tbuckley/cabot-search huggingface dataset:
Cancer Risks Associated With Germline Mutations in &lt;emph type="ital"&gt;MLH1&lt;/emph&gt;, &lt;emph type="ital"&gt;MSH2&lt;/emph&gt;, and &lt;emph type="ital"&gt;MSH6&lt;/emph&gt; Genes in Lynch Syndrome
Authors: Valérie Bonadona, Bernard Bonaïti, Sylviane Olschwang, Sophie Grandjouan, Laetitia Huiart, Michel Longy, Rosine Guimbaud, Bruno Buecher, Yves-Jean Bignon, Olivier Caron, Chrystelle Colas, Catherine Noguès, Sophie Lejeune-Dumoulin, Laurence Olivier-Faivre, Florence Polycarpe-Osaer, Tan Dat Nguyen, Françoise Desseigne, Jean-Christophe Saurin, Pascaline Berthet, Dominique Leroux, Jacqueline Duffour, Sylvie Manouvrier, Thierry Frébourg, Hagay Sobol, Christine Lasset, Catherine Bonaïti-Pellié
Journal: JAMA (2011)

Providing accurate estimates of cancer risks is a major challenge in the clinical management of Lynch syndrome.To estimate the age-specific cumulative risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes.Families with Lynch syndrome enrolled between January 1, 2006, and December 31, 2009, from 40 French cancer genetics clinics participating in the ERISCAM (Estimation des Risques de Cancer chez les porteurs de mutation des gènes MMR) study; 537 families with segregating mutated genes (248 with MLH1; 256 with MSH2; and 33 with MSH6) were analyzed.Age-specific cumulative cancer risks estimated using the genotype restricted likelihood (GRL) method accounting for ascertainment bias.Significant differences in estimated cumulative cancer risk were found between the 3 mutated genes (P = .01). The estimated cumulative risks of colorectal cancer by age 70 years were 41% (95% confidence intervals [CI], 25%-70%) for MLH1 mutation carriers, 48% (95% CI, 30%-77%) for MSH2, and 12% (95% CI, 8%-22%) for MSH6. For endometrial cancer, corresponding risks were 54% (95% CI, 20%-80%), 21% (95% CI, 8%-77%), and 16% (95% CI, 8%-32%). For ovarian cancer, they were 20% (95% CI, 1%-65%), 24% (95% CI, 3%-52%), and 1% (95% CI, 0%-3%). The estimated cumulative risks by age 40 years did not exceed 2% (95% CI, 0%-7%) for endometrial cancer nor 1% (95% CI, 0%-3%) for ovarian cancer, irrespective of the gene. The estimated lifetime risks for other tumor types did not exceed 3% with any of the gene mutations.MSH6 mutations are associated with markedly lower cancer risks than MLH1 or MSH2 mutations. Lifetime ovarian and endometrial cancer risks associated with MLH1 or MSH2 mutations were high but do not increase appreciably until after the age of 40 years.
A CASE FOR DIAGNOSIS:? RETICULOSIS CUTIS BENIGNA
Authors: H. D. CHAMBERS
Journal: British Journal of Dermatology (1949)

Journal Article A CASE FOR DIAGNOSIS:? RETICULOSIS CUTIS BENIGNA Get access H. D. CHAMBERS H. D. CHAMBERS Kingston Hospital, Jamaica Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 61, Issue 12, 1 December 1949, Pages 416–421, https://doi.org/10.1111/j.1365-2133.1949.tb11054.x Published: 01 December 1949
Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients.
Authors: B S Levine, M Song
Journal: Journal of the American Society of Nephrology (1996)

Because intravenous (iv) calcitriol has greater bioavailability than oral calcitriol, it may be more efficacious in suppressing parathyroid hormone (PTH) secretion. In this study, the pharmacokinetics and efficacy of pulse oral and i.v. calcitriol were compared. Patients were randomized to receive 2 micrograms of i.v. or oral calcitriol after each dialysis. Two pharmacokinetic studies (PK1, PK2) were performed 10 days apart, during which the patients received calcitriol after each dialysis. Calcitriol bioavailability was determined from the area under the curve (AUCtime interval (hours) in pg/mL per h). After the PK phase, PTH was lowered to < 200 pg/mL by titrating calcitriol to a maximum of 12 micrograms/wk over 4 wk. Calcitriol was then maintained for another 18 wk unless serum calcium exceeded 11.5 mg/dL or Ca x P product exceeded 70; when these limits were reached, calcitriol was held and then restarted at a lower dose. After i.v. administration, peak serum calcitriol exceeded that achieved orally but by 1 h, calcitriol levels were similar. The AUC0-0.5 (105 +/- 12, i.v.; 9 +/- 4, oral) and AUC0.5-1 (68 +/- 6, i.v.; 30 +/- 7, oral) were higher with i.v. (P < 0.05), but cumulative AUC0-48 did not differ. Individual t1/2 values ranged from 10 to 129 h for PK1 and from 10 to 50 h for PK2. The t1/2 for oral calcitriol was 38 +/- 14 h for PK1 and 30 +/- 4 h for PK2 (not significant (NS)). The t1/2 for i.v. calcitriol was 26 +/- 5 h for PK1 and 19 +/- 3 h for PK2 (NS, PK1 versus PK2 and oral versus i.v.). When the PK1 oral and i.v. data were combined, the mean t1/2 was 32 +/- 7 h whereas the t1/2 for PK2 (oral and i.v.) was 22 +/- 3 h (P < 0.05). Baseline PTH levels were 510 +/- 90 pg/mL and 499 +/- 79 pg/mL, oral and i.v., respectively. Serum PTH level at 22 wk was not different between oral and i.v. groups, 153 +/- 38 pg/mL and 214 +/- 124 pg/mL in i.v. (NS). The percentage of PTH suppression was 66 +/- 7.4% in the oral group and 69 +/- 12% in the i.v. group (NS). A major degree of serum iPTH suppression occurred during the initial 4 wk of treatment, concomitant with a rise in serum calcium levels. Adverse effects were similar between groups, as were the average dosages of calcitriol and phosphate binders. In conclusion, the efficacy of intravenous and pulse oral calcitriol were similar in hemodialysis patients with secondary hyperparathyroidism. The early rise in serum calcium levels observed with treatment may have contributed significantly to the suppression of serum iPTH levels. The difference in bio-availability between the different routes does not have a clinically apparent effect. The t1/2 varied widely among individuals, whereas exposure to calcitriol may decrease the t1/2.
The Dual-Specificity Phosphatase MKP-1 Limits the Cardiac Hypertrophic Response In Vitro and In Vivo
Authors: Orlando F. Bueno, Leon J. De Windt, Hae W. Lim, Kevin M. Tymitz, Sandra A. Witt, Thomas R. Kimball, Jeffery D. Molkentin
Journal: Circulation Research (2001)

Abstract —Mitogen-activated protein kinase (MAPK) signaling pathways are important regulators of cell growth, proliferation, and stress responsiveness. A family of dual-specificity MAP kinase phosphatases (MKPs) act as critical counteracting factors that directly regulate the magnitude and duration of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. Here we show that constitutive expression of MKP-1 in cultured primary cardiomyocytes using adenovirus-mediated gene transfer blocked the activation of p38, JNK1/2, and ERK1/2 and prevented agonist-induced hypertrophy. Transgenic mice expressing physiological levels of MKP-1 in the heart showed (1) no activation of p38, JNK1/2, or ERK1/2; (2) diminished developmental myocardial growth; and (3) attenuated hypertrophy in response to aortic banding and catecholamine infusion. These results provide further evidence implicating MAPK signaling factors as obligate regulators of cardiac growth and hypertrophy and demonstrate the importance of dual-specificity phosphatases as counterbalancing regulatory factors in the heart.
High-dose intravenous immunoglobulins for immediate control of severe pemphigus vulgaris
Authors: G. Messer, N. Sizann, H. Feucht, M. Meurer
Journal: British Journal of Dermatology (1995)

Journal Article High‐dose intravenous immunoglobulins for immediate control of severe pemphigus vulgaris Get access G. Messer, G. Messer Dermatolagische Klinik und Paliklinik, Ludwig‐Maximilians‐Universität München, Frauenlobstr. 9‐11, 80337 München, Germany Search for other works by this author on: Oxford Academic Google Scholar N. Sizann, N. Sizann Dermatolagische Klinik und Paliklinik, Ludwig‐Maximilians‐Universität München, Frauenlobstr. 9‐11, 80337 München, Germany Search for other works by this author on: Oxford Academic Google Scholar H. Feucht, H. Feucht Medizinische Klinik des Klinikums Innenstadt, Ludwig‐Maximilians‐Universität München, Ziemssenstr. 1 80 336 München Germany Search for other works by this author on: Oxford Academic Google Scholar M. Meurer M. Meurer Dermatolagische Klinik und Paliklinik, Ludwig‐Maximilians‐Universität München, Frauenlobstr. 9‐11, 80337 München, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 6, 1 December 1995, Pages 1014–1016, https://doi.org/10.1111/j.1365-2133.1995.tb06952.x Published: 01 December 1995
Computed tomography based estimates of regional gas and tissue volume of the lung in supine subjects with chronic airflow limitation or fibrosing alveolitis.
Authors: A B Millar, B Fromson, B A Strickland, D M Denison
Journal: Thorax (1986)

Twelve patients with chronic airflow limitation and 12 patients with a histological diagnosis of fibrosing alveolitis were studied. The calculated mean (SD) tissue volume of a single lung at total lung capacity was 467 (91) ml in the patients with alveolitis, which was 43% (14%) more than predicted for healthy people of the same age, sex, and height. The tissue volume of a single lung at total lung capacity was 436 (82) ml in the patients with chronic airflow limitation, which was 26% (21%) more than predicted. At residual volumes the tissue contents of the fibrotic and the obstructed lungs changed very little (to 407 (84) ml and 433 (84) ml respectively). This allowed tissue volume to be used as a marker of position within the lung, to match inspiratory and expiratory slices and to calculate regional ventilation. In both groups local ventilation was diminished and more variable than in healthy lungs--that is, in the mid 70% of lung volume the local residual volume to total gas volume ratios (RV/TGV) were 32% (10%) in the fibrotic group and 66% (14%) in the group with chronic airflow limitation, compared with 23% (5%) in healthy subjects. As expected, the fibrotic lungs were much denser (0.246 (0.036) g/ml) and the lungs with chronic airflow obstruction were less dense (0.114 (0.026) g/ml) than were healthy lungs (0.126 (0.017) g/ml).
Relationship between early life respiratory illness, family size over time, and the development of asthma and hay fever: a seven year follow up study
Authors: A.-L. Ponsonby, D. Couper, T. Dwyer, A. Carmichael, A. Kemp
Journal: Thorax (1999)

<h3>BACKGROUND</h3> The timing and mechanism of the inverse association between increasing sibling number and atopic disease are not yet understood. A study was undertaken to examine how family size at birth predicts early respiratory illness, to report the association between infant respiratory illness and childhood atopic disease, and to determine whether the protective effect of large family size operates during infancy or later childhood. <h3>METHODS</h3> A prospective follow up study was carried out on 863 children (78%) of 1111 participants in the Tasmanian Infant Health Survey performed in 1988. In 1988 household size and history of respiratory illness were obtained by parental interview at home (median age 35 days) and later by telephone (median age 85 days). In 1995 asthma, hay fever, and household size were assessed by parental questionnaire in a large cross sectional survey. <h3>RESULTS</h3> In 1988 increasing resident number (per resident) (adjusted odds ratio (AOR) 1.17 (95% CI 1.05 to 1.31)) and resident density (AOR 1.77 (95% CI 1.07 to 2.94)) were related to parental report of an upper respiratory tract infection (URTI) by one month of age. Children with a reported URTI by home interview were more likely to have subsequent asthma (adjusted relative risk (ARR) 1.27 (95% CI 1.05 to 1.53)). The association between lower respiratory tract infection (LRTI) at telephone interview (relative risk (RR) 1.34 (95% CI 1.02 to 1.75) and asthma was reduced after adjustment for family history of asthma (ARR 1.27 (95% CI 0.98 to 1.66)). Antibiotic use by home interview was not associated with subsequent asthma or hay fever. Indicators of family size in 1988 were associated with hay fever but not asthma but, in contrast, resident number in 1995 was inversely associated with asthma (AOR 0.82 (95% CI 0.72 to 0.92) per resident) and hay fever (AOR 0.82 (95% CI 0.71 to 0.96) per resident). Children with no siblings were at risk for current asthma, particularly if symptoms began after the age of four (RR 2.81 (95% CI 1.36 to 5.84)). <h3>CONCLUSIONS</h3> The apparent protective effect of large household size and asthma could not be explained by an increase in reported early respiratory illness. The first year of life may not be the most critical time for the protective effect of large household size to be mediated in relation to asthma, but this effect occurred by the seventh year of life.
Splanchnic ischaemia and multiple organ failure
Authors: M R B Keighley
Journal: Gut (1990)

cence of 5-aminosalicylate decreased, suggesting a chemical reaction between 5-aminosalicylate and hypochlorite.Activated neutrophils also produced a peroxidasegenerated oxygen metabolite which reacted with 5-aminosalicylate to produce a non- fluorescent product.6We therefore propose that 5-aminosalicylate acts as a hypochlorite scavenger and also as a hypochlorite indicator.Identification and detection of neutrophil derived metabolites of 5-aminosalicylate in the faecal stream of patients receiving 5-aminosalicylate would thus provide evidence for the production of hypochlorite in the inflamed bowel and may also be useful for monitoring the progress of the disease.
World Health Organization reference values for human semen characteristics*‡
Authors: Trevor G. Cooper, Elizabeth Noonan, Sigrid von Eckardstein, Jacques Auger, H.W. Gordon Baker, Hermann M. Behre, Trine B. Haugen, Thinus Kruger, Christina Wang, Michael T. Mbizvo, Kirsten M. Vogelsong
Journal: Human Reproduction Update (2009)

Semen quality is taken as a surrogate measure of male fecundity in clinical andrology, male fertility, reproductive toxicology, epidemiology and pregnancy risk assessments. Reference intervals for values of semen parameters from a fertile population could provide data from which prognosis of fertility or diagnosis of infertility can be extrapolated. Semen samples from over 4500 men in 14 countries on four continents were obtained from retrospective and prospective analyses on fertile men, men of unknown fertility status and men selected as normozoospermic. Men whose partners had a time-to-pregnancy (TTP) of ≤12 months were chosen as individuals to provide reference distributions for semen parameters. Distributions were also generated for a population assumed to represent the general population. The following one-sided lower reference limits, the fifth centiles (with 95th percent confidence intervals), were generated from men whose partners had TTP ≤ 12 months: semen volume, 1.5 ml (1.4–1.7); total sperm number, 39 million per ejaculate (33–46); sperm concentration, 15 million per ml (12–16); vitality, 58% live (55–63); progressive motility, 32% (31–34); total (progressive + non-progressive) motility, 40% (38–42); morphologically normal forms, 4.0% (3.0–4.0). Semen quality of the reference population was superior to that of the men from the general population and normozoospermic men. The data represent sound reference distributions of semen characteristics of fertile men in a number of countries. They provide an appropriate tool in conjunction with clinical data to evaluate a patient's semen quality and prospects for fertility.
Association of the toll-like receptor 4 gene polymorphisms with Behcet's disease
Authors: A Meguro, M Ota, Y Katsuyama, A Oka, S Ohno, H Inoko, N Mizuki
Journal: Annals of the Rheumatic Diseases (2007)

Behcet’s disease (BD) is a multisystemic inflammatory disorder characterised by recurrent ocular symptoms, oral and genital ulcers, and skin lesions.1 2 The aetiology of BD remains unclear, but likely both genetic and environmental factors play an important part in BD development.

We performed a whole-genome association analysis of BD using 23 465 microsatellite markers and ultimately found significant association for 147 markers (unpublished data). One of the 147 markers is located within 100 kb from the toll-like receptor (TLR) 4 gene on chromosome 9. Among the TLR family members, TLR4 is the receptor most exhaustively investigated and has been shown to recognise and interact with heat shock protein (HSP) and …
Death Due to Bioterrorism-Related Inhalational Anthrax
Authors: L Borio, D Frank, V Mani, C Chiriboga, M Pollanen, M Ripple, S Ali, C DiAngelo, J Lee, J Arden, J Titus, D Fowler, T O'Toole, H Masur, J Bartlett, T Inglesby
Journal: JAMA (2001)

On October 9, 2001, a letter containing anthrax spores was mailed from New Jersey to Washington, DC. The letter was processed at a major postal facility in Washington, DC, and opened in the Senate's Hart Office Building on October 15. Between October 19 and October 26, there were 5 cases of inhalational anthrax among postal workers who were employed at that major facility or who handled bulk mail originating from that facility. The cases of 2 postal workers who died of inhalational anthrax are reported here. Both patients had nonspecific prodromal illnesses. One patient developed predominantly gastrointestinal symptoms, including nausea, vomiting, and abdominal pain. The other patient had a "flulike" illness associated with myalgias and malaise. Both patients ultimately developed dyspnea, retrosternal chest pressure, and respiratory failure requiring mechanical ventilation. Leukocytosis and hemoconcentration were noted in both cases prior to death. Both patients had evidence of mediastinitis and extensive pulmonary infiltrates late in their course of illness. The durations of illness were 7 days and 5 days from onset of symptoms to death; both patients died within 24 hours of hospitalization. Without a clinician's high index of suspicion, the diagnosis of inhalational anthrax is difficult during nonspecific prodromal illness. Clinicians have an urgent need for prompt communication of vital epidemiologic information that could focus their diagnostic evaluation. Rapid diagnostic assays to distinguish more common infectious processes from agents of bioterrorism also could improve management strategies.
Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes
Authors: Peter Tamás, Simon A. Hawley, Rosemary G. Clarke, Kirsty J. Mustard, Kevin Green, D. Grahame Hardie, Doreen A. Cantrell
Journal: The Journal of Experimental Medicine (2006)

The adenosine monophosphate (AMP)–activated protein kinase (AMPK) has a crucial role in maintaining cellular energy homeostasis. This study shows that human and mouse T lymphocytes express AMPKα1 and that this is rapidly activated in response to triggering of the T cell antigen receptor (TCR). TCR stimulation of AMPK was dependent on the adaptors LAT and SLP76 and could be mimicked by the elevation of intracellular Ca2+ with Ca2+ ionophores or thapsigargin. AMPK activation was also induced by energy stress and depletion of cellular adenosine triphosphate (ATP). However, TCR and Ca2+ stimulation of AMPK required the activity of Ca2+–calmodulin-dependent protein kinase kinases (CaMKKs), whereas AMPK activation induced by increased AMP/ATP ratios did not. These experiments reveal two distinct pathways for the regulation of AMPK in T lymphocytes. The role of AMPK is to promote ATP conservation and production. The rapid activation of AMPK in response to Ca2+ signaling in T lymphocytes thus reveals that TCR triggering is linked to an evolutionally conserved serine kinase that regulates energy metabolism. Moreover, AMPK does not just react to cellular energy depletion but also anticipates it.
Comorbidity: The case of developmental psychopathology
Authors: Aribert Rothenberger, Tobias Banaschewski, Andreas Becker, Veit Roessner
Journal: Behavioral and Brain Sciences (2010)

In developmental psychopathology, differentiating between the coexistence and the clinical entity of two problem areas is of utmost importance. So far, logistic regression analysis has already provided helpful answers, as shown in studies on comorbidity of tic disorders. While the concept of bridging symptoms may be investigated adequately by both logistic regression and the network approach, the former (latent variable) seems to be of advantage with regard to the problems of multiple comorbidities and development.
Comparative Expression Analysis Reveals Lineage Relationships between Human and Murine Gliomas and a Dominance of Glial Signatures during Tumor Propagation<i>In Vitro</i>
Authors: Nico V. Henriquez, Tim Forshew, Ruth Tatevossian, Matthew Ellis, Angela Richard-Loendt, Hazel Rogers, Thomas S. Jacques, Pablo Garcia Reitboeck, Kerra Pearce, Denise Sheer, Richard G. Grundy, Sebastian Brandner
Journal: Cancer Research (2013)

Brain tumors are thought to originate from stem/progenitor cell populations that acquire specific genetic mutations. Although current preclinical models have relevance to human pathogenesis, most do not recapitulate the histogenesis of the human disease. Recently, a large series of human gliomas and medulloblastomas were analyzed for genetic signatures of prognosis and therapeutic response. Using a mouse model system that generates three distinct types of intrinsic brain tumors, we correlated RNA and protein expression levels with human brain tumors. A combination of genetic mutations and cellular environment during tumor propagation defined the incidence and phenotype of intrinsic murine tumors. Importantly, in vitro passage of cancer stem cells uniformly promoted a glial expression profile in culture and in brain tumors. Gene expression profiling revealed that experimental gliomas corresponded to distinct subclasses of human glioblastoma, whereas experimental supratentorial primitive neuroectodermal tumors (sPNET) correspond to atypical teratoid/rhabdoid tumor (AT/RT), a rare childhood tumor.
Oestrogen plus progestin and lung cancer in postmenopausal women (Women's Health Initiative trial): a post-hoc analysis of a randomised controlled trial
Authors: Rowan T Chlebowski, Ann G Schwartz, Heather Wakelee, Garnet L Anderson, Marcia L Stefanick, JoAnn E Manson, Rebecca J Rodabough, Jason W Chien, Jean Wactawski-Wende, Margery Gass, Jane Morley Kotchen, Karen C Johnson, Mary Jo O'Sullivan, Judith K Ockene, Chu Chen, F Allan Hubbell
Journal: The Lancet (2009)