tbuckley/cabot-search huggingface dataset:
<i>APOE</i>,<i>MAPT</i>, and<i>SNCA</i>Genes and Cognitive Performance in Parkinson Disease
Authors: Ignacio F. Mata, James B. Leverenz, Daniel Weintraub, John Q. Trojanowski, Howard I. Hurtig, Vivianna M. Van Deerlin, Beate Ritz, Rebecca Rausch, Shannon L. Rhodes, Stewart A. Factor, Cathy Wood-Siverio, Joseph F. Quinn, Kathryn A. Chung, Amie L. Peterson, Alberto J. Espay, Fredy J. Revilla, Johnna Devoto, Shu-Ching Hu, Brenna A. Cholerton, Jia Y. Wan, Thomas J. Montine, Karen L. Edwards, Cyrus P. Zabetian
Journal: JAMA Neurology (2014)

Cognitive impairment is a common and disabling problem in Parkinson disease (PD) that is not well understood and is difficult to treat. Identification of genetic variants that influence the rate of cognitive decline or pattern of early cognitive deficits in PD might provide a clearer understanding of the etiopathogenesis of this important nonmotor feature.To determine whether common variation in the APOE, MAPT, and SNCA genes is associated with cognitive performance in patients with PD.We studied 1079 PD patients from 6 academic centers in the United States who underwent assessments of memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), attention and executive function (Letter-Number Sequencing Test and Trail Making Test), language processing (semantic and phonemic verbal fluency tests), visuospatial skills (Benton Judgment of Line Orientation test), and global cognitive function (Montreal Cognitive Assessment). Participants underwent genotyping for the APOE ε2/ε3/ε4 alleles, MAPT H1/H2 haplotypes, and SNCA rs356219. We used linear regression to test for association between genotype and baseline cognitive performance with adjustment for age, sex, years of education, disease duration, and site. We used a Bonferroni correction to adjust for the 9 comparisons that were performed for each gene.Nine variables derived from 7 psychometric tests.The APOE ε4 allele was associated with lower performance on the HVLT-R Total Recall (P = 6.7 × 10(-6); corrected P [Pc] = 6.0 × 10(-5)), Delayed Recall (P = .001; Pc = .009), and Recognition Discrimination Index (P = .004; Pc = .04); a semantic verbal fluency test (P = .002; Pc = .02); the Letter-Number Sequencing Test (P = 1 × 10(-5); Pc = 9 × 10(-5)); and Trail Making Test B minus Trail Making Test A (P = .002; Pc = .02). In a subset of 645 patients without dementia, the APOE ε4 allele was associated with lower scores on the HVLT-R Total Recall (P = .005; Pc = .045) and the semantic verbal fluency (P = .005; Pc = .045) measures. Variants of MAPT and SNCA were not associated with scores on any tests.Our data indicate that the APOE ε4 allele is an important predictor of cognitive function in PD across multiple domains. Among PD patients without dementia, the APOE ε4 allele was only associated with lower performance on word list learning and semantic verbal fluency, a pattern more typical of the cognitive deficits seen in early Alzheimer disease than PD.
Smoking-Related Gene Expression in Laser Capture–Microdissected Human Lung
Authors: Xiang-Lin Tan, Tao Wang, Shengli Xiong, Shalini V. Kumar, Weiguo Han, Simon D. Spivack
Journal: Clinical Cancer Research (2009)

PURPOSE: Interindividual differences in quantitative expression could underlie a propensity for lung cancer. To determine precise individual gene expression signatures on a lung compartment-specific basis, we investigated the expression of carcinogen metabolism genes encoding cytochromes P450 (CYP) 1B1, 2A13, GSTP1, and a tumor suppressor gene p16 in laser capture-microdissected samples of human alveolar compartment (AC) and bronchial epithelial compartment (BEC) lung tissue from 62 smokers and nonsmokers. EXPERIMENTAL DESIGN: Tobacco exposure was determined by plasma nicotine, cotinine, and smoking history. Precise mRNA expression was determined using our RNA-specific qRT-PCR strategy, and correlated with detailed demographic and clinical characteristics. RESULTS: Several correlations of mRNA expression included (a) CYP1B1 in AC (positively with plasma nicotine level, P = 0.008; plasma cotinine level, P = 0.001), (b) GSTP1 in AC (positively with plasma cotinine level, P = 0.003), and (c) GSTP1 in BEC (negatively with smoke dose, P = 0.043; occupational risk, P = 0.019). CYP2A13 was rarely expressed in AC and not expressed in BEC. p16 expression was not correlated with any measured factor. For each gene, subjects showed expression that was individually concordant between these compartments. No clear association of mRNA expression with lung cancer risk was observed in this pilot analysis. CONCLUSIONS: The association between lung mRNA expression and tobacco exposure implies that gene-tobacco interaction is a measurable quantitative trait, albeit with wide interindividual variation. Gene expression tends to be concordant for alveolar and bronchial compartments for these genes in an individual, controlling for proximate tobacco exposure. (Clin Cancer Res 2009;15(24):7562-70).
Activating Germline R776H Mutation in the Epidermal Growth Factor Receptor Associated With Lung Cancer With Squamous Differentiation
Authors: Jan van Noesel, Ward H. van der Ven, Theo A.M. van Os, Peter W.A. Kunst, Jitske Weegenaar, Roy J.A. Reinten, Rama K. Kancha, Justus Duyster, Carel J.M. van Noesel
Journal: Journal of Clinical Oncology (2013)
SUPRAPUBIC PROSTATECTOMY UNDER NITROUS OXID ANESTHESIA.
Authors: JOSEPH WIENER
Journal: JAMA (1904)

That the removal of the prostate gland is the ideal surgical procedure in the treatment of prostatic hypertrophy is now very generally recognized. The chief contraindication to the performance of a prostatectomy up to the present time, according to the consensus of opinion, has been the danger resulting from the administration of ether or chloroform. Many surgeons have hesitated to offer some of their old prostatic cases the benefits of the operation on account of the presence of cardiac, nephritic or other lesions. It is in the hope of widening the field of usefulness of prostatectomy, and of extending the splendid benefits of the operation to patients who have heretofore had the advantage only of palliative operations, that this paper has been prepared. The cases which form the basis of the paper are, so far as I have been able to ascertain, the first cases of
Lipid mediators in oxygen-induced airway remodeling and hyperresponsiveness in newborn rats.
Authors: J S Burghardt, V Boros, D F Biggs, D M Olson
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We examined whether lipid mediators have a causal role in neonatal hyperoxia-induced lung damage, specifically, airway remodeling and hyperresponsiveness. Newborn rat pups were exposed to hyperoxia (> 95% O2 from Days 4 to 14 and 65% from Days 14 to 32) or normoxia. The 5-lipoxygenase inhibitor, LTD4 receptor antagonist, and inhibitor of platelet-activating factor synthesis, Wy-50,295 (30 mg/kg), or vehicle was administered daily from Days 3 to 32. Oxygen exposure significantly increased (p < 0.05) the production of one potential lipid mediator group, peptido-LTs, from explanted lung slices and large airways from 2-wk-old rat pups. At 4 wk, only the large airway tissue output showed significant elevation because of oxygen exposure. At both ages, Wy-50,295 significantly decreased (p < 0.05) the production of peptido-LTs in the lung and large airways of oxygen-exposed pups. Pulmonary function and airway wall morphometry were studied in 5-wk-old rat pups 2 to 3 d after oxygen exposure and drug administration ceased. The resistance change in response to methacholine (0 to 20 microg/kg body weight given intravenously) was greater (p < 0.02) in oxygen-exposed animals. Oxygen exposure caused significant (60% increase) smooth muscle thickening (p < 0.05). Wy-50,295 prevented the oxygen-induced airway hyperresponsiveness and smooth muscle thickening. We conclude that chronic hyperoxic exposure causes an increase in pulmonary production of at least one lipid mediator, peptido-LTs, from newborn rats and that this is associated with airway smooth muscle layer thickening and, consequently, airway hyperresponsiveness.
Mechanism of action of the antifibrogenic compound gliotoxin in rat liver cells
Authors: James G. Orr, Val Leel, Gary A. Cameron, Carylyn J. Marek, Emma L. Haughton, Lucy J. Elrick, Julie E. Trim, Gabrielle M. Hawksworth, Andrew P. Halestrap, Matthew C. Wright
Journal: Hepatology (2004)

Gliotoxin has been shown to promote a reversal of liver fibrosis in an animal model of the disease although its mechanism of action in the liver is poorly defined. The effects of gliotoxin on activated hepatic stellate cells (HSCs) and hepatocytes have therefore been examined. Addition of gliotoxin (1.5 μM) to culture-activated HSCs resulted in its rapid accumulation, resulting in increased levels of glutathione and apoptosis without any evidence of oxidative stress. In contrast, although hepatocytes also rapidly sequestered gliotoxin, cell death only occurred at high (50-μM) concentrations of gliotoxin and by necrosis. At high concentrations, gliotoxin was metabolized by hepatocytes to a reduced (dithiol) metabolite and glutathione was rapidly oxidized. Fluorescent dye loading experiments showed that gliotoxin caused oxidative stress in hepatocytes. Antioxidants—but not thiol redox active compounds—inhibited both oxidative stress and necrosis in hepatocytes. In contrast, HSC apoptosis was not affected by antioxidants but was potently abrogated by thiol redox active compounds. The adenine nucleotide transporter (ANT) is implicated in mitochondrial-dependent apoptosis. HSCs expressed predominantly nonliver ANT isoform 1, and gliotoxin treatment resulted in a thiol redox-dependent alteration in ANT mobility in HSC extracts, but not hepatocyte extracts. In conclusion, these data suggest that gliotoxin stimulates the apoptosis of HSCs through a specific thiol redox-dependent interaction with the ANT. Further understanding of this mechanism of cell death will aid in finding therapeutics that specifically stimulate HSC apoptosis in the liver, a promising approach to antifibrotic therapy. Supplementary material for this article can be found on the Hepatology website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (Hepatology 2004;40:232-242.)
159 Natural history and determinants of disease progression in non alcoholic fatty liver disease-good and bad news
Authors: S SAKSENA
Journal: Hepatology (2003)

A significant increased risk of complications and mortality in immunocompromised patients affected by COVID-19 has been described. However, the impact of COVID-19 in solid organ transplant (SOT) recipients is an issue still under debate, due to conflicting evidence that has emerged from different observational studies.We performed a systematic review with a meta-analysis to assess the clinical outcome in SOT recipients with COVID-19 compared with the general population.PubMed-MEDLINE and Scopus were independently searched until 13 October 2021.Prospective or retrospective observational studies comparing clinical outcome in SOT recipients versus general populations affected by COVID-19 were included. The primary endpoint was 30-day mortality.Participants were patients with confirmed COVID-19.Interventions reviewed were SOTs.The quality of the included studies was independently assessed with the Risk of Bias in Non-randomized Studies of Interventions tool for observational studies. The meta-analysis was performed by pooling ORs retrieved from studies providing adjustment for confounders using a random-effects model with the inverse variance method. Multiple subgroups and sensitivity analyses were conducted to investigate the source of heterogeneity.A total of 3501 articles were screened, and 31 observational studies (N = 590 375; 5759 SOT recipients vs. 584 616 general population) were included in the meta-analyses. No difference in 30-day mortality rate was found in the primary analysis, including studies providing adjustment for confounders (N = 17; 3752 SOT recipients vs. 159 745 general population; OR: 1.13; 95% CI, 0.94–1.35; I2 = 33.9%). No evidence of publication bias was reported. A higher risk of intensive care unit admission (OR: 1.56; 95% CI, 1.03–2.63) and occurrence of acute kidney injury (OR: 2.50; 95% CI, 1.81–3.45) was found in SOT recipients.No increased risk in mortality was found in SOT recipients affected by COVID-19 compared with the general population when adjusted for demographic and clinical features and COVID-19 severity.
Thromboxane A2 Mediates Augmented Polymorphonuclear Leukocyte Adhesiveness
Authors: Philip J. Spagnuolo, Jerrold J. Ellner, Aviv Hassid, Michael J. Dunn
Journal: Journal of Clinical Investigation (1980)

We examined the role of prostaglandins and thromboxanes as mediators of plasma-dependent increased polymorphonuclear leukocyte adhesiveness induced by Escherichia coli lipopolysaccharide. The cyclo-oxygenase inhibitors—indomethacin and d,l-6-chloro-α-methyl-carbozole-2-acetic acid (R020-5720)—reduced lipopolysaccharide-induced adherence of polymorphonuclear leukocytes by 74 and 62%, respectively. In addition, inhibitors of thromboxane synthetase—imidazole, 9,11-azoprosta-5,13-dienoic acid, and 1-benzylimidazole—suppressed the stimulation of adherence by 31, 66, and 83%, respectively. Exogenous prostaglandins E1, E2, and F2α did not increase polymorphonuclear leukocyte adherence, nor were they detected in significant quantities in supernates of polymorphonuclear leukocytes exposed to lipopolysaccharide. However, inhibitors of both cyclo-oxygenase and thromboxane synthetase reduced increases in adherence induced by arachidonic acid (10 μg/ml), suggesting that lipopolysaccharide-mediated increases in adherence were due to an arachidonic acid product other than prostaglandin E2 or F2α. 8,11,14-Eicosatrienoic acid, a precursor of monoenoic prostaglandins, did not enhance polymorphonuclear leukocyte adhesiveness.
Primary cutaneous adenoid cystic carcinoma: case report, immunohistochemistry, and review of the literature
Authors: TH.H KWAST, V.D. VUZEVSKI, F. RAMAEKERS, M.T. BOUSEMA, TH. JOOST
Journal: British Journal of Dermatology (1988)

We report a case of primary cutaneous adenoid cystic carcinoma in a 75‐year‐old man. Electron microscopy revealed similar features to those previously described in adenoid cystic carcinomas of salivary gland origin: wide intercellular spaces, pseudocysts containing replicated basement membrane‐like material and true lumina lined by cytoplasmic membranes with numerous microvilli. Immunohistochemistry using antibodies to several cytoskeletal proteins (keratins and actin) indicated the presence of two epithelial tumour cell populations, one with the phenotype of myoepithelial cells, lining the pseudocysts and the periphery of the tumour fields, and another with the phenotype of acinar cells of the secretory coil of sweat glands. In addition, the tumour showed immunoreactivity for epithelial membrane antigen, but not carcinoembryonic antigen. A review of the literature on other cases of primary cutaneous adenoid cystic carcinoma showed that this tumour generally affects older patients with a female to male ratio of 4:1. The most common tumour site appears to be the scalp (40%), and the recurrence rate is 50%. Surgical treatment with extensive resection margins is recommended. Adenoid cystic carcinomas (ACC) most commonly originate in the major and minor salivary glands. Other, rare, primary locations may be the breast,1 the major bronchi,2 the uterine cervix,3 the external auditory canal,4 and the skin.5–16 Cutaneous localization of ACC may also result from direct extension of ACC of the minor salivary glands situated in the paranasal sinuses,17 and rarely a distant cutaneous metastasis of a primary salivary gland ACC occurs.18 Primary cutaneous ACCs are generally considered as eccrine sweat gland carcinoma.19 Electron microscopic and immunofluorescence studies have implicated myoepithelial cells as the histogenetic precursors of ACC of the salivary glands and uterine cervix.20,21
Give me shelter: the global housing crisis.
Authors: Valerie J Brown
Journal: Environmental Health Perspectives (2003)

In both developed and developing countries around the world, the health of significant numbers of people is adversely affected by a lack of adequate housing. Large-scale migrations into already crowded developing nation cities compound existing health problems associated with poor indoor air quality, contaminated drinking water, and limited sanitation infrastructure. In the developed world, lead exposure, indoor air quality, and asthma are among the most serious and costly housing-related health risks.
Chronic Pelvic Pain as a Somatoform Disorder
Authors: U. Ehlert, C. Heim, D.H. Hellhammer
Journal: Psychotherapy and Psychosomatics (1999)

&lt;i&gt;Background:&lt;/i&gt; The purpose of this study was to determine whether psychiatric disturbances, particularly somatization, and an increased number of traumatic and critical life events, which have been found in women with idiopathic chronic pelvic pain (ICPP), can also be observed in women with chronic pelvic pain and abdominal adhesions (ACPP). &lt;i&gt;Methods:&lt;/i&gt; Forty women who underwent diagnostic laparoscopy were subdivided into three groups according to blind rated somatic pathologies: ICPP patients (n = 16), ACPP patients (n = 10), infertile controls without pain (n = 14). Besides the standardized assessment of DSM-III-R diagnosis, questionnaires and semistandardized interviews were used to estimate depression, somatization, pain, the prevalence of sexual and physical abuse, and the number of critical life events. &lt;i&gt;Results:&lt;/i&gt; Diagnostic criteria for somatoform pain disorder were fullfilled in 73.3% of the ICPP patients, 60% of the ACPP patients and none of the controls. With respect to the somatization symptom checklist the two pain groups scored significantly higher than the controls (p &lt; 0.05). Referring to perceived pain, ACPP patients differed from the ICPP patients by one out of seven subscales (higher persistence of pain; p &lt; 0.05). No correlation was found between the intensity of pain and the severity of classified adhesions. The two groups of pain patients significantly differed from controls by a higher prevalence of sexual abuse (p &lt; 0.05). Depression was found neither in the pain groups nor in the controls. &lt;i&gt;Conclusions:&lt;/i&gt; Because high somatization and high prevalence rates of abuse were not only found in patients suffering from ICPP but also in ACPP patients, it seems to be doubtful that the somatic pathology may fully explain the psychopathology in patients with ACPP.
Face to Face with Toy Safety: Understanding an Unexpected Threat
Authors: Charles W. Schmidt
Journal: Environmental Health Perspectives (2008)

Focus | Face to Face with Toy Safety Lushpix U ntil March 2007, thousands of kids around the country could be found playing with toy trucks, helicopters, and soldiers sold under the Elite Operations brand name.The toys were fun, and they looked great with their thick coat of glossy paint.Trouble was, that paint was loaded with 5,000 ppm lead, a potent developmental neurotoxicant with no known safe exposure level.When the high lead levels were detected during a routine inspection, the Consumer Product Safety Commission (CPSC) issued a recall, the first for a leadcontaminated toy in 2007.Lead-triggered toy recalls were rare, but not unheard of in the United States, with just a handful issued in the last decade.Eventually, nearly 130,000 Elite Operations units-made by a Hong Kong company called Toy Century Industrial and imported by Toys R Us-would be recalled.
Phage Display–Derived Human Monoclonal Antibodies Isolated by Binding to the Surface of Live Primary Breast Cancer Cells Recognize GRP78
Authors: Charlotte G. Jakobsen, Nicolaj Rasmussen, Anne-Vibeke Laenkholm, Henrik J. Ditzel
Journal: Cancer Research (2007)

Abstract Clinical trials using monoclonal antibodies (mAb) against cell-surface markers have yielded encouraging therapeutic results in several cancer types. Generally, however, anticancer antibodies are only efficient against a subpopulation of cancers, and there is a strong need for identification of novel targets and human antibodies against them. We have isolated single-chain human mAbs from a large naïve antibody phage display library by panning on a single-cell suspension of freshly isolated live cancer cells from a human breast cancer specimen, and these antibodies were shown to specifically recognize cancer-associated cell-surface proteins. One of the isolated human antibody fragments, Ab39, recognizes a cell-surface antigen expressed on a subpopulation of cancer cell lines of different origins. Immunohistochemical analysis of a large panel of cancerous and normal tissues showed that Ab39 bound strongly to several cancers, including 45% breast carcinomas, 35% lung cancers, and 86% melanomas, but showed no or weak binding to normal tissues. A yeast two-hybrid screen of a large human testis cDNA library identified the glucose-regulated protein of 78 kDa (GRP78) as the antigen recognized by Ab39. The interaction was confirmed by colocalization studies and antibody competition experiments that also mapped the epitope recognized by Ab39 to the COOH terminus of GRP78. The expression of GRP78 on the surface of cancer cells, but not normal cells, makes it an attractive target for cancer therapies including mAb-based immunotherapy. Our results suggest that the human antibody Ab39 may be a useful starting point for further genetic optimization that could render it a useful diagnostic and therapeutic reagent for a variety of cancers. [Cancer Res 2007;67(20):9507–17]
Should We Emergently Revascularize Occluded Coronaries for Cardiac Arrest?
Authors: Eisuke Kagawa, Keigo Dote, Masaya Kato, Shota Sasaki, Yoshinori Nakano, Masato Kajikawa, Akifumi Higashi, Kiho Itakura, Akihiko Sera, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Satoshi Kurisu
Journal: Circulation (2012)

Extracorporeal membrane oxygenation (ECMO) and percutaneous coronary intervention (PCI) may be useful in cardiopulmonary resuscitation. However, little is known about the combination of ECMO and intra-arrest PCI. This study investigated the efficacy of rapid-response ECMO and intra-arrest PCI in patients with cardiac arrest complicated by acute coronary syndrome who were unresponsive to conventional cardiopulmonary resuscitation.This multicenter cohort study was conducted with the use of the database of ECMO in Hiroshima City, Japan. Between January 2004 and May 2011, rapid-response ECMO was performed in 86 patients with acute coronary syndrome who were unresponsive to conventional CPR. The median age of the study patients was 63 years, and 81% were male. Emergency coronary angiography was performed in 81 patients (94%), and intra-arrest PCI was performed in 61 patients (71%). The rates of return of spontaneous heartbeat, 30-day survival, and favorable neurological outcomes were 88%, 29%, and 24%, respectively. All of the patients who received intra-arrest PCI achieved return of spontaneous heartbeat. In patients who survived up to day 30, the rate of out-of-hospital cardiac arrest was lower (58% versus 28%; P=0.01), the intra-arrest PCI was higher (88% versus 70%; P=0.04), and the time interval from collapse to the initiation of ECMO was shorter (40 [25-51] versus 54 minutes [34-74 minutes]; P=0.002).Rapid-response ECMO plus intra-arrest PCI is feasible and associated with improved outcomes in patients who are unresponsive to conventional cardiopulmonary resuscitation. On the basis of these findings, randomized studies of intra-arrest PCI are needed.
A full genome search in multiple sclerosis
Authors: George C. Ebers, Kim Kukay, Dennis E. Bulman, Adele D. Sadovnick, George Rice, Carol Anderson, Holly Armstrong, Keith Cousin, Robert B. Bell, Walter Hader, Donald W. Paty, Stanley Hashimoto, Joel Oger, Pierre Duquette, Sharon Warren, Trevor Gray, Paul O'Connor, Avindra Nath, Anthony Auty, Luanne Metz, Gordon Francis, John E. Paulseth, T. John Murray, William Pryse-Phillips, Robert Nelson, Mark Freedman, Donald Brunet, Jean-Pierre Bouchard, David Hinds, Neil Risch
Journal: Nature Genetics (1996)