tbuckley/cabot-search huggingface dataset:
Frequency of p16INK4A alterations and k-ras mutations in intrahepatic cholangiocarcinoma of the liver
Authors: A Tannapfel
Journal: Gut (2000)

Inactivation of the tumour suppressor gene p16 (CDKN2/MTS-1/INK4A) and K-ras mutations are among the most frequent genetic alterations in human malignancies.To investigate the tumour suppressor gene p16 and its possible association with K-ras mutations in intrahepatic cholangiocarcinomas of the liver.The status of p16 was evaluated in 41 cholangiocarcinomas by methylation specific polymerase chain reaction, microsatellite analysis, DNA sequencing, and immunohistochemical staining. K-ras mutations were determined by direct DNA sequencing analyses after microdissection. The results obtained were correlated with histopathological variables and patient survival.Hypermethylation of the 5' CpG island of the p16 gene was found in 34 of 41 (83%) carcinomas. Homozygous deletion at the p16 region was present in two (5%), and loss of heterozygosity (LOH) in eight cases (20%). We failed to detect p16 gene missense mutations. K-ras mutations were found in 22 of 41 (54%) cholangiocarcinomas and in two cases of tumour surrounding non-neoplastic liver tissue. All 22 cancers with K-ras mutations also exhibited methylated p16. We failed to observe a correlation between K-ras or p16 status and histopathological factors or prognosis of patients.These data suggest that inactivation of the p16 gene is a frequent event in cholangiocarcinoma. The most common somatic alteration is promotor methylation of the p16 gene which is closely associated with K-ras mutations. We failed to establish p16 or K-ras status as independent prognostic factors in these tumours.
Effect of topical tretinoin on non-sun-exposed human skin connective tissue: induction of tenascin but no major effect on collagen metabolism
Authors: K.-M. HAAPASAARI, M. KALLIOINEN, K. TASANEN, M. SUTINEN, A.P ANNALA, J. RISTELI, A. OIKARINEN
Journal: British Journal of Dermatology (1997)

The effects of topical tretinoin on collagen synthesis and degradation were studied in 29 volunteers. The subjects applied 0.1% tretinoin cream on their non-sun-exposed abdominal skin once a day for 1 week (n = 10) (experiment 1) or twice a day for 2 weeks (n = 8) (experiment 2) or once a day for 2 months (n = 11) (experiment 3). After the treatments, suction blisters were induced and amino-terminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) (experiments 1 and 3) and carboxy-terminal propeptide of type I procollagen (PICP) (experiment 2) were assayed as an index of de novo collagen synthesis by radioimmunoassays. Matrix metalloproteases 2 (MMP-2) and 9 (MMP-9) were assayed by the zymography method in experiment 2. In experiment 3, histology, immunohistochemistry of type I and III procollagens, tenascin, mRNA levels of type I collagen alpha 1-chain [alpha 1 (I)], interstitial collagenase (MMP-1), MMP-2, MMP-9 by slot-blot analysis and the levels of alpha 1 (I) collagen mRNA by a quantitative polymerase chain reaction method were studied. The proportional area of elastic fibres visualized in Verhoeff-stained sections was analysed by computerized digital image analysis. The results indicated that treatment with topical tretinoin does not markedly induce de novo synthesis of collagen in vivo or affect matrix metalloproteases. In the immunohistochemical staining, tenascin was increased in the papillary dermis. As it has been suggested that tretinoin could counteract the atrophogenic effect of corticoids on the dermis, the effect of a combination of betamethasone-17-valerate (once a day) and tretinoin (once a day) on the propeptide levels was also studied. Betamethasone alone caused a 60% decrease in the concentrations of PINP and PIIINP, and a similar decrease was found after the combination treatment, indicating that topical tretinoin administered during short treatment periods does not counteract the inhibitory effect of a potent corticoid on collagen propeptides.
A comparison of wedge and segmental resection of the lung.
Authors: M J Jacobson, L Zand, R T Fox, W Lees
Journal: Thorax (1976)

In the past few years there has been increasing use of limited resection for pulmonary carcinoma, especially in patients with restricted cardiorespiratory function. Because there is frequently a choice as to the type of limited resection, it was considered worth while to review the safety and efficiency of the two principal types. In total, 212 wedge resections and 281 segmental resections are reported. Despite certain theoretical advantages to segmentectomy, wedge resection carried a lower complication rate. Seventy-one per cent of wedge resections were free of complications compared to 54% of segmental resections. Minor complications were defined as apical air space and apical haematoma. The incidence of minor complications was similar for each group, 22% for wedge resections and 27% for segmentectomies. However, there was a significantly higher major complication rate in the segmental resection group (19%) compared to the wedge group (7%). This is understandable, considering the amount of raw lung surface exposed after segmental resection. It appears that where it is surgically feasible, wedge resection should be practised.
Medical ethics. Is there a broader view?
Authors: N. Cousins
Journal: JAMA (1979)

THE 1978 report of the National Endowment for the Humanities lists current grants to 108 schools of medicine or research organizations for work in the field of medical ethics and human values. In dealing with ethical questions, however, the medical profession has a tendency to be somewhat selective and even restrictive in its concerns. The issues receiving the most attention are visible, mutable, pertinent, accessible, and demonstrable. Not that such questions are insignificant. The availability and distribution of medical care, decisions to share or withhold vital information, referral patterns, fee splitting, carrying out experiments without informed consent, inadequate credit in medical papers for the work of others, and unresponsiveness to the needs of poor patients—these are among the ethical questions that clearly justify the attention being given to them. However, they represent a fairly narrow window on the subject of ethical concerns in medicine. The moment we accept the importance
Multiple Cutaneous Carcinoma after Creosote Exposure
Authors: Norman Lenson
Journal: New England Journal of Medicine (1956)

CREOSOTE is a fractionated chemical mixture obtained by the commercial distillation of gas or wood tars. The tar fractions distill over at various temperatures. Considering the upper limits of temperature in a still as an index, ammoniacal liquor and crude naphtha distill at 180°C., and light oil and carbolic (middle) oil at 225°C. Creosote oil distills at approximately 275°C., and anthracene oil and pitch distill at temperatures greater than 275°C. It is of interest that the three fractions with distilling points at 275°C. and higher — that is, creosote oil, anthracene oil and pitch — are carcinogenic.Creosote is widely . . .
Significance of commonly used prognostic factors differs for children with T cell acute lymphocytic leukemia (ALL), as compared to those with B-precursor ALL. A Pediatric Oncology Group (POG) study
Authors: J Pullen, JJ Shuster, M Link, M Borowitz, M Amylon, AJ Carroll, V Land, AT Look, B McIntyre, B Camitta
Journal: Leukemia (1999)
BMA calls for action on “epidemic” of alcohol related problems
Authors: Andrew Cole, Zosia Kmietowicz
Journal: BMJ (2007)

Doctors' representatives have called for a range of new measures to tackle what they say is a growing “epidemic” of alcohol related problems. These include a national roll-out of local schemes to outlaw consumption of alcohol in the street, more funding for alcohol services, and a rise in tax on drink that is proportionate to products' alcohol content.

In a separate motion, representatives at the annual meeting in Torquay pressed the BMA to fight for a legal limit for drinking and driving that throughout Europe was no more than 50 mg of alcohol per 100 ml of blood and to support random roadside testing without the need for prior suspicion of intoxication.

An amendment that would have changed BMA policy to make the legal limit 20 mg per 100 ml was narrowly defeated. But Kate Adams, of London, predicted: “Next year I …
A Rare Case of Sebaceous Carcinoma with Very Malignant Characteristics
Authors: H VERLOOY, L. MORTELMANS, C SCHIEPERS, M DE ROO
Journal: Clinical Nuclear Medicine (1993)

A case of a sebaceous carcinoma is presented. This carcinoma of the skin appendages requires diagnosis by histopathology because the clinical appearance is often atypical. Because of the frequency of metastases to local lymph nodes and bone, a careful physical examination and appropriate radiologic/scintigraphic examinations of these organs should be performed routinely. The case presented illustrates the very malignant character of this tumor.
Influence of antigen dose and costimulation on the primary response of CD8+ T cells in vitro.
Authors: Z Cai, J Sprent
Journal: The Journal of Experimental Medicine (1996)

The influence of costimulation on the primary response of CD8+ T cells to class I alloantigens was studied with the aid of a T cell receptor transgenic model and defined peptides as antigen. With small doses of antigen, the proliferative response of CD8+ cells was high early in culture but was of brief duration and declined to low levels by day 4; this abbreviated response was associated with limited production of interleukin 2 (IL-2) and was strongly dependent upon costimulation via CD8-major histocompatibility complex class I and CD28-B7 interactions. The response to large doses of antigen was quite different in two respects. First, large doses of antigen inhibited the early (day 3) proliferative response but caused a marked elevation of the response late in culture (day 5); these altered kinetics were associated with increased production of IL-2. Second, the initial proliferative response to large doses of antigen did not require costimulation: indeed, blocking costimulation with CTLA4lg or anti-CD8 monoclonal antibody enhanced the early proliferative response. However, blocking costimulation impaired IL-2 production and prevented the late proliferative response. These findings indicate that the requirement for costimulation of T cells can be partly overcome by increasing the dose of antigen to a high level. However, costimulation plays a key role in prolonging the response, presumably by triggering strong and sustained production of IL-2.
LOWER ACHIEVED SYSTOLIC PRESSURE (≤130 MM HG) IS ASSOCIATED WITH WORSE RENAL FUNCTION BUT A SLOWER DECLINE IN GFR IN HYPERTENSIVE PATIENTS WITH ELECTROCARDIOGRAPHIC LEFT VENTRICULAR HYPERTROPHY: THE LIFE STUDY
Authors: Peter M. Okin, Sverre Kjeldsen, Bjorn Dahlof, Richard Devereux
Journal: Journal of the American College of Cardiology (2014)
Cancer Chemotherapy and the Structure of DNA
Authors: L. D. Hamilton
Journal: CA A Cancer Journal for Clinicians (1955)

Our increasing knowledge of nucleic acids has been a major factor in dissipat ing the pessimism that has long shrouded the search for cancer-controlling chemi cals.Indeed, a leading scientist in the nucleic acid field has recently entitled a paper Metabolic Basis for Optimism Re gare/ing Chemotherapy [Cancerl wit/i Nucleic Acid Derivatives'.The nucleic
Scottish judge rules smoking ban in psychiatric hospital breached patient's human rights
Authors: C. Dyer
Journal: BMJ (2013)

A patient detained in Carstairs high security psychiatric hospital in Scotland has won a court ruling that a total ban on smoking in the hospital and its grounds breached his human rights.

Lord Stewart ruled at the Court of Session in Edinburgh that the decision that compelled Charles McCann to stop smoking in December 2011 was “flawed in every possible way.”

McCann, who has schizophrenia, has been detained in the hospital since 1995, when a …
A Proposal to Develop Meaningful Labeling for Cigarettes
Authors: Jack E. Henningfield, Lynn T. Kozlowski, Neal L. Benowitz
Journal: JAMA (1994)

SINCE the 1980s, tobacco researchers have understood that the advertised nicotine-yield ratings of cigarettes do not accurately predict nicotine intake by individual cigarette smokers.<sup>1-5</sup>Cigarette smokers obtain an average of 1 mg of nicotine from each cigarette they smoke, whether the nicotine yield is 0.1 mg or 2 mg.<sup>4,6</sup>However, smokers with whom we have spoken believe that their "light" or "ultralight" cigarettes are providing them with substantially lower doses of nicotine and other constituents of tobacco smoke. These smokers seem to assume that nicotine-yield ratings are equivalent to the content ratings provided on food products, and they are often distressed to learn that nicotine-yield ratings are not indicative of how much nicotine they can obtain. We propose a new strategy for testing and labeling cigarettes that would provide consumers with improved information about how much nicotine they will absorb by smoking a particular brand of cigarette. Our
The OECD Program to Validate the Rat Hershberger Bioassay to Screen Compoundsfor <i>in Vivo</i> Androgen and Antiandrogen Responses. Phase 1: Use of a Potent Agonistand a Potent Antagonist to Test the Standardized Protocol
Authors: William Owens, Errol Zeiger, Michael Walker, John Ashby, Lesley Onyon, L. Earl Gray
Journal: Environmental Health Perspectives (2006)

The Organisation for Economic Cooperation and Development (OECD) has completed phase 1 of the Hershberger validation intended to identify in vivo activity of suspected androgens and antiandrogens. Seventeen laboratories from 7 countries participated in phase 1, and results were collated and evaluated by the OECD with the support of an international committee of experts. Five androgen-responsive tissues (ventral prostate, paired seminal vesicles and coagulating glands, levator ani and bulbocavernosus muscles, glans penis, and paired Cowper's or bulbourethral glands) were evaluated. The standardized protocols used selected doses of a reference androgen, testosterone propionate (TP), and an antiandrogen, flutamide (FLU). All laboratories successfully detected TP-stimulated increases in androgen-responsive tissue weight and decreases in TP-stimulated tissue weights when FLU was co-administered. The standardized protocols performed well under a variety of conditions (e.g., strain, diet, housing protocol, bedding). There was good agreement among laboratories with regard to the TP doses inducing significant increases in tissue weights and the FLU doses decreasing TP-stimulated tissue weights. Several additional procedures (e.g., weighing of the dorsolateral prostate and fixation of tissues before weighing) and serum component measurements (e.g., luteinizing hormone) were also included by some laboratories to assess their potential utility. The results indicated that the OECD Hershberger protocol was robust, reproducible, and transferable across laboratories. Based on this phase 1 validation study, the protocols have been refined, and the next phase of the OECD validation program will test the protocol with selected doses of weak androgen agonists, androgen antagonists, a 5alpha-reductase inhibitor, and chemicals having no androgenic activity.
Abstract 2365: Analysis of angiogenesis pathway-related gene expression impacted by MDM2 using PCR array
Authors: Thiagarajan Venkatesan, Corine Stinson, Sivanesan Dhandayuthapani, Appu Rathinavelu
Journal: Cancer Research (2014)

Abstract The Murine Double Minute 2 (MDM2) gene encodes an oncogenic MDM2 protein, which is a negative regulator of the p53 tumor suppressor. MDM2 amplification or over expression is found in many tumors that eventually lead to the inactivation of the cell cycle control and loss of pro-apoptotic functions that are typically exerted by wild type p53. Many of the oncogenic effects of MDM2 are resulting from the inactivation of p53 through direct binding or degradation of p53 following E3 ligase mediated ubiquitination. However, our recent findings have indicated that MDM2 over expression can also promote tumor angiogenesis through p53 independent pathways and thereby enhance the metastatic potential of cancer cells. In this respect increasing the levels of pro-angiogenic factors such as VEGF has been confirmed as one of the mechanisms regulated by MDM2. However, the actual cluster of genes or pathways regulated by MDM2 leading to such increase in the metastatic potentials of cancer cells have not been clearly identified. Therefore, the main purpose of our study was to understand the impact of MDM2 over expression on the levels of angiogenesis related genes that can also increase growth rate and metastatic potential. Hence, for our study we used the Human Angiogenesis PCR Array to compare the gene expression profile of LNCaP (prostate cancer cells) and LNCaP-MST (MDM2 transfected prostate cancer) cells. The MST cells expressed at least 10 fold increase in the levels of MDM2 after transfection. As a result of the elevated levels of MDM2 in LNCaP-MST cells the expression of genes such as THBS1 (125 fold), TNF-α (14 fold), MMP-9 (1.4 fold) were found to be significantly up-regulated compared to the MDM2 non-transfected cells. Cluster analysis further confirmed that these gene expression profiles are positively correlated with the pro-angiogenic potential of the LNCaP-MST cells compared to the non-transfected cells. In addition, the levels of EREG, TIMP1 and CXCL3 were down regulated significantly that favors the suppression of anti-angiogenic mechanisms. Our results offer a conclusive evidence that MDM2 can impact the cancer growth and metastatic potential of cancer cells by shifting the balance towards pro-angiogenic mechanisms (The financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida is gratefully acknowledged). Citation Format: Thiagarajan Venkatesan, Corine Stinson, Sivanesan Dhandayuthapani, Appu Rathinavelu. Analysis of angiogenesis pathway-related gene expression impacted by MDM2 using PCR array. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2365. doi:10.1158/1538-7445.AM2014-2365
Food Allergy Herbal Formula-2 silences peanut-induced anaphylaxis for a prolonged posttreatment period via IFN-γ–producing CD8+ T cells
Authors: Kamal D. Srivastava, Chunfeng Qu, Tengfei Zhang, Joseph Goldfarb, Hugh A. Sampson, Xiu-Min Li
Journal: Journal of Allergy and Clinical Immunology (2009)
TUBERCULOMA OF THE PITUITARY BODY
Authors: T. W. Letchworth
Journal: BMJ (1924)

A lowering of the energy expenditure under quinine thus occurred in onlly a very small proportion of cases, and even in these the effects did not last for quite three hours.To economize materially the energy expenditure would thus involve the repetition of the full pliarmacopoeial doses (0.6 gram quinine hydrochloride for the adult) at intervals of aboi;t three hours.Even this heroic treatment might well Iail to maintain the effect, and the other symptoms from such doses would certainly be undesirable; it is thus not practicable to attain any conisidelable saving of energy through quinine in a prolonged febrile illness.I have not laid any stress upon the extent of temperature reduction, for it is not so important in itself, ancd it is well recognized that quinine is not as good an antipyretic in nion-malarial as in malarial fevers.We have already a large mass of evideniee to disprove the location of its action in the tissues.It lhas, accordingto Feri,16 no effect, prevenitive or curative, upon the fever caused by tetrahydro-beta-niaphthylaimiine, wlhich acts centrally.Senta'7 founid that while it is capable of reducing the oxygen used by muscular tissue in vitro, the conicentration required to effect this (1 in 5,000 or higher) is much hiigher than that attained by a therapeutic dose.Lastly, and most illmportant of all, Barbour and WA'ingl8 have showni that direct application of quininie to the lheat centres causes a certain amounit of aiitipyresis.CONCLUSIONS.
TCTAP A-138 Mode of Presentation of Patients with ST-segment Elevation Myocardial Infarction in Singapore and Its Impact on Door-to-balloon Time and Clinical Outcome
Authors: Kevin Kien Hung Quah, Than Htike Aung, David Foo, Paul Jau Lueng Ong, Hee Hwa Ho
Journal: Journal of the American College of Cardiology (2014)
A local potent glucocorticosteroid decreases the induction of galactosylhydroxylysyl glucosyltransferase in suction blisters but has no effect on basement membrane structures
Authors: A. OIKARINEN, L. PELTONEN, J. HINTIKKA, J. M. FOIDART, U. KIISTALA
Journal: British Journal of Dermatology (1983)

The effects of local glucocorticosteroid treatment on collagen biosynthesis and basement membrane components were studied in suction blisters in human abdominal skin. Pretreatment with clobetasol‐17‐propionate, applied three times a day for 4 days, did not affect the activity of galactosylhydroxylysyl glucosyltransferase (GGT) in fresh blisters but post‐blistering treatment for 3 days with the steroid markedly inhibited the increase of this enzyme activity during the initial phases of re‐epithelialization. The GGT activity was over 50% lower in steroidtreated blisters compared with control values. Protein concentrations and blister fluid volumes were also significantly decreased in healing 3‐day blisters after steroid treatment. These results suggest that local glucocorticosteroid decreases either the synthesis of GGT or its release from the tissue into the blister fluid. The treatment did not affect the blister histology nor the early process of re‐epithelialization. Immunohistochemically, type IV and V collagens and laminin of the basement membrane zone were similarly located in blisters of steroid‐treated and placebo‐treated skin, suggesting that local glucocorticosteroid does not affect the integrity of the basement membrane.
Accidental Exposures (AE) to Peanut in Children with Peanut Allergy
Authors: N NGUYENLUU, R KAGAN, R ALIZADEHFAR, M PRIMEAU, M BENSHOSHAN, L JOSEPH, N NICOLAS, L HARADA, C DUFRESNE, M ALLEN
Journal: Journal of Allergy and Clinical Immunology (2008)
Allopurinol and the Role of Uric Acid in Hypertension
Authors: Allen D. Brinker
Journal: JAMA (2009)

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