tbuckley/cabot-search huggingface dataset:
Abstract 3172: ZEB1 regulation in breast epithelial cells: Role of IGF-1 in the CCN6 modulation pathway
Authors: Guadalupe Lorenzatti, Anupama Pal, Wei Huang, Ana M. Cabanillas, Celina G. Kleer
Journal: Cancer Research (2010)

Abstract Background: During cancer progression, the transcription factor ZEB1 has been implicated in the regulation of key genes triggering the EMT (Epithelial to Mesenchymal Transition) program. We previously reported that the matricellular protein CCN6 is lost or reduced in highly aggressive breast carcinomas. Furthermore, we have identified CCN6 as a tumor suppressor in breast cancer whose down-regulation enhances IGF-1 signaling on breast epithelial cells. Recently, our lab observed that stable inhibition of CCN6 in benign mammary epithelial cells causes EMT and invasion with marked up-regulation of ZEB1. Since IGF-1 is shown to up-regulate ZEB1 expression in epithelial prostate cancer cells we hypothesize that CCN6 may regulate EMT in breast cancers by modulating IGF-1 signaling and thereby regulating ZEB1 expression. Methods: Stable CCN6-deficient HME (Human Mammary Epithelial cells)(HME-CCN6 KD) were incubated with 500 ng/mL rhCCN6 protein. Western blots (WB) for ZEB1 and vimentin, inmunofluorescence, invasion and proliferation assays were performed. ZEB1 mRNA levels were evaluated by RT-qPCR (Taqman). IGF-1 expression was analyzed by RT-qPCR and WB on MDA-MB-231 and HME-CCN6 KD (pre- and post-rhCCN6 treatment) while IGF-1R, phospho-IGF-1R, IRS-1 and phospho-IRS-1 expression were investigated by WB. Lentivirus-mediated (pLK.O1) short hairpin RNA targeting IGF1-R was performed in HME control and HME-CCN6 KD cells. WBs were done to assess expression of proteins of interest. mRNA content was evaluated by RT-qPCR. Results: CCN6 incubation of HME-CCN6 KD cells induced down-regulation of ZEB1 mRNA and protein levels as well as subcellular localization changes of the mesenchymal marker vimentin (“cap” pattern) evidenced as a decrease in vimentin expression by WB. hrCCN6 protein treatment also reduced proliferation and invasion abilities of HME-CCN6 KD cells compared to controls. In Addition, cell lines expressing low levels of CCN6 such us HME-CCN6 KD and MDA-MB-231 secreted IGF-1 in the conditioned media and showed activation of the IGF-1 signaling pathway. This phenomenon was reverted by CCN6 treatment, with reduction of both, IGF-1 protein and mRNA levels. IGF-1R down-regulation in HME-CCN6 KD cells decreased ZEB1 expression and induced the re-expression of cytokeratin-18 (epithelial marker). Conclusions: Our results suggest that CCN6 regulates ZEB1 expression and EMT in breast epithelial cells by modulating the IGF-1 signaling pathway. 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 3172.
In vitro dissolution rates of six 8-methoxypsoralen formulations
Authors: L.M.L. STOLK, A. PASMAN, R.H. CORMANE, P.A. ZWEITEN
Journal: British Journal of Dermatology (1987)

Dissolution rates in water of six oral 8-methoxypsoralen formulations were determined with both the rotating basket method and a column type flow-through method. Comparable and reproducible results were obtained with both methods. In view of the necessity in psoralen-UVA (PUVA) therapy that effective tissue concentrations of the drug be present in the skin during the irradiation period, we propose a requirement for a dissolution rate of 8-MOP tablets or capsules of at least 80% within 25 min. None of the three preparations registered in The Netherlands met this requirement. However, two preparations from abroad and a new capsule formulated in our pharmacy department with solid 8-MOP dispersed in polyethylene glycol 6000 showed satisfactory dissolution profiles.
Digital Necrosis Associated with Dexfenfluramine
Authors: Mark A. Marinella, Beth Anne Berrettoni
Journal: New England Journal of Medicine (1997)

Valvular Heart Disease Associated with Fenfluramine-PhentermineTo the Editor: Nineteen of the 24 patients described by Connolly et al. (Aug.28 issue) 1 in the primary report linking fenfluramine and phentermine with cardiac valvular abnormalities were identified in Fargo, North Dakota, a city with only 74,111 residents in 1990. 2 Twelve of the Fargo cases, and perhaps the association itself, were initially identified by an astute echocardiographic sonographer.This relation had not been discovered previously despite the fact that fenfluramine has been approved since 1973 and that 18 million prescriptions for these drugs were filled in 1996 alone. 1 Diagnosis of a cardiac abnormality in 18 of the 24 patients was based on echocardiographic findings of valvular insufficiency and "unusual valvular morphology." 1 The key unanswered question is whether these echocardiographic abnormalities have clinical import for the majority of patients using these drugs or whether they are simply a visual finding.The drugs are so widely used and these reports have prompted such widespread concern that all efforts should be taken to be certain that the association with important heart disease is real.On the other hand, if the incidence rate in Fargo is confirmed and if the echocardiographic abnormalities frequently lead to clinically significant disease, these drugs will be responsible for a major epidemic of valvular heart disease that could have been far worse if not detected by the echocardiographer.
An X-ray Microscopic Study of the Vasa Vasorum of the Normal Human Aortic Arch
Authors: J. A. Clarke
Journal: Thorax (1965)

1.

The arterial and venous sides of the microcirculation in the normal human abdominal aorta have been shown.




2.

The arterial vasa originate extramurally from the lumbar and mesenteric arteries to be distributed to the outer two thirds of the media.




3.

The venous vasoriginate in the inner third of the media, and drain through the aortic wall into circumferential adventitial veins, which are tributaries of the lumbar veins.




4.

The capillary-venule bed lay in the inner third of the media.




5.

No injection medium entered the intima.
O63 EFFICACY AND SAFETY OF THE ALL-ORAL REGIMEN, MK-5172/MK-8742 +/− RBV FOR 12 WEEKS IN GT1 HCV/HIV CO-INFECTED PATIENTS: THE C-WORTHY STUDY
Authors: M. Sulkowski, J. Mallolas, S. Pol, M. Bourliere, J. Gerstoft, O. Shibolet, R. Nahass, E. DeJesus, M. Shaughnessy, P. Hwang, J. Wahl, M.N. Robertson, B. Haber
Journal: Journal of Hepatology (2014)
Mental illness--not a laughing matter
Authors: N. Mukadam
Journal: BMJ (2009)

Part of every introduction in small talk is the discussion of what one does for a living. Most people, on finding out that I am a psychiatrist, will cast a pitying glance at my husband, giggle nervously, and edge away from me saying something to the effect that, “Oh, I had better watch what I say and do then.” All of this, of course, is meant to imply that I have, by virtue of my training, some sort of psychic or mind reading abilities and that mere mortals had better beware. It’s mostly done in jest, and I sometimes play along. After all, psychic powers would make my …
Impact of counselling on careseeking behaviour in families with sick children: cluster randomised trial in rural India
Authors: Pavitra Mohan, Sharad D Iyengar, Jose Martines, Simon Cousens, Kalpana Sen
Journal: BMJ (2004)

To assess whether training doctors in counselling improves careseeking behaviour in families with sick children.Pair matched, community randomised trial conducted in 12 primary health centres (six pairs). Doctors in intervention centres were trained in counselling, communication, and clinical skills, using the integrated management of childhood illness approach.Rural district in Rajasthan, India.Children aged under 5 years presenting for curative care and their mothers were recruited and visited monthly at home for six months. A total of 2460 children were recruited (1248 intervention, 1212 control).Careseeking behaviour of mothers for sick children; mothers' knowledge and perceptions of seeking care; counselling performance of doctors.For episodes of illness with at least one reported danger sign, 15% of intervention group mothers and 10% of control group mothers reported having sought care from an appropriate provider promptly; this difference was not statistically significant (relative risk reduction 5%, 95% confidence interval -0.4% to 11%; P = 0.07). One month after training, intervention site doctors counselled more effectively than control group doctors, but at six months their performance had declined. A greater proportion of mothers in the intervention group than in the control group recalled having had at least one danger sign explained (45% v 8%; P = 0.02).Mothers' appreciation of the need to seek prompt and appropriate care for severe episodes of childhood illness increased, but their careseeking behaviour did not improve significantly.
Risks and benefits of omega 3 fats: A few thoughts on systematic review
Authors: Ka He, Yiqing Song
Journal: BMJ (2006)

EDITOR—Hooper et al's conclusions that omega 3 fats have no effect on total mortality, combined cardiovascular events, or cancer are somewhat misleading.1

Firstly, their null findings could be partly explained by the use of the composite end points. They ignore strong biological evidence for the potentially disease specific effects of omega 3 fat. The underlying hypotheses for this study are not clearly …
Atropine poisoning in early infancy due to Eumydrin drops
Authors: J. Lagerfelt
Journal: BMJ (1982)

been in a surgical bed for a prolonged period is a "bed-blocker."On our evidence, most such patients are likely to be appropriately placed.Preservation and expansion of residential, geriatric, and psychogeriatric facilities are essential if some of the major needs of the aged population are to be met.It would be wrong, however, to expect such an expansion to solve the problem of prolonged surgical bed occupancy by the elderly.
Circulating Insulin and Insulin Growth Factor-1 Are Independent Determinants of Left Ventricular Mass and Geometry in Essential Hypertension
Authors: Paolo Verdecchia, Gianpaolo Reboldi, Giuseppe Schillaci, Claudia Borgioni, Antonella Ciucci, Maria Pia Telera, Fausto Santeusanio, Carlo Porcellati, Paolo Brunetti
Journal: Circulation (1999)

Background —It is unclear whether insulin and insulin-like growth factor-1 (IGF-1) are independent determinants of left ventricular (LV) mass in essential hypertension. Methods and Results —We studied 101 never-treated nondiabetic subjects with essential hypertension. All had 24-hour noninvasive ambulatory blood pressure (ABP) monitoring and a 75-g oral glucose tolerance test. We determined fasting glucose, insulin, and IGF-1 and postload glucose and insulin 2 hours after glucose. Insulin resistance was estimated by the homeostasis model assessment (HOMA IR ) formula. LV mass showed an association with body mass index (BMI) ( r =0.47; P &lt;0.01), postload insulin ( r =0.54; P &lt;0.01), HOMA IR ( r =0.39; P &lt;0.01), and IGF-1 ( r =0.43; P &lt;0.01) and a weaker association with average 24-hour systolic and diastolic ABPs ( r =0.29 and r =0.26; P &lt;0.05) and basal insulin ( r =0.31; P &lt;0.05). Relative wall thickness was positively related to IGF-1 ( r =0.39; P &lt;0.01) but not to fasting or 2-hour postload insulin, HOMA IR , and glucose. In a multiple regression analysis, the final LV mass model ( R 2 =0.64) included IGF-1, postload insulin, average 24-hour systolic ABP, sex, and BMI. IGF-1 and postload insulin accounted for &gt;40% of variability of LV mass. The final model ( R 2 =0.36) for relative wall thickness included IGF-1 (16% total explained variability), average 24-hour systolic ABP, sex, BMI, and age but not insulin and HOMA IR . Conclusions —These data indicate that insulin and IGF-1 are powerful independent determinants of LV mass and geometry in untreated subjects with essential hypertension and normal glucose tolerance.
Reduced intensity stem cell transplantation for treatment of class 3 Lucarelli severe thalassemia patients
Authors: Suradej Hongeng, Samart Pakakasama, Ampaiwan Chuansumrit, Nongnuch Sirachainan, Thanyachai Sura, Artit Ungkanont, Suporn Chuncharunee, Saengsuree Jootar, Surapol Issaragisil
Journal: American Journal of Hematology (2007)

Abstract Bone marrow transplantation is the only therapeutic option that can potentially eliminate thalassemic disease. Early results indicated that children in Class 3 Lucarelli had a much worse outcome because of high nonrejection mortality and high rejection rate. In the present study, reduced intensity stem cell transplantation (RIT) was performed in eight Class 3 Lucarelli patients conditioned by busulfan, fludarabine, and antilymphpcute globulin. One of the eight patients additionally received thiotepa, and total lymphoid irradiation (TLI), while one only received TLI. All patients received hydroxyurea 20 mg/kg/day daily ≥3 months before RIT. Peripheral blood stem cell (PBSCs) were given to a target number of CD34 + cells more than 5 × 10 6 cells/kg of recipient weight. Seven patients received T cell nondepleted PBSCs from matched siblings while one patient received purified CD34 + cells from two HLA antigen mismatched maternal PBSCs. The graft‐versus‐host disease (GvHD) prophylaxis included cyclosporine or tacrolimus and mycophenolate mofetil. Initially, an engraftment of donor cells was observed in all eight patients, but subsequently only six of eight patients had stable full donor engraftment. There were no deaths or Grade 3–4 acute GvHD in our patients. The present study lends support that the regimens described here produced minimal toxicity and resulted in stable full donor engraftment in the majority of the severe Class 3 Lucarelli thalassemia patients. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
The facts must be available
Authors: J. Fooks
Journal: BMJ (1996)

How the health service deals with severe mental illness which might pose a danger to others is always a matter of concern to the public. But it is often overlooked that it is the sufferer who is at the greatest risk. My daughter, who suffered from manic depression, received no treatment and committed suicide, aged 26, in September 1995.

I have been trying to ascertain what went wrong, how she could have been helped, and who is interested in preventing such tragedies in the future. So far I have had little success. It seems as if general practitioners are not as well informed about mental illness as they might be. My daughter had registered with a general practitioner in the south of England on starting a job there towards the end of 1994. She presented with severe weight loss and gastric disturbance; in January 1995 I …
Palliative Irradiation for Liver Metastases
Authors: Milada Turek-Maischeider
Journal: JAMA (1975)

Eleven patients underwent palliative irradiation for symptomatic liver metastases. The whole liver is included in the radiation field. The treatment is given with a cobalt teletherapy unit. Daily doses are 150 rads calculated in the midliver plane. The total dose employed is 2,500 rads given in a three-week period. Eight patients had good response, two moderate response, and one patient failed to respond to treatment. Liver function studies and liver scans also reflected the treatment response. All patients tolerated the treatment and no deaths were attributed to liver irradiation. The impression is that radiation therapy is valuable for the treatment of symptomatic liver metastases in the young patient who does not have a terminal condition.
CAN METABOLIC SYNDROME PREDICT THE VULNERABLE PLAQUE IN PATIENTS WITH CHRONIC STABLE ANGINA? INTRAVASCULAR ULTRASOUND ANALYSIS
Authors: Lee Min Goo, Myung Ho Jeong, Keun Ho Park, Doo Sun Sim, Young Joon Hong, Ju Han Kim, Youngkeun Ahn, Jeong Gwan Cho, Jong Chun Park, Jung Chaee Kang
Journal: Journal of the American College of Cardiology (2011)
THE PES CAVUS OF CONGENITAL SYPHILIS
Authors: C. W. GOFF
Journal: JAMA (1926)

In the course of a systematic study of congenital syphilis in the Kings County Hospital and the Long Island College Dispensary, Brooklyn, interesting features were brought to light, which do not break entirely new ground but aid in establishing certain hitherto obscure clinical findings as stigmas of congenital syphilis. Fournier, in 1875, first stated that syphilis was the cause of tabes dorsalis, and Erb later confirmed Fournier's work. While these two well known pioneers in neurosyphilography developed the specific side of tabes, Hutchinson, in 1896, brought out certain now generally acknowledged clinical findings as stigmas of congenital or hereditary syphilis, the Hutchinson triad, consisting of interstitial keratitis, notched incisors and eighth nerve deafness. Since these early times, a great mass of work has been carried out in the field of clinical and pathologic syphilis, which has brought about a clearer understanding of the disease. But, as yet, certain cases of
A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B
Authors: Toshimasa Yamauchi, Kazuo Hara, Shiro Maeda, Kazuki Yasuda, Atsushi Takahashi, Momoko Horikoshi, Masahiro Nakamura, Hayato Fujita, Niels Grarup, Stephane Cauchi, Daniel P K Ng, Ronald C W Ma, Tatsuhiko Tsunoda, Michiaki Kubo, Hirotaka Watada, Hiroshi Maegawa, Miki Okada-Iwabu, Masato Iwabu, Nobuhiro Shojima, Hyoung Doo Shin, Gitte Andersen, Daniel R Witte, Torben Jørgensen, Torsten Lauritzen, Annelli Sandbæk, Torben Hansen, Toshihiko Ohshige, Shintaro Omori, Ikuo Saito, Kohei Kaku, Hiroshi Hirose, Wing-Yee So, Delphine Beury, Juliana C N Chan, Kyong Soo Park, E Shyong Tai, Chikako Ito, Yasushi Tanaka, Atsunori Kashiwagi, Ryuzo Kawamori, Masato Kasuga, Philippe Froguel, Oluf Pedersen, Naoyuki Kamatani, Yusuke Nakamura, Takashi Kadowaki
Journal: Nature Genetics (2010)
Thinking about repairing thinking
Authors: R. M. Ridley
Journal: Behavioral and Brain Sciences (1995)

Abstract The work of Sinden et al. suggests that it may be possible to produce improvement in the “highest” areas of brain function by transplanting brain tissue. What appears to be the limiting factor is not the complexity of the mental process under consideration but the discreteness of the lesion which causes the impairment and the appropriateness and accuracy of placement of the grafted tissue.
Graft regeneration and host liver atrophy after auxiliary heterotopic liver transplantation for chronic liver failure
Authors: Pierre J. A. Willemse, Lambert Ausema, Onno T. Terpstra, Eric P. Krenning, Fibo W. J. Ten Kate, Solko W. Schalm
Journal: Hepatology (1992)

We studied the size of the liver graft and the host liver in six consecutive patients undergoing auxiliary heterotopic liver transplantation for chronic end-stage liver disease. In all cases, a liver reduced in size by left lateral hepatectomy was inserted. The sizes of the graft and host liver were estimated by planimetry of two-dimensional di-isopropyl iminodiacetic acid scintigrams taken 3, 7, 21, 90 and 180 days after surgery. Graft size increased from a mean of 12.2 cm2 (95% confidence interval = 10.2 to 14.1) on day 3 to a maximum of 14.8 cm2 (95% confidence interval = 13.4 to 16.1) on day 21 and remained stable thereafter; in contrast, the host liver decreased in size from 9.6 cm2 (95% confidence interval = 6.8 to 12.3) on day 3 to 3.9 cm2 (95% confidence interval = 3.0 to 4.8) at mo 6. We conclude that in patients with chronic liver failure, an auxiliary allograft reduced in size and placed adjacent to the host liver shows regenerative growth within 3 wk, whereas the host liver atrophies in 3 to 6 mo.
NHS is told to think radically and move quickly to survive public spending squeeze
Authors: C. White
Journal: BMJ (2009)

The time has come for some radical thinking and nimble footwork if the health service is to survive the squeeze on public spending without compromising the quality of care, NHS leaders have warned.

Speaking in Liverpool last week at the annual conference of the NHS Confederation, the representative body for most NHS organisations, Mike Farrar, chief executive of NHS North West, said that the NHS faced a “very, very difficult” future with the enforced contraction of public sector spending.

“If the recession has any benefit, it’s that it can be a great catalyst for doing things differently,” he said. “Arguably, we should have been doing for the past five years what we are going to have to do …
The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice
Authors: Shigetomo Fukuhara, Szandor Simmons, Shunsuke Kawamura, Asuka Inoue, Yasuko Orba, Takeshi Tokudome, Yuji Sunden, Yuji Arai, Kazumasa Moriwaki, Junji Ishida, Akiyoshi Uemura, Hiroshi Kiyonari, Takaya Abe, Akiyoshi Fukamizu, Masanori Hirashima, Hirofumi Sawa, Junken Aoki, Masaru Ishii, Naoki Mochizuki
Journal: Journal of Clinical Investigation (2012)

The bioactive lysophospholipid mediator sphingosine-1-phosphate (S1P) promotes the egress of newly formed T cells from the thymus and the release of immature B cells from the bone marrow. It has remained unclear, however, where and how S1P is released. Here, we show that in mice, the S1P transporter spinster homolog 2 (Spns2) is responsible for the egress of mature T cells and immature B cells from the thymus and bone marrow, respectively. Global Spns2-KO mice exhibited marked accumulation of mature T cells in thymi and decreased numbers of peripheral T cells in blood and secondary lymphoid organs. Mature recirculating B cells were reduced in frequency in the bone marrow as well as in blood and secondary lymphoid organs. Bone marrow reconstitution studies revealed that Spns2 was not involved in S1P release from blood cells and suggested a role for Spns2 in other cells. Consistent with these data, endothelia-specific deletion of Spns2 resulted in defects of lymphocyte egress similar to those observed in the global Spns2-KO mice. These data suggest that Spns2 functions in ECs to establish the S1P gradient required for T and B cells to egress from their respective primary lymphoid organs. Furthermore, Spns2 could be a therapeutic target for a broad array of inflammatory and autoimmune diseases.
Miliary Tuberculosis in a Case of Acute Disseminated Lupus Erythematosus Treated with A.C.T.H
Authors: B. Walker
Journal: BMJ (1952)

MEDICs JoHuRwere, examined over a period of three months..They con- tained no atypical or abnormal cells, but on review cysto- scopy a small papilloma was discovered in his bladder.Ideally, in order to reduce the risk of false negatives to a minimum, the urine should be collected on rising, should be fresh when examined, and at least four smears should be studied from each deposit.Since the Papanicolaou staining method does not always show red blood cells clearly even when these are present in considerable numbers, it is desirable to devise new fixing and staining methods whereby both tumour cells and blood cells can be well seen in the same preparation.Hygiene Research Laboratories, at whose instance this work was carried out, and who has assisted in the preparation of this paper.