tbuckley/cabot-search huggingface dataset:
Cellular Location and Expression Pattern of NHERF1 in Human Breast Cancer and the Impact of NHERF1 on the Growth of Breast Cancer Cells.
Authors: S. Cheng, S. Cheng, J. He, T. Martin, L. Ye, R. Mansel, W. Jiang
Journal: Cancer Research (2009)

Abstract BACKGROUND: The Na+/H+ exchange regulatory factor 1 (NHERF1) is an adapter protein that, when present in the cytoplasmic region, regulates trafficking and signaling of several G protein-coupled receptors (GPCRs). However, it has been recently suggested that, when located in the nucleus of cells, NHERF1 may have an oncogenic role in cancer. Recent work has shown that NHERF1 may be involved in the progression of certain solid tumours including breast cancer. The aim of the current study were: first to evaluate the spatial and cellular location of the NHEREF1 protein in mammary tissues, mammary epithelial and cancer cells, second to determine the expression pattern of the NHERF1 transcript in human breast cancer and deduce a possible association with clinical and pathological factors and, finally, to investigate the cellular impact of NHERF1 expression on breast cancer cells.MATERIALS AND METHODS: Expression of NHERF1 was examined in a cohort of breast tissue samples. The protein levels and distributions were assessed using immunohistochemical staining (IHC) and imaging analysis tools. The distribution of the NHERF1 protein in nucleus and cytoplasm was calculated using the protein staining intensity ratio between the two compartments. The transcript level was determined using quantitative real time-PCR. Constructed ribozyme transgenes were used to knock-down NHERF1 in MCF-7 cells, and the effect this had on in vitro cell growth was examined using in vitro methods.RESULTS: NHERF1 protein staining was seen in both normal epithelial cells and cancer cells in tissues. However, the staining pattern in cancer cells and normal epithelial cells was different. The protein was seen at a higher level in the nucleaus of cancer cells, as shown by a higher nuclear/cytoplasmic ratio of NHERF1 staining in breast cancer cells when compared with that in normal mammary epithelial cells (p=0.038). NHERF1 expression was increased in high grade tumours compared with low grade tumours (p=0.0016, grade-3 vs grade-1). Quantitative analysis of the NHERF1 transcript revealed a higher level expression in samples from patients with poor prognosis and that this was linked to the long term survival: mean survival for patients with high NHERF1 was 102 (55-148.8, 95%CI) months compared with 136 (126.6-145.9) months for patients with low NHERF1 transcripts. Using human breast cancer cell line, MCF7, we created NHERF1 knockdown subline. Loss of NHERF1 in the MCF-7 subline resulted in an increase in the growth rate, in vitro.CONCLUSION: This study shows that NHERF1 influences the growth of breast cancer cells. However, the effect of NHERF1 is dependent upon the levels of expression of NHERF1 in breast cancer tissues and most importantly determined by the cellular location of this protein in cancer cells. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3155.
Epstein-Barr virus microRNAs repress BCL6 expression in diffuse large B-cell lymphoma
Authors: D Martín-Pérez, P Vargiu, S Montes-Moreno, E A León, S M Rodríguez-Pinilla, L D Lisio, N Martínez, R Rodríguez, M Mollejo, J Castellvi, D G Pisano, M Sánchez-Beato, M A Piris
Journal: Leukemia (2011)
The Effect on Cardiac Output of the Conversion from Atrial Fibrillation to a Normal Sinus Mechanism.
Authors: Theodore Rodman
Journal: Annals of Internal Medicine (1964)

s1 October 1964The Effect on Cardiac Output of the Conversion from Atrial Fibrillation to a Normal Sinus Mechanism.Theodore Rodman, M.D., F.A.C.P., Bernard H. Pastor, M.D., F.A.C.P.Theodore Rodman, M.D., F.A.C.P.Search for more papers by this author, Bernard H. Pastor, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-61-4-799_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe recent introduction of direct-current external electric shock for the restoration of a normal sinus mechanism in patients with atrial fibrillation has reopened the question of the desirability of restoring a normal sinus pacemaker. To determine whether restoration of a sinus rhythm is hemodynamically beneficial to some or all patients, we have measured the cardiac output in a group of 47 patients with atrial fibrillation in whom an attempt at conversion was about to be made. The cardiac output determination was repeated if restoration of a normal sinus rhythm was accomplished.All patients were given digitalis in doses sufficient to... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Theodore Rodman, M.D., F.A.C.P.; Bernard H. Pastor, M.D., F.A.C.P.Affiliations: Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1964Volume 61, Issue 4Page: 799-800KeywordsAtrial fibrillationCardiac outputPacemakersShock ePublished: 1 December 2008 Issue Published: 1 October 1964 PDF downloadLoading ...
Age and activity effects on rate of bone mineral loss.
Authors: D M Smith, M R Khairi, J Norton, C C Johnston
Journal: Journal of Clinical Investigation (1976)

It has been postulated that the rate of mineral loss in postmenopausal women remains constant with aging and that the decreased activities of daily living associated with aging contribute to mineral loss. These hypothese were examined by measuring the bone mineral content at the midshaft of the radius with the photon absorption technique. The estimated rate of loss was calculated in a cross-sectional study as the regression coefficient of bone mineral content vs. age and in a longitudinal study as the regression coefficient of bone mineral content vs. time. In the cross-sectional study, Group A, which consisted of 264 women aged 50-72 yr, had an estimated rate of loss of -0.0114 +/- 0.0014 (SE) g/cm per yr. Group B, which consisted of 266 women aged 73-96 yr, had an estimated rate of loss of -0.0055 +/- 0.0017 g/cm per yr. In the longitudinal study, Group C consisted of 33 women aged 51-65 yr who were followed for an average of 4.5 yr with a mean number of 16 visits per subject; they were found to have a mean rate of loss of -0.00990 +/- 0.00107 g/cm per yr. Group D consisted of 38 women aged 70-91 yr who were followed for an average of 3.8 yr with a mean number of 31 visits per subjects; they were found to have a mean rate of loss of -0.00020 +/- 0.00236 g/cm per yr. The estimated and directly measured rates of loss were more rapid in the younger groups than in the older groups (A vs. B, P less than 0.001; C vs. D, P less than 0.001). These data demonstrate that the mean rate of mineral loss is not constant with aging and that in elderly subjects it is significantly slower than that of the earlier postmenopausal years. Since the elderly women were the less active, these findings suggest that factors other than decreased physical activity are more important in determining the rates of mineral loss.
Anti–Tumor Necrosis Factor Therapy Inhibits Pancreatic Tumor Growth and Metastasis
Authors: Jan-Hendrik Egberts, Vera Cloosters, Andreas Noack, Bodo Schniewind, Lutz Thon, Stefanie Klose, Bastian Kettler, Corinna von Forstner, Christian Kneitz, Jürgen Tepel, Dieter Adam, Harald Wajant, Holger Kalthoff, Anna Trauzold
Journal: Cancer Research (2008)

Chronic inflammation has been implicated in the pathogenesis of many severe autoimmune disorders, as well as in diabetes, pulmonary diseases, and cancer. Inflammation accompanies most solid cancers including pancreatic ductal adenocarcinoma (PDAC), one of the most fatal cancers with surgery being the only curative therapeutic approach currently available. In the present work, we investigated the role of the major proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) in the malignancy of PDAC cells in vitro and in vivo. In vitro, TNFalpha strongly increased invasiveness of Colo357, BxPc3, and PancTuI cells and showed only moderate antiproliferative effect. TNFalpha treatment of mice bearing orthotopically growing PDAC tumors led to dramatically enhanced tumor growth and metastasis. Notably, we found that PDAC cells themselves secrete TNFalpha. Although inhibition of TNFalpha with infliximab or etanercept only marginally affected proliferation and invasiveness of PDAC cells in vitro, both reagents exerted strong antitumoral effects in vivo. In severe combined immunodeficient mice with orthotopically growing Colo357, BxPc3, or PancTuI tumors, human-specific anti-TNF antibody infliximab reduced tumor growth and metastasis by about 30% and 50%, respectively. Importantly, in a PDAC resection model performed with PancTuI cells, we found an even stronger therapeutic effect for both anti-TNF compounds. Infliximab and etanercept reduced the number of liver metastases by 69% and 42%, respectively, as well as volumes of recurrent tumors by 73% and 51%. Thus, tumor cell-derived TNFalpha plays a profound role in malignancy of PDAC, and inhibition of TNFalpha represents a promising therapeutic option particularly in adjuvant therapy after subtotal pancreatectomy.
Pulmonary carcinogenicity of inhaled particles and the maximum tolerated dose.
Authors: G Oberdörster
Journal: Environmental Health Perspectives (1997)

Chronic inhalation bioassays in rodents are used to assess pulmonary carcinogenicity for purposes of hazard identification and potentially for risk characterization. The influence of high experimental doses on tumor development has been recognized for some time and has led to the concept of maximum tolerated dose (MTD) for dose selection, with the highest dose being at the MTD. Exposure at the MTD should ensure that the animals are sufficiently challenged while at the same time the animal's normal longevity is not altered from effects other than carcinogenicity. A characteristic of exposure-dose-response relationships for chronically inhaled particles is that lung tumors are significantly increased only at high exposure levels, and that lung tumors are seen in rats only but not in mice or hamsters. This lung tumor response in rats is thought to be secondary to persistent alveolar inflammation, indicating that the MTD may have been exceeded. Thus, mechanisms of toxicity and carcinogenicity may be dose dependent and may not operate at lower doses that humans normally experience. Despite awareness of this problem, carcinogenicity bioassays that evaluate particulate compounds in rodents have not always been designed with the MTD concept in mind. This is due to several problems associated with determining an appropriate MTD for particle inhalation studies. One requirement for the MTD is that some toxicity should be observed. However, it is difficult to define what degree of toxic response is indicative of the MTD. For particle inhalation studies, various noncancer end points in addition to mortality and body weight gain have been considered as indicators of the MTD, i.e., pulmonary inflammation, increased epithelial cell proliferation, increased lung weight, impairment of particle clearance function, and significant histopathological findings at the end of a subchronic study. However, there is no general agreement about quantification of these end points to define the MTD. To determine whether pulmonary responses are indicative of the MTD, we suggest defining an MTD based on results of a multidose subchronic and chronic inhalation study with a known human particulate carcinogen, e.g., asbestos or crystalline silica. Quantification of effects in such a study using the noncancer end points listed above would identify a dose level without significant signs of toxicity at the end of the subchronic study. If this dose level still results in significant lung tumor incidence at the end of the chronic study. We will have a sound basis for characterizing the MTD and justifying its use in future particle inhalation studies. Also, a better understanding of cellular and molecular mechanisms of particle-induced lung tumors is needed to support the MTD concept.
THE TREATMENT OF BONE CAVITIES.REPORT OF A CASE OF COMPOUND COMMINUTED FRACTURE OF THE HIP, FOLLOWED BY BONY UNION AND A MOVABLE JOINT.
Authors: JAMES E. MOORE
Journal: JAMA (1906)

I have had so many inquiries concerning an article on the treatment of bone cavities published inThe Journal, May 20, 1905, that it seemed that a brief paper on the same topic might interest the members of this Section. The obliteration of dead space in the soft tissues is a very simple matter since we have learned to use buried catgut sutures, and the treatment of abscesses of the soft parts by incision and drainage is usually followed by speedy convalescence. The obliteration of dead space in bone, however, has been very unsatisfactory. In fact, it has been so difficult that in the majority of cases we have not tried to fill the cavity, but have treated it as an open wound until Nature furnished an epithelial lining for the whole cavity. The method of Neuber, in which the integument is turned into the bottom of the wound and
Should we screen for aortic aneurysm? No
Authors: James N Johnson
Journal: BMJ (2008)

In January, the government announced pilot screening programmes for men aged 65 in England, with national screening to follow. <b>Stephen Brearley </b>(doi: 10.1136/bmj.39517.443796.AD) describes the rationale for this proposal while <b>James Johnson</b> argues that it is not without pitfalls
Nocturia and nocturnal polyuria are symptoms of obstructive sleep apnoea
Authors: R. N. Khadr, A. Riaz, C. S. Biyani
Journal: BMJ (2014)

Greenstone and Hack comprehensively reviewed the diagnosis and management of obstructive sleep apnoea (OSA).1 From a urological standpoint, another important symptom of OSA is nocturia, particularly nocturnal polyuria. Nocturia is often the primary reason for urological referral and rated by patients as their …
A Case of Chloroform Poisoning; Recovery
Authors: W. Martin
Journal: BMJ (1886)

My method of prescribing the drug was sometimes pure terebene alone-10 drops on sugar three times a day.In other cases, I com- bined it with cod-liver oil, as follows: pure terebene, two drachmscod-liver oil, to four ounces; two drachms three times daily.I could not say, however, that the effects produced were any better in the one case than the other.If there were any difference, pure terebene alone had the preference.Some of the patients complained that the medicine made them sick others that their appetite was improved by it.In a few of the cases, it appeared to have a laxative effect.In a very large proportion, drowsiness was complained of; while in some giddiness, or even a slight transient intoxication, was observed.
Depleted uranium and public health
Authors: M. A McDiarmid
Journal: BMJ (2001)

Depleted uranium, used in anti-tank weapons, provides a common thread that links concerns about leukaemia and other health effects in peacekeeping forces returned from the Balkans and worries about the environmental impact of debris from weapons in this war-weary segment of Europe. Unlike many agents that seem suddenly to prompt health concerns,1 however, we know quite a lot about the health effects of depleted uranium.

Depleted uranium is derived from natural uranium mined from the earth's crust. Uranium is composed of three radioactive isotopes, U238, U235, and U234, which decay to other radioactive elements and ultimately to stable non-radioactive isotopes of lead.2–4 Uranium isotopes emit α particles during decay, which possess high energy but are poorly penetrating. Thus, uranium poses primarily an internal radiation hazard to tissue in close proximity.

Uranium is not very radioactive, owing to its isotopes' relatively long half lives (105-109 years). These compare with radon, a prominent member of the daughter progeny of the uranium decay cascade, which possesses a half life of 3.8 days and a radiological activity 10 000 times greater.2–4 Depleted uranium possesses only 60% of the radioactivity of natural uranium, having been “depleted” of much of its most highly radioactive U234 and U …
Jean Baptiste Charcot — Physician, Explorer, Oceanographer
Authors: Joseph A. Gélinas
Journal: New England Journal of Medicine (1956)

THROUGH the years, many physicians have left the practice of medicine to seek fame and fortune in other fields. Some have attained prominence and distinction in politics, philosophy or letters. Few, however, have established a reputation in the field of polar exploration. One such physician who abandoned medicine to devote his life to the exploration of polar areas was Jean Baptiste Auguste Etienne Charcot.Born at Neuilly-sur-Seine near Paris on July 15, 1867, Jean Baptiste was the son of the illustrious French neurologist, Jean Martin Charcot. From his earliest years, young Charcot was attracted and fascinated by the sea. His . . .
ANTISERUM TO KLEBSIELLA K43 BTS 1 SPECIFICALLY LYSES LYMPHOCYTES OF HLA-B27-POSITIVE PATIENTS WITH ANKYLOSING SPONDYUTIS FROM A LONDON POPULATION
Authors: J.K. Archer, M.M. Stubbs, H.L.F. Currey, A.F. Geczy
Journal: The Lancet (1985)
Mismatch repair deficit: a gain for diagnostic histopathology
Authors: I C TALBOT
Journal: Gut (1999)

See article on page 409 

Cawkwell and colleagues, in this issue (see page 409), describe an immunohistochemical method which enables the status of a colorectal carcinoma with respect to the two mismatch repair (MMR) genes, hMLH1 and hMSH2, to be ascertained from paraffin wax sections produced by any diagnostic histopathology laboratory.

Despite many advances in the pathological management of colorectal cancer since Dukes and Bussey1—for example, taking account of the number of lymph nodes containing metastatic tumour or the nature of the infiltrating margin of the tumour,2staging systems have not hitherto provided precise information about the biology and likely behaviour of the tumour in individual cases. By adopting the relatively simple methodology proposed by Cawkwell and colleagues, it should now be possible to assign patients reliably to one of the two main specific categories of MMR status, thereby …
Beneficial Effects of Combined Treatment With Rosiglitazone and Exercise on Cardiovascular Risk Factors in Patients With Type 2 Diabetes
Authors: Nikolaos P.E. Kadoglou, Fotios Iliadis, Christos D. Liapis, Despina Perrea, Nikoleta Angelopoulou, Miltiadis Alevizos
Journal: Diabetes Care (2007)

Physical activity attenuates metabolic and cardiovascular maladaptations in diabetes by improving glycemic control, insulin resistance, cardiorespiratory fitness, and adipocytokines levels (adiponectin, resistin, tumor necrosis factor [TNF]-α, and interleukin [IL]-6) (1,2). Likewise, thiazolidinediones favorably influence the above indexes (3,4). We hypothesized that the combination of exercise training and rosiglitazone, a thiazolidinedione, would confer additional benefits in the metabolic and cardiovascular profiles of diabetic patients, exceeding those of each treatment alone.

A total of 100 Caucasian, overweight/obese (BMI> 25 kg/m2) patients with type 2 diabetes consented to participate. They were treated with half-maximal doses of metformin (1,700 mg) and gliclazide (180 mg) for at least 6 months, with poor glycemic control eventually occurring (A1C > 7%). Smokers and patients receiving lipid-lowering medications, insulin, or thiazolidinediones were rejected. Those with vascular complications, life-threatening diseases, orthopedic problems, and heart, liver, or renal impairment were also excluded. After baseline examination, participants were randomized to one of the following age- and sex-matched groups: 1 ) the control group ( n = 25); 2 ) the exercise group ( n = 25), who underwent 8 months’ exercise training; 3 ) the rosiglitazone group ( n = 25), who had adjunctive therapy with 8 mg/day rosiglitazone; and 4 ) the rosiglitazone plus exercise (RSG + EX) group ( n = 25), who participated in the 8-month exercise program (as in the exercise group) while simultaneously receiving treatment with 8 mg/day rosiglitazone.

The prescription of the exercise program was based on initial ergocycle testing results. Afterward, its workload was gradually increased until patients achieved 50–80% V o2max during 45–60 min sessions four times a week (5). After the fourth week, the intensity and duration of each session remained constant. …
Clinical governance made simple
Authors: C. Douglas
Journal: BMJ (1998)

The Auchendreich Medical Golf Society, for decades an all male bastion, has moved with the times and now brings together men and women in a spirit of equality and healthy outdoor competition. The weather could not have been more kind for our summer event and there were some truly surprising scores and results.

But, as so often in the past, the most interesting moments of the day came later, when a dozen or so survivors of the dinner convened once more beneath the stags' heads and trophy cabinets of the club's agreeably old fashioned bar.

Though the business of this part of the evening is for obvious reasons normally confidential, the overwhelming importance to the whole of the NHS …
TUMORS OF THE CONJUNCTIVA.ILLUSTRATED BY THE PRESENT EXHIBIT OF MORBID GROWTHS.
Authors: EDWARD ADAMS SHUMWAY
Journal: JAMA (1903)

In response to the request of the Chairman of your Committee on Exhibit of Pathologic Preparations for a paper on some points in the pathology of the eye, as illustrated by our exhibit of the present year, it occurred to me that it would be well to confine myself within the limits of a comparatively narrow subject, and I have therefore attempted to make a résumé of our knowledge of tumors of the conjunctiva. With this aim in view I have obtained a number of preparations showing the various growths which are found on this membrane, and I desire at this time to express my thanks to the gentlemen who have assisted me by loaning sections and mounted specimens from their collections, especially to Drs. G. E. de Schweinitz, Clarence A. Veasey, William Campbell Posey and L. Webster Fox, of Philadelphia; John E. Weeks, Peter A. Callan, Wilbur Marple, Emil
Predictive value of sputum cytology.
Authors: J Benbassat, A Regev, P E Slater
Journal: Thorax (1987)

A 60 year old woman non-smoker with bronchial asthma of 6 years9 duration, treated with aminophylline, salbutamol, and oral corticosteroids, was admitted because of increasing dyspnoea and productive cough. On examination she was in moderate respiratory distress with inspiratory and expiratory wheezes. Her chest radiograph was interpreted as normal. Two consecutive sputum examinations requested by a junior doctor reveal "malignant" cells.
Creatine Phosphokinase in Facioscapulohumeral Muscular Dystrophy
Authors: B. P. Hughes
Journal: BMJ (1971)

Study of the serum creatine kinase levels in young patients with facioscapulohumeral muscular dystrophy suggests that enzyme assay may be valuable as a screening procedure for assessing the status of relatives of an affected individual who have no previous clinical history, and that consequently it may be of use in genetic counselling.
Diagnosis of Obscure Lesions of the Skeleton
Authors: Donald C. Stahl
Journal: JAMA (1967)

A study was made of 85 patients with obscure lesions of the skeleton admitted to the Orthopedic Service of the Bronx Veterans Administration Hospital and the Hospital for Special Surgery. A wide spectrum of lesions were diagnosed, including malignant neoplasms in 66% of the patients. The relative merits and success rates of open and closed biopsy were compared. Although a higher percentage of satisfactory results was obtained with open biopsy (88%) than with closed biopsy (62%), the advantages associated with closed biopsy warrant its use in most instances.
Granulocyte-stimulating factor and severe aplastic anemia: a survey by the European Group for Blood and Marrow Transplantation (EBMT)
Authors: Gerard Socie, Jean-Yves Mary, Hubert Schrezenmeier, Judith Marsh, Andrea Bacigalupo, Anna Locasciulli, Monica Fuehrer, Albert Bekassy, Andre Tichelli, Jakob Passweg
Journal: Blood (2006)