tbuckley/cabot-search huggingface dataset:
Air pollution and health effects: A study of medical visits among children in Santiago, Chile.
Authors: B D Ostro, G S Eskeland, J M Sanchez, T Feyzioglu
Journal: Environmental Health Perspectives (1999)

Many epidemiological studies conducted in the last several years have reported associations between exposure to airborne particulate matter, measured as PM10 (<10 microm in diameter), and daily morbidity and mortality. However, much of the evidence involves effects on the elderly population; there is less evidence about the effects of particulates on children, especially those under 2 years of age. To examine these issues, we conducted time-series analyses of 2 years of daily visits to primary health care clinics in Santiago, Chile, where counts were computed for either upper or lower respiratory symptoms and for cohorts of children 3-15 years of age and below age 2. Daily PM10 and ozone measurements and meteorological variables were available from instruments located in downtown Santiago. The multiple regression analysis indicates a statistically significant association between PM10 and medical visits for lower respiratory symptoms in children ages 3-15 and in children under age 2. PM10 is also associated with medical visits related to upper respiratory symptoms in the older cohort, while ozone is associated with visits related to both lower and upper respiratory symptoms in the older cohort. For children under age 2, a 50- microg/m3 change in PM10 (the approximate interquartile range) is associated with a 4-12% increase in lower respiratory symptoms. For children 3-15 years of age, the increase in lower respiratory symptoms ranges from 3 to 9% for a 50- microg/m3 change in PM10 and 5% per 50 ppb change in ozone. These magnitudes are similar to results from studies of children undertaken in Western industrial nations.
Prospective Study of Neurological Abnormalities in Offspring of Women With Psychosis: Birth to Adulthood
Authors: Erland W. Schubert, Thomas F. McNeil
Journal: American Journal of Psychiatry (2004)

The authors prospectively investigated neurological abnormalities in 75 young adult offspring of mothers with psychotic disorders and 91 offspring of comparison mothers with no psychosis history. They also studied the stability of these abnormalities from birth to adulthood.Neurological abnormalities were previously studied in infancy and at 6 years of age. In this study, they were blindly assessed with a comprehensive neurological assessment scale at a mean age of 22.4 years in a 93.3% effective follow-up of the sample.In relation to the comparison subjects (N=88) and offspring of mothers with affective psychosis (N=22), the adult offspring of mothers with schizophrenia (N=28) had significantly more neurological abnormalities. More soft signs, primitive reflexes, involuntary movements, and cranial nerve abnormalities characterized a subgroup (32%) among these offspring. The offspring of mothers with affective psychosis were not different from comparison subjects. The extension of schizophrenia and affective psychosis risk groups to include additional maternal "spectrum cases" (N=10 and N=14, respectively) generally yielded similar results. Neurological abnormalities at 22 years were significantly associated with neurological abnormalities at age 6, but not in infancy, among the total high-risk group, offspring of mothers with schizophrenia, and comparison offspring.High levels of neurological abnormalities are found in a substantial proportion of offspring of mothers with schizophrenia but not offspring of mothers with affective psychosis. This suggests that familial risk for schizophrenia is associated with neurodevelopmental disturbance that is manifest throughout life and belongs to a different biological continuum from that of affective psychosis.
Liver Transplantation in European Patients with the Hepatitis B Surface Antigen
Authors: Didier Samuel, Rainer Muller, Graeme Alexander, Luigi Fassati, Beatrice Ducot, Jean-Pierre Benhamou, Henri Bismuth
Journal: New England Journal of Medicine (1993)

The role of liver transplantation in patients positive for the hepatitis B surface antigen (HBsAg) is controversial because of the high rate of recurrent hepatitis B virus (HBV) infection. It has not been determined whether this risk is greater for certain patients and whether the administration of anti-hepatitis B surface antigen (anti-HBs) immune globulin is beneficial.
169 REJECTION IS ASSOCIATED WITH MATRIX METALLOPROTEINASE-2 GENOTYPE CHIMERISM AFTER ORTHOTOPIC LIVER TRANSPLANTATION
Authors: K. Sebib Korkmaz, W.R. ten Hove, B.-J.F. de Rooij, B. van Hoek, J.J. van der Reijden, M.J. Coenraad, J. Dubbeld, H. Verspaget
Journal: Journal of Hepatology (2012)
WNT5A enhances resistance of melanoma cells to targeted BRAF inhibitors
Authors: Jamie N. Anastas, Rima M. Kulikauskas, Tigist Tamir, Helen Rizos, Georgina V. Long, Erika M. von Euw, Pei-Tzu Yang, Hsiao-Wang Chen, Lauren Haydu, Rachel A. Toroni, Olivia M. Lucero, Andy J. Chien, Randall T. Moon
Journal: Journal of Clinical Investigation (2014)

About half of all melanomas harbor a mutation that results in a constitutively active BRAF kinase mutant (BRAF(V600E/K)) that can be selectively inhibited by targeted BRAF inhibitors (BRAFis). While patients treated with BRAFis initially exhibit measurable clinical improvement, the majority of patients eventually develop drug resistance and relapse. Here, we observed marked elevation of WNT5A in a subset of tumors from patients exhibiting disease progression on BRAFi therapy. WNT5A transcript and protein were also elevated in BRAFi-resistant melanoma cell lines generated by long-term in vitro treatment with BRAFi. RNAi-mediated reduction of endogenous WNT5A in melanoma decreased cell growth, increased apoptosis in response to BRAFi challenge, and decreased the activity of prosurvival AKT signaling. Conversely, overexpression of WNT5A promoted melanoma growth, tumorigenesis, and activation of AKT signaling. Similarly to WNT5A knockdown, knockdown of the WNT receptors FZD7 and RYK inhibited growth, sensitized melanoma cells to BRAFi, and reduced AKT activation. Together, these findings suggest that chronic BRAF inhibition elevates WNT5A expression, which promotes AKT signaling through FZD7 and RYK, leading to increased growth and therapeutic resistance. Furthermore, increased WNT5A expression in BRAFi-resistant melanomas correlates with a specific transcriptional signature, which identifies potential therapeutic targets to reduce clinical BRAFi resistance.
Relation between small airways disease and parenchymal destruction in surgical lung specimens.
Authors: L N Willems, J A Kramps, T Stijnen, P J Sterk, J J Weening, J H Dijkman
Journal: Thorax (1990)

The relation between small airways disease and parenchymal destruction was investigated in lungs and lobes removed at surgery from 27 patients aged 15-70 years. Eight of the 27 patients were life-long non-smokers. The degree of small airways disease was assessed by semi-quantitative grading (SAD score) and by measuring diameter and wall thickness of membranous bronchioles. Parenchymal destruction was measured in three ways. Firstly, the number of alveolar attachments on membranous bronchioles per millimetre of circumference (AA/mm) was counted; the number of broken attachments was subtracted from the total AA/mm to give the numbers of intact attachments (normal AA/mm). Secondly, a point counting technique was used to give a destructive index (DI). Thirdly, the mean linear intercept (Lm) was determined. Total and normal AA/mm correlated negatively with the SAD score of membranous bronchioles (rs = -0.48 and -0.51) and with wall thickness (rs = -0.37 and -0.45) and DI correlated with wall thickness (rs = 0.5) and with the SAD score of respiratory bronchioles (rs = 0.53). Lm did not correlate with indices of small airway disease and total and normal AA/mm did not correlate with diameter. Multiple regression analyses showed that the correlation of total AA/mm with the SAD score of membranous and respiratory bronchioles and with wall thickness were not confounded by age or smoking. It is concluded that small airways disease is related to destruction of peribronchiolar alveoli, and it is postulated that small airways disease has a direct role in the causation of centrilobular emphysema.
The TAPS project. 17: Readmission to hospital for long term psychiatric patients after discharge to the community.
Authors: G. Thornicroft, C. Gooch, D. Dayson
Journal: BMJ (1992)

OBJECTIVE--To identify risk factors which increase the likelihood of readmission for long stay psychiatric patients after discharge from hospital. DESIGN--Follow up for five years of all long stay patients discharged from two large psychiatric hospitals to compare patients readmitted and not readmitted. SETTING--Friern and Claybury Hospitals in north London and their surrounding catchment areas. Most patients were discharged to staffed or unstaffed group homes. SUBJECTS--357 psychiatric patients who had been in hospital for over one year, of whom 118 were "new" long stay and 239 "old" long stay patients. MAIN OUTCOME MEASURES--Readmission to hospital and length of subsequent stay. RESULTS--Of all discharged patients 97 (27%) were readmitted at some time during the follow up period, 57 (16%) in the first year after discharge, and 31 (9%) then remained in hospital for over a year. The best explanatory factors for readmission were: male sex, younger age group, high number of previous admissions, higher levels of symptomatic and social behavioural disturbance, a diagnosis of manic-depressive psychosis, and living in a non-staffed group home. CONCLUSIONS--During the closure of psychiatric hospitals, facilities need to be preserved for acute relapses among long term, and especially younger, discharged patients. Staffed group homes may help prevent relapse and reduce the number of admission beds required.
Metallothionein expression in basaloid proliferations overlying dermatofibromas and in basal cell carcinomas
Authors: K. ROSSEN, T. HAERSLEV, K. HOU-JENSEN, G.KRAG JACOBSEN
Journal: British Journal of Dermatology (1997)

Basaloid proliferations overlying dermatofibromas which morphologically resemble superficial basal cell carcinomas have been interpreted as both reactive/regressive and frankly malignant. Metallothioneins (MTs) are low-molecular-weight proteins with a selective binding affinity for heavy metal ions. MTs has been proposed to represent a biological marker of carcinogenesis and, in a variety of human tumours, a correlation between immunohistochemically overexpression of MT and aggressive clinical behaviour has been shown. In order to clarify the nature of basaloid proliferations overlying dermatofibromas, we examined, immunohistochemically, 10 dermatofibromas with overlying simple hyperplasia, 16 dermatofibromas with overlying basaloid proliferation, and 35 basal cell carcinomas, for expression of MT. In normal epidermis, the basal keratinocytes showed cytoplasmatic MT immunoreactivity. The staining intensity was stronger in the basal cells of the rete ridges, an observation which is in accordance with the high proportion of S-phase cells in this area. Simple hyperplasia showed the same MT expression pattern as normal epidermis. Basaloid proliferations stained like superficial and nodular basal cell carcinomas. Of nodular basal cell carcinomas, 92% (12 of 13) showed decreased/absent MT immunoreactivity, while 86% (six of seven) of infiltrating/morphoea-like basal cell carcinomas showed overexpression of MT (P = 0.001, Fisher's exact test). The results demonstrate that MT overexpression in basal cell carcinomas is correlated with infiltrative growth pattern. The similar expression of MT in basaloid proliferations and 'non-infiltrating' basal cell carcinomas suggests that these lesions share a common change in metabolism and/or differentiation.
Mononuclear phagocytes (MP) in rheumatoid arthritis (RA): Discordance of internalization and digestion functions
Authors: A.P. Tsybulkin, M.I. Arleevskaja, D.G. Khaliullina, A.I. Zabotin, V.N. Tsybulkina
Journal: Journal of Allergy and Clinical Immunology (2003)
Microarray-Based Expression Profiling of Normal and Malignant Immune Cells
Authors: Rheem D. Medh
Journal: Endocrine Reviews (2002)

Recent advances in gene microarray technology have facilitated global analyses of gene expression profiles in normal and malignant immune cells. Great strides have been made in our understanding of molecular differences among various types of immune cells, the process of T and B cell activation, and the genomic changes that convert normal cells to malignant ones. Genomic analysis has become a crucial aspect of cancer classification, diagnosis, therapy, and prognosis. This technology has the potential to reveal the comprehensive transcriptional alterations that dictate fundamental biological processes such as signal transduction in response to specific stimuli, cell growth, differentiation, and apoptosis. While reaping the benefits of genomic analyses, it is important to realize its limitations with respect to accuracy of interpretation, reproducibility, and signal detection. It is crucial to optimize signals for individual probe-target pairs and to develop a uniform set of criteria for data analyses. The development of a public-access database of results from individual laboratories will pave the way for identifying discrepancies and advancing scientific breakthroughs.
Livedo Reticularis with Ulcerations
Authors: MAURI FELDAKER, EDGAR A. HINES, ROBERT R. KIERLAND
Journal: Circulation (1956)

Idiopathic livedo reticularis may be associated with ulcerations of the lower extremities beginning primarily during the warmer or summer months, as well as the more usual occurrence of winter ulcerations. Summer ulceration apparently is a new and rare entity which has many clinical and histopathologic features similar to winter ulcerations. Hypertension, Raynaud's phenomena, acrocyanosis and thrombosis of digital arteries were noted only in patients with winter ulcerations, while edema of the legs and feet was a more prominent feature in patients with summer ulcerations. Medical treatment, including rest in bed, elastic supportive bandages and a trial of hexamethonium (bistrium bromide) injections, seemed to be the treatment of choice. Lumbar sympathectomy did not seem to be of great permanent value.
Ethnic specificity of lupus-associated loci identified in a genome-wide association study in Korean women
Authors: Hye-Soon Lee, Taehyeung Kim, So Young Bang, Young Ji Na, Il Kim, Kwangwoo Kim, Jae-Hoon Kim, Yeun-Jun Chung, Hyoung Doo Shin, Young Mo Kang, Seung-Cheol Shim, Chang-Hee Suh, Yong-Beom Park, Jong-Sung Kim, Changwon Kang, Sang-Cheol Bae
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To identify novel genetic candidates for systemic lupus erythematosus (SLE) in the Korean population, and to validate the risk loci for SLE identified in previous genome-wide association studies (GWAS). <h3>Methods</h3> We performed a GWAS in 400 Korean female SLE patients and 445 controls. Selected single-nucleotide polymorphisms (SNP) were then replicated in an independent cohort of 385 SLE patients and 583 controls (replication cohort 1), and in a further 811 SLE patients and 1502 controls (replication cohort 2). <h3>Results</h3> In the GWAS phase, rs9275428 located near <i>HLA-DQB1</i> showed the strongest association with SLE (OR 0.50, false discovery rate (FDR) p=3.07×10<sup>−6</sup>). Although no loci reached genome-wide significance outside major histocompatibility complex (MHC), <i>C8orf13-BLK, STAT4</i>, <i>CSMD1</i>, <i>DIAPH3</i>, <i>GLDC</i> and <i>TNFSF4</i> showed FDR p &lt; 0.05. Our results suggest that <i>STAT4</i>, <i>BLK</i>, <i>IRF5</i>, <i>PTTG1-miR-146a</i>, <i>UBE2L3</i> and <i>TNFAIP3</i> are shared susceptibility loci among Caucasians and Asians, while <i>ETS1</i>, <i>IKZF1</i>, <i>SLC15A4</i> are likely to be Asian-specific loci. In a combined analysis of 1596 SLE patients and 2540 controls for selected 22 candidate SNP, <i>STAT4</i> and <i>BLK</i> as positive controls showed a strong association with SLE (FDR p=9.85×10<sup>−13</sup> and 2.28×10<sup>−8</sup>, respectively). Of these, 16 candidates (<i>PEX5L</i>, <i>TRAJ50</i>, <i>MYO18B</i>, <i>SOS1</i>, <i>ARHGAP26</i>, <i>SMURF1</i>, <i>CADPS</i>, <i>HAND1</i>, <i>FAM78B</i>, <i>DIAPH3</i>, <i>TBL1XR1</i>, <i>CSMD1</i>, <i>ZBTB20</i>, <i>C3orf21</i>, <i>HIPK1</i> and <i>AP001042.1</i>) showed only nominal significance (7.05×10<sup>−4</sup>≤FDR p≤4.38×10<sup>−2</sup>). <h3>Conclusions</h3> There are similarities and differences in genetic susceptibility for SLE between Caucasian and Asian ethnic groups. Although 16 putative novel loci for SLE have been suggested in the Korean population, further research on a larger sample is required to discriminate truth from error.
Misleading communication of risk
Authors: G. Gigerenzer, O. Wegwarth, M. Feufel
Journal: BMJ (2010)

Editors should enforce transparent reporting in abstracts

In 1996 a review of mammography screening reported in its abstract a 24% reduction of breast cancer mortality1; a review in 2002 claimed a 21% reduction.2 Accordingly, health pamphlets, websites, and invitations broadcast a 20% (or 25%) benefit.3 Did the public know that this impressive number corresponds to a reduction from about five to four in every 1000 women, that is, 0.1%? The answer is, no. In a representative quota sample in nine European countries, 92% of about 5000 women overestimated the benefit 10-fold, 100-fold, and more, or they did not know.4 For example, 27% of women in the United Kingdom believed that out of every 1000 women who were screened, 200 fewer would die of breast cancer. But it is not only patients who are misled. When asked what the “25% mortality reduction from breast cancer” means, 31% of 150 gynaecologists answered that for every 1000 women who were screened, 25 or 250 fewer would die⇓.3



David Page Photography/Alamy

In 1995, the UK Committee on Safety of Medicines issued a warning that third generation oral contraceptive pills increased the risk of potentially life …
Significance of natural polymerized albumin and its receptor in hepatitis B infection of hepatocytes
Authors: Srikant Dash, Kanury V. S. Rao, Beenu Joshi, Nabeen C. Nayak, Subrat K. Panda
Journal: Hepatology (1991)

Lack of information regarding the presence of native albumin polymer in serum and its structural similarity to the one produced by glutaraldehyde treatment casts doubt on the postulate that hepatitis B virus attachment to hepatocytes is mediated through polymerized albumin. We used a sandwich enzyme-linked immunosorbent assay with murine monoclonal antibodies raised against glutaraldehyde-polymerized albumin to detect native albumin polymer in human serum and its cross-reactivity with other albumin polymers. Presence of polymerized albumin receptor on the HepG2 cell was studied by radioreceptor assay. Purified hepatitis B virus and synthetic peptide analogous to part of pre-S2 sequence (120-145) were used to study polymerized albumin-dependent attachment of the virus to HepG2 cells. Antibodies raised against pre-S2 peptide were used to inhibit the pre-S2 and hepatitis B virus attachment to HepG2 cells. Glutaraldehyde-treated polymerized albumin was found to be immunologically cross-reactive with native albumin polymer. Its levels were found to be significantly raised in sera of patients with liver diseases. Polymerized albumin has specific saturable receptor on HepG2 cells with two classes of binding sites of different equilibrium dissociation constant (Kd1 = (16 +/- 9.6)pmol/L and Kd2 = (1,019 +/- 172)pmol/L. Albumin monomer was unable to compete for the polymerized albumin receptor sites on HepG2 cells. Anti-pre-S2 antibodies inhibit hepatitis B virus and pre-S2 binding to hepatocyte by 40% and 70%, respectively. Added extraneous polymerized albumin and the antibody against it did not interfere with virus attachment to HepG2 cells.
Abstract 1508: Development of a strategy to knock down SDF-1 using shRNA as a means to prevent pulmonary metastasis
Authors: Anand C. Annan, Meredith A. Preuss, Anton V. Borovjagin, Hideyo Ugai, David T. Curiel
Journal: Cancer Research (2010)

Abstract Metastasis, a poor prognostic indicator causing increased mortality, occurs in an organ specific pattern with lungs and lymph nodes most commonly involved. Cancer cells expressing ‘CXC'-chemokine family Receptor-4 (CXCR4) are chemo-attracted to the pulmonary tissue expressing its cognate ligand Stromal Derived Factor-1 (SDF-1), which aid in formation of metastasis. In this regard, we propose to modulate this axis through knock down of SDF-1 specifically in pulmonary vasculature to prevent lung metastasis. Our laboratory has previously shown that human adenovirus (Ad), when injected via the tail vein into human Coxsackie Adenovirus Receptor (hCAR) transgenic mice, mice that ubiquitously express the hCAR native Ad receptor, transduces pulmonary vasculature preferentially. To this end, we plan to knock- down SDF-1 using shRNA against SDF-1 employing Ad as the vector to deliver them in vivo to achieve pulmonary targeting. To establish a pulmonary metastatic model in the “hCAR” mouse, we injected B16-F10 melanoma cells stably expressing CXCR4 (to cause metastasis) and firefly luciferase (to track tumor cells) via tail vein. Presence of lung metastasis was confirmed by histopathological analysis, immunohistochemistry for CXCR4 and luciferase assay of the tissues. In order to identify a shRNA to deliver to the pulmonary vasculature to decrease SDF-1, we evaluated several plasmid shRNAs for their ability to suppress SDF-1 expression at the mRNA level using qRT-PCR in vitro. From this experiment, we identified one shRNA which gave significant decrease in mRNA of SDF-1 measured by qRT-PCR (&amp;gt;70%). We created an Ad vector expressing this particular shRNA and measured its efficiency of inhibiting SDF-1 expression of approximately 75% for mRNA by qRT-PCR and approximately 90% for protein by Western Blot. Future studies include demonstrating the functional knock-down of SDF-1 in vitro by transwell chamber assay and subsequently analyzing the biological effect of knocking down SDF-1 in vivo in the pulmonary metastatic model established in “hCAR” mouse. In conclusion, therapies available for prevention of metastasis are limited despite different treatment modalities available for cancer. Our approach of targeted knock down of SDF-1 would reduce the metastatic burden to the lungs with potential for clinical translation into a therapeutic approach to prevent lung metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1508.
An Unusual Case of Cardiac Arrest
Authors: C. M. T. Gleave, C. P. Monty
Journal: BMJ (1963)

COMMUNICATIONS-~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~MCI OMU four of our patients treated with 9a-fluorocortisol in whom a gain in weight resulted, the secretion rates fell to between 20 and 70 /ig./day,with a mean for the four of 45 I&g.In neither of the severely magnesium-depleted subjects was the aldosterone secretion rate low enough to indicate any significant degree of inhibition.It must be concluded, therefore, that even severe mag- nesium depletion results in no significant change in the aldosterone secretion rate, and that fluctuations in mag- nesium metabolism have a negligible influence on aldo- sterone secretion.We are grateful to Dr. C.