tbuckley/cabot-search huggingface dataset:
Relevance of particle-induced rat lung tumors for assessing lung carcinogenic hazard and human lung cancer risk.
Authors: J L Mauderly
Journal: Environmental Health Perspectives (1997)

Rats and other rodents are exposed by inhalation to identify agents that might present hazards for lung cancer in humans exposed by inhalation. In some cases, the results are used in attempts to develop quantitative estimates of human lung cancer risk. This report reviews evidence for the usefulness of the rat for evaluation of lung cancer hazards from inhaled particles. With the exception of nickel sulfate, particulate agents thought to be human lung carcinogens cause lung tumors in rats exposed by inhalation. The rat is more sensitive to carcinogenesis from nonfibrous particles than mice or Syrian hamsters, which have both produced false negatives. However, rats differ from mice and nonhuman primates in both the pattern of particle retention in the lung and alveolar epithelial hyperplastic responses to chronic particle exposure. Present evidence warrants caution in extrapolation from the lung tumor response of rats to inhaled particles to human lung cancer hazard, and there is considerable uncertainty in estimating unit risks for humans from rat data. It seems appropriate to continue using rats in inhalation carcinogenesis assays of inhaled particles, but the upper limit of exposure concentrations must be set carefully to avoid false-positive results. A positive finding in both rats and mice would give greater confidence that an agent presents a carcinogenic hazard to man, and both rats and mice should be used if the agent is a gas or vapor. There is little justification for including Syrian hamsters in assays of the intrapulmonary carcinogenicity of inhaled agents.
Selective inhibition of human diploid fibroblast collagen synthesis by interferons.
Authors: S A Jimenez, B Freundlich, J Rosenbloom
Journal: Journal of Clinical Investigation (1984)

The effects of alpha- and gamma-interferons (IFNs) on collagen production by confluent human diploid fibroblasts in culture were examined. It was found that partially purified alpha-IFNs and affinity purified gamma-IFNs caused greater than 50% inhibition of collagen synthesis by these cells independently of their effect on cell proliferation. Recombinant alpha-IFNs showed a similar effect (38.8% inhibition), indicating that collagen synthesis inhibition was a constitutive property of IFNs. Collagen synthesis inhibition by IFNs was concentration dependent. Gel filtration chromatography of the newly synthesized proteins from the media of fibroblasts incubated with partially purified alpha-IFNs demonstrated a selective depression of molecules eluting in the region of procollagen. No detectable increase in collagen degradation products or underhydroxylation of procollagen was observed. Short-term kinetic studies further demonstrated that the major effect of IFNs was due to a net decrease in fibroblast collagen production rather than to impairment of secretion or increased extracellular degradation of the newly synthesized molecules. These results indicate that alpha- and gamma-IFNs are potent inhibitors of human fibroblast collagen production and suggest that they may play an important role in the regulation of normal and pathologic fibrogenesis.
Induction of Rapid T Cell Activation and Tolerance by Systemic Presentation of an Orally Administered Antigen
Authors: Ines Gütgemann, Aude M Fahrer, John D Altman, Mark M Davis, Yueh-hsiu Chien
Journal: Immunity (1998)

To understand how orally introduced antigen regulates peripheral immune responses, we fed cytochrome c protein to mice transgenic for the beta chain of a cytochrome c-specific TCR and followed the antigen-specific T cell responses with a cyt c/I-Ek tetramer staining reagent. We find that within 6 hr of cytochrome c administration, antigen-specific systemic T cell activation is induced, and spleen cells gain the ability to stimulate cytochrome c-specific T cell responses. Feeding multiple low doses of cytochrome c down-regulates the systemic immune response, which can be correlated with a reduction of antigen-specific T cells and not with immune deviation. These results suggest that systemic distribution of antigen contributes significantly to oral tolerance induction.
Medicine as a Social Instrument: Tropical Medicine
Authors: Wilbur A. Sawyer
Journal: New England Journal of Medicine (1951)

BEFORE undertaking to evaluate the progress that has been made in tropical medicine during the first half of the twentieth century, one should explore the content of this commonly accepted field of medicine. A simple definition based on climate or geography would give a false idea of the concept of tropical medicine as it has been built up in text-books, graduate schools and professional parlance to include the study, prevention and treatment of a wide range of diseases found within the tropics and to a large extent outside. What, then, are the criteria that today determine the inclusion of diseases . . .
Antinuclear antibodies in the relatives and spouses of patients with systemic sclerosis.
Authors: P J Maddison, R P Skinner, R S Pereira, C M Black, B M Ansell, M I Jayson, N R Rowell, K I Welsh
Journal: Annals of the Rheumatic Diseases (1986)

The families of 65 patients with systemic sclerosis were examined clinically and serum samples from each subject were tested for antinuclear antibodies (ANA) by immunofluorescence on HEp2 cells and for precipitating antibodies to soluble cellular antigens including Scl-70. Of 217 blood relatives, 58 (27%) had ANA (42 speckled, 13 nucleolar, one centromere, two homogeneous); 22 (10%) had precipitins, one anti-Scl-70, one anti-PM-Scl, one anti-nRNP, two anti-Ro(SSA), the remainder unidentified). Family members tended to share ANA patterns. Of 38 spouses, nine (24%) had ANA (all speckled) and two showed unidentified precipitins. This compares with an incidence of ANA and precipitins in a control population of 8% and 1% respectively. Antibodies were more common in female than male relatives (particularly in mothers and sisters of probands). Twenty one of the 58 family members with ANA had clinical features of connective tissue disease; the remainder were asymptomatic. The presence of genetic factors influencing autoimmunity is suggested by the incidence of autoantibodies in first degree relatives. Similar observations in spouses, however, indicate that environmental factors may also have a role in these immune abnormalities.
Rapsyn Interaction with Calpain Stabilizes AChR Clusters at the Neuromuscular Junction
Authors: Fei Chen, Lei Qian, Zhi-Hua Yang, Ying Huang, Shyuan T. Ngo, Nan-Jie Ruan, Jia Wang, Claudio Schneider, Peter G. Noakes, Yu-Qiang Ding, Lin Mei, Zhen-Ge Luo
Journal: Neuron (2007)
Poor prescribing is continual
Authors: Jeffrey K Aronson, David B Barnett, Robin E Ferner, Albert Ferro, Graeme Henderson, Simon R Maxwell, Michael D Rawlins, David J Webb
Journal: BMJ (2006)

EDITOR—An editorial should bring an important topic to readers' attention and engage their interest, provoke a reaction, and trigger debate. We are delighted that the recent editorial on poor prescribing in the United Kingdom seems to have done all of these things.1

We did not give a thorough account of all the evidence, but we are surprised that Rubin thinks that we provided no evidence at all.2 We cited …
Transgastric peritoneoscopy and appendectomy: thoughts on our first experience in humans
Authors: P. Park, M. Bergström
Journal: Endoscopy (2010)

We present a series of three patients operated on by means of natural-orifice transgastric peritoneoscopy, including one appendectomy. A standard double-lumen gastroscope was used together with standard endoscopic tools. In all patients abdominal access through the gastric wall was smooth using a needle-knife/guide-wire/balloon technique. The whole abdominal cavity could be visualized and the appendix was found in two patients. In one patient the procedure was converted to laparoscopic appendectomy and in one to open surgery. In the third patient transgastric appendectomy was performed. The gastric access site was closed with the T-tag technique. Patients were allowed to drink and eat as soon as they woke up. Postoperatively patients were followed clinically and with standard laboratory tests daily until discharged. One patient (converted to open surgery) had a serious complication (pneumothorax). The transgastric approach to the abdominal cavity was shown to be feasible, but significant technical problems remain to be resolved.
Synthesis of the minor fetal hemoglobin F<sub>ic</sub> in colonies of erythropoietic precursors isolated from human umbilical cord blood
Authors: E. C. Abraham, A. L. Reese, M. Stallings, A. Abraham, G. J. Garbutt, T. H. J. Huisman
Journal: American Journal of Hematology (1982)

Abstract The biosynthesis of the minor hemoglobin F Ic , which contains acetylated γ chains, and the major hemoglobin F o was studied during erythroid cell differentiation and maturation in cultures of erythroid precursors isolated from five human umbilical cord blood samples. A gradual decrease in the synthesis of Hb F Ic was observed during the maturation of the erythroid cells when cultured from 7 to 15 days. The synthesis of Hb F o did not show a consistent change; however, the relative synthesis of Hb F Ic was the highest in the 7‐day‐old colonies and decreased at day 15 to levels observed in the reticulocytes. The addition of sodium butyrate, which is known to promote histone acetylation, significantly increased the synthesis of Hb F Ic in 7‐day‐old colonies.
Comparative Transcriptomics of Convergent Evolution: Different Genes but Conserved Pathways Underlie Caste Phenotypes across Lineages of Eusocial Insects
Authors: Ali J. Berens, James H. Hunt, Amy L. Toth
Journal: Molecular Biology and Evolution (2014)

An area of great interest in evolutionary genomics is whether convergently evolved traits are the result of convergent molecular mechanisms. The presence of queen and worker castes in insect societies is a spectacular example of convergent evolution and phenotypic plasticity. Multiple insect lineages have evolved environmentally induced alternative castes. Given multiple origins of eusociality in Hymenoptera (bees, ants, and wasps), it has been proposed that insect castes evolved from common genetic "toolkits" consisting of deeply conserved genes. Here, we combine data from previously published studies on fire ants and honey bees with new data for Polistes metricus paper wasps to assess the toolkit idea by presenting the first comparative transcriptome-wide analysis of caste determination among three major hymenopteran social lineages. Overall, we found few shared caste differentially expressed transcripts across the three social lineages. However, there is substantially more overlap at the levels of pathways and biological functions. Thus, there are shared elements but not on the level of specific genes. Instead, the toolkit appears to be relatively "loose," that is, different lineages show convergent molecular evolution involving similar metabolic pathways and molecular functions but not the exact same genes. Additionally, our paper wasp data do not support a complementary hypothesis that "novel" taxonomically restricted genes are related to caste differences.
Bowel cancer treatment gets better, report says
Authors: Toby Reynolds
Journal: BMJ (2006)

The treatment of bowel cancer has improved in the United Kingdom in the past five years, with the quality of surgery and histopathology rising, an audit has shown. 

The report of the National Bowel Cancer Audit Project aims to encourage the collection of more data to improve standards and better inform patients. The report was produced for the Healthcare Commission. 

The report says that the proportion of hospital trusts meeting the National Institute for Health and Clinical Excellence (NICE) guideline target of examining a median of 12 lymph nodes after surgery has risen to 50% in 2005 …
Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden
Authors: K. G Nicholson, J. Kent, V. Hammersley, E. Cancio
Journal: BMJ (1997)

To evaluate the disease burden of upper respiratory infections in elderly people living at home.Prospective surveillance of elderly people.None.Leicestershire, England533 subjects 60 to 90 years of age.Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death.231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001). The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections. Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus.Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.
A CDD Polymorphism as Predictor of Capecitabine-Induced Hand–Foot Syndrome—Letter
Authors: Joseph Ciccolini, Alexandre Evrard, Bruno Lacarelle
Journal: Clinical Cancer Research (2012)

In their recently published clinical study (1), Caronia and colleagues investigated various polymorphisms affecting 5 key enzymes implicated in the pharmacogenetics of the widely prescribed drug capecitabine as putative markers for treatment-related toxicities. They conclude, from this candidate-gene approach, that severe hand–foot syndrome (HFS) could be attributed to the deleted allele of rs3215400 across the cytidine deaminase (CDD) promoter.Because this deleted allele was associated with increased CDD gene expression and enhanced transcription, extensive CDD phenotype could also explain the higher incidence of capecitabine-induced HFS, although surprisingly, no data on its impact on other toxicities (e.g., hematologic) were made available. At our institute, we have found evidence of lethal toxicity from capecitabine intake, which occurred in a woman with an extensive CDD phenotype (2), thus showing that CDD deregulation could indeed be associated with life-threatening toxicities in capecitabine-treated patients. As outlined by Caronia and colleagues, genotype-to-phenotype relationships with CDD are, however, far from being clear, and the relevance of the 79 A>C polymorphism for anticipating severe toxicities from gemcitabine treatment remains in question (3). Such debate is not surprising, given the numerous events that interfere with establishment of genotype-to-phenotype relationships, as many polymorphisms have yet to be discovered; also, CDD epigenetics are far from being elucidated (3). Concerning the relevance of the rs3215400 genetic variation, similar conflicting results are available in light of a previous study that failed to find an association between this very polymorphism and HFS (4). Caronia and colleagues provide in silico evidence that the C deletion abolishes a binding site for the transcriptional regulator E2F, leading to enhanced CDD transcription in vitro. However, according to dbSNP, the allelic frequency of this variant is surprisingly high (0.564 vs. 0.436 for the C allele) and does not match the frequency of the extensive phenotype recorded in our own patients (3). Consequently, and because no single-nucleotide polymorphism entirely accounts for the variability in CDD activity among patients, haplotype analysis might be a more powerful way to predict CDD transcription, as suggested by other studies (5).In conclusion, we believe that, along with dihydropyrimidine dehydrogenase (DPYD) impairment, screening for CDD polymorphisms, including rs3215400, is probably of interest as a means to identify patients at risk of developing HFS upon capecitabine intake. However, in light of our own expertise, we consider that a functional approach (e.g., phenotyping patients) is another mandatory step to fully address the issue of CDD status determination and its actual impact on capecitabine-related severe toxicities.No potential conflicts of interest were disclosed.
Case-control analysis of bone resorption markers, disability, and hip fracture risk: the Rotterdam study
Authors: P. L A van Daele, M. J Seibel, H. Burger, A. Hofman, D. E Grobbee, J. P T M van Leeuwen, J. C Birkenhager, H. A P Pols
Journal: BMJ (1996)

Several factors besides bone mineral mass have been related to the risk of hip fracture. Bone quality, the rate of bone loss, and non-skeletal factors have been identified as important.1 2 High rates of bone resorption may be associated with disruption of the trabecular network as well as with an increased rate of bone loss. Furthermore, immobility associated with disability induces bone resorption not followed by increased bone formation.3

Urinary pyridinium crosslinks are markers of bone resorption. We investigated whether these were associated with the risk of hip fracture and also whether such an association was attributable to disability.

This nested case-control analysis was conducted as part of the Rotterdam study, a prospective cohort study of the incidence of and risk factors for chronic disabling diseases.4 Briefly, all 10275 residents of a district of Rotterdam aged 55 or over were invited to participate. The study consisted of an initial home interview followed by a series …
Establishing tolerable dungeness crab (Cancer magister) and razor clam (Siliqua patula) domoic acid contaminant levels.
Authors: K Mariën
Journal: Environmental Health Perspectives (1996)

Domoic acid has been found in razor clams (Siliqua patula) and dungeness crabs (Cancer magister) in Washington State and elsewhere on the West Coast of the United States. Due to toxic effects associated with domoic acid exposure, an effort has been made to establish tolerable domoic acid levels in crabs and clams obtained from commercial harvest and sale and from individual recreational harvesting. To accomplish this, the amount of clams and crabs consumed by populations of concern was determined, a tolerable daily intake (TDI) was developed for individuals most sensitive to effects of this compound, and the TDI was equated with consumption patterns to determine tolerable clam and crab domoic acid levels. Results indicate that the primary health effects associated with domoic acid toxicity can be averted in populations of concern and for others consuming crabs or clams less frequently (or in lesser quantity) if domoic acid contaminant concentration does not exceed 30 mg/kg in the hepatopancreas and viscera of dungeness crabs or 20 mg/kg in clams.
Effect of ethanol and high-fat feeding on hepatic ?-glutamylcysteine synthetase subunit expression in the rat
Authors: Shelly C. Lu, Zong-Zhi Huang, Jin May Yang, Hidekazu Tsukamoto
Journal: Hepatology (1999)

Glutathione (GSH) is important in antioxidant defense. A major determinant of the rate of GSH synthesis is the activity of the rate-limiting enzyme, γ-glutamylcysteine synthetase (GCS). A heavy (HS) and light subunit (LS) make up GCS; oxidative stress regulates both transcriptionally. Cis -acting elements important for the oxidative stress-induced transcriptional up-regulation of both subunits are antioxidant response element (ARE) and activator protein-1 (AP-1). Nuclear factor-κB (NF-κB) may also regulate the heavy subunit. Chronic ethanol ingestion causes oxidative stress, increases AP-1 expression, and depletes hepatic GSH. Data conflict regarding GSH synthesis and are lacking regarding GCS subunit gene expression. We examined the effect of chronic ethanol ingestion on ARE, AP-1, and NF-κB activity and GCS subunit expression. Male Wistar rats were fed an ethanol and high-fat (28.7% cal) diet intragastrically for 9 weeks. Liver GSH level fell by 40%, although GCS activity doubled. GCS-HS mRNA level doubled, whereas GCS-LS mRNA level remained unchanged. Electrophoretic mobility shift assay (EMSA) showed that binding to ARE, AP-1, and NF-κB probes all increased. In conclusion, chronic ethanol ingestion increased GCS-HS expression and GCS activity by activating cis -acting elements important for transcriptional up-regulation of GCS-HS. GCS-LS mRNA level remained unchanged despite activation of ARE and AP-1, suggesting that negative transcriptional factors may be involved or the mRNA may be unstable. Despite induction in GCS activity, GSH level fell because of alterations in the other factors important in determining the steady-state GSH level.
Releasing Pressure in Tumors: What Do We Know So Far and Where Do We Go from Here? A Review
Authors: Arlizan B. Ariffin, Patrick F. Forde, Saleem Jahangeer, Declan M. Soden, John Hinchion
Journal: Cancer Research (2014)

Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment. It causes heterogenous intratumoral distribution of drugs and macromolecules. It also causes the development of hypoxia within tumor bulk, leading to reduced efficacy of therapeutic drugs and radiotherapy. Tumor pressure has been associated with increased metastatic potential and poor prognosis in some tumors. The formation of increased pressure in solid tumors is multifactorial. Factors known to affect tumor pressure include hyperpermeable tortuous tumor vasculatures, the lack of functional intratumoral lymphatic vessels, abnormal tumor microenvironment, and the solid stress exerted by proliferating tumor cells. Reducing this pressure is known to enhance the uptake and homogenous distribution of many therapies. Pharmacologic and biologic agents have been shown to reduce tumor pressure. These include antiangiogenic therapy, vasodilatory agents, antilymphogenic therapy, and proteolytic enzymes. Physical manipulation has been shown to cause reduction in tumor pressure. These include irradiation, hyperbaric oxygen therapy, hyper- or hypothermic therapy, and photodynamic therapy. This review explores the methods to reduce tumor pressure that may open up new avenues in cancer treatment.
Increased blood glucose levels following intra-articular injection of methylprednisolone acetate in patients with controlled diabetes and symptomatic osteoarthritis of the knee
Authors: G S Habib, M Bashir, A Jabbour
Journal: Annals of the Rheumatic Diseases (2008)

The effect of oral or intravenous steroid treatment on glucose metabolism is well known.1 Intra-articular steroid injection (IASI) at the knee joint is a common procedure,2 however there are no studies on the effect of IASI on glucose metabolism. Patients with controlled diabetes (HgA1C<7), using modern versions of blood glucose monitoring devices, with knee pain due to osteoarthritis of the knee (OAK) for more than 3 months without sufficient response to non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy were offered an IASI of 50 mg of methylprednisolone acetate (MPA) (Pharmacia & Upjohn, Puurs, Belgium) at the knee joint. If they agreed, patients were asked to …