tbuckley/cabot-search huggingface dataset:
Translation of β-Globin m-RNA in β-Thalassemia and the S and C Hemoglobinopathies
Authors: Ronald F. Rieder
Journal: Journal of Clinical Investigation (1972)

Genetic and biochemical evidence indicates that in beta-thalassemia there is impaired synthesis of the beta-globin chains of hemoglobin A. In patients heterozygous for the hemoglobinopathies, hemoglobin S and hemoglobin C, the mutant beta-chain is produced in smaller amounts than normal beta(A). Defective m-RNA translation has been suggested as a possible cause of decreased beta-globin polypeptide synthesis in thalassemia and the hemoglobinopathies. In the present study, the ribosomal assembly of beta-globin chains was examined in the peripheral, nucleated red blood cells and reticulocytes of patients with Cooley's anemia, thalassemia intermedia, sickle thalassemia, sickle cell anemia, hemoglobin C disease, and in hemolytic anemias not associated with a hemoglobinopathy. The translation times of beta(A), beta(S), and beta(C) did not differ significantly (average times; beta(A) = 75 sec, range 43-114, beta(S) = 69 sec, beta(C) = 92 sec). In thalassemia, no evidence was found for a delay in translation as the cause of the marked impairment of beta-globin synthesis. In several specimens of peripheral blood from thalassemic patients, the translation time of the beta-chain was even shorter than in nonthalassemic specimens (average time = 45 sec, range 35-59). The results suggest that the defect in beta-globin synthesis in beta-thalassemia is due to impaired initiation of beta-globin chain assembly or a quantitative deficiency in m-RNA.
"IMMUNOLOGIC OBSERVATIONS IN AUTUMNAL HAY-FEVER"
Authors: William Scheppegrell
Journal: JAMA (1924)

<h3>To the Editor:</h3> —In his paper on immunologic observations in autumnal hay-fever (The Journal, May 3), Dr. Harry S. Bernton discusses the Scheppegrell four-group classification of hay-fever pollens as published in the<i>Boston Medical and Surgical Journal</i>, July 12, 1917. This, however, has since been revised, the new classification of three major and five minor groups having been published in the<i>New York Medical Journal and Record</i>, June 20, 1923. In this report, the following statement is made: "While the grouping of hay-fever pollens from a biologic"—and botanic; the ragweeds and artemisias, for instance, both belong to the<i>Compositae</i>family, but are divided into separate groups— "viewpoint has proved of great advantage in simplifying the diagnostic tests and treatment of hay-fever, our experience has demonstrated that the most common member in the patient's vicinity, of the group to which he reacts, should be selected for his immunization." Regarding the ragweed
Projecting Cancer Incidence and Deaths to 2030: The Unexpected Burden of Thyroid, Liver, and Pancreas Cancers in the United States
Authors: Lola Rahib, Benjamin D. Smith, Rhonda Aizenberg, Allison B. Rosenzweig, Julie M. Fleshman, Lynn M. Matrisian
Journal: Cancer Research (2014)

Cancer incidence and deaths in the United States were projected for the most common cancer types for the years 2020 and 2030 based on changing demographics and the average annual percentage changes in incidence and death rates. Breast, prostate, and lung cancers will remain the top cancer diagnoses throughout this time, but thyroid cancer will replace colorectal cancer as the fourth leading cancer diagnosis by 2030, and melanoma and uterine cancer will become the fifth and sixth most common cancers, respectively. Lung cancer is projected to remain the top cancer killer throughout this time period. However, pancreas and liver cancers are projected to surpass breast, prostate, and colorectal cancers to become the second and third leading causes of cancer-related death by 2030, respectively. Advances in screening, prevention, and treatment can change cancer incidence and/or death rates, but it will require a concerted effort by the research and healthcare communities now to effect a substantial change for the future.
The Clinical Significance of Fusion Oncogenes in Cancer
Authors: T.H. Rabbitts
Journal: New England Journal of Medicine (1998)

The study of chromosomal translocations in tumors has revealed much about the molecular biology of cancer.1 The report by Kawai et al.2 in this issue of the Journal highlights an important question: how useful to patient care are discoveries in the molecular biology of cancer? It also poses the longer-term question of how realistic it is to attempt to use this information to design effective therapies. Chromosomal translocations have been particularly well studied in hematopoietic tumors, which can easily be prepared for detailed cytogenetic studies.1 Other types of tumors have also been studied, but with respect to solid tumors, consistent . . .
Quality of Life and Symptom Burden among Long-Term Lung Cancer Survivors
Authors: Ping Yang, Andrea L. Cheville, Jason A. Wampfler, Yolanda I. Garces, Aminah Jatoi, Matthew M. Clark, Stephen D. Cassivi, David E. Midthun, Randolph S. Marks, Marie-Christine Aubry, Scott H. Okuno, Brent A. Williams, Francis C. Nichols, Victor F. Trastek, Hiroshi Sugimura, Linda Sarna, Mark S. Allen, Claude Deschamps, Jeff A. Sloan
Journal: Journal of Thoracic Oncology (2011)
Hyperglycemia inhibits endothelial nitric oxide synthase activity by posttranslational modification at the Akt site
Authors: X L Du, D Edelstein, S Dimmeler, Q Ju, C Sui, M Brownlee
Journal: Journal of Clinical Investigation (2001)

Endothelial nitric oxide synthase (eNOS) is activated by phosphorylation of serine 1177 by the protein kinase Akt/PKB. Since hyperglycemia-induced mitochondrial superoxide overproduction increases O-linked N-acetylglucosamine modification and decreases O-linked phosphorylation of the transcription factor Sp1, the effect of hyperglycemia and the hexosamine pathway on eNOS was evaluated. In bovine aortic endothelial cells, hyperglycemia inhibited eNOS activity 67%, and treatment with glucosamine had a similar effect. Hyperglycemia-associated inhibition of eNOS was accompanied by a twofold increase in O-linked N-acetylglucosamine modification of eNOS and a reciprocal decrease in O-linked serine phosphorylation at residue 1177. Both the inhibition of eNOS and the changes in its post-translational modifications were reversed by antisense inhibition of glutamine:fructose-6-phosphate amidotransferase, the rate-limiting enzyme of the hexosamine pathway, or by blocking mitochondrial superoxide overproduction with uncoupling protein-1 (UCP-1) or manganese superoxide dismutase (MnSOD). Immunoblot analysis of cells expressing myc-tagged wild-type human eNOS confirmed the reciprocal increase in O-linked N-acetylglucosamine and decrease in O-linked serine 1177 phosphorylation in response to hyperglycemia. In contrast, when myc-tagged human eNOS carried a mutation at the Akt phosphorylation site (Ser1177), O-linked N-acetylglucosamine modification was unchanged by hyperglycemia and phospho-eNOS was undetectable. Similar changes in eNOS activity and covalent modification were found in aortae from diabetic animals. Chronic impairment of eNOS activity by this mechanism may partly explain the accelerated atherosclerosis of diabetes.
Altered Expression of the Early Mitotic Checkpoint Protein, CHFR, in Breast Cancers: Implications for Tumor Suppression
Authors: Lisa M. Privette, Maria E. González, Lei Ding, Celina G. Kleer, Elizabeth M. Petty
Journal: Cancer Research (2007)

Checkpoint with FHA and Ring Finger (CHFR) is hypothesized to mediate a delay in cell cycle progression early in mitosis in response to microtubule stress, independent of the spindle assembly checkpoint. As a potential regulator of cell cycle progression, CHFR naturally becomes an interesting target for understanding cancer cells. In recent years, there has been increasing evidence supporting the role of CHFR as a tumor suppressor, most of which report loss of expression, occasionally due to promoter hypermethylation, in cancers compared with patient-matched normal tissues. We studied both a panel of breast cancer cell lines as well as primary tissue samples from breast cancer patients to investigate CHFR as a relevant tumor suppressor in breast cancer and to determine whether CHFR expression was associated with clinical and pathologic variables. We report that 41% of cell lines and 36% of patient samples showed low or negative CHFR protein expression or staining. In addition, lack of CHFR detection was associated with increased tumor size and weakly correlated with estrogen receptor-negative tumors from patients. To study the effects of low CHFR expression in vitro, we stably expressed a short hairpin RNA construct targeting CHFR in two lines of immortalized human mammary epithelial cells. Notably, decreased CHFR expression resulted in the acquisition of many phenotypes associated with malignant progression, including accelerated growth rates, higher mitotic index, enhanced invasiveness, increased motility, greater aneuploidy, and amplified colony formation in soft agar, further supporting the role of CHFR as a tumor suppressor in breast cancer.
Abstract 5557: Steady DNA adduct accumulation by dibenzo[<i>a,l</i>]pyrene implants
Authors: Jeyaprakash Jeyabalan, Farrukh Aqil, Srivani Ravoori, Manicka V. Vadhanam, Ramesh C. Gupta
Journal: Cancer Research (2011)

Abstract The past and current trends in determining the DNA-damaging and carcinogenicity potential of environmental toxicants rely largely on treatment of rodents with single or multiple bolus doses. To simulate the human scenario where the exposure is generally continuous to low doses, we have developed polymeric implants embedded with carcinogens. When grafted subcutaneously, polymeric implants provide continuous (“24/7”) low dose exposure. In this study we report the effects of sustained low doses of a highly potent environmental carcinogen, dibenzo[a,l]pyrene (DBP) on DNA adduct accumulation. Different size DBP implants (10 – 20 mm long, 1.4 – 2.4 mm dia; 5% DBP load) were tested first in a pilot study using female A/J mice to optimize the implant surface area. Two 20-mm implants (1.4 mm dia), which produced maximal lung DNA adducts, were used subsequently. Groups of female A/J mice (n = 4 – 6) were grafted with sham or DBP implants. For comparison, animals were also treated in parallel with a bolus carcinogenic dose of DBP intraperitoneally (6 mg/kg) or vehicle alone. Animals from both the treatment groups were euthanized at different time intervals and selected tissues were collected. Analysis of the target (lung) DNA adducts by 32P-postlabeling showed qualitative identical adduct patterns by the two routes of administration; the sham treatments showed no detectable adducts. As expected, the bolus dose treatment resulted in higher DNA adducts (in adducts /109 nucleotides) (72 ± 18) compared with the implant group (33 ± 17) one week post-treatment. However, 3 weeks later, adduct levels in the implant group increased (54 ± 17) but a significant declined occurred in the i.p treatment group (19 ± 13). The adduct levels after 4 weeks in the implant group (66 ± 19) were somewhat higher than the 3 week group, suggesting that the adduct levels plateaued. The steady accumulation of DNA adducts was consistent with continuous release of DBP from the implant (about 10 µg/day based on in vitro release). The study is ongoing to determine if the low-dose continuous exposure which provides steady accumulation of DNA adducts in the target tissue will be tumorigenic. In summary, the steady-state adduct level reflect human exposure scenario and this approach will be ideal to determine both carcinogenicity and biological/pathological changes due to low-dose exposure as well as for screening potential chemopreventive agents. This exposure system has been used to determine efficacy of chemopreventive agents (accompanying abstracts by Aqil et al.; Gupta et al.) (Supported from CA-118114, KLCRP and Agnes Brown Duggan Endowment). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5557. doi:10.1158/1538-7445.AM2011-5557
Effects of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women
Authors: David J.A. Jenkins, Cyril W.C. Kendall, Philip W. Connelly, Chung-Ja C. Jackson, Tina Parker, Dorothea Faulkner, Edward Vidgen
Journal: Metabolism (2002)
PERSISTENT PAIN IN LESIONS OF THE PERIPHERAL AND CENTRAL NERVOUS SYSTEM
Authors: W. Harris
Journal: BMJ (1921)

PERSISTENT pain, wlhiclh miiay be defined as acute bodily discomfort, varying in degrec from a sensation of soreness or achling to one of intense and intolerable agony of torment, may be due to a variety of diseases affecting primarilv otlher structutns and tissues than the nervous system.Thjus carciniolmia naturally occurs to us, or other malignant growlth, as a probable cause of any deep-seated pain, persistent in clharacter, and lasting for weelks and months, more especially if accomnpanied by progressive emaciation.The appreciation of any sen1sationi of pain due to visceral or bone disease niecessarily involves the agenicy of tlle nervous systemn in the transferenice of the sensory impulses from periplhery to tllalamiius anid cerebral cortex, but I am linmitincg my remarlks as far as possib!e to diseases involving the nervous system itself, and slhall omit discussion of tlle referred pains of visceral disease, sucll as dental neuralgias, errors of refraction, angina, the colics, sinus suppuration, abscesses, acute inflammationis, and the like.For tlle sale of convenience I lhave in tlle followina classification arranged the causes of persistent pain in diseases of the nervous system in five classes progressing from peripliery to centre, or from nerve ending to cerebral cortex.
Right Versus Left Ventricular Failure
Authors: Mark K. Friedberg, Andrew N. Redington
Journal: Circulation (2014)

V entricular failure manifests in many forms, its underlying physiology ranging from overt left ventricular (LV) systolic dysfunction to isolated right ventricular (RV) diastolic dysfunction, and the wide portfolio of resulting symptoms vary from chronic fluid retention to acute multiorgan dysfunction and death.In this review, we discuss the morphological, functional, and molecular similarities and differences in RV and LV responses to adverse loading and failure.We further discuss whether LV and RV function and failure can truly be discussed as separate entities and thereby examine interactions between the ventricles that on one hand contribute to ventricular dysfunction but on the other may be harnessed for therapeutic benefit.
Antibiotic Combinations
Authors: Maxwell Finland, Charles V. Pryles, Wilfred F. Jones, Clare Wilcox, Ann Najarian
Journal: New England Journal of Medicine (1958)

THIS paper is another in a series dealing with controlled studies of the antibacterial action of human plasma after ingestion of antibiotics singly and in pairs.¶ The combination of chloramphenicol and penicillin with which it is concerned was among the first for which an antagonistic effect of two anti-biotics was clearly demonstrated both in vitro and in the treatment of an experimental infection of mice.7 , 8 However, since subsequent investigations by many workers have yielded markedly variable results, a résumé of the available reports on studies with this combination should be of interest.Previous Reports on the Combined Effects of Penicillin . . .
Editorial ignored 17 reviews on wind turbines and health
Authors: S. Chapman
Journal: BMJ (2012)

Hanning and Evans, who declare histories of anti-wind farm activity, say that a large body of evidence now exists that wind turbines within permissible distances from housing disturb sleep and impair health.1 They are correct about a large body of evidence, but not in their interpretation of its conclusions. 

There are 17 reviews of the evidence, nearly all with an “independent” provenance.2 None …
A new method of intralesional bleomycin therapy in the treatment of recalcitrant warts
Authors: S.E. MUNN, E. HIGGINS, M. MARSHALL, M. CLEMENT
Journal: British Journal of Dermatology (1996)

We have used a new technique of bleomycin injection to treat intractable palmar, plantar and periungual warts. Following local anaesthesia with topical EMLA (lignocaine and prilocaine) cream, 1 mg/ml bleomycin solution was dropped on to the wart and 'pricked' into the wart using a Monolet needle. We achieved 92% success rate which compares well with other authors whose success rates with intralesional bleomycin vary between 33 and 92%. We conclude that this technique of intralesional bleomycin therapy is an effective, safe and generally well tolerated treatment for recalcitrant warts.
No evidence that presumed consent increases organ donation
Authors: L. Hitchen
Journal: BMJ (2008)

No evidence supports the view that changing to a policy of presumed consent for organ donation leads to an increase in the number of donated organs, say transplant experts.

Currently the consent rate for organ donation in the United Kingdom is 60%. The chief medical officer Liam Donaldson and the prime minister, Gordon Brown, have indicated that they want a system of presumed consent to be considered. A report commissioned by the government from the organ donation taskforce, which will weigh up the evidence, is due later this month.

Speaking in London last …
Detection of hepatitis B virus dna in hepatocellular carcinoma: Analysis by hybridization with subgenomic dna fragments
Authors: Jen-Yang Chen, Tim J. Harrison, Chue-Shue Lee, Ding-Shinn Chen, Arie J. Zuckerman
Journal: Hepatology (1988)

We have previously reported an analysis of DNA extracted from 31 primary liver tumors where, in 25 cases, we found chromosomal integration of hepatitis B virus DNA sequences. We describe here an investigation of the extent of the viral genome at each integration site in 15 of the hepatitis B virus DNA-positive tumors using subgenomic fragments of the viral genome as probes. Probes were roughly equivalent to the pre-S region, the surface antigen gene, the region containing the enhancer, the x gene and the core antigen gene. We found the core antigen gene to be that most underrepresented in the tumors and speculate that, since cells which express core antigen in the infected liver may be targeted for lysis by the immune system, modifications of the integrated viral DNA which prevent core antigen expression may be selected. Conversely, the region of the genome present in the greatest number of integrations was the surface antigen gene and, because it is known that the major surface antigen promoter is active in the integrated state, we find promoter insertion an attractive hypothesis to explain oncogenesis by hepatitis B virus.
Uptake and Intracellular Fate of Fluorescent‐Magnetic Glyco‐nanoparticles
Authors: Juan Gallo, Nuria Genicio, Soledad Penadés
Journal: Advanced Healthcare Materials (2012)

Abstract Iron oxide based nanoparticles are finding their way as leading actors in nanotechnology applications to medicine. Magnetite nanoparticles are currently being used in clinics for the detection of hepatic tumors based on their unspecific accumulation in liver. More and more works are being published on potential applications of magnetic nanoparticles in diagnostics and therapy. But the interaction between magnetic nanoparticles and human cells at the subcellular level is only now beginning to be studied and more basic research is needed in this field. This work studies the interaction between carbohydrate functionalized gold‐coated magnetite nanoparticles and C33 tumoural human cells as the first step towards the in vivo application of these nanoparticles. The uptake of this magnetic material follows a similar trend to that described for other nanoparticles. The intracellular fate of these nanoparticles once internalized has been unveiled, and an automatic methodology for the analysis of co‐localization data has also been tested and compared to a more classic approach. These results can help in the optimization of the design of magnetic nanoparticles depending on their final application.
Atypical Adenomatous Hyperplasia in the Liver Detected by F-18 FDG PET/CT
Authors: Xiang Chen, Jinhua Zhao, Jianhua Song, Yan Xing, Taisong Wang
Journal: Clinical Nuclear Medicine (2010)

A 55-year-old asymptomatic woman underwent F-18 fluorodeoxyglucose PET/CT scan to evaluate a hepatic nodule incidentally detected by ultrasonography during her health examination. The PET/CT images revealed a focus of abnormal fluorodeoxyglucose uptake in a hypoattenuating lesion seen on CT in the medial left lobe of the liver, suggestive of possible malignancy. Surgery was performed and histopathology revealed atypical adenomatous hyperplasia accompanied by extensive fatty degeneration.
P226High platelets adrenoreactivity determines resistance to double antiplatelet therapy among patients with myocardial infarction
Authors: KI Gatina, ON Sulaieva
Journal: Cardiovascular Research (2014)

Resistance to double antiplatelet therapy, impairing outcome of myocardial infarction (MI), is manifested by the hyperreactive platelets' phenotype as evaluated by high in vitro response to ADP. As patients with high adrenoreactivity belong to the group of high cardiovascular risk, it was reasonable to investigate whether high platelets' adrenoreactivity was responsible for resistance to P2Y12 blocking agents.

Materials and Methods. Light transmission platelets aggregometry  following ADP and epinephrine (Sigma) stimulation in EC50 (5mkM both) or subthreshold concentration (0.5mkM, 0.1 mkM respectively) was carried out on plasma of 39 patients with MI receiving double antiplatelet therapy. After evaluating platelets' response to epinephrine and distributing patients into two groups (response less/more than 50%), they were compared on the basis of their response to ADP. Further, influence of subthreshold concentration of epinephrine and ADP on the overall platelets' reactivity was analysed. MedCalc sowtware was used for statistical analysis.

Results: A strong correlation existed between a high response to epinephrine and ADP (r=0.64, p=0.0002); moreover, two groups differed on the basis of their response to ADP (p=0.0017). Thus, platelets' adrenoreactivity influenced overall responsiveness to antiplatelet therapy as measured by response to ADP.

Since a hypoxic tissue releases ADP to the regional microcirculation, and, furthermore, since MI is accompanied by a high level of catecholamines in plasma, it was reasonbale to investigate whether a high response to the combination of those two agonists in low doses determined the hyperreactive platelets' phenotype. It was revealed that a strong correlation existed between a high platelet reactivity as measured with the help of EC50 of epinephrine, and their high response (more than 50%) to the pair of ADP and epinephrine (r=0.73).

In conclusion, high platelets' adrenoreactivity determines resistance to double antiplatelet therapy among patients with myocardial infarction.
A case of small-bowel perforation caused by a migrated duodenal stent
Authors: P. Moxey, A. Khan, N. Karanjia
Journal: Endoscopy (2007)

Metal stents are used to palliate advanced malignant gastric outlet and duodenal obstruction [1] [2]. We present a rare complication due to a migrated duodenal stent, that highlights the need for a diagnosis of malignancy before deployment.