tbuckley/cabot-search huggingface dataset:
Loss of Retinoblastoma Tumor Suppressor Protein Makes Human Breast Cancer Cells More Sensitive to Antimetabolite Exposure
Authors: Massimo Derenzini, Giulio Donati, Giuliano Mazzini, Lorenzo Montanaro, Manuela Vici, Claudio Ceccarelli, Donatella Santini, Mario Taffurelli, Davide Treré
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The RB tumor-suppressor activity may influence the therapeutic response in human breast cancers. The effect of adjuvant therapy on clinical outcome of breast cancer patients was analyzed, and the sensitivity to 5-fluorouracil (5-FU) and methotrexate was investigated in MCF-7 and HCT-116 human cancer cells, according to their RB status. Experimental Design: RB protein (pRB) expression was prospectively evaluated by immunocytochemistry in 518 consecutive patients and its predictive value was determined according to the adjuvant therapeutic treatments. MCF-7 and HCT-116 human cancer cells silenced for RB1 expression were treated with 5-FU and methotrexate, at the same concentrations and time exposures as determined in the interstitium of breast cancers of patients treated with adjuvant chemotherapy. Results: Multivariate analysis of disease-free survival, including all the established clinical and histopathologic prognostic variables, indicated that the absence of pRB expression was the only predictive factor of good clinical outcome in patients treated with standard systemic chemotherapy (cyclophosphamide, methotrexate, and 5-FU) but not in patients treated with endocrine therapy alone. 5-FU and methotrexate significantly reduced the growth rate of RB1-silenced but not of control MCF-7 and HCT-116 cells. This was likely due to the absence of a DNA damage checkpoint with accumulation of DNA double-strand breaks in RB1-silenced but not in control cells. Conclusions: The absence of pRB expression renders human breast cancer cells more sensitive to 5-FU and methotrexate and predicts a good clinical outcome for patients treated with adjuvant chemotherapy. We suggest that patients with RB-negative breast cancers should be treated with systemic chemotherapy.
Suicide and antidepressants
Authors: J G. Edwards
Journal: BMJ (1995)

<h3>Abstract</h3> <h3>Background</h3> Hepatitis E virus is responsible for outbreaks of acute jaundice in Africa and Asia, many of which occur among displaced people or in crisis settings. While an efficacious vaccine for HEV has been developed, we lack key epidemiologic data needed to understand how best to use the vaccine for hepatitis E control in endemic countries. <h3>Methods</h3> We conducted a systematic review of articles published on hepatitis E in low and lower-middle-income countries (LMIC) in Africa and Asia. We searched PubMed, Scopus, and Embase databases to identify articles with data on anti-HEV IgG seroprevalence, outbreaks of HEV, or risk factors for HEV infection, disease, or death, and all relevant data were extracted. Using these data we describe the evidence around temporal and geographical distribution of HEV transmission and burden. We estimated pooled age-specific seroprevalence and assessed the consistency in risk factor estimates. <h3>Results</h3> We extracted data from 148 studies. Studies assessing anti-HEV IgG antibodies used 18 different commercial assays. Most cases of hepatitis E during outbreaks were not confirmed. Risk factor data suggested an increased likelihood of current or recent HEV infection and disease associated with fecal-oral transmission of HEV, as well as exposures to blood and animals. <h3>Conclusion</h3> Heterogeneity in diagnostic assays used and exposure and outcome assessment methods hinder public health efforts to quantify burden of disease and evaluate interventions over time and space. Prevention tools such as vaccines are available, but require a unified global strategy for hepatitis E control to justify widespread use.
Risk factors for injuries and other health problems sustained in a marathon.
Authors: P Satterthwaite, R Norton, P Larmer, E Robinson
Journal: British Journal of Sports Medicine (1999)

OBJECTIVES: To identify risk factors for injuries and other health problems occurring during or immediately after participation in a marathon. METHODS: A prospective cohort study was undertaken of participants in the 1993 Auckland Citibank marathon. Demographic data, information on running experience, training and injuries, and information on other lifestyle factors were obtained from participants before the race using an interviewer-administered questionnaire. Information on injuries and other health problems sustained during or immediately after the marathon were obtained by a self administered questionnaire. Logistic regression analyses were undertaken to identify significant risk factors for health problems. RESULTS: This study, one of only a few controlled epidemiological studies that have been undertaken of running injuries, has identified a number of risk factors for injuries and other health problems sustained in a marathon. Men were at increased risk of hamstring and calf problems, whereas women were at increased risk of hip problems. Participation in a marathon for the first time, participation in other sports, illness in the two weeks before the marathon, current use of medication, and drinking alcohol once a month or more, were associated with increased self reported risks of problems. While increased training seemed to increase the risk of front thigh and hamstring problems, it may decrease the risk of knee problems. There are significant but complex relations between age and risk of injury or health problem. CONCLUSIONS: This study has identified certain high risk subjects and risk factors for injuries and other health problems sustained in a marathon. In particular, subjects who have recently been unwell or are taking medication should weigh up carefully the pros and cons of participating.
Relapse of Major Depression During Pregnancy in Women Who Maintain or Discontinue Antidepressant Treatment
Authors: Lee S. Cohen
Journal: JAMA (2006)

ContextPregnancy has historically been described as a time of emotional well-being, providing “protection” against psychiatric disorder. However, systematic delineation of risk of relapse in women who maintain or discontinue pharmacological treatment during pregnancy is necessary.ObjectiveTo describe risk of relapse in pregnant women who discontinued antidepressant medication proximate to conception compared with those who maintained treatment with these medications.Design, Setting, and PatientsA prospective naturalistic investigation using longitudinal psychiatric assessments on a monthly basis across pregnancy; a survival analysis was conducted to determine time to relapse of depression during pregnancy. A total of 201 pregnant women were enrolled between March 1999 and April 2003 from 3 centers with specific expertise in the treatment of psychiatric illness during pregnancy. The cohort of women was recruited from (1) within the hospital clinics, (2) self-referral via advertisements and community outreach detailing the study, and (3) direct referrals from the community. Participants were considered eligible if they (1) had a history of major depression prior to pregnancy, (2) were less than 16 weeks' gestation, (3) were euthymic for at least 3 months prior to their last menstrual period, and (4) were currently or recently (&lt;12 weeks prior to last menstrual period) receiving antidepressant treatment. Of the 201 participants, 13 miscarried, 5 electively terminated their pregnancy, 12 were lost to follow-up prior to completion of pregnancy, and 8 chose to discontinue participation in the study.Main Outcome MeasureRelapse of major depression defined as fulfilling Structured Clinical Interview for DSM-IV [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition] Diagnosis (SCID) criteria.ResultsAmong the 201 women in the sample, 86 (43%) experienced a relapse of major depression during pregnancy. Among the 82 women who maintained their medication throughout their pregnancy, 21 (26%) relapsed compared with 44 (68%) of the 65 women who discontinued medication. Women who discontinued medication relapsed significantly more frequently over the course of their pregnancy compared with women who maintained their medication (hazard ratio, 5.0; 95% confidence interval, 2.8-9.1; P&lt;.001).ConclusionsPregnancy is not “protective” with respect to risk of relapse of major depression. Women with histories of depression who are euthymic in the context of ongoing antidepressant therapy should be aware of the association of depressive relapse during pregnancy with antidepressant discontinuation.
When Pestilence Prevails … Physician Responsibilities in Epidemics
Authors: Samuel J. Huber, Matthew K. Wynia
Journal: The American Journal of Bioethics (2004)

The threat of bioterrorism, the emergence of the SARS epidemic, and a recent focus on professionalism among physicians, present a timely opportunity for a review of, and renewed commitment to, physician obligations to care for patients during epidemics. The professional obligation to care for contagious patients is part of a larger "duty to treat," which historically became accepted when 1) a risk of nosocomial infection was perceived, 2) an organized professional body existed to promote the duty, and 3) the public came to rely on the duty. Physicians' responses to epidemics from the Hippocratic era to the present suggests an evolving acceptance of the professional duty to treat contagious patients, reaching a long-held peak between 1847 and the1950's. There has been some professional retrenchment against this duty to treat in the last 40 years but, we argue, conditions favoring acceptance of the duty are met today. A renewed embrace of physicians' duty to treat patients during epidemics, despite conditions of personal risk, might strengthen medicine's relationship with society, improve society's capacity to prepare for threats such as bioterrorism and new epidemics, and contribute to the development of a more robust and meaningful medical professionalism.
An antigen shared by a human T cell subset and B cell chronic lymphocytic leukemic cells. Distribution on normal and malignant lymphoid cells.
Authors: L Boumsell, H Coppin, D Pham, B Raynal, J Lemerle, J Dausset, A Bernard
Journal: The Journal of Experimental Medicine (1980)

We obtained a monoclonal antibody, A50, after immunizing Biozzi's high responder strain of mice with T cell chronic lymphocytic leukemia (T-CLL) cells. A50 recognized an antigen present on the surface of B cell chronic lymphocytic leukemia cells from many patients and from cells of T lineage from any subject we tested. We could not find this antigen either on the surface of normal B cell or on other non-T cell malignancies. On T cells, this antigen was present on a subpopulation of thymus cells, and on most peripheral T cells. The antigen was present on the surface of cells from T-CLL, Sézary's disease, and a subset o T cell lymphoma. The antigen seemed to belong to a complex set of antigenic determinants that we had defined with rabbit antisera.
FCCP is cardioprotective at concentrations that cause mitochondrial oxidation without detectable depolarisation
Authors: J BRENNAN, R BERRY, M BAGHAI, M DUCHEN, M SHATTOCK
Journal: Cardiovascular Research (2006)

The role of mitochondria and in particular of mitochondrial uncoupling in the mechanism of cardioprotection is not defined. In the accompanying paper we have shown that pretreatment of isolated rat hearts with a low concentration (100 nM) of FCCP, prior to global ischaemia, is cardioprotective, while 300 nM FCCP exacerbates injury. Here we define the mitochondrial responses to increasing concentrations of FCCP and also to explore the equivalence of the cardioprotective doses of diazoxide.Changes in mitochondrial respiration in response to FCCP and diazoxide were determined in isolated rat ventricular myocytes. In addition, mitochondrial state was monitored using confocal microscopy to record mitochondrial potential (TMRM) and redox state (NADH) during FCCP and diazoxide treatment. Myocytes were also voltage-clamped and whole cell currents recorded in response to 100 nM FCCP.FCCP (10-1000 nM) caused significant dose-dependent increase in oxygen consumption. Diazoxide (30 microM) failed to cause any measurable change in mitochondrial function. FCCP at 100 nM caused mitochondrial oxidation, but no change in mitochondrial membrane potential or (sarc)K(ATP) channel current, while at 300 nM, FCCP caused significant mitochondrial depolarisation. Diazoxide failed to induce any mitochondrial oxidation or depolarisation.Concentrations of FCCP that cause mitochondrial oxidation without depolarisation are cardioprotective. Higher FCCP concentrations dissipate mitochondrial membrane potential and exacerbate injury. This establishes the principle that mild mitochondrial uncoupling activates a protective mechanism. Diazoxide did not cause mitochondrial oxidation or mitochondrial depolarisation, suggesting it induces protection via another mechanism.
Lymph node ratio is a stronger prognotic factor than microsatellite instability in colorectal cancer patients: Results from a 7 years follow-up study
Authors: Mario Ferri, Laura Lorenzon, Mariadele Rapazzotti Onelli, Marco La Torre, Paolo Mercantini, Edoardo Virgilio, Genoveffa Balducci, Luigi Ruco, Vincenzo Ziparo, Emanuela Pilozzi
Journal: International Journal of Surgery (2013)
DECOMPOSITION OF THE CAPSULAR POLYSACCHARIDE OF PNEUMOCOCCUS TYPE III BY A BACTERIAL ENZYME
Authors: René Dubos, Oswald T. Avery
Journal: The Journal of Experimental Medicine (1931)

1. An organism has been isolated from peat soil which decomposes the specific capsular polysaccharide of Type III Pneumococcus. 2. The isolation has been made possible by the use of a synthetic mineral medium containing the specific polysaccharide as sole source of carbon. By repeated transfers in this medium the potential capacity of the organism to decompose the specific substance has been progressively increased. 3. The organism is a pleomorphic bacillus, motile and spore-bearing, exhibiting metachromatic granules; its reaction to the Gram stain varies according to the medium on which it is grown. It is strictly aerobic and grows well in plain broth and peptone solutions; it does not produce gas in any media and it forms small amounts of acid only on dextrin, galactose, lactose, salicin, and trehalose; its growth is inhibited by glucose. 4. The organism decomposes the capsular polysaccharide of Type III Pneumococcus aerobically, between pH 6.2 and 7.8, at room temperature and at 37.5 degrees C., but not at 54 degrees C. The decomposition of the specific substance is inhibited by the presence in the medium of other nutrients, such as peptones, which act as a more readily available source of energy. The action of the organism is specific; it does not attack the soluble specific substance of Type I or Type II Pneumococcus, nor any of the other bacterial polysaccharides thus far tested. 5. The organism possesses an endocellular enzyme. This enzyme has been extracted by autolysis of the bacterial cells; in sterile solution it exhibits the same specific action as do the organisms from which it is derived, decomposing only the capsular polysaccharide of Type III Pneumococcus. 6. This enzyme decomposes the Type III specific polysaccharide under anaerobic as well as under aerobic conditions; it is inactivated at 60-65 degrees C.; the rate of decomposition of the specific substance is not affected by the presence of normal serum. 7. There exists a quantitative relationship between the total amount of specific substance decomposed and the amount of enzyme preparation used; the existence of this relation makes it possible to express the activity of a given enzyme preparation in terms of the minimal amount required for the complete decomposition of a given amount of specific substance. 8. The specific decomposition of the capsular polysaccharide of Type III Pneumococcus, by the organism as well as by the enzyme it produces, illustrates once more the specificity of the types of Pneumococcus and confirms the fact that the capsular polysaccharides, and not some impurities carried along with them, are responsible for type specificity.
Lung Cancer and Other Causes of Death Among Licensed Pesticide Applicators
Authors: A Blair, D J Grauman, J H Lubin, J F Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1983)

The mortality experience of a cohort of 3,827 white men licensed to apply pesticides in Florida was evaluated to investigate health effects associated with chronic exposure to pesticides. Although the overall standardized mortality ratio (SMR) for these structural pest control workers was not significantly elevated (SMR = 103), excess deaths were observed for leukemia, particularly acute myeloid leukemia (3 observed vs. 0.9 expected), and cancers of the brain (SMR = 200) and lung (SMR = 135). The risk of lung cancer rose with the number of years licensed with SMR of 101, 155, and 289 among those licensed for less than 10 years, for 10-19 years, and for 20 years or more, respectively. Ratios of directly adjusted rates showed similar patterns with observed-to-expected ratios of 100, 175, and 186 for the length of licensure categories. Mortality from lung cancer was greater among persons first licensed before age 40 (SMR = 234) than among those first licensed after age 40 (SMR = 115). Although information on tobacco use was not available, the increasing risk of lung cancer with number of years licensed and the capacity of certain pesticides to produce neoplasms in laboratory animals suggested that some pesticides may be carcinogenic in humans.
Age-related changes in ouabain pharmacology. Ouabain exhibits a different volume of distribution in adult and young dogs.
Authors: S A Glantz, R Kernoff, R H Goldman
Journal: Circulation Research (1976)

To better understand why one must administer much higher doeses of digitalis glycosides to immature than to mature humans and animals, we studied ouabain pharmacokinetics in adult and young dogs. Consistent with reported observations that ouabain-binding, metabolism, and excretion do not change with age, we found no significant differences in the transfer coefficients in a linear two-compartment open model for ouabain pharmacokinetics following a bolus of 0.05 mg/kg. We did find, however, that young dogs had nearly twice the ouabain volumes of distribution per kilogram of body weight as adults (155.4 +/- 1.2 (SE) ml/kg vs. 80 +/- 0.6, P less than 0.0005) and that one could account for this difference with the fact that young dogs had nearly twice the plasma volume 108 +/- 9.8, vs. 68 +/- 7.3, P = 0.001) and interstitial fluid space (318 +/- 35 vs. 190 +/- 6.5, P = 0.006) as the adults. For the same dose per kilogram, left and right ventricular ouabain concentrations were inversely related to the volume of distribution, with the adults having significantly higher tissue levels and incidence of arrhythmias. One must give more ouabain to a young dog to get the same plasma concentration as in an adult because the mass of ouabain in rapid equilibrium with the plasma is diluted in a larger volume of distribution.
Tracheotomy and ventilator-associated pneumonia: the importance of oral care
Authors: P. Frost, M. P. Wise
Journal: European Respiratory Journal (2007)

To the Editors: 

We read with interest the recent study of Nseir et al. 1, which demonstrated that tracheotomy was independently associated with a decreased risk of ventilator-associated pneumonia (VAP). The authors offered several potential explanations as to why tracheotomised patients should be at decreased risk of VAP compared to patients with …
Salutary effect of disopyramide on left ventricular diastolic function in hypertrophic obstructive cardiomyopathy
Authors: Hiromi Matsubara, Satoshi Nakatani, Seiki Nagata, Fuminobu Ishikura, Yuichi Katagiri, Tohru Ohe, Kunio Miyatake
Journal: Journal of the American College of Cardiology (1995)
A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes.
Authors: W H Li, C I Wu, C C Luo
Journal: Molecular Biology and Evolution (1985)

A new method is proposed for estimating the number of synonymous and nonsynonymous nucleotide substitutions between homologous genes. In this method, a nucleotide site is classified as nondegenerate, twofold degenerate, or fourfold degenerate, depending on how often nucleotide substitutions will result in amino acid replacement; nucleotide changes are classified as either transitional or transversional, and changes between codons are assumed to occur with different probabilities, which are determined by their relative frequencies among more than 3,000 changes in mammalian genes. The method is applied to a large number of mammalian genes. The rate of nonsynonymous substitution is extremely variable among genes; it ranges from 0.004 X 10(-9) (histone H4) to 2.80 X 10(-9) (interferon gamma), with a mean of 0.88 X 10(-9) substitutions per nonsynonymous site per year. The rate of synonymous substitution is also variable among genes; the highest rate is three to four times higher than the lowest one, with a mean of 4.7 X 10(-9) substitutions per synonymous site per year. The rate of nucleotide substitution is lowest at nondegenerate sites (the average being 0.94 X 10(-9), intermediate at twofold degenerate sites (2.26 X 10(-9)). and highest at fourfold degenerate sites (4.2 X 10(-9)). The implication of our results for the mechanisms of DNA evolution and that of the relative likelihood of codon interchanges in parsimonious phylogenetic reconstruction are discussed.
Survivorship Beyond Convalescence: 48-Month Quality-of-Life Outcomes After Treatment for Localized Prostate Cancer
Authors: John L. Gore, Lorna Kwan, Steve P. Lee, Robert E. Reiter, Mark S. Litwin
Journal: JNCI Journal of the National Cancer Institute (2009)

Decision making for treatment of localized prostate cancer is often guided by therapeutic side-effect profiles. We sought to assess health-related quality-of-life outcomes for patients 48 months after treatment for localized prostate cancer. Men treated for localized prostate cancer (N = 475) were evaluated before treatment and at 11 intervals during the 48 months after intervention. Changes in mean health-related quality-of-life scores and the probability of regaining baseline levels of health-related quality of life were compared between treatment groups. All statistical tests were two-sided. Urinary incontinence was more common after prostatectomy (n = 307) than after brachytherapy (n = 90) or external beam radiation therapy (n = 78) (both P < .001), whereas voiding and storage urinary symptoms were more prevalent after brachytherapy than after prostatectomy (both P < .001). Sexual dysfunction profoundly affected all three treatment groups, with a lower likelihood of regaining baseline function after prostatectomy than after external beam radiation therapy or brachytherapy (P < .001). Bowel dysfunction was more common after either form of radiation therapy than after prostatectomy. These results may guide decision making for treatment selection and clinical management of patients with health-related quality-of-life impairments after treatment for localized prostate cancer.