tbuckley/cabot-search huggingface dataset:
Rearrangements of immunoglobulin and T cell receptor beta and gamma genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia.
Authors: R Foa, G Casorati, M C Giubellino, G Basso, R Schirò, G Pizzolo, F Lauria, M P Lefranc, T H Rabbitts, N Migone
Journal: The Journal of Experimental Medicine (1987)

The cell origin of the rare terminal deoxynucleotidyl transferase (TdT)-positive acute myeloid leukemias (AML) was investigated at the molecular level, by examining the configuration of the Ig H (Igh) and L (Ig kappa, Ig lambda) chain gene regions, and of the T cell receptor (TCR) beta and T cell rearranging (TRG) gamma loci. In 8 of the 10 TdT+ AML analyzed (classified as myeloid according to morphological and cytochemical criteria, and to the reactivity with one or more antimyeloid mAbs), a rearrangement of the Igh chain gene was found. In TdT- AML, evidence of an Igh gene reorganization was instead observed only in 2 of the 42 patients studied. Furthermore, evidence of TCR-beta and/or TRG-gamma gene rearrangement was observed in four AML, all of which belonged to the Igh-rearranged TdT+ group. In three cases (one TdT+ and two TdT-), the Ig kappa L chain gene was also in a rearranged position. These findings demonstrate a highly significant correlation between TdT expression and DNA rearrangements at the Igh and TCR chain gene regions and support the view that this enzyme plays an important role in the V-(D)-J recombination machinery. Overall, the genomic configuration, i.e., JH gene rearrangement sometimes coupled to a kappa L chain and TCR gene reorganization, similar to that found in non-T-ALL, suggests that in most cases of TdT+ AML, the neoplastic clone, despite the expression of myeloid-related features, is characterized by cells molecularly committed along the B cell lineage.
Senescence-Associated Exosome Release from Human Prostate Cancer Cells
Authors: Brian D. Lehmann, Matthew S. Paine, Adam M. Brooks, James A. McCubrey, Randall H. Renegar, Rong Wang, David M. Terrian
Journal: Cancer Research (2008)

Abstract Males of advanced age represent a rapidly growing population at risk for prostate cancer. In the contemporary setting of earlier detection, a majority of prostate carcinomas are still clinically localized and often treated using radiation therapy. Our recent studies have shown that premature cellular senescence, rather than apoptosis, accounts for most of the clonogenic death induced by clinically relevant doses of irradiation in prostate cancer cells. We show here that this treatment-induced senescence was associated with a significantly increased release of exosome-like microvesicles. In premature senescence, this novel secretory phenotype was dependent on the activation of p53. In addition, the release of exosome-like microvesicles also increased during proliferative senescence in normal human diploid fibroblasts. These data support the hypothesis that senescence, initiated either by telomere attrition (e.g., aging) or DNA damage (e.g., radiotherapy), may induce a p53-dependent increase in the biogenesis of exosome-like vesicles. Ultrastructural analysis and RNA interference–mediated knockdown of Tsg101 provided significant evidence that the additional exosomes released by prematurely senescent prostate cancer cells were principally derived from multivesicular endosomes. Moreover, these exosomes were enriched in B7-H3 protein, a recently identified diagnostic marker for prostate cancer, and an abundance of what has recently been termed “exosomal shuttle RNA.” Our findings are consistent with the proposal that exosomes can transfer cargos, with both immunoregulatory potential and genetic information, between cells through a novel mechanism that may be recruited to increase exosome release during accelerated and replicative cellular senescence. [Cancer Res 2008;68(19):7864–71]
Risk factors for hemorrhage from gastric fundal varices
Authors: T Kim, H Shijo, H Kokawa, H Tokumitsu, K Kubara, K Ota, N Akiyoshi, T Iida, M Yokoyama, M Okumura
Journal: Hepatology (1997)

The incidence and the risk factors of hemorrhage from gastric fundal varices (FV) have not been fully evaluated. We therefore conducted a retrospective and prospective study to define the incidence and risk factors for such episodes. We investigated 132 patients with cirrhosis and gastric FV. Of these 132 patients, 15 patients had hemorrhagic FV at the time of enrollment. The clinical characteristics were compared between these patients and those without a first hemorrhage from FV. In the patients who had never previously bled, the incidence and risk factors were prospectively investigated. The size of FV was greater and red-spot on the FV were more prevalent in patients with hemorrhagic FV. Child's status was also more severe in these patients. In the 117 patients who had never bled, 34 hemorrhages from FV occurred during the follow-up period. The cumulative risk for such hemorrhage at 1, 3, and 5 years was 16%, 36%, and 44%, respectively. A multiple regression analysis (Cox's model) revealed the size of varices, red-spot on the FV, and Child's status to be statistically significant, as well as independent predictors for hemorrhage from FV. The endoscopic criteria (size of the largest varix and presence of red-spot), as well as the hepatic functional reserve, provide the most essential information for predicting a hemorrhage from FV. An estimation of the probability for hemorrhage from FV based on Cox's model may therefore be beneficial in the clinical management of patients with high-risk FV.
Metastatic basal cell carcinoma: report of two cases treated with cetuximab
Authors: J. Caron, O. Dereure, D. Kerob, C. Lebbe, B. Guillot
Journal: British Journal of Dermatology (2009)

Journal Article Metastatic basal cell carcinoma: report of two cases treated with cetuximab Get access J. Caron, J. Caron Department of Dermatology, University of Montpellier I, Hôpital Saint‐Eloi 80 avenue Augustin Fliche, F34295 Montpellier Cedex 5, France Search for other works by this author on: Oxford Academic Google Scholar O. Dereure, O. Dereure Department of Dermatology, University of Montpellier I, Hôpital Saint‐Eloi 80 avenue Augustin Fliche, F34295 Montpellier Cedex 5, France Search for other works by this author on: Oxford Academic Google Scholar D. Kerob, D. Kerob Department of Dermatology, Hôpital Saint Louis, 1 avenue Claude Vellefaux F75475 Paris Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar C. Lebbe, C. Lebbe Department of Dermatology, Hôpital Saint Louis, 1 avenue Claude Vellefaux F75475 Paris Cedex 10, France Search for other works by this author on: Oxford Academic Google Scholar B. Guillot B. Guillot Department of Dermatology, University of Montpellier I, Hôpital Saint‐Eloi 80 avenue Augustin Fliche, F34295 Montpellier Cedex 5, France Correspondence: Bernard Guillot. E‐mail: b‐guillot@chu‐montpellier.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 161, Issue 3, 1 September 2009, Pages 702–703, https://doi.org/10.1111/j.1365-2133.2009.09359.x Published: 01 September 2009
Recurrent macroscopic haematuria due to bladder blood vessels after exercise induced haematuria
Authors: P Lüthje, I Nurmi
Journal: British Journal of Sports Medicine (2004)

The case is reported of exercise induced asymptomatic macroscopic haematuria, which became recurrent haematuria no longer induced by exercise. The cause, diagnosis, and management are discussed. An overview of the potential causes of sport related haematuria is presented.
Recombinant Leptin for Weight Loss in Obese and Lean Adults
Authors: Steven B. Heymsfield, Andrew S. Greenberg, Ken Fujioka, Russell M. Dixon, Robert Kushner, Thomas Hunt, John A. Lubina, Janet Patane, Barbara Self, Pam Hunt, Mark McCamish
Journal: JAMA (1999)

ContextThe protein hormone leptin is important to the homeostatic regulation of body weight. Treatment with exogenous leptin may affect weight loss.ObjectiveTo determine the relationship between increasing doses of exogenous leptin administration and weight loss in both lean and obese adults.DesignA randomized, double-blind, placebo-controlled, multicenter, escalating dose cohort trial conducted from April 1997 to October 1998.SettingFour university nutrition and obesity clinics and 2 contract clinical research clinics.ParticipantsFifty-four lean (body mass index, 20.0-27.5 kg/m2; mean [SD] body weight, 72.0 [9.7] kg) and 73 obese (body mass index, 27.6-36.0 kg/m2; mean [SD] body weight, 89.8 [11.4] kg) predominantly white (80%) men (n = 67) and women (n = 60) with mean (SD) age of 39 (10.3) years.InterventionsRecombinant methionyl human leptin self-administered by daily morning subcutaneous injection (0 [placebo], 0.01, 0.03, 0.10, or 0.30 mg/kg). In part A, lean and obese subjects were treated for 4 weeks; in part B, obese subjects were treated for an additional 20 weeks. Lean subjects consumed a eucaloric diet to maintain body weight at the current value, and obese subjects were prescribed a diet that reduced their daily energy intake by 2100 kJ/d (500-kcal/d) from the amount needed to maintain a stable weight.Main Outcome MeasuresBody weight, body fat, and incidence of adverse events.ResultsWeight loss from baseline increased with increasing dose of leptin among all subjects at 4 weeks (P = .02) and among obese subjects at 24 weeks (P = .01) of treatment. Mean (SD) weight changes at 4 weeks ranged from −0.4 (2.0) kg for placebo (n = 36) to −1.9 kg (1.6) kg for the 0.1 mg/kg dose (n = 29). Mean (SD) weight changes at 24 weeks ranged from −0.7 (5.4) kg for the 0.01 mg/kg dose (n = 6) to –7.1 (8.5) kg for the 0.30 mg/kg dose (n = 8). Fat mass declined from baseline as dose increased among all subjects at 4 weeks (P = .002) and among obese subjects at 24 weeks of treatment (P = .004); more than 95% of weight loss was fat loss in the 2 highest dose cohorts at 24 weeks. Baseline serum leptin concentrations were not related to weight loss at week 4 (P = .88) or at week 24 (P = .76). No clinically significant adverse effects were observed on major organ systems. Mild-to-moderate reactions at the injection site were the most commonly reported adverse effects.ConclusionsA dose-response relationship with weight and fat loss was observed with subcutaneous recombinant leptin injections in both lean and obese subjects. Based on this study, administration of exogenous leptin appears to induce weight loss in some obese subjects with elevated endogenous serum leptin concentrations. Additional research into the potential role for leptin and related hormones in the treatment of human obesity is warranted.
Overexpression of SSAT in Kidney Cells Recapitulates Various Phenotypic Aspects of Kidney Ischemia-reperfusion Injury
Authors: Zhaohui Wang, Kamyar Zahedi, Sharon Barone, Kathy Tehrani, Hamid Rabb, Karl Matlin, Robert A. Casero, Manoocher Soleimani
Journal: Journal of the American Society of Nephrology (2004)

To ascertain the role of spermidine/spermine N-1-acetyl-transferase (SSAT; the rate-limiting enzyme in polyamine catabolism) in cell injury, cultured kidney (HEK 293) cells conditionally overexpressing SSAT were generated. The SSAT expression was induced and its enzymatic activity increased 24 h after addition of tetracycline and remained elevated over the length of the experiments. Induction of SSAT upregulated the expression of polyamine oxidase and resulted in the reduction of cellular concentration of spermidine and spermine, increased concentration of putrescine, and inhibited cell growth. SSAT overexpression increased the expression of heme oxygenase-1 (HO-1) by 350% 24 h after addition of tetracycline, indicating the induction of oxidative stress. The presence of catalase significantly prevented the upregulation of HO-1 in SSAT overexpressing cells, indicating that generation of H2O2 is partially responsible for the induction of oxidative stress. Overexpression of SSAT caused rounding and loss of cell anchorage and significantly altered the morphology of actin-containing filopodia, suggesting an adhesion defect. SSAT upregulation may mediate majority of the oxidative stress in kidney ischemia-reperfusion injury (IRI) as manifested by decreased cell growth, generation of toxic metabolites (H2O2 and putrescine), upregulation of HO-1, disruption of cell anchorage, and defect in cell adhesion. These data point to the inhibition of polyamine catabolism as a therapeutic approach for the prevention of tissue injury in kidney IRI.
Plasma Isoflavones and Subsequent Risk of Prostate Cancer in a Nested Case-Control Study: The Japan Public Health Center
Authors: Norie Kurahashi, Motoki Iwasaki, Manami Inoue, Shizuka Sasazuki, Shoichiro Tsugane
Journal: Journal of Clinical Oncology (2008)

Purpose The incidence of prostate cancer is much lower in Japanese than Western populations. Given the preventive effects of isoflavones on carcinogenesis in the prostate in many nonhuman studies and the high consumption of isoflavones in Japanese, this low incidence may be partly due to the effects of soy. Patients and Methods We conducted a nested case-control study within the Japan Public Health Center–based Prospective Study. A total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples were observed from 1990 to 2005. During a mean of 12.8 years of follow-up, 201 newly diagnosed prostate cancers were identified. Two matched controls for each case were selected from the cohort. Conditional logistic regression model was used to estimate the odds ratios (ORs) and 95% CIs for prostate cancer in relation to plasma levels of isoflavone. Results Plasma genistein level tended to be inversely associated with the risk of total prostate cancer. Although plasma daidzein showed no association, the highest tertile for plasma equol, a metabolite of daidzein, was significantly associated with a decreased risk of total prostate cancer (OR = 0.60; 95% CI, 0.36 to 0.99; P trend = .04). These inverse associations were strengthened after analysis was confined to localized cases, with ORs in the highest group of plasma genistein and equol compared with the lowest of 0.54 (95% CI, 0.29 to 1.01; P trend = .03) and 0.43 (95% CI, 0.22 to 0.82; P trend = .02), respectively. Plasma isoflavone levels were not statistically significantly associated with the risk of advanced prostate cancer. Conclusion Isoflavones may prevent the development of prostate cancer.
Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial
Authors: Lars Klareskog, Désirée van der Heijde, Julien P de Jager, Andrew Gough, Joachim Kalden, Michel Malaise, Emilio Martín Mola, Karel Pavelka, Jacques Sany, Lucas Settas, Joseph Wajdula, Ronald Pedersen, Saeed Fatenejad, Marie Sanda
Journal: The Lancet (2004)
Two Primary Configurations of Psychopathology and Change in Thought Disorder in Long-Term Intensive Inpatient Treatment of Seriously Disturbed Young Adults
Authors: Sidney J. Blatt, Avi Besser, Richard Q. Ford
Journal: American Journal of Psychiatry (2007)

Objective: Change in three types of thought disorder as measured by Rorschach responses (contaminations, confabulations, and fabulized combinations) were assessed during intensive, long-term, psychodynamically oriented inpatient treatment. Method: Rorschach protocols for 90 seriously disturbed, treatment-resistant patients, 42 of whom were primarily preoccupied with primitive issues of interpersonal relatedness and used avoidant defenses (anaclitic patients) and 48 primarily preoccupied with primitive issues of self-definition and self-worth and used counteractive defenses (introjective patients), were evaluated at the beginning of treatment and, on average, 15 months into treatment. Results: Change in anaclitic patients occurred primarily in more pathological forms of thought disorder (contaminations and confabulations) that express boundary disturbances; change in introjective patients occurred primarily in the less disturbed thought disorder (fabulized combinations) that expresses tendencies toward referential thinking. Conclusions: Seriously disturbed anaclitic and introjective patients expressed therapeutic progress in different but theoretically consistent ways.
TGF-β1 polymorphisms and asthma severity, airway inflammation, and remodeling
Authors: Despo Ierodiakonou, Dirkje S. Postma, Gerard H. Koppelman, Jorrit Gerritsen, Nick H.T. ten Hacken, Wim Timens, H. Marike Boezen, Judith M. Vonk
Journal: Journal of Allergy and Clinical Immunology (2012)
Symptoms Adversely Impact Survival Among Patients With Cancer and Unsuspected Pulmonary Embolism
Authors: Casey Lee O'Connell, Pedram A. Razavi, Howard A. Liebman
Journal: Journal of Clinical Oncology (2011)

significant beneficial effect of cetuximab on overall survival in patients in the experimental arm all the more impressive (median, 19.9 v 18.6 months; HR, 0.878; P ϭ .042).In patients with KRAS wild-type tumors, 11% of patients in the cetuximab plus FOLFIRI arm received subsequent EGFR-targeted therapy, compared with 31% of patients in the control arm (median survival, 23.5 v 20.0 months; HR, 0.796; P ϭ .009).Also, the baseline characteristics were well balanced across the treatment groups; the percentage of patients with a European Cooperative Oncology Group performance status of 0 and the percentage with liver-limited disease (patients with good prognosis) were essentially the same in both arms. 2 Other considerations include the fact that the proportion of patients who can be effectively treated decreases with each line of treatment; only 75% of patients receive second-line treatment, and only 50% to 60% of patients receive third-line treatment.This means that the 30% cross-over in our study actually represents 50% of the available patient population.We agree with Rother 1 that it would be nice to know the proportion of the survival gain that was attributable to EGFR therapy in the 30% of patients who were treated with FOLFIRI alone and received subsequent-line EGFR therapy.However, it is important to note that the CRYSTAL study was not designed to determine to what extent patients would benefit from a sequential treatment strategy with cetuximab.Also, the choice of EGFR therapy in the subsequent-line setting was unspecified.Inherent selection bias in terms of treatment choice on the basis of the extent of disease and patient health could also distort the results.Thus, the interpretation of such data could, at best, be only speculative.Therefore, in the absence of such data, we are left to conclude that because cetuximab has been shown to demonstrate a significant survival benefit in combination with chemotherapy in the first-line setting, despite the fact that nearly a third of patients in the control arm received subsequent-line EGFR therapy, the CRYSTAL study might actually have underestimated the survival benefit that is attributable to cetuximab in this setting.
Case of Poisoning by Carbolic Acid
Authors: G. J. Hearder
Journal: BMJ (1873)

ABOUT ten o'clock on the morning of November 27th, I was called to see a man aged 36, who had swallowed carbolic acid with suicidal intent.He said that he had "swallowed poison".About five minutes afterwards, when I first saw him, he was evidently in mortal agony.His countenance was livid, his eyeballs protruded, and he uttered a continuous subdued cry, of wild and fear-inspiring tone, which was
Commentary: measuring quality and impact of the world wide web
Authors: J C Wyatt
Journal: BMJ (1997)

Objective: To assess the reliability of healthcare information on the world wide web and therefore how it may help lay people cope with common health problems.Methods: Systematic search by means of two search engines, Yahoo and Excite, of parent oriented web pages relating to home management of feverish children.Reliability of information on the web sites was checked by comparison with published guidelines.Main outcome measures: Minimum temperature of child that should be considered as fever, optimal sites for measuring temperature, pharmacological and physical treatment of fever, conditions that may warrant a doctor's visit.Results: 41 web pages were retrieved and considered.28 web pages gave a temperature above which a child is feverish; 26 pages indicated the optimal site for taking temperature, most recommending rectal measurement; 31 of the 34 pages that mentioned drug treatment recommended paracetamol as an antipyretic; 38 pages recommended non-drug measures, most commonly tepid sponging, dressing lightly, and increasing fluid intake; and 36 pages gave some indication of when a doctor should be called.Only four web pages adhered closely to the main recommendations in the guidelines.The largest deviations were in sponging procedures and how to take a child's temperature, whereas there was a general agreement in the use of paracetamol.Conclusions: Only a few web sites provided complete and accurate information for this common and widely discussed condition.This suggests an urgent need to check public oriented healthcare information on the internet for accuracy, completeness, and consistency.
Pilot Study of Rosiglitazone Therapy in Women with Breast Cancer: Effects of Short-term Therapy on Tumor Tissue and Serum Markers
Authors: Lisa D. Yee, Nita Williams, Ping Wen, Donn C. Young, Joanne Lester, Maria V. Johnson, William B. Farrar, Michael J. Walker, Stephen P. Povoski, Saul Suster, Charis Eng
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Peroxisome proliferator-activated receptor γ (PPARγ) is a steroid nuclear receptor that is activated by natural compounds such as specific fatty acids and synthetic drugs such as thiazolidinedione antidiabetic agents. Expressed in normal and malignant mammary epithelial cells, activation of PPARγ is associated with antiproliferative effects on human breast cancer cells in preclinical studies. The purpose of this study was to test the hypothesis that PPARγ ligand therapy might inhibit tumor growth and progression in human breast cancer. Experimental Design: We conducted a pilot trial of short-term (2-6 weeks) treatment with the thiazolidinedione rosiglitazone in 38 women with early-stage (Tis-T2, N0-1, M0) breast cancer, administered between the time of diagnostic biopsy and definitive surgery. Results: Short-term treatment with rosiglitazone (8 mg/d) did not elicit significant effects on breast tumor cell proliferation using Ki67 expression as a measure of cell proliferation and surrogate marker of tumor growth and progression. In pretreatment tumors notable for nuclear expression of PPARγ by immunohistochemistry, down-regulation of nuclear PPARγ expression occurred following rosiglitazone administration (P = 0.005). No PPARG mutations were identified, and the incidence of P12A and H446H polymorphisms did not differ relative to U.S. controls (P = 0.5). Treatment with rosiglitazone resulted in increased serum adiponectin (P &amp;lt; 0.001), decreased insulin levels (P = 0.005), and increased insulin sensitivity (P = 0.004). Rosiglitazone was well tolerated without serious adverse events. Conclusion: Our data indicate that short-term rosiglitazone therapy in early-stage breast cancer patients leads to local and systemic effects on PPARγ signaling that may be relevant to breast cancer.
Response to Letter Regarding Article, “Incidence of Infective Endocarditis due to Viridans Group Streptococci Before and After Publication of the 2007 American Heart Association’s Endocarditis Prevention Guidelines”
Authors: Daniel C. DeSimone, Imad M. Tleyjeh, Daniel D. Correa de Sa, Nandan S. Anavekar, Brian D. Lahr, Muhammad R. Sohail, James M. Steckelberg, Walter R. Wilson, Larry M. Baddour
Journal: Circulation (2013)