tbuckley/cabot-search huggingface dataset:
Effect of mammography screening on surgical treatment for breast cancer in Norway: comparative analysis of cancer registry data
Authors: P. Suhrke, J. Maehlen, E. Schlichting, K. J. Jorgensen, P. C. Gotzsche, P.-H. Zahl
Journal: BMJ (2011)

<b>Objective</b> To determine the effect of mammography screening on surgical treatment for breast cancer. <b>Design</b> Comparative analysis of data from Norwegian cancer registry. <b>Setting</b> Mammography screening, Norway (screening of women aged 50-69 was introduced sequentially from 1996 to 2004). <b>Participants</b> 35 408 women aged 40-79 with invasive breast cancer or ductal carcinoma in situ treated surgically from 1993 to 2008. <b>Main outcome measures</b> Rates of breast surgery (mastectomy plus breast conserving treatment) and rates of mastectomy for three age groups of women: 40-49, 50-69, and 70-79. Changes in rates from pre-screening period (1993-5) to introduction of screening phase (1996-2004) and then to screening period (2005-8) are presented as hazard ratios in invited and non-invited women. <b>Results</b> The annual rate for breast surgery from the pre-screening period (1993-5) to screening period (2005-8) in Norway increased by 70% (hazard ratio 1.70, 95% confidence interval 1.62 to 1.78), from 180 to 305 per 100 000 women in the invited age group (50-69 years). In the younger, non-invited age group (40-49 years), however, the increase was only 8% (1.08, 1.00 to 1.16), from 133 to 144 per 100 000 women per year, whereas in the older, non-invited age group (70-79 years) the rate decreased by 8% (0.92, 0.86 to 1.00), from 227 to 214 per 100 000 women per year. The rates for mastectomy decreased similarly from the pre-screening period to screening period in invited and non-invited women. From the pre-screening period to the introduction phase of screening (1996-2004), however, the annual mastectomy rate in women aged 50-69 invited to screening increased by 9% (1.09, 1.03 to 1.14), from 156 to 167 per 100 000 women, and in the younger non-invited women declined by 17% (0.83, 0.78 to 0.90), from 109 to 91 per 100 000 women. In consequence, the mastectomy rate was 31% (1.31, 1.20 to 1.43) higher in the invited than in the non-invited younger age group. <b>Conclusions</b> Mammography screening in Norway was associated with a noticeable increase in rates for breast cancer surgery in women aged 50-69 (the age group invited to screening) and also an increase in mastectomy rates. Although over-diagnosis is likely to have caused the initial increase in mastectomy rates and the overall increase in surgery rates in the age group screened, the more recent decline in mastectomy rates has affected all age groups and is likely to have resulted from changes in surgical policy.
Lyt-2 glycoprotein is synthesized as a single molecular species.
Authors: E Rothenberg, D Triglia
Journal: The Journal of Experimental Medicine (1983)

We investigated the possibility that the Lyt-2 molecules made by uncloned mouse T lymphocytes would show variable primary structures like those of immunoglobulins. Newly synthesized Lyt-2/3 complexes were found to include only two major components, both discrete glycoproteins with apparent molecular weights of 31,000 (31 K) and 35,000 (35 K). When products of Lyt-2.1 and Lyt-2.2 thymocytes were compared by two-dimensional nonequilibrium pH gradient electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis, the isoelectric points of the 35 K molecules were different; thus, the 35 K component was likely to be encoded by the Lyt-2 locus itself. However, the 35 K molecules made by any one genotype were homogeneous in charge as well as in size. The homogeneity was obscured rapidly by post-translational modification. Most strikingly, within 30 min of initial synthesis, these processing events generated the conspicuous array of microheterogeneous products that form the "38 K" component of cell-surface Lyt-2/3.
Mitochondrial DNA reveals formation of nonhybrid frogs by natural matings between hemiclonal hybrids.
Authors: H Hotz, P Beerli, C Spolsky
Journal: Molecular Biology and Evolution (1992)

The European water frog Rana esculenta (RL), a natural hybrid between R. ridibunda (RR) and R. lessonae (LL), reproduces by hybridogenesis: haploid gametes usually contain an intact chromosome set of R. ridibunda (R); the lessonae nuclear genome (L) is lost from the germ line. Hybridity is restored in the next generation, via fertilization by syntopic R. lessonae. Matings between two hybrids (RL x RL) usually give inviable R. ridibunda (RR) progeny. The adult R. ridibunda subpopulation of Trubeschloo, a gravel pit in northern Switzerland, consists only of females. Fragment patterns for mitochondrial DNA (mtDNA) of these R. ridibunda were identical with those of syntopic R. esculenta and of local populations of R. lessonae; they differed from the patterns in eastern European populations of R. lessonae and of R. ridibunda mtDNAs (3.7% and 9.3% estimated sequence divergence, respectively). In contrast, mtDNAs of two R. ridibunda from an introduced Swiss population with both sexes, although different (2.7% divergence) from each other, were typical R. ridibunda rather than R. lessonae mtDNAs. These data, together with unisexuality, demonstrate conclusively that the all-female R. ridibunda population at Trubeschloo originated from matings between two R. esculenta. The formation of independently reproducing R. ridibunda populations via such hybrid x hybrid matings is precluded because progeny of these matings are unisexual. Recombination in the regenerated fertile R. ridibunda females, followed by matings with R. lessonae, nevertheless provides a mechanism for meiotic reshuffling of genetic material in ridibunda haplotypes that is not typically available in hemiclonal lineages.
Safety and Potential Efficacy of an Aerosolized Surfactant in Human Sepsis-Induced Adult Respiratory Distress Syndrome
Authors: J G Weg, R A Balk, R S Tharratt, S G Jenkinson, J B Shah, D Zaccardelli, J Horton, E N Pattishall
Journal: JAMA (1994)

<h3>Objective.</h3> —To evaluate the safety and potential efficacy of aerosolized surfactant in intubated patients with adult respiratory distress syndrome (ARDS). <h3>Design.</h3> —A prospective, double-blind, placebo-controlled, randomized, parallel, mutlicenter pilot clinical trial. <h3>Patients.</h3> —A total of 51 patients with sepsis-induced ARDS were entered into the study within 18 hours of developing sepsis or sepsis syndrome. <h3>Intervention.</h3> —Patients were randomized into four treatment groups in a 2:1:2:1 ratio, as follows: 12 hours of surfactant per day, 12 hours of 0.6% saline per day, 24 hours of surfactant per day, and 24 hours of 0.6% saline per day. Surfactant or saline was aerosolized continuously for up to 5 days using an in-line nebulizer that aerosolized only during inspiration. <h3>Main Outcome Measures.</h3> —Ventilatory data, arterial blood gases, and hemodynamic parameters were measured at baseline, every 4 or 8 hours during the 5 days of treatment, 24 hours after treatment, and 30 days after treatment, at which time mortality was also assessed. Safety was evaluated throughout the 30 days of the study. <h3>Results.</h3> —Surfactant was administered safely in ventilated patients when given continuously throughout the 5 days using the nebulizer system. Although there were no differences in any physiological parameter between the treatment groups, there was a dose-dependent trend in reduction of mortality from 47% in the combined placebo group to 41% and 35% in the groups treated with 12 hours and 24 hours of surfactant per day, respectively. <h3>Conclusions.</h3> —Aerosolized surfactant was well tolerated when administered on a continuous basis for up to 5 days; however, at the doses given, it did not result in significant improvements in patients with sepsis-induced ARDS. (<i>JAMA</i>. 1994;272:1433-1438)
Bcl-2 Inhibitors Sensitize Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis by Uncoupling of Mitochondrial Respiration in Human Leukemic CEM Cells
Authors: Ji-Hui Hao, Ming Yu, Feng-Ting Liu, Adrian C. Newland, Li Jia
Journal: Cancer Research (2004)

Abstract Previous studies have shown that the lymphoblastic leukemia CEM cell line is resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis because of a low expression of caspase-8. Bcl-2 inhibitors, BH3I-2′ and HA14-1, are small cell-permeable nonpeptide compounds, are able to induce apoptosis by mediating cytochrome c release, and also lead to dissipation of the mitochondrial membrane potential (ΔΨm). This study aimed to use the Bcl-2 inhibitors to sensitize CEM cells to TRAIL-induced apoptosis by switching on the mitochondrial apoptotic pathway. We found that a low dose of BH3I-2′ or HA14-1, which did not induce cytochrome c release, greatly sensitized CEM cells to TRAIL-induced apoptosis. In a similar manner to the classical uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), both BH3I-2′ and HA14-1 induced a reduction in ΔΨm, a generation of reactive oxygen species (ROS), an increased mitochondrial respiration, and a decreased ATP synthesis. This uncoupling function of the Bcl-2 inhibitors was responsible for the synergy with TRAIL-induced apoptosis. CCCP per se did not induce apoptosis but again sensitized CEM cells to TRAIL-induced apoptosis by uncoupling mitochondrial respiration. The uncoupling effect facilitated TRAIL-induced Bax conformational change and cytochrome c release from mitochondria. Inhibition of caspases failed to block TRAIL-mediated cell death when mitochondrial respiration was uncoupled. We observed that BH3I-2′, HA14-1, or CCCP can overcome resistance to TRAIL-induced apoptosis in TRAIL-resistant cell lines, such as CEM, HL-60, and U937. Our results suggest that the uncoupling of mitochondrial respiration can sensitize leukemic cells to TRAIL-induced apoptosis. However, caspase activation per se does not represent an irreversible point of commitment to TRAIL-induced cell death when mitochondrial respiration is uncoupled.
Regular use of inhaled corticosteroids and the long term prevention of hospitalisation for asthma
Authors: S Suissa
Journal: Thorax (2002)

<b>Background:</b> Inhaled corticosteroids are effective at preventing asthma morbidity and mortality. Most studies, however, have focused on short term effects, raising uncertainty about their effectiveness in the long term. <b>Methods:</b> The Saskatchewan Health databases were used to form two population based cohorts of asthma patients aged 5–44 between 1975 and 1991. The first cohort included all subjects from the start of asthma treatment, while the second included subjects hospitalised for asthma from the date of discharge. Subjects were followed up, starting 1 year after cohort entry and continuing until 1997, 54 years of age, or death. The outcome was the first asthma hospital admission and readmission, respectively, to occur during follow up. A nested case-control design was used by which all cases were matched on calendar time and several markers of asthma severity to all available controls within the cohort. <b>Results:</b> The full cohort included 30 569 asthmatic subjects of which 3894 were admitted to hospital for asthma and 1886 were readmitted. The overall rate of asthma hospitalisation was 42.4 per 1000 asthma patients per year. Regular use of inhaled corticosteroids was associated with reductions of 31% in the rate of hospital admissions for asthma (95% confidence interval (CI) 17 to 43) and 39% in the rate of readmission (95% CI 25 to 50). The rate reduction found during the first 4 years of follow up was sustained over the longer term. Regular use of inhaled corticosteroids can potentially prevent between five hospital admissions and 27 readmissions per 1000 asthma patients per year. <b>Conclusion:</b> Regular use of low dose inhaled corticosteroids prevents a large proportion of hospital admissions with asthma, both early and later on in the course of the disease.
FAVL elevation in human tumors disrupts Fanconi anemia pathway signaling and promotes genomic instability and tumor growth
Authors: Jun Zhang, Deping Zhao, Hwan Ki Park, Hong Wang, Roy B. Dyer, Wanguo Liu, George G. Klee, Mark A. McNiven, Donald J. Tindall, Julian R. Molina, Peiwen Fei
Journal: Journal of Clinical Investigation (2010)

Fanconi anemia (FA) is a rare human genetic disease caused by mutations in any one of 13 known genes that encode proteins functioning in one common signaling pathway, the FA pathway, or in unknown genes. One characteristic of FA is an extremely high incidence of cancer, indicating the importance of the FA pathway in tumor suppression. However, the role of this pathway in the development and progression of human cancers in individuals who do not have FA has not been clearly determined. Here, we report that elevated expression of what we believe to be a novel splice variant of FA complementation group L (FANCL), which we identified and named FAVL, can impair the FA pathway in non-FA human tumor cells and act as a tumor promoting factor. FAVL expression was elevated in half of the human carcinoma cell lines and carcinoma tissue samples tested. Expression of FAVL resulted in decreased FANCL expression by sequestering FANCL to the cytoplasm and enhancing its degradation. Importantly, this impairment of the FA pathway by FAVL elevation provided human cancer cells with a growth advantage, caused chromosomal instability in vitro, and promoted tumor development in a xenograft mouse model. These data indicate that FAVL impairment of the FA pathway likely contributes to the development of non-FA human cancers and therefore add a challenging layer of complexity to the pathogenesis of human cancer. We further believe that these data will prove useful for developing additional tools for fighting human cancer.
The relationships between functional exercise capacity, respiratory muscle strength, peripheral muscle strength and endurance in patients with metabolic syndrome
Authors: Cemile Bozdemir, Hulya Arikan, R. Nesrin Demirtas, Ozgen Celer, Aysen Akalin, Fusun Alatas, Melda Saglam, Naciye Vardar-Yagli, Ebru Calik, Deniz Inal-Ince
Journal: European Respiratory Journal (2013)

Introduction and aim: The metabolic syndrome is a cluster of cardiovascular risk factors, including elevated blood pressure, dyslipidemia, impaired glycemic control, and abdominal obesity. The aim of this study was to assess the relationships among functional exercise capacity, respiratory muscle strength, peripheral muscle strength and endurance in patients with metabolic syndrome.

Materials and methods: Twenty patients with metabolic syndrome (BMI: 35.5±3.7 kg/m2) were participated. Functional exercise capacity was evaluted using six-minute walk test (6MWT). Respiratory muscle (MIP, MEP) was assessed with cabin body-plethysmography. Hand grip strength was evaluated using a Jamar dynamometer. Peripheral muscle endurance was determined using squat test.

Results: The 6MWT distance (84.7±13.3%), dominant-hand grip strength (60.6±18.7%), MEP (41.2±12.3%), MIP (59.2±17.6%) were decreased based on reference values. The 6MWT distance was significantly associated with MIP (r=0.64, p=0.003), MEP (r=0.61, p=0.004), hand grip strength (r=0.47, p=0.03), and number of squats (r=0.59, p=0.007). Hand grip strength was significantly related MIP (r=0.56, p=0.01), MEP (r=0.63, p=0.03) and number of squats (r=0.53, p=0.01).

Conclusion: Functional exercise capacity is related with respiratory and hand grip muscle strength and peripheral muscle endurance in patients with metabolic syndrome. Aerobic exercise, respiratory and peripheral muscle training should be included in the rehabilitation programs of patients with metabolic syndrome.
Effect of pattern and severity of respiratory muscle weakness on carbon monoxide gas transfer and lung volumes
Authors: N. Hart, D. Cramer, S.P. Ward, A.H. Nickol, J. Moxham, M.I. Polkey, N.B. Pride
Journal: European Respiratory Journal (2002)

In clinical practice, an elevated carbon monoxide (CO) transfer coefficient ( K CO ) and restrictive ventilatory defect are taken as features of respiratory muscle weakness (RMW). However, the authors hypothesised that both pattern and severity of RMW effect gas transfer and lung volumes. Measurements of CO transfer and lung volumes were performed in patients with isolated diaphragm weakness (n=10), inspiratory muscle weakness (n=12), combined inspiratory and expiratory muscle weakness (n=5) and healthy controls (n=6). Patients with diaphragm weakness and inspiratory muscle weakness had reduced total lung capacity (TLC) (83.6% predicted and 68.9% pred, respectively), functional residual capacity (FRC) (83.9% pred and 83.6% pred) and transfer factor of the lung for CO ( T L,CO ) (86.2% pred and 66.2% pred) with increased K CO (114.1% pred and 130.2% pred). Patients with combined inspiratory and expiratory muscle weakness had reduced TLC (80.9% pred) but increased FRC (109.9% pred) and RV (157.4% pred) with decreased T L,CO (58.0% pred) and K CO (85.5% pred). In patients with diaphragm weakness, the increase in carbon monoxide transfer coefficient was similar to that of normal subjects when alveolar volume was reduced. However, the increase in carbon monoxide transfer coefficient in inspiratory muscle weakness was often less than expected, while in combined inspiratory and expiratory muscle weakness, the carbon monoxide transfer coefficient was normal/reduced despite further reductions in alveolar volume, which may indicate subtle abnormalities of the lung parenchyma or pulmonary vasculature. Thus, this study demonstrates the limitations of using carbon monoxide transfer coefficient in the diagnosis of respiratory muscle weakness, particularly if no account is taken of the alveolar volume at which the carbon monoxide transfer coefficient is made.
Defective biliary excretion of copper in Wilson's disease
Authors: D. J. Frommer
Journal: Gut (1974)

The biliary excretion of copper was measured in eight patients with Wilson's disease (three untreated, with hepatic dysfunction) and 10 control subjects (three with hepatic dysfunction). The duodenum was perfused with an amino-acid solution containing a non-absorbed marker, (51)CrCl(3), and juice was aspirated from the duodeno-jejunal junction. The mean concentration of copper in the duodenal aspirate in Wilson's disease was significantly lower than in the control group. The mean biliary copper excretion rate in Wilson's disease of 8.6 +/- 0.8 mug/20 min (SEM) was also significantly below that of the control group (16.4 +/- 0.8 mug/20 min). The presence of liver dysfunction made no significant difference to the excretion rates in either group of patients. These results suggest that the copper accumulation in Wilson's disease is due to the inability of the liver to excrete copper into bile in adequate amounts.
Plasma Melatonin Circadian Rhythm Disturbances During Pregnancy and Postpartum in Depressed Women and Women With Personal or Family Histories of Depression
Authors: Barbara L Parry, Charles J Meliska, Diane L Sorenson, Ana M Lopez, Luis F Martinez, Sara Nowakowski, Jeffrey A Elliott, Richard L Hauger, Daniel F Kripke
Journal: American Journal of Psychiatry (2008)

The purpose of this study was to test the hypothesis that disturbances in levels of plasma melatonin differentiate pregnant and postpartum women with major depression from matched pregnant and postpartum healthy comparison women.Participants were 25 pregnant women (10 with major depression, 15 healthy) and 24 postpartum women (13 with major depression, 11 healthy). Healthy comparison women were matched on the number of weeks pregnant or postpartum. Plasma melatonin levels for each subject were measured every 30 minutes, in dim light (<30 lux), from 6:00 p.m. to 11:00 a.m. The values of plasma melatonin levels were log-transformed, and calculations were determined for the following measures: baseline and synthesis onset and offset times, duration, peak concentration, and area under the curve. Groups were compared by analyses of covariance, with age, number of weeks pregnant or postpartum, breast-feeding status, and body mass index as covariates.Morning melatonin levels from 2:00 a.m. to 11:00 a.m. were significantly lower in pregnant women with major depression relative to healthy pregnant women. However, these levels were significantly higher in postpartum women with major depression across time intervals relative to postpartum healthy women. Pregnant but not postpartum women with a personal or family history of depression, regardless of their current diagnosis, had significantly earlier melatonin synthesis and baseline offset times relative to women without a family history of depression. In pregnant healthy women but not pregnant women with major depression, melatonin levels increased during the course of pregnancy. This association was not found among postpartum women with major depression or postpartum healthy women.Plasma nocturnal melatonin concentrations, particularly during morning hours, were lower in depressed pregnant women but elevated in depressed postpartum women relative to matched healthy comparison women. In addition, melatonin timing measures were advanced in pregnant women with a personal or family history of depression. These findings implicate disturbances in the regulation of the melatonin generating system in pregnancy and postpartum depression.
Retinoic acid-induced glandular differentiation of the oesophagus
Authors: C.-L. Chang, P. Lao-Sirieix, V. Save, G. De La Cueva Mendez, R. Laskey, R. C Fitzgerald
Journal: Gut (2006)

<b>Background:</b> Retinoic acid (RA) is a powerful differentiation agent. Barrett's oesophagus occurs when duodeno-gastro-oesophageal reflux causes squamous epithelium (SE) tissue to become columnar epithelium tissue by an unknown mechanism. The bile acid lithocholic acid (LCA) competes for the retinoid X receptor retinoid binding site. Hence, RA pathways may be implicated in Barrett's oesophagus. <b>Methods:</b> RA activity in tissues and cell lines treated with all<i>-trans</i> retinoic acid (ATRA) with or without LCA was assessed using a reporter. Expression of p21 was determined by real-time PCR in Barrett's oesophagus cell lines with or without LCA. SE and Barrett's oesophagus biopsy specimens were exposed to 100 μM of ATRA or 20 mM of a RA inhibitor, citral, in organ culture for &gt;72 h. Characteristics of treated specimens, compared with untreated controls, were analysed by immunohistochemical analysis (cytokeratins (CKs), vimentin) and RT-PCR (CKs). Confocal microscopy assessed temporal changes in co-localisation of CK8/18 and vimentin. Cell proliferation was assessed by bromo-deoxyuridine incorporation and immunohistochemical analysis for Ki67 and p21. <b>Results:</b> RA biosynthesis was increased in Barrett's oesophagus compared with SE (p&lt;0.001). LCA and ATRA caused a synergistic increase in RA signalling as shown by increased p21 (p&lt;0.01). Morphological and molecular analysis of SE exposed to ATRA showed columnar differentiation independent of proliferation. Metaplasia could be induced from the stromal compartment alone and vimentin expression co-localised with CK8/18 at 24 h, which separated into CK8/18-positive glands and vimentin-positive stroma by 48 h. Citral-treated Barrett's oesophagus led to phenotypic and immunohistochemical characteristics of SE, which was independent of proliferation. <b>Conclusion:</b> RA activity is increased in Barrett's oesophagus and is induced by LCA. Under conditions of altered RA activity and an intact stroma, the oesophageal phenotype can be altered independent of proliferation.