tbuckley/cabot-search huggingface dataset:
Acquisition of Chemoresistance and EMT Phenotype Is Linked with Activation of the Endothelin A Receptor Pathway in Ovarian Carcinoma Cells
Authors: Laura Rosanò, Roberta Cianfrocca, Francesca Spinella, Valeriana Di Castro, Maria Rita Nicotra, Alessandro Lucidi, Gabriella Ferrandina, Pier Giorgio Natali, Anna Bagnato
Journal: Clinical Cancer Research (2011)

Emerging evidence suggests molecular and phenotypic association between chemoresistance and epithelial-mesenchymal transition (EMT) in cancer. Endothelin-1 (ET-1)/endothelin A receptor (ET(A)R) axis is implicated in the pathobiology of epithelial ovarian cancer (EOC) by driving tumor-promoting effects, including EMT. Here, we analyzed how ET(A)R regulates chemoresistance and EMT in EOC.The effects of ET-1 axis on cell proliferation, drug-induced apoptosis, invasiveness, and EMT were analyzed in cultured EOC cells sensitive and resistant to cisplatinum and taxol. Tumor growth in response to ET(A)R antagonist was examined in EOC xenografts. ET(A)R expression was examined in 60 human EOC tumors by immunohistochemistry and correlated with chemoresistance and EMT.In resistant EOC cells ET-1 and ET(A)R are upregulated, paralleled by enhanced mitogen activated protein kinase (MAPK) and Akt phosphorylation and cell proliferation. Moreover, in these cells the expression of E-cadherin transcriptional repressors, including Snail, Slug, and Twist, as well as of mesenchymal markers, such as vimentin and N-cadherin, were upregulated and linked with enhanced invasive behavior. Interestingly, ET(A)R blockade with zibotentan, a specific ET(A)R antagonist, or its silencing, downregulated Snail activity, restored drug sensitivity to cytotoxic-induced apoptosis, and inhibited the invasiveness of resistant cells. In vivo, zibotentan inhibited tumor growth of sensitive and resistant EOC xenografts, and sensitized to chemotherapy. Analysis of EOC human tissues revealed that ET(A)R is overexpressed in resistant tumors and is associated with EMT phenotype.Our data provide the first evidence that blockade of ET(A)R-driven EMT can overcome chemoresistance and inhibit tumor progression, improving the outcome of EOC patients' treatment.
HIV Incidence Among Injection Drug Users Enrolled in a Los Angeles Methadone Program
Authors: Peter R. Kerndt
Journal: JAMA (1995)

To the Editor.  —To estimate the human immunodeficiency virus (HIV) seroconversion rate among injection drug users (IDUs) entering a methadone treatment (maintenance or 21-day detoxification) program in Los Angeles, Calif, we retrospectively reviewed the records of all clients confidentially tested for HIV at one drug treatment center in Los Angeles between March 1989 and January 1994. All IDUs who had a negative HIV test when they first entered drug treatment, who had at least two HIV tests in the first or any subsequent treatment episode during the study period, and who had a history of injection drug use in the 12 months before they entered treatment were included in the analysis. The date of seroconversion was assigned as the midpoint between the last negative and first positive test. Seroconversion rate was calculated as the number of new HIV infections per 1000 person-years of observation.  During the 56-month study period, 3931
SLEEP PARALYSIS WITHOUT NARCOLEPSY OR CATAPLEXY
Authors: Jerome M. Schneck
Journal: JAMA (1960)

Almost invariably sleep paralysis is reported in combination with narcolepsy and cataplexy. During the past 12 years I have encountered at least six patients with sleep paralysis alone. Narcolepsy or cataplexy were not concurrent, nor was a history of either elicited. Patients generally do not seek help for sleep paralysis in isolation, and as a matter of fact the symptoms apart from those of the narcoleptic triad are apparently not often correctly diagnosed. The dramatic aspects of narcolepsy are more readily identified. When sleep paralysis is mentioned in publications it is usually included in articles stressing narcolepsy.<sup>1</sup>Only a few articles published during the past 20 years have given special attention to various aspects of sleep paralysis, such as psychodynamics and treatment.<sup>2</sup>Since the diagnosis of sleep paralysis appears to be missed often, the affliction probably is more widespread than general physicians and specialists realize. Sleep paralysis occurs
Plasma catecholamine modulation of alpha 2 adrenoreceptor agonist affinity and sensitivity in normotensive and hypertensive human platelets.
Authors: A S Hollister, J Onrot, S Lonce, J H Nadeau, D Robertson
Journal: Journal of Clinical Investigation (1986)

We measured alpha 2-adrenoreceptor density as well as affinity for and sensitivity to agonist on intact platelets of normotensive and hypertensive subjects before and after physiological increases in plasma catecholamines. In normotensives, posture-induced rises in plasma catecholamines correlated with reduced alpha 2-adrenoreceptor agonist affinity and fewer high affinity state receptors. Platelet aggregation and inhibition of adenylate cyclase by L-epinephrine also was reduced. Hypertensive subjects had similar rises in plasma catecholamines with upright posture, but showed no change in receptor affinity or sensitivity. No change in platelet alpha 2-adrenoreceptor number occurred in these studies. In vitro incubation with L-epinephrine revealed that platelets from hypertensives had slower desensitization than those from normotensives. Binding studies at different temperatures and with varying sodium concentrations found no thermodynamic or sodium-dependent differences between normotensive and hypertensive groups. These studies demonstrate that platelets from hypertensive subjects exhibit a defect in the ability of physiological concentrations of agonist to desensitize the alpha 2-adrenoreceptor.
Conjugal Loss and Syndromal Depression in a Sample of Elders Aged 70 Years or Older
Authors: Carolyn L. Turvey, Caroline Carney, Stephan Arndt, Robert B. Wallace, Regula Herzog
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The goal of this study was to describe the association between conjugal loss and both syndromal depression and depressive symptoms in a prospective cohort study of people aged 70 years or older. METHOD: A measure of syndromal depression, the short-form Composite International Diagnostic Interview (CIDI), and a revised version of the Center for Epidemiologic Studies—Depression Scale (CES-D Scale) were administered to a group of 5,449 elders in a longitudinal cohort study. The authors compared the rates of syndromal depression (CIDI diagnosis) and depressive symptoms (six CES-D Scale symptoms) in married participants and those who lost spouses between the first and second waves of assessment. RESULTS: The rate of syndromal depression in the newly bereaved was nearly nine times as high as the rate for married individuals, and the rate of depressive symptoms was nearly four times as high. The percentage of the bereaved respondents who had scores above threshold on the revised CES-D Scale was higher for those interviewed up to 2 years after loss of a spouse than for married respondents. Age, sex, prior psychiatric history, and the expectedness of the death did not differ between depressed and nondepressed newly bereaved subjects. CONCLUSIONS: Recent bereavement is a significant risk factor for syndromal depression in the elderly. Some widows and widowers experienced high levels of depressive symptoms up to 2 years after the loss of their spouses. Neither demographic variables nor variables concerning the nature of the spouse's death predicted bereavement-related depression.
Comparative effects of AT1-antagonism and angiotensin-converting enzyme inhibition on markers of inflammation and platelet aggregation in patients with coronary artery disease
Authors: Bernhard Schieffer, Christoph Bünte, Jana Witte, Kirsten Hoeper, Rainer H. Böger, Edzard Schwedhelm, Helmut Drexler
Journal: Journal of the American College of Cardiology (2004)
The Question of Normal Height in Patients With Vitamin D-Resistant Rickets
Authors: Edgar J. Schoen
Journal: JAMA (1966)

In order to determine whether normal height is possible in persons with vitamin D-resistant rickets, treatment should begin in infancy, since characteristic leg deformities and short stature are a result of weight bearing on the softened bones. Early treatment depends upon the discovery of hypophosphatemia in the neonatal period. A 19-month-old boy with familial hypophosphatemic vitamin D-resistant rickets, who received adequate vitamin D therapy starting at age 3 months, now shows no physical manifestations of rickets and is of normal height. In his mother and grandmother, the diagnosis was made and therapy attempted at 12 and 46 years, respectively. Typical rachitic findings, including shortness of stature, are permanently present in them.
‘We had to change to single beds because I itch in the night’: a qualitative study of the experiences, attitudes and approaches to coping of patients with cutaneous T-cell lymphoma
Authors: T. Beynon, L. Selman, E. Radcliffe, S. Whittaker, F. Child, D. Orlowska, C. Morgans, S. Morris, R. Harding
Journal: British Journal of Dermatology (2015)

Primary cutaneous T-cell lymphoma (CTCL) is a rare but prevalent condition which can have a significant impact on many aspects of quality of life. However, there is little evidence of patients' lived experience of CTCL.To understand in greater depth patients' experiences of living and coping with CTCL, and to inform the development of models of care for this population in line with U.K.Semi-structured interviews were conducted with a purposive sample of patients with CTCL who attended an inner-city teaching hospital. Participants were purposively selected according to their disease stage, age, sex and ethnicity.Nineteen patients with CTCL (stages IB-IVB), aged between 41 and 83 years, participated in a single interview. This included 10 men; 15 people identified themselves as white British. Interviews lasted a median of 55 (range 28-170) min. Two main themes emerged: issues regarding diagnosis, particularly a perceived delay in diagnosis, and the impact of CTCL (subthemes related to physical well-being, practical concerns and psychological and social well-being and coping).Findings from this study illuminate the diverse effects of CTCL on patients' lives. The universal experience of delays in diagnosis was striking and a concern to patients. The disease, particularly its physical symptoms, had a significant impact on patients' lives, including employment, leisure and relationships. Despite the symptom burden and its impact, participants described effective coping strategies such as drawing on social support, maintaining normal lives and becoming well informed about CTCL. Proactive holistic assessment and management of the range of patient concerns is needed in providing care for patients with CTCL and their family and friends.
Increased atherosclerosis in streptozotocin-induced diabetic mice.
Authors: V V Kunjathoor, D L Wilson, R C LeBoeuf
Journal: Journal of Clinical Investigation (1996)

Premature and extensive atheroscleroses involving renal, peripheral, and cardiovascular sites remain major complications of diabetes mellitus. Controversy exists as to the contribution of hyperglycemia versus elevated local or systemic concentrations of insulin to atherosclerosis risk. In this report, we developed the first murine model susceptible to both atherosclerosis and diabetes to determine which diabetogenic factors contribute to vascular disease. C57BL/6 and BALB/c mice were treated with multiple low-dose streptozotocin (STZ) or control citrate buffer and fed rodent chow or an atherogenic-promoting (Ath) diet for 12-20 wk. STZ treatment resulted in sustained hyperglycemia (250-420 mg/dl) and a modest reduction in plasma insulin levels for both strains regardless of diet. Citrate-treated C57BL/6 mice fed the Ath diet showed extensive oil red O-staining fatty streak aortic sinus lesions (20,537+/-2,957 micron2), the size of which did not differ for Ath-fed mice treated with STZ (16,836+/-2,136 micron2). In contrast, hyperglycemic BALB/c mice fed the Ath diet showed a 17-fold increase in atherosclerotic lesion area (7,922+/-2,096 micron2) as compared with citrate-treated mice fed the Ath diet (467+/-318 micron2). Correlations between lesion size and plasma glucose levels were significant for BALB/c (r = 0.741, P < 0.009), but not C57BL/6 (r = 0.314, P<0.3) mice. Lesion size correlated significantly with plasma cholesterol for C57BL/6 (r = 0.612, P<0.03) but not BALB/c (r = 0.630, P<0.1) mice. Immunohistochemistry showed that aortic sinus lesions from both strains contained macrophages, but smooth muscle cells were clearly present in lesions of BALB/c mice. In summary, we present the first small animal model showing accelerated atherosclerosis in response to hyperglycemia. Fatty streaks resembled those of human type II lesions in that both macrophages and smooth muscle cells were evident. In addition, our results support the concept that hyperglycemia as opposed to hyperinsulinemia contributes heavily to risk of atherosclerosis.
Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells
Authors: Ben Roediger, Ryan Kyle, Kwok Ho Yip, Nital Sumaria, Thomas V Guy, Brian S Kim, Andrew J Mitchell, Szun S Tay, Rohit Jain, Elizabeth Forbes-Blom, Xi Chen, Philip L Tong, Holly A Bolton, David Artis, William E Paul, Barbara Fazekas de St Groth, Michele A Grimbaldeston, Graham Le Gros, Wolfgang Weninger
Journal: Nature Immunology (2013)
Opioids for chronic non-cancer pain
Authors: R. Freynhagen, G. Geisslinger, S. A. Schug
Journal: BMJ (2013)

A 36 year old carpenter has a six month history of lower back pain with no specific clinical or radiological findings. As his pain has not responded to paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), he asks his doctor if he can have “stronger painkillers” such as morphine.

Opioids are a group of compounds that act by binding to opioid receptors (μ, κ, and δ), which are widely distributed in the brain, spinal cord, and peripheral tissues. They are the mainstay in the management of cancer pain, but published data show a continual increase in the volume of prescribed opioids to manage moderate to severe, chronic, non-cancer pain.1 2

Changes in attitude and aggressive marketing have driven a dramatic increase in use, with more adverse events, including deaths from overdose (now the second leading cause of accidental death in the US).3 Proponents claim that opioids are underused for chronic pain,4 but lack of good scientific data has prevented the formulation of evidence based guidelines for their use, especially in primary care.

Several meta-analyses of the effectiveness of opioids have been published. Most of the randomised clinical trials summarised in these meta-analyses were funded by the pharmaceutical industry and report heterogeneous, short term outcomes in highly selected patients. Non-randomised and uncontrolled observational studies make up the rest of the literature. Nevertheless, most studies have consistently shown some effectiveness in chronic non-cancer pain by reducing pain intensity. In particular, meta-analyses show the efficacy of opioids in neuropathic pain,5 6 7 although most guidelines regard opioids only as second or third line treatment for such pain because of their risk:benefit profile.8 9 The data are even less encouraging for chronic non-neuropathic pain, the focus of this paper. A 2009 Cochrane review of 10 randomised or quasi-randomised controlled trials compared …
Early Experience with Prospective Payment of Hospitals
Authors: John K. Iglehart
Journal: New England Journal of Medicine (1986)

The federal government's march to nationalize hospital-payment rates under Medicare's new reimbursement mechanism — an action that is flawed by a lack of data, sharp differences among hospitals in the severity of patient illnesses, and mounting congressional concern over whether the quality of care is deteriorating under this economic incentive — is nevertheless moving forward with bipartisan political support and general industry acceptance. What troubles the hospital industry most about the new prospective payment mechanism is not the concept, but the Reagan administration's zeal for employing it as an instrument to moderate sharply the growth of Medicare spending.Medicare, like . . .
Molecular Epidemiology and the Genetics of Environmental Cancer
Authors: P G Shields, C C Harris
Journal: JAMA (1991)

Environmental, occupational, and recreational exposures to carcinogens contribute to cancer risk in humans. Cancer formation is a multistage process involving tumor initiation, promotion, conversion, and progression. Carcinogens can affect any of these stages through genetic and epigenetic mechanisms. The association of a suspected carcinogenic exposure and cancer risk can be studied in populations with classic epidemiologic techniques. However, these techniques are not applicable to the assessment of risk in individuals. Molecular epidemiology, in contrast, is a field that integrates molecular biology, in vitro and in vivo laboratory models, biochemistry, and epidemiology to infer individual cancer risk. Carcinogen-macromolecular adduct levels, and somatic cell mutations can be measured to determine the biologically effective dose of a carcinogen. Molecular epidemiology also explores host cancer susceptibilities, such as carcinogen metabolic activation, DNA repair, endogenous mutation rates, and inheritance of mutated tumor suppressor genes. Substantial interindividual variation for each of these biologic end points has been shown and, therefore, highlights the need for assessing cancer risk on an individual basis. Given the pace of the last decade, it is feasible that the next 10 years will allow molecular epidemiologists to develop a cancer-risk profile for an individual that includes assessment of a number of factors. This will help focus preventive strategies and strengthen quantitative risk assessments.
Rheumatoid synovitis and joint disease. Relationship between arthroscopic and histological changes.
Authors: D B Yates, J T Scott
Journal: Annals of the Rheumatic Diseases (1975)

Arthroscopic and histological synovial features have been studied in forty-two patients with classical or definite rheumatoid arthritis. A total index of disease activity as judged arthroscopically correlates significantly with a total index of histological activity. In those patients who have dense, waxy looking villi, the intensity of the villus-proliferation is associated with lymphocytic infiltration of the synovium. No relationship between synovial lining cell proliferation and cartilage disease nor between sparsity of lymphocyte infiltration and cartilage disease could be established.
Inflammatory joint disease and HIV infection.
Authors: D. Fuchs, H. Wachter
Journal: BMJ (1988)

while in a friend's walker that we bought our son one, not because of any desire to speed up his development.We minimised any risk by choosing a well designed walker and providing adequate supervision.We would encourage safer design and better education to reduce the unacceptable injury rate.Well designed walkers with circular bases wider than their tops will prevent finger entrapment injuries and reduce the risk of tipping injuries.An 8 month old child is just as capable of falling down steps while crawling, and the message must be more supervision and stairgates, not a ban on babywalkers.Your correspondent has a rather narrow view on the potential benefits of babywalkers which ignores their "entertainment value" for the infant.Attempts to ban them because of a lack of proved clinical benefit smacks of medical arrogance.Instead, given well designed walkers and adequate information on potential risks and how to avoid them parents should be free to make their own decisions.
ABC of allergies: Good allergy practice
Authors: A B Kay
Journal: BMJ (1998)

<h3>Abstract</h3> Allergic diseases result from an exaggerated response of the immune system to external substances. They are a common and increasing cause of illness and in Britain affect about 1 in 6 of the population. The annual cost to the NHS and the Department of Health for asthma alone is in excess of £750m. Although the public is concerned that the NHS has inadequate facilities for diagnosing and treating allergic diseases, there are many allergy clinics in the NHS. These are usually linked to specific specialties (such as chest diseases; ear, nose, and throat disease; paediatrics; dermatology; and gastroenterology). The British Society for Allergy and Clinical Immunology provides a regularly updated list of allergy clinics in the NHS (obtainable from the BSACI Secretariat, Membership Services, 66 Weston Park, Thames Ditton, Surrey, KT7 0HL). Most major hospitals have facilities for allergy testing <h3>Good allergy practice</h3> Teamwork by doctors, nurses, and dietitians is essential The investigation of allergic diseases includes skin tests and challenge procedures—that is, tests for food allergy—as well as various specialised laboratory investigations Good clinical practice by providers and the effective use of allergy services by purchasers should improve prognosis and cut the costs of treating allergic diseases
Safety of Abortion
Authors: William V. Dolan
Journal: JAMA (1977)

To  Editor.—  The question of incomplete reporting notwithstanding,  article by Cates et al (237:452-455, 1977) on  mortality presents an unwarranted impression of maternal safety. To claim that legal  in  first trimester was nearly nine times safer than carrying  pregnancy to term ignores significant, well-documented risk factors for women. Indeed, the termination of pregnancy, even in  early weeks, is neither simple nor safe. 1 Aside from  early sequelae (infection, hemorrhage, uterine perforation), long-term morbidity in  form of subsequent prematurity and infertility are clearly evolving as ravages of  liberal  era. 2 Iffy, among others, has written forcefully on  sinister remote effects of therapeutic abortion 3 increasing premature births and perinatal mortality. 4 Secondary infertility is becoming an additional untoward result of artificial pregnancy termination. 5   In summary, published data contrast markedly with  relatively safe surgical procedure that induced