tbuckley/cabot-search huggingface dataset:
Bariatric Surgery and Long-term Cardiovascular Events
Authors: Lars Sjöström, Markku Peltonen, Peter Jacobson, C. David Sjöström, Kristjan Karason, Hans Wedel, Sofie Ahlin, Åsa Anveden, Calle Bengtsson, Gerd Bergmark, Claude Bouchard, Björn Carlsson, Sven Dahlgren, Jan Karlsson, Anna-Karin Lindroos, Hans Lönroth, Kristina Narbro, Ingmar Näslund, Torsten Olbers, Per-Arne Svensson, Lena M. S. Carlsson
Journal: JAMA (2012)

Obesity is a risk factor for cardiovascular events. Weight loss might protect against cardiovascular events, but solid evidence is lacking.To study the association between bariatric surgery, weight loss, and cardiovascular events.The Swedish Obese Subjects (SOS) study is an ongoing, nonrandomized, prospective, controlled study conducted at 25 public surgical departments and 480 primary health care centers in Sweden of 2010 obese participants who underwent bariatric surgery and 2037 contemporaneously matched obese controls who received usual care. Patients were recruited between September 1, 1987, and January 31, 2001. Date of analysis was December 31, 2009, with median follow-up of 14.7 years (range, 0-20 years). Inclusion criteria were age 37 to 60 years and a body mass index of at least 34 in men and at least 38 in women. Exclusion criteria were identical in surgery and control patients. Surgery patients underwent gastric bypass (13.2%), banding (18.7%), or vertical banded gastroplasty (68.1%), and controls received usual care in the Swedish primary health care system. Physical and biochemical examinations and database cross-checks were undertaken at preplanned intervals.The primary end point of the SOS study (total mortality) was published in 2007. Myocardial infarction and stroke were predefined secondary end points, considered separately and combined.Bariatric surgery was associated with a reduced number of cardiovascular deaths (28 events among 2010 patients in the surgery group vs 49 events among 2037 patients in the control group; adjusted hazard ratio [HR], 0.47; 95% CI, 0.29-0.76; P = .002). The number of total first time (fatal or nonfatal) cardiovascular events (myocardial infarction or stroke, whichever came first) was lower in the surgery group (199 events among 2010 patients) than in the control group (234 events among 2037 patients; adjusted HR, 0.67; 95% CI, 0.54-0.83; P < .001).Compared with usual care, bariatric surgery was associated with reduced number of cardiovascular deaths and lower incidence of cardiovascular events in obese adults.
Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets
Authors: Alicia K. Olivier, Yaling Yi, Xingshen Sun, Hongshu Sui, Bo Liang, Shanming Hu, Weiliang Xie, John T. Fisher, Nicholas W. Keiser, Diana Lei, Weihong Zhou, Ziying Yan, Guiying Li, Turan I.A. Evans, David K. Meyerholz, Kai Wang, Zoe A. Stewart, Andrew W. Norris, John F. Engelhardt
Journal: Journal of Clinical Investigation (2012)

Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis. The lack of an animal model for CF-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. We evaluated the structure and function of the neonatal CF endocrine pancreas using a new CFTR-knockout ferret model. Although CF kits are born with only mild exocrine pancreas disease, progressive exocrine and endocrine pancreatic loss during the first months of life was associated with pancreatic inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly, prior to major exocrine pancreas disease, CF kits demonstrated significant abnormalities in blood glucose and insulin regulation, including diminished first-phase and accentuated peak insulin secretion in response to glucose, elevated peak glucose levels following glucose challenge, and variably elevated insulin and C-peptide levels in the nonfasted state. Although there was no difference in lobular insulin and glucagon expression between genotypes at birth, significant alterations in the frequencies of small and large islets were observed. Newborn cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion in comparison to controls, suggesting intrinsic abnormalities in CF islets. These findings demonstrate that early abnormalities exist in the regulation of insulin secretion by the CF endocrine pancreas.
Analysis of quantitative changes in hair growth during treatment with chemotherapy or tamoxifen in patients with breast cancer: a cohort study
Authors: V. Kanti, R. Nuwayhid, J. Lindner, K. Hillmann, A. Stroux, N. Bangemann, A. Kleine-Tebbe, U. Blume-Peytavi, N. Garcia Bartels
Journal: British Journal of Dermatology (2013)

In women with breast cancer, chemotherapy-induced alopecia is a highly feared but common side-effect of antineoplastic treatment. The onset, pattern and amount of hair loss differ depending on the therapy regimen and have not yet been quantified using standardized techniques.To evaluate objectively and compare the effect of antineoplastic therapy with chemotherapy or tamoxifen on hair loss, quantifying trichological parameters.Female patients with breast cancer were included (n = 34), who were receiving chemotherapy (group C, n = 17) or tamoxifen (group T, n = 17) after surgery. Trichological parameters were evaluated once before [week 0 (w0)], twice during (w3, w6) and twice after (w18, w28) the normal 16-week course of chemotherapy, or at corresponding time points during continuous tamoxifen intake. At each visit, anagen and telogen hairs and hair density were quantified by automated phototrichogram in two defined areas: frontal and occipital.Group T generally showed no changes in anagen and telogen hairs or hair density. In group C, anagen hairs and hair density generally followed the same course, decreasing until w6, remaining at a low level during w6-18 and increasing after cessation of chemotherapy, reaching values comparable with or higher than baseline at w28. Telogen hairs increased until w3 then decreased until w6, remaining stable afterwards.Diffuse hair loss begins shortly after initiation of chemotherapy, mainly as anagen effluvium, with a proportion of anagen to telogen conversion. Hair loss is most prominent after 6 weeks of chemotherapy. Within 3 months after cessation of chemotherapy, hair growth rate returns to baseline values. Tamoxifen did not affect hair growth parameters.
Atrial Fibrillation and Stroke Associated With Intravenous Bisphosphonate Therapy in Older Patients With Cancer
Authors: Gregg S. Wilkinson, Jacques Baillargeon, Yong-Fang Kuo, Jean L. Freeman, James S. Goodwin
Journal: Journal of Clinical Oncology (2010)

Recent studies have linked the use of intravenous and orally administered bisphosphonates with subsequent development of atrial fibrillation. Patients with cancer who receive intravenous bisphosphonate therapy may be at particular risk for this adverse event because they receive higher doses of these drugs than do patients treated for other indications. We examined the association of intravenous bisphosphonates with atrial fibrillation, all classifications of supraventricular tachycardia (SVT), and stroke among older patients with cancer.Using Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data, we identified older (≥ age 65 years) patients with cancer who were treated with intravenous infusions of bisphosphonates between January 1, 1995 and December 31, 2003. We then matched 13,714 bisphosphonate nonusers to 6,857 bisphosphonate users, at a 2:1 ratio, on cancer type, age, sex, presence of bone metastases, and SEER geographic region. Patients were observed until December 31, 2003 or until they lost coverage from Medicare Parts A and B; enrolled in a health maintenance organization; received a diagnosis of atrial fibrillation, any SVT, or stroke; or died.Receipt of intravenous bisphosphonates was modestly associated with an increased risk for atrial fibrillation (hazard ratio [HR] = 1.30; 95% CI, 1.18 to 1.43), all SVT (HR = 1.28; 95% CI, 1.19 to 1.38), and stroke (HR = 1.30; 95% CI, 1.09 to 1.54). The risk for all SVT increased 7% for each increase of five bisphosphonate dose equivalents (HR = 1.07; 95% CI, 1.02 to 1.12).Clinicians who treat patients with cancer who have received intravenous bisphosphonates should be aware of the possible cardiovascular adverse events associated with this treatment.
Retinoic acid pathway activity in wilms tumors and characterization of biological responses in vitro
Authors: Jenny Wegert, Sabrina Bausenwein, Susanne Kneitz, Sabine Roth, Norbert Graf, Eva Geissinger, Manfred Gessler
Journal: Molecular Cancer (2011)

Abstract Background Wilms tumor (WT) is one of the most common malignancies in childhood. With current therapy protocols up to 90% of patients can be cured, but there is still a need to improve therapy for patients with aggressive WT and to reduce treatment intensity where possible. Prior data suggested a deregulation of the retinoic acid (RA) signaling pathway in high-risk WT, but its mode of action remained unclear. Results The association of retinoid signaling and clinical parameters could be validated in a large independent tumor set, but its relevance in primary nephrectomy tumors from very young children may be different. Reduced RA pathway activity and MYCN overexpression were found in high risk tumors as opposed to tumors with low/intermediate risk, suggesting a beneficial impact of RA especially on advanced WT. To search for possible modes of action of retinoids as novel therapeutic options, primary tumor cell cultures were treated in vitro with all -trans -RA (ATRA), 9 cis- RA, fenretinide and combinations of retinoids and a histone deacetylase (HDAC) inhibitor. Genes deregulated in high risk tumors showed opposite changes upon treatment suggesting a positive effect of retinoids. 6/7 primary cultures tested reduced proliferation, irrespective of prior RA signaling levels. The only variant culture was derived from mesoblastic nephroma, a distinct childhood kidney neoplasm. Retinoid/HDAC inhibitor combinations provided no synergistic effect. ATRA and 9 cis- RA induced morphological changes suggestive of differentiation, while fenretinide induced apoptosis in several cultures tested. Microarray analysis of ATRA treated WT cells revealed differential expression of many genes involved in extracellular matrix formation and osteogenic, neuronal or muscle differentiation. The effects documented appear to be reversible upon drug withdrawal, however. Conclusions Altered retinoic acid signaling has been validated especially in high risk Wilms tumors. In vitro testing of primary tumor cultures provided clear evidence of a potential utility of retinoids in Wilms tumor treatment based on the analysis of gene expression, proliferation, differentiation and apoptosis.
Endothelial Cells Require STAT3 for Protection against Endotoxin-induced Inf lammation
Authors: Arihiro Kano, Michael J. Wolfgang, Qian Gao, Joerg Jacoby, Gui-Xuan Chai, William Hansen, Yoshiki Iwamoto, Jordan S. Pober, Richard A. Flavell, Xin-Yuan Fu
Journal: The Journal of Experimental Medicine (2003)

Endothelial cells (ECs) are believed to be an important component in the protection from lipopolysaccharide (LPS)-induced endotoxic shock. However, the cellular and molecular mechanism is not well defined. Here, we report that signal transducer and activator of transcription (STAT) 3 is an essential regulator of the antiinflammatory function of ECs in systemic immunity. Because STAT3 deficiency results in early embryonic lethality, we have generated mice with a conditional STAT3 deletion in endothelium (STAT3E−/−). STAT3E−/− mice are healthy and fertile, and isolated ECs initiate normal tube formation in vitro. Conditional endothelial but not organ-specific (i.e., hepatocyte or cardiomyocyte) STAT3 knockout mice show an increased susceptibility to lethality after LPS challenge. The LPS response in STAT3E−/− mice shows exaggerated inflammation and leukocyte infiltration in multiple organs combined with elevated activity of serum alanine aminotransferase and aspartate aminotransferase, indicating organ damage. Concomitantly, proinflammatory cytokines are produced at an exaggerated level and for a prolonged period. This defect cannot be explained by lack of antiinflammatory cytokines, such as interleukin 10 and transforming growth factor β. Instead, we have shown that a soluble activity derived from endothelia and dependent on STAT3 is critical for suppression of interferon γ. These data define STAT3 signaling within endothelia as a critical antiinflammatory mediator and provide new insight to the protective function of ECs in inflammation.
Extremely rare anal nodules in a rare disease
Authors: H. S. Far, V. de Parades, P. Atienza, M. Mozer, S. Chaussade, H. Guyot
Journal: Gut (2007)

A 55-year-old woman presented with chronic anal itching. She had a history of diffuse digestive polyposis with variant histological forms (hyperplastic and adenomatous polyps), and in …
Active Smoking and Breast Cancer Risk: Original Cohort Data and Meta-Analysis
Authors: Mia M. Gaudet, Susan M. Gapstur, Juzhong Sun, W. Ryan Diver, Lindsay M. Hannan, Michael J. Thun
Journal: JNCI Journal of the National Cancer Institute (2013)

The relationship between active cigarette smoking and breast cancer risk remains controversial because of unresolved issues of confounding and dose response.To investigate these issues further, we analyzed data from 73 388 women in the American Cancer Society's Cancer Prevention Study II (CPS-II) Nutrition Cohort. Analyses were based on 3721 invasive breast cancer case patients identified during a median follow-up of 13.8 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from multivariable-adjusted Cox proportional hazard regression models. P values were two-sided. We also conducted meta-analyses of our results with those published from 14 other cohort studies.In CPS-II, incidence was higher in current (HR = 1.24, 95% CI = 1.07 to 1.42) and former smokers (HR =1.13, 95% CI = 1.06 to 1.21) than in never smokers. Women who initiated smoking before menarche (HR = 1.61, 95% CI = 1.10 to 2.34) or after menarche but 11 or more years before first birth (HR = 1.45, 95% CI = 1.21 to 1.74) had higher risk (P trend = .03). No relationships were observed with other smoking parameters. Alcohol consumption did not confound associations with smoking status, although neither current nor former smoking were associated with risk among never drinkers (P interaction = .11). In meta-analyses, current (HR = 1.12, 95% CI = 1.08 to 1.16) and former smoking (HR = 1.09, 95% CI = 1.04 to 1.15) were weakly associated with risk; a stronger association (HR = 1.21, 95% CI = 1.14 to 1.28) was observed in women who initiated smoking before first birth.These results support the hypothesis that active smoking is associated with increased breast cancer risk for women who initiate smoking before first birth and suggest that smoking might play a role in breast cancer initiation.
Prostate Cancer Diagnosis Among Men With Isolated High-Grade Intraepithelial Neoplasia Enrolled Onto a 3-Year Prospective Phase III Clinical Trial of Oral Toremifene
Authors: Samir S. Taneja, Ronald Morton, Gary Barnette, Paul Sieber, Michael L. Hancock, Mitchell Steiner
Journal: Journal of Clinical Oncology (2013)

Purpose Prostate cancer (PCa) prevention remains an appealing strategy for the reduction of overtreatment and secondary adverse effects. We evaluated the efficacy of toremifene citrate 20 mg in PCa prevention among men with isolated high-grade prostatic intraepithelial neoplasia (HGPIN) on biopsy. Patients and Methods One thousand five hundred ninety men with HGPIN, or HGPIN and atypia, and no PCa on prostate biopsy were randomly assigned 1:1 to receive toremifene citrate 20 mg or placebo in a 3-year phase III, double-blind, multicenter trial. Men underwent annual biopsy until cancer detection or study end. Efficacy analysis was performed in 1,467 men who underwent at least one on-study biopsy. Baseline risk factors were evaluated to determine influence on cancer detection. Results Cancer was detected in 34.7% and 32.3% of men in the placebo and treatment groups, respectively, with no observed difference (P = .39, log-rank test) in PCa-free survival. The 3-year Kaplan-Meier PCa-free survival estimate was 54.9% (99% CI, 43.3% to 66.5%) in the placebo group and 59.5% (99% CI, 48.1% to 70.9%) in the treatment group. Exploration of baseline risk factors demonstrated no subset in which a risk reduction was observed. In the placebo group, 17.9%, 12.9%, and 13.6% of men at risk at the beginning of years 1, 2, and 3, respectively, were diagnosed with PCa. Conclusion Although toremifene 20 mg did not lower the PCa detection rate, men with isolated HGPIN have a high likelihood of eventual PCa diagnosis, demonstrating they are ideal candidates for inclusion in chemoprevention trials and require surveillance by periodic prostate biopsy.
Why Hasn't Eliminating Acute Rejection Improved Graft Survival?
Authors: JogiRaju Tantravahi, Karl L. Womer, Bruce Kaplan
Journal: Annual Review of Medicine (2006)

Although patients with end-stage renal disease can be maintained with dialysis therapy, the superiority of patient survival with renal transplantation makes transplantation the preferred method of renal replacement. Potent immunosuppressive therapies, particularly calcineurin inhibitors, have greatly reduced the incidence of acute rejection. However, long-term allograft survival remains limited. We discuss the impact of acute rejection on long-term allograft survival and discuss other factors leading to late allograft loss, including calcineurin inhibitor toxicity, chronic allograft nephropathy, and BK virus nephropathy, as well as donor and recipient factors associated with long-term allograft loss.
<b> <i>USP6 (Tre2)</i> </b> Fusion Oncogenes in Aneurysmal Bone Cyst
Authors: Andre M. Oliveira, Bae-Li Hsi, Stanislawa Weremowicz, Andrew E. Rosenberg, Paola Dal Cin, Nora Joseph, Julia A. Bridge, Antonio R. Perez-Atayde, Jonathan A. Fletcher
Journal: Cancer Research (2004)

Abstract Aneurysmal bone cyst (ABC) is a locally aggressive osseous lesion that typically occurs during the first two decades of life. ABC was regarded historically as a nonneoplastic process, but recent cytogenetic data have shown clonal rearrangements of chromosomal bands 16q22 and 17p13, indicating a neoplastic basis in at least some ABCs. Herein we show that a recurring ABC chromosomal translocation t(16;17)(q22;p13) creates a fusion gene in which the osteoblast cadherin 11 gene (CDH11) promoter region on 16q22 is juxtaposed to the entire ubiquitin-specific protease USP6 (Tre2) coding sequence on 17p13. CDH11-USP6 fusion transcripts were demonstrated only in ABC with t(16;17) but other ABCs had CDH11 or USP6 rearrangements resulting from alternate cytogenetic mechanisms. CDH11 is expressed strongly in bone, and our findings implicate a novel oncogenic mechanism in which deregulated USP6 transcription results from juxtaposition to the highly active CDH11 promoter.
Respiratory functional status after intrapleural t-PA administration for complicated parapneumonic effusions
Authors: Dionisios Spyratos, Maria Sionidou, Marina Antoniou, Theodoros Kontakiotis, Konstantinos Zarogolidis, Lazaros Sichletidis
Journal: European Respiratory Journal (2012)

Background: In a multicentered randomized trial, intrapleural administration of streptokinase has been proved unsuccessful.

Aims: To investigate lung function and exercise capacity after intrapleural administration of t-PA in patients with complicated parapneumonic pleural effusion (CPE).

Methods: 18 consecutive patients with CPE were included. Chest tube was inserted under guidance of CT. After pleural fluid drainage has stopped, 25 mg t-PA/day was administered for 2 consecutive days. We evaluated patients with spirometry before t-PA, one day after chest tube removal and one month after discharge. During the second and third time-points, 6 minute walking test was also performed.

Results: Patients reported symptoms 10.2±6.8 days days before hospital admission while all have demonstrated loculated effusions. The mean production of fluid was 717±775 ml before and 1.516±240 ml after t-PA administration (p<0.001). Lung function and exercise capacity tests are presented on table 1. Adverse events were pain (9/18) and minor bleeding (2/18) at the site of insertion.

Conclusion: Intrapleural administration of t-PA for CPE was an effective treatment considering lng function status during follow-up.

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High resolution banding analysis of the involvement of strain BALB/c- and AKR-derived chromosomes No. 15 in plasmacytoma-specific translocations.
Authors: F Wiener, M Babonits, U Bregula, G Klein, A Léonard, J S Wax, M Potter
Journal: The Journal of Experimental Medicine (1984)

Plasmacytomas were induced in (BALB/c X AKR 6;15) X BALB/c backcross mice where one of the BALB/c-derived chromosomes No. 15 was replaced by the AKR(6;15)-derived Robertsonian 6;15 chromosome. (BALB/c X AKR 6;15)F2 mice that were homozygous for Rb 6;15 were mated to BALB/c mice. Plasmacytomas were induced in the progeny by intraperitoneal injection of pristane. The cytogenetic marker permitted the distinctive identification of the two chromosome 15 homologues, including the distal segment involved in the plasmacytoma-specific translocations. 7 of the 10 plasmacytomas contained the typical t(12;15) translocation. The BALB/c-derived 15 chromosome served as the donor of the translocated segment in six of them. In the seventh, the Rb 6;15 chromosome of the AKR strain was the donor. The remaining three tumors contained the same type of intrachromosomal rearrangement. It arose by the pericentric inversion of the Rb 6;15 chromosome, leading to a variant plasmacytoma-associated rcpt (6;15) translocation. Unlike the usual 6;15 variant that arises by a reciprocal exchange between two separate chromosomes, it was generated by an exchange of the distal segments of a single chromosomal element. High resolution banding analysis of the tumors showed that all translocated breakpoints on chromosomes 15, 12, and 6 were identical with the previously described breakpoints characteristic for the typical 12;15 and the variant 6;15 translocation in murine plasmacytomas. It is known that the distal segment of chromosome 15 carries the c-myc oncogene (23). The PC-associated translocations cut across the 5'-exon of c-myc in the majority of the cases (24,26). The severed oncogene is transposed to the Ig-region on the recipient chromosome. Since the BALB/c strain is highly sensitive to PC-induction, we were interested to examine the question whether its chromosome 15 is preferred as the oncogene donor in AKR X BALB/c backcross mice that carry cytogenetically distinguishable 15 chromosomes. Our results show that this is not the case, since the same segment of the AKR-derived chromosome 15 could also serve in the same capacity. This is in contrast with T cell leukemogenesis where we have previously found that the trisomization-associated duplication of chromosome 15 occurred in a highly asymmetrical fashion, depending on the donor strain of No. 15 (9-11).