tbuckley/cabot-search huggingface dataset:
241 REDUCING ALPHA-FETOPROTEIN WITH INTERFERON THERAPY SUPPRESSES HEPATOCARCINOGENESIS IN HEPATITIS C VIRUS-INFECTED PATIENTS WHO ARE VIROLOGICAL RESPONDERS AND NON-RESPONDERS
Authors: Y. Asahina, K. Tsuchiya, N. Tamaki, M. Sato, T. Tanaka, I. Hirayama, Y. Yasui, K. Ueda, T. Kuzuya, H. Nakanishi, J. Itakura, M. Kurosaki, N. Izumi
Journal: Journal of Hepatology (2010)
Routine ultrasound scanning in pregnancy: Link with left handedness not established: Authors' reply
Authors: K. a Salvesen, S. H Eik-Nes, L. J Vatten, K. Hugdahl, L. S Bakketeig
Journal: BMJ (1993)

Data quoted by McGavock and colleagues are sometimes misleading.They quote relapse rates for peptic ulceration of 30% after bismuth chelate treatment.However, the references they quote indicated relapse rates of 61% and 47% in patients treated with bismuth chelate alone.45To obtain the quoted improved rates of relapse with, for example, bismuth chelate and tinidazole would incur additional net NHS costs of about C69 per patient for tinidazole.Such discrepancies in quoted data further weaken the conclusions of the paper.Consideration of crude prescribing figures without regard to morbidity data, secular trends, and emerging evidence of efficacy is an insecure foundation for the criticisms which the authors make of general practitioners in Northern Ireland and, by extension, the pharmaceutical industry.Neither general practitioners nor administrators should act on the conclusions drawn from such inadequate data.
Differential effects of MCP-1 and leptin on collateral flow and arteriogenesis
Authors: S SCHIRMER, I BUSCHMANN, M JOST, I HOEFER, S GRUNDMANN, J ANDERT, S ULUSANS, C BODE, J PIEK, N VANROYEN
Journal: Cardiovascular Research (2004)

Strategies to therapeutically stimulate collateral artery growth in experimental models have been studied intensively in the last decades. However, the experimental methods to detect collateral artery growth are discussed controversially and vary significantly. We compared different methods in a model of arteriogenesis in the rabbit hind limb and determined the effects on collateral flow of a known pro-arteriogenic factor, monocyte chemoattractant protein-1 (MCP-1), and a cytokine not previously evaluated for its arteriogenic efficacy, the adipocytokine leptin.Forty-two New Zealand White rabbits received either MCP-1, leptin or PBS after ligation of the right femoral artery. The pro-arteriogenic effect of MCP-1 was confirmed by flow measurements during reactive hyperemia, as demonstrated by increased flow ratio (PBS 0.56+/-0.07 vs. MCP-1 0.77+/-0.06, no unit, p<0.0001), ankle-brachial index and microsphere-based conductance measurements (PBS 50.8+/-2.1 vs. MCP-1 225.8+/-8.8 ml/min/100 mm Hg, p<0.001). Biological activity of leptin on rabbit monocytes was shown by a dose dependent increase in Mac-1 expression. In-vivo administration of leptin also led to an increase in hyperemic flow and flow ratio (leptin 0.69+/-0.03, p<0.05 vs. PBS), but not to an increase in collateral conductance (leptin 54.7+/-4.1 ml/min/100 mm Hg, p=ns vs. PBS) or proliferation of vascular smooth muscle cells (Ki-67 staining: PBS 24.7+/-3.9%, leptin 22.7%+/-0.8% (p=ns), MCP-1 32.0+/-1.9% (p<0.01)). Ki-67 mRNA measured by real-time polymerase chain reaction increased (8.8+/-3.1-fold, p<0.01) during natural arteriogenesis, and was further enhanced (25.5+/-8.1-fold, p<0.005) after stimulation with MCP-1.MCP-1 and leptin increase collateral flow in the rabbit hind limb model. In contrast to MCP-1, leptin does not enhance direct markers of vascular proliferation such as collateral conductance under maximal vasodilation and proliferation indices. The observed increase in hyperemic collateral flow thus most probably can be attributed to the well-documented vasodilatory effects of leptin. These data stress the necessity of the use of proliferation markers and microsphere-based conductance measurements under maximal vasodilation in order to separate effects of substances on vascular proliferation from effects on vasodilation.
Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE)
Authors: A. Blauvelt, J.C. Prinz, A.B. Gottlieb, K. Kingo, H. Sofen, M. Ruer-Mulard, V. Singh, R. Pathan, C. Papavassilis, S. Cooper
Journal: British Journal of Dermatology (2014)

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, demonstrated efficacy and safety in moderate-to-severe plaque psoriasis when administered via subcutaneous injection. Self-administration by pre-filled syringe (PFS) can offer patients clinical benefits of a drug, with increased convenience.To assess efficacy, safety and usability of secukinumab administration via PFS in subjects with moderate-to-severe plaque psoriasis.Subjects in this phase 3 trial were randomized 1 : 1 : 1 to secukinumab 300 or 150 mg or matching placebo. Results to week 12 are presented here. Each treatment was delivered using a PFS once weekly to week 4, and again at week 8. Co-primary endpoints were secukinumab superiority over placebo for week 12 PASI 75 (≥ 75% reduction in Psoriasis Area and Severity Index) and IGA mod 2011 (2011 modified Investigator's Global Assessment) 0/1 response rates. Secondary endpoints included PFS usability, determined by observer rating of successful, hazard-free self-injection and subject rating of acceptability by the Self-Injection Assessment Questionnaire (SIAQ).Co-primary endpoints were met, with demonstration of superiority for each secukinumab dose vs. placebo at week 12 (PASI 75: 75·9%, 69·5% and 0% for secukinumab 300 mg, 150 mg and placebo; IGA mod 2011 0/1: 69·0%, 52·5% and 0%, respectively; P < 0·0001 for all comparisons vs. placebo). PFS usability was high: 100% of subjects successfully self-administered treatment at week 1, and subjects reported high SIAQ-assessed acceptability of the PFS throughout the trial. No new/unexpected safety signals were observed.Secukinumab administration by PFS was effective, with an acceptable safety profile and high usability. The PFS provides a reliable, convenient form of secukinumab administration in subjects with moderate-to-severe plaque psoriasis.
Reproductive Endocrinology, Surgery and Technology
Authors: Irwin E. Thompson
Journal: JAMA (1997)

This book is almost certainly the most ambitious publishing project yet undertaken in the field of reproductive medicine. It contains over 2400 pages of text and illustrations in two volumes. As the editors state, "It is divided into the three main areas of the discipline: the ontogeny and function of the reproductive axis, the diagnosis and management of disorders of the reproductive axis and the diagnosis and management of human infertility." By design, part 1 is virtually an independent textbook of reproductive physiology, extremely comprehensive, well edited, and beautifully illustrated. Herein lies the only minor problem of this two-volume text: the index naturally is at the end of volume 2, thereby making any needed reference to volume 1 a bivolume endeavor. Nonetheless, part 1 is full of extremely well-written chapters contributed by distinguished authors and represents a completely contemporary review of reproductive physiology as we understand it today. Chapter 7,
It’s not all in the cilium, but on the road to it: Genetic interaction network in polycystic kidney and liver diseases and how trafficking and quality control matter
Authors: Carsten Bergmann, Ralf Weiskirchen
Journal: Journal of Hepatology (2011)

Autosomal dominant polycystic liver disease results from mutations in PRKCSH or SEC63. The respective gene products, glucosidase IIb and SEC63p, function in protein translocation and quality control pathways in the endoplasmic reticulum. Here we show that glucosidase IIb and Sec63p are required in mice for adequate expression of a functional complex of the polycystic kidney disease gene products, polycystin-1 and polycystin-2. We find that polycystin-1 is the rate-limiting component of this complex and that there is a dose–response relationship between cystic dilation and levels of functional polycystin-1 following mutation of Prkcsh or Sec63.Reduced expression of polycystin-1 also serves to sensitize the kidney to cyst formation resulting from mutations in Pkhd1, the recessive polycystic kidney disease gene. Finally, we show that proteasome inhibition increases steady-state levels of polycystin-1 in cells lacking glucosidase IIb and that treatment with a proteasome inhibit or reduces cystic disease in orthologous gene models of human autosomal dominant polycystic liver.
Pityriasis rubra pilaris: Was it the first manifestation of colon cancer in a patient with pre-existing psoriasis?
Authors: Magalys Vitiello, Maria Miteva, Paolo Romanelli, Jorge Castaneda, Dagoberto Garces-Milanes, Robert Kirsner, Francisco A. Kerdel
Journal: Journal of the American Academy of Dermatology (2013)
Simultaneous expression of H-2-restricted and alloreactive recognition by a cloned line of influenza virus-specific cytotoxic T lymphocytes.
Authors: T J Braciale, M E Andrew, V L Braciale
Journal: The Journal of Experimental Medicine (1981)

Based on theoretical considerations and several types of experimental evidence with heterogeneous cell populations it has been proposed that alloreactive T cells and major histocompatibility complex (MHC)-restricted T cells directed to foreign non-NHC antigens represent overlapping subsets. In this report we provide direct evidence for this hypothesis at the clonal level. We have isolated a cloned continuous influenza virus-specific cytotoxic T cell (CTL) line derived from a single (H-2b X H-2d)F1 CTL precursor which simultaneously exhibits H-2-restricted cytotoxicity of influenza A/Japan/305/57 virus in association with H-2Kd and alloreactive cytotoxicity for H-2Kk alloantigen. Cold target inhibition data demonstrate that both MHC-restricted and alloreactive recognition is mediated by the same cell population. In addition to cross-reactivity at the target cell level, we shown that this cloned CTL line can be specifically stimulated to proliferate either by A/Japan/305/57 virus-infected cells expressing H-2Kd or by uninfected cells of the H-2Kk haplotype.
Abstract 1735: Silencing survivin splice variant 2B leads to antitumor activity in taxane-resistant ovarian cancer
Authors: Cristian Rodriguez-Aguayo, Pablo E. Vivas-Mejia, Hee-Dong Han, Mian M.K. Shahzad, Fatma Valiyeva, Mineko Shibayama, Arturo Chavez-Reyes, Anil K. Sood, Gabriel Lopez-Berestein
Journal: Cancer Research (2011)

Abstract Survivin, a protein highly expressed in human cancers is involved in both control of cell cycle progression and inhibition of apoptosis. Transcription of the survivin gene locus (BIRC-5) yields at least 5 alternative splice variants including survivin wild-type (WT), survivin ΔEx3, survivin 2B, survivin 3B, and survivin 2α. Here, we studied the role of survivin and its splice variants in taxane-resistant ovarian cancer. Taxane-resistant ovarian cancer cells express higher survivin mRNA levels than their taxane-sensitive counterparts. Survivin 2B expression was significantly higher in taxane-resistant compared to sensitive cells. Small-interference RNAs (siRNAs) targeting survivin were designed to silence all survivin splice variants (T-siRNA) or survivin 2B (2B-siRNA). Silencing survivin 2B induced growth inhibitory effects similar to silencing total survivin in vitro. In addition, survivin 2B siRNA incorporated into DOPC nanoliposomes resulted in significant reduction in tumor growth (p&amp;lt;0.05) in the HeyA8.MDR and SKOV3.TR models, and these effects were similar to T-siRNA-DOPC. The anti-tumor effects were further enhanced in combination with docetaxel chemotherapy (p&amp;lt;0.01). Finally, we found a significant association between survivin 2B expression and progression free survival in 117 epithelial ovarian cancers obtained at primary debulking surgery. These data identify survivin 2B as an important target in ovarian cancer, and provide a translational path forward for developing new therapies against this target. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1735. doi:10.1158/1538-7445.AM2011-1735
Abstract 754: Development of death receptor agonists for breast cancer therapy
Authors: Rakesh K. Srivastava, Chris Jackman, Rachel Davis, Sharmila Shankar
Journal: Cancer Research (2010)

Abstract TRAIL and death receptor (TRAIL-R1 and TRAIL-R2) agonistic antibodies have been shown to induce apoptosis in cancer cells and their clinical trials have produced positive results. However, there are no small organic molecular weight compounds that bind to TRAIL-death receptors and induce apoptosis specifically in cancer cells. The purpose of this study was to identify and characterize death receptor agonists (DRAs)/ small molecular weight organic compounds that induce apoptosis in breast cancer cells. The pharmacokinetics of the DRA with a single oral dose was characterized in nude mice. Blood was collected over 72 hour period after drug administration, and analyzed by HPLC-MS/MS for plasma drug concentration. The Cmax, tmax, and AUC of DRA was measured. DRAs inhibited cell viability and colony formation, and induced apoptosis in estrogen-dependent (MCF-7) and independent (MDA-MB-231 and MDA-MB-468) human breast cancer cell lines, but had no effect on human normal mammary epithelial cells and hepatocytes. The ability of DRAs to induce apoptosis was further enhanced in the presence of TRAIL. DRAs formed active TRAIL-DISC (death-inducing signaling complex) similar to that of TRAIL. DRAs inhibited the growth of orthotopically implanted MDA-MB-231 and MDA-MB-468 tumors in nude mice. Histological examination of tumor tissues derived from DRAs-treated nude mice revealed massive caspase-3 activation and apoptosis. Pharmacokinetic data demonstrate that DRA possesses a long terminal half-life, which is acceptable for further clinical development. In conclusion, we have identified, for the first time, DRAs that can be used in the clinic for the treatment of human breast cancer. 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 754.
EXCRETION OF THE LIGNANS ENTEROLACTONE AND ENTERODIOL AND OF EQUOL IN OMNIVOROUS AND VEGETARIAN POSTMENOPAUSAL WOMEN AND IN WOMEN WITH BREAST CANCER
Authors: H. Adlercreutz, R. Heikkinen, M. Woods, T. Fotsis, J.T. Dwyer, B.R. Goldin, S.L. Gorbach
Journal: The Lancet (1982)
Abstract 3596: Comparison of intravenous microdialysis sampling to standard blood sampling to determine free etoposide exposure in non-human primates
Authors: Devang Pastakia, Cynthia McCully, Diane Cole, John Bacher, Rafael Cruz, Jaishri Blakeley, Brigitte Widemann, Frank Balis, Elizabeth Fox
Journal: Cancer Research (2010)

Abstract Background: Microdialysis (MD) is a method for continuously sampling small molecules in tissue extracellular fluid in vivo. To determine if free (non-protein bound) drug exposure (AUC) in plasma could be accurately measured by MD under non-steady state conditions, we compared intravenous MD to standard serial plasma sampling during and after a short infusion of etoposide. Methods: CMA IView 64 catheters (10 mm PAES membrane with 20 kD MWT cutoff) were surgically implanted into the external jugular vein of Rhesus monkeys (Macaca mulatta). Catheter inflow and outflow tubing was tunneled subcutaneously from neck to the area on back between shoulder blades, brought through skin and attached to a MD pump (CMA 106 pump with fixed flow rate of 0.3 μL/min). The MD pump was secured in a fitted mesh jacket on the dorsum of the awake animal. Retrodialysis using 10 µM etoposide was used to measure in vivo relative recovery (RR) in each catheter. Following retrodialysis and catheter re-equilibration with normal saline, etoposide (5 mg/kg) was administered IV over 1 h. Serial plasma samples were collected during the infusion and for 8 h post-infusion. Free etoposide was extracted by ultrafiltration. MD samples were collected continuously over a single collection interval (0-9 h) or split into two collection intervals (0-3 h and 3-9 h). Etoposide was quantified using HPLC-electrochemical detection (linear range 0.05 - 10 μM). The etoposide concentration in MD samples was corrected for in vivo RR. The AUC was calculated by the linear trapezoidal method for serial plasma sampling and by summation of the concentration x time intervals for MD. Results: Simultaneous MD and serial plasma sampling was performed in 5 animals. The in vivo RR of etoposide ranged from 86.9 - 99.4%. The mean AUC0-9h for plasma free etoposide was 3.27 (median 3.81, range 2.11 - 5.15) μM·h. The mean AUC0-9h for MD sampling was 2.68 (median 3.02, range 1.75 - 3.65) μM·h. The mean ratio of AUCMD:AUCplasma was 0.81. The mean (95% CI) for the difference in the paired MD and plasma AUC was − 0.7 (−1.94, 0.54) µM·h. Conclusions: Quantitative MD sampling for pharmacokinetic studies is feasible and the in vivo RR of etoposide is high. Free etoposide exposure by MD slightly underestimates the AUC compared to serial plasma sampling. Intravenous MD sampling may be a promising alternative to standard plasma sampling for calculating free etoposide exposure. 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 3596.
Abstract 5275: Biglycan is a specific marker and an autocrine angiogenic factor of tumor endothelial cells
Authors: Kazuyuki Yamamoto, Noritaka Ohga, Yasuhiro Hida, Nako Maishi, Taisuke Kawamoto, Kazuko Kitayama, Kosuke Akiyama, Takahiro Osawa, Miyako Kondoh, Kichizo Kaga, Satoshi Hirano, Nobuo Shinohara, Masanobu Shindoh, Kyoko Hida
Journal: Cancer Research (2012)

Abstract Tumor angiogenesis is necessary for solid tumor progression and metastasis. Tumor blood vessels are morphologically different from their normal counterparts. We isolated tumor endothelial cells (TECs), demonstrated their abnormalities, compared gene expression profiles of TECs and normal endothelial cells (NECs) by microarray analysis and identified several genes upregulated in TECs. We focused on the gene encoding biglycan, a small leucine-rich repeat proteoglycan. Biglycan is overexpressed in inflammation and fibrosis. However, there has been no report about the expression or the function of biglycan in TEC. In this study, we investigated the expression and the role of biglycan in TECs. Real-time PCR, western blotting and immunocytochemistry revealed higher biglycan expression levels in TECs than in NECs. Furthermore, we confirmed that biglycan was secreted from TECs. Biglycan knockdown inhibited cell migration and tube formation in TECs. TLR2 and TLR4 are the biglycan receptors. TLR2 and TLR4 blocking antibodies suppressed biglycan mediated cell migration and tube formation. We isolated TECs from human renal cell carcinoma tissue and NECs from normal renal tissue in the same patients. TECs and NECs were obtained from six patients. Real-time RT-PCR revealed that the biglycan expression levels were significantly higher in four of the six TEC samples than in the corresponding NEC samples. Furthermore, immunostaining revealed strong biglycan expression in vivo in several human tumor vessels, as in mouse TECs. Biglycan was detected in the sera of cancer patients but was hardly detected in those of healthy volunteers. Biglycan is an autocrine angiogenic factor stimulating tumor endothelial cell migration and tube formation. These findings suggested that biglycan is a novel TEC marker and a target for anti-angiogenic therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5275. doi:1538-7445.AM2012-5275
Type II diabetes of early onset: a distinct clinical and genetic syndrome?
Authors: S O'Rahilly, R S Spivey, R R Holman, Z Nugent, A Clark, R C Turner
Journal: BMJ (1987)

The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes.
New Zealand's health reforms: a clash of cultures
Authors: A. Hornblow
Journal: BMJ (1997)

The recent election in New Zealand resulted in the new coalition government rejecting key aspects of the National government's controversial, Treasury led health reforms implemented in 1993. 1 2 Based on the largely successful economic and state sector reforms of the 1980s, the health reforms had two key goals: improved efficiencies and better access, especially to elective surgery. 3Superficial assessment of the hospital sector had led to expectations that savings of 20-30% could be achieved through competitive and commercial incentives. 3 Yet actual expenditure has increased by this amount, and waiting lists have grown by 50% since 1993. 1 4 The new government favours collaboration over competition, and its health policy is to abolish the market oriented CHEs (Crown health enterprises) and replace them with regional hospital and community service units, which will be required to improve the health of their communities. 2The four regional purchasers that have a contract with providers are to be replaced with a central funding authority.The funder-provider split remains, but "purchasing" has been rejected as being too commercial.The government now seems to recognise that health is primarily a social service, not a business.The bottom line is not profit; it is better health outcomes.Up the garden path-New Zealand's prime minister expresses qualms to the minister of health about the direction of the health reforms