tbuckley/cabot-search huggingface dataset:
Combining Gene Expression Profiles and Clinical Parameters for Risk Stratification in Medulloblastomas
Authors: Ana Fernandez-Teijeiro, Rebecca A. Betensky, Lisa M. Sturla, John Y.H. Kim, Pablo Tamayo, Scott L. Pomeroy
Journal: Journal of Clinical Oncology (2004)

Purpose Stratification of risk in patients with medulloblastoma remains a challenge. As clinical parameters have been proven insufficient for accurately defining disease risk, molecular markers have become the focus of interest. Outcome predictions on the basis of microarray gene expression profiles have been the most accurate to date. We ask in a multivariate model whether clinical parameters enhance survival predictions of gene expression profiles. Patients and Methods In a cohort of 55 young patients (whose medulloblastoma samples have been analyzed previously for gene expression profile), associations between clinical and gene expression variables and survival were assessed using Cox proportional hazards models. Available clinical variables included age, stage (ie, the presence of disseminated disease at diagnosis), sex, histologic subtype, treatment, and status. Results Univariate analysis demonstrated expression profiles to be the only significant clinical prognostic factor (P = .03). In multivariate analysis, gene expression profiles predicted outcome independent of other criteria. Clinical criteria did not significantly contribute additional information for outcome predictions, although an exploratory analysis noted a trend for decreased survival of patients with metastases at diagnosis but favorable gene expression profile. Conclusion Gene expression profiling predicts medulloblastoma outcome independent of clinical variables. These results need to be validated in a larger prospective study.
Editorial Note
Authors: J LEIBMAN, F A GOTCH, I S EDELMAN
Journal: Circulation Research (1960)

Data have been presented which indicate that the liquid scintillation spectrometer provides a convenient and accurate method for the assay of tritium in body fluids. By means of arterial disappearance curves and comparative measurements of concentrations in plasma, transudates, and cerebrospinal fluid from 1 to 6 hours after simultaneous injection, the distribution rates of tritiated water were compared to those of deuterium oxide. No significant difference was found in the behavior of these tracers under the conditions of this study. It is concluded, therefore, that THO and D 2 O are equally reliable for studies on the kinetics of water distribution and for the measurement of total body water.
Effects of monoclonal antibodies against the platelet glycoprotein IIb/IIIa complex on thrombosis and hemostasis in the baboon.
Authors: S R Hanson, F I Pareti, Z M Ruggeri, U M Marzec, T J Kunicki, R R Montgomery, T S Zimmerman, L A Harker
Journal: Journal of Clinical Investigation (1988)

To assess the hemostatic consequences and antithrombotic effectiveness of blocking the platelet glycoprotein (GP) IIb/IIIa receptor for fibrinogen and other adhesive glycoproteins in vivo, well characterized murine monoclonal antibodies against the platelet GP IIb/IIIa complex, AP-2 and LJ-CP8, were infused intravenously into baboons. Four animals each received doses of 0.2, 0.4, and 1.0 mg/kg of purified AP-2 IgG, and three animals were given 1.0 mg/kg of the F(ab)2 fragment of AP-2. Five additional animals were given 10 mg/kg LJ-CP8 IgG. At the highest dose, radiolabeled AP-2 IgG bound to an average of 33,000 sites on the circulating platelets. Serial measurements included platelet count, bleeding time, platelet aggregation (induced by ADP, collagen, and gamma-thrombin), and 111In-platelet deposition onto Dacron vascular grafts. Bleeding times were markedly prolonged after injection of 1.0 mg/kg AP-2 IgG (19.2 +/- 3.4 min), 1.0 mg/kg AP-2 F(ab)2 (16.5 +/- 1.8 min), and 10 mg/kg LJ-CP8 (greater than 30 min) vs. control studies (4.6 +/- 0.2 min), and remained prolonged for 48 h. With each antibody platelet aggregation was initially reduced or absent, with partial recovery over 48 h in a manner that was inversely related to dose. AP-2, both whole IgG and F(ab)2 fragment, but not LJ-CP8, caused a dose-dependent reduction (20-46%) in the circulating platelet count over 24 h. Neither AP-2 nor LJ-CP8 caused a reduction in intraplatelet platelet factor 4, beta-thromboglobulin, or [14C]serotonin. Graft-associated platelet thrombus formation was reduced by 73% (1.0 mg/kg AP-2 IgG and 10 mg/kg LJ-CP8) and 53% (1.0 mg/kg AP-2 F(ab)2) relative to control values. In contrast, neither heparin (100 U/kg) nor aspirin (32.5 mg/kg twice a day) showed antithrombotic efficacy in this model. Thus, antibodies that functionally alter the platelet GP IIb/IIIa complex may produce immediate, potent, and transient, antihemostatic, and antithrombotic effects.
Intratumoral injection of plasmid-encoded flagellin inhibits growth of NSCLC-cells in murine lung cancer model
Authors: Marek Jankowski, Tomasz Wandtke, Robert Lenartowski, Olga Haus, Piotr Kopinski
Journal: European Respiratory Journal (2012)

Lack of progress in the treatment of NSCLC urges to look for experimental therapeutic methods, such as gene therapy. Currently used therapeutic vectors can cause adverse effects, or have a limited potential to transduce cells. The aim of this work was 1) to construct a vector suited for gene therapy allowing for selective transduction of only tumor cells 2) to assess therapeutic potential of  Salmonella  flagellin (FliC).  Engineered plasmid vector was obtained by PCR synthesis. For the purpose of tumor-specific transcriptional activity it was necessary to design a two-step promoter unit system based on telomerase minimal promoter.  Influence of FliC on NSCLC cells was assessed by measuring proliferation of tansfected cells and by phenotyping of maturation markers on DCs incubated with A549 cells. NSCLC tumors in mice were injected with empty or FliC-coding vector. Tumor growth and survival of the mice were analyzed.  FliC-transfected A549 cells had significantly lower proliferative potential. Such cells enhanced maturation of MoDC as suggested by higher expression of CD80 and CD83. NSCLC-inoculated mice administered with a vector containing FliC gene had a significantly longer survival time (p  Designed two-step promoter unit allows for efficient and tumor-selective expression of therapeutic gene. Results suggest that NSCLC transduction with FliC gene may inhibit its proliferation  in vitro  and tumor growth  in vivo  and increase survival rate. Due to ambiguous results obtained in co-culture of transfected A549 and DC antitumor properties of FliC other than induction of DC maturation need to be considered.
Impact of Maternal Depression Across the First 6 Years of Life on the Child’s Mental Health, Social Engagement, and Empathy: The Moderating Role of Oxytocin
Authors: Yael Apter-Levy, Michal Feldman, Adam Vakart, Richard P. Ebstein, Ruth Feldman
Journal: American Journal of Psychiatry (2013)

Maternal depression across the postbirth period has long-term negative consequences for infant development. Little is known of the neurobiological underpinnings, but they could involve oxytocin, a neuropeptide that is dysfunctional in depression and is implicated in birth and parenting.The authors recruited a community cohort of women with high or low depression scores 2 days after childbirth and measured depression again at 6 and 9 months. When the child was 6, the authors evaluated the families of 46 chronically depressed mothers and 103 mothers reporting no depression since childbirth. The child was assessed for psychiatric diagnoses, social engagement, and empathy. Mother, father, and child were tested for salivary oxytocin level and variation in the rs2254298 single nucleotide polymorphism on the OXTR gene.Of the children of the chronically depressed mothers, 61% displayed axis I disorders, mainly anxiety and oppositional defiant disorder, compared with 15% of the children of nondepressed mothers. In the depressed mothers' families, salivary oxytocin was lower in mothers, fathers, and children, and the children had lower empathy and social engagement levels. The rs2254298 GG homozygous genotype was overrepresented in depressed mothers and their families, and it correlated with lower salivary oxytocin. Presence of a single rs2254298 A allele (GA or AA genotype) in depressed mothers markedly decreased risk of child psychopathology.The negative effect of chronic maternal depression on child social outcomes was related to genetic and peripheral biomarkers of the oxytocin system. This suggests a potential for oxytocin-based interventions.
Radiologic Aspects of Renovascular Hypertension
Authors: Joseph J. Bookstein
Journal: JAMA (1972)

Urograms were analyzed and correlated with arteriographic findings and therapeutic results in order to evaluate the reliability of the urogram screening procedure for unilateral renovascular disease and its usefulness in predicting surgical results. Major urographic features were disparity in renal length, calyceal appearance time, and concentration on late films. Minor urographic features analyzed included ureteral notching, decreased volume of the collecting system, parenchymal atrophy, and renal ptosis. All the major urographic features occurred more frequently in the presence of renovascular disease than in a comparable population of patients with essential hypertension. Delayed appearance time seemed to be the single most valuable urographic feature. The urogram was considered to be a satisfactory method for diagnosing the presence or absence of moderate or severe renovascular disease. Urography alone did not enable discrimination between patients who would respond favorably to surgery and those who would not.
PEDIATRICS LABORATORY RESEARCH
Authors: V. Caretti, A. Noll, P. Woo, M. Monje, J. Cockle, A. Bruning-Richardson, S. Picton, J. Levesley, E. Ilett, S. Short, A. Melcher, S. Lawler, L. Garzia, A. Dubuc, G. Pitcher, P. Northcott, A. Mariampillai, S. Mack, K. Zayne, T. Chan, P. Skowron, X. Wu, A. Lionel, S. Morrisy, C. Hawkins, P. Kongkham, J. Rutka, A. Huang, A. Kenney, V. Yang, M. Salter, M. Taylor, L. Garzia, S. Morrisy, P. Skowron, S. Jelveh, P. Lindsay, D. Largaespada, L. Collier, A. Dupuy, R. Hill, M. Taylor, T.-H. Hsieh, H.-W. Wang, W.-C. Cheng, T.-T. Wong, X. Huang, Y. He, A. Dubuc, R. Hashizume, W. Zhang, S. Stehbens, S. Younger, S. Barshow, S. Zhu, X. Wu, M. Taylor, S. Mueller, W. Weiss, D. James, M. Shuman, Y. N. Jan, L. Jan, M. Marigil, P. Jauregi, M. A. Idoate, E. Xipell, G. Aldave, M. Gonzalez-Huarriz, S. Tejada-Solis, R. Diez-Valle, A. Montero-Carcaboso, J. Mora, M. M. Alonso, K. Taylor, A. Mackay, N. Truffaux, O. Morozova, Y. Butterfield, C. Phillipe, M. Vinci, C. de Torres, O. Cruz, J. Mora, D. Hargrave, M. Monje, S. Puget, S. Yip, C. Jones, J. Grill, A. Kaul, Y.-H. Chen, S. Dahiya, R. Emnett, S. Gianino, D. Gutmann, T. Miwa, S. Oi, Y. Nonaka, H. Sasaki, K. Yoshida, E. Lopez, A. P. de Leon, C. Sepulveda, L. Zarate, J. Diego-Perez, W. Pong, L. Ding, M. McLellan, I. Hussain, R. Emnett, S. Gianino, S. Higer, J. Leonard, A. Guha, E. Mardis, D. Gutmann, C. Sarkar, P. Pathak, P. Jha, S. Purkait, V. Sharma, M. C. Sharma, V. Suri, M. Faruq, M. Mukherjee, B. Sivasankaran, R. P. Velayutham, I. R. Fraschilla, K. J. Morris, T. J. MacDonald, T.-A. Read, D. Sturm, P. Northcott, D. Jones, A. Korshunov, D. Picard, P. Lichter, A. Huang, S. Pfister, M. Kool, T.-W. Yao, J. Zhang, B. Anna, T. Brummer, N. Gupta, T. Nicolaides, K.-M. Chan, D. Fang, H. Gan, R. Hashizume, C. Yu, M. Schroeder, N. Gupta, S. Mueller, D. James, R. Jenkins, J. Sarkaria, Z. Zhang
Journal: Neuro-Oncology (2013)
The Address in Medicine
Authors: J. B. Bradbury
Journal: BMJ (1880)

that we must be judged.The greater the force, the greater the waste, uiless it be well applied.Our Sections, with the masterly addres es on various, subjects, are well calculated to tell of progress and to aid it, to thrash out the many questions of medical science, to ascertain the results of new medical practice, 1nd to stimulate thought and invention.Our meetings pro- mote business habits and administrative qualities, as well as sociality and friendship.Our JOURNAL is one of the best, and I believe it is the cheapest, of the media of medical intelligence which, the world possesses.Thus far we may be well content.But one work-a work that especially appertains to the Association, the work of collective action, of the pull altogether of eight thousand members of the profes- sion, I mean the work of cumulative observation, or accumulated data -has been too little attempted; or, if attempted, has been productive of too little result.I am aware that anything on a large scale of this kind is a serious undertaking, a gigantic enterprise; and I feel it, therefore, to be worthy of this gigantic Association.It is, perhaps, the only work in which all, or a large part, of the members can really and fully participate, and to which each can contribute his mite.It is almost the only way in which questions relating to temperamental, climac- teric, and topographical agencies upon disease and many others can be fully investigated and solved.To engage the members of the Association as
Outcome of Anti-Egfr Antibody Therapy in Metastatic Colorectal Cancer with Low-Frequency Kras Mutations
Authors: T. Hikosaka, K. Yamazaki, T. Tsushima, A. Todaka, T. Yokota, N. Machida, A. Fukutomi, Y. Onozawa, T. Nakajima, H. Yasui
Journal: Annals of Oncology (2013)
Bronchial rupture secondary to blunt chest trauma.
Authors: C Hartley, G N Morritt
Journal: Thorax (1993)

Bronchial injury due to blunt chest trauma is rare, and its rarity and the fact that it has two distinct modes of presentation may considerably delay diagnosis. Two recent cases illustrate the two main types of injury and presentation. In the first the rupture is intrapleural and air escapes into the pleural space; insertion of a chest drain leads to a continuous air leak. In the second type the rupture is largely extrapleural with little communication with the pleural cavity; initially symptoms may be mild or absent but complications may occur later.
Dispersion of Indicator Measured from Microvessels of Cat Mesentery
Authors: STEPHEN H. NELLIS, JEN-SHIH LEE
Journal: Circulation Research (1974)

The indicator-dilution method was used to investigate blood flow in the microvascular network of the mesenteric membrane of the cat by replacing the normal blood flow into the mesenteric artery with a dextran-saline solution for a finite period of time. The dilution of the dextran-saline bolus as it flowed downstream was measured in a selected arteriole and its adjacent venule with a microphotometric system. Based on an in vitro calibration study done on glass capillary tubes, the measured optical density was converted to the hematocrit. The dilution curve for a finite injection and for a step injection, the mean transit time (MTT), and the appearance time for the arteriole and the venule were computed. The dispersion found in the arterial system, a network of diverging branches, was reasonably well simulated by the dispersion in a parabolic flow system. However, the dispersion found in the venules, where the irregular capillary blood flow converges, was considerably skewed from that in a parabolic system. A wide distribution of MTT was found for the arterioles and the venules, and there was considerable overlap in the MTT distribution for these two groups. This finding cannot be simulated by a network with a parallel arrangement. The difference in MTT for pairs of arterioles and venules was distributed over a narrow range, probably indicating shunt flow in the mesenteric microvascular network.
Randomised trial of coronary intervention with antibody against platelet IIb/IIIa iritegrin for reduction of clinical restenosis: results at six months
Authors: E J Topol, R M Califf, H F Weisman, S G Ellis, J E Tcheng, S Worley, R Ivanhoe, B S George, D Fintel, M Weston
Journal: The Lancet (1994)
Epidemiology of Borderline Ovarian Tumors
Authors: Bernard L. Harlow, Noel S. Weiss, Steven Lofton
Journal: JNCI Journal of the National Cancer Institute (1987)

Ovarian tumors of low malignant potential, often termed "borderline tumors," have been defined as those that have some but not all of the morphologic features of malignancy (i.e., they are not invasive). With the use of data obtained by the western Washington population-based Cancer Surveillance System for 1975-83, the incidence of serous and mucinous borderline epithelial ovarian tumors was analyzed, as well as the survival of women who developed them. The incidence of borderline tumors increased with increasing age, although at a pace somewhat slower than that of malignant ovarian tumors. There was an upward trend in the incidence of borderline tumors starting in the late 1970's, a trend not present for malignant tumors. Only 12% of borderline tumors were not confined to the ovary, as opposed to 40% of malignant Grade I and 73% of other malignant ovarian neoplasms. At 5 years following diagnosis, the survival of women with borderline tumors was 93% that of the general female population. This percentage varied little by stage or histologic type. Given the reduced survival of women with these ovarian tumors and the lack of a sharp histologic distinction between borderline and Grade I malignant lesions, it is recommended that borderline ovarian tumors be routinely ascertained by population-based cancer registries.
Long-term results of the co-operative German–Austrian–Swiss osteosarcoma study group’s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs
Authors: N. Fuchs, S.S. Bielack, D. Epler, P. Bieling, G. Delling, D. Körholz, N. Graf, U. Heise, H. Jürgens, R. Kotz, M. Salzer-Kuntschik, P. Weinel, M. Werner, K. Winkler
Journal: Annals of Oncology (1998)
Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial
Authors: Michael J Yelland, Kent R Sweeting, John A Lyftogt, Shu Kay Ng, Paul A Scuffham, Kerrie A Evans
Journal: British Journal of Sports Medicine (2009)

To compare the effectiveness and cost-effectiveness of eccentric loading exercises (ELE) with prolotherapy injections used singly and in combination for painful Achilles tendinosis.A single-blinded randomised clinical trial. The primary outcome measure was the VISA-A questionnaire with a minimum clinically important change (MCIC) of 20 points.Five Australian primary care centres.43 patients with painful mid-portion Achilles tendinosis commenced and 40 completed treatment protocols.Participants were randomised to a 12-week program of ELE (n=15), or prolotherapy injections of hypertonic glucose with lignocaine alongside the affected tendon (n=14) or combined treatment (n=14).VISA-A, pain, stiffness and limitation of activity scores; treatment costs.At 12 months, proportions achieving the MCIC for VISA-A were 73% for ELE, 79% for prolotherapy and 86% for combined treatment. Mean (95% CI) increases in VISA-A scores at 12 months were 23.7 (15.6 to 31.9) for ELE, 27.5 (12.8 to 42.2) for prolotherapy and 41.1 (29.3 to 52.9) for combined treatment. At 6 weeks and 12 months, these increases were significantly less for ELE than for combined treatment. Compared with ELE, reductions in stiffness and limitation of activity occurred earlier with prolotherapy and reductions in pain, stiffness and limitation of activity occurred earlier with combined treatment. Combined treatment had the lowest incremental cost per additional responder ($A1539) compared with ELE.For Achilles tendinosis, prolotherapy and particularly ELE combined with prolotherapy give more rapid improvements in symptoms than ELE alone but long-term VISA-A scores are similar.ACTRN: 12606000179538.
PUMA Suppresses Intestinal Tumorigenesis in Mice
Authors: Wei Qiu, Eleanor B. Carson-Walter, Shih Fan Kuan, Lin Zhang, Jian Yu
Journal: Cancer Research (2009)

Defective apoptosis contributes to tumorigenesis, although the critical molecular targets remain to be fully characterized. PUMA, a BH3-only protein essential for p53-dependent apoptosis, has been shown to suppress lymphomagenesis. In this study, we investigated the role of PUMA in intestinal tumorigenesis using two animal models. In the azoxymethane (AOM)/dextran sulfate sodium salt model, PUMA deficiency increased the multiplicity and size of colon tumors but reduced the frequency of beta-catenin hotspot mutations. The absence of PUMA led to a significantly elevated incidence of precursor lesions induced by AOM. AOM was found to induce p53-dependent PUMA expression and PUMA-dependent apoptosis in the colonic crypts and stem cell compartment. Furthermore, PUMA deficiency significantly enhanced the formation of spontaneous macroadenomas and microadenomas in the distal small intestine and colon of APC(Min/+) mice. These results show an essential role of PUMA-mediated apoptosis in suppressing intestinal tumorigenesis in mice.
Engineered Zinc Finger–Activating Vascular Endothelial Growth Factor Transcription Factor Plasmid DNA Induces Therapeutic Angiogenesis in Rabbits With Hindlimb Ischemia
Authors: Qunsheng Dai, Jianhua Huang, Bruce Klitzman, Chunming Dong, Pascal J. Goldschmidt-Clermont, Keith L. March, Joseph Rokovich, Brian Johnstone, Edward J. Rebar, S. Kaye Spratt, Casey C. Case, Christopher D. Kontos, Brian H. Annex
Journal: Circulation (2004)

Background— Therapeutic angiogenesis seeks to promote blood vessel growth to improve tissue perfusion. Vascular endothelial growth factor (VEGF) exists in multiple isoforms. We investigated an engineered zinc finger–containing transcription factor plasmid designed to activate the endogenous VEGF gene (ZFP-VEGF). Methods and Results— New Zealand White rabbits (n=56) underwent unilateral femoral artery ligation and excision. At day 10 postoperatively, the ischemic muscle received ZFP treatment (500 μg ZFP-VEGF plasmid) or no ZFP treatment (β-galactosidase, empty, or no plasmid). Group 1 (n=13) was harvested 3 days after injection to examine VEGF mRNA by real-time polymerase chain reaction and protein by ELISA. Groups 2 (n=13) and 3 (n=10) were harvested 11 days after injection. Group 2 was studied by histology and group 3, by histology and changes in blood flow. Groups 4 and 5 (n=10 each) were harvested 22 and 32 days after injection, respectively, and studied for changes in blood flow. In group 1, VEGF mRNA copy numbers were significantly higher for VEGF 121 , VEGF 165 , VEGF 189 , and protein in the ZFP-VEGF-treatment versus no-ZFP-treatment arms. In groups 2 and 3, capillary density and proliferating cells were significantly greater and apoptosis significantly lower in the treatment versus no-treatment arms. Changes in the blood flow ratio of the ischemic to the nonischemic limb were significantly greater in the treatment versus no-ZFP-treatment groups (6.57±1.52% versus 3.38±0.87%, P &lt;0.005; 13.15±1.77% versus 6.13±1.55%, P &lt;0.001; and 20.16±2.84% versus 13.88±3.14%, P &lt;0.01, for groups 3, 4, and 5, respectively). Conclusions— This engineered ZFP-VEGF–activating transcription factor may provide a novel approach to treat peripheral arterial disease.
Clobetasol propionate ointment reduces inflammation after cryotherapy
Authors: T.C. HINDSON, J. SPIRO, LINDSEY V. SCOTT
Journal: British Journal of Dermatology (2006)

A double‐blind, randomized, placebo‐controlled trial was carried out comparing the effects of clobetasol propionate ointment and the ointment base on the inflammation induced by cryotherapy of basal cell carcinomata and warts. A single application of the steroid was shown to be significantly better at reducing erythema, pain and swelling than the ointment base.