tbuckley/cabot-search huggingface dataset:
Multiple Genome Alignments Facilitate Development of NPCL Markers: A Case Study of Tetrapod Phylogeny Focusing on the Position of Turtles
Authors: X.-X. Shen, D. Liang, J.-Z. Wen, P. Zhang
Journal: Molecular Biology and Evolution (2011)

In recent years, the increasing availability of genomic resources has provided an opportunity to develop phylogenetic markers for phylogenomics. Efficient methods to search for candidate markers from the huge number of genes within genomic data are particularly needed in the era of phylogenomics. Here, rather than using the traditional approach of comparing genomes of two distantly related taxa to develop conserved primers, we take advantage of the multiple genome alignment resources from the the University of California-San Cruz Genome Browser and present a simple and straightforward bioinformatic approach to automatically screen for candidate nuclear protein-coding locus (NPCL) markers. We tested our protocol in tetrapods and successfully obtained 21 new NPCL markers with high success rates of polymerase chain reaction amplification (mostly over 80%) in 16 diverse tetrapod taxa. These 21 newly developed markers together with two reference genes (RAG1 and mitochondrial 12S-16S) are used to infer the higher level relationships of tetrapods, with emphasis on the debated position of turtles. Both maximum likelihood (ML) and Bayesian analyses on the concatenated data combining the 23 markers (21,137 bp) yield the same tree, with ML bootstrap values over 95% and Bayesian posterior probability equaling 1.0 for most nodes. Species tree estimation using the program BEST without data concatenation produces similar results. In all analyses, turtles are robustly recovered as the sister group of Archosauria (birds and crocodilians). The jackknife analysis on the concatenated data showed that the minimum sequence length needed to robustly resolve the position of turtles is 13-14 kb. Based on the large 23-gene data set and the well-resolved tree, we also estimated evolutionary timescales for tetrapods with the popular Bayesian method MultiDivTime. Most of the estimated ages among tetrapods are similar to the average estimates of the previous dating studies summarized by the book The Timetree of Life.
Topical nicotinamide modulates cellular energy metabolism and provides broad-spectrum protection against ultraviolet radiation-induced immunosuppression in humans
Authors: G. Sivapirabu, E. Yiasemides, G.M. Halliday, J. Park, D.L Damian
Journal: British Journal of Dermatology (2009)

Ultraviolet (UV) radiation can profoundly suppress the cutaneous immune system, thus enhancing carcinogenesis. Agents that prevent UV-induced immunosuppression may thus reduce skin cancer. Nicotinamide (vitamin B3) prevents UV-induced immunosuppression and carcinogenesis in mice, and solar-simulated (ss) UV-induced immunosuppression in humans. Its effectiveness against different UV wavebands and mechanism of action is as yet unknown.To determine the effects and mechanisms of topical nicotinamide on UV-induced suppression of delayed type hypersensitivity (DTH) responses in humans.Healthy Mantoux-positive volunteers in four randomised, double-blinded studies were irradiated with solar-simulated (ss)UV (UVB + UVA) or narrowband UVB (300 nm) or UVA (385 nm). Topical nicotinamide (0.2% or 5%) or its vehicle were applied immediately after each irradiation. Mantoux testing was performed at irradiated sites and adjacent unirradiated control sites 48 h after the first irradiation and measured 72 h later. Immunosuppression was calculated as the difference in Mantoux-induced erythema and induration at test sites compared to control sites. Human keratinocyte cell cultures, with and without ssUV and nicotinamide, were used for quantitative real-time reverse transcriptase-polymerase chain reaction assessment of TP53 and enzymes that regulate oxidative phosphorylation.Nicotinamide cooperated with ssUV to increase enzymes involved in cellular energy metabolism and p53, and significantly protected against immunosuppression caused by UVB, longwave UVA and single and repeated ssUV exposures.Longwave UVA, which is poorly filtered by most sunscreens, was highly immune suppressive even at doses equivalent to 20 min of sun exposure. Nicotinamide, which protected against both UVB and UVA, is a promising agent for skin cancer prevention.
Epidemic of Tonsillitis.
Authors: R. H. Jenkins
Journal: JAMA (1898)

Hogansville, Ga., May, 1898. <h3>To the Editor:</h3> —An epidemic of tonsillitis appeared in our village and vicinity, July 1, terminating Dec. 1, 1897. <h3>Case 1.</h3> —Roy P., white, age nine years. Upon examination I found both tonsils congested, and the size of a full-grown almond; tongue thickly covered with a lemon-colored fur, from the base to the tip. On the second day, on left tonsil, one ulcer one-fourth of an inch in length, from above downward, by one-eighth of an inch in width antero-posteriorly, made its appearance notwithstanding the use of strong astringents locally as a gargle, and the internal administration of mild mercurous chlorid in one-quarter grain doses every hour until six grains had been given; cauterized with molded nitrate of silver. The third day a similar ulcer formed upon the right tonsil; treatment was the same, with nitrate of silver. The fourth day both ulcers were covered with
Lysophosphatidic Acid as a Potential Biomarker for Ovarian and Other Gynecologic Cancers
Authors: Yan Xu
Journal: JAMA (1998)

Context.-Lysophosphatidic acid (LPA) has been shown to stimulate proliferation of ovarian cancer cells and is present in the ascitic fluid of patients with ovarian cancer.Objectives.-To determine whether elevated levels of LPA are present in plasma from patients with ovarian cancer and other gynecologic malignancies compared with healthy controls and to evaluate whether an elevated LPA plasma level may be a biomarker for these diseases.Design.-A research assay was used to measure total LPA levels in plasma from healthy women and women with different diseases.All LPA assays and comparison of LPA levels and CA125 (an ovarian cancer biomarker) levels were performed by observers blinded to patient status or group.Setting.-The Cleveland Clinic Foundation.Participants.-Aconvenience sample of 48 healthy control women, 48 women with ovarian cancer, 36 women with other gynecologic cancers, 17 women with benign gynecologic diseases, 11 women with breast cancer, and 5 women with leukemias.Main Outcome Measures.-TotalLPA levels in plasma samples from patients and controls.Results.-Patients in the ovarian cancer group had significantly higher plasma LPA levels (mean, 8.6 µmol/L; range, 1.0-43.1 µmol/L) compared with the healthy control group (mean, 0.6 µmol/L; range, Ͻ0.1-6.3 µmol/L) (PϽ.001).Elevated plasma LPA levels were detected in 9 of 10 patients with stage I ovarian cancer, 24 of 24 patients with stage II, III, and IV ovarian cancer, and 14 of 14 patients with recurrent ovarian cancer.Of 36 patients with other gynecologic cancers, 33 also showed higher LPA levels (mean, 14.9 µmol/L; range, Ͻ0.1-63.2µmol/L), compared with healthy controls (PϽ.001).Elevated plasma LPA levels were detected in 5 of 48 controls and 4 of 17 patients with benign gynecologic diseases and in no women with breast cancer or leukemia.In comparison, among a subset of patients with ovarian cancer, 28 of 47 had elevated CA125 levels, including 2 of 9 patients with stage I disease.Conclusions.-PlasmaLPA levels may represent a potential biomarker for ovarian cancer and other gynecologic cancers.However, these findings are preliminary and require confirmation in larger studies.
Successful pregnancy in a woman with systemic sclerosis while taking nifedipine.
Authors: A G Wilson, J D Kirby
Journal: Annals of the Rheumatic Diseases (1990)

The case is reported of successful conception and pregnancy in a woman with systemic sclerosis while receiving continuous treatment with nifedipine 30 mg/day, after a previously poor obstetric record and involuntary secondary infertility.
The Dingell Hearings on Scientific Misconduct -- Blunt Instruments Indeed
Authors: B Healy
Journal: New England Journal of Medicine (1993)

In the 1992 Shattuck Lecture, Congressman John Dingell of Michigan woefully admits that “congressional hearings are rather blunt instruments, poorly suited to making fine distinctions of fact”1. One would assume that Congressman Dingell would take advantage of the prestigious forum of the Shattuck Lecture and this scholarly journal to make the fine distinctions that he is unable to make in his hearing room as chairman of the House Subcommittee on Oversight and Investigations. Unfortunately, this is not the case in his recently published Shattuck Lecture1.My purpose here is to make some important distinctions of fact, and also . . .
JAMES GARLICK COBURN
Authors: G. Arckland
Journal: British Journal of Dermatology (1972)

Journal Article JAMES GARLICK COBURN Get access G. Arckland G. Arckland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 86, Issue 2, 1 February 1972, Page 192, https://doi.org/10.1111/j.1365-2133.1972.tb16086.x Published: 01 February 1972
HISTOLOGICAL STUDIES OF THE BONE MARROW IN FASTED AND POLYNEURITIC PIGEONS
Authors: Robert A. Moore, O. W. Barlow
Journal: The Journal of Experimental Medicine (1931)

1. The histological changes of the bone marrow in fasted and rice disease pigeons are essentially the same. 2. The histological changes of the bone marrow in pure vitamin B deficiency consist of degeneration and edema and slight endothelial proliferation of the small vascular channels, but with active hematopoiesis. 3. The anemia of rice disease in pigeons is in large part a starvation anemia and not directly related to vitamin B deficiency.
Tortuosity of both Internal Carotid Arteries
Authors: G. H. Edington
Journal: BMJ (1901)

State on Examination and Treatment.-I saw him first on April 8th, when he complained of pain in both knee-joints and the right ankle, and they were slightly swollen, but not red.He was sweating a little, and his temperature was 3030.I put him on a milk diet, and prescribed 15 grs. of
ST. BRENDA'S PRIVATE HOSPITAL, BRISTOL: A HOSPITAL FOR PAYING PATIENTS
Authors: S. V. Stock
Journal: BMJ (1921)

I[DJA 'headings; (b) secondarily, by tho inclusion under saturnism of cases of death due to other causes."2.As to morbidity, by defects in notification and certifica- tion and by other imperfections."As to the second question tlle Committee reported that:" By far the most important danger is from dust which enters through the nose and mouth."Of late years I lhave given muclh further attention to the effect of chemically neutral substances, anaesthetics and antiseptics, on living tissues.Their penetrating power and their power of exciting disturbances within the normal cell is astounding.My considered opinion is that the medical profession has yet to appreciate the insidious and often deep-seated effects thiat may be pro- duced by repeated and continued exposure even to small amounts of vapours suclh as that of turpentine.Painters are known to be subject to sicknesses from which lead workers are as a rule free-suclh as kidney complaints and lhardening of the arteries.It will be necessary to take careful note of the influence of suclh exposure in any future attempts to diagnose the symptoms and assess the danger arising from the use of lead paints.REFEIrENCE:8s. 1 The Origin of Osumotic Effects.III.-The Function of Hormones in Stimulating Enzynuic Change in Relation to Narcosis and the Pbenomena of Degenerative and Regenerative Change in Living
Publication Guidelines for Improvement Studies in Health Care: Evolution of the SQUIRE Project
Authors: Frank Davidoff, Paul Batalden, David Stevens, Greg Ogrinc, Susan Mooney
Journal: Annals of Internal Medicine (2008)

In 2005, draft guidelines were published for reporting studies of quality improvement as the initial step in a consensus process for development of a more definitive version. The current article contains the revised version, which we refer to as Standards for QUality Improvement Reporting Excellence (SQUIRE). This narrative progress report summarizes the special features of improvement that are reflected in SQUIRE and describes major differences between SQUIRE and the initial draft guidelines. It also explains the development process, which included formulation of responses to informal feedback, written commentaries, and input from publication guideline developers; ongoing review of the literature on the epistemology of improvement and methods for evaluating complex social programs; and a meeting of stakeholders for critical review of the guidelines' content and wording, followed by commentary on sequential versions from an expert consultant group. Finally, the report discusses limitations of and unresolved questions about SQUIRE; ancillary supporting documents and alternative versions under development; and plans for dissemination, testing, and further development of SQUIRE.
OBSTRUCTIVE JAUNDICE CAUSED BY A ROUND WORM IN THE COMMON BILE DUCT.
Authors: J. G. HILLEARY
Journal: JAMA (1905)

The patient was a bright, well-developed boy, aged 10, who had never been confined to bed on account of sickness in his life. I was asked to see him on the eighth day of his illness. Besides being intensely jaundiced, his trunk and limbs were covered with large patches of urticaria, which caused him great annoyance from the burning and itching. Nausea and vomiting, with loss of appetite were present throughout the attack. The tongue was coated and the mouth dry. Bowels were constipated; stools clay colored, pasty and fetid. Temperature was normal; pulse 60. The lungs and heart were normal; the abdomen was normal except for pain and tenderness over the region of the gall bladder. Having lately read an abstract of an article in the October number of the American Journal of the Medical Sciences, by W. Epstein, on the diagnostic significance of strangulation marks on round worms,
Cholesterol in the Elderly
Authors: Stephen B. Hulley
Journal: JAMA (1994)

There is a growing tendency to encourage measurement of and treatment for high blood cholesterol levels in elderly people. The 1993 adult treatment guidelines from the National Cholesterol Education Program (NCEP) note an "enhanced recognition [since 1988] that... high-risk elderly patients who are otherwise in good health are candidates for cholesterol-lowering therapy."<sup>1</sup>This policy shift is based on the belief that the association between blood cholesterol and coronary heart disease (CHD) persists after age 65 years and on a growing willingness to extrapolate to older people the reduced CHD rates observed in clinical trials of hypolipidemic treatment in middle-aged men. See also p 1335. In this issue ofThe Journal, the contention that an association between cholesterol and CHD persists in the elderly is called into question in a report by Krumholz et al.<sup>2</sup>The report finds no association between blood cholesterol level and CHD incidence or death
Profound digital collagen atrophy: a new cutaneous presentation of adrenal-dependent Cushing's syndrome
Authors: R.W. GROVES, L.M. MACDONALD, D.M. MACDONALD
Journal: British Journal of Dermatology (1990)

A 59‐year‐old Caucasian housewife presented with a 2‐year history of marked loss of tissue substance from the finger and toe pulps and the heel pads. There was no clinical evidence or history of urticaria or other inflammatory change. Investigations demonstrated a raised plasma cortisol secondary to a left adrenal adenoma. Skin biopsies showed abnormalities of dermal collagen, but no evidence of elastin destruction. This case presents an unusual variant of the cutaneous atrophy associated with Cushing's syndrome.
Abstract 1511: mda-7/IL-24 potently induces apoptosis in human leukemia cells through a process involving induction of ER stress
Authors: Mohamed Rahmani, Mandy Mayo, Rupesh Dash, Paul Dent, Paul B. Fisher, Steven Grant
Journal: Cancer Research (2010)

Abstract mda-7/IL-24, a member of the IL-10 cytokine gene family, has been shown to induce cell death in various epithelial cancer cell types while exhibiting relatively little toxicity toward normal cells. Currently, the effects of mda7/IL-24 on myeloid leukemia cells (AML) have not been extensively characterized. In the present study, we report that treatment with recombinant GST-mda7/IL24 strikingly induces apoptosis in diverse myeloid leukemia cell lines including U937, MV4-11, EOL-1 (both FLT3 mutant), and MLL/ENL cells, which display certain leukemia stem cell-like properties. In addition, mda7/IL24 potently induces apoptosis in and suppresses the colony formation capacity (L-CFU) of primary blasts isolated from multiple patients with AML. In contrast, mda-7/IL-24 exerted only minimal effects on normal CD34+ progenitor cells. These effects were associated with profound mitochondrial injury manifested by cytochrome c and AIF release into the cytosol, caspase-3 activation, and PARP cleavage. The apoptotic effects of mda7/IL24 were associated with a potent induction of ER stress in leukemia cell lines as well as in primary AML blasts, manifested by accumulation of GADD153/CHOP, GADD34, GRP78, and IRE1α. Notably molecular studies with shRNA directed against IRE1α revealed that knockdown of IRE1α significantly enhanced mda7/IL24-mediated apoptosis in U937 cells, suggesting that induction of IRE1α plays a protective role against mda7/IL24 lethality. In addition treatment with mda7/IL24 resulted in down-regulation of the anti-apoptotic protein Mcl-1, and marked accumulation of the pro-apoptotic proteins Bim and Noxa. Notably, ectopic expression of Mcl-1 or knock-down of Bim or Noxa with shRNA markedly decreased mda7/IL24-mediated cell death in leukemia cells. Collectively, these findings indicate that mda7/IL24 strikingly induces apoptosis in human myeloid leukemia through a process that involves ER stress induction, Mcl-1 downregulation, and Bim and Noxa upregulation. They also suggest that mda7/IL24 warrants attention as a potential addition to the therapeutic armamentarium in leukemia and possibly other hematologic malignancies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1511.
Microtubule Disruption and Tumor Suppression by Mitogen-Activated Protein Kinase Phosphatase 4
Authors: Yuangang Liu, James Lagowski, Aaron Sundholm, Alexandra Sundberg, Molly Kulesz-Martin
Journal: Cancer Research (2007)

Abstract The extracellular signal-regulated kinase (Erk) is one of the downstream effectors of the Ras pathway whose activation is essential for the proliferation and survival of cancer cells. Erk activation is negatively regulated by mitogen-activated protein kinase (MAPK) phosphatases (MKP), which are generally up-regulated by Erk activation, thus forming a feedback loop for regulation of Erk activity. In searching for early alterations in the Ras pathway in epidermal carcinogenesis, we identified MKP4, a cytosolic MKP with specificity to not only Erk, but also, to a lesser extent, c-jun-NH2-kinase and p38. MKP4 is down-regulated at initiation and lost at malignant conversion in a clonal model of epidermal carcinogenesis that lacks Ras mutation. The loss of MKP4 was associated with squamous cell carcinoma (SCC) but not benign papilloma clonal lineages and with independently induced SCC relative to benign tumors in mouse skin. Reconstitution of MKP4 expression in malignant tumor cells leads to cell death and tumor suppression. Unlike Erk inhibition that blocks cell cycle entry, MKP4 reconstitution resulted in G2-M associated cell death and microtubule disruption. Thus, microtubule disruption by MKP4 provides a novel mechanism for tumor suppression by a cytosolic MKP and implies a novel therapeutic strategy through combined MAPK inhibitions that mimic the function of MKP4. [Cancer Res 2007;67(22):10711–9]
Renal Clearance Studies
Authors: George Dunea
Journal: JAMA (1968)

Clearance studies are widely used to assess glomerular filtration rate and renal blood flow and to study the excretion of various substances by the kidney. The renal clearance of a substance represents the virtual or theoretical volume of plasma which is completely cleared of this substance in a given unit of time. It is usually expressed in milliliters per minute and calculated from the formula UV÷P, where U and P represent the urine and plasma concentration and V is the volume of the urine.<sup>1-3</sup>Clearances have played an important role in the study of renal physiology and have provided much circumstantial evidence regarding the relative importance of glomerular and tubular excretory mechanisms. <h3>Urea Clearance</h3> Since retention of urea in the blood is accompanied by decreased urinary excretion, students of renal disease in the early 1900's had attempted to evaluate renal function by relating the concentration of urea in urine
The role of intestinal endotoxin in liver injury: A long and evolving history
Authors: James P. Nolan
Journal: Hepatology (2010)

From the mid-1950s, it was observed that liver injury by a variety of toxins greatly sensitized the host to the effects of administered lipopolysaccharide. In the nutritional cirrhosis of choline deficiency, and in acute toxic injury as well, the need for the presence of enteric endotoxin was demonstrated. The universality of this association was striking for almost all agents associated with liver injury. In addition, the presence of endotoxemia in human liver disease was documented in the 1970s, when the hypothesis was first proposed, and correlated with the severity of the disease. Despite imposing evidence of the critical role of enteric endotoxin in liver injury, it did not excite much interest in investigators until the 1980s. With the ability to study effects of alcohol in newer delivery systems, and an increased understanding of the role of Kupffer cells in the process, the original hypothesis has been accepted. This historical review details the progress of this novel concept of disease initiation and suggests future directions to bring potential therapies to the bedside. (Hepatology 2010.)
Attenuated Cardiac Allograft Vasculopathy in Mice With Targeted Deletion of the Transcription Factor STAT4
Authors: Jörg Koglin, Troels Glysing-Jensen, Silpa Gadiraju, Mary E. Russell
Journal: Circulation (2000)

To study transcription factor signaling pathways that mediate cardiac allograft vasculopathy, we used mice with targeted gene deletion of signal transducer and activator of transcription (STAT)4 and STAT6 as recipients in our mouse cardiac transplant model of chronic rejection.At day 55 after transplantation, cardiac grafts placed into STAT4 -/- (n=10) had reduced frequency (24+/-2%) and severity (9+/-4%) of vascular occlusion compared with wild-type controls (n=7, frequency 70+/-12% [P<0.001], severity 25+/-6% [P<0.05]). This decrease was associated with reduced intragraft expression ((32)P RT-PCR and immunohistochemistry) of the Th1 signature cytokines interferon-gamma (P<0.001) and interleukin (IL)-2 (P<0.001). Furthermore, cardiac grafts in STAT4 -/- had fewer infiltrating CD45(+) mononuclear cells (99+/-27 cells/mm(3) compared with 551+/-168 cells/mm(3) in wild-type controls [P<0.05]) and reduced expression of P-selectin (P<0.001) and E-selectin (P<0.01) ligand, recently shown to regulate Th1 cell recruitment. In contrast, in grafts placed into STAT6 -/- (n=11), the development of cardiac allograft vasculopathy (frequency 62+/-8%, severity 28+/-6%) and Th2 cytokine profiles (IL-4, IL-10) were comparable to those in wild-type controls.Hence, we show that immune responses mediated by STAT4, but not STAT6, contribute to the development of cardiac allograft vasculopathy. We speculate that when present, STAT4-mediated signaling pathways may promote cardiac allograft vasculopathy by directing Th1-specific lymphocyte recruitment, activation, and effector functions.