tbuckley/cabot-search huggingface dataset:
Biomonitoring exposure to metal compounds with carcinogenic properties.
Authors: A Léonard, A Bernard
Journal: Environmental Health Perspectives (1993)

Several metals such as arsenic, beryllium, chromium and nickel are carcinogenic to man when they occur in certain well-defined physicochemical forms. The carcinogenic potential of these metals is linked to their mutagenic properties. The determination of the metal or possibly of its metabolites in biological media and the cytogenetic examination of somatic cells are two methods that can currently be used to monitor exposure of populations at risk. Due to the use of inappropriate methodology, the value of the positive cytogenetic results published so far appears questionable. By contrast, the concentrations of metals in blood, urine, or other biological materials can be determined with accurate and precise methods. Although it does not permit a direct assessment of the carcinogenic risk, this approach is currently the most suitable for monitoring exposed populations.
THE CONSTRUCTION AND OPERATION OF EXPERIMENTAL ROOMS FOR THE STUDY OF AIR-BORNE INFECTION
Authors: O. H. Robertson, Theodore T. Puck, Henry Wise
Journal: The Journal of Experimental Medicine (1946)

This communication describes the construction and operation of two identical experimental rooms in which it is possible to produce and maintain a wide range of temperature and humidity with or without exchange of the room air. The ability to maintain a large air mass under constant conditions makes it possible to study the effects of different atmospheric states on air-suspended bacteria and viruses in relation to their survival, particle size, humidification, killing by lethal vapors, and host susceptibility. A brief description of the functioning of the rooms under experimental conditions is given.
Relationship between diabetes and mortality: a population study using record linkage.
Authors: C L Morgan, C J Currie, J R Peters
Journal: Diabetes Care (2000)

OBJECTIVE: To determine patterns and causes of mortality for patients with diabetes in a district health authority RESEARCH DESIGN AND METHODS: The study used cross-sectional record linkage, combining an electronic death register with a diabetic patient register constructed from a variety of routine health data sources collected from 1991 to 1997. The study was conducted in Cardiff and the Vale of Glamorgan, Wales, U.K., and included all diabetic deaths between 1993 and 1996. RESULTS: Of 1,694 deaths in patients with known diabetes, only 674 (39.8%) had diabetes recorded as an immediate or antecedent cause of death. Mortality rates were 41.8 per 1,000 for the diabetic population and 10.1 per 1,000 for the nondiabetic population. The standard mean ratio for the diabetic population was 1.24 (95% CI 1.12-1.35), with the risk of mortality relative to the nondiabetic population decreasing with age. Males with diabetes lost an average of 7.0 years from the year of diagnosis, and females with diabetes lost an average of 7.5 years. The most common cause of death was cardiovascular disease, which accounted for 49.1% of deaths in the diabetic population. CONCLUSIONS: Diabetes is recorded as a cause of death on a minority of death certificates for patients with diabetes. Using death certificates in isolation, therefore, is a poor method of estimating diabetic mortality, but results can be improved with the use of record linkage techniques. Patients with diabetes have an excess risk of mortality compared with the nondiabetic population. Life-years lost for patients with diabetes is strongly related to age at diagnosis and is a means of expressing mortality without relying on accurate prevalence data.
The Quantitative Practice of Anesthesia: Use of Closed Circuit
Authors: Ronald M. Meyer
Journal: JAMA (1981)

A large proportion of anesthetics in this country are administered using a "semiclosed" gas delivery system. This technique presents an excess of drug to the lungs to achieve easily predictable alveolar (thus arterial, thus cerebral) anesthetic concentrations. It is analogous to running a rapid dopamine infusion with three fourths of the solution leaking out of a poorly connected intravenous tubing before entering the patient. Not only is the semiclosed system wasteful, but the absence of knowledge of total dose of drug given makes informed analysis of the response difficult. The act of sealing the anesthetic system (closing the circuit) has many advantages, the greatest being the skill and comprehension required to maintain safe anesthesia under this condition. The authors of this book derive rules for closed-circuit anesthesia from basic physiology and pharmacology. Physical-chemical properties of anesthetics acquire new relevance. The authors emphasize practicality. Although they use differential calculus to present
The Contribution of Genetic and Epigenetic Changes in Granulosa Cell Tumors of Ovarian Origin
Authors: Varinderpal S. Dhillon, Mohammad Aslam, Syed Akhtar Husain
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Granulosa cell tumors (GCTs) are relatively rare and are subtypes of the sex-cord stromal neoplasms. A better understanding of the molecular genetics underlying various steps in malignant transformation is critical to success in the battle against this disease. Changes in the status of methylation, known as epigenetic alterations, are one of the most common molecular alterations in human cancers, including GCTs. Chromosomal instability and microsatellite instability (MSI) are common in these GCTs. We tested the hypothesis that C→T transition polymorphism in the promoter region of cytosine DNA-methyltransferase-3B (DNMT3B) and its altered expression are also associated with hypermethylation of the genes. We also attempted to determine the relationship between MSI of ovarian carcinoma and hMLH1 hypermethylation in these tumors. Experimental Design: We studied chromosome instability in 25 GCTs by detecting gross chromosome rearrangements in cultured peripheral blood lymphocytes. MSI was assessed using six microsatellite markers (BAT25, BAT26, D2S123, D5S346, D11S1318, and D17S250). Using sensitive methylation-specific PCR, we searched for aberrant promoter hypermethylation in a panel of genes including p16, BRCA1, RASSF1A, ER-α, TMS1, TIMP3, Twist, GSTP1, AR, and hMLH1. Polymorphism in the DNMT3B gene was assessed by the PCR-RFLP method, and DNMT3B expression was studied by reverse transcription-PCR assay. Results: Chromosome instability was indicated by significantly higher frequencies of chromosome aberrations (6.24%; P &amp;lt; 0.001) compared with controls (2.12%). The most frequently observed changes include trisomy 14 and monosomy 22. MSI has been found in 19 of 25 tumors, and loss of heterozygosity has been found in 9 of 25 tumors. Frequencies of methylation in GCTs were 40% for p16 and ER-α; 36% for BRCA1 and RASSF1A; 28% for hMLH1; 24% for TIMP3, Twist, and GSTP1; and 20% in TMS1 and AR. TT genotype was found only in two cases; the remainder were either CC or CT type. There was no significant alteration in the expression of DNMT3B in these patients. Conclusions: Coexistence of chromosome instability, MSI, and hypermethylation suggests that both genetic and epigenetic mechanisms may act in concert to inactivate the above-mentioned genes in these GCTs. These mechanisms can be an early event in the pathogenesis of these tumors, and it can be a critical step in the tumorigenic process. All these events might play an important role in early clinical diagnosis and in chemotherapeutic management and treatment of the disease. Larger studies may lend further understanding to the etiology and clinical behavior of these tumors.
Vitamin A supplementation in children and hearing loss
Authors: F. T. Wieringa, M. A. Dijkhuizen, J. Berger
Journal: BMJ (2012)

<h3>Abstract</h3> Oxidative stress and neuroinflammation play a central role in Alzheimer’s Disease (AD) pathogenesis. However, the mechanism by which these processes lead to neurodegeneration is still not fully understood. Thioredoxin-1 (Trx1) is an antioxidant protein that can be cleaved into a peptide known as Thioredoxin-80 (Trx80), which modulates monocyte function in the periphery and shows anti-amyloidogenic properties in the brain. In this study we aimed to further clarify the biological function of this peptide and its regulation in the brain. We show that neurons are the main producers of Trx80 in the brain. Trx80 levels increase in vivo both in normal aging and in young APP<i><sup>NL-G-F</sup></i> mouse model of amyloid pathology. Trx80 levels were increased in neurons in primary culture treated with either rotenone or 27-hydroxycholesterol, what suggests that Trx80 production is stimulated upon oxidative stress. RNA-sequencing followed by differential gene expression analysis revealed that Trx80 induces microglia activation into a phenotype compatible with interferon response microglia. Finally, we determine that the induction of this microglia phenotype by Trx80 is Trem2-dependent. This study identifies Trx80 as a novel neuron-derived signaling mechanism that modulates microglia function under stress conditions. Strategies to regulate Trx80 levels could be beneficial against AD pathology.
ELEVATED SOLUBLE LECTIN-LIKE OXIDIZED LDL RECEPTOR-1 (LOX-1) IN CORONARY CIRCULATION OF PATIENTS WITH ACUTE CORONARY SYNDROME
Authors: Hiroyuki Kunii, Yasuto Hoshino, Tomofumi Misaka, Hiroyuki Mizukami, Nobuo Sakamoto, Koichi Sugimoto, Kazuhiko Nakazato, Yoshiko Fujita, Tetsuya Sawamura, Toshiyuki Ishibashi, Yasuchika Takeishi
Journal: Journal of the American College of Cardiology (2010)
THE RELATION OF LEUKOSIS TO SARCOMA OF CHICKENS
Authors: E. L. Stubbs, J. Furth
Journal: The Journal of Experimental Medicine (1935)

A transmissible strain of sarcoma (Strain 13) is described that took its origin in a chicken inoculated with leukosis of Strain 1. The virus of Strain 13 produces sarcoma in the breast muscle injected with it and after intravenous inoculation it produces diffuse sarcomatosis of the spleen, bone marrow, and several other organs. The available evidence suggests that Strain 13 is caused by a single virus with ability to produce diffuse endothelial growth in the blood-forming organs associated with extensive hematomata, and erythroblastic proliferation. The strain can be readily transmitted by material free from live cells and preserved by drying. As small amounts of blood as 0.00001 cc. from chickens with sarcomatosis of the internal organs transmit Strain 13 by the intravenous route. By implantation sarcoma of Strain 13 can be transferred to chickens that are resistant to repeated inoculations with leukotic viruses.
Macropinocytosis of Polyplexes and Recycling of Plasmid via the Clathrin-Dependent Pathway Impair the Transfection Efficiency of Human Hepatocarcinoma Cells
Authors: Christine Gonçalves, Eric Mennesson, Renate Fuchs, Jean-Pierre Gorvel, Patrick Midoux, Chantal Pichon
Journal: Molecular Therapy (2004)

Knowledge of the entry mechanism and intracellular routing of polyplexes is of major importance for designing efficient gene delivery systems. We therefore investigated the internalization and trafficking of polyplexes in HepG2 cells. pDNA encoding the luciferase was complexed with histidylated polylysine (His-pLK), a polymer that requires acidic pH for pDNA endosomal release. Fluoresceinylated polyplexes (F-His-pLK or F-pDNA) were internalized by clathrin-dependent and -independent pathways. The latter most likely occurred by macropinocytosis since it was stimulated by phorbol myristate and blocked by dimethylamiloride. Intracellular routing of the plasmid was analyzed by confocal microscopy and flow cytometry. These data revealed that: (i) one part of the plasmid was present in vesicles that were not labeled with any known organelle-specific marker, (ii) the other part was in transferrin receptor-positive vesicles, and (iii) the plasmid was not transferred to late endosomes/lysosomes. Using luciferase activity as a readout for gene expression, we found that it was strongly reduced when macropinocytosis was stimulated, whereas macropinocytosis inhibitors had no effect. However, blocking clathrin-dependent internalization by chlorpromazine completely prevented gene expression. These findings demonstrate that: (i) macropinocytosis of polyplexes and (ii) plasmid recycling impair the transfection efficiency and (iii) clathrin-dependent endocytosis is the most productive route for transfection of HepG2 cells.
Acquired Immunodeficiency Syndrome with<i>Pneumocystis carinii</i>Pneumonia and<i>Mycobacterium avium-intracellulare</i>Infection in a Previously Healthy Patient with Classic Hemophilia
Authors: MAN-CHIU POON
Journal: Annals of Internal Medicine (1983)

A previously healthy patient with classic hemophilia who was on a home infusion program with factor VIII concentrates developed an acquired immunodeficiency syndrome manifested by a dramatic weight loss (47 kg over 12 months), lassitude, transient thrombocytopenia, and opportunistic infections with Varicella zoster, Pneumocystis carinii, and Mycobacterium avium-intracellulare. The patient was not homosexual and had no history of intravenous drug abuse. Immunologic studies showed a persistent lymphopenia with reversal of helper/ suppressor-cytotoxic T-lymphocyte ratios, depression of human natural killer cell function, and in-vitro lymphocyte proliferative responses to mitogens and viral antigens. Serum IgA levels were also elevated. Serum antibodies against cytomegalovirus, herpes simplex viruses 1 and 2, Epstein-Barr virus, Varicella zoster, and hepatitis B virus were shown, suggesting previous infection by these agents. Reactivation of cytomegalovirus infection was suggested by a rising titer of antibodies against cytomegalovirus concurrent with Pneumocystis pneumonia, and was confirmed by the growth of this virus in a throat culture 2 months later.
Causes of Impotence
Authors: IBE O. IBE
Journal: JAMA (1983)

<h3>To the Editor.—</h3> The report by Slag et al (1983;249:1736) entitled "Impotence in Medical Clinic Outpatients" indicated that 14% of the patient study group had impotence of psychogenic origin. Final diagnosis for each of the patients was made at the conclusion of history taking, physical examination, and elaborate endocrine laboratory studies. Those with psychogenic impotence were said to have normal physical examination and normal endocrine study findings. The rest of the patients were classified into their diagnostic categories based on drug history and abnormal laboratory test results and physical findings. The most frequent cause of impotence was drug effects. Medication effect was prominent in those with hypertension. Some antihypertensive medications such as methyldopa, β-blockers, and reserpine could cause depression. Impotence per se, whatever its cause, is anxiety provoking for many. Both depression and anxiety have profound effects on sexual performance. The impression one gets from reading the study is that
Results of the IDEAL trial: “Mirror, mirror on the wall … Which's the fairest peg-interferon of them all?”
Authors: Julian Schulze zur Wiesch, Ansgar W. Lohse
Journal: Hepatology (2009)

Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared. Methods: At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 μg per kilogram of body weight per week or a low dose of 1.0 μg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 μg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa- 2b regimen and the peginterferon alfa-2a regimen. Results: Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P = 0.20 for standard dose vs. low-dose peginterferon alfa-2b; P = 0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], −2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and −1.1% (95% CI, −5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for low dose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa-2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively. Conclusions: In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferon-ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials. gov number, NCT00081770.)
Transforming growth factor beta 2 in labial salivary glands in Sjogren's syndrome.
Authors: H Koski, Y T Konttinen, X H Gu, J Hietanen, M Malmstrom
Journal: Annals of the Rheumatic Diseases (1995)

OBJECTIVE--To compare the distribution and the amount of transforming growth factor beta (TGF beta) in labial salivary glands (LSG) in patients with Sjögren9s syndrome (SS) and healthy controls. METHODS--LSG from SS patients (n = 10) and healthy controls (n = 6) were labelled with peroxidase-antiperoxidase staining for TGF beta 2, which was quantitated in image analysis using Video Interactive Display System software. RESULTS--In all LSGs in SS and healthy controls, TGF beta 2 was found in endothelial cells of the capillaries and in the capsular and stromal fibroblasts. In LSGs in SS, TGF beta 2 was also found in some lymphocytes in the inflammatory cell foci and in fibroblasts in fibrotic areas. The TGF beta 2 staining index (microns 2/mm2 tissue) was greater in SS than in control LSGs (3670 (SEM 430) v 2061 (176); p &lt; 0.01), with no difference between the primary and secondary forms of SS (p &gt; 0.05). CONCLUSION--The localisation and the level of expression of TGF beta 2 indicate its involvement in local tissue fibrosis, and may reflect attempts at immunosuppression.
A Cross-Sectional Study of Exercise Performance During the First 2 Decades of Life After the Fontan Operation
Authors: Stephen M. Paridon, Paul D. Mitchell, Steven D. Colan, Richard V. Williams, Andrew Blaufox, Jennifer S. Li, Renee Margossian, Seema Mital, Jennifer Russell, Jonathan Rhodes
Journal: Journal of the American College of Cardiology (2008)
Alterations of human placental epidermal growth factor receptor in intrauterine growth retardation.
Authors: C Fondacci, E Alsat, R Gabriel, P Blot, C Nessmann, D Evain-Brion
Journal: Journal of Clinical Investigation (1994)

We studied human placental microvillous EGF receptor (EGFR) and its relationship with maternal and placental features in 14 cases of intrauterine growth retardation. Placental EGFR phosphorylation was significantly decreased or absent in 12 cases of small for gestational age neonates, as shown by SDS-PAGE, autoradiography, and scanning analysis. Specific [125I]EGF binding and Scatchard plots of the binding data showed a decreased number of EGFR in 6 of the 12 cases, with a mean maximal binding capacity of 1.09 +/- 0.32 pmol/mg for high affinity sites (mean control value = 2.30 +/- 0.23 pmol/mg). Most of the hypertensive women and smokers belonged to this subgroup. In three of the remaining six cases of small gestational age placentas with low EGFR phosphorylation, there was no maternal pathology or significant parenchymatous placental lesions. Five showed a 175-kD EGFR species when probed by [125I]EGF cross-linking and Western blotting with RK2 and C-Term, two polyclonal anti-EGFR antibodies, suggesting abnormal transduction of the EGF-induced signal. The sixth placenta yielded a single 145-kD EGFR band consistent with an abnormal EGFR structure; Western blot analysis showed no immunoreactive band. In conclusion, maternal and placental pathologies in intrauterine growth retardation are associated with various alterations of placental EGFR, pointing out the importance of EGFR ligands in the regulatory pathway of placental and fetal growth.
Differences between neurological and neurosurgical approaches in the management of malignant brain tumours.
Authors: S J Wroe, P M Foy, M D Shaw, I R Williams, D W Chadwick, C West, G Towns
Journal: BMJ (1986)

The management and outcome in 205 patients diagnosed as having cerebral gliomas over five years were reviewed. Patients referred to neurologists and neurosurgeons had similar clinical features and similar results on computed tomography. Patients referred to neurologists underwent burr hole biopsy less often and had better short term morbidity than patients referred to neurosurgeons, although final outcome was the same in both groups. Few patients underwent other surgical procedures. Referral for radiotherapy was usually by neurosurgeons, although this did not significantly affect long term survival. The implications for the management of patients with primary malignant brain tumours and the need for prospective studies are discussed.
Cystatin C, Albuminuria, and Mortality Among Older Adults With Diabetes
Authors: Ian H. de Boer, Ronit Katz, Jie J. Cao, Linda F. Fried, Bryan Kestenbaum, Ken Mukamal, Dena E. Rifkin, Mark J. Sarnak, Michael G. Shlipak, David S. Siscovick
Journal: Diabetes Care (2009)

Albuminuria and impaired glomerular filtration rate (GFR) are each associated with poor health outcomes among individuals with diabetes. Joint associations of albuminuria and impaired GFR with mortality have not been comprehensively evaluated in this population.This is a cohort study among Cardiovascular Health Study participants with diabetes, mean age 78 years. GFR was estimated using serum cystatin C and serum creatinine. Albumin-to-creatinine ratio (ACR) was measured in single-voided urine samples.Of 691 participants, 378 died over 10 years of follow-up. Cystatin C-estimated GFR <60 ml/min per 1.73 m(2), creatinine-based estimated GFR <60 ml/min per 1.73 m(2), and urine ACR > or =30 mg/g were each associated with increased mortality risk with hazard ratios of 1.73 (95% CI 1.37-2.18), 1.54 (1.21-1.97), and 1.73 (1.39-2.17), respectively, adjusting for age, sex, race, diabetes duration, hypoglycemic medications, hypertension, BMI, smoking, cholesterol, lipid-lowering medications, prevalent cardiovascular disease (CVD), and prevalent heart failure. Cystatin C-estimated GFR and urine ACR were additive in terms of mortality risk. Cystatin C-estimated GFR predicted mortality more strongly than creatinine-based estimated GFR.Albuminuria and impaired GFR were independent, additive risk factors for mortality among older adults with diabetes. These findings support current recommendations to regularly assess both albuminuria and GFR in the clinical care of patients with diabetes; a focus on interventions to prevent or treat CVD in the presence of albuminuria, impaired GFR, or both; and further consideration of cystatin C use in clinical care.