumors. In this review, we describe the activation of the PI3K pathway in GBM, explore why inhibition of this pathway may be a compelling therapeutic target for this disease, and provide an update of the data on PI3K inhibitors in clinical trials and from earlier investigation.