tbuckley/cabot-search huggingface dataset:
Three different autoimmune bullous diseases in one family: is there a common genetic base?
Authors: None KIRTSCHIG, None MITTAG, None WOLF, None GORSKI, None HAPPLE
Journal: British Journal of Dermatology (1999)

We report an unusual familial occurrence of autoimmune bullous diseases. Three members of a family suffered from three different autoimmune bullous diseases: pemphigus vulgaris (PV), linear IgA disease (LAD) and cicatricial pemphigoid (CP). The HLA type was determined in five family members: all were positive for HLA-DQ5/DR6, which is reported to be associated with susceptibility to PV. The CP patient was DQ7(3) positive, which is in concordance with enhanced susceptibility to ocular CP and CP. The LAD patient was B8 and DR3 negative but positive for HLA-A1. Our study supports the hypothesis that there is a genetically transmitted susceptibility to autoimmune bullous diseases but that additional factors seem necessary actually to develop a particular disease.
Increased Arginase Activity in Cystic Fibrosis Airways
Authors: Hartmut Grasemann, Raphael Schwiertz, Sonja Matthiesen, Kurt Racké, Felix Ratjen
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Airway nitric oxide concentrations are reduced in cystic fibrosis (CF). Arginases compete for L-arginine, the substrate of nitric oxide synthesis.We hypothesized that increased arginase activity may be one factor contributing to nitric oxide deficiency in CF.We therefore studied sputum arginase activity, exhaled nitric oxide, and pulmonary function in patients with cystic fibrosis.Mean (+/- SEM) sputum arginase activity was significantly higher in patients admitted for pulmonary exacerbation compared with patients with stable disease (1.032 +/- 0.148 vs. 0.370 +/- 0.091 U/mg protein, p = 0.004). Fourteen days of intravenous antibiotic treatment resulted in significantly decreased sputum arginase activity in all patients (p = 0.0002). However, arginase activity was still significantly (p = 0.0001) higher in CF sputum after treatment for exacerbation compared with induced sputum from healthy control subjects (0.026 +/- 0.006 U/mg protein). Negative correlations were found for sputum arginase activity at admission with FEV1 (r = -0.41, p = 0.01), as well as changes in arginase activity with percent change in FEV1 during antibiotic therapy (r = -0.4, p < 0.01) in CF. Exhaled nitric oxide in CF was positively correlated to FEV1 (r = 0.34, p = 0.007), and in patients admitted for pulmonary exacerbation negatively correlated to sputum arginase activity (r = -0.45, p = 0.03).These data suggest that increased sputum arginase activity contributes to nitric oxide deficiency in CF lung disease and may be relevant in the pathogenesis of CF airway disease.
Getting tar struck
Authors: Theodore Dalrymple
Journal: BMJ (2007)

There is nothing so stupid, said Cicero, but that some philosopher has not said it. Goodness knows what he would have said about the medical profession had the history of medicine been available to him. There is no treatment so ludicrous that doctors have not prescribed it, perhaps.

Still, one will try anything when nothing else is available. The greatest minds are capable of the greatest absurdity when it comes to health preservatives. For example, Bishop Berkeley (1685-1753), the great Anglo-Irish empiricist philosopher who denied the existence of matter, was a great devotee of tar water, which he believed was efficacious against almost all known distempers. He wrote a book in praise of Tar Water entitled Siris: …
Morphology of the Human Tricuspid Valve
Authors: M. D. SILVER, J. H. C. LAM, N. RANGANATHAN, E. D. WIGLE
Journal: Circulation (1971)

The morphology of 50 normal tricuspid valves was studied. The surface of the leaflets was divided into three zones: (1) the rough zone, into which most of the chordae tendineae are inserted, (2) the basal zone, and (3) the clear zone, which lies between the rough and basal zones. Five types of chordae were distinguished by their morphology and mode of insertion: fan-shaped, rough zone, basal, free edge, and deep chordae. The last two types are unique to the tricuspid valve. If fan-shaped chordae, used to define the commissures between the leaflets, are absent, other landmarks may be used for commissural definition. Once defined, all tissue between the commissures was regarded as part of the anterior, posterior, or septal leaflet. The recognition that the free edges of the anterior and septal leaflets contain notches, that rough zone chordae insert into them, and that the posterior leaflet has scallops further aids identification of a leaflet's components. Thus, structures formerly regarded as accessory leaflets were incorporated into one of the three leaflets.
Passive flooding of paranasal sinuses and middle ears as a method of equalisation in extreme breath-hold diving
Authors: Peter Germonpré, Costantino Balestra, Patrick Musimu
Journal: British Journal of Sports Medicine (2010)

Breath-hold diving is both a recreational activity, performed by thousands of enthusiasts in Europe, and a high-performance competitive sport. Several ‘disciplines’ exist, of which the ‘no-limits’ category is the most spectacular: using a specially designed heavy ‘sled,’ divers descend to extreme depths on a cable, and then reascend using an inflatable balloon, on a single breath. The current world record for un-assisted descent stands at more than 200 m of depth. Equalising air pressure in the paranasal sinuses and middle-ear cavities is a necessity during descent to avoid barotraumas. However, this requires active insufflations of precious air, which is thus unavailable in the pulmonary system. The authors describe a diver who, by training, is capable of allowing passive flooding of the sinuses and middle ear with (sea) water during descent, by suppressing protective (parasympathetic) reflexes during this process. Using this technique, he performed a series of extreme-depth breath-hold dives in June 2005, descending to 209 m of sea water on one breath of air.
cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas
Authors: S. Hu
Journal: Journal of Clinical Investigation (2005)

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas is associated with independent chromosomal translocations that lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. While both BCL10 and MALT1 are critically involved in antigen receptor–mediated NF-κB activation, the role of cIAP2 is not clear. Here we show that cIAP2 is a ubiquitin ligase (E3) of BCL10 and targets it for degradation, inhibiting antigen receptor–mediated cytokine production. cIAP2-MALT1 lacks E3 activity, and concomitantly, the BCL10 protein is stabilized in MALT lymphomas harboring this fusion. Furthermore, BCL10 and cIAP2-MALT1 synergistically activate NF-κB. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.
Celebrity Endorsements of Cancer Screening
Authors: Robin J. Larson, Steven Woloshin, Lisa M. Schwartz, H. Gilbert Welch
Journal: JNCI Journal of the National Cancer Institute (2005)

Celebrities often promote cancer screening by relating personal anecdotes about their own diagnosis or that of a loved one. We used data obtained from a random-digit dialing survey conducted in the United States from December 2001 through July 2002 to examine the extent to which adults of screening age without a history of cancer had seen or heard or been influenced by celebrity endorsements of screening mammography, prostate-specific antigen (PSA) testing, or sigmoidoscopy or colonoscopy. The survey response rate was 72% among those known to be eligible and 51% among potentially eligible people accounting for those who could not be contacted. A total of 360 women aged 40 years or older and 140 men aged 50 years or older participated in the survey. Most respondents reported they "had seen or heard a celebrity talk about" mammography (73% of women aged 40 years or older), PSA testing (63% of men aged 50 years or older), or sigmoidoscopy or colonoscopy (52% of adults aged 50 years or older). At least one-fourth of respondents who had seen or heard a celebrity endorsement said that the endorsement made them more likely to undergo mammography (25%), PSA testing (31%), or sigmoidoscopy or colonoscopy (37%).
The Lung as an Immunologic Organ
Authors: J Bienenstock
Journal: Annual Review of Medicine (1984)

Considerable information exists and is reviewed and summarized to support the suggestion that the lungs are a major contributor to immunity. The immune response differs in quantity and quality in different parts of the lung and this response depends in magnitude and type on a number of factors such as previous exposure, nature of the antigen, amount, etc. The ways in which these pulmonary immune responses are regulated and may be augmented and harnessed are discussed.
Demonstration of non-specific B-cell stimulation in patients with cirrhosis.
Authors: G Holdstock, W B Ershler, E L Krawitt
Journal: Gut (1982)

Using a sensitive enzyme-linked immunosorbent assay technique to measure immunoglobulins produced by peripheral lymphocytes, patients with cirrhosis with, and without, hypergammaglobulinaemia were found to produce significantly more spontaneous IgG than controls (p less than 0.005). There was no difference in IgG production when pokeweed mitogen, a T-cell dependent B-cell mitogen, was added to the system. Contrary to our findings in a T-cell proliferative assay, there was no evidence of increased prostaglandin-producing suppressor cell activity in this system. To study the importance of B-cell stimulation in cirrhotic hyperglobulinaemia, normal mononuclear cells were exposed either to cirrhotic or to control sera before measuring spontaneous IgG production. Cells exposed to cirrhotic sera produced significantly more IgG than those exposed to the control sera (p less than 0.02). These findings suggest that non-specific B-cell activity occurs with patients in cirrhosis and it is argued that the severity of the hypergammaglobulinaemia in patients with cirrhosis is more likely to depend on the degree of non-specific B-cell stimulation than on the competence of the immunoregulatory system.
Infant swimming in chlorinated pools and the risks of bronchiolitis, asthma and allergy
Authors: C Voisin, A Sardella, F Marcucci, A Bernard
Journal: European Respiratory Journal (2010)

Recent studies suggest that swimming in chlorinated pools during infancy may increase the risks of lower respiratory tract infection. The aim of the present study was to assess the influence of swimming in chlorinated pools on the risks of bronchiolitis and its late consequences. A total of 430 children (47% female; mean age 5.7 yrs) in 30 kindergartens were examined. Parents completed a questionnaire regarding the child’s health history, swimming practice and potential confounders. Attendance at indoor or outdoor chlorinated pools ever before the age of 2 yrs was associated with an increased risk of bronchiolitis (OR 1.68; 95% CI 1.08–2.68; p = 0.03), which was exposure-dependent for both types of pool (p-value for trend &lt;0.01). Associations persisted, and were even strengthened, by the exclusion of other risk factors. Among children with no parental antecedents of atopic disease or no day-care attendance, odds ratios for bronchiolitis amounted to 4.45 (1.82–10.9; p = 0.001) and 4.44 (1.88–10.5; p = 0.007) after &gt;20 h spent in chlorinated pools during infancy. Infant swimmers who developed bronchiolitis also showed higher risks of asthma and respiratory allergies later in childhood. Swimming pool attendance during infancy is associated with a higher risk of bronchiolitis, with ensuing increased risks of asthma and allergic sensitisation.
The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance
Authors: Monika Mortensen, Elizabeth J. Soilleux, Gordana Djordjevic, Rebecca Tripp, Michael Lutteropp, Elham Sadighi-Akha, Amanda J. Stranks, Julie Glanville, Samantha Knight, Sten-Eirik W. Jacobsen, Kamil R. Kranc, Anna Katharina Simon
Journal: The Journal of Experimental Medicine (2011)

The role of autophagy, a lysosomal degradation pathway which prevents cellular damage, in the maintenance of adult mouse hematopoietic stem cells (HSCs) remains unknown. Although normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs leads to leukemia. Therefore, mechanisms protecting HSCs from cellular damage are essential to prevent hematopoietic malignancies. In this study, we crippled autophagy in HSCs by conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system. This resulted in the loss of normal HSC functions, a severe myeloproliferation, and death of the mice within weeks. The hematopoietic stem and progenitor cell compartment displayed an accumulation of mitochondria and reactive oxygen species, as well as increased proliferation and DNA damage. HSCs within the Lin−Sca-1+c-Kit+ (LSK) compartment were significantly reduced. Although the overall LSK compartment was expanded, Atg7-deficient LSK cells failed to reconstitute the hematopoietic system of lethally irradiated mice. Consistent with loss of HSC functions, the production of both lymphoid and myeloid progenitors was impaired in the absence of Atg7. Collectively, these data show that Atg7 is an essential regulator of adult HSC maintenance.
Long-Term Exposure to Air Pollution and Cardiorespiratory Disease in the California Teachers Study Cohort
Authors: Michael J. Lipsett, Bart D. Ostro, Peggy Reynolds, Debbie Goldberg, Andrew Hertz, Michael Jerrett, Daniel F. Smith, Cynthia Garcia, Ellen T. Chang, Leslie Bernstein
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: Several studies have linked long-term exposure to particulate air pollution with increased cardiopulmonary mortality; only two have also examined incident circulatory disease.Objectives: To examine associations of individualized long-term exposures to particulate and gaseous air pollution with incident myocardial infarction and stroke, as well as all-cause and cause-specific mortality.Methods: We estimated long-term residential air pollution exposure for more than 100,000 participants in the California Teachers Study, a prospective cohort of female public school professionals. We linked geocoded residential addresses with inverse distance-weighted monthly pollutant surfaces for two measures of particulate matter and for several gaseous pollutants. We examined associations between exposure to these pollutants and risks of incident myocardial infarction and stroke, and of all-cause and cause-specific mortality, using Cox proportional hazards models.Measurements and Main Results: We found elevated hazard ratios linking long-term exposure to particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), scaled to an increment of 10 μg/m3 with mortality from ischemic heart disease (IHD) (1.20; 95% confidence interval [CI], 1.02–1.41) and, particularly among postmenopausal women, incident stroke (1.19; 95% CI, 1.02–1.38). Long-term exposure to particulate matter less than 10 μm in aerodynamic diameter (PM10) was associated with elevated risks for IHD mortality (1.06; 95% CI, 0.99–1.14) and incident stroke (1.06; 95% CI, 1.00–1.13), while exposure to nitrogen oxides was associated with elevated risks for IHD and all cardiovascular mortality.Conclusions: This study provides evidence linking long-term exposure to PM2.5 and PM10 with increased risks of incident stroke as well as IHD mortality; exposure to nitrogen oxides was also related to death from cardiovascular diseases.
Serial Echocardiographic-Doppler Assessment of Left Ventricular Geometry and Function in Rats With Pressure-Overload Hypertrophy
Authors: Sheldon E. Litwin, Sarah E. Katz, Ellen O. Weinberg, Beverly H. Lorell, Gerard P. Aurigemma, Pamela S. Douglas
Journal: Circulation (1995)

Background Although chronic pressure overload may progress to left ventricular (LV) failure, the pathophysiology of this transition is not well understood. In addition, the effects of chronic angiotensin-converting enzyme (ACE) inhibition on this transition are largely undefined. Methods and Results To examine changes in LV structure and function during the transition to heart failure, rats with LV hypertrophy due to banding of the ascending aorta (LVH, n=22) and age-matched sham-operated rats (n=6) were studied 6, 12, and 18 weeks after aortic banding. Two-dimensionally guided transthoracic M-mode echocardiograms and transmitral Doppler spectra were recorded for assessment of LV geometry and systolic and diastolic functions. LVH rats were randomized to no treatment (n=10) or treatment with the ACE inhibitor fosinopril (50 mg/kg per day, n=12) after the baseline echocardiogram. Six weeks after banding, LVH rats had increased LV wall thickness with normal cavity dimensions and supranormal endocardial systolic shortening. However, midwall shortening was mildly depressed, and a restrictive diastolic filling pattern was present. After 18 weeks of untreated pressure overload, LV wall thickness was unchanged, but cavity dilation, a fall in endocardial shortening, and further deterioration of diastolic filling were evident. In contrast to untreated LVH rats, the fosinopril-treated rats showed no change in LV diastolic cavity dimension, and systolic and diastolic functions did not deteriorate or improved. Closed chest LV systolic pressures at 18 weeks were not different in LVH or LVH-fosinopril rats (197 versus 198 mm Hg), although end-diastolic pressure was higher in the untreated rats (18 versus 11 mm Hg). Calculated LV systolic wall stress was lower in fosinopril-treated than untreated LVH rats. The severity of LV diastolic filling abnormalities correlated strongly with operating LV chamber stiffness ( r =.88, P &lt;.0001). Conclusions This model of pressure overload is characterized initially by concentric LV hypertrophy with compensated LV chamber performance; however, markedly abnormal diastolic filling is present. The transition from compensated hypertrophy to early failure is heralded by LV dilation, impairment of systolic function, and progression of the abnormalities in LV filling. Chronic ACE inhibition in rats with supravalvular aortic banding (1) does not change in vivo LV systolic pressure but prevents increased LV cavity size and increased LV wall stress and (2) attenuates impairment of (or improves) both systolic and diastolic functions. The effects of fosinopril could be explained in part by inhibition of an intracardiac renin-angiotensin system.
Donepezil for the Treatment of Agitation in Alzheimer's Disease
Authors: Robert J. Howard, Edmund Juszczak, Clive G. Ballard, Peter Bentham, Richard G. Brown, Roger Bullock, Alistair S. Burns, Clive Holmes, Robin Jacoby, Tony Johnson, Martin Knapp, James Lindesay, John T. O'Brien, Gordon Wilcock, Cornelius Katona, Roy W. Jones, Julia DeCesare, Michaela Rodger
Journal: New England Journal of Medicine (2007)

Agitation is a common and distressing symptom in patients with Alzheimer's disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for behavioral disturbances are unclear.
Features of lung cancer in young people: Report of 14 cases
Authors: Bianca Maria Paraschiv, Claudia Lucia Toma, Ionela Nicoleta Belaconi, Stefan Dumitrache-Rujinski, Tudor Constantinescu, Diana Leonte, Miron Alexandru Bogdan
Journal: European Respiratory Journal (2012)

Introduction : Lung cancer is one of the most common cancers in all ages. Little is known about clinical factors associated with the development of lung cancer in young patients. That is why mistakes are often made in radiological diagnosis of lung cancer in young people.   Method : In this report were included 14 patients admitted in our institute between 2003 and 2012, 8 males/6 females with the mean age of 29 years. Eight patients were non-smokers, 6 patients were smokers (10-65 pack-years).The patients were initially diagnosed with different lung diseases: asthma (2), pneumonia (7), tuberculosis (5). All patients were evaluated with chest X-ray, CT-scan, bronchoscopy.   Results : Patients presented at the doctor for several symptoms: dyspnea, fatigue, cough in all cases, fever (2), wheezing (2). Ten patients had inflammatory syndrome. The radiological aspects were: lung tumor (11), multiple nodules (2), and atelectasis (1). All patients had negative exams for My. Tuberculosis. The mean delay of diagnosis was 3.5 months. Cancer was confirmed on histological examinations: bronchial biopsy (12), tumor removed during surgery (1), necropsy (1). The type of carcinoma was adenocarcinoma (6), epidermoid (7), macrocellular (1). Six patients died during initial hospitalization, 8 cases were operated and received postoperative chemotherapy.   Conclusions : Lung cancer is unfortunately not the first diagnosis taken into account in young people with respiratory problems. The young patient9s condition deteriorates rapidly and the diagnosis of cancer is made when disease is already in an advanced stage. Diagnosis is often delayed and patients might lose the opportunity of curative treatment.
Association Between Human Papillomavirus Type and Clonal Status of Cervical Squamous Intraepithelial Lesions
Authors: Tjoung Won Park, Ralph M. Richart, Xiao-Wei Sun, Thomas C. Wright
Journal: JNCI Journal of the National Cancer Institute (1996)

Lesions that are histologically classified as precursors of cervical cancer, which are often referred to as squamous intraepithelial lesions (SILs), represent a heterogeneous clinical entity that can be associated with many different types of human papillomaviruses (HPVs) and have a variable biologic behavior. Approximately one half of low-grade SILs behave as non-neoplastic, productive viral lesions that frequently regress spontaneously, whereas the other half behave as neoplasms and either persist or progress to a histologically higher grade lesion. Identification of biomarkers that reliably differentiate those low-grade SILs with the properties of a non-neoplastic viral infection from those with the properties of neoplasia would provide a more rational basis for decisions about disease management. Since monoclonality is a hallmark of neoplasia irrespective of organ site, clonal status might represent one such biomarker. To better understand the pathobiology of SILs, we analyzed the clonality of low-grade and high-grade SILs and compared their clonal status with their associated HPV types. One hundred forty formalin-fixed, paraffin-embedded cervical biopsy and loop electrosurgical specimens, originally diagnosed as SILs, were obtained from the pathology archives of both the Columbia Presbyterian Medical Center and Kyto Diagnostics in New York. Clonality was determined with the use of a polymerase chain reaction (PCR) based method that detects nonrandom X-chromosome inactivation. This PCR-method amplifies a polymorphic region of the androgen receptor gene that is flanked by several differentially methylated enzyme sites. The same tissue was also analyzed for HPV DNA with the use of PCR and both L1 and E6 “consensus” primers. All 25 evaluable cases of high-grade SILs were determined to be monoclonal. Although 54 (68%) of 79 evaluable low-grade SILs were monoclonal, 25 (32%) of 79 low-grade SILs were polyclonal. A strong association was observed between HPV type and clonal status, with a total of 71 (47 low-grade and 24 high-grade) SILs determined to be monoclonal and containing HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. In contrast, 22 (92%) of the 24 low-grade SILs that contained another type of HPV were polyclonal (Fisher's exact test, two-sided, P ≤.001). Our findings suggest that the histopathologic entity termed low-grade SIL consists of two different types of lesions that are biologically distinct. One lesion is monoclonal and is associated with HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. The second type of low-grade SIL is polyclonal and is associated with other types of HPV. [J Natl Cancer Inst 1996;88:355–8]