tbuckley/cabot-search huggingface dataset:
Toxicity of firemaster FF-1 and 2,2',4,4',5,5'-hexabromobiphenyl in cultures of C3H/10T 1/2 mammalian fibroblasts.
Authors: F Bairstow, M T Hsia, D H Norback, J R Allen
Journal: Environmental Health Perspectives (1978)

A procedure for purifying 2,2', 4,4',5,5'-hexabromobiphenyl (HBB) from FireMaster FF-1 in gram amounts by crystallization is presented. Following purification, the structural assignment of HBB was made by using proton and carbon-13 nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, and mass spectroscopy (MS). The growth of C3H/10T 1/2 cells treated with 5, 37, 75, and 150 microgram of HBB and FF-1 per milliliter of medium was measured at 4, 8, and 13 days following treatment. FF-1 was more toxic at 37 and 75 microgram/ml at both 4 and 8 days, but the same at 13 days. At 150 microgram/ml cell growth was completely inhibited by both compounds. Growth of cells was stimulated at 5 microgram/ml, by HBB at 4 and 8 days, and FF-1 at 8 and 12 days. HCB was compared with HBB and FF-1 for cell growth toxicity at 37 and 75 microgram/ml. At 75 microgram/ml, HCB was more toxic than HBB and FF-1 during the entire time period. At 37 microgram/ml, HCB was more toxic than HBB and FF-1 at 4 and 8 days. Cells seeded at high densities and treated with HBB for three days lost the high degree of postconfluence inhibition of cell division observed in control cultures. Cells treated with FF-1 for three days did not adhere well to the plastic growth surface. Ultrastructural features of the HBB- and FF-1-treated cells included decreased surface villi and increased lysosomes relative to the control cells.
Long-Term Exposure to Ambient Fine Particulate Matter and Renal Function in Older Men: The Veterans Administration Normative Aging Study
Authors: Amar J. Mehta, Antonella Zanobetti, Marie-Abele C. Bind, Itai Kloog, Petros Koutrakis, David Sparrow, Pantel S. Vokonas, Joel D. Schwartz
Journal: Environmental Health Perspectives (2016)

It is unknown if ambient fine particulate matter (PM2.5) is associated with lower renal function, a cardiovascular risk factor.We investigated whether long-term PM2.5 exposure was associated with estimated glomerular filtration rate (eGFR) in a cohort of older men living in the Boston Metropolitan area.This longitudinal analysis included 669 participants from the Veterans Administration Normative Aging Study with up to four visits between 2000 and 2011 (n = 1,715 visits). Serum creatinine was measured at each visit, and eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration equation. One-year exposure to PM2.5 prior to each visit was assessed using a validated spatiotemporal model that utilized satellite remote-sensing aerosol optical depth data. eGFR was modeled in a time-varying linear mixed-effects regression model as a continuous function of 1-year PM2.5, adjusting for important covariates.One-year PM2.5 exposure was associated with lower eGFRs; a 2.1-μg/m3 interquartile range higher 1-year PM2.5 was associated with a 1.87 mL/min/1.73 m2 lower eGFR [95% confidence interval (CI): -2.99, -0.76]. A 2.1 μg/m3-higher 1-year PM2.5 was also associated with an additional annual decrease in eGFR of 0.60 mL/min/1.73 m2 per year (95% CI: -0.79, -0.40).In this longitudinal sample of older men, the findings supported the hypothesis that long-term PM2.5 exposure negatively affects renal function and increases renal function decline.Mehta AJ, Zanobetti A, Bind MC, Kloog I, Koutrakis P, Sparrow D, Vokonas PS, Schwartz JD. 2016. Long-term exposure to ambient fine particulate matter and renal function in older men: the VA Normative Aging Study. Environ Health Perspect 124:1353-1360; http://dx.doi.org/10.1289/ehp.1510269.
Smoking Deaths Soar in Central and Eastern Europe
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Smoking Deaths Soar in Central and Eastern Europe Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 18, 20 September 1995, Pages 1348–1349, https://doi.org/10.1093/jnci/87.18.1348 Published: 20 September 1995
Abstract P1-05-04: Expression of Quiescin Sulfhydryl Oxidase 1 is associated with a highly invasive phenotype and correlates with a poor prognosis in Luminal B breast cancer.
Authors: BA Katchman, T Ocal, G Hostetter, HE Cunliffe, A Wantanabe, DF Lake
Journal: Cancer Research (2012)

Abstract Quiescin sulfhydryl oxidase 1 (QSOX1) oxidizes sulfhydryl groups to form disulfide bonds in proteins. Informatic analysis using the newly available “Gene Expression Based Outcome for Breast Cancer Online” (GOBO) tool indicated high levels of QSOX1 expression in Estrogen Receptor positive (ER+) subtypes of breast cancer. We confirmed this finding by evaluation of QSOX1 protein expression in breast tumors and in a panel of breast cancer cell lines. In addition, Kaplan Meyer analyses revealed QSOX1 as a significant predictive marker for both relapse and poor overall survival in Luminal B tumors, but not in other intrinsic subtypes. To investigate malignant cell mechanisms in which QSOX1 might play a key role, we suppressed QSOX1 protein expression using short hairpin (sh) RNA in ER+ MCF7 and ER− BT549 breast cancer cell lines. Suppression of QSOX1 protein dramatically slowed cell proliferation but did not significantly effect apoptosis or cell cycle regulation. Inhibition of QSOX1 did however dramatically inhibit MCF7 and BT549 breast tumor cells from invading through Matrigel in a modified Boyden chamber assay. Inhibition of invasion could be rescued by the exogenous addition of recombinant QSOX1. Gelatin zymography indicated that QSOX1 plays an important role in activation of MMP-9 a key mediator of breast cancer invasive behavior. Taken together, our results suggest that QSOX1 is a novel biomarker for risk of relapse and poor survival in Luminal B breast cancer, and has a pro-invasive role in malignant progression through post-translational activation of MMP-9. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-05-04.
SAT0221 Survival in lupus patients with end-stage renal disease: A brazilian cohort
Authors: F.M. Ribeiro, C.L. Fabris, I. Bendet, J.R. Lugon
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ten to twenty-five percent of systemic lupus erythemathosus (SLE) patients will progress to end-stage renal disease (ESRD). Data about the survival rate of lupus patients on dialysis is controversial. <h3>Objectives</h3> The present study reports the survival of SLE patients undergoing dialysis and analyzes factors associated with mortality. <h3>Methods</h3> Twenty dialysis centers were visited between May/2003 and February/2004. Disease activity was evaluated using the SLE disease activity index (SLEDAI) without the renal related parameters (nrSLEDAI); Clinical examination and laboratory tests were performed at entrance in the study. The control group consisted of hemodialysis patients without SLE, matched for gender, race, age, time on dialysis, and hepatitis C virus (HCV) infection. Patients were followed for 60 months. The end-point was death of any cause. Kaplan-Meier method was used to estimate survival. Associations of risk factors with mortality were tested with the Cox proportional hazards model. <h3>Results</h3> Each group was composed of 57 patients. The group of SLE tended to have a slightly shorter time on dialysis (54±50 months vs. 71±53 months, P=0.0829). Twelve patients (21%) in each group had HCV infection. The prevalence of flare in SLE patients approached 44%. The 1- and 5-year survival rates of SLE patients and controls were 88 and 70%, 93 and 84%, respectively. When analyzing the Kaplan Meier curves, survival of the control group and the one from SLE patients with nrSLEDAI ≤8 were similar but significantly better than the one of SLE patients with nrSLEDAI&gt;8 (P&lt;0.001). In the univariate analysis, only nrSLEDAI (either as a continuous or a categorical variable, HR 1.176, 95%CI 1.043-1.326, P=0.008, and HR 5.746, 95%CI 1.983-16.651, P=0.001, respectively), immunosuppressive use (HR 2.713, 95%CI 1.032-7.133, P=0.043), and URR (HR 0.967, 95% CI 0.930-1.005, P=0.086) were significantly associated with mortality. In the multivariate analysis, only nrSLEDAI&gt;8 (HR 6.368, 95%CI 1.798-22.548, P=0.004), and URR (HR 0.953, 95%CI 0.917-0.990, P=0.014) emerged as independent factors associated with mortality in lupus patients. <h3>Conclusions</h3> A high nrSLEDAI was strongly associated with five year mortality in lupus patients on dialysis. <h3>Disclosure of Interest</h3> None Declared
Elevation of Serum Acid Phosphatase in Certain Myeloproliferative Diseases
Authors: Robert Bases
Journal: New England Journal of Medicine (1962)

PREVIOUS work1 from this laboratory has demonstrated that certain patients with myeloproliferative disorders with hepatosplenomegaly have enhanced reticuloendothelial function as indicated by ability to clear colloidal material (denatured albumin) from the circulation at greater than normal rates. Thorbecke et al.2 have shown that acid phosphatase activity in mouse liver rises upon progressive stimulation of the reticuloendothelial system in these animals. It therefore seemed of interest to test the serum of cases of myeloproliferative disease for increased acid phosphatase activity.MethodsPatients with proved diagnoses of chronic granulocytic leukemia or myeloid metaplasia were tested for serum acid phosphatase activity with beta-glycerophosphate . . .
Clinical Findings in Four Children with Biotinidase Deficiency Detected through a Statewide Neonatal Screening Program
Authors: Barry Wolf, Gregory S. Heard, Linda G. Jefferson, Virginia K. Proud, Walter E. Nance, Karen A. Weissbecker
Journal: New England Journal of Medicine (1985)

Four children with biotinidase deficiency were identified during the first year of a neonatal screening program for this disease in the Commonwealth of Virginia. Two unrelated probands were identified among the 81,243 newborn infants who were screened. In addition, two siblings of one of these infants were found to be affected. Both probands had mild neurologic symptoms at two and four months, respectively, and the two older children had more severe neurologic abnormalities, cutaneous findings, and developmental delay at two and three years of age. However, none of the affected children had acute metabolic decompensation. Previous studies have shown that the administration of biotin to affected children can be a lifesaving procedure that can reverse acute symptoms and prevent irreversible neurologic damage. Our findings demonstrate that subtle neurologic abnormalities may appear as early as at two months of age and that developmental abnormalities may occur even in the absence of episodes of overt metabolic decompensation. Since screening and treatment are both inexpensive and effective and the incidence of the disease is well within the range of that of other metabolic diseases for which screening is performed, biotinidase deficiency should be added to the group of metabolic diseases for which screening is done in the neonatal period.
Abstract 2975: Two putative founder MSH6 mutations associated with inherited cancer susceptibility in Ashkenazi Jewish population
Authors: Frank Schwenter, Leon Raskin, Marina Freytsis, Faina Bogomolniy, Melyssa Aronson, Gad Rennert, Steven Gallinger, Douglas A. Levine, Marc Tischkowitz, Stephen B. Gruber, William Foulkes
Journal: Cancer Research (2010)

Abstract Background Inherited mutations in DNA mismatch-repair genes are the cause of several cancers associated with Lynch syndrome. The most common mutations affect MLH1 and MSH2 genes, while the MSH6 gene is less commonly involved. Furthermore, MSH6 mutations have been observed to result in an attenuated form of the syndrome. We report here case-control studies of two putative MSH6 founder mutations in the Ashkenazi Jewish (AJ) population. Methods Case-control studies were performed using DNA extracted from the blood of individuals of AJ descent presenting cancers compatible with Lynch syndrome and AJ individuals unaffected by cancer as controls. The DNA samples were screened for the presence of the two mutations in exon 9. The frequency of the mutations and the range of malignancies were analyzed. Results Among 2104 population-based AJ colorectal cancer cases (CRC), 8 carried a 4 bp duplication mutation, c.3984_3987dupl (0.38%), and 3 carried a 4 bp deletion mutation, c.3959_3962del (0.14%), in the exon 9 of the MSH6 gene. In comparison, 1 duplication (0.06%) and no deletions were observed in 1813 control individuals. The odds ratio for the c.3984_3987dupl and the c.3959_3962del in this population are OR = 8.64 (exact 95%CI 1.23-375, Fisher's exact test two-sided P = 0.04) and OR = NA, P = 0.25, respectively. Notably, the one control found to carry the duplication was, during the course of follow-up, diagnosed with both cecal and endometrial cancer. In a hospital-based series of 78 CRC, one individual carried the deletion, but no duplications were seen. Among 136 hospital-based AJ endometrial cancer cases, 2 carried the duplication, leading to an OR of 27.0 (95%CI: 1.39-1596, P = 0.014) when compared with the 1813 controls. In a series of 61 hospital-based AJ pancreas cancer cases, no duplication carriers were seen, but 1 individual carried the deletion (OR NA, P = 0.033). Notably, this individual developed 3 independent primary cancers - pancreas cancer, CRC and rhabdomyosarcoma. Testing for microsatellite instability and loss of MSH6 protein is in progress in these samples. Conclusion These rare, probable founder, MSH6 truncating mutations reported here are of great importance for the screening, genetic counseling and follow-up of Ashkenazi Jewish families presenting malignant tumors compatible with Lynch syndrome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2975.
Abstract 484: Treatment strategy to reverse osteolytic breast cancer metastasis using osteoblasts in a murine xenograft model
Authors: Thomas M. Bodenstine, Benjamin H. Beck, Danny R. Welch
Journal: Cancer Research (2010)

Abstract The most common site of breast cancer metastasis is bone. The majority of these metastases are osteolytic, characterized by an increase in bone degradation via an upregulation of osteoclast activity. These effects lead to complications including fracture, contractile pain and hypercalcemia, significantly reducing the quality of life in these patients. The role of bone forming osteoblasts at sites of osteolytic lesions is less understood. We have recently shown that breast cancer cells are capable of inducing apoptosis of osteoblasts in vitro as well as in vivo using murine xenograft models. This effect would further exacerbate osteolytic disease, and may explain why treatment strategies capable of inhibiting osteolysis (bisphosphonates) are not capable of repairing lost bone. We hypothesize that modulating the number of osteoblasts at sites of osteolytic metastases, may aid in the repair of resorbed bone. To provide proof-of-principle evidence, we have engineered the murine pre-osteoblast cell line, MC3T3-E1, to overexpress Bcl2, conferring resistance to apoptosis. These cells will be used with an in vivo model of osteolysis using GFP-labeled breast cancer cells previously reported by our laboratory. Apoptosis resistant MC3T3-E1 will be injected into bone both before, and after induction of osteolysis and rates of bone resorption and repair will be measured. The results of this project will provide the first in vivo evidence that restoration of osteoblasts at sites of osteolytic metastases can aid in the repair of lost bone and will test for the first time, experimental manipulation of osteoblast number and function in osteolytic breast cancer metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 484.
CIERRE DE GASTROSTOMÍA MEDIANTE GASTROPEXIA PARA N.O.T.E.S
Authors: A Benages Curell, M Abu-suboh Abadia, J Dot Bach, J Armengol Bertrolí, M Masachs Peracaula, JC Salord Oses, SV Kantsevoy, M Moris, H De Leon, JR Armengol-Miró
Journal: Endoscopy (2011)

Introducción: Dos de los retos y de las barreras más importantes para la introducción segura de la cirugía transluminal endoscópica por orificios natural (N.O.T.E.S.) fueron el acceso peritoneal y el cierre gástrico. El desarrollo de dispositivos endoscópicos de cierre está en desarrollo actualmente. Algunos de estos dispositivos son complejos, no están disponibles comercialmente y son difíciles de manejar. Proponemos un método de acceso transgastrico y su cierre mediante el uso de los principios de la técnica combinada de una gastrostomia endoscopia percunatea (PEG) con una gastropexia.
Alteration of Sphingolipid Metabolism in Leukocytes from Patients with the Chediak–Higashi Syndrome
Authors: Julian N. Kanfer, Ralph S. Blume, Ronald A. Yankee, Sheldon M. Wolff
Journal: New England Journal of Medicine (1968)

The synthesis and degradation of sphingolipids by mixed peripheral leukocytes from four patients with the Chediak—Higashi syndrome were studied in vitro. Incorporation of glucose uniformly labeled with radioactive carbon into glucocerebroside and radioactive phosphate into sphingomyelin was greater than normal, as was the degradation of specifically labeled sphingomyelin and glucocerebroside. These observations can be interpreted as demonstrating an accelerated turnover of sphingolipids in leukocytes from patients with the Chediak—Higashi syndrome.
Abstract 314: The interaction between chronic alcohol consumption and melanoma skews the iNKT cell cytokine profile towards IL-4 dominance
Authors: Hui Zhang, Zhaohui Zhu, Gary G. Meadows
Journal: Cancer Research (2012)

Abstract Despite the growing evidence that alcohol consumption is associated with the incidence of many different types of cancer, there is little research regarding the effect of continued alcohol consumption on growth, progression and subsequent survival of cancer patients. Using a well-established mouse model we previously found that chronic alcohol consumption impairs the anti-melanoma functions of CD8+T cells and NK cells, and this leads to decreased survival of melanoma-bearing mice. The underlying mechanism for these effects is not known. Herein we examined the relationship of NKT cells to regulation of anti-tumor responses in alcohol consuming mice since NKT cells play important roles in the regulation of the anti-tumor immune response. The phenotype and function of invariant (i)NKT cells were examined in female B16BL6-bearing C57BL6 mice given 20% alcohol for three months. We found that alcohol consumption increased iNKT cells in the liver of mice not inoculated with melanoma, but did not alter iNKT cells in other organs. iNKT cells were dramatically increased in the blood and liver of chronic alcohol consuming, melanoma-bearing mice; however, these cells were not increased in the spleen or draining lymph nodes. Immature NK1.1- iNKT cells decreased 2-4 fold in the blood, spleen and liver of the alcohol-consuming, melanoma-bearing mice, suggesting that alcohol interacting with the melanoma tumors stimulates iNKT cells maturation. Upon activation, fewer iNKT cells produced IFN-gamma in these mice compared to water-drinking, melanoma-bearing mice. The ratio of IL-4:IFN-gamma-producing iNKT cells increased 2-fold as a result of the alcohol/tumor interaction, thus skewing the cytokine profile toward Th2 dominance. The Th2 dominant cytokine profile could negatively regulate the anti-tumor activities of CD8+ T cell and NK cells as well as increase myeloid derived suppressor cells, which we previously reported. Collectively, these data support an important role for iNKT cells in regulation of melanoma progression. (Supported by NIH grants R01AA07293 and K05AA017149, and WSU Alcohol and Drug Abuse Research Program grant 13B-2957-1246). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 314. doi:1538-7445.AM2012-314
Radio: The Consultants
Authors: S. A Spence
Journal: BMJ (2001)

BBC Radio 4, 2 and 9 January at 8 00 pm

In this radio documentary, producer Edi Stark has provided what appears to be a candid insight into the contemporary experiences of consultants working in medical and surgical specialties in Britain—in Glasgow and London specifically. The preview tape contained the first of two scheduled programmes, the focus of which is the cost to consultants' private lives incurred by massive undertakings within the NHS. Stark trails doctors along the corridors and up the stairs; she eavesdrops at handover time, and in small, untidy offices she samples the ambience of the confessional.

Though the narratives are compelling, and Stark's account is clear and unadorned, what stands out for me is the quality of these consultants' voices—their tense and clipped expression of what upsets them. Any mirth is tinged with anxiety, and at times the interviews and those interviewed invoke a double dose of deja vu: for the grind of the hospital regime and also for those interviews with survivors of catastrophic experiences, which we may become inured to on television. However, these experiences (of the NHS) will not cease, and as successive interviewees refer elliptically to relationships they've lost or colleagues who have died too soon or children who do not see their parents, we are reminded that a great many clinicians seem to be barely holding on. Just surviving; giving everything to keep the show on the road. As one surgeon remarks towards the end of the programme, “The NHS has had its pound of flesh.”

I'm not sure that I would choose to listen to this programme if not required to do so. There is no light at the end of this particular tunnel, and for the second instalment (advertised but not available for preview) we are promised the following: how “next week” consultants will “talk openly about mistakes they've made.” If only all sectors of society were so open and confiding.

There is a certain voyeurism implicit in the first programme, comprised, I think, of its intrusion into other people's pain. To know the extent of such pain within the system one would need to know how many consultants Stark had approached to compile these interviews. Certainly, she has assayed many points of view.

Though Stark is sympathetic to these voices, her ire is raised by the question of private practice. Why do those who complain of tiredness, relentless pressure, and a falling away of private life apparently let themselves in for more of the same by practising privately out of hours? As Stark says to one doctor, “People will say he's his own worst enemy.” Some of the voices fall away and do not respond. They sound uncomfortable when they decline to state how much they earn.

The Consultants rehearses the ambivalence that is central to many accounts of medicine, proffered from within: depressed voices stating how rewarding it all is. It says something strange, sad, beautiful, or frankly absurd about the human condition that so many are prepared to sacrifice those whom they say they love (at home) for the welfare of strangers they meet in hospitals.