tbuckley/cabot-search huggingface dataset:
Carcinogenesis of the Uterine Cervix in Mice: Effect of Castration After Limited Application of 3-Methylcholanthrene&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Edwin D. Murphy
Journal: JNCI Journal of the National Cancer Institute (1968)

Castration after limited exposure of the endocervical epithelium of strain A virgin females to 3-methylcholanthrene (MCA) markedly decreased the incidence of invasive cervical carcinoma. Threads bearing approximately 0.04 and 0.4 mg of MCA were placed in the endocervical canal of intact females and left for 8 and 12 weeks. When the threads were removed, alternate animals were castrated. Animals were killed when they had palpable pelvic masses or appeared moribund. At the 0.04 mg dose level for 8 and 12 weeks, the incidence of invasive squamous cell carcinoma decreased from 26.7% in intact animals to 2.0% in castrates. After 0.4 mg for 8 weeks, it decreased from 85.7–28.3% and after 0.4 mg for 12 weeks, from 100–62.3%. Implications in terms of biological and morphological stages of carcinogenesis are discussed.
Preventing Prostate Cancer: New Analyses Put Finasteride Back on the Map
Authors: B. Vastag
Journal: JNCI Journal of the National Cancer Institute (2008)

fi ndings underestimated the benefi ts of fi nasteride and overestimated its risks. The new analyses dismiss the two main concerns surrounding fi nasteride for prostate cancer prevention, Thompson said. Therefore, they are the “most important papers to come out of the study. They wrap it all up, and they show that [fi nasteride] is a home run,” he said. With the new analyses in place, the PCPT now “proves that we can actually prevent this disease,” said Christopher Logothetis , M.D., director of the genitourinary program at the University of Texas M. D. Anderson Cancer Center in Houston. Logothetis was not involved in the original study or the new analyses.
Adverse Reactions to Drug Formulation Agents: A Handbook of Excipients
Journal: Thorax (1990)

Subglottic stenosis in Wegener's granulomatosis: development during cyclophosphamide treatment with response to carbon dioxide laser therapy 301 the area of stenosis in a dose of 1250 rads (12-5 Gy) over three weeks was of symptomatic benefit to one patient.7 Mechanical relief of tracheal-obstruction has -been-obtained with
Results of arthroscopic debridement for osteochondritis dissecans of the elbow
Authors: F Th G Rahusen, J-M Brinkman, D Eygendaal
Journal: British Journal of Sports Medicine (2006)

To determine the clinical outcome of arthroscopic debridement for osteochondritis dissecans of the elbow.A prospective cohort study was started in 2000; between 2000 and 2005, 15 patients (six male, nine female, mean age 28 years (range 16-49)) were treated for osteochondritis dissecans of the elbow with arthroscopic debridement. The lesion was graded during surgery using the classification of Baumgarten. The dominant side was operated on in seven of 15 patients, and all patients were involved in a sport in which the elbow is used extensively. Elbow function was assessed before and after surgery using the modified Andrews elbow scoring system (MAESS); pain was scored on a visual analogue scale (0, no pain; 10, severe pain). Evaluation was performed an average of 45 (range 18-59) months after surgery. Statistical analysis (Student's t test) was carried out using SPSS statistical software. p<0.005 was considered significant.There were no complications. The range of motion did not improve significantly. The mean MAESS score improved from 65.5 (poor) before surgery to 90.8 (excellent) after (p<0.001). The mean level of pain at rest decreased from 3 to 1, and the level of pain after provocation decreased from 7 to 2 (p<0.001). All patients were able to return to work 3 months after surgery, and 80% were able to resume their pre-injury level of sport activity.The clinical outcome after arthroscopic debridement for osteochondritis dissecans of the elbow shows good results, with pain relief during activities of daily living and sport. The function of the elbow, as reflected by the MAESS score, improved from poor to excellent. All patients in this series will be reviewed after 5 years to determine long-term results.
Epidemiologic evidence for early onset of mental disorders and higher risk of drug abuse in young adults
Authors: K A Christie, J D Burke, D A Regier, D S Rae, J H Boyd, B Z Locke
Journal: American Journal of Psychiatry (1988)

Data from the National Institute of Mental Health (NIMH) Epidemiologic Catchment Area Program, an epidemiologic survey of five communities, showed that four major disorders commonly begin in late adolescence or young adulthood. The median age at onset for anxiety disorders is 15 years; for major depressive episode, 24 years; for drug abuse or dependence, 19 years; and for alcohol abuse or dependence, 21 years. Findings also suggest that for respondents 18-30 years old, having a major depressive episode or anxiety disorder doubles the risk for later drug abuse or dependence.
Tumor Residual After Surgical Cytoreduction in Prediction of Clinical Outcome in Stage IV Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: William E. Winter, G. Larry Maxwell, Chunqiao Tian, Michael J. Sundborg, G. Scott Rose, Peter G. Rose, Stephen C. Rubin, Franco Muggia, William P. McGuire
Journal: Journal of Clinical Oncology (2007)

Purpose To identify factors predictive of poor prognosis in a similarly treated population of women with stage IV epithelial ovarian cancer (EOC). Patients and Methods A retrospective review of 360 patients with International Federation of Gynecology and Obstetrics stage IV EOC who underwent primary surgery followed by six cycles of intravenous platinum/paclitaxel was performed. A proportional hazards model was used to assess the association of potential prognostic factors with progression-free survival (PFS) and overall survival (OS). Results The median PFS and OS for this group of stage IV ovarian cancer patients was 12 and 29 months, respectively. Multivariate regression analysis revealed that histology, malignant pleural effusion, intraparenchymal liver metastasis, and residual tumor size were significant prognostic variables. Whereas patients with microscopic residual disease had the best outcome, patients with 0.1 to 1.0 cm residual disease and patients with 1.1 to 5.0 cm residual disease had similar PFS and OS. Patients with a residual size more than 5 cm had a diminished PFS and OS when compared with all other groups. Median OS for microscopic, 0.1 to 5.0 cm, and more than 5.0 cm residual disease was 64, 30, and 19 months, respectively. Conclusion Patients with more than 5 cm residual disease have the shortest PFS and OS, whereas patients with 0.1 to 1.0 and 1.1 to 5.0 cm have similar outcome. These findings suggest that ultraradical cytoreductive procedures might be targeted for selected patients in whom microscopic residual disease is achievable. Patients with less than 5.0 cm of disease initially and significant disease and/or comorbidities precluding microscopic cytoreduction may be considered for alternative therapeutic options other than primary cytoreduction.
Variations in airways impedance during respiratory cycle derived from combined measurements of input and transfer impedances
Authors: W Tomalak, R Peslin, C Duvivier
Journal: European Respiratory Journal (1998)

Simultaneous measurement of input (Zin) and transfer impedances (Ztr) allows separation of airway and tissue properties at a single frequency, without making assumptions concerning the structure of the two compartments. This approach offers the possibility of studying the variation in airway impedance (Zaw) during the respiratory cycle. Zin and Ztr were measured at frequencies of 10, 20, 30 and 40 Hz in eight healthy subjects to study the variations in Zaw according to a modification of the Rohrer's equation: X=K1+K2(V'ao)-K3V, where V is volume and V'ao the flow at the airway opening. The results showed that Zaw could be modelled as a simple resistance-inertance pathway. Variations in airway resistance (Raw) with flow were greater during expiration than during inspiration with K2 values varying from 0.76-0.90 hPa x s2 x L(-2) during inspiration and 0.84-1.47 hPa x s2 x L(-2) during expiration, independently of frequency. Raw was negative volume dependent; it decreased more with increasing volume during inspiration than during expiration. Airways inertance calculated from the imaginary part of Zaw also underwent systematic variations during the respiratory cycle, but, in contrast to Raw, flow dependence was negative during both phases. In conclusion, the approach used in this study allows flow and volume dependencies of airways mechanical properties to be studied and can also provide indices of airway patency independently of flow, which is of great potential interest for studying variations in airway resistance during bronchomotor tests.
Involvement of Tweak in Interferon γ–Stimulated Monocyte Cytotoxicity
Authors: Masafumi Nakayama, Nobuhiko Kayagaki, Noriko Yamaguchi, Ko Okumura, Hideo Yagita
Journal: The Journal of Experimental Medicine (2000)

TWEAK, a new member of the tumor necrosis factor (TNF) family, induces cell death in some tumor cell lines, but its physiological functions are largely unknown. In this study, we investigated the expression and function of TWEAK in human peripheral blood mononuclear cells (PBMCs) by using newly generated anti–human TWEAK mAbs. Although freshly isolated PBMCs expressed no detectable level of TWEAK on their surfaces, a remarkable TWEAK expression was rapidly observed on monocytes upon stimulation with interferon (IFN)-γ but not with IFN-α or lipopolysaccharide. Cytotoxic activity of IFN-γ–stimulated monocytes against human squamous carcinoma cell line HSC3 was inhibited partially by anti-TWEAK mAb alone and almost completely by combination with anti-TRAIL (TNF-related apoptosis-inducing ligand) mAb. These results revealed a novel pathway of monocyte cytotoxicity against tumor cells that is mediated by TWEAK and potentiated by IFN-γ.
Therapeutic Efficacy of Granulocyte-Macrophage Colony-Stimulating Factor in Patients with Idiopathic Acquired Alveolar Proteinosis
Authors: JOHN F. SEYMOUR, JEFFREY J. PRESNEILL, OTTO D. SCHOCH, GORDON H. DOWNIE, PAUL E. MOORE, IAN R. DOYLE, JANETTE M. VINCENT, KOH NAKATA, TAKAYUKI KITAMURA, DAVID LANGTON, MICHAEL C. PAIN, ASHLEY R. DUNN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte–macrophage colony-stimulating factor (GM–CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of GM–CSF in patients with idiopathic AP. Fourteen patients received 5 μ g/kg/d GM–CSF for 6 to 12 wk with serial monitoring of the alveolar–arterial oxygen gradient ([A–a]Do 2), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 μ g/kg/d GM–CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for GM–CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 μ g/kg/d GM– CSF, and one of four patients responded after dose escalation (20 μ g/kg/d). The overall response rate was 43% (mean improvement in [A–a]Do 2 = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. GM–CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was GM–CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM–CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM– CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.
Intestinal ABCA1 directly contributes to HDL biogenesis in vivo
Authors: L. R. Brunham
Journal: Journal of Clinical Investigation (2006)

Plasma HDL cholesterol levels are inversely related to risk for atherosclerosis. The ATP-binding cassette, subfamily A, member 1 (ABCA1) mediates the rate-controlling step in HDL particle formation, the assembly of free cholesterol and phospholipids with apoA-I. ABCA1 is expressed in many tissues; however, the physiological functions of ABCA1 in specific tissues and organs are still elusive. The liver is known to be the major source of plasma HDL, but it is likely that there are other important sites of HDL biogenesis. To assess the contribution of intestinal ABCA1 to plasma HDL levels in vivo, we generated mice that specifically lack ABCA1 in the intestine. Our results indicate that approximately 30% of the steady-state plasma HDL pool is contributed by intestinal ABCA1 in mice. In addition, our data suggest that HDL derived from intestinal ABCA1 is secreted directly into the circulation and that HDL in lymph is predominantly derived from the plasma compartment. These data establish a critical role for intestinal ABCA1 in plasma HDL biogenesis in vivo.
Sulfasalazine induces haem oxygenase-1 via ROS-dependent Nrf2 signalling, leading to control of neointimal hyperplasia
Authors: Ju-Young Kim, Hyun-Jai Cho, Jung-Ju Sir, Baek-Kyung Kim, Jin Hur, Seock-Won Youn, Han-Mo Yang, Soo-In Jun, Kyung-Woo Park, Seok-Jae Hwang, Yoo-Wook Kwon, Hae-Young Lee, Hyun-Jae Kang, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Cardiovascular Research (2009)

Inflammation, and the subsequent proliferative activity of vascular smooth muscle cells (VSMCs), is one of the major pathophysiological mechanisms associated with neointimal hyperplasia following vascular injury. Although sulfasalazine (SSZ) has been used as an anti-inflammatory and immune-modulatory agent in various inflammatory diseases, its primary targets and therapeutic effects on vascular disease have not yet been determined. We investigated whether SSZ could suppress VSMC growth and prevent neointimal hyperplasia. SSZ was found to have pro-apoptotic and anti-proliferative activity in cultured VSMCs. Unexpectedly, these effects were not mediated by nuclear factor kappa B (NF-κB) inhibition, which has been suggested to be the anti-inflammatory mechanism associated with the effects of SSZ. Instead, cell-cycle arrest of the VSMCs was observed, which was mediated by induction of haem oxygenase-1 (HO-1) followed by an increased expression of p21waf1/Cip1. The underlying mechanism for SSZ-induced HO-1 expression was by reactive oxygen species (ROS)-dependent nuclear translocation and activation of nuclear factor erythroid-2-related factor 2 (Nrf2). In a rat carotid artery balloon injury model, administration of SSZ significantly suppressed neointimal growth. In a series of reverse experiments, inhibition of HO-1 by shRNA, ROS by N-acetylcysteine (NAC) or Nrf2 by dominant-negative Nrf2 abrogated the beneficial effects of SSZ. Our data demonstrate that SSZ inhibits VSMC proliferation in vitro and in vivo through a novel signalling pathway and may be a promising therapeutic option for the treatment of proliferative vascular disease.
Mortality Trends Among People With Type 1 and Type 2 Diabetes in Australia: 1997–2010
Authors: Jessica L. Harding, Jonathan E. Shaw, Anna Peeters, Tenniel Guiver, Susan Davidson, Dianna J. Magliano
Journal: Diabetes Care (2014)

With improvements in cardiovascular disease (CVD) rates among people with diabetes, mortality rates may also be changing. However, these trends may be influenced by coding practices of CVD-related deaths on death certificates. We analyzed trends of mortality over 13 years in people with diabetes and quantified the potential misclassification of CVD mortality according to current coding methods.A total of 1,136,617 Australians with diabetes registered on the National Diabetes Services Scheme between 1997 and 2010 were linked to the National Death Index. Excess mortality relative to the Australian population was reported as standardized mortality ratios (SMRs). Potential misclassification of CVD mortality was determined by coding CVD according to underlying cause of death (COD) and then after consideration of both the underlying and other causes listed in part I of the death certificate.For type 1 diabetes, the SMR decreased in males from 4.20 in 1997 to 3.08 in 2010 (Ptrend < 0.001) and from 3.92 to 3.46 in females (Ptrend < 0.01). For type 2 diabetes, the SMR decreased in males from 1.40 to 1.21 (Ptrend < 0.001) and from 1.56 to 1.22 in females (Ptrend < 0.001). CVD deaths decreased from 35.6 to 31.2% and from 31.5 to 27.2% in males and females with type 1 diabetes, respectively (Ptrend < 0.001 for both sexes). For type 2 diabetes, CVD decreased from 44.5 to 29.2% in males and from 45.5 to 31.6% in females (Ptrend < 0.001 for both sexes). Using traditional coding methods, ∼38 and 26% of CVD deaths are underestimated in type 1 diabetes and type 2 diabetes, respectively.All-cause and CVD mortality has decreased in diabetes. However, the total CVD mortality burden is underestimated when only underlying COD is considered. This has important ramifications for understanding mortality patterns in diabetes.
Cord blood comprises antigen-experienced T cells specific for maternal minor histocompatibility antigen HA-1
Authors: Bregje Mommaas, Janine A. Stegehuis-Kamp, Astrid G. van Halteren, Michel Kester, Jürgen Enczmann, Peter Wernet, Gesine Kögler, Tuna Mutis, Anneke Brand, Els Goulmy
Journal: Blood (2004)
Second-generation RIBA to confirm diagnosis of HCV infection
Authors: Alberto León, Rafael Canton, Matilde Elía, Marisa Mateos, Danila Bassetti, Vincenzo Cutrupi, Bianca Dallago, Pietro Alfonsi, Freja Ebeling, Ruth Naukkarinen, Gunnar Myllylä, Juhani Leikola
Journal: The Lancet (1991)
P214 Acute exacerbations of COPD: a review of resuscitation status and associations with prognostic factors in hospital admissions
Authors: B. Rudran, L. Idris, C. Childs, F. Riccio, S. Loganathan, T. J. Shaw
Journal: Thorax (2011)

<h3>Introduction</h3> Acute exacerbations of COPD are among the most common reasons for hospital admission in the UK. Exacerbations can lead to respiratory failure requiring ventilatory support, and so decisions regarding “escalation” or “ceilings” of treatment are often made early in admission. Such decisions on intubation are inevitably linked to decisions regarding resuscitation status. Prognostic factors should be used when making these decisions and FEV<sub>1</sub> should not be used exclusively. We reviewed admissions with exacerbations of COPD, categorised by resuscitation status, to see if there were differences in prognostic features between groups. <h3>Methods</h3> 53 acute admissions with exacerbations of COPD were reviewed between 1 December 2010 and 31 January. Groups were divided by resuscitation status: documented decision not to attempt resuscitation (DNR), no documented decision (NoD) and documented decision for resuscitation (ForR). Data were collected on individual prognostic factors; we then calculated prognostic indices against known criteria. P values were calculated using Mann–Whitney U test. <h3>Results</h3> The significant findings were that patients in the DNR group had lower FEV<sub>1</sub>, more likely to have home oxygen and had a poorer functional status. Age, comorbidity, BMI and previous ITU admission were not found to be significantly different between the groups. When the prognostic indices were calculated the patients in the DNR group were found to have higher scores, correlating with poorer prognosis. <h3>Conclusions</h3> From the results we can infer which factors are being used for resuscitation decisions in patients with COPD. Functional status and home oxygen are most relied upon with FEV<sub>1</sub> somewhat less so. Age, comorbidity and BMI are not being taken into account, despite evidence to suggest they should be considered. We have also discovered that ADO and GSF are strong prognostic indicators for this cohort, although their application may not be appropriate (only two patients of the DNR group had a predicted 3-year mortality &gt;50% on ADO index). This may reflect other factors (such as patient choice) that we have not evaluated. We feel that as many prognostic factors as available should be considered when making decisions on resuscitation as ultimately, this may also be the decision not to intubate.
Effect of Cigarette Smoking and Nicotine on Serum Free Fatty Acids
Authors: ALFRED KERSHBAUM, SAMUEL BELLET, EDWARD R. DICKSTEIN, LEONARD J. FEINBERG
Journal: Circulation Research (1961)

The effect of cigarette smoking on serum free fatty acids (FFA) was studied in human subjects. After smoking two cigarettes there was an average maximal elevation in FFA of 351 µEq./L. This usually occurred 10 minutes after smoking and, in most instances, there was still some elevation 20 and 40 minutes after smoking. There was essentially no effect on serum cholesterol and triglyceride levels. In subjects who "chain-smoked" six cigarettes, all showed a rise in FFA during a 60-minute period, one showing a three-fold elevation. The effect of intravenous nicotine on serum FFA was studied in dogs. In 13 of 15 observations there was a rise in FFA. The mean maximal elevation of 166 µEq./L. occurred after 10 minutes of nicotine infusion. These effects are probably due to sympathetic and adrenal stimulation by nicotine. This results in a rise in circulating catecholamines which rapidly effect a mobilization of FFA from the fat stores in the body.
Functional Polymorphisms in the Vascular Endothelial Growth Factor Gene Are Associated with Development of End-Stage Renal Disease in Males
Authors: Kent Doi, Eisei Noiri, Akihide Nakao, Toshiro Fujita, Shuzo Kobayashi, Katsushi Tokunaga
Journal: Journal of the American Society of Nephrology (2006)

This study elucidates the genetic role of vascular endothelial growth factor (VEGF) as a predisposing factor for progression of chronic kidney disease. Single-nucleotide polymorphisms were genotyped and haplotype structures were determined in the 3' untranslated region (UTR) of VEGF gene, and the distribution of each haplotype in male patients with ESRD (n=101) and healthy male control subjects (n=189) was examined. The 936C/T and 1451C/T polymorphisms in the 3' UTR were in nearly absolute linkage disequilibrium, and haplotype analysis demonstrated that they were the primary responsible single-nucleotide polymorphisms. The distribution of the 936CC-1451CC genotype was significantly more frequent among patients with ESRD than among the age-matched healthy control subjects. In addition to case-control association study, the 936CC-1451CC genotype was also associated with significantly higher plasma VEGF levels in healthy individuals, but a significant association was found only in males, not in females. We also examined the effect of the 936C-1451C haplotype on mRNA stability. Consistent with the results of plasma VEGF levels, mRNA carrying 936C-1451C haplotype showed higher stability. The 936CC-1451CC genotype in the 3' UTR showed not only susceptibility for ESRD but also higher plasma VEGF levels and mRNA stability, indicating the contribution of VEGF to chronic kidney disease progression, especially in males.