tbuckley/cabot-search huggingface dataset:
The Poetry of Medicine
Authors: Julie Fishbein
Journal: JAMA (1990)

In 1985 I went to graduate school to become a writer. It was a fascinating time for me, surrounded by famous poets, and everyone involved in the act of making art. In fact, everyone was writing about the process of art, writing poetry about writing poetry. But I soon felt something was missing in the poems, something vital and vibrant, which I couldn't quite pinpoint. Until I returned to medicine, and there it was in every room. I want to take you there, to one particular 10 × 12-foot room on the pédiatrie ward, a spacious room for a short stay. My friend Sarah lives there. Sarah is 3 years old. She has aplastic anemia. You can spot her any day in her red plastic high-heeled slippers, costume jewelry, and underwear, as she comes clickety-clack down the hall. Sarah can't read, but we often find her sitting at the nurses' station, thumbing through her own hospital chart, considering each page carefully. If you need to borrow the chart, you must ask her permission and be prepared to come back later. She is a powerful child.
Autoimmune diabetes can be induced in transgenic major histocompatibility complex class II-deficient mice.
Authors: T M Laufer, M G von Herrath, M J Grusby, M B Oldstone, L H Glimcher
Journal: The Journal of Experimental Medicine (1993)

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease marked by hyperglycemia and mononuclear cell infiltration of insulin-producing beta islet cells. Predisposition to IDDM in humans has been linked to the class II major histocompatibility complex (MHC), and islet cells often become aberrantly class II positive during the course of the disease. We have used two recently described transgenic lines to investigate the role of class II molecules and CD4+ T cells in the onset of autoimmune insulitis. Mice that are class II deficient secondary to a targeted disruption of the A beta b gene were bred to mice carrying a transgene for the lymphocytic choriomenigitis virus (LCMV) glycoprotein (GP) targeted to the endocrine pancreas. Our results indicate that class II-deficient animals with and without the GP transgene produce a normal cytotoxic T lymphocyte response to whole LCMV. After infection with LCMV, GP-transgenic class II-deficient animals develop hyperglycemia as rapidly as their class II-positive littermates. Histologic examination of tissue sections from GP-transgenic class II-deficient animals reveals lymphocytic infiltrates of the pancreatic islets that are distinguishable from those of their class II-positive littermates only by the absence of infiltrating CD4+ T cells. These results suggest that in this model of autoimmune diabetes, CD4+ T cells and MHC class II molecules are not required for the development of disease.
Provision for the Mentally Handicapped
Authors: A. Shearer
Journal: BMJ (1971)

the real obstacles to a renal transplantation programme, which should be rapidly ex- panding and for which there is such need.Such expansion will not occur until there is an improvement in the nursing establish- ment and medical junior staffing on the average acute medical or surgical ward, par- ticularly in hospitals where the actual renal transplantation is not done.-Iam, etc.,
Hydrogen sulfide inhibits the renal fibrosis of obstructive nephropathy
Authors: Kai Song, Fen Wang, Qian Li, Yong-Bing Shi, Hui-Fen Zheng, Hanjing Peng, Hua-Ying Shen, Chun-Feng Liu, Li-Fang Hu
Journal: Kidney International (2013)

Hydrogen sulfide has recently been found decreased in chronic kidney disease. Here we determined the effect and underlying mechanisms of hydrogen sulfide on a rat model of unilateral ureteral obstruction. Compared with normal rats, obstructive injury decreased the plasma hydrogen sulfide level. Cystathionine-β-synthase, a hydrogen sulfide-producing enzyme, was dramatically reduced in the ureteral obstructed kidney, but another enzyme cystathionine-γ-lyase was increased. A hydrogen sulfide donor (sodium hydrogen sulfide) inhibited renal fibrosis by attenuating the production of collagen, extracellular matrix, and the expression of α-smooth muscle actin. Meanwhile, the infiltration of macrophages and the expression of inflammatory cytokines including interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in the kidney were also decreased. In cultured kidney fibroblasts, a hydrogen sulfide donor inhibited the cell proliferation by reducing DNA synthesis and downregulating the expressions of proliferation-related proteins including proliferating cell nuclear antigen and c-Myc. Further, the hydrogen sulfide donor blocked the differentiation of quiescent renal fibroblasts to myofibroblasts by inhibiting the transforming growth factor-β1-Smad and mitogen-activated protein kinase signaling pathways. Thus, low doses of hydrogen sulfide or its releasing compounds may have therapeutic potentials in treating chronic kidney disease.
Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability
Authors: Katrina Tatton-Brown, Sheila Seal, Elise Ruark, Jenny Harmer, Emma Ramsay, Silvana del Vecchio Duarte, Anna Zachariou, Sandra Hanks, Eleanor O'Brien, Lise Aksglaede, Diana Baralle, Tabib Dabir, Blanca Gener, David Goudie, Tessa Homfray, Ajith Kumar, Daniela T Pilz, Angelo Selicorni, I Karen Temple, Lionel Van Maldergem, Naomi Yachelevich, Robert van Montfort, Nazneen Rahman
Journal: Nature Genetics (2014)
Findings of Diffuse Lymphadenitis Secondary to Rheumatoid Arthritis and Synovitis on Tc-99m Labeled Leukocyte Scan
Authors: SUNG M. KIM, CHAN H. PARK, CHARLES M. INTENZO, JACK R. McEWAN
Journal: Clinical Nuclear Medicine (1994)

Diffuse lymph node activity was observed within the axillary and inguinal regions in a patient with a biopsy-proven synovitis and rheumatoid arthritis on a Tc-99m HMPAO labeled leukocyte scan.
Some screening is necessary to identify excessive drinkers early in primary care
Authors: N. Heather
Journal: BMJ (2003)

<b>Background:</b> Janus Kinases (JAKs) mediate activity of many asthma-relevant cytokines. GDC-0214, an inhaled small molecule JAK1 inhibitor, has reduced FeNO ~40% in patients with mild asthma. <b>Aim:</b> To assess whether GDC-4379, a structurally related JAK inhibitor, also reduces FeNO. <b>Methods:</b> This double-blind, randomized, placebo-controlled, Phase 1 study assessed activity of GDC-4379 in patients with mild asthma. Patients&nbsp;were adults (18–65y) with a diagnosis of asthma for ≥6 months, FeNO &gt;40 ppb, using as-needed relief medication only. Three sequential, 14-day, ascending-dose cohorts (Table) were randomized 2:1 (GDC-4379:placebo). The primary activity outcome was percent change from baseline (CFB) in FeNO to Day 14. We assessed pharmacokinetics, safety, and tolerability. <b>Results:</b> Of 36 enrolled patients (mean age, 25y), 56% were female. Baseline mean FeNO was 92 ppb. GDC-4379 treatment led to dose-dependent&nbsp;reductions in FeNO; at 40 mg BID, mean FeNO decreased 58% (-52 ppb) vs. pooled placebo (Table). Higher plasma drug concentrations corresponded with greater FeNO reductions. No dose-limiting adverse events (AEs), serious AEs, or treatment discontinuations occurred. Most common AEs were headache and oropharyngeal pain (sore throat), without imbalances in AEs or laboratory findings between groups. <b>Conclusions:</b> In patients with mild asthma, 14-day treatment with GDC-4379 reduced FeNO. Treatment was well tolerated, without evidence of systemic toxicity.
Meningococcal Meningitis Treated with Penicillin
Authors: G. H. Tee
Journal: BMJ (1945)

THYROID HYPERPLASIA AFTER THIOURAC1L BRICTISH with 6.6 g. of thiouracil daily for 20 days, and was then given a maintenance dose of 0.2 g. daily for a week.She was discharged from hospital feeling very well.Her weight had increased by half a stone in a month, and her B.M.R. had fallen from + 55 to + 8.A mild tachycardia was the only residual sign of her thyrotoxicosis.She was told to continue 'to take 0.2 g. of thiouracil daily, but owing to a misunderstanding she actually took 0.4 g.As her home was in the far North of Scotland it was impossible for her to report to us regularly, and she was seen once a month by her own doctor.The first three reports from him were most satisfactory, but the fourth stated that she was not quite so well, though no specific symptom was noted beyond some lack of energy.By the fifth month this symptom had become pronounced, and a swelling of the neck was reported.The patient was immediately sent for, and on readmission, five and a half months after her discharge, was found to have a very large soft goitre.This was associated with a mild degree of myxoedema.Her weight had increased by one stone since discharge from hospital, her B.M.R. had fallen to -20, and her blood cholesterol had .risenfrom 220 to 266 mg. per 100 c.cm.Her white blood count of 5,600 showed no significant alteration.Thiouracil was immediately stopped, and in two weeks' time she felt considerably better, her B.M.R. having risen from -20 to -3.No change had occurred, however, in the' size or consistency of the goitre, and thyroidectorny was undertaken, principally for cosmetic reasons.At operation the thyroid was obviously enlarged, and was firm though not hard.The cut surface was typical of the hypertrophy associated with a primary toxic goitre which had not been treated by iodine.A section of the gland is shown in the accompanying photomicrograph.It can be seen that there is extreme parenchymatous hyperplasia and an almost com- plete absence of colloid, the picture being similar to that produced by Mackenzie in animals treated with goitrogenic substances.After the operation the patient made an uninterrupted recovery, and was discharged home feeling well.
Immobilization hypercalcaemia in patients on regular haemodialysis.
Authors: G Drivas, M Ward, D Kerr
Journal: BMJ (1975)

Immobilization of normal people causes reabsorption of calcium from bone, a small rise in serum ionized calcium, and, rarely, frank hypercalcaemia. The hazard is increased when patients with renal osteodystrophy are immobilized because of pathological fractures.
A SIMPLE TEST FOR THE DIAGNOSIS OF THROMBOSIS OF THE LATERAL SINUS
Authors: Charles E. Dowman
Journal: JAMA (1925)

Compression of both jugular veins produces a congestion of the cerebral sinuses and veins, which in turn causes an immediate rise in cerebrospinal fluid pressure. Quickenstedt made a practical application of jugular compression in determining the presence or absence of spinal canal obstruction. This test may be of value also in diagnosing thrombosis of the lateral sinus, and its simplicity adds to its value. <h3>TECHNIC</h3> A lumbar puncture is made and the spinal fluid pressure recorded with either a mercury or a water manometer. The internal jugular vein on the side opposite that of the suspected thrombosis of the lateral sinus is compressed by applying digital pressure anterior to the upper portion of the sternocleidomastoid muscle. If there is an immediate rise in spinal fluid pressure, it is reasonable to conclude that the circulation in the jugular vein or lateral sinus on the opposite side is obstructed. If there is
pH of Infusion Fluids: A Predisposing Factor in Thrombophlebitis
Authors: R. L. Tse
Journal: JAMA (1971)

<h3>To the Editor.—</h3> It is known that the pH of glucose infusion fluids sterilized by autoclaving is maintained in the vicinity of 4.0 in order to prevent caramelization during the sterilization procedure. The acidity of these solutions has long been suspected as an important factor in the development of infusion thrombophlebitis.<sup>1,2</sup>Controlled studies by Elfving and Saikku<sup>3</sup>and Fonkalsrud et al<sup>4</sup>clearly demonstrated a significant decrease in the incidence of thrombophlebitis when buffered glucose solutions (buffered to pH 6.8 and 7.4, respectively) were used. Recently we have measured the pH of some commonly used intravenously given fluids. With the exception of lactated Ringer's solution, all were found to be acidic (Table). These solutions have no significantbuffering capacity and are easily buffered by blood. A ready explanation for the genesis of infusion phlebitis lies in the relative sizes of the needle or polyethylene catheter and the vein
Rad6B Is a Positive Regulator of β-Catenin Stabilization
Authors: Malathy P.V. Shekhar, Brigitte Gerard, Robert J. Pauley, Bart O. Williams, Larry Tait
Journal: Cancer Research (2008)

Abstract Mutations in β-catenin or other Wnt pathway components that cause β-catenin accumulation occur rarely in breast cancer. However, there is some evidence of β-catenin protein accumulation in a subset of breast tumors. We have recently shown that Rad6B, an ubiquitin-conjugating enzyme, is a transcriptional target of β-catenin/TCF. Here, we show that forced Rad6B overexpression in MCF10A breast cells induces β-catenin accumulation, which despite being ubiquitinated is stable and transcriptionally active. A similar relationship between Rad6B, β-catenin ubiquitination, and transcriptional activity was found in WS-15 and MDA-MB-231 breast cancer cells, and mouse mammary tumor virus–Wnt-1 mammary tumor—derived cells, implicating Rad6B in physiologic regulation of β-catenin stability and activity. Ubiquitinated β-catenin was detectable in chromatin immunoprecipitations performed with β-catenin antibody in MDA-MB-231 but not MCF10A cells. Rad6B silencing caused suppression of β-catenin monoubiquitination and polyubiquitination, and transcriptional activity. These effects were accompanied by a reduction in intracellular β-catenin but with minimal effects on cell membrane–associated β-catenin. Measurement of β-catenin protein stability by cycloheximide treatment showed that Rad6B silencing specifically decreases the stability of high molecular β-catenin with minimal effect upon the 90-kDa nascent form. In vitro ubiquitination assays confirmed that Rad6B mediates β-catenin polyubiquitination, and ubiquitin chain extensions involve lysine 63 residues that are insensitive to 26S proteasome. These findings, combined with our previous data that Rad6B is a transcriptional target of β-catenin, reveal a positive regulatory feedback loop between Rad6B and β-catenin and a novel mechanism of β-catenin stabilization/activation in breast cancer cells. [Cancer Res 2008;68(6):1741–50]
The Sad Odyssey of the New White House Science Office
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1976)

On June 9, 1975, President Ford asked Congress to re-establish the Executive Office science advisory organization that his predecessor had abolished. Since Congressional sentiment already favored the restoration, there was no reason to doubt that it would swiftly be accomplished. Nevertheless, 13 months later, there was still no presidential science office, despite a duly enacted statute saying that there shall be one. Lesson-drawers may proceed as they please; I will confine myself to relating a bizarre tale of science and government.It was in 1973 that Mr. Nixon dissolved the 15-year-old Office of Science and Technology and the accompanying post . . .
Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma.
Authors: R Sgonc, M S Gruschwitz, H Dietrich, H Recheis, M E Gershwin, G Wick
Journal: Journal of Clinical Investigation (1996)

The mechanism that may cause degenerative fibrotic skin lesions was studied in situ using skin biopsies from patients with systemic sclerosis (SSc), localized scleroderma, or keloids, and at the initial disease stage in the University of California at Davis (UCD) lines 200/206 chickens, which develop a hereditary systemic connective tissue disease resembling human SSc and permit study of disease stages not accessible in humans. Frozen skin sections were analyzed simultaneously for apoptosis by terminal deoxynucleotidyl transferase-mediated FITC-dUTP nick end labeling and indirect immunofluorescence staining of cell markers with tetramethylrhodamine isothiocyanate conjugates. The results showed that endothelial cells are clearly the first cells to undergo apoptosis in the skin of UCD-200/206 chickens, a process that seems to be induced by anti-endothelial cell antibodies. In human fibrotic skin diseases, apoptotic endothelial cells could only be detected in early inflammatory disease stages of SSc and localized scleroderma.
JUVENILE HYPERTENSION ASSOCIATED WITH UNILATERAL LESIONS OF THE UPPER URINARY TRACT
Authors: JOHN H. POWERS
Journal: JAMA (1942)

Hypertension in childhood is frequently associated with abnormalities of the upper urinary tract. Lesions may be unilateral or bilateral, congenital or acquired, inflammatory, neoplastic or obstructive. If bilateral the renal disease often advances rapidly to terminate in hypertensive crises and death from apoplexy or from renal or cardiac failure. If the disease is unilateral removal of the involved kidney or correction of the obstruction may effect a decline in blood pressure to lower or normal levels and remission of the hypertensive symptoms. The purpose of this paper is threefold: (1) to present in detail 1 case of juvenile hypertension associated with pyelonephritis and aplasia of one kidney, relieved by nephrectomy, (2) to review the few reported cases in which surgical treatment has been employed for unilateral renal disease with hypertension in childhood and (3) to discuss certain deductions pertinent to the earlier recognition and diagnosis of this syndrome. <h3>REPORT OF</h3>
Hammerhead Ribozyme Suppresses the Expression of MLN64 and Affects the Function of Breast Cancer Cells In Vitro.
Authors: W. Cai, W. Cai, L. Ye, R. Mansel, W. Jiang
Journal: Cancer Research (2009)

Abstract Background: The MLN64 gene, which is localized in q12-q21 of the human chromosome 17, encodes a novel transmembrane protein that shares homology with the cholesterol binding domain (START domain) of the steroidogenic acute regulatory protein. The function of MLN64, initially reported in the metastatic lymph nodes, remains unclear, but has been indicated to probably regulate cholesterol transport. MLN64 is highly expressed in certain breast carcinomas, often co-amplified with erbB-2, and thus may contribute to the development and progression of breast tumours. The present study investigated the molecular and cellular impact of MLN64 on the functions of breast cancer cells.Methods: An anti-human MLN64 hammerhead ribozyme transgene was constructed using the mammalian expression vector pEF6/V5-His TOPO, and transfected into breast cancer cells MDA MB 231 and MCF-7 by electroporation. Expression of MLN64 mRNA and protein was determined using RT-PCR and Western blotting respectively. Cell growth, invasiveness, adhesion, motility and migration assays were used to assess, in vitro, the impact of MLN64 knockdown on the cells. In addition, expression of MLN64 was evaluated in a cohort of breast tumours, at protein and message levels.Result: Loss of MLN64 in MCF-7 cells resulted in a significant reduction of cellular growth (growth index for MCF-7ΔMLN64 being 0.87±0.07, P&amp;lt;0.01 vs wild type control (MCF-7WT 1.13±0.06) and transfection control (MCF-7pEF 1.27±0.05). Interestingly, the same change in cell growth was not seen with MDA-MB-231 cells, in that MDA-MB-231ΔMLN64 didn't exhibit a significant effect on the cell growth comparing with corresponding WT and PEF controls. In matrix adhesion assay, MDA-MB-231ΔMLN64 cells showed a significant increase in adhesion (86±14), compared with MDA-MB-231WT and MDA-MB-231pEF (61 ±20 and 45±27, respectively, P&amp;lt;0.01). In MCF-7 cell line, no significant differences were observed between the knockdown mutants and the wild types and pEF type. Breast cancer tissues showed a higher levels of MLN64 transcript than normal tissues (median (IQR) 1.08 (0.19-4.7) copies vs 0.5 (0.18-1.3) copies. Furthermore, ER positive tumours had significantly higher levels of MLN64 transcript (2.86(0.53-11.9) copies) than ER negative tumours (0.59 (0.15-2.68) copies), p=0.0012.Conclusion: In this first report on the functions of MLN64 in breast cancer cell lines, we have shown that MLN64 levels are correlated with the growth and adhesion of breast cancer cells in vitro. It is suggested that MLN64 has a direct influence on the aggressiveness of breast cancer cells and may play a role in progression and metastasis of breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6163.
CXC chemokine signaling in the liver: Impact on repair and regeneration
Authors: Heather L. Van Sweringen, Nozomu Sakai, Amit D. Tevar, Justin M. Burns, Michael J. Edwards, Alex B. Lentsch
Journal: Hepatology (2011)

The process of liver repair and regeneration following hepatic injury is complex and relies on a temporally coordinated integration of several key signaling pathways. Pathways activated by members of the CXC family of chemokines play important roles in the mechanisms of liver repair and regeneration through their effects on hepatocytes. However, little is known about the signaling pathways used by CXC chemokine receptors in hepatocytes. Here we review our current understanding of the pathways involved in both CXC chemokine receptor signaling in other cell types, most notably neutrophils, and similar pathways operant during hepatocyte proliferation/liver regeneration to formulate a basis for the function of CXC chemokine receptor signaling in hepatocytes. (Hepatology 2011;)
Exercise Tests After Myocardial Infarction
Authors: Samuel Vaisrub
Journal: JAMA (1980)

Early ambulation after myocardial infarction is no longer news. We have taken in our stride the speed with which patients traverse the trajectory of intensive coronary care unit—ward— home.<sup>1</sup> It may take longer to adjust to early exercise testing after myocardial infarction, even though this practice is not altogether new<sup>2</sup>and its safety has been demonstrated by a number of observers.<sup>3,4</sup>Until recently the main purpose in such testing has been to assess the working capacity during the convalescent phase, as indicated by untoward symptoms, ST-T wave changes, and arrhythmias. Dillahunt and Miller<sup>5</sup>have designed a study of early exercise testing with a more ambitious aim of predicting the extent of coronary artery disease and left ventricular dysfunctions. They accomplished this by correlating the results of a treadmill test soon after the onset of myocardial infarction, with angiographic and hemodynamic data obtained at a later date.