tbuckley/cabot-search huggingface dataset:
Stimulation of Cyclooxygenase-2 Expression by Bone-Derived Transforming Growth Factor-β Enhances Bone Metastases in Breast Cancer
Authors: Toru Hiraga, Akira Myoui, Mary E. Choi, Hideki Yoshikawa, Toshiyuki Yoneda
Journal: Cancer Research (2006)

Abstract Cyclooxygenase-2 (COX-2), the rate-limiting enzyme of prostaglandin synthesis, has been implicated in invasiveness and distant metastases of cancer. Bone is one of the most common target sites of cancer metastasis. However, the role of COX-2 in bone metastasis is unclear. We examined the surgical specimens of bone metastases from patients with various types of cancers by using immunohistochemistry and observed evident COX-2 expression in these bone metastases. In a nude mouse model of bone metastasis, the MDA-MB-231 human breast cancer cells showed no COX-2 expression at orthotopic sites, whereas these cells, when metastasized to bone, intensely expressed COX-2, suggesting that the bone microenvironment induced COX-2 expression. Consistent with this notion, inhibition of bone resorption by the bisphosphonate ibandronate reduced COX-2 expression in MDA-MB-231 cells in bone. Transforming growth factor-β (TGFβ), one of the most abundant growth factors stored in bone, increased COX-2 expression and prostaglandin E2 production in MDA-MB-231 cells in culture. MDA-MB-231 cells overexpressing dominant-negative TGFβ type II receptors showed decreased bone metastases and reduced osteoclastic bone resorption with impaired COX-2 expression. The COX-2 inhibitors, NS-398 and nimesulide, significantly suppressed bone metastases with decreased osteoclast number and increased apoptosis in MDA-MB-231 cells. These results suggest that bone-derived TGFβ up-regulates COX-2 expression in breast cancer cells, thereby increasing prostaglandin E2 production, which in turn, stimulates osteoclastic bone destruction, leading to the progression of bone metastases. Our results also suggest that COX-2 is a potential therapeutic target for bone metastases in breast cancer. (Cancer Res 2006; 66(4): 2067-73)
A Tick Antioxidant Facilitates the Lyme Disease Agent's Successful Migration from the Mammalian Host to the Arthropod Vector
Authors: Sukanya Narasimhan, Bindu Sukumaran, Ulas Bozdogan, Venetta Thomas, Xianping Liang, Kathleen DePonte, Nancy Marcantonio, Raymond A. Koski, John F. Anderson, Fred Kantor, Erol Fikrig
Journal: Cell Host & Microbe (2007)
Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV
Authors: Yuang-Taung Juang, Ying Wang, Elena E. Solomou, Yansong Li, Christian Mawrin, Klaus Tenbrock, Vasileios C. Kyttaris, George C. Tsokos
Journal: Journal of Clinical Investigation (2005)

Systemic lupus erythematosus (SLE) T cells express high levels of cAMP response element modulator (CREM) that binds to the IL-2 promoter and represses the transcription of the IL-2 gene. This study was designed to identify pathways that lead to increased binding of CREM to the IL-2 promoter in SLE T cells. Ca2+/calmodulin–dependent kinase IV (CaMKIV) was found to be increased in the nucleus of SLE T cells and to be involved in the overexpression of CREM and its binding to the IL-2 promoter. Treatment of normal T cells with SLE serum resulted in increased expression of CREM protein, increased binding of CREM to the IL-2 promoter, and decreased IL-2 promoter activity and IL-2 production. This process was abolished when a dominant inactive form of CaMKIV was expressed in normal T cells. The effect of SLE serum resided within the IgG fraction and was specifically attributed to anti–TCR/CD3 autoantibodies. This study identifies CaMKIV as being responsible for the increased expression of CREM and the decreased production of IL-2 in SLE T cells and demonstrates that anti–TCR/CD3 antibodies present in SLE sera can account for the increased expression of CREM and the suppression of IL-2 production.
Abortion Laws and the Physician
Authors: Donald Hayes Russell, Neil L. Chayet
Journal: New England Journal of Medicine (1967)

THE current social climate has produced a new movement toward the reformation of abortion laws, and the considerable controversy arises once again with gathering force. Since abortion, legal or illegal, is considered to be a medical practice, it falls within the province of medicine from a technical standpoint, and the law has placed it there in terms of the restrictions and exceptions governing the practice. There is much feeling that the demands for abortion, together with the narrowness and rigidity of the law, place physicians in a hypocritical and indefensible position. Although the actual medical indications for therapeutic abortions have . . .
Cauliflower ears, opium, and Errol Flynn.
Authors: D. Owens, M. Humphries
Journal: BMJ (1988)

Generally the syndrome is thought to be caused by patients "playing" with their pacemaker, hence the name twiddler.Few, if any, patients admit to such interference, but convincing their doctors of their innocence may be difficult.Are they guilty?Could this 9 year old Weimaraner have twiddled his pacemaker (situated on the superior aspect of his neck) with his hind paws?We believe that rotation of the pacemaker caused by local muscular action during normal activities is more likely.
STUDIES ON THE INFLUENCE OF THE LOW SODIUM CARDIAC DIET AND THE KEMPNER REGIMEN ON RENAL HEMO-DYNAMICS AND ELECTROLYTE EXCRETION IN HYPERTENSIVE SUBJECTS 123
Authors: R. E. Weston, L. Hellman, D. J. W. Escher, I. S. Edelman, J. Grossman, L. Leiter
Journal: Journal of Clinical Investigation (1950)

Until recently, renal function in man has been considered to be relatively unaffected by variations in dietary salt and protein (1, 2), which produce marked renal hemodynamic changes in the dog (3, 4).However, studies on normal subjects and patients in congestive failure suggest that changes in glomerular filtration rate may influence urinary sodium output as sodium intake is varied (5).The present report is concerned with the effects of dietary salt and protein restriction on renal function and electrolyte excretion in a series of hypertensive subjects, who were studied on a regular hospital diet, a low salt cardiac diet, and the Kempner rice diet (6), in which both salt and protein are markedly reduced. CLINICAL MATERIAL AND METHODSThe nine hypertensive patients in this series all had long established hypertension without any clinical or laboratory evidence of either cardiac failure or renal pathology other than that associated with essential hypertension.Because of a previous episode of congestive failure, one patient (J.B.) was maintained on digitalis and remained well compensated throughout the course of these investigations.Another .(R.G.) had a previous cerebral accident with no residual neurological signs.A third (M.C.) had a coexisting chronic lymphatic leu- kemia.On the basis of the usual criteria (7), one patient 1 Presented to American Physiological Society, Atlan- tic City, N.J., March 18, 1948.
DIAGNOSIS AND DIFFERENTIATION OF INFILTRATIVE, STORAGE, AND INFLAMMATORY DISEASE FROM HYPERTROPHIC CARDIOMYOPATHY USING 320 SLICE CT AND ELECTROCARDIOGRAM
Authors: Masae Uehara, Nobusada Funabashi, Hiroyuki Takaoka, Koya Ozawa, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2012)
Alcohol in Breath, Blood, And Cerebrospinal Fluid
Authors: Jorge Viamontes
Journal: JAMA (1972)

<h3>To the Editor.—</h3> Several studies indicate that the alcohol content of cerebrospinal fluid (CSF) roughly parallels that of blood.<sup>1,2</sup>It is not known whether cellular and chemical constituents of spinal fluid are affected by alcohol. The present study had two goals, to compare breath, blood, and CSF alcohol concentrations in severely intoxicated alcoholics; and secondly to ascertain whether CSF constituents were abnormal when high levels of alcohol were present. <h3>Methods.—</h3> Ten male alcoholics between the ages of 25 and 50 were admitted to an alcoholism inpatient service with blood alcohol levels, as determined by breath analysis, exceeding 150 mg/100 ml. Blood and lumbar spinal fluid samples were obtained immediately after the determination of breath alcohol. The blood and CSF were tested for alcohol, uric acid, sodium, chloride, potassium, magnesium, and glucose. The CSF additionally was tested for total protein, cells, and specific gravity, and the blood was tested for
Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase–β
Authors: Yuk Yin Cheung, So Youn Kim, Wai Han Yiu, Chi-Jiunn Pan, Hyun-Sik Jun, Robert A. Ruef, Eric J. Lee, Heiner Westphal, Brian C. Mansfield, Janice Y. Chou
Journal: Journal of Clinical Investigation (2007)

Neutropenia and neutrophil dysfunction are common in many diseases, although their etiology is often unclear. Previous views held that there was a single ER enzyme, glucose-6-phosphatase–α (G6Pase-α), whose activity — limited to the liver, kidney, and intestine — was solely responsible for the final stages of gluconeogenesis and glycogenolysis, in which glucose-6-phosphate (G6P) is hydrolyzed to glucose for release to the blood. Recently, we characterized a second G6Pase activity, that of G6Pase-β (also known as G6PC), which is also capable of hydrolyzing G6P to glucose but is ubiquitously expressed and not implicated in interprandial blood glucose homeostasis. We now report that the absence of G6Pase-β led to neutropenia; defects in neutrophil respiratory burst, chemotaxis, and calcium flux; and increased susceptibility to bacterial infection. Consistent with this, G6Pase-β–deficient (G6pc3–/–) mice with experimental peritonitis exhibited increased expression of the glucose-regulated proteins upregulated during ER stress in their neutrophils and bone marrow, and the G6pc3–/– neutrophils exhibited an enhanced rate of apoptosis. Our results define a molecular pathway to neutropenia and neutrophil dysfunction of previously unknown etiology, providing a potential model for the treatment of these conditions.
How doctors are re-engineering the immune system to fight HIV infection
Authors: B. Roehr
Journal: BMJ (2011)

An important step towards a possible cure for HIV was unveiled at the 18th Conference on Retroviruses in Boston, Massachusetts on 28 February. It involves changing the genes of a patient’s immune cells so that they are nearly invulnerable to infection by the virus.

The phase I safety study includes only six patients, and the data are only an interim six month analysis. But all patients show a substantial increase in the number of CD4 T cells, a key part of the immune system in which HIV replicates. Most of those cells are resistant to HIV.

The science behind it is complex. The virus most commonly infects a CD4 cell by grabbing on to a co-receptor molecule on the surface of the cell called CCR5. However, a genetic mutation inherited from both parents prevents that …
Case 17391
Authors: Sven M. Gundersen, Paul Dudley White, William B. Breed, James Howard Means, George W. Holmes, Tracy B. Mallory
Journal: New England Journal of Medicine (1931)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 17391 — Syphilitic versus Rheumatic Heart Disease and the Importance of History in Differential Diagnosis
Population Genetic Variation in Genome-Wide Gene Expression
Authors: J. P. Townsend
Journal: Molecular Biology and Evolution (2003)

Evolutionary biologists seek to understand which traits display variation, are heritable, and influence differential reproduction, because such traits respond to natural selection and underlie organic evolution. Selection acts upon individual differences within a population. Whether individual differences within a natural population include variation in gene expression levels has not yet been addressed on a genome-wide scale. Here we use DNA microarray technology for measuring comparative gene expression and a refined statistical analysis for the purpose of comparing gene expression levels in natural isolates of the wine yeast Saccharomyces cerevisiae. A method for the Bayesian analysis of gene expression levels is used to compare four natural isolates of S. cerevisiae from Montalcino, Italy. Widespread variation in amino acid metabolism, sulfur assimilation and processing, and protein degradation—primarily consisting of differences in expression level smaller than a factor of 2—is demonstrated. Genetic variation in gene expression among isolates from a natural population is present on a genomic scale. It remains to be determined what role differential gene expression may play in adaptation to new or changing environments.
Mortimer Francis Howlett Kelleher
Authors: A J M Blumer
Journal: BMJ (2006)

Plastic surgeon and creator of the first collection of American penny arcade antique toys Before movies and television, small town Americans went to penny arcades for amusement, dropping coins into devices that entertained them by making mechanical figures move or-like today's slot machines-rewarded them with more coins if they played a game correctly.The devices were also found in bars, amusement parks, restaurants, and hotels.Their popularity peaked before the first world war and they went out of style when prohibition closed America's bars.When James Smith was a boy in East Liverpool, Ohio, the son of a dignified banker, he often rode the trolley car across the state line to an amusement park in Chester, West Virginia, where he enjoyed dropping pennies and nickels (five cent pieces) into machines that told fortunes, tested one's strength, played games, or offered penny candy.He said he loved the challenge of trying to beat the machines, but his father discouraged his son's gaming habits.
A medical memoir
Authors: G. Graham
Journal: BMJ (2001)

My first encounter with a doctor was when I was two years old. I remember being propped up on the kitchen worktop while he examined (with cold fingers) my private parts. He, or my parents, had decided that I should be circumcised. They did not consult me. I cried.

Throughout my childhood, in the 1920s and 1930s, I had a series of the customary childhood illnesses. My parents became Christian Scientists in 1925 and so, when I fell ill, I was tucked into bed, given warm milk, tender loving care, prayer, and spiritual treatment. There was no medicine in the house. It was a loving, if somewhat Spartan, upbringing.

Schooled in the belief that spiritual healing was natural, I tended to take injuries rather casually. Once, in my teens, I fell off a rock face when I was climbing alone and gashed my leg to the bone. I cycled 30 miles home with a handkerchief over it. When I got home, a fresh handkerchief was substituted.

> This period of illness has …
Multiple Autoepitope Presentation for Specific Detection of Antibodies in Primary Biliary Cirrhosis
Authors: Jean-Paul Briand, Chantal Andre, Nadine Tuaillon, Laurence Herve, Jean Neimark, Sylviane Muller
Journal: Hepatology (1992)

Antimitochondrial autoantibodies are present in sera from close to 95% of patients with primary biliary cirrhosis. The so–called primary biliary cirrhosis–specific antigen, named M2, was found to be associated with an enzyme complex of the inner mitochondrial membrane and, more precisely, with the E2 component, dihydrolipoamide acetyltransferase, of the pyruvate dehydrogenase complex. We recently established that an immunodominant epitope recognized in direct enzyme–linked immunosorbent assay by primary biliary cirrhosis M2 + sera, but not by non—primary biliary cirrhosis M2 + sera, could be mimicked by a synthetic peptide encompassing residues 167-184 of the E2 component and associated with lipoic acid. This fragment is present in the natural inner lipoyl–binding site of the human enzyme, and the presence of lipoic acid located on Iysine 173 was found to be essential to allow IgG antibody binding. In this study we have improved the enzyme–linked immunosorbent assay test based on the synthetic peptide—lipoic acid conjugate by using a multiple antigen peptide system containing eight copies of the peptide as antigen. This approach avoids the use of a peptide conjugated to a carrier protein and was found to be particularly efficient because 23 of 27 primary biliary cirrhosis M2 + sera (85%) could be identified. A multiple antigen peptide without lipoic acid was not recognized by primary biliary cirrhosis antibodies. The peptide used in the multiple antigen peptide construction was a short 13–mer peptide encompassing a highly conserved sequence present in both the outer (residues 40-52) and the inner (residues 167-179) lipoyl–binding sites of the enzyme. Our results thus confirm that the highly conserved lipoate site, when associated with lipoic acid, constitutes a major conformational epitope of E2. The multiple antigen peptide construction with peptide—lipoic acid conjugate could be used as a valuable probe for primary biliary cirrhosis diagnosis.
Preoperative Scintigraphic Visualization of an Orbital Metastasis Before Identification of Carcinoma in a Nonfunctioning Thyroid Nodule
Authors: Sami Boughattas, Habib Khochtali, Nadia Arifa, Maryem Degdegui, Habib Hassine, Ali Bakir, Habib Essabbah
Journal: Clinical Nuclear Medicine (2004)

Preoperative accumulation of Tc-99m pertechnetate and radioiodine in metastases of well-differentiated thyroid carcinoma is uncommon. The authors report the case of a 51-year-old woman with follicular thyroid carcinoma revealed by a right orbital metastasis. I-131 scintigraphy performed before thyroidectomy showed intense uptake in an orbital metastasis despite the presence of an intact thyroid gland.
Patch testing discordance alert: False-negative findings with rubber additives and fragrances
Authors: Elizabeth F. Sherertz, Anthony F. Fransway, Donald V. Belsito, Vincent A. DeLeo, Joseph F. Fowler, Howard I. Maibach, James G. Marks, C.G.Toby Mathias, Melanie D. Pratt, Robert L. Rietschel, James S. Taylor
Journal: Journal of the American Academy of Dermatology (2001)
An update on the medical management of breast cancer
Authors: B. Yeo, N. C. Turner, A. Jones
Journal: BMJ (2014)

#### Summary points

Breast cancer remained the most common cancer in women in 2013 and its incidence continues to rise.1 Nonetheless, mortality is falling, partly as a result of earlier diagnosis through mammographic screening,2 improved surgical techniques and attention to margins, improved delivery of radiotherapy, and better adjuvant medical therapies (fig 1⇓). Despite these improvements, breast cancer remains the second most common cause of death from cancer in women.



Fig 1 Incidence of breast cancer in women and mortality rates in the United Kingdom over the past 30 years. Data from Cancer Research UK1



This review focuses on the medical treatment of breast cancer in the adjuvant and metastatic settings, with particular attention to recent advances and changes in practice since our last review in 2008.3 4 We discuss how targeted therapies can be used to individualise and tailor the management of breast cancer according to tumour biology and molecular subtype.

#### Sources and selection criteria

We used PubMed to identify recent published updates on the medical management of breast cancer. We also referenced presentations from international conferences and consulted with other experts in the breast cancer field.

### Diagnosis

Guidelines on the diagnosis of early breast cancer have changed little since our last review. Population based mammography screening for asymptomatic women is currently …
COMMENTARIES ON DISEASES OF THE LACHRYMAL PASSAGES.Read in the Section on Ophthalmology, at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: H. GRADLE
Journal: JAMA (1893)

The objective sign of disease of the tear passages, viz: the overflow of tears, varies in degree in different patients. From the history and by the personal examination, it can be learned that while the eyes of some patients water continuously as long as they are awake, others notice the watering only when exposed to wind, smoke or dust, or on using their eyes under the condition of eye strain. In this class of patients the tears accumulate only while some stimulus excites the tear gland; but in the first mentioned class the activity of the tear gland is a continuous one. As far as we know, the secretion of the lachrymal gland is, however, not a continuous one under normal circumstances. Thus it has been noticed in congenital, absolute impermeability of the tear passage and after surgical obliteration of the tear sac, that the tears appear only when some
Letter on the Liverpool Dispensaries, and gratuitous medical advice
Authors: T. Jeffreys
Journal: BMJ (1841)

GRATUI'TOUS SERV'ICES OF MEDICAL MEN. that in an infirmary, capable of accommodating, at one time, as many as 150 in-patients, two or- dinary physicians and twi-o surgeons are enough to transact the business; but he recommends, where the number of beds is so considerable, the appointment of a similar number of assistant medical officers, to supply the places of the ordinary physicians andl surgeons, in cases of absence, death, or resignation.*In a table of provincial infirmaries, drawn up by Dr. Wal'ker, and in some hospital reports nowv before me, I find that the following hospitals have each two physicians and two sulrgeons, viz.York, Lancaster, Gloucester, Chichester, Durhain Dumfries, Hereford, and Chester.'Th-e following have each three physicians and three sur- geons, Hull, Liverpool, Leeds, Norfolk, Sheffield Worcester, and Reading.Derby, Northampton, Huddersfield, and Stafford have each two physi-
Mediastinal Hemorrhage after Treatment of Thyrotoxicosis Using Radioiodine
Authors: DO A. PIERS, SVEN JANSSEN, HESSEL R. OOSTEN, KEES B. PRENGER
Journal: Clinical Nuclear Medicine (1988)

A patient presented with a massive mediastinal hemorrhage due to a ruptured thyroid artery, occurring eight weeks after treatment with radioiodine for thyrotoxicosis. Suspicion of a causal relation is supported by vascular abnormalities found in the thyroid after treatment with radioiodine.
Group Therapy in the Treatment of Diabetes
Authors: Robert B Tattersall, David K McCulloch, Mark Aveline
Journal: Diabetes Care (1985)

The psychological burden imposed by diabetes is large but is often ignored by health care professionals who concentrate on its technical aspects. In this article we review the need for psychosocial support in the treatment of diabetes. Group psychotherapy, although most widely used in psychiatry, was in fact started by a physician almost 80 yr ago and has been used as an adjunct to the management of many medical conditions. Limited experience of group psychotherapy among diabetic patients has given encouraging results. Issues remain, however, as to which groups of patients might benefit most, who should act as group leader, and how one can best assess outcome.
Studies in Peripheral Arterial Occlusive Disease
Authors: STANFORD WESSLER, NORMAN R. SILBERG
Journal: Circulation (1953)

A controlled clinical-pathologic study of peripheral arteriosclerotic gangrene is reported in which all amputated specimens were examined by a special technic of injection and dissection of the arteries. The type of patient in whom gangrene usually develops is defined. The effect of various clinical and pathologic conditions on the degree of arterial insufficiency is discussed from the viewpoints of pathogenesis and therapy.