tbuckley/cabot-search huggingface dataset:
Are we really dying for a tan?
Authors: A. R Ness, S. J Frankel, D. J Gunnell, G. D. Smith
Journal: BMJ (1999)

Professionals in health care and health promotion have embraced the notion that sunlight (particularly in doses that lead to sunburn) is bad for health.1–3 This was not always the case. In the early years of this century sunlight was regarded as an effective treatment for tuberculosis of the skin, and was also thought to be generally beneficial to health (box). Even today there are health resorts around the world offering heliotherapy—particularly for diseases of the skin such as psoriasis. The public have been slow to accept the message that exposure to sunlight is bad for health. Many people still sunbathe. In a survey carried out in England in 1995, 40% of those aged 16-24 reported being sunburnt in the preceding year, and just under 40% regarded a tan as being important to them.4 Furthermore, qualitative research with people in Scotland aged 20-35 who regularly travelled abroad for pleasure, suggested that at least part of the attraction of a tan was the perceived feeling of healthiness.5

#### Summary points

There is discordance between the health message to reduce exposure to sunlight and the health beliefs and behaviour of the public

The health promotion message aims to reduce skin cancer incidence and mortality

Increased exposure to sunlight may have beneficial effects on other diseases

Health educators should weigh up explicitly the potential risks and benefits of reduced exposure to sunlight to ensure that the health education message is appropriate

The prevention paradox, as described by Rose, arises because many interventions that aim to improve health have relatively small influences on the health of most people. Thus, for one person to benefit, many people will have to change their behaviour and receive no benefit from these changes. Perhaps sensing that public awareness of this paradox might act as a disincentive to …
Walking the ethical highwire: Genetic screening and hereditary tyrosinemia
Authors: René Romero, Joel E. Lavine
Journal: Hepatology (1995)

Background: Hereditary tyrosinemia type I is an autosomal recessive inborn error of metabolism caused by a deficiency of the enzyme fumarylacetoacetate hydrolase. The disorder clusters in the Saguenay-Lac-St.-Jean area of Quebec. In this region, 1 of 1846 newborns is affected and 1 of every 22 persons is thought to be a carrier. Recently, we identified a splice mutation and two nonsense mutations in the fumarylacetoacetate hydrolase gene in two patients from Quebec with tyrosinemia type I. Methods: We used allele-specific-oligonucleotide hybridization to examine the frequency of these three candidate mutations in patients with tyrosinemia type I and in the population of Quebec. Results: The splice mutation was found in 100 percent of patients from the Saguenay-Lac-St.-Jean area and in 28 percent of patients from other regions of the world. Of 25 patients from the Saguenay-Lac-St.-Jean region, 20 (80 percent) were homozygous for this mutation, a guanine-to-adenine change in the splice-donor sequence in intron 12 of the gene, indicating that it causes most cases of tyrosinemia type I in the region. The frequency of carrier status, based on screening of blood spots from newborns, was about 1 per 25 in the Saguenay-Lac-St.-Jean population and about 1 per 66 overall in Quebec. Conclusions: This study identified the most prevalent mutation causing hereditary tyrosinemia in French Canada; it also showed the feasibility of DNA-based testing for carriers in the population at risk. (N Engl J Med 1994;331:353-7.)
TIPE3 Is the Transfer Protein of Lipid Second Messengers that Promote Cancer
Authors: Svetlana A. Fayngerts, Jianping Wu, Camilla L. Oxley, Xianglan Liu, Anastassios Vourekas, Terry Cathopoulis, Zhaojun Wang, Jian Cui, Suxia Liu, Honghong Sun, Mark A. Lemmon, Lining Zhang, Yigong Shi, Youhai H. Chen
Journal: Cancer Cell (2014)
Variants of self-assembling peptide, KLD-12 that show both rapid fracture healing and antimicrobial properties
Authors: Jitendra K. Tripathi, Subhashis Pal, Bhanupriya Awasthi, Amit Kumar, Anshika Tandon, Kalyan Mitra, Naibedya Chattopadhyay, Jimut Kanti Ghosh
Journal: Biomaterials (2015)
Radionuclide Angiography in Suspected Acute Cholecystitis: Further Observations
Authors: PATRICK M. COLLETTI, KENNETH M. CIRIMELLI, D RANDALL RADIN, PARAKRAMA CHANDRASOMA, PHILIP W. RALLS, MICHAEL E. SIEGEL
Journal: Clinical Nuclear Medicine (1989)

Radionuclide angiography (RNA) and cholescintigraphy were performed prospectively in 300 patients with suspected acute cholecystitis (AC). Of 79 patients with positive RNA, 63 had AC (80%). Positive RNA was seen in 23 of 26 cases with gangrenous AC (88%) while 12 of the 26 had a positive "rim" sign (46%). All 12 patients with a positive "rim" sign had positive RNA. The "rim" sign may be caused by increased perfusion. Five of 6 patients with positive RNA and "obstructive" pattern had AC (83%). Patients with negative RNA and positive cholescintigraphy had a positive predictive value of 54% (31/57), while those with positive RNA and positive cholescintigraphy had a positive predictive value of 85% (57/67). RNA showed increased perfusion to nonbiliary pathology such as liver abscesses and pyelonephritis. Positive RNA increases the predictive value of cholescintigraphy and may be useful to shorten cholescintigraphic examinations.
Mortality in Adults With Sickle Cell Disease and Pulmonary Hypertension
Authors: Alem Mehari, Mark T. Gladwin, Xin Tian, Roberto F. Machado, Gregory J. Kato
Journal: JAMA (2012)

To the Editor: Dr Olshansky's research letter on the accelerated aging of US presidents concluded that presidents do not age faster than other men. 1 That may be true, but this study cannot demonstrate it due to a faulty comparison.Olshansky compared presidents' actual age at death (adjusted for aging by subtracting 2 days for every day in office) against average life expectancy for men matched to the date of inauguration.However, the correct comparison is with men who have the same profile of risk factors for premature death.For example, as Olshansky notes, education, wealth, and access to medical care strongly influence life expectancy, and these factors undoubtedly contributed to longer lives for many presidents.The real question is if, despite these advantages, presidents' lives were shortened.That requires comparison with other men of similar education, wealth, and access to medical care, and possibly with similar risk factors, such as smoking and alcohol consumption.Absent data permitting proper restriction, stratification, or control for confounding, the only conclusion that can be drawn is that presidents tend to be blessed with certain advantages that allow them to outlive men without those advantages.
Unbalanced globin chain synthesis by Hb lincoln park (anti‐lepore) reticulocytes
Authors: George R. Honig, R. George Mason, Larry M. Tremaine, Loyda N. Vida
Journal: American Journal of Hematology (1978)

Abstract Hemoglobin synthesis was studied in vitro in reticulocytes from a patient with the anti‐Lepore variant Hb Lincoln Park. Incorporation of L‐leucine‐ 3 H into the α and βδ chains of Hb Lincoln Park was substantially less than the incorporation into the corresponding globin chains of Hb A, with the rate of synthesis of the βδ chain being similar to that of the δ chain of Hb A 2 . Synthcis of the a and total non‐α globin components was unbalanced, with a substantial excess of α chain synthesis. These findings help to explain the mild hemolytic disease present in individuals with this hemoglobin variant.
Use of Antiretroviral Drugs in HIV Disease Declines Following Preliminary Results From Concorde Trial
Authors: Paul Cotton
Journal: JAMA (1994)

THE USE of antiretroviral therapy to treat asymptomatic human immunodeficiency virus (HIV) infection appears to be sharply down. Records kept by the Ontario HIV Project Centre in Canada, which distributes all antiretroviral drugs in the province, show an overall decrease by 45.4% in the number of patients starting therapy with zidovudine (Retrovir, commonly called AZT, Burroughs Wellcome, Research Triangle Park, NC) since the July 1993 Ninth International Conference on AIDS, held in Berlin, Germany. Rates are now the lowest since the first-line antiretroviral was first licensed in 1987, says Anita Rachlis, MD, medical director of the HIV Project Centre. She reported the finding at the First National Conference on Human Retroviruses and Related Infections, held in Washington, DC. Among asymptomatic patients, the records show that there has been a 52% decrease, apparently because of the presentation at the Berlin meeting of data with the longest follow-up time to date on
The long non-coding RNA, GAS5, enhances gefitinib-induced cell death in innate EGFR tyrosine kinase inhibitor-resistant lung adenocarcinoma cells with wide-type EGFR via downregulation of the IGF-1R expression
Authors: Siyuan Dong, Xiaohan Qu, Wenya Li, Xinwen Zhong, Peiwen Li, Shize Yang, Xitao Chen, Mingrui Shao, Lin Zhang
Journal: Journal of Hematology & Oncology (2015)

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are approved for patients with recurrent non-small cell lung cancer (NSCLC). However, the efficacy of EGFR-TKIs in NSCLC therapy is limited by primary and acquired resistance. Recent studies have revealed that long non-coding RNAs (LncRNA) may be involved in EGFR-TKI resistance. Therefore, a better understanding of the interactive mechanisms underlying LncRNA-mediated EGFR-TKIs resistance may help us to improve clinical response rates.To investigate the expression of growth arrest-specific 5 (GAS5) in lung adenocarcinoma, we performed real-time reverse-transcriptase polymerase chain reaction. The correlation between GAS5 expression levels and the samples' clinicopathological features was also analyzed. Primary resistance to EGFR-TKIs was identified in the human lung adenocarcinoma cell line A549. Plasmid vectors were used to overexpress GAS5 in A549 cells. MTT (3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide) colony formation assays and EdU (5-ethynyl-2'-deoxyuridine) assays were used to assess cell proliferation, and flow-cytometric analysis was used to evaluate the apoptosis rate. The expression levels of our target proteins, namely, EGFR, p-EGFR, ERK, p-ERK, Akt, p-Akt, IGF-1R (insulin-like growth factor 1 receptor), and p-IGF-1R, were analyzed by western blotting. A549 cells transfected with pcDNA-GAS5 were injected into nude mice. The transplanted mice were treated with gefitinib to study the effect of GAS5 on the resistance to EGFR-TKIs in vivo.Our results showed that GAS5 was significantly downregulated in lung adenocarcinoma tissues compared with the paired adjacent non-tumorous tissue samples. Furthermore, lower GAS5 expression levels were associated with larger tumor sizes, poor tumor differentiation, and advanced pathological stages. However, GAS5 was almost equally expressed between benign tumors compared with the adjacent normal tissues. GAS5 was also overexpressed in EGFR-TKI sensitive cell lines compared with the resistant cell line. Using MTT, EdU incorporation, and colony formation assays, we showed that GAS5-expressing A549 cells displayed an elevated level of cell death. In addition to its pro-apoptotic effect in the A549 cell line, GAS5 overexpression also suppressed the growth of A549-derived tumors in nude mice treated with gefitinib. GAS5 overexpression was inversely correlated with the expression of the EGFR pathway and IGF-1R proteins.Collectively, our results indicated that GAS5 LncRNA may represent a potential biomarker for the diagnosis of lung adenocarcinoma and that GAS5 might play a novel role in the development of the resistance to gefitinib, which could be reversed by overexpressing GAS5.
Cerebrotendinous xanthomatosis: a defect in mitochondrial 26-hydroxylation required for normal biosynthesis of cholic acid.
Authors: H Oftebro, I Björkhem, S Skrede, A Schreiner, J I Pederson
Journal: Journal of Clinical Investigation (1980)

Oxidation of side chain of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was studied in a patient with cerebrotendinous xanthomatosis (CTX) and in control subjects, using various subcellular fractions of liver homogenate and a method based on isotope dilution-mass spectrometry. In the control, 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol was converted into 5 beta-cholestane-3 alpha,7 alpha,12 alpha,26-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid by the mitochondrial fraction, and into 5 beta-cholestane-3 alpha,7 alpha,12 alpha,-25-tetrol by the microsomal fraction. In the CTX patient, liver mitochondria were completely devoid of 26-hydroxylase activity. The same mitochondrial fraction catalyzed 25-hydroxylation of vitamin D3. The microsomal fraction of liver of the subject with CTX contained more than 50-fold the normal amount of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol. The basic metabolid defect in CTX appears to be a lack of the mitochondrial 26-hydroxylase. The excretion in the bile of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 alpha,25-pentol observed in CTX patients may be secondary to the accumulation of the major substrate for the 26-hydroxylase, i. e., 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, and exposure of this substrate to the normally less active microsomal 25-and 24-hydroxylases. It is concluded that the major pathway in the biosynthesis of cholic acid in human liver involves a mitochondrial C27-steroid 26-hydroxylation.
Nonadherence to Adjuvant Tamoxifen Therapy in Women With Primary Breast Cancer
Authors: Ann H. Partridge, Philip S. Wang, Eric P. Winer, Jerry Avorn
Journal: Journal of Clinical Oncology (2003)

Although clinical trials have clearly demonstrated the benefits of tamoxifen in women with primary breast cancer, little is known about how this drug is actually used in the general population. We sought to estimate adherence and predictors of nonadherence in women starting tamoxifen as adjuvant breast cancer therapy.Subjects were age 18 years or older initiating tamoxifen for primary breast cancer and enrolled in New Jersey's Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs during the study period, from 1990 to 1996 (N = 2,378). Main outcome measures were number of days covered by filled prescriptions for tamoxifen in the first year of therapy with the 4 years after tamoxifen initiation for a subset; predictors of good versus poor adherence.Twenty-three percent of patients missed taking tamoxifen on more than one fifth of days studied, although on average, patients filled prescriptions for tamoxifen for 87% of their first year of treatment. The youngest, oldest, nonwhite, and mastectomy patients had significantly lower rates of adherence; patients who had seen an oncologist before taking tamoxifen had significantly higher rates of adherence. Overall adherence decreased to 50% by year 4 of therapy.The mean level of adherence to tamoxifen is high compared with other chronic medications. However, nearly one fourth of patients may be at risk for inadequate clinical response because of poor adherence. Because of the efficacy of tamoxifen therapy in preventing recurrence and death in women with early-stage breast cancer, further efforts are necessary to identify and prevent suboptimal adherence.
Data from short-term tests on motor vehicle exhausts
Authors: Ulf Rannug
Journal: Environmental Health Perspectives (1983)

The mutagenicity of motor vehicle exhausts has been studied by using Salmonella typhimurium strains TA 98 and TA 100. Acetone extracts of the particulate phase and the gas phase have been tested in the presence and absence of a metabolizing system (S9). The particulate phases from medium- and heavy-duty diesel vehicles were tested. The vehicles were driven according to a modified 13 mode test, and the particulate phase was sampled at mode 6 (maximum load and intermediate engine speed) and mode 12 (10% load and rated speed). In mode 6 all vehicles gave approximately the same mutagenicity in strain TA 98 (50,000-90,000 revertants/kW-hr) as well as in TA 100 (200,000-360,000 revertants/kW-hr). A higher mutagenic effect, in some cases up to 10 times, was seen with mode 12.Light-duty vehicles of different year models were tested using different fuel/engine combinations. The vehicles were driven according to FTP 72 or ECE driving cycle. Cold starts at two different temperature levels, approx. 0 degrees C and 23 degrees C, respectively, were also compared. Based on the mutagenicity of the particulate extracts (given as revertants per km), the light-duty vehicles could be divided into three main groups. The first group, the high mutagenicity group, giving 100,000-700,000 revertants/km, consists only of diesel cars. In the medium mutagenicity group, giving between 20,000 and 100,000 revertants/km, different gasoline fuels are placed, i.e., leaded and lead-free gasoline as well as alcohol/gasoline fuels. Two other fuels, methanol (M95) and propane (LPG), constitute the low mutagenicity group, giving less than 20,000 revertants/km. Fuels from the medium effect group will produce a particulate phase with low mutagenicity if the vehicle is equipped with a three way catalyst with closed loop, or fuel injection. The cold start temperature did not change this classification, since all samples gave a somewhat higher mutagenic effect at the low temperature. With the ECE driving cycle, much lower mutagenicity was noted with the diesel cars than in the tests with the FTP-72 driving cycle, at least with tester strain TA 98. On strain TA 100 the diesel exhaust samples still showed a much higher mutagenicity than other samples. Acetone extracts of the gas phase from diesel and gasoline exhaust (trapped in ice/water condensers and CO(2)/ethanol condensers) also gave mutagenic effects. The contribution of the gas phase to the mutagenic effects seems to be more important in the absence of S9 and more important in the case of gasoline exhausts.
Continuing Education Courses for Physicians
Authors: Glen R. Shepherd
Journal: JAMA (1964)

THE TENTH ANNUAL LISTING of courses and other more formally planned activities for the continuing education of physicians appears in the following pages. It covers the period from Sept 1, 1964, through Aug 31, 1965. Included are 1,569 courses by 405 institutions and organizations in the United States. The information presented in this listing is unevaluated data obtained by questionnaires completed by the sponsors.<i>Neither approval nor disapproval by the Council on Medical Education is implied by the presence of a course in the listing or by its absence from the listing which follows</i>. The newly initiated program by the Council for a voluntary institutional survey and accreditation of continuing medical education, could not be implemented in relation to the current listing. Since the detailed information contained in this list must be collected up to 15 months in advance, it is possible that dates may be changed before a course
Protein Kinase C: A Novel Target for Inhibiting Gastric Cancer Cell Invasion
Authors: Gary. K. Schwartz, J. Jiang, D. Kelsen, A. P. Albino
Journal: JNCI Journal of the National Cancer Institute (1993)

Gastric adenocarcinoma is a common neoplasm worldwide. Patients with completely resected disease often have locoregional recurrence, and adjuvant chemotherapy has failed to reduce the common occurrence of metastases. Protein kinase C (PKC) is thought to be important in tumor cell invasion, but its relationship to gastric cancer cell invasion, and thus metastases, remains unexplored. We recently identified and established invasive and noninvasive human gastric adenocarcinoma cell lines, which can now be used to test agents for inhibition of tumor cell invasion by inhibition of PKC activity.The objectives were (a) to test threo-dihydrosphingosine (SPC100221), a specific inhibitor of PKC at its regulatory site, and staurosporine, a potent but nonspecific inhibitor of PKC at its catalytic site, for their effects on gastric cancer cell invasion in vitro and (b) to determine whether the expression of PKC isoforms can distinguish invasive from noninvasive gastric cancer cells.Gastric cancer cell invasion through Matrigel-coated Nuclepore filters in the Boyden chamber assay was analyzed in the presence of graded concentrations of SPC100221 and staurosporine. The invasive SK-GT-1 and SK-GT-5 cell lines and the noninvasive SK-GT-2 and SK-GT-4 cell lines were used. PKC isoform expression was determined by reverse transcription of messenger RNAs to complementary DNA and subsequent amplification by the polymerase chain reaction.The effects of staurosporine and SPC100221 on tumor cell invasion were tested at drug concentrations that did not inhibit cell proliferation, as evidenced by [3H]thymidine uptake. Staurosporine and SPC100221 at subtoxic doses inhibited human gastric cancer cell invasion by 50% at 5 x 10(-9) M and 2 x 10(-7) M, respectively. The expression of PKC beta was observed in the invasive but not the noninvasive gastric cancer cells. Both types of cells, however, expressed the PKC alpha and PKC gamma isoforms.Gastric cancer cell invasion can be inhibited by PKC inhibitors, and expression of PKC beta may be a marker of invasiveness in gastric cancer.PKC appears to represent a new target for inhibition of gastric cancer cell invasion, and SPC100221, in view of its PKC specificity, may provide a model for future drug development in this area. Moreover, PKC beta may have a fundamental role in the development of invasive potential in gastric cancer.
Diseases of the Skin: For Practitioners and Students
Authors: Louis A. Brunsting
Journal: JAMA (1964)

This fifth edition of Andrews' popular text appears after a lapse of nine years, extensively revised and elaborated, and graced by the talent of Anthony N. Domonkos as junior author. The body of the book consists of 38 sections, as before, each one followed by up-to-date references. A two-column format and a slightly larger page improve readability and save 128 pages. The illustrations are superb.  A text cannot be all things to all men. Since this one is directed chiefly to students and practitioners, it is good to see the emphasis placed on the details of the clinical features and treatment of the commoner dermatoses. Histopathological coverage is not detailed, but is adequate.  A number of sections will appeal to an audience beyond the confines of this country. These include sections on leprosy, spirochetoses, and exotic affections and the especially brilliant discussion of diseases caused by animal parasites.  The coverage