tbuckley/cabot-search huggingface dataset:
Exposure to dioxin and nonneoplastic mortality in the expanded IARC international cohort study of phenoxy herbicide and chlorophenol production workers and sprayers.
Authors: J Vena, P Boffetta, H Becher, T Benn, H B Bueno-de-Mesquita, D Coggon, D Colin, D Flesch-Janys, L Green, T Kauppinen, M Littorin, E Lynge, J D Mathews, M Neuberger, N Pearce, A C Pesatori, R Saracci, K Steenland, M Kogevinas
Journal: Environmental Health Perspectives (1998)

The authors studied noncancer mortality among phenoxyacid herbicide and chlorophenol production workers and sprayers included in an international study comprising 36 cohorts from 12 countries followed from 1939 to 1992. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin or higher chlorinated dioxins (TCDD/HCD) was discerned from job records and company questionnaires with validation by biologic and environmental measures. Standard mortality ratio analyses suggested a moderate healthy worker effect for all circulatory diseases, especially ischemic heart disease, among both those exposed and those not exposed to TCDD/HCD. In Poisson regression analyses, exposure to TCDD/HCD was not associated with increased mortality from cerebrovascular disease. However, an increased risk for circulatory disease, especially ischemic heart disease (rate ratio [RR] 1.67, 95% confidence interval [Cl] 1.23-2.26) and possibly diabetes (RR 2.25, 95% Cl 0.53-9.50), was present among TCDD/HCD-exposed workers. Risks tended to be higher 10 to 19 years after first exposure and for those exposed for a duration of 10 to 19 years. Mortality from suicide was comparable to that for the general population for all workers exposed to herbicides or chlorophenols and was associated with short latency and duration of exposure. More refined investigations of the ischemic heart disease and TCDD/HCD exposure association are warranted.
New Horizons in the Treatment of Autoimmune Diseases: Immunoablation and Stem Cell Transplantation
Authors: Alberto M. Marmont
Journal: Annual Review of Medicine (2000)

▪ Abstract The prevalence of autoimmune diseases (ADs) in Western countries is estimated to be from 3–7%, and the treatment of severe, relapsing/refractory cases is still not satisfactory. The concept of utilizing intense immunosuppression followed by allogeneic or even autologous hemolymphopoietic stem cells (HSCs) to treat AD is based on encouraging results in experimental animals and from serendipitous cases of patients with both ADs and malignancies who were allotransplanted for the latter. However, rare unexpected relapses despite donor immune engraftment have been reported following HSC transplantation for AD. Autologous transplantation is a more feasible procedure with lower toxicity than allogeneic transplantation. This article analyzes the experimental basis for stem cell transplantation in AD and discusses the most important clinical results of both allogeneic and autologous HSC transplants.
THE RHODESIAN SKULL
Authors: G. E. Smith
Journal: BMJ (1922)

BmRprogress of the disease once they become phthisical.Dr. Sam.son suggests that in the interests of public health special regulations shoul(d be tuade for the control of the tuberculous prostitute; on this account the book should be read* by medial officers of health.Dr. EWALD'S book on Abderhalden's reaction15 is a laborious attemupt to establislh the value and validity of this reaction, now nmuch called in question, as a lueans of diagnosis; or, slhould its failure here be admitted, to prove that Abder- halden's work hias at any rate eiariqhed our theories of cellular activity.The volume is,LMq# written and full of detail, particularly with regard to.-temployment of thc reaction in psychiatric practice.The Union ATdicale dut Canada, which is a monthly medical journal, published in French at Montreal, has just celebrated its jubilee, having been founded in 1872; Dr. A. Lesage is the present editor-in-chief.Before giving an order for a German book the intendina purchlaser should ascertain the price at which it can actually be supplied by the agent in this country.
Cartilage Tissue Remodeling in Response to Mechanical Forces
Authors: Alan J. Grodzinsky, Marc E. Levenston, Moonsoo Jin, Eliot H. Frank
Journal: Annual Review of Biomedical Engineering (2000)

Recent studies suggest that there are multiple regulatory pathways by which chondrocytes in articular cartilage sense and respond to mechanical stimuli, including upstream signaling pathways and mechanisms that may lead to direct changes at the level of transcription, translation, post-translational modifications, and cell-mediated extracellular assembly and degradation of the tissue matrix. This review focuses on the effects of mechanical loading on cartilage and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair of this tissue. The effects of compression and tissue shear deformation are compared, and approaches to the study of mechanical regulation of gene expression are described. Of particular interest regarding dense connective tissues, recent experiments have shown that mechanotransduction is critically important in vivo in the cell-mediated feedback between physical stimuli, the molecular structure of newly synthesized matrix molecules, and the resulting macroscopic biomechanical properties of the tissue.
Available carbon source influences the resistance of <i>Neisseria meningitidis</i> against complement
Authors: Rachel M. Exley, Jonathan Shaw, Eva Mowe, Yao-hui Sun, Nicholas P. West, Michael Williamson, Marina Botto, Harry Smith, Christoph M. Tang
Journal: The Journal of Experimental Medicine (2005)

Neisseria meningitidis is an important cause of septicaemia and meningitis. To cause disease, the bacterium must acquire essential nutrients for replication in the systemic circulation, while avoiding exclusion by host innate immunity. Here we show that the utilization of carbon sources by N. meningitidis determines its ability to withstand complement-mediated lysis, through the intimate relationship between metabolism and virulence in the bacterium. The gene encoding the lactate permease, lctP, was identified and disrupted. The lctP mutant had a reduced growth rate in cerebrospinal fluid compared with the wild type, and was attenuated during bloodstream infection through loss of resistance against complement-mediated killing. The link between lactate and complement was demonstrated by the restoration of virulence of the lctP mutant in complement (C3−/−)-deficient animals. The underlying mechanism for attenuation is mediated through the sialic acid biosynthesis pathway, which is directly connected to central carbon metabolism. The findings highlight the intimate relationship between bacterial physiology and resistance to innate immune killing in the meningococcus.
Everolimus for Advanced Pancreatic Neuroendocrine Tumors
Authors: James C. Yao, Manisha H. Shah, Tetsuhide Ito, Catherine Lombard Bohas, Edward M. Wolin, Eric Van Cutsem, Timothy J. Hobday, Takuji Okusaka, Jaume Capdevila, Elisabeth G.E. De Vries, Paola Tomassetti, Marianne E. Pavel, Sakina Hoosen, Tomas Haas, Jeremie Lincy, David Lebwohl, Kjell Öberg
Journal: New England Journal of Medicine (2011)

Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study.
Superoxide production and reducing activity in human platelets.
Authors: A J Marcus, S T Silk, L B Safier, H L Ullman
Journal: Journal of Clinical Investigation (1977)

Human platelets contain the cuprozinc (cytoplasmic) and manganese (mitochondrial) forms of superoxide dismutase. Nevertheless, superoxide radicals were detectable in the surrounding medium of metabolically viable platelet suspensions by using two assay systems: cytochrome c and nitroblue tetrazolium. The quantity of superoxide generated by platelets (5 X 10(5) superoxide radicals/platelet per 10 min) was constant and did not increase after aggregation by agents such as collagen and thrombin. The superoxide-generating system was present in the supernate of both aggregated and resting platelets and therefore was not platelet-bound. Platelet superoxide production was unaffected by prior ingestion of aspirin, indicating that the prostaglandin and thromboxane pathways were not involved. Both resting and aggregated platelets exhibited a reductive capacity toward cytochrome c and nitroblue tetrazolium which was unrelated to superoxide production. Furthermore, the aggregation process always resulted in a marked increase in this reduction. The nonsuperoxide reduction associated with aggregation was found to be membrane bound and to decrease with an apparent first order reaction rate (k1 = 0.067 min-1). In addition, accumulative, time-dependent nonsuperoxide-related cytochrome c reduction was also detected. Since there is no superoxide dismutase in plasma, the presence of superoxide radicals in the surrounding medium of platelets may have in vitro significance for platelet and leukocyte concentration and storage and in vivo significance for hemostasis, coagulation, and thrombosis. The nonsuperoxide-related reducing activities may represent a biochemical basis for platelet-blood vessel interactions, with particular reference to blood vessel integrity.
US endorses testing for cystic fibrosis in pregnant women
Authors: N. Macready
Journal: BMJ (1997)

Doctors should offer testing for cystic fibrosis (CF) to people with a family history of CF and the partners of people who have the disease, according to recommendations issued last week by a panel convened by the National Institutes of Health. The panel also recommended that CF testing be offered to pregnant women and couples currently planning a pregnancy.

However, the panel did not advocate testing for the general population, nor did it recommend that newborn infants be screened …
Can gene expression profiling predict survival for patients with squamous cell carcinoma of the lung?
Authors: Zhifu Sun, Ping Yang, Marie-Christine Aubry, Farhad Kosari, Chiaki Endo, Julian Molina, George Vasmatzis
Journal: Molecular Cancer (2004)

Lung cancer remains to be the leading cause of cancer death worldwide. Patients with similar lung cancer may experience quite different clinical outcomes. Reliable molecular prognostic markers are needed to characterize the disparity. In order to identify the genes responsible for the aggressiveness of squamous cell carcinoma of the lung, we applied DNA microarray technology to a case control study. Fifteen patients with surgically treated stage I squamous cell lung cancer were selected. Ten were one-to-one matched on tumour size and grade, age, gender, and smoking status; five died of lung cancer recurrence within 24 months (high-aggressive group), and five survived more than 54 months after surgery (low-aggressive group). Five additional tissues were included as test samples. Unsupervised and supervised approaches were used to explore the relationship among samples and identify differentially expressed genes. We also evaluated the gene markers' accuracy in segregating samples to their respective group. Functional gene networks for the significant genes were retrieved, and their association with survival was tested. Unsupervised clustering did not group tumours based on survival experience. At p < 0.05, 294 and 246 differentially expressed genes for matched and unmatched analysis respectively were identified between the low and high aggressive groups. Linear discriminant analysis was performed on all samples using the 27 top unique genes, and the results showed an overall accuracy rate of 80%. Tests on the association of 24 gene networks with study outcome showed that 7 were highly correlated with the survival time of the lung cancer patients. The overall gene expression pattern between the high and low aggressive squamous cell carcinomas of the lung did not differ significantly with the control of confounding factors. A small subset of genes or genes in specific pathways may be responsible for the aggressive nature of a tumour and could potentially serve as panels of prognostic markers for stage I squamous cell lung cancer.
Induction chemotherapy plus high-dose radiotherapy versus radiotherapy alone in locally advanced unresectable non-small-cell lung cancer
Authors: L. Crinò, P. Latini, M. Meacci, E. Corgna, E. Maranzano, S. Darwish, V. Minotti, A. Santucci, M. Tonato
Journal: Annals of Oncology (1993)
Donor Age and Renal P-Glycoprotein Expression Associate with Chronic Histological Damage in Renal Allografts
Authors: Maarten Naesens, Evelyne Lerut, Hylke de Jonge, Boudewijn Van Damme, Yves Vanrenterghem, Dirk R. J. Kuypers
Journal: Journal of the American Society of Nephrology (2009)

The contributions of donor kidney quality (partially determined by donor age), allograft rejection, and calcineurin inhibitor nephrotoxicity on the progression of histologic damage of renal allografts are not completely defined. Moreover, the determinants of individual susceptibility to calcineurin inhibitor nephrotoxicity are not known but may include variability in drug transport and metabolism. In a prospective cohort of 252 adult renal allograft recipients treated with a combination of tacrolimus, mycophenolate mofetil, and corticosteroids, we studied 744 renal allograft biopsies obtained regularly from time of transplantation for 3 yr. We assessed determinants of histologic evolution, including tacrolimus exposure, renal P-glycoprotein (ABCB1) expression, and polymorphisms in the CYP3A4, CYP3A5, and ABCB1 genes. Within the first 3 yr after transplantation, we noted a progressive increase in interstitial fibrosis, tubular atrophy, glomerulosclerosis, and vascular intimal thickening. Older donor age, absence of P-glycoprotein expression at the apical membrane of tubular epithelial cells, and combined donor-recipient homozygosity for the C3435T variant in ABCB1 significantly associated with increased susceptibility to chronic allograft damage independent of graft quality at implantation. Changes in graft function over time reflected these associations with donor age and ABCB1 polymorphisms, but it was acute T cell-mediated and antibody-mediated rejection that determined early graft survival. In conclusion, the effects of older donor age reach beyond the quality of the allograft at implantation and continue to be important for histologic evolution in the posttransplantation period. In addition, ABCB1 genotype and expression of P-glycoprotein in renal tubular epithelial cells determine susceptibility to chronic tubulointerstitial damage of transplanted kidneys.
Effectiveness Of Specific Immunotherapy Against Alternaria Alternata In Patients With Asthma and Or Allergic Rhinitis
Authors: Silvia Martínez Blanco, Ana Antón-Laiseca, R. Mielgo Ballesteros, Consuelo Fernández Rodríguez, Ruth Barranco Jiménez, R. Vives Conesa
Journal: Journal of Allergy and Clinical Immunology (2014)
Efficacy and Cost of Postpartum Screening Strategies for Diabetes Among Women With Histories of Gestational Diabetes Mellitus
Authors: Catherine Kim, William H. Herman, Sandeep Vijan
Journal: Diabetes Care (2007)

OBJECTIVE—To compare the cost and time to diagnosis associated with several screening strategies for diabetes in women with histories of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS—We simulated screening for diabetes with fasting plasma glucose (FPG), a 2-h oral glucose tolerance test (OGTT), and A1C annually, every 2 years, and every 3 years over a period of 12 years. We assumed that women had negative screening tests 6 weeks after delivery, progressed to diabetes at 8% per year, and that each positive FPG and A1C was followed by a confirmatory FPG. For each strategy, we calculated the cost per case detected, cost per woman screened, the percent of cases detected, and the time elapsed with undiagnosed diabetes. In sensitivity analyses, we considered the inclusion of indirect costs, the impact of imperfect adherence to screening strategies, exclusion of confirmatory tests, and lower rates of progression to diabetes. RESULTS—When annual, biannual, or every 3-year screening strategies were utilized, OGTTs resulted in lower costs per case detected than FPG or A1C. Testing every 3 years resulted in lower costs per case detected compared with more frequent testing. These patterns persisted in sensitivity analyses, except that FPG resulted in lower cost per case detected than OGTT, assuming annual screening and inclusion of indirect costs or assuming annual screening without a confirmatory FPG. CONCLUSIONS—Screening every 3 years with OGTTs results in the lowest cost per case of detected diabetes.
Evolving Diagnostic and Treatment Strategies for Pancreatic Neuroendocrine Tumors
Authors: Matthew H Kulke, Johanna Bendell, Larry Kvols, Joel Picus, Rodney Pommier, James Yao
Journal: Journal of Hematology & Oncology (2011)

Pancreatic neuroendocrine tumors (NET) have diverse clinical presentations. Patients with symptoms of hormone secretion may require specific medical interventions to control those symptoms prior to antitumor intervention. In some patients, tumors in the pancreas may be occult and specialized diagnostic imaging or surgery may be required for diagnosis. Other patients may present with more advanced disease, presenting with symptoms of tumor bulk rather than hormone secretion. Treatment options for patients with advanced pancreatic neuroendocrine tumors include surgical resection and hepatic directed therapies, including partial hepatectomy, hepatic artery embolization, or other ablative techniques. Streptozocin or temozolomide-based chemotherapy regimens are active against pancreatic NET, and can also play an important role in the palliation of patients with advanced disease. A number of biologically targeted agents targeting the VEGF and mTOR signaling pathways have recently shown promise, with recent trials showing treatment with the VEGFR tyrosine kinase inhibitor sunitinib or the mTOR inhibitor everolimus improves progression-free survival in patients with advanced NET.
When Is It Appropriate to Use Vasopressin Receptor Antagonists?
Authors: Ruediger W. Lehrich, Arthur Greenberg
Journal: Journal of the American Society of Nephrology (2008)

Hyponatremia is a common and challenging disorder. The mainstays of treatment until recently were water restriction and hypertonic saline. The first nonpeptide vasopressin receptor antagonist (VRA) is now approved by the US Food and Drug Administration for use in patients with euvolemic and hypervolemic hyponatremia. VRA induce urinary dilution with an aquaresis that leads to an increase in serum sodium concentration. In patients with heart failure, VRA modestly improve congestive symptoms but have no effect on short- or long-term mortality. Long-term effects have not been extensively studied, but serious adverse effects of VRA are rare, and the rate of rise in serum sodium that they produce seems unlikely to lead to osmotic demyelination. Beneficial effects beyond changing serum tonicity and alternative uses, such as in polycystic kidney disease, need further exploration. This commentary discusses the current and potential indications for use of VRA.
Sleep Fragmentation and Morning Cerebrovasomotor Reactivity to Hypercapnia
Authors: ADNAN I. QURESHI, W. CHRISTOPHER WINTER, DONALD L. BLIWISE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Impaired vasomotor reactivity of the cerebral vessels on morning awakening has been suggested as one of the mechanisms underlying the predisposition to stroke in the morning. This study investigated cerebrovascular reactivity to hypercapnia on morning awakening and its association with specific sleep-related parameters, including sleep-disordered breathing. Thirty patients undergoing nocturnal diagnostic polysomnography for sleep apnea underwent transcranial Doppler ultrasonography of the middle cerebral artery immediately before going to bed and immediately on morning awakening. Results indicated a morning reduction in cerebral blood flow velocity (CBFV) relative to values from the preceding evening both while breathing room air and 5% CO2. Hypercapnia was associated with the expected increase in CBFV in both evening and morning. The evening-to-morning difference in CBFV during CO2 inhalation was independently associated with both overnight CO2 retention and number of movements with arousal per hour of sleep. Results indicated that more fragmented sleep and greater CO2 retention during sleep predicted a diminished hypercapnic vasomotor response in the morning. Sleep fragmentation predicted approximately twice the variance in morning hypercapnic vasomotor reactivity relative to overnight CO2 retention (24 versus 13%). No other polysomnographic measures predicted evening-to-morning differences in vasomotor reactivity. These results are consistent with a body of literature suggesting that sleep loss and sleep fragmentation are associated with blunted hypercapnic ventilatory response.
Isocyanate asthma: respiratory symptoms caused by diphenyl-methane di-isocyanate
Authors: A. R. Tanser, M. P. Bourke, A. G. Blandford
Journal: Thorax (1973)

<b>Tanser, A. R., Bourke, M. P., and Blandford, A. G. (1973).</b><i>Thorax</i>, <b>28</b>, 596-600. <b>Isocyanate asthma: respiratory symptoms caused by diphenyl-methane di-isocyanate.</b> We investigated 57 employees of a factory where diphenyl-methane di-isocyanate (MDI) was used to prepare the materials for making rigid polyurethane foam. Four employees had developed hypersensitivity to MDI. Two had severe, and one moderate asthma, while the fourth had symptoms resembling the delayed hypersensitivity type of reaction. Ten other employees had experienced unpleasant, mainly respiratory, irritant effects from MDI vapour. A past history of bronchitis or of allergy was found more commonly in those with symptoms from MDI than in those without symptoms. It is not known if MDI causes permanent damage to the respiratory tract. The most severely affected cases in the present series had normal spirometric values after recovery, and no persisting symptoms. MDI is safer than other isocyanates used in industry but may cause both major and minor illness. It should be handled with the same precautions as those used with the more toxic compounds.
Gene Expression Profiling of Microsatellite Unstable and Microsatellite Stable Endometrial Cancers Indicates Distinct Pathways of Aberrant Signaling
Authors: John I. Risinger, G. Larry Maxwell, Gadisetti V.R. Chandramouli, Olga Aprelikova, Tracy Litzi, Asad Umar, Andrew Berchuck, J. Carl Barrett
Journal: Cancer Research (2005)

Microsatellite instability (MSI) is a molecular phenotype present in approximately 25% of endometrial cancers. We examined the global gene expression profiles of early-stage endometrioid endometrial cancers with and without the MSI phenotype to test the hypothesis that MSI phenotype may determine a unique molecular signature among otherwise similar cancers. Unsupervised principal component analysis of the expression data from these cases indicated two distinct groupings of cancers based on MSI phenotype. A relatively small number of array features (392) at high statistical value (P < 0.001) were identified that drive the instability signature in these cancers; 109 of these transcripts differed by at least 2-fold. These data identify distinct gene expression profiles for MSI and microsatellite stable (MSS) cancers, which suggest that cancers with MSI develop in part by different mechanisms from their similar stable counterparts. In particular, we found evidence that two members of the secreted frizzled related protein family (SFRP1 and SFRP4) were more frequently down-regulated in MSI cancers as compared with MSS cancers. Down-regulation was accompanied by promoter hypermethylation for SFRP1. SFRP1 was hypermethylated in 8 of 12 MSI cancers whereas only 3 of 16 MSS cancers were methylated. The WNT target fibroblast growth factor 18 was found to be up-regulated in MSI cancers. These data classify histologically similar endometrioid endometrial cancers into two distinct groupings with implications affecting therapy and prevention.