tbuckley/cabot-search huggingface dataset:
Blocking Angiogenesis and Tumorigenesis with GFA-116, a Synthetic Molecule that Inhibits Binding of Vascular Endothelial Growth Factor to its Receptor
Authors: Jiazhi Sun, Michelle A. Blaskovich, Rishi K. Jain, Frederic Delarue, Daniel Paris, Steven Brem, Marguerite Wotoczek-Obadia, Qing Lin, Domenico Coppola, Kihang Choi, Michael Mullan, Andrew D. Hamilton, Saïd M. Sebti
Journal: Cancer Research (2004)

Abstract A small synthetic library of cyclohexapeptidomimetic calixarenes was prepared to identify disrupters of vascular endothelial growth factor (VEGF) binding to its receptor that inhibits angiogenesis. From this library, we discovered GFA-116, which potently inhibits 125I-VEGF binding to Flk-1 in Flk-1-overexpressing NIH 3T3 cells and human prostate tumor cells with an IC50 of 750 nm. This inhibition is highly selective for VEGF in that 125I- platelet-derived growth factor binding to its receptor is not affected. GFA-116 inhibits VEGF-stimulated Flk-1 tyrosine phosphorylation and subsequent activation of Erk1/2 mitogen-activated protein kinases. Furthermore, epidermal growth factor, platelet-derived growth factor, and fibroblast growth factor-dependent stimulation of Erk1/2 phosphorylation are not affected at concentrations as high as 10 μm. In vitro, GFA-116 inhibits angiogenesis as measured by inhibition of migration and formation of capillary-like structures by human endothelial cells as well as suppression of microvessel outgrowth in rat aortic rings and rat cornea angiogenesis. In vivo, GFA-116 (50 mpk/day) inhibits tumor growth and angiogenesis as measured by CD31 staining of A-549 human lung tumors in nude mice. Furthermore, GFA-116 is also effective at inhibiting tumor growth and metastasis to the lung of B16-F10 melanoma cells injected into immunocompetent mice. Taken together, these results demonstrate that a synthetic molecule capable of disrupting the binding of VEGF to its receptor selectively inhibits VEGF-dependent signaling and suppresses angiogenesis and tumorigenesis.
Mycetoma Involving the Heart
Authors: Gilberto Szarf, Alex Rocha Obac, Andrea Puchnick, Carlos Gustavo Yuji Verrastro, Alfredo Augusto Eyer Rodrigues, Marly Uellendahl, Maria Veronica Camara Santos, Arnaldo Lopes Colombo, Artur da Rocha Correa Fernandes, Henrique Manoel Lederman
Journal: Circulation (2013)
Human Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation and Neointima Formation After Balloon Injury in Rats
Authors: Stefan Janssens, Declan Flaherty, Zengxuan Nong, Olivier Varenne, Natasha van Pelt, Carine Haustermans, Pierre Zoldhelyi, Robert Gerard, Desire Collen
Journal: Circulation (1998)

Loss of endothelial NO production after arterial injury may contribute to restenosis, characterized by neointima formation and elastic recoil. Adenovirus-mediated transfer of the gene encoding NO synthase (NOS) in balloon-injured arteries may restore NO production and inhibit neointima formation.After balloon injury, rat carotid arteries were transduced with 3x10(10) pfu/mL recombinant adenovirus carrying the human endothelial constitutive NOS cDNA (AdCMVceNOS, n=8) or no cDNA (AdRR5, n=8). ceNOS expression was confirmed by immunoblot analysis of vascular extracts and was localized by immunostaining in 30% of medial smooth muscle cells (SMCs) and in the adventitia of AdCMVceNOS-transduced arteries. Vascular cGMP levels were reduced from 3.9 pmol/g wet wt in uninjured arteries to 0.7 pmol cGMP/g after AdRR5 but were restored after ceNOS gene transfer (3.8 pmol cGMP/g wet wt, P<.05 versus AdRR5). Intima-to-media ratio 2 weeks after injury was significantly reduced (0.19+/-0.02 in AdCMVceNOS-infected versus 0.69+/-0.07 in AdRR5-infected arteries, P<.05). In vitro, BrdU incorporation of AdCMVceNOS-infected SMCs was reduced by 28% compared with AdRR5-infected SMCs. Transduced cells from injured carotid arteries subjected to FACS sorting showed a significantly lower BrdU labeling index in ceNOS-infected rats (29+/-6% versus 43+/-5% and 45+/-4% in control, injured, and AdRR5-infected rats, respectively, P<.05).AdCMVceNOS gene transfer to balloon-injured rat carotid arteries restores vascular NO production and reduces neointima formation, at least in part because of an antiproliferative effect on medial SMCs. Adenovirus-mediated ceNOS gene transfer might reduce arterial restenosis after balloon angioplasty.
To children with love.
Authors: K T Kumar
Journal: BMJ (1992)

People debating population growth in India and why adults in India choose to bear so many children seem to either not  understand or overlook that people in India like children; the more the better.  Indeed children interest every Indian with new mothers receiving advice on baby care from all quarters.  The child is king in India spoiled but generally well-behaved.  It could be that children receive so much attention from many loving relatives that they do not need to act out in order to get attention.  Having a child is the focus and meaning of married life.  Without a child life loses its color and joy.  Moreover childless couples face the insecurity of not having children to care for them once they grow old.  The author notes her failure to observe children who were poorly adjusted and sad because they habitually shared a bed with their parents.  As concerned individuals ponder the perils of global population growth they might consider the merit of the Indian view on the subject.
The Evolutionary Repertoires of the Eukaryotic-Type ABC Transporters in Terms of the Phylogeny of ATP-binding Domains in Eukaryotes and Prokaryotes
Authors: Y. Igarashi
Journal: Molecular Biology and Evolution (2004)

ABC (ATP-binding cassette) transporters play an important role in the communication of various substrates across cell membranes. They are ubiquitous in prokaryotes and eukaryotes, and eukaryotic types (EK-types) are distinguished from prokaryotic types (PK-types) in terms of their genes and domain organizations. The EK-types and PK-types mainly consist of exporters and importers, respectively. Prokaryotes have both the EK-types and the PK-types. The EK-types in prokaryotes are usually called "bacterial multidrug ABC transporters," but they are not well characterized in comparison with the multidrug ABC transporters in eukaryotes. Thus, an exhaustive search of the EK-types among diverse organisms and detailed sequence classification and analysis would elucidate the evolutionary history of EK-types. It would also help shed some light on the fundamental repertoires of the wide variety of substrates through which multidrug ABC transporters in eukaryotes communicate. In this work, we have identified the EK-type ABC transporters in 126 prokaryotes using the profiles of the ATP-binding domain (NBD) of the EK-type ABC transporters from 12 eukaryotes. As a result, 11 clusters were identified from 1,046 EK-types ABC transporters. In particular, two large novel clusters emerged, corresponding to the bacterial multidrug ABC transporters related to the ABCB and ABCC families in eukaryotes, respectively. In the genomic context, most of these genes are located alone or adjacent to genes from the same clusters. Additionally, to detect functional divergences in the NBDs, the Kullback-Leibler divergence was measured among these bacterial multidrug transporters. As a result, several putative functional regions were identified, some corresponding to the predicted secondary structures. We also analyzed a phylogeny of the EK-type ABC transporters in both prokaryotes and eukaryotes, which revealed that the EK-type ABC transporters in prokaryotes have certain repertoires corresponding to the conventional ABC protein groups in eukaryotes. On the basis of these findings, we propose an updated evolutionary hypothesis in which the EK-type ABC transporters in both eukaryotes and prokaryotes consisted of several kinds of ABC transporters in putative ancestor cells before the divergence of eukaryotic and prokaryotic cells.
Atypical Melanocytic Proliferations and New Primary Melanomas in Patients With Advanced Melanoma Undergoing Selective <i>BRAF</i> Inhibition
Authors: Lisa Zimmer, Uwe Hillen, Elisabeth Livingstone, Mario E. Lacouture, Klaus Busam, Richard D. Carvajal, Friederike Egberts, Axel Hauschild, Mohammed Kashani-Sabet, Simone M. Goldinger, Reinhard Dummer, Georgina V. Long, Grant McArthur, André Scherag, Antje Sucker, Dirk Schadendorf
Journal: Journal of Clinical Oncology (2012)

Selective inhibition of mutant BRAF by using class I RAF inhibitors in patients with metastatic melanoma has resulted in impressive clinical activity. However, there is also evidence that RAF inhibitors might induce carcinogenesis or promote tumor progression via stimulation of MAPK signaling in RAF wild-type cells. We analyzed melanocytic lesions arising under class I RAF inhibitor treatment for dignity, specific genetic mutations, or expression of signal transduction molecules.In all, 22 cutaneous melanocytic lesions that had either developed or considerably changed in morphology in 19 patients undergoing treatment with selective BRAF inhibitors for BRAF-mutant metastatic melanoma at seven international melanoma centers within clinical trials in 2010 and 2011 were analyzed for mutations in BRAF and NRAS genes and immunohistologically assessed for expression of various signal transduction molecules in comparison with 22 common nevi of 21 patients with no history of BRAF inhibitor treatment.Twelve newly detected primary melanomas were confirmed in 11 patients within 27 weeks of selective BRAF blockade. In addition, 10 nevi developed of which nine were dysplastic. All melanocytic lesions were BRAF wild type. Explorations revealed that expression of cyclin D1 and pAKT was increased in newly developed primary melanomas compared with nevi (P = .01 and P = .03, respectively). There was no NRAS mutation in common nevi, but BRAF mutations were frequent.Malignant melanocytic tumors might develop with increased frequency in patients treated with selective BRAF inhibitors supporting a mechanism of BRAF therapy-induced growth and tumorigenesis. Careful surveillance of melanocytic lesions in patients receiving class I RAF inhibitors seems warranted.
TCT-284 Impact of female gender on bleeding complications and 1-year outcomes of transradial coronary intervention. A propensity score matched analysis: Korea TransRadial coronary Intervention registry
Authors: Jeoung-sook Shin, Seung-Jea Tahk, Hyoung-Mo Yang, Hong Seok Lim, Byoung-Joo Choi, So-Yeon Choi, Myeong- Ho Yoon
Journal: Journal of the American College of Cardiology (2013)
OUTLYING ACIDOSIS DUE TO FUNCTIONAL ISCHEMIA
Authors: Peyton Rous, Douglas R. Drury
Journal: The Journal of Experimental Medicine (1929)

In various functional conditions involving peripheral vasoconstriction a more or less widespread change toward acidity takes place within certain tissues. The change is frequently independent of any in the blood. Indeed the blood can become more alkaline while the tissue acidosis is developing. When the blood volume is diminished abruptly but not too greatly, by hemorrhage or by anhydremia, the acidosis which develops in the superficial connective tissue and in the skeletal muscles is patchy in distribution, being limited to areas of local ischemia themselves the result of a compensatory vasoconstriction which affects certain regions only. There is a second type of patchy ischemia (and of acidosis) which occurs under circumstances of moderate depletion and is referable to local pressure differences that are so slight as to be ineffective under normal circumstances. A generalized acidosis throughout the superficial tissue develops when depletion is extreme. All these are outlying acidoses, since they lie without the influence of the blood. In the viscera no such acidoses have been found.
The Relationship Between Provider Coordination and Diabetes-Related Foot Outcomes
Authors: James S. Wrobel, Martin P. Charns, Paula Diehr, Jeffrey M. Robbins, Gayle E. Reiber, Kristin M. Bonacker, Linda B. Haas, Leonard Pogach
Journal: Diabetes Care (2003)

OBJECTIVE—To investigate the relationship between provider coordination and amputations in patients with diabetes. RESEARCH DESIGN AND METHODS—The study design was a cross-sectional, descriptive study of process and outcomes for diabetes-related foot care at 10 Department of Veterans Affairs (VA) medical centers representing different geographic regions, population densities, patient populations, and amputation rates. The subjects included all providers of diabetes foot care and a random sample of primary care providers at each medical center. The main outcome measures were the Foot Systems Assessment Tool (FootSAT), nontraumatic lower extremity amputation rates, and investigators’ ordinal ranking of site effectiveness based on site visits. RESULTS—The survey response rate was 48%. Scale reliability, as measured by Cronbach’s α, ranged from 0.73 to 0.93. The scale scores for programming coordination (i.e., electronic medical record, policies, reminders, protocols, and educational seminars) and feedback coordination (i.e., discharge planning, quality of care meetings, and curbside consultations) were negatively associated with amputation rates, suggesting centers with higher levels of coordination had lower amputation rates. Statistically significant associations were found for programming coordination with minor amputations (P = 0.02) and total amputations (P = 0.04). CONCLUSIONS—The FootSAT demonstrated a stronger association with amputation rates than site visit rankings. Among these 10 VA facilities, those with higher levels of programming and feedback coordination had significantly lower amputation rates.
Stereotactic Brachytherapy With Iodine-125 Seeds for the Treatment of Inoperable Low-Grade Gliomas in Children: Long-Term Outcome
Authors: Maximilian I. Ruge, Thorsten Simon, Bogdana Suchorska, Ralph Lehrke, Christina Hamisch, Friederike Koerber, Mohammad Maarouf, Harald Treuer, Frank Berthold, Volker Sturm, Jürgen Voges
Journal: Journal of Clinical Oncology (2011)

Resection is generally considered the gold standard for treatment of low-grade (WHO grades I and II) gliomas (LGGs) in childhood. However, approximately 30% to 50% of these tumors are inoperable because of their localization in highly eloquent brain areas. A few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 ((125)I) seeds as a safe and effective local treatment alternative. This single-center study provides a summary of the long-term outcome after SBT in one of the largest reported patient series.All pediatric patients treated with SBT ((125)I seeds; cumulative therapeutic dose 50-65 Gy within 9 months) by our group for LGG with follow-up of more than 6 months were included. Clinical and radiologic outcome, time to progression, and overall survival were evaluated. Prognostic factors (age, sex, Karnofsky performance score, tumor volume, and histology) for survival and disease progression were investigated.In all, 147 of 160 pediatric patients treated with SBT (from 1982 through 2009) were analyzed in detail. Procedure-related mortality was zero, and the 30-day morbidity was transient and low (5.4%). Survival rates at 5 and 10 years were 93%, and 82%, respectively, with no significant difference between WHO grades I and II tumors (median follow-up, 67.1 ± 57.7 months). Twenty-one (14.8%) of 147 patients presented with tumor relapse. The remaining 126 patients revealed complete response in 24.6%, partial response in 31.0%, and stable disease in 29.6%. Neurologic status improved (57.8%) or remained stable (23.0%). None of the evaluated factors had significant impact on the study's end points except tumor volume more than 15 mL, which caused significantly higher rates of tumor recurrence (P < .05).We demonstrate that SBT represents a safe, minimally invasive, and highly effective local treatment option for pediatric patients with inoperable LGG WHO grades I and II.
Insulin Signaling to the Glomerular Podocyte Is Critical for Normal Kidney Function
Authors: Gavin I. Welsh, Lorna J. Hale, Vera Eremina, Marie Jeansson, Yoshiro Maezawa, Rachel Lennon, Deborah A. Pons, Rachel J. Owen, Simon C. Satchell, Mervyn J. Miles, Christopher J. Caunt, Craig A. McArdle, Hermann Pavenstädt, Jeremy M. Tavaré, Andrew M. Herzenberg, C. Ronald Kahn, Peter W. Mathieson, Susan E. Quaggin, Moin A. Saleem, Richard J.M. Coward
Journal: Cell Metabolism (2010)
How to Fix the Edge Effect of Catheter-Based Radiation Therapy in Stented Arteries
Authors: Edouard Cheneau, Ron Waksman, Hamid Yazdi, Rosanna Chan, Jana Fourdnadjiev, Chalak Berzingi, Vivek Shah, Andrew E. Ajani, Laurent Leborgne, Fermin O. Tio
Journal: Circulation (2002)

Edge stenosis remains a serious limitation of catheter-based vascular brachytherapy (VBT). This study aims to identify the mechanisms and evaluate strategies to minimize edge restenosis in patients treated with VBT.Thirty-four porcine stented coronary arteries were irradiated (doses of 15 or 22 Gy) with (192)Ir trains of either 6 seeds (23 mm) with 0 mm coverage at the distal stent edge and 10 mm at the proximal stent edge or 14 seeds (55 mm) centered at the distal edge of the stent with 27.5 and 14.5 mm coverage at the distal and proximal edges, respectively. After VBT, an additional 13-mm stent was positioned overlapping the distal margin of the first stent. Animals were killed at 28 days, and arteries were analyzed. Longer radiation margins were associated with reduced intimal area (IA) at the stent edge: 2.3+/-0.9, 3.6+/-2.0, and 5.3+/-2.2 mm(2) with 15 Gy for a radiation margin of 14.5, 10, and -13 mm (-13 versus 10, P=0.06; 10 versus 14.5, P=0.06). Additional stenting was associated with an increase of IA: 4.0+/-2.3 mm(2) at the overlapped segment. Increasing the dose to 22 Gy resulted in a reduction of the IA at the overlap segment to 1.31+/-0.57 mm(2) with 14 seeds (27.5 mm coverage) but was not helpful with 6 seeds (0 mm coverage): IA, 5.56+/-2.28 mm(2).Extending the radiation margins to 14.5 mm from each end of the stent minimized the edge-effect phenomenon. A higher dose is essential to eliminate further increases in IA at the overlapped segment with additional stents.
Long-term therapy of HIV-associated Kaposi's sarcoma with recombinant interferon α-2a
Authors: F.M. SCHAART, B. BRATZKE, Zb. RUSZCZAK, R. STADLER, G. EHLERS, C.E. ORFANOS
Journal: British Journal of Dermatology (1991)

Five young male patients with HIV-associated Kaposi's sarcoma (KS) were treated with recombinant interferon alpha 2a (rIFN-alpha-2a) over a period of 2-2.5 years. An IFN dose of 18 x 10(6) IU was given subcutaneously every day during the first 3 months of treatment and then on alternate days. Additional treatment with radiotherapy and laser therapy was given and, in some cases, isolated skin nodules were excised. Within 7 months of initiation of therapy one patient had a complete remission of his tumours, however, tumour progression recurred after the patient discontinued treatment. In another patient the tumour cleared within 9 months of rIFN therapy, and after 52 months he is still free of KS. The condition of a third patient tended to become stabilized during the first 6 months of therapy, but after 60 months there has been a slow progression. The fourth and fifth patients died 25 and 28 months, respectively, after the histological diagnosis of KS and the initiation of treatment. While on therapy with rIFN-alpha-2a, no life-threatening opportunistic infections occurred. The side-effects were mostly well tolerated, and no severe changes in haematological parameters were caused by the therapy.
Combining site specificities of mouse hybridoma antibodies to dextran B1355S.
Authors: B Newman, S Sugii, E A Kabat, M Torii, B L Clevinger, J Schilling, M Bond, J M Davie, L Hood
Journal: The Journal of Experimental Medicine (1983)

The combining sites of 12 mouse hybridoma antibodies to dextran B1355S have been characterized by quantitative precipitin assay. All antibodies preferentially bind the immunizing antigen B1355S and two other class I dextrans, B1498S and B1501S, but show substantial differences in the extents to which they cross react with class I dextrans, suggesting their clustering into five groups. Three myeloma proteins, CAL20 TEPC1035, J558, and MOPC104E, which bind dextran B1355S, each fall into a different group. There appears to be a substantial, but imperfect, correlation of DH region structure and individual idiotypic determinants with dextran binding patterns. Proteins with RY DH segments and IdI (J558) idiotypes are in groups 1 or 3, and proteins with YD DH segments and IdI (MOPC104E) idiotypes are exclusively in group 5. However, identical patterns of precipitin curves accompany very different sequences in CDR3. Antibodies of group 1, which react only with class II dextrans, differ the most in primary sequence, a finding suggesting that subsites responsible for cross reactivity with class I dextrans may be blocked and that this may be effected by side chains of different amino acids. This finding delineates a new aspect of the relationship of variability in amino acid sequence to antibody complementarity.
Circulating tumor cells (CTCs) in metastatic breast cancer (MBC): prognosis, drug resistance and phenotypic characterization
Authors: A. Gradilone, G. Naso, C. Raimondi, E. Cortesi, O. Gandini, B. Vincenzi, R. Saltarelli, E. Chiapparino, F. Spremberg, M. Cristofanilli, L. Frati, A.M. Aglianò, P. Gazzaniga
Journal: Annals of Oncology (2010)
Electronic Communication With Patients
Authors: E. Andrew Balas
Journal: JAMA (1997)

<h3>Objective.</h3> —To evaluate controlled evidence on the efficacy of distance medicine technologies in clinical practice and health care outcome. <h3>Data Sources.</h3> —Systematic electronic database and manual searches (1966-1996) were conducted to identify clinical trial reports on distance medicine applications. <h3>Study Selection.</h3> —Three eligibility criteria were applied: prospective, contemporaneously controlled clinical trial with random assignment of the intervention; electronic distance technology application in the intervention group and no similar intervention in the control group; and measurement of the intervention effect on process or outcome of care. <h3>Data Extraction.</h3> —Data were abstracted by independent reviewers using a standardized abstraction form and the quality of methodology was scored. Distance technology applications were described in 6 categories: computerized communication, telephone follow-up and counseling, telephone reminders, interactive telephone systems, after-hours telephone access, and telephone screening. <h3>Data Synthesis.</h3> —Of 80 eligible clinical trials, 61 (76%) analyzed providerinitiated communication with patients and 50 (63%) reported positive outcome, improved performance, or significant benefits, including studies of computerized communication (7 of 7), telephone follow-up and counseling (20 of 37), telephone reminders (14 of 23), interactive telephone systems (5 of 6), telephone access (3 of 4), and telephone screening (1 of 3). Significantly improved outcomes were demonstrated in studies of preventive care, management of osteoarthritis, cardiac rehabilitation, and diabetes care. <h3>Conclusions.</h3> —Distance medicine technology enables greater continuity of care by improving access and supporting the coordination of activities by a clinician. The benefits of distance technologies in facilitating communication between clinicians and patients indicate that application of telemedicine should not be limited to physician-to-physician communication.