tbuckley/cabot-search huggingface dataset:
Achalasia: outcome of patients treated with intrasphincteric injection of botulinum toxin.
Authors: C Cuilliere, P Ducrotte, F Zerbib, E H Metman, D de Looze, F Guillemot, H Hudziak, H Lamouliatte, J C Grimaud, A Ropert, M Dapoigny, R Bost, M Lemann, M A Bigard, P Denis, J L Auget, J P Galmiche, S Bruley des Varannes
Journal: Gut (1997)

BACKGROUND: To evaluate the safety and clinical efficacy of botulinum toxin (BT) in patients with achalasia followed up for six months. METHODS: Fifty five symptomatic patients with manometrically proven achalasia were included in a multicentre prospective trial. Before and two weeks and two months after intrasphincteric injection of BT, symptoms of dysphagia, regurgitation, and chest pain were scored on a 0-3 scale, and lower oesophageal sphincter pressure (LOSP) was assessed. The symptom score was determined again at six months, clinical improvement being defined by &lt; or = 3, relapse by &gt; 3, and failure as a relapse after two injections or loss to follow up. RESULTS: Except for transient chest or epigastric pain (22%), no side effects were observed. There was a significant decrease in LOSP after treatment. Symptom scores were significantly improved at two weeks (2.0 (SD 1.6)), two months (1.7 (1.8)), and six months (1.9 (2.0)) compared with pretreatment values (5.1 (1.8), p &lt; 0.001). At six months, 33 patients had clinical improvement (27 after one injection), 17 were considered failures, and five had just relapsed. Although there was a trend for age (older patients being more responsive), age, sex, prior duration of symptoms, initial symptom score, weight loss, LOSP, magnitude of oesophageal contractions, vigorous or non-vigorous achalasia, previous dilatations, and radiological features were not predictive of results. CONCLUSIONS: This multicentre series confirms that intrasphincteric injection of BT is a safe procedure, resulting in clinical improvement in 60% of patients with achalasia at six months. The therapeutic role of BT in achalasia needs further evaluation with regard to other alternatives.
Fibre does not protect against colon cancer
Authors: S. Gottlieb
Journal: BMJ (1999)

<h3>Summary</h3> We compare the trajectory of deaths (both in hospitals and care homes) on a daily basis in Sweden and England and Wales (which constitute 90 per cent of the UK population) from 11 March to 12 June 2020, the latest date at which the relevant data is available for England and Wales. Deaths in both Sweden and England and Wales peaked on 8 April. The build up to the peak was very similar in both. Given the time lag between infection and death, the lockdown would have had little effect on the peak number of deaths. By 12 June, the deaths are virtually the same in both. However, from early May the decline in England and Wales has been much sharper. We estimate that to 12 June, lockdown saved just under 6,000 lives in England and Wales, or around 6,500 extrapolating to a UK level.
Topical 5-fluorouracil solution in the treatment of warts—clinical experience and percutaneous absorption
Authors: H. SENFF, D. REINEL, C. MATTHIES, D. WITTS
Journal: British Journal of Dermatology (1988)

Disseminated warts in six patients were pre-treated with topical 5-fluorouracil solution three times daily for 5 consecutive days. Curettage was then carried out under local anaesthesia. During pre-treatment less than 0.1% of the dose applied was absorbed through the skin. The warts had not reappeared in 5 of the 6 patients at follow-up 1 year later.
563 ACUTE AND CHRONIC REJECTION DURING INTERFERON THERAPY IN HCV RECURRENT TRANSPLANT PATIENTS: RESULTS FORM THE AISF-RECOLT-C GROUP
Authors: M. Rendina, N.M. Castellaneta, S. Fagiuoli, F. Ponziani, R. Vigano, R.M. Iemmolo, M.F. Donato, P. Toniutto, L. Pasulo, M.C. Morelli, P. Burra, L. Miglioresi, V. Giannelli, D. Di Paolo, A. Di Leo
Journal: Journal of Hepatology (2011)
Molecular epidemiology of hepatitis C infection among intravenous drug users in Guangxi Province, Southern China
Authors: None MIZOKAMI
Journal: Hepatology (1995)

Nous rapportons un cas de spondylodiscite à Enterobacter cloacae, en rapport avec les pratiques à risque chez les usagers de drogues intraveineuses (IVDU).Il s’agissait d’un usager de drogues, ancien héroïnomane, sous traitement de substitution au long cours par la buprénorphine haut dosage avec un mésusage quotidien par voie intraveineuse de ce traitement depuis plusieurs mois. Cette infection a permis de découvrir la séropositivité du patient pour le VIH. L’évolution clinique a été remarquable par son caractère subaigu, l’apyrexie et un syndrome inflammatoire minime habituels chez les IVDU.Toute dorsolombalgie chez un patient IVDU, y compris dans le cas de la prescription régulière d’un traitement médical de substitution, et en particulier dans le cadre de l’infection par le VIH, doit faire évoquer une spondylodiscite en raison de la grande sensibilité aux infections de ces patients et des fréquentes bactériémies induites par la persistance ou la rechute transitoire de pratiques d’injection à risque (échange de matériel, réutilisation des aiguilles, des seringues, des cotons, risque manu-porté et/ou salivo-porté).We report a case of Enterobacter cloacae spondylodiscitis related to risk practices in intravenous drug addicts (IVDA).The patient, a former heroin addict, was receiving long-term, high-dose buprenorphine maintenance treatment. He had been misusing the treatment, injecting it daily for several months. The clinical course included several uncommon features that are usually found in IVDA patients: subacute infection, apyrexia, and minimal inflammatory syndrome. This infection also led to the discovery of his HIV infection.Any dorsolumbar pain in IVDA patients, including those receiving regular drug maintenance treatment and especially those with HIV infection, should suggest spondylodiscitis, because of these patients’ enhanced sensitivity to infection and the frequent bacteremia caused by persistent or transitory relapse involving injection (exchange of material, reuse of needles, syringes, cotton swabs, and risk of contamination through the hands or saliva).
Abstract B29: Genetic interactions between AKT/mTOR and Ras/MAPK pathways in liver cancer pathogenesis: from animal models to targeted therapy
Authors: Xin Chen, Coral Ho, Chunmei Wang, Susie Lee, Matthias Evert, Frank Dombrowski, Diego Calvisi
Journal: Clinical Cancer Research (2010)

Abstract Introduction: Hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC) are deadly malignant liver tumors lacking of efficient treatment options. Akt/mTOR and Ras/MAPK pathways have been implicated in hepatic carcinogenesis. Our study is to define the genetic interactions between Akt/mTOR and Ras/MAPK pathways in liver carcinogenesis. Methods: Activation of Akt/mTOR and Ras/MAPK signaling was assayed in 62 human HCC and 25 CCC samples. An activated Akt (myr-Akt) was stably transfected into the mouse liver alone or together with activated N-Ras (RasV12) via hydrodynamic gene delivery. Molecular and biochemical features of liver lesions were analyzed. A primary cell line (Akt/Ras) was isolated from a tumor co-injected with Akt and Ras protooncogenes. Akt/Ras cells and human HCC cell lines were treated with different mTOR inhibitors, including NVP-BEZ235, PP242 and Rapamcyin, as well as the MEK inhibitor AZD6244. Results: Using human HCC samples, we demonstrated the coordinated activation of Akt/mTOR and Ras/MAPK pathways in subsets of HCC and CCC characterized by poor prognosis. We found that coexpression of myr-Akt with RasV12 synergizes to promote liver tumor development in mice, leading to HCC and CCC formation within 4 to 6 weeks post injection. At cellular level, tumors from Akt/N-Ras co-injection cells are characterized by high proliferation and low apoptotic index, and disrupted expression of genes involved in cell cycle regulation. At the molecular level, liver tumors show high levels of activated Akt/mTOR and Erk cascades. A primary cell line (Akt/Ras) was isolated from a tumor and used to test the response to different mTOR and MEK inhibitors. We found that dual PI3K/mTOR inhibitor NVP-BEZ235 has superior activity inhibiting Akt/Ras cell proliferation with IC50 around 2nM. It also efficiently inhibits phospho-S6, phospho-4EBP1 and cyclin D1 expression in Akt/Ras cells. Furthermore, NVP-BEZ235 synergizes with the MEK inhibitor AZD6244 to dramatically reduce the growth of the Akt/Ras cell line. Equivalent results were obtained in human HCC cell lines with the same inhibitors. Conclusion: Coordinated activation of Akt/mTOR and Ras/MAPK signaling is the hallmark of aggressive subtypes of human HCC and CCC. Activated Akt cooperates with activated Ras/MAPK to rapidly promote liver tumor formation in mice. The Akt/Ras mouse model is a useful pre-clinical system to test anti-neoplastic therapeutic approaches against HCC and CCC in vivo. In addition, our preliminary studies suggest that the combination of a dual PI3K/mTOR inhibitor with a MEK inhibitor may represent a promising novel targeted therapy for treating human HCC harboring activated Akt/mTOR and Ras/MAPK pathways. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B29.
Abstract 4978: Lung cancers regulate the immune suppressor PD-L1 by multiple mechanisms, altering its role in tumor survival.
Authors: Edward (Ward) E. Kadel, Kimberly Walter, Rupal Desai, Juliet Carbon, Marigold Boe, David Shames, Marcin Kowanetz
Journal: Cancer Research (2013)

Abstract The immune system has multiple mechanisms by which it can eliminate cancer and yet, tumors are able to adapt resistance to host immune surveillance and continue to survive and grow. One critical resistance mechanism involves Programmed cell death 1 ligand 1 (PD-L1, CD274, B7-H1), the predominant ligand for PD-1, an inhibitory receptor expressed on T cells following activation. PD-L1 also binds to B7.1 (CD80), inhibiting its ability to provide an immune stimulatory signal. PD-L1 is expressed broadly on multiple peripheral blood mononuclear cell subtypes, placenta, and numerous cancers, including NSCLC. Tumor-specific T cells infiltrate tumors and recognize tumor cells, releasing Interferon-gamma (IFNγ), initiating signaling of the Janus kinase/Signal Transducer and Activator of Transcription (JAK/STAT) pathway in the tumor cells. IFNγ induces and/or greatly enhances the expression of PD-L1 in the tumor, among other cell types, allowing the tumor to become resistant to the host T cell response. Blockade of PD-L1 binding to PD-1 and B7.1 can reinvigorate the host immune response against the tumor and overcome tumor adaptive resistance. The regulation of PD-L1 expression is complex and likely involves multiple types of pre- and post-translational events. We show that basal PD-L1 expression levels can vary greatly in cancer cells, as can PD-L1 induction by IFNγ. Here we describe the different categories of PD-L1 basal expression and IFNγ–dependent regulation across multiple lung cell lines and human tumor samples. Reverse Phase Protein Array and RNA microarray data show that the JAK/STAT canonical pathways are still intact among all of these distinct categories, so alternative mechanisms of expression regulation must be active in these cell lines and tumor samples. We provide evidence that a combination of mechanisms regulate both the basal and stimulated expression levels of PD-L1 across these distinct categories. This data regarding PD-L1 expression regulation provides valuable information to better understand the PD-1/PD-L1 pathway as a therapeutic target. Citation Format: Edward (Ward) E. Kadel, Kimberly Walter, Rupal Desai, Juliet Carbon, Marigold Boe, David Shames, Marcin Kowanetz. Lung cancers regulate the immune suppressor PD-L1 by multiple mechanisms, altering its role in tumor survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4978. doi:10.1158/1538-7445.AM2013-4978
Bladder tumours among rodent operatives handling ANTU.
Authors: J M Davies, H F Thomas, D Manson
Journal: BMJ (1982)

The rodenticide ANTU (alpha-naphthylthiourea) was used in the United Kingdom mainly in the late 1940s and early 1950s. The product then contained up to 0.2% of beta-naphthylamine as an impurity, and it was finally withdrawn in 1967 as a suspected carcinogen. Fourteen cases of urothelial tumours among rodent operatives exposed to ANTU are reported: in one district four out of 27 staff were affected, and in another area two out of 10. These cases strongly suggest that the early ANTU manufactured in the United Kingdom posed a cancer hazard to users. ANTU is still made or used in various countries, though the current product may be relatively pure and no longer contaminated by beta-naphthylamine. Recent laboratory evidence shows that even pure ANTU is mutagenic in the Ames test, and the safety of this rodenticide may need review.
Vascular Endothelial Cadherin Promotes Breast Cancer Progression via Transforming Growth Factor β Signaling
Authors: Myriam Labelle, Hans J. Schnittler, Daniela E. Aust, Katrin Friedrich, Gustavo Baretton, Dietmar Vestweber, Georg Breier
Journal: Cancer Research (2008)

Abstract Epithelial-to-mesenchymal transition (EMT) is an important event during carcinoma progression and leads to increased tumor cell malignancy. Here, we show that vascular endothelial (VE)-cadherin is induced during EMT in mammary tumor cells and is aberrantly expressed in invasive human breast carcinomas. VE-cadherin enhanced the capacity of fibroblastoid tumor cells to proliferate, form cord-like invasive structures, and adhere to endothelial cells, characteristics that are key contributors to their increased malignancy and metastatic potential. Consistently, VE-cadherin expression in malignant fibroblastoid tumor cells promoted the growth of experimental mammary carcinomas in vivo. Analysis of the signaling mechanisms involved revealed that VE-cadherin expression influences the levels of Smad2 phosphorylation and expression of target genes of transforming growth factor-β (TGF-β), a major mediator of advanced tumor progression and malignant tumor cell proliferation. VE-cadherin might thus promote tumor progression not only by contributing to tumor angiogenesis but also by enhancing tumor cell proliferation via the TGF-β signaling pathway. This article provides evidence for a novel function of VE-cadherin in tumor progression and reveals a previously unknown molecular link between VE-cadherin expression and TGF-β signaling. Our findings may have important implications for the clinical application of anti–VE-cadherin strategies. [Cancer Res 2008;68(5):1388–97]
Prognostic Impact of Tumor Size Eliminating the Ground Glass Opacity Component: Modified Clinical T Descriptors of the Tumor, Node, Metastasis Classification of Lung Cancer
Authors: Shota Nakamura, Takayuki Fukui, Tetsuo Taniguchi, Noriyasu Usami, Koji Kawaguchi, Futoshi Ishiguro, Akihiro Hirakawa, Kohei Yokoi
Journal: Journal of Thoracic Oncology (2013)
Quantifying anomalous intestinal sterol uptake, lymphatic transport, and biliary secretion inAbcg8−/− mice
Authors: Helen H. Wang, Shailendra B. Patel, Martin C. Carey, David Q.‐H. Wang
Journal: Hepatology (2007)

Sitosterolemia is caused by mutations in either ABCG5 or ABCG8, but simultaneous mutations of these genes have never been observed. To explore whether ABCG8, the sterol efflux (hemi-)transporter, plays a major role in determining intestinal absorption efficiency and hepatic secretion rates of cholesterol and sitostanol, we performed direct measurements of the absorption and lymphatic transport of these sterols in mice with chronic biliary and lymphatic fistulae, as well as the transport rates of radiolabeled cholesterol and sitostanol from plasma high-density lipoprotein (HDL) into bile in male Abcg8−/− and wild-type mice. We observed that the absorption and lymphatic transport rates of radiolabeled cholesterol and sitostanol were increased by ≈40% and ≈500%, respectively, in Abcg8−/− mice in the setting of constant intraduodenal infusion of micellar taurocholate and lecithin. Both strains displayed identical intestinal Npc1l1 expression levels and small intestinal transit rates. After 45 minutes of intraduodenal infusion, acute intestinal uptake rates of trace [14C]cholesterol and [3H]sitostanol were essentially similar in both groups of mice with intact biliary secretion. Furthermore, in wild-type mice, mass transport rate of [3H]sitostanol from plasma HDL into bile was significantly faster than that of [14C]cholesterol; however, no [3H]sitostanol and only traces of [14C]cholesterol were detected in bile of Abcg8−/− mice. Conclusion: Deletion of the Abcg8 gene alone significantly increases the mass of intestinal cholesterol and sitostanol absorption and reduces but does not eliminate hepatic secretion of cholesterol. Moreover, the mutation has no influence on acute uptake of cholesterol and sitostanol by the enterocyte nor small intestinal transit time. (HEPATOLOGY 2007;45:998–1006.)
PROBLEMS OF SOCIAL ADJUSTMENT FOLLOWING LOBOTOMY
Authors: C. KNIGHT ALDRICH
Journal: American Journal of Psychiatry (1950)

The problems of all 10 of the clients of a family agency who have had psychosurgery are reviewed. From the point of view of several of the families, continued hospitalization of the patient would have presented fewer problems than resulted from surgery and discharge, although in many cases the patients themselves seemed to be more comfortable after operation. From a consideration of these cases, the following conclusions are drawn: 1. The problems of social adjustment following lobotomy are of such magnitude that a conservative approach to the selection of patients is indicated. 2. The attitudes and resources of the family should receive greater consideration in the selection of patients for lobotomy. 3. The motives and feelings of the responsible relative should be more carefully explored prior to surgery, and the possible aftereffects of the operation explained. 4. Patients who have undergone lobotomy require a great deal of predischarge reeducation and postdischarge supervision, particularly when they return to homes with children.
Clinicopathologic Features of the Severe Form of Acute Type 1 Autoimmune Hepatitis
Authors: Masanori Abe, Morikazu Onji, Keiko Kawai–Ninomiya, Kojiro Michitaka, Bunzo Matsuura, Yoichi Hiasa, Norio Horiike
Journal: Clinical Gastroenterology and Hepatology (2007)
Vascular tumours in infants. Part<scp>II</scp>: vascular tumours of intermediate dignity and malignant tumours
Authors: I. Colmenero, P.H. Hoeger
Journal: British Journal of Dermatology (2014)

Malignant cutaneous vascular tumours are very uncommon in children. As in adults, they are aggressive neoplasms with metastatic potential and a high mortality rate. Some nonmalignant vascular tumours may exhibit a locally aggressive behaviour and some of them can be associated with life-threatening systemic complications such as Kasabach-Merritt syndrome. Early diagnosis of these aggressive neoplasms in children is very important in order to start appropriate therapy as soon as possible, as this can have a significant impact on the prognosis of these patients. This review focuses on cutaneous vascular tumours of intermediate dignity (tufted angioma, kaposiform haemangioendothelioma, multifocal lymphangioendotheliomatosis with thrombocytopenia, papillary intralymphatic angioendothelioma, retiform haemangioendothelioma, adult-type haemangioendotheliomas) and malignant vascular tumours in young children (Kaposi sarcoma, angiosarcoma).
DIAGNOSIS AND TREATMENT OF SCAPULOCOSTAL SYNDROME
Authors: Allen S. Russek
Journal: JAMA (1952)

The scapulocostal syndrome is manifested by the insidious development of pain in the superior or posterior aspect of the shoulder girdle with radiation into one or more of the following regions: (1) the neck and occiput, often associated with severe headache; (2) the upper arm, particularly in the upper triceps and point of insertion of the deltoid muscle; (3) around the chest to the front of the thoracic wall; and (4) down the medial aspect of the forearm into the hand and fingers. Often there is numbness and tingling of the fingers, most commonly the fourth and fifth. The syndrome is caused by long-standing alteration of the relationship between the scapula and the posterior thoracic wall. It is characterized by remissions and exacerbations and may become acute, but it is more often chronic and can persist for years. It is refractory to the usual forms of physical therapy and is
Abstract 23: Sanguinarine suppresses survivin expression and inhibits the growth of prostate cancer cells
Authors: Meng Sun, Jae Yeon Chun, Wei Lou, Allen C. Gao
Journal: Cancer Research (2010)

Abstract Background: Prostate cancer is a frequently occurring disease and is the second leading cause of cancer related deaths of men in the United States. Current treatments have proved inadequate in curing or controlling prostate cancer and a search for agents for the management of this disease is urgently needed. Survivin plays an important role in both progression of castration-resistant prostate cancer and resistance to chemotherapy. Altered expression of survivin in prostate cancer cells is associated with cancer progression, drug/radiation resistance, poor prognosis and short patient survival. Methods: We performed a cell based rapid screen of the Prestwick Chemical Library consisting of 1120 FDA-approved compounds with known safety and bioavailability in humans to identify potential inhibitors of survivin and anti-cancer agents for prostate cancer. Results: Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified as a novel inhibitor of survivin that selectively kills prostate cancer cells over “normal” prostate epithelial cells. We found that sanguinarine inhibits survivin protein expression through protein degradation via the ubiquitin-proteasome system. Sanguinarine induces apoptosis and inhibits tumor formation and growth of human prostate cancer cells. Administration of sanguinarine, beginning 3 days post ectopic implantation of DU145 human prostate cancer cells, reduces both tumor weight and volume by more than 70% compared to the control treated mice with no apparent toxicity. In addition, sanguinarine sensitized prostate cancer cells to paclitaxel-mediated growth inhibition and apoptosis, offering a potential therapeutic strategy for overcoming taxol resistance. Conclusions: These results suggest that sanguinarine may be developed as an agent either alone or in combination with taxol for treatment of castration-resistant prostate cancer overexpressing survivin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 23.
Studies of Breast-feeding and Infections
Authors: Howard Bauchner
Journal: JAMA (1986)

We assessed the extent to which studies of the association between breast-feeding and infection met four important methodological standards that relate to both the scientific validity and the generalizability of the studies. Of the 20 studies (14 cohort, six case-control), only six met three or four of the methodological standards. Four of these six studies found that breast-feeding was not protective against infections and two found that breast-feeding was protective against infections. In the three studies in which statistical adjustments were made for three additional potentially important confounding variables—size of the family, smoking of cigarettes by the mother, and the mother's level of education—the apparent protective effect of breast-feeding against respiratory tract infections disappeared after the adjustments were made. We found that most of the studies have major methodological flaws that may have compromised their conclusions. The studies that met important methodological standards and controlled for confounding variables suggest that breast-feeding has at most a minimal protective effect in industrialized countries. (<i>JAMA</i>1986;256:887-892)