tbuckley/cabot-search huggingface dataset:
Toxicological foundations of ecological risk assessment: biomarker development and interpretation based on laboratory and wildlife species.
Authors: R L Dickerson, M J Hooper, N W Gard, G P Cobb, R J Kendall
Journal: Environmental Health Perspectives (1994)

Ecological risk assessments based on chemical residue analysis and species demographics tend to ignore the bioavailability and bioaccumulation of the chemicals of concern. This study describes the incorporation of mechanistically based biomarkers into an ecological risk assessment of a poly-cyclic aromatic hydrocarbon (PAH)-contaminated site. A combination of soil residue analysis, tissue residue analysis, biomarkers in one-site trapped animals and biomarkers in animals confined to enclosures was used. In particular, the use of captured deer mice (Peromyscus maniculatus) for these studies is compared to the use of laboratory-raised deer mice placed in enclosures. This study indicates that the higher degree of variability in the responses of wild deer mice make the use of enclosure studies advantageous. Positive control studies performed by dosing laboratory-raised deer mice with the same PAHs as found on the site were used to validate this approach. These studies indicate that immune suppression occurred at PAH concentrations an order of magnitude below those required for the induction of ethoxyresorufin-O-dealkylase activity.
Azathioprine for the nephrotic syndrome.
Authors: M Bianchessi, G B Porro, M Tagliabue
Journal: BMJ (1969)

MEDICALJOUR 111 magnitude of possible causative agents ove: a long period.It is for this reason that the first studies suggesting dietary sugar is such an agent deliberately excluded informatior from subjects who admitted to -changing their intake of 'sugar.'It is, of course, not pos- sible to measure precise sugar consumptior over a lifetime, but since habitual intakes of sugar differ widely between individuals we believe it can be adequately measured by a careful dietary questionary.We feel toc that this assumption was supported by the findings, in two separate surveys, of consider- able differences between individuals with and without occlusive arterial disease, and by the fact that the values were very similar in the three groups of controls that we studied, and in the three groups of patients.Although Mr. R. W. Howell and Dr. D. G. Wilson (19 July, p. 145) include separate data for subjects who claim not to have changed their intake of sugar, they do so almost as an afterthought.Similarly, having given the figures for all their subjects, they match for age only at the end of their presentation, although in early studies' ' it was pointed out that sugar intake varies with age.These factors of age and of reasonable constancy of sugar intake were thus made
Sympathoinhibitory effects of total paracentesis (TP) in cirrhosis: microneurographic studies
Authors: M Pozzi, V Pecci, C Turri, S Vailati, L Roffi, S Massironi, G Boari, S Carugo, C Giannattasio, G Grassi, G Mancia
Journal: Journal of Hepatology (1998)
Response to Letter Regarding Article, “Donor Pretreatment With Hypertonic Saline Attenuates Primary Allograft Dysfunction: A Pilot Study in a Porcine Model”
Authors: Mitesh V. Badiwala, Vivek Rao, Laura C. Tumiati, Christopher M. Feindel, Danny Ramzy, Elissa D. Tepperman, Rohit Sheshgiri, Jessica L. Prodger
Journal: Circulation (2010)
Low molecular weight hydroxyethyl starch 6% compared to albumin 4% during intentional hemodilution
Authors: J. -F. Baron, D. De Kegel, A. C. Prost, O. Mundler, M. Arthaud, G. Basset, G. Maistre, F. Masson, A. Carayon, C. Landault, E. Barré, P. Viars
Journal: Intensive Care Medicine (1991)
Passive smoking and lung function in alpha1-antitrypsin heterozygote schoolchildren
Authors: G M Corbo
Journal: Thorax (2003)

A study was performed to determine whether Pi heterozygotes exposed to smoking have a higher risk of reduced lung function than Pi M homozygotes.The effect of passive smoking on lung function was investigated in a cross sectional study of 997 primary and secondary schoolchildren aged 11-13 years categorised by Pi phenotype as either PiM homozygotes or Pi heterozygotes. Data on respiratory health and risk factors were collected by questionnaire, lung function was measured by spirometric tests, bronchial hyperresponsiveness was evaluated by methacholine test, atopic status was evaluated by skin prick testing, and a blood sample was collected to determine Pi phenotype. Urinary cotinine and creatinine concentrations were determined and assessment of exposure was made from questionnaire data and urinary cotinine concentrations. The results were analysed by multiple regression analysis.Sixty one subjects (6.1%) were found to be Pi heterozygotes. Lung function did not differ between homozygotes and heterozygotes. There was a reduction in lung function in subjects exposed to parental smoking in the overall sample: FEV(1)/FVC ratio (-0.78%), FEF(25-75) (-0.11 litres), and FEF(75) (-0.13 litres). Interaction terms between parental smoking and Pi status were significant with regard to FEV(1)/FVC ratio (p=0.035) and FEF(50) (p=0.023). In subjects exposed to parental smoking the decrement in lung function in Pi heterozygotes tended to be greater (FEV(1)/FVC ratio = -2.57, FEF(25-75) = -0.30, FEF(50) = -0.43, and FEF(75) = -0.29) than in PiM homozygotes. These results did not change significantly when the urinary cotinine concentration was used as an exposure variable.The detrimental effect of environmental tobacco smoke on lung function in schoolchildren is confirmed. This harmful effect is greater in Pi heterozygotes than in PiM homozygotes.
Therapeutic interventions for enhancing collateral development by administration of growth factors: basic principles, early results and potential hazards
Authors: Stephen E. Epstein, Shmuel Fuchs, Yi Fu Zhou, Richard Baffour, Ran Kornowski
Journal: Cardiovascular Research (2001)

The importance of spontaneously developing collateral vessels to supplement perfusion of tissue rendered ischemic by vascular obstruction was recognized many years ago. However, it was not until potent angiogenesis factors were identified, purified, and produced in sufficient quantities, that the field began its rapid development. In the early 1990s it was first shown that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) proteins could actually stimulate collateral flow. However, additional studies also demonstrated that the duration of exposure of the vessels to angiogenesis factors was critical, and that the administration of proteins, with their relativly brief half-lives, may pose important practical limitations. The demonstration that gene therapy can improve collateral function presents one of the solutions to the conundrum, since gene therapy can be considered a sophisticated form of a sustained delivery system. The results of several clinical trials have been reported. All involve administration of single angiogenesis agents, and most are Phase I trials. The two studies rising to Phase II status demonstrated no treatment effect on the primary end-point. It may therefore be relevant to consider that the molecular mechanisms responsible for angiogenesis are extraordinarily complex, and an optimal angiogenesis intervention may require a ‘multiple factor’ strategy. It is important to note that no serious side-effects ascribable to an angiogenesis agent were recognized in these trials. However, angiogenesis agents are potent molecules with multiple activities. It is therefore possible that they might occasionally cause side-effects, some serious. Among these, based on their biologic activities, are neovascularization of non-targeted tissues, expansion and induction of instability of atherogenic plaque, and growth of tumors. In summary, there is ample experimental evidence justifying an optimistic outlook relating to our eventually being successful in enhancing collateral flow to ischemic tissue in a clinical setting. However, we are not there yet, and identification of the optimal angiogenesis strategy is still unclear. Additional experimental work, in parallel with large, carefully controlled clinical trials are needed to continue the exciting advances of the last decade, and to achieve the goal of providing patients with alternative potent therapies to improve collateral flow, and thereby to alleviate their symptoms and perhaps to prolong their lives.
Hypertensive Crisis and Death Associated With Phencyclidine Poisoning
Authors: Jay W. Eastman
Journal: JAMA (1975)

Phencyclidine hydrochloride is a dangerous drug. Its incidence as the causative agent in childhood poisoning is increasing. A pressor effect of phencyclidine has been noted in studies both in man and in experimental animals. We summarize seven cases of poisoning with this drug, including one in which death occurred following a hypertensive crisis. Patients who have ingested this drug should have continuous monitoring of blood pressure in an intensive care unit.
Pulmonary damage with gold or penicillamine.
Authors: A Bamji, N Cooke
Journal: Annals of the Rheumatic Diseases (1981)

Pulmonary damage with gold or penicillamine SIR, We were interested to read the report of Scott et al.1 but consider that they have confused 2 clinical entities and that their conclusions are misleading.We agree that gold causes an acute pulmonary syndrome as they have described.Our own review article2 has summarised the usual features-the onset of dyspnoea and cough, sometimes with fever, the finding of fine basal rales clinically, a restrictive ventilatory defect, and the radiological evidence of pulmonary infiltrates, which all occur after a total gold dose of between 175 and 840 mg in the reported cases.We have termed this syndrome 'gold lung.'However, of the 7 patients treated with D-penicillamine reviewed by Scott et al.only 3 had an undoubted acute syndrome akin to gold lung, which might be called 'penicillamine lung.'The other 4 patients developed a form of Goodpasture's syndrome.Radiological 'infil- trates' seen in this condition are due to haemorrhage, and any fibrosis that may be seen is secondary to haemosiderin deposition.We cannot accept that Goodpasture's syndrome is a form of pulmonary interstitial fibrosis or of 'diffuse interstitial lung disease,' a rather loose term used by Scott et al. following the criteria of Walker and Wright. 3 We would further point out that in the quoted paper by Sternleib4 all 3 patients had Wilson's disease and were given much larger doses of D-penicillamine than are used in rheumatoid arthritis, and that the lung histology reported (and this only in one patient) does not support a diagnosis of 'diffuse interstitial lung disease.' Our own review article shows that in cases of 'gold lung' recovery is the rule.2Goodpasture's syndrome was untreatable, and nearly always fatal, at the time of Sternleib's paper, but the prognosis is now much better following the introduction of plasmapheresis.Thus it is most important from the point of view of management to make a clear distinction between the syndrome of 'penicillamine lung' and penicillamine-induced Good- pasture's syndrome.The contention that 'diffuse interstitial lung disease is a serious adverse reaction to gold and penicillamine' is un- supportable.Of the 4 deaths described in Scott et al.'s report 3 were of patients with Goodpasture's syndrome, which is unsurprising.The fourth death was of a patient in Gould's series5 with gold lung, but this was not the cause)of death-the patient died of a myocardial infarction 24 hours after admission.The figures now look rather different.Twenty-three cases of gold or penicillamine lung are reported; 10 resolved completely, 10 improved, and one died for another reason.Of the 2 who failed to improve, one had pre-existing pulmonary fibrosis and one was treated with penicillamine for a further 5 months after the onset of symptoms.Earlier recognition of
Public inquiry hears how Shipman killed patients with diamorphine
Authors: C. Dyer
Journal: BMJ (2001)

The former GP, Harold Shipman, Britain's most prolific serial killer, used massive doses of diamorphine to kill his victims, the public inquiry into his patients' deaths was told as it got under way last week.

The inquiry, at Manchester town hall, chaired by High Court judge Dame Janet Smith, is expected to take two years to unravel how the GP was able to evade …
Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor- deficient mice.
Authors: T Rajavashisth, J H Qiao, S Tripathi, J Tripathi, N Mishra, M Hua, X P Wang, A Loussararian, S Clinton, P Libby, A Lusis
Journal: Journal of Clinical Investigation (1998)

Previous studies of osteopetrotic (op) mice lacking macrophage colony-stimulating factor (M-CSF) have revealed an inhibition of atherosclerosis development in the apolipoprotein E (apo E)-deficient model and in a diet-induced model. Using LDL receptor-deficient mice, we now show that atheroma development depends on M-CSF concentration, as not only did homozygous osteopetrotic (op/op) mice have dramatically reduced lesions (approximately 0.3% of control lesion size) but heterozygous (op/+) mice had lesions < 1% of controls. Mice heterozygous for the op mutation (op/+) had plasma levels of M-CSF about half those in controls (+/+). The finding that an approximately 2-fold reduction in M-CSF expression reduced lesion size approximately 100-fold suggests the requirement for a threshold level of M-CSF. The effect of M-CSF on atherosclerosis did not appear to be mediated either by changes in plasma lipoprotein levels or alterations in the number of circulating monocytes, since both op/op and op/+ mice exhibited higher levels of atherogenic lipoprotein particles and (op/+) mice showed a near normal number of circulating monocytes. LDL receptor-null littermates of genotypes from op/op, op/+, to +/+ showed monocyte differentials of approximately 4.5, 8, and 10%, respectively. Taken together, these results suggest that the effects of M-CSF on atherogenesis may not be mediated by expression of M-CSF systemically or by modulation of the number of circulating monocytes. These studies support the conclusion that M-CSF participates critically in fatty streak formation and progression to a complex fibrous lesion.
Minimally Invasive Coronary-Artery Bypass Surgery without Extracorporeal Circulation
Authors: Anno Diegeler, Volkmar Falk, Thomas Walther, Friedrich Wilhelm Mohr
Journal: New England Journal of Medicine (1997)

To the Editor: Dr. Mangano and other investigators in the Multicenter Study of Perioperative Ischemia Research Group (Dec. 5 issue) 1 have failed to report directly the outcome of the eight patients in the placebo group who were taking beta-blockers preoperatively.There were 12 deaths from cardiac causes in the placebo group.If all eight patients who were taking beta-blockers preoperatively died from cardiac events, then what the authors have really found is that the sudden perioperative withdrawal of beta-blockers is deleterious.This is quite possible, given the well-supported position, which the authors promote, that the effects of tachycardia and hypertension are deleterious.The fact that many of the patients in the atenolol group were also receiving beta-blockers does not compensate for this type of bias, since those patients never underwent short-term perioperative withdrawal of the beta-blockers but, rather, were maintained on this therapy throughout hospitalization by virtue of receiving the drug rather than the placebo.
Abstract 219: Treatment with survivin siRNA augments cytotoxicity of paclitaxel in primary ovarian cancer cells
Authors: Rajarshi Kar, Jayanth K. Palanichamy, Chandresh Sharma, Parthaprasad Chattopadhyay, Sunesh K. Jain, Lalit Kumar, Neeta Singh
Journal: Cancer Research (2010)

Abstract Introduction Chemoresistance is a major problem encountered during the treatment of ovarian cancer. Paclitaxel one of the first line drugs is less effective in patients whose cancer cells overexpress survivin. This study investigates whether reducing expression of survivin by siRNA treatment of primary cultures of ovarian cancer cells can increase sensitivity to paclitaxel. Methodology Five primary cultures were established from ascites obtained from untreated ovarian cancer patients. Ascites mixed with MCDB 105 and M199 medium (ratio 1:1) was plated in 75 mm2 flasks for establishment of primary cultures. Survivin siRNA was synthesized using in-vitro transcription technique and was quantified using pico green. A dose of 15 nM of Survivin siRNA was used for further experiments. Primary cultures were treated with survivin siRNA using olgofectamine as the transfecting agent. After 24 hours Survivin expression was quantified by RT-PCR. Cells plated in 96 well plates were treated with survivin siRNA (15nM). After 24 hours, paclitaxel treatment was given at four different doses (0.1, 1, 5 and 25 µg/ml) in separate wells. Untransfected cells, cells transfected with oligofectamine alone (mock transfection) and with universal control siRNA were also treated with same doses of paclitaxel after 24 hours. Cell survival was quantified using MTT assay. All experiments were done in triplicates. Results On treating the primary cultures with survivin siRNA there was a 6 fold decrease in Survivin expression. Survivin siRNA alone caused 23 ±3% cell deaths in the 5 primary cultures. When these cultures were treated with paclitaxel alone (untansfected cells) at different doses (0.1, 1, 5 and 25 µg/ml) the average cell death was 21.2%, 22.4%, 26% and 37.5% respectively. There was no significant difference in cell death in mock transfected and control siRNA transfected cells when compared to untransfected cells. However when the cells were pretreated with survivin siRNA and then followed by same doses of paclitaxel after 24 hours, cell death increased to 52.8%, 55.4%, 60% and 70% respectively. All the primary cultures were resistant to paclitaxel treatment as 62.5% of the cells survived the highest dose of paclitaxel. Survivin siRNA treatment could significantly increase the sensitivity of the primary ovarian cancer cell cultures to paclitaxel. Conclusion Survivin appears to play a major role in the response of ovarian cancer cells to paclitaxel treatment and knocking off survivin expression may prove beneficial in the treatment of ovarian cancer patients with paclitaxel whose tumors overexpress Survivin. 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 219.
Stromal Cell–Derived Factor-1 and CXCR4 Interaction Is Critical for Development of Transplant Arteriosclerosis
Authors: Hideyasu Sakihama, Taro Masunaga, Kenichiro Yamashita, Taku Hashimoto, Manabu Inobe, Satoru Todo, Toshimitsu Uede
Journal: Circulation (2004)

Posttransplant chronic allograft deterioration associated with development of transplant arteriosclerosis (TA) remains an unresolved problem. Recent studies suggest that the smooth muscle cells (SMCs) constituting the neointima are derived from recipient hematopoietic stem cells (HSCs). However, the underlying mechanisms of the process are not yet fully elucidated.We examined the genes expressed in allografts at different stages of TA development using a mice aortic transplantation model. Genes were analyzed by a differential mRNA display technique. We show that stromal cell-derived factor-1alpha (SDF-1alpha) is a critical molecular target for the treatment of TA. During the course of TA, intragraft SDF-1alpha expression was upregulated with time, and the circulating HSCs expressing its counterreceptor CXCR4 increased in the recipients receiving allografts. CXCR4-positive HSCs, derived from transplant recipients, migrated into allografts via microvessels in the adventitia and then toward the luminal side. The HSCs differentiated into SMC-like cells, contributing to the in situ formation of the neointima. In support of a functional role for these molecules, in vivo neutralization of SDF-1alpha inhibited HSC mobilization and significantly attenuated neointimal formation.Interaction between SDF-1alpha and CXCR4 plays a key role in TA development. Blockade of SDF-1alpha may become a new therapeutic modality for TA.
Clinical features of amiodarone-induced pulmonary toxicity.
Authors: R E Dusman, M S Stanton, W M Miles, L S Klein, D P Zipes, N S Fineberg, J J Heger
Journal: Circulation (1990)

The incidence and clinical predictors of amiodarone pulmonary toxicity were examined in 573 patients treated with amiodarone for recurrent ventricular (456 patients) or supraventricular (117 patients) tachyarrhythmias. Amiodarone pulmonary toxicity was diagnosed in 33 of the 573 patients (5.8%), based on symptoms and new chest radiographic abnormalities (32 of 33 patients) and supported by abnormal pulmonary biopsy (13 of 14 patients), low pulmonary diffusion capacity (DLCO) (nine of 13 patients), and/or abnormal gallium lung scan (11 of 16 patients). Toxicity occurred between 6 days and 60 months of treatment for a cumulative risk of 9.1%, with the highest incidence occurring during the first 12 months (18 of 33 patients). Older patients developed it more frequently (62.7 +/- 1.7 versus 57.4 +/- 0.5 years, p = 0.018), with no cases diagnosed in patients who started therapy at less than 40 years of age. Gender, underlying heart disease, arrhythmia, and pretreatment chest radiographic, spirometric, or lung volume abnormalities did not predict development of amiodarone pulmonary toxicity, whereas pretreatment DLCO was lower in the group developing it (76.0 +/- 5.5% versus 90.4 +/- 1.4%, p = 0.01). There was a higher mean daily amiodarone maintenance dose in the pulmonary toxicity group (517 +/- 25 versus 409 +/- 6 mg, p less than 0.001) but no difference in loading dose. No patient receiving a mean daily maintenance dose less than 305 mg developed pulmonary toxicity. Patients who developed toxicity had higher plasma desethylamiodarone (2.34 +/- 0.18 versus 1.92 +/- 0.04 micrograms/ml, p = 0.009) but not amiodarone concentrations during maintenance therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Connections between signal transduction components and cellular responses initiated by antigen receptor on B lymphocytes.
Authors: R H Scheuermann, J W Uhr
Journal: The Journal of Experimental Medicine (1995)

Cells translate environmental cues into various cellular responses, including proliferation, differentiation, and death. In many cases, these responses are initiated through a specific interaction between an extracellular ligand and a membrane-bound receptor, which then triggers a series of biochemical events collectively termed signal transduction. Much progress has been made in the identification of second messengers and understanding the interactions between signaling proteins. Moreover, correlations between specific biochemical signaling events and a cellular response can be observed; however, demonstration of a direct cause and effect relationship is more difficult to achieve. Two observations have complicated this analysis. First, the binding of a ligand to its receptor can result in several different responses within the same cell, e.g., changes in growth characteristics, transcription patterns, adhesion properties, cytokine secretion profiles, et cetera. Any intracellular biochemical event induced by the ligand-receptor interaction might be involved in signaling one of these downstream