tbuckley/cabot-search huggingface dataset:
Telomerase Template Antagonist GRN163L Disrupts Telomere Maintenance, Tumor Growth, and Metastasis of Breast Cancer
Authors: Amelia E. Hochreiter, Hongling Xiao, Erin M. Goldblatt, Sergei M. Gryaznov, Kathy D. Miller, Sunil Badve, George W. Sledge, Brittney-Shea Herbert
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Maintenance of telomeres by telomerase is critical for the continuing proliferation of most advanced cancer cells. Telomerase activity has been detected in the vast majority of cancer cells but not most normal cells, making the enzyme an attractive target for anticancer therapy. The aim of this study was to address the breast cancer translational potential of the novel telomerase inhibitor, GRN163L. Experimental Design: In the present study, we investigated the effects of GRN163L treatment on a panel of breast cancer cells representing different tumor subtypes with varying genetic backgrounds, including ER+, ER−, HER2+, BRCA1 mutant breast tumor cells as well as doxorubicin-resistant cancer cells. To investigate the in vivo effects of GRN163L, we employed a breast cancer xenograft and metastasis model that simulates a clinical situation in which a patient arrives with a primary tumor that may be then treated or surgically removed. Results: GRN163L effectively inhibited telomerase activity in a dose-dependent fashion in all breast cancer cell lines resulting in progressive telomere shortening. A mismatch control oligonucleotide showed no effect on telomerase activity and GRN163L did not significantly affect telomere shortening in normal human mammary epithelial cells or in endothelial cells. Breast cancer cells that exhibited telomerase inhibition also exhibited significant reduction in colony formation and tumorigenicity. Furthermore, GRN163L suppressed tumor growth and lung metastases (P = 0.017) of MDA-MB-231 cells in vivo after 4 weeks of treatment. Conclusions: These results show in vivo effectiveness of GRN163L in breast cancer and support its promising clinical potential for breast cancer treatment.
A BIOLOGIC CLASSIFICATION OF PNEUMOCOCCI BY MEANS OF IMMUNITY REACTIONS
Authors: A. R. DOCHEZ
Journal: JAMA (1913)

The early work of Koch on etiology led him to formulate certain laws which he demanded should be fulfilled before the relationship of any micro-organism to disease could be regarded as satisfactorily established. Subsequent students have sought to fulfil the requirements of Koch, and the result has been that with the elucidation of each well-recognized infection, a single bacteriologic unit has become accepted as the causative agent. Bacteria, however, are not strictly limited in the pathologic process which they induce, and the lesion caused by a single variety may vary somewhat with its location in the animal body. The pathologic and clinical study of disease is, however, so extensive to-day that the various types of activity of the same bacterial race have been thoroughly described and correlated, so that the nature of the infectious agent can in most instances be assumed from the character of the pathologic process. From the
Severity of inflammation of tympanic membrane as predictor of clinical course of recurrent acute otitis media.
Authors: C L Appelman, J Q Claessen, F W Touw-Otten, G J Hordijk, R A de Melker
Journal: BMJ (1993)

with standard management, reporting that they seemed to be a routine case for junior medical staff and had to wait until the end of regular operating lists for treatment.4Medical management of miscarriage has the potential for resolving some of these issues and may have economic implications by freeing surgical resources for other uses.5 Randomised studies comparing medical with surgical management are required to evaluate this new method of treatment.
Immune complex processing in patients with systemic lupus erythematosus. In vivo imaging and clearance studies.
Authors: K A Davies, A M Peters, H L Beynon, M J Walport
Journal: Journal of Clinical Investigation (1992)

Abnormal processing of immune complexes (IC) may be important in the pathogenesis of systemic lupus erythematosus (SLE). The clearance of large soluble IC (comprising hepatitis B surface antigen (HBsAg)/anti-HBsAg) radiolabeled with 123I was examined in 12 normal subjects and 10 patients with SLE. IC localization was analyzed by static and dynamic gamma-scintigraphy. Initial IC clearance from blood was more rapid in patients (median t1/2 = 2.15 min) than normals (median t1/2 = 5.15 min) due to more rapid uptake in the liver. However, in the SLE group, up to 12% of complexes were released from the liver after 30-50 min. Splenic uptake of immune complexes was reduced in the patients and there was reduced ability to retain IC in this organ. Plasma complement levels and erythrocyte complement receptor type 1 numbers were reduced in the patients, resulting in defective opsonization of IC and reduced red cell binding in vivo. These observations support the hypothesis that IC handling is abnormal in SLE.
Prostaglandin A_1 in Hypertensive Crisis
Authors: LAWRENCE M. SLOTKOFF
Journal: Annals of Internal Medicine (1974)

Prostaglandin A1 (PGA1) causes vasodilation, natriuresis, and is inotropic. Its onset of action is rapid. PGA1 was administered, in doses ranging from 0.6 to 2.4 µg/kg body weight · min, to a woman with severe hypertension in congestive heart failure. The infusion was continued for more than 2 hours. During that time her blood pressure fell from 220/110 to 100/60 mm Hg, a diuresis of 18 ml/min was reached, and within several hours symptoms and signs of congestive heart failure cleared. These effects were dose-related. Within minutes after cessation of the PGA1 infusion, blood pressure and renal functions returned to pretreatment levels. Peripheral renin levels were low and did not rise significantly in response to PGA1, probably because of previously administered adrenergic blockers. Despite previous sympathetic blockade and low renin levels, PGA1 had all the previously reported effects on renal function. This case illustrates a possible therapeutic use for PGA1 in hypertensive crisis.
Reverse Mismatch Between Perfusion and Aerosol Ventilation in Transplanted Lungs
Authors: C C KUNI, R P DUCRET, R E NAKHLEH, R J BOUDREAU
Journal: Clinical Nuclear Medicine (1993)

Thirty ventilation-perfusion pulmonary scintigraphic studies were performed in 13 patients who had undergone unilateral lung transplantation. Ventilation–perfusion mismatch (ventilation better than perfusion) was judged absent, mild, moderate, or severe in the transplanted and native lungs. Ventilation-perfusion mismatch was significantly worse in the transplanted lungs (p<.0001). Findings of lung biopsies and chest roentgenograms failed to correlate with the severity of ventilation-perfusion mismatch. Hypoxic pulmonary vasoconstriction appears to be significantly impaired in most unilateral lung transplants; the mechanism for this impairment is unclear.
A Comprehensive Assessment of the Avoidability of Long-Term Complications of Diabetes. A case-control study. SID-AMD Italian Study Group for the Implementation of the St. Vincent Declaration
Authors: Antonio Nicolucci, Donatella Cavaliere, Nicola Scorpiglione, Fabrizio Carinci, Fabio Capani, Gianni Tognoni, Massimo Massi Benedetti
Journal: Diabetes Care (1996)

OBJECTIVE To identify and quantify risk factors for the development of long-term diabetic complications (i.e., critical limb ischemia, amputation, chronic renal failure [creatinine &amp;gt; 3 mg/dl], dialysis treatment, proliferative retinopathy, blindness), with particular emphasis on those variables that, being related to quality of care, can be considered avoidable. RESEARCH DESIGN AND METHODS We designed a case-control study that enrolled 886 patients with long-term diabetic complications and 1,888 control subjects without complications from 35 diabetic outpatient clinics and 49 general practitioners' offices during a 6-month period. Selected socioeconomic, pathophysiologic, self-care, health care, and lifestyle information were collected for all patients. RESULTS A logistic regression analysis showed that several factors are related to the development of major diabetic complications. Among patient characteristics, male sex (odds ratio [OR] = 1.8, 95% CI 1.4–2.3) and age (OR = 1.7, 95% CI 1.2–2.4 for patients between 50 and 69 years of age as opposed to those younger than 50 years of age) were associated with an increased risk of complication. Among clinical variables, the type and the duration of diabetes were the most important predictors of diabetic complications. The presence of hypertension was also associated with the development of diabetic complications, particularly when it was poorly controlled by treatment (OR = 3.1, 95% CI 2.3–4.3). Patients who needed help to reach a health care facility and those who did not regularly attend such a facility were at higher risk of developing complications (OR = 1.5, 95% CI 1.2–1.9; OR = 1.7, 95% CI 1.3–2.2, respectively). Educational aspects were also related to the outcome: patients who did not receive any kind of educational intervention had an increased risk of developing complications (OR = 4.1, 95% CI 1.7–9.7), while self-management of insulin therapy had a protective effect (OR = 0.6, 95% CI 0.5–0.8). The summary attributable risk related to avoidable risk factors (i.e., uncontrolled hypertension, poor compliance with visit scheduling, inadequate diabetes education, no self-management of insulin treatment) was 0.39. CONCLUSIONS Our data suggest that, by removing avoidable risk factors, the number of diabetic complications considered could be reduced by more than one-third. The case-control methodology represents an efficient way of monitoring clinical practice and relating it to important outcomes. It can be of help for policy makers in identifying the more effective strategies and in tailoring specific interventions aimed at improving the quality of the care delivered to diabetic patients.
THE GENERAL CONDITIONS ASSOCIATED WITH INSANITY.THEIR CONNOTATIONS AND CERTAIN DEDUCTIONS AS TO THEIR SIGNIFICANCE.
Authors: H. A. TOMLINSON
Journal: JAMA (1906)

The thesis to be defended in this paper is formulated in the following statement: There can not be special change in an organ without general disease in the rest of the organism, and in the study and treatment of the special condition the general involvement and its extent are the most important. There are two assumptions in this connection which may be made concerning the human organism, based on what is known of its cytology and what has been demonstrated as to the processes of its functional activity. First, that the primary functions are those of vegetation, and that all others are related and in sequence to some form of activity involved in the processes of nutrition; second, that the nervous system is the last in the order of development and the most complex in its structure; also, the complexity of the structure and functions of the nervous system has
P346 TAUROURSODESOXICOLATE (TUDC) PREVENTS ACTIVATION OF THE PRO-CHOLESTATIC SIGNALLING PATHWAYS, cPKC AND PI3K/Akt, IN ESTRADIOL 17β-D-GLUCURONIDE (E217G)-INDUCED CHOLESTASIS
Authors: A.C. Boaglio, G.S. Miszczuk, I.R. Barroso, F.D. Toledo, F.A. Crocenzi, M.G. Roma
Journal: Journal of Hepatology (2014)
Content first, frame later
Authors: John J. Ohala
Journal: Behavioral and Brain Sciences (1998)

There is not enough reason to believe that syllables are primary in speech and evolved from the cyclic movements of chewing. There are many differences between chewing and speech and it is equally plausible that what is primary in speech is a succession of auditorily robust modulations of various acoustic parameters (amplitude, periodicity, spectrum, pitch); syllables could have evolved from this.
Temperature Biofeedback for Raynaud's Syndrome
Authors: Robert R. Freedman
Journal: JAMA (1989)

<h3>To the Editor.—</h3> I read with interest your recent article entitled "Behavioral Treatment of Raynaud's Syndrome"<sup>1</sup>and thought that recent work on the treatment of idiopathic Raynaud's disease with biofeedback and the mechanisms of this treatment would be relevant. A controlled study comparing finger temperature feedback, finger temperature feedback under mild cold stress, autogenic relaxation, and electromyogram biofeedback found that the first two methods produced reported symptom reductions of 67% and 92%, respectively, at 1-year follow-up, whereas the latter two treatments were ineffective.<sup>2</sup>These results were corroborated by ambulatory recordings of finger and ambient temperatures and by laboratory tests of the ability to increase finger temperature voluntarily without feedback. Three-year follow-up data showed that the symptomatic improvement in the two temperature feedback groups was retained.<sup>3</sup> A series of subsequent studies<sup>4</sup>replicated the above findings and demonstrated that elevations in finger temperature were accompanied by increased finger
Influence of combinations of human major histocompatibility complex genes on the course of HIV–1 infection
Authors: R.A. Kaslow, M. Carrington, R. Apple, L. Park, A. Muñoz, A.J. Saah, J.J. Goedert, C. Winkler, S.J. O'Brien, C. Rinaldo, R. Detels, W. Blattner, J. Phair, H. Erlich, D.L. Mann
Journal: Nature Medicine (1996)
THE INFLUENCE OF LOW TEMPERATURE ON THE SYMBIOSIS OF MICROORGANISMS WITH REFERENCE TO PNEUMONIA.Read in the Section of Stale Medicine at the Forty-first Annual Meeting of the American Medical Association, held in Nashville, Tenn., May 21, 1890.
Authors: J. J. KINYOUN
Journal: JAMA (1890)

It is a well established fact in bacteriology that a certain temperature range is requisite for the propagation of microorganisms, some of which may have a wide range of temperature, while others require a more limited degree, which can not be departed from without jeopardizing the life of the microorganism. The same may be said in a general way concerning their resistance to high temperature; some are killed at 50° C., while others live for a considerable time at a temperature over 100° C.  The bacteria, which are widely distributed, seldom exist alone, being usually associated with others, which constitutes the state of symbiosis. In this condition the bacteria exist and exert peculiar influence upon each other as to their manner of growth and individual virulency. A good example can be given showing the dependence upon each other of the different varieties of bacteria found in common garden earth, where
PROFESSOR KITASATO'S PRESENT WORK.
Authors: None MIAJIMA
Journal: JAMA (1904)

Under the direct supervision of the Minister of Interior, there now exist in Japan three institutes of an allied nature, namely, the Institute for Infectious Diseases, the Serum Institute, and the Lymph Institute, of which the founder and present director is Professor Kitasato, a name so well known to the world associated with that of the famous Professor Koch. The Institute for Infectious Diseases is especially designed for investigating the causes of infectious diseases, and the other two are the factories where are prepared several kinds of remedies for public demands. A brief sketch of these three institutes may perhaps be found interesting to you. Permit me, before proceeding on this subject, to digress for a moment. In the Philippine Islands several dangerous diseases are prevalent throughout the year, plague, cholera, dysentery, malaria, etc., from which many thousands of American people have already suffered and
Abnormal T-cell subset proportions in vitamin-A-deficient children
Authors: R.D. Semba, K.P. West, None Ph, A. Sommer, D.E. Griffin, B.J. Ward, D.E. Griffin, R.D. Semba, A.L. Scott, None Muhilal, G. Natadisastra
Journal: The Lancet (1993)

Although vitamin A deficiency in children seems to increase susceptibility to infection and community trials have shown that vitamin A supplementation can reduce childhood mortality from infectious diseases, the underlying biological mechanisms are largely unknown. We conducted a randomised, double-masked, placebo-controlled clinical trial among children in West Java, Indonesia, to determine whether vitamin A deficiency is associated with abnormalities in T-cell subsets and whether vitamin A supplementation affects T-cell subsets.We studied 55 children aged 3-6 years—30 with xerophthalmia and 25 without. Acutely malnourished children (<80% of reference weight-for-height) were excluded. CD4/CD8 ratios and the proportions of circulating CD4 naive, CD4 memory, CD8, CD45RA, and CD8, CD45R0 T-cell subsets were measured. Children with xerophthalmia had lower CD4/CD8 ratios (p<0·08), lower proportions of CD4 naive T cells (p<0·03), and higher proportions of CD8, CD45RO T cells (p<0·04) than those without xerophthalmia. 26 children were given vitamin A supplementation (60 mg retinol equivalent) and 29 received placebo. 5 weeks later the vitamin A group had higher CD4/CD8 ratios (p<0·001), higher proportions of CD4 naive T cells (p<0·01), and lower proportions of CD8, CD45RO T cells (p<0·05) than the placebo group.Vitamin-A-deficient children have underlying immune abnormalities in T-cell subsets and these abnormalities are reversible with vitamin A supplementation.
For Whose Benefit Do You Write?
Authors: W. P. Howle
Journal: JAMA (1899)

Oran, Mo., March 23, 1899. <h3>To the Editor:</h3> —I received a booklet last week containing "Six reprints on important topics, from recent issues of medical journals." Glancing over this booklet, I noticed that each of these six eminent men had something special to say of a certain compound, and I asked myself: Were these articles written for my benefit? Did these authors have the good of the profession in mind when they penned these lines, or were they writing for the benefit of the proprietor of this special compound? I see so much of this kind of literature that I am almost forced to the conclusion that there is a "nigger in the wood pile," and whether this colored "gent" can be ousted or not, is a debatable question. If writers would adopt the course of writers of twenty years ago, this gentleman would soon have no hiding-place. We realize
A critical role for neutrophil elastase in experimental bullous pemphigoid
Authors: Zhi Liu, Steven D. Shapiro, Xiaoye Zhou, Sally S. Twining, Robert M. Senior, George J. Giudice, Janet A. Fairley, Luis A. Diaz
Journal: Journal of Clinical Investigation (2000)

Bullous pemphigoid (BP) is an autoimmune skin disease characterized by subepidermal blisters and autoantibodies against 2 hemidesmosome-associated proteins, BP180 and BP230. The immunopathologic features of BP can be reproduced in mice by passive transfer of anti-BP180 antibodies. Lesion formation in this animal model depends upon complement activation and neutrophil recruitment. In the present study, we investigated the role of neutrophil elastase (NE) in antibody-induced blister formation in experimental BP. Abnormally high levels of caseinolytic activity, consistent with NE, were detected in extracts of lesional skin and blister fluid of mice injected with anti-BP180 IgG. The pathogenic anti-BP180 IgG failed to induce subepidermal blistering in NE-null (NE(-/-)) mutant mice. NE(-/-) mice reconstituted with neutrophils from wild-type mice became susceptible to experimental BP. Wild-type mice given NE inhibitors (alpha1-proteinase inhibitor and Me-O-Suc-Ala-Ala-Pro-Val-CH(2)Cl), but not mice given cathepsin G/chymase inhibitors (alpha1-antichymotrypsin or Z-Gly-Leu-Phe-CH(2)Cl), were resistant to the pathogenic activity of anti-BP180 antibodies. Incubation of murine skin with NE induced BP-like epidermal-dermal detachment. Finally, NE cleaved BP180 in vitro and in vivo. These results implicate NE directly in the dermal-epidermal cleavage induced by anti-BP180 antibodies in the experimental BP model.
Obstructive sleep apnoea syndrome as a risk factor for hypertension: population study
Authors: P. Lavie
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To assess whether sleep apnoea syndrome is an independent risk factor for hypertension. <b>Design:</b> Population study. <b>Setting:</b> Sleep clinic in Toronto. <b>Participants:</b> 2677 adults, aged 20-85 years, referred to the sleep clinic with suspected sleep apnoea syndrome. <b>Outcome measures:</b> Medical history, demographic data, morning and evening blood pressure, and whole night polysomnography. <b>Results:</b> Blood pressure and number of patients with hypertension increased linearly with severity of sleep apnoea, as shown by the apnoea-hypopnoea index. Multiple regression analysis of blood pressure levels of all patients not taking antihypertensives showed that apnoea was a significant predictor of both systolic and diastolic blood pressure after adjustment for age, body mass index, and sex. Multiple logistic regression showed that each additional apnoeic event per hour of sleep increased the odds of hypertension by about 1%, whereas each 10% decrease in nocturnal oxygen saturation increased the odds by 13%. <b>Conclusion:</b> Sleep apnoea syndrome is profoundly associated with hypertension independent of all relevant risk factors.
Management of retained biliary calculi: relaxation of sphincter induced by ceruletide.
Authors: A Cuschierj
Journal: BMJ (1984)

Methode simple appliquee peu apres la cholecystectomie au moyen d'un tube en T. A propos de 4 observations. La perfusion de ceruletide permet l'administration de volumes importants de solution saline pour l'elimination des calculs residuels, sans augmentation dangereuse de la pression dans les voies biliaires
A Child Case of Anaphylaxis to Polyvinylpyrrolidone Containing Medicines
Authors: T. Itazawa, Y. Adachi, Y. Okabe, Y.S. Adachi, M. Nakabayashi, T. Harai, K. Miya, K. Uese, T. Miyawaki
Journal: Journal of Allergy and Clinical Immunology (2006)
Blood Pressure and Skin Color
Authors: D. A. Nelson
Journal: JAMA (1991)

<h3>Tb the Editor.—</h3> The study by Klag et al<sup>1</sup>typifies a common fallacy in epidemiologic studies: the assumption of concordanceof genetically variable traits in human populations.<sup>2</sup>In fact, the distributions of different traits are typically discordant. A common misconception is that if a trait or disease is more or less prevalent in blacks, it must be related to skin color, since this is how we classify individuals into races. It is not widely appreciated that race is a social construct, not a biologically meaningful one; therefore, one should study sociocultural variables to help explain observed racial differences in disease prevalence.2 Klag et al demonstrate this very convincingly. Unfortunately, the casual reader may be left with the impression that a link has been found between skin color and disease. In our own work,<sup>3,4</sup>we have sought to refute the equally illogical claim that osteoporosis is associated with decreased skin pigmentation because it is more prevalent in whites. In this case, there is some logical biochemical con