tbuckley/cabot-search huggingface dataset:
The approach to the surgical management of cancer in four European countries
Authors: C K Connolly, P E Y Van Schil, R Milroy, O Braendli, R J Prescott
Journal: European Respiratory Journal (2003)

Outcome of lung cancer appears poorer in the UK than elsewhere in Europe. This may be due to a less aggressive approach in treatment. This study investigated whether clinicians9 perceptions of their approach differed between European countries. A questionnaire was circulated to cancer specialists in four countries (Belgium, Greece, Switzerland and the UK) asking about management. An aggression score was calculated using the proportion of standard cases that would proceed to operation at different ages and levels of pulmonary function. The principle problems suggested by most of the 314 respondents were inoperability before symptoms (particularly in the UK) and confounding effects of comorbidity. Surgeons particularly blamed delay in referral. The aggression scores (Belgium 54%, UK 49%, Switzerland 47% and Greece 37%) did not suggest the UK is an outlier, but the UK was more conservative in its approach to N2 disease and isolated cerebral metastasis. The aggression scores of surgeons were greater than those of the others (51% <i>versus</i> 42%). Lung cancer was felt to present late with potentially confounding symptoms, but delay in the clinical process was thought to be less important. Although the UK was more conservative with special cases, its approach to typical cases could account for differences in patient survival.
Dynamics of the Pulmonary Venous Flow in the Fetus and Its Association With Vascular Diameter
Authors: Paulo Zielinsky, Antônio Piccoli, Eduardo Gus, João Luiz Manica, Fabíola Satler, Luiz Henrique Nicoloso, Stelamaris Luchese, Silvana Marcantonio, Marlui Scheid, Domingos Hatém
Journal: Circulation (2003)

The usual positioning of the Doppler sample volume to assess fetal pulmonary vein flow is in the distal portion of the vein, where the vessel diameter is maximal. This study was performed to test the association of the pulmonary vein pulsatility index (PVPI) with the vessel diameter.Twenty-three normal fetuses (mean gestational age, 28.6+/-5.3 weeks) were studied by Doppler echocardiography. Pulmonary right upper vein flow was assessed adjacent to the venoatrial junction ("distal" position) and in the middle of the vein ("proximal" position). The vessel diameter was measured by 2D echocardiography with power Doppler, and the PVPI was obtained by the ratio (maximal velocity [systolic or diastolic peak]-minimal velocity [presystolic peak])/mean velocity. The statistical analysis used t test and exponential correlation studies. Mean distal diameter was 0.33+/-0.10 cm (0.11 to 0.57 cm), and mean proximal diameter was 0.16+/-0.08 cm (0.11 to 0.25 cm) (P<0.0001). Mean distal PVPI was 0.84+/-0.21 (0.59 to 1.38), and mean proximal PVPI was 2.09+/-0.59 (1.23 to 3.11) (P<0.0001). Exponential inverse correlation between pulmonary vein diameter and pulsatility index was highly significant (P<0.0001), with a determination coefficient of 0.439.In the normal fetus, the pulmonary venous flow pulsatility decreases from the lung to the heart, and this parameter is inversely correlated to the diameter of the pulmonary vein, which increases from its proximal to its distal portion. This study emphasizes the importance of the correct positioning of the Doppler sample volume, adjacent to the venoatrial junction, to assess pulmonary venous flow dynamics.
The Earliest Step in B Lineage Differentiation from Common Lymphoid Progenitors Is Critically Dependent upon Interleukin 7
Authors: Juli P. Miller, David Izon, William DeMuth, Rachel Gerstein, Avinash Bhandoola, David Allman
Journal: The Journal of Experimental Medicine (2002)

Little is known about the signals that promote early B lineage differentiation from common lymphoid progenitors (CLPs). Using a stromal-free culture system, we show that interleukin (IL)-7 is sufficient to promote the in vitro differentiation of CLPs into B220(+) CD19(+) B lineage progenitors. Consistent with current models of early B cell development, surface expression of B220 was initiated before CD19 and was accompanied by the loss of T lineage potential. To address whether IL-7 receptor (R) activity is essential for early B lineage development in vivo, we examined the frequencies of CLPs and downstream pre-pro- and pro-B cells in adult mice lacking either the alpha chain or the common gamma chain (gamma(c)) of the IL-7R. The data indicate that although gamma(c)(-/-) mice have normal frequencies of CLPs, both gamma(c)(-/-) and IL-7R(alpha)(-/-) mice lack detectable numbers of all downstream early B lineage precursors, including pre-pro-B cells. These findings challenge previous notions regarding the point in B cell development affected by the loss of IL-7R signaling and suggest that IL-7 plays a key and requisite role during the earliest phases of B cell development.
Improved Procedure for Determination of Serum Lipid-Associated Sialic Acid: Application for Early Diagnosis of Colorectal Cancer
Authors: C. Tautu, G. Verazin, J. J. Prorok, J. A. Alhadeff
Journal: JNCI Journal of the National Cancer Institute (1988)

We have developed a simple and reliable procedure for determining serum levels of lipid-associated sialic acid (LASA) in crude preparations. This method extracts essentially all gangliosides, excludes glycoprotein-bound sialic acid, and gives LASA values (0.5-1.0 mg/dL) in good agreement with values for isolated serum gangliosides. The procedure was used to determine serum levels of LASA in patients with colorectal cancer, in patients with nonmalignant diseases (pathological control subjects), and in normal control subjects. The results indicated that the percentages of total sialic acid (TSA) comprised by LASA (LASA/TSA X 100) were elevated in patients with the earliest stages of colorectal cancer, compared with percentages in normal control subjects (P less than .001) and pathological control subjects (P less than .01).
Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses
Authors: P. S. Noakes, J. Hale, R. Thomas, C. Lane, S. G. Devadason, S. L. Prescott
Journal: European Respiratory Journal (2006)

Infants of smokers have much higher rates of respiratory infection, asthma and airway disease. The current study assessed the effects of maternal smoking in pregnancy on neonatal toll-like-receptor (TLR)-mediated immune responses as a possible contributing factor to the elevated rates of respiratory illness. In a prospective birth cohort, the cord blood immune responses of neonates of smoking and nonsmoking mothers were compared. Maternal and cord serum cotinine were measured to confirm the level of cigarette smoke exposure. Neonatal cytokine responses were assessed to optimal doses of TLR2, TLR3, TLR4 and TLR9 ligands. Cotinine levels confirmed maternal reporting of cigarette smoking in pregnancy, with significantly higher cotinine levels in maternal and cord blood compared with the nonsmoking group. Infants of smoking mothers showed significantly attenuated innate TLR-mediated responses compared with infants of nonsmokers. The current findings indicate that in addition to effects on developing airways, maternal smoking also has significant immunological effects in pregnancy, which could contribute to the well recognised, subsequent increased risk of respiratory infections and asthma. These effects appear to be mediated through effects on toll-like receptor-mediated innate response pathways, which also promote regulatory pathways in the inhibition of allergic immune responses in the postnatal period, suggesting that other environmental interactions are highly relevant to the “hygiene hypothesis”.
Microsatellite Instability Testing in Genetically Heterogeneous Populations
Authors: Silvia L. Cossio, Patricia Ashton-Prolla, Maria-Cátira Bortolini, Renata S. Coura, Roberto Giugliani, João C. Prolla
Journal: Journal of Clinical Oncology (2007)

As stated in our article, we agree that preimplantation genetic diagnosis for common cancer syndromes "has not been incorporated into common practice," 1 and will not be appropriate in some cases for psychological or other personal reasons.However, increasing physician awareness of assisted reproductive technologies (ART) is not synonymous with imposing discussion of these options on every individual.Without communicating availability of these options to reproductive-age patients, how can they make truly informed decisions?For example, such discussions will come up in the setting of patients of reproductive age with newly diagnosed cancer who may consider ART for fertility preservation, or infertile individuals with cancer predisposing mutations who seek to utilize in vitro fertilization to achieve pregnancy.Oncologists can recognize those instances when ART may be of potential interest to a couple at risk for hereditary cancer, and then make referrals to professionals who can reliably discuss reproductive options with sensitivity to the emotional aspects and ethical issues.In an effort to guide clinicians and policy makers as they attempt to distinguish circumstances for which discussions of preimplantation genetic diagnosis may be appropriate for families affected by cancer, we have recently provided an analytic framework. 2This framework takes into consideration: the age at onset of the disorder, the penetrance of the syndrome, the severity of the syndrome, the means available to decrease genetically acquired cancer risk, the availability of assisted reproduction options and the potential risks of preimplantation genetic diagnosis itself (eg, exposure to exogenous hormones).A broader discussion of the medical aspects, as well as ethical challenges of assisted reproduction will ensure its most responsible transition to clinical practice.
Integrin-Linked Kinase Expression Is Elevated in Human Cardiac Hypertrophy and Induces Hypertrophy in Transgenic Mice
Authors: Huanzhang Lu, Paul W. M. Fedak, Xiaojing Dai, Changqing Du, Yu-Qing Zhou, Mark Henkelman, Perry S. Mongroo, Arthur Lau, Hideaki Yamabi, Aleksander Hinek, Mansoor Husain, Gregory Hannigan, John G. Coles
Journal: Circulation (2006)

Background— Although numerous signaling pathways are known to be activated in experimental cardiac hypertrophy, the molecular basis of the hypertrophic response inherent in human heart diseases remains largely unknown. Integrin-linked kinase (ILK) is a multifunctional protein kinase that physically links β-integrins with the actin cytoskeleton, suggesting a potential mechanoreceptor role. Methods and Results— Here, we show a marked increase in ILK protein levels in hypertrophic ventricles of patients with congenital and acquired outflow tract obstruction. This increase in ILK was associated with activation of the Rho family guanine triphosphatases, Rac1 and Cdc42, and known hypertrophic signaling kinases, including extracellular signal-related kinases (ERK1/2) and p70 S6 kinase. Transgenic mice with cardiac-specific expression of a constitutively active ILK (ILK S343D ) or wild-type ILK (ILK WT ) exhibited a compensated ventricular hypertrophic phenotype and displayed an activation profile of guanine triphosphatases and downstream protein kinases concordant with that seen in human hypertrophy. In contrast, transgenic mice with cardiomyocyte-restricted expression of a kinase-inactive ILK (ILK R211A ) were unable to mount a compensatory hypertrophic response to angiotensin II in vivo. Conclusions— Taken together, these results identify ILK-regulated signaling as a broadly adaptive hypertrophic response mechanism relevant to a wide range of clinical heart disease.
Emergency Postexposure Vaccination With Vesicular Stomatitis Virus–Vectored Ebola Vaccine After Needlestick
Authors: Lilin Lai, Richard Davey, Allison Beck, Yongxian Xu, Anthony F. Suffredini, Tara Palmore, Sarah Kabbani, Susan Rogers, Gary Kobinger, Judie Alimonti, Charles J. Link, Lewis Rubinson, Ute Ströher, Mark Wolcott, William Dorman, Timothy M. Uyeki, Heinz Feldmann, H. Clifford Lane, Mark J. Mulligan
Journal: JAMA (2015)

Safe and effective vaccines and drugs are needed for the prevention and treatment of Ebola virus disease, including following a potentially high-risk exposure such as a needlestick.To assess response to postexposure vaccination in a health care worker who was exposed to the Ebola virus.Case report of a physician who experienced a needlestick while working in an Ebola treatment unit in Sierra Leone on September 26, 2014. Medical evacuation to the United States was rapidly initiated. Given the concern about potentially lethal Ebola virus disease, the patient was offered, and provided his consent for, postexposure vaccination with an experimental vaccine available through an emergency Investigational New Drug application. He was vaccinated on September 28, 2014.The vaccine used was VSVΔG-ZEBOV, a replicating, attenuated, recombinant vesicular stomatitis virus (serotype Indiana) whose surface glycoprotein gene was replaced by the Zaire Ebola virus glycoprotein gene. This vaccine has entered a clinical trial for the prevention of Ebola in West Africa.The vaccine was administered 43 hours after the needlestick occurred. Fever and moderate to severe symptoms developed 12 hours after vaccination and diminished over 3 to 4 days. The real-time reverse transcription polymerase chain reaction results were transiently positive for vesicular stomatitis virus nucleoprotein gene and Ebola virus glycoprotein gene (both included in the vaccine) but consistently negative for Ebola virus nucleoprotein gene (not in the vaccine). Early postvaccination cytokine secretion and T lymphocyte and plasmablast activation were detected. Subsequently, Ebola virus glycoprotein-specific antibodies and T cells became detectable, but antibodies against Ebola viral matrix protein 40 (not in the vaccine) were not detected.It is unknown if VSVΔG-ZEBOV is safe or effective for postexposure vaccination in humans who have experienced a high-risk occupational exposure to the Ebola virus, such as a needlestick. In this patient, postexposure vaccination with VSVΔG-ZEBOV induced a self-limited febrile syndrome that was associated with transient detection of the recombinant vesicular stomatitis vaccine virus in blood. Strong innate and Ebola-specific adaptive immune responses were detected after vaccination. The clinical syndrome and laboratory evidence were consistent with vaccination response, and no evidence of Ebola virus infection was detected.
Chlamydia Trachomatis and Inflammatory Bowel Disease - a Coincidence?
Authors: R Orda, Z Samra, Y Levy, Y Shperber, E Scapa
Journal: Journal of the Royal Society of Medicine (1990)

Serological tests of 35 patients suffering from inflammatory bowel disease were compared to those of 35 healthy controls. The tests were performed using the indirect immunoperoxidase assay. Ninety-three per cent of 15 patients with Crohn's disease had IgG antibodies against Chlamydia, compared to 26% in the control group. In the 20 patients with ulcerative colitis, 45% had IgG antibodies against Chlamydia, compared to 10% in the control group. High serum titres of IgG antibodies were found in most of the patients with inflammatory bowel disease, mainly with Crohn's disease, while weak reactions appeared in most of the controls in which antibodies were detected. These results suggest a high incidence of Chlamydia infection in the studied patients with inflammatory bowel disease, especially in those with Crohn's disease. The possible association between Chlamydia trachomatis and inflammatory bowel disease is discussed.
Cough threshold to citric acid in diabetic patients with and without autonomic neuropathy.
Authors: L G Vianna, S G Gilbey, N C Barnes, R J Guy, B J Gray
Journal: Thorax (1988)

The cough reflex has been investigated in insulin dependent diabetic patients with and without autonomic neuropathy. The cough response to inhaled citric acid was determined in eight patients with diabetes who had severe autonomic neuropathy and compared with that in 10 who had no evidence of neuropathy. The patients with autonomic neuropathy had a higher median threshold for the cough response to citric acid (median 50%, range 20- greater than 100%) than non-neuropathic control patients (median 10%, range 2-20%). These results suggest that vagal innervation of the bronchial tree is damaged by diabetic autonomic neuropathy.
Estimating the contribution of occupational solar ultraviolet exposure to skin cancer
Authors: A. Milon, J.-L. Bulliard, L. Vuilleumier, B. Danuser, D. Vernez
Journal: British Journal of Dermatology (2013)

Exposure to solar ultraviolet (UV) radiation is the main causative factor for skin cancer. Outdoor workers are at particular risk because they spend long working hours outside, may have little shade available and are bound to take their lunch at their workplace. Despite epidemiological evidence of a doubling in risk of squamous cell carcinoma (SCC) in outdoor workers, the recognition of skin cancer as an occupational disease remains scarce.To assess occupational solar UV doses and their contribution to skin cancer risk.A numerical model (SimUVEx) was used to assess occupational and lunch break UV exposure, and to characterize exposure patterns and anatomical distribution. Risk of SCC was estimated from an existing epidemiological model.Horizontal body locations received 2.0-2.5 times more UV than vertical locations. The dose associated with having lunch outdoors every day was similar to that from doing outdoor work 1 day per week, but only half that of a seasonal worker. Outdoor work is associated with an increased risk of SCC and also with frequent acute episodes.Occupational solar exposure contributes greatly to overall lifetime UV dose, resulting in an excess risk of SCC. The magnitude of the estimated excess in risk supports the recognition of SCC as an occupational disease.
Health-related Quality of Life and Mortality in Male Patients with Chronic Obstructive Pulmonary Disease
Authors: Antònia Domingo-Salvany, Rosa Lamarca, Montserrat Ferrer, Judith Garcia-Aymerich, Jordi Alonso, Miquel Félez, Ahmad Khalaf, Ramon M. Marrades, Eduard Monsó, Joan Serra-Batlles, Josep M. Antó
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

To assess whether generic and specific health-related quality of life (HRQL) are independently associated with total and specific mortality in patients with chronic obstructive pulmonary disease (COPD), we followed until 1999 a cohort of 321 male patients with COPD, recruited in 1993-1994 at outpatient respiratory clinics. Baseline characteristics recorded under stable clinical conditions included forced spirometry, arterial blood gas tensions, dyspnea scales, 11 comorbid conditions, St. George's Respiratory Questionnaire (SGRQ), and SF-36 Health Survey. Vital status was assessed through reinterviews, the Mortality Register, and clinical records. Subjects who died (106) were older (69.8 versus 62.5 years) (p < 0.001), had lower body mass index (BMI) (25.4 versus 27.1) (p < 0.01), were more impaired in the clinical characteristics studied (%FEV(1), 34.0 versus 51.0) (p < 0.001), and had long-term oxygen therapy more frequently (31% versus 7%) (p < 0.001). Survival was shorter when worse HRQL was reported. SGRQ total and SF-36 physical summary scores were independently associated with total and respiratory mortality in Cox models, including age, FEV(1), and BMI. The total mortality-standardized hazard ratios for both HRQL measures were 1.3, whereas those for FEV(1) were 1.6. HRQL measures provide independent and relevant information on the health status of male patients with COPD. Their use should be considered for a more thorough evaluation and staging of patients with COPD.
Inverse Effects of Mucin on Survival of Matched Hereditary Nonpolyposis Colorectal Cancer and Sporadic Colorectal Cancer Patients
Authors: Jeng-Fu You, Ling-Ling Hsieh, Chung Rong Changchien, Jinn-Shiun Chen, Jim-Ray Chen, Jy-Ming Chiang, Chien Yuh Yeh, Pao-Shiu Hsieh, Chung-Wei Fan, Chun-Ting Liu, Reiping Tang
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To compare survival and histologic features of hereditary nonpolyposis colorectal cancer (HNPCC; Lynch syndrome) cases to well-matched sporadic colon cancers from the same patient population. Experimental Design: Between January 1995 and March 2002, a total of 5,138 consecutive patients underwent resection of primary colorectal adenocarcinoma in a single institution. According to the Amsterdam criteria, 56 HNPCC patients were matched to 147 sporadic colorectal cancer (SCRC) with no family history of cancer and with the same gender, tumor location, and age within 3 years. Immunohistochemical analyses were done for MUC1, MUC2, MUC3, and MUC5AC. Results: The HNPCC group had a marginally significantly better long-term outcome than the SCRC group (P = 0.058). The trend disappeared after adjustment by tumor-node-metastasis stage in a Cox model (P = 0.774). We noted a difference of &amp;gt;50% in the 5-year cancer-specific survival rates of HNPCC- and SCRC-mucinous groups (92% versus 31%, P = 0.0003). Interaction between mucin and HNPCC and its effects on survival were further confirmed by comparing the Cox models with and without interaction terms (hazard ratio, 0.1; P = 0.034 with adjusting stage). Patients with tumors showing dual expression of mucin and MUC1, which appeared in 11% of those with HNPCC and 50% of those with SCRC, had a lower 5-year cancer-specific survival rate than patients without (30% versus 60%; P = 0.004 by log-rank test; P = 0.039 with adjustment for tumor-node-metastasis stage). Conclusions: These results suggest that mucin has an inverse effect on survival in patients with HNPCC and SCRC, which might be partly explained by a lower prevalence of MUC1 expression in the mucinous HNPCC group than in the SCRC groups.
Balancing diversity and tolerance
Authors: Annett M. Jacobi, Betty Diamond
Journal: The Journal of Experimental Medicine (2005)

The autoimmune disease systemic lupus erythematosus (SLE) is caused by a failure of B cell tolerance. Recent studies in mouse models of SLE have identified several distinct tolerance checkpoints that must each function appropriately to protect against disease. However, studies of B cell repertoire selection in humans are essential to understand which checkpoints are defective in human autoimmune diseases.
Diffuse fibrosing alveolitis (diffuse interstitial fibrosis of the lungs): Correlation of histology at biopsy with prognosis
Authors: J. G. Scadding, K. F. W. Hinson
Journal: Thorax (1967)

`Fibrosing alveolitis9 refers to a broad general category of disease characterized by an inflammatory process in the lung beyond the terminal bronchiole having as its essential features (1) cellular thickening of the alveolar walls with a strong tendency to fibrosis, and (2) the presence of large mononuclear cells, presumably of alveolar origin, within the alveolar spaces. Sixteen cases in which lung biopsies conformed to this general pattern and whose course is known thereafter for at least two years or until death have been reviewed. There was an inverse relationship between the degree of alveolar wall thickening and the number of large mononuclear cells of granular type in the alveolar spaces. Corticosteroid treatment suppressed symptoms and signs in a few of the patients whose biopsy specimens showed only slight alveolar wall thickening and many intra-alveolar mononuclear cells but in none of those with much thickened alveolar walls. More or less prolonged remissions of progression of the disease were observed in a few patients, both with and without prominent alveolar wall thickening. There was no evident relationship between the histology at the time of biopsy and the total duration of the disease from onset to death.
Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341
Authors: Teru Hideshima, Constantine Mitsiades, Masaharu Akiyama, Toshiaki Hayashi, Dharminder Chauhan, Paul Richardson, Robert Schlossman, Klaus Podar, Nikhil C. Munshi, Nicholas Mitsiades, Kenneth C. Anderson
Journal: Blood (2003)