tbuckley/cabot-search huggingface dataset:
Application of Antibiotics (Polybactrin) in Surgical Practice, Using the Aerosol Technique
Authors: R. M. Gibson
Journal: BMJ (1958)

CURE OF HOMOSEXUALITYin his desire and co-operative, but, in spite of great persistence on both sides, he was not cured.As there did not seem to be any constitutional abnormality, it can only be assumed that this failure was due to some defect in technique.Analytic treatment is in itself no solution to the whole problem of homosexuality, because of the time-consuming factor.But the continued investigation of such cases is desirable, for, if the causes of homosexuality as lying in infantile experiences can be substantiated it should be possible by avoiding these experiences to prevent it.If the causes in each of the cases mentioned are studied, it is evident that they could have been prevented by different treatment at the hands of the parent.The prevention of homosexuality, like that of all the other neuroses, seems to lie in right parenthood.SummaryThe origin of homosexuality and other deviations from the normal seems to originate in very early childhood experiences.Cases are given, some relating to treatment 30 years back, and others more recent, which indicate that when these causes are discovered and the experiences revived the patient is able to adjust himself to them in a way he was unable to do as an infant, and is thereby cured.This process of cure is a long one, and cannot be considered a practical answer to the wide- spread incidence of homosexuality.Probably the main benefit in analysing these cases and the discovery of their causes is that we may find the means to prevent -them.
Cotargeting the PI3K and RAS Pathways for the Treatment of Neuroendocrine Tumors
Authors: Joseph D. Valentino, Jing Li, Yekaterina Y. Zaytseva, W. Conan Mustain, Victoria A. Elliott, Ji Tae Kim, Jennifer W. Harris, Katherine Campbell, Heidi Weiss, Chi Wang, Jun Song, Lowell Anthony, Courtney M. Townsend, B. Mark Evers
Journal: Clinical Cancer Research (2014)

The precise involvement of the PI3K/mTOR and RAS/MEK pathways in carcinoid tumors is not well defined. Therefore, the purpose of our study was to evaluate the role these pathways play in carcinoid cell proliferation, apoptosis, and secretion and to determine the effects of combined treatment on carcinoid tumor inhibition.The human neuroendocrine cell lines BON (pancreatic carcinoid), NCI-H727 (lung carcinoid), and QGP-1 (somatostatinoma) were treated with either the pan-PI3K inhibitor, BKM120, or the dual PI3K-mTOR inhibitor, BEZ235, alone or in combination with the MEK inhibitor, PD0325901; proliferation, apoptosis, and protein expression were assessed. Peptide secretion was evaluated in BON and QGP-1 cells. The antiproliferative effect of BEZ235, alone or combined with PD0325901, was then tested in vivo.Both BKM120 and BEZ235 decreased proliferation and increased apoptosis; combination with PD0325901 significantly enhanced the antineoplastic effects of either treatment alone. In contrast, neurotensin peptide secretion was markedly stimulated with BKM120 treatment, but not BEZ235. The combination of BEZ235 + PD0325901 significantly inhibited the growth of BON xenografts without systemic toxicity.Both BKM120 and BEZ235 effectively inhibited neuroendocrine tumor (NET) cell proliferation and stimulated apoptosis. However, inhibition of the PI3K pathway alone with BKM120 significantly stimulated neurotensin peptide secretion; this did not occur with the dual inhibition of both PI3K and mTOR using BEZ235 suggesting that this would be a more effective treatment regimen for NETs. Moreover, the combination of BEZ235 and the MEK inhibitor PD0325901 was a safe and more effective therapy in vivo compared with single agents alone.
Synaptic pathology and therapeutic repair in adult retinoschisis mouse by AAV-RS1 transfer
Authors: Jingxing Ou, Camasamudram Vijayasarathy, Lucia Ziccardi, Shan Chen, Yong Zeng, Dario Marangoni, Jodie G. Pope, Ronald A. Bush, Zhijian Wu, Wei Li, Paul A. Sieving
Journal: Journal of Clinical Investigation (2015)

Strategies aimed at invoking synaptic plasticity have therapeutic potential for several neurological conditions. The human retinal synaptic disease X-linked retinoschisis (XLRS) is characterized by impaired visual signal transmission through the retina and progressive visual acuity loss, and mice lacking retinoschisin (RS1) recapitulate human disease. Here, we demonstrate that restoration of RS1 via retina-specific delivery of adeno-associated virus type 8-RS1 (AAV8-RS1) vector rescues molecular pathology at the photoreceptor-depolarizing bipolar cell (photoreceptor-DBC) synapse and restores function in adult Rs1-KO animals. Initial development of the photoreceptor-DBC synapse was normal in the Rs1-KO retina; however, the metabotropic glutamate receptor 6/transient receptor potential melastatin subfamily M member 1-signaling (mGluR6/TRPM1-signaling) cascade was not properly maintained. Specifically, the TRPM1 channel and G proteins Gαo, Gβ5, and RGS11 were progressively lost from postsynaptic DBC dendritic tips, whereas the mGluR6 receptor and RGS7 maintained proper synaptic position. This postsynaptic disruption differed from other murine night-blindness models with an electronegative electroretinogram response, which is also characteristic of murine and human XLRS disease. Upon AAV8-RS1 gene transfer to the retina of adult XLRS mice, TRPM1 and the signaling molecules returned to their proper dendritic tip location, and the DBC resting membrane potential was restored. These findings provide insight into the molecular plasticity of a critical synapse in the visual system and demonstrate potential therapeutic avenues for some diseases involving synaptic pathology.
Surgical Decisions in the Elderly: The Importance of Biological Age
Authors: S M Farquharson, Ramesh Gupta, R J Heald, B J Moran
Journal: Journal of the Royal Society of Medicine (2001)

Surgeons will sometimes advise against an operation because the patient is 'old and frail'. A simple starring system (one to five), based on performance and lifestyle, has been devised to assess the biological age of elderly patients. 10 consultant surgeons and 10 trainees answered questions about their treatment recommendations for hypothetical patients of standard age and medical history but with various star ratings and surgical conditions. 1000 decisions were available for analysis. The four and five star patients (those leading an independent existence) were recommended 266 interventions, the one and two star patients 55. Trainees were more inclined to intervene than consultants, recommending operations in half the patients rather than one-third. These results indicate that decisions on surgical management are strongly influenced by the patient's star rating or biological age. If the starring method proves reproducible in other patient groups and settings, it could allow better communication on an important factor in clinical decisions.
Curcumin Inhibits the Proteasome Activity in Human Colon Cancer Cells <i>In vitro</i> and <i>In vivo</i>
Authors: Vesna Milacic, Sanjeev Banerjee, Kristin R. Landis-Piwowar, Fazlul H. Sarkar, Adhip P.N. Majumdar, Q. Ping Dou
Journal: Cancer Research (2008)

Abstract Curcumin (diferuloylmethane) is the major active ingredient of turmeric (Curcuma longa) used in South Asian cuisine for centuries. Curcumin has been shown to inhibit the growth of transformed cells and to have a number of potential molecular targets. However, the essential molecular targets of curcumin under physiologic conditions have not been completely defined. Herein, we report that the tumor cellular proteasome is most likely an important target of curcumin. Nucleophilic susceptibility and in silico docking studies show that both carbonyl carbons of the curcumin molecule are highly susceptible to a nucleophilic attack by the hydroxyl group of the NH2-terminal threonine of the proteasomal chymotrypsin-like (CT-like) subunit. Consistently, curcumin potently inhibits the CT-like activity of a purified rabbit 20S proteasome (IC50 = 1.85 μmol/L) and cellular 26S proteasome. Furthermore, inhibition of proteasome activity by curcumin in human colon cancer HCT-116 and SW480 cell lines leads to accumulation of ubiquitinated proteins and several proteasome target proteins, and subsequent induction of apoptosis. Furthermore, treatment of HCT-116 colon tumor–bearing ICR SCID mice with curcumin resulted in decreased tumor growth, associated with proteasome inhibition, proliferation suppression, and apoptosis induction in tumor tissues. Our study shows that proteasome inhibition could be one of the mechanisms for the chemopreventive and/or therapeutic roles of curcumin in human colon cancer. Based on its ability to inhibit the proteasome and induce apoptosis in both HCT-116 and metastatic SW480 colon cancer cell lines, our study suggests that curcumin could potentially be used for treatment of both early-stage and late-stage/refractory colon cancer. [Cancer Res 2008;68(18):7283–92]
Levels of Phosphate Compounds in Experimental Cardiac Hypertrophy
Authors: PAUL R. MINTON, PAUL M. ZOLL, LEONA R. NORMAN
Journal: Circulation Research (1960)

Arterial hypertension was produced in 66 rats by means of constricting latex capsules about the kidneys, by the intramuscular implantation of desoxycorticosterone pellets, and by the subcutaneous injection of desoxycorticosterone. The most satisfactory method was the intramuscular implantation of desoxycorticosterone pellets. Myocardial hypertrophy was produced in 43 rats. Biochemical analysis of the ventricles of 80 control and 45 hypertrophied rats were performed for creatine phosphate, adenosine triphosphate, and free inorganic phosphate. Cardiac hypertrophy in rats was accompanied by a statistically significant decrease in the ventricular concentration of creatine phosphate, while levels of adenosine triphosphate and free inorganic phosphate were not significantly altered. It is suggested that congestive heart failure in hypertrophied hearts is related to a defect in the utilization of phosphate-bond energy by the hypertrophied myocardial fiber.
Are reference equations for spirometry an appropriate criterion for diagnosing disease and predicting prognosis?
Authors: Guy B Marks
Journal: Thorax (2011)

In the last few years, there has been considerable debate on the use of threshold criteria for the diagnosis of obstructive lung disease based on FEV<sub>1</sub> and FEV<sub>1</sub>/FVC ratio. It has been argued that a fixed ratio and fixed percentage criterion result in misclassification. The author argues that this critique is based on a false presumption about the validity of reference equations as a criterion for normality. The flaw lies in the methods used to derive reference equations, which involve arbitrary and circular criteria for exclusion of some members of the population, use potentially non-representative reference populations and include predictive variables that are really risk factors for disease or for adverse outcomes of disease. The author argues for a new interpretative approach for the use of lung function data in clinical practice based on prognostic equations analogous to the Framingham cardiovascular risk factor equations. These interpretative equations should be based on data from cohort studies and randomised controlled trials, rather than cross-sectional studies, and if properly formulated, will prove to be valuable aids to clinical decision making.
Visual Improvement after Cultivated Oral Mucosal Epithelial Transplantation
Authors: Chie Sotozono, Tsutomu Inatomi, Takahiro Nakamura, Noriko Koizumi, Norihiko Yokoi, Mayumi Ueta, Kotone Matsuyama, Keiko Miyakoda, Hideaki Kaneda, Masanori Fukushima, Shigeru Kinoshita
Journal: Ophthalmology (2012)
Suppression of Tumor Growth by Galectin-7 Gene Transfer
Authors: Shugo Ueda, Ichiro Kuwabara, Fu-Tong Liu
Journal: Cancer Research (2004)

Abstract Galectin-7 is a β-galactoside-binding animal lectin specifically expressed in stratified epithelia. Its expression is inducible by p53 and is down-regulated in squamous cell carcinomas. Other investigators previously showed that galectin-7 is a proapoptotic protein, and we showed that ectopic expression of galectin-7 in HeLa cells renders the cells more sensitive to a variety of apoptotic stimuli. In the present study, we showed that ectopic expression of galectin-7 in the human colon carcinoma cell line DLD-1 also made the cells more sensitive to apoptosis under various conditions. We also found that galectin-7-transfected DLD-1 (DLD-1-Gal7) cells grew significantly more slowly than control transfectants (DLD-1-V) under normal culture conditions in the absence of apoptosis. Moreover, a significantly lower number of colonies were formed from DLD-1-Gal7 cells than from DLD-1-V cells under anchorage-independent cell growth conditions. Most importantly, tumor formation from DLD-1-Gal7 cells was dramatically reduced compared with DLD-1-V cells when these cells were inoculated s.c. into severe combined immunodeficient mice. DLD-1-Gal7 tumors showed a significantly lower proliferation rate than DLD-1-V tumors as determined by in vivo 5-bromo-2′-deoxyuridine incorporation. DLD-1-Gal7 tumors also contained a lower density of blood vessels than DLD-1-V tumors, suggesting that ectopic expression of galectin-7 suppresses angiogenesis. This may partially account for the greater suppressive effect of galectin-7 on tumor growth in vivo than in vitro. Our results show that galectin-7 has a suppressive effect on tumor growth, suggesting that galectin-7 gene transfer or other means of specifically inducing galectin-7 expression may be a new approach for management of cancers.
Sepsis: a roadmap for future research
Authors: Jonathan Cohen, Jean-Louis Vincent, Neill K J Adhikari, Flavia R Machado, Derek C Angus, Thierry Calandra, Katia Jaton, Stefano Giulieri, Julie Delaloye, Steven Opal, Kevin Tracey, Tom van der Poll, Eric Pelfrene
Journal: The Lancet Infectious Diseases (2015)
High Blood Pressure in Coarctation of Aorta
Authors: E. J. Rooke
Journal: BMJ (1938)

practically equivalent to proseptasine, at the Maternity Department of the Western General Hospital.Our inten- tion there was to put every alternate case on prophylactic sulphonamide, but this routine has not been strictly adhered to, and there has been a tendency to select cases, the more serious ones and those more likely to be followee by infection being given the prophylactic doses.Two 72-grain tablets were given four times a day for the first four days and one tablet three times a day for the next three days, so that the patients who were on this treat- ment received 3074grains of sulphonamide in the week following delivery.No toxic symptoms of any signifi- cance or moment were observed, except in one case where a skin eruption occurred which was thought to be due to the sulphonamide medication.Among 322 patients who received prophylactic sulphonamide there were twenty cases of morbid puerperia, but of these only six were due to local uterine infection, while one developed definite puerperal sepsis.Of 383 cases to which the sulphonamide was not given there were fifteen who showed signs of morbid puerperia, but of these again only six showed symptoms of local uterine infection, while one developed puerperal septicaemia.In this investigation, therefore, the general result seems negative.My colleagues and I desire to express our thanks to Messrs. May and Baker and to Bayer Products Ltd. for their generosity in providing their drugs.
Royal Medical Benevolent Fund Christmas Gifts Appeal
Authors: G. H. Bateman
Journal: BMJ (1973)

BRITISH MEDICAL JOURNAL 24 NOVEMBER 1973 then decide how to make the child as safe as possible, as a first-aid measure, and also try to make provision for the long-term support, supervision, and re-education which the family are going to need.All this is going to be difficult and de- manding for someone, probably several people, and the long-term results may be disappointing.But "prompt referral to the nearest hospital," without thought, is not good enough.-Iam, etc.,
Effective treatment of advanced-stage childhood lymphoblastic lymphoma without prophylactic cranial irradiation: results of St Jude NHL13 study
Authors: J T Sandlund, C-H Pui, Y Zhou, F G Behm, M Onciu, B I Razzouk, N Hijiya, D Campana, M M Hudson, R C Ribeiro
Journal: Leukemia (2009)
Low‐dose α‐interferon treatment of chronic myeloid leukemia
Authors: Angel Sanchez, William A. Robinson, Allen Cohn, Rene Gonzalez, Arun Adlakha
Journal: American Journal of Hematology (1992)

We treated 29 patients with chronic-phase and accelerated chronic myeloid leukemia (CML) with alpha-interferon in a dose of 2 mU/m2 given subcutaneously daily for 30 days and then three times per week. Most had received prior treatment. Three patients have had sustained hematologic and karyotypic remissions after a median of 22 months of treatment. Three further patients have had complete hematologic and partial karyotypic remissions. At a median follow-up of 48 months, the median survival has not been reached. This dose of alpha-interferon may induce sustained remissions even in pretreated patients and may prolong survival in CML.
Akt-dependent phosphorylation on AIB1 serine 967 contributes to breast cancer tamoxifen resistance.
Authors: J Shou, KC Osborne, J Gee, R Nicholson, R Schiff
Journal: Cancer Research (2009)

Abstract Abstract #3021 AIB1, a coactivator for nuclear receptors and other transcription factors, is involved in breast cancer development and progression. Overexpression of both AIB1 and HER2/neu (HER2) results in tamoxifen (Tam) resistance in clinical and experimental breast cancer. We hypothesized that HER2 signaling, via its downstream kinase Akt, leads to phosphorylation and activation of AIB1, which may then contribute to development of Tam resistance by reducing its antagonist activity.&amp;#x2028; We have previously shown that Akt synergizes with AIB1 to enhance estrogen- and Tam-induced estrogen receptor (ER)-dependent transcriptional activity. This synergy is mainly mediated by Akt phosphorylation of AIB1 on serine 967, which is located between the nuclear receptor and the CBP/p300 interacting domains. We showed that this serine residue was phosphorylated specifically by Akt both in vitro and in vivo, including in both acquired and de novo Tam-resistant xenograft models that are associated with increased Akt signaling. More recent data showed that serine 967 of AIB1 is phosphorylated in Tam-resistant MCF7 tumors, and that this phosphorylation is stable in the resistant cells. By using immunoprecipitation and Western blot analysis, in ER positive breast tumors from patients, 90% of tumors were positive for total AIB, while AIB1 phosphorylation was detectable in 60% of tumors. Phosphorylated AIB1 was positively correlated with total and phosphorylated HER2 (Tyrosine 1248) (p=0.004 and p=0.0008 respectively, Fisher's exact test), implying that phophorylation of serine 967 of AIB1 may be stimulated by HER2 in these AIB1 positive tumors. Serine 967 of AIB1 was also phosphorylated in breast cancer cell lines, including both basal (HCC1954, BT20 and SUM190PT) and luminal (T47D, ZR7530, MDAMB361, and UACC812) subtypes, in which HER2 (except BT20) and Akt were activated .&amp;#x2028; Taken together, Akt phosphorylation of AIB1 serine 967 appears important for AIB1 to function as an ER coactivator and regulator of breast cancer proliferation, and for Tam agonistic activity. Thus phosphorylation at serine 967 of AIB1 may be an essential factor required for Tam resistance as well as for tumor growth independent of ER. Additional regulatory roles of serine 967 in AIB1 function are currently under investigation. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3021.
Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia: data from a nationwide fungaemia surveillance programme
Authors: M.C. Arendrup, E. Dzajic, R.H. Jensen, H.K. Johansen, P. Kjaldgaard, J.D. Knudsen, L. Kristensen, C. Leitz, L.E. Lemming, L. Nielsen, B. Olesen, F.S. Rosenvinge, B.L. Røder, H.C. Schønheyder
Journal: Clinical Microbiology and Infection (2013)
P103 Culture and culture independant identification of bacterial communities in the cystic fibrosis respiratory tract
Authors: GG Einarsson, J McCaughan, AA Fodor, MC Wolfgang, MM Tunney, JS Elborn
Journal: Thorax (2013)

<h3>Introduction and Aims</h3> The identification of complex chronic polymicrobial infections, such as those observed in the cystic fibrosis (CF) airways, are often a diagnostic challenge. Few studies have compared culture-dependent methods with molecular identification making it hard to describe bacterial communities in a comprehensive manner. The aim of the study is to compare four different methods with respect to their similarities and differences in detection of bacteria. <h3>Methods</h3> We compared41 sputum samples fromroutine clinical-culture, extended-culture (aerobic and anaerobic), and molecular identification such as Roche 454-FLX Titanium and T-RFLP to assess concurrence between methodologies in detecting bacteria. The agreement between methodologies in detecting either absence or presence of bacterial taxa was assessed by Kappa (κ) statistics. <h3>Results</h3> The majority of bacterial taxa identified by culture were also identified with molecular analysis. In total 2, 60, 25, and 179 different bacterial taxa were identified with clinical-culture, extended-culture, T-RFLP and 454-FLX respectively. Clinical-culture, extended-culture and T-RFLP were poor predictors of species richness when compared to 454-FLX (p &lt; 0.0001). Agreement between methods for detecting <i>Pseudomonas</i> sp. and <i>Burkholderia</i> sp. was good with κ ≥ 0.7 [p &lt; 0.0001] and κ ≥ 0.9 [p &lt; 0.0001] respectively. Detection of anaerobic bacteria, such as <i>Prevotella </i>sp. and <i>Veillonella</i> sp., was moderate between extended-culture and 454-FLX with κ = 0.461 [p &lt; 0.0001] and κ = 0.311 [p = 0.032] respectively, and good between T-RFLP and 454-FLX with κ = 0.577 [p &lt; 0.0001] and κ = 0.808 [p &lt; 0.0001] respectively. Agreement between methods for other main bacterial taxa, such as <i>Staphylcoccus</i> sp. and <i>Streptococcus</i> sp., was poor with only a moderate agreement for detection of <i>Streptococcus</i> sp. observed between T-RFLP and 454-FLX (κ = 0.221 [p = 0.024]). <h3>Conclusions</h3> This study demonstrates the increased sensitivity culture-independent microbial identification such as the 454-FLX have over clinical-culture, extended-culture and T-RFLP methodologies. The extended-culture detected majority of the most prevalent bacterial taxa associated with chronic colonisation of the CF airways which were also detected by culture-independent methodologies. However, agreement between methods in detecting number of potentially relevant bacteria is largely lacking.