tbuckley/cabot-search huggingface dataset:
Soluble Vascular Endothelial Growth Factor Decoy Receptor FP3 Exerts Potent Antiangiogenic Effects
Authors: De-Chao Yu, Jung-Sun Lee, Ji Young Yoo, Hyewon Shin, Hongxin Deng, Yuquan Wei, Chae-Ok Yun
Journal: Molecular Therapy (2012)

The binding of vascular endothelial growth factor (VEGF) to its receptors stimulates tumor growth; therefore, modulation of VEGF would be a viable approach for antiangiogenic therapy. We constructed a series of soluble decoy receptors containing different VEGF receptor 1 (FLT1) and VEGF receptor 2 (KDR) extracellular domains fused with the Fc region of human immunoglobulin (Ig) and evaluated their antiangiogenic effects and antitumor effects. Results of in vitro binding and cell proliferation assays revealed that decoy receptor FP3 had the highest affinity to VEGF-A and -B. Compared with bevacizumab, FP3 more effectively inhibited human umbilical vein endothelial cell (HUVEC) migration and vessel sprouting from rat aortic rings. FP3 significantly reduced phosphorylation of AKT and ERK1/2, critical proteins in the VEGF-mediated survival pathway in endothelial cells. Moreover, FP3 inhibited tumor growth in human hepatocellular carcinoma (HepG2), breast cancer (MCF-7), and colorectal cancer (LoVo) tumor models, and reduced microvessel density in tumor tissues. The FP3-mediated inhibition of tumor growth was significantly higher than that of bevacizumab at the same dose. FP3 also demonstrated synergistic antitumor effects when combined with 5-fluorouracil (5-FU). Taken together, FP3 shows a high affinity for VEGF and produced antiangiogenic effects, suggesting its potential for treating angiogenesis-related diseases such as cancer. The binding of vascular endothelial growth factor (VEGF) to its receptors stimulates tumor growth; therefore, modulation of VEGF would be a viable approach for antiangiogenic therapy. We constructed a series of soluble decoy receptors containing different VEGF receptor 1 (FLT1) and VEGF receptor 2 (KDR) extracellular domains fused with the Fc region of human immunoglobulin (Ig) and evaluated their antiangiogenic effects and antitumor effects. Results of in vitro binding and cell proliferation assays revealed that decoy receptor FP3 had the highest affinity to VEGF-A and -B. Compared with bevacizumab, FP3 more effectively inhibited human umbilical vein endothelial cell (HUVEC) migration and vessel sprouting from rat aortic rings. FP3 significantly reduced phosphorylation of AKT and ERK1/2, critical proteins in the VEGF-mediated survival pathway in endothelial cells. Moreover, FP3 inhibited tumor growth in human hepatocellular carcinoma (HepG2), breast cancer (MCF-7), and colorectal cancer (LoVo) tumor models, and reduced microvessel density in tumor tissues. The FP3-mediated inhibition of tumor growth was significantly higher than that of bevacizumab at the same dose. FP3 also demonstrated synergistic antitumor effects when combined with 5-fluorouracil (5-FU). Taken together, FP3 shows a high affinity for VEGF and produced antiangiogenic effects, suggesting its potential for treating angiogenesis-related diseases such as cancer.
Irreversible deformation of the spectrin-actin lattice in irreversibly sickled cells.
Authors: S E Lux, K M John, M J Karnovsky
Journal: Journal of Clinical Investigation (1976)

Irreversibly sickled cells (ISC's) are circulating erythrocytes in patients with sickle cell disease that retain a sickled shape even when oxygenated. Evidence points to a membrane defect that prevents the return of these cells to the normal biconcave shape. The erythrocyte membrane protein spectrin is believed to help control erythrocyte shape and deformability. Recent studies suggest that normally spectrin and an erythrocyte actin form a self-supporting, fibrillar, lattice-like network on the cytoplasmic membrane surface. When normal erythrocyte ghosts are extracted with Triton X-100 all the integral membrane proteins and most of the membrane lipids are removed, leaving a ghost-shaped residue composed principally of spectrin and actin. We concentrated ISC's from patients with sickle cell anemia and compared the morphology and protein composition of ghosts and Triton-extracted ghost residues prepared from these ISC's with similar preparations of reversibly sickable cells and normal cells. (a) Many ISC's formed ISC-shaped ghosts. (b) All ISC-shaped ghosts formed ISC-shaped Triton residues. (c) Spectrin, erythrocyte actin (Band 5), an unidentified Band 3 component, and Band 4.1 were the major protein components of the Triton residues. All membrane-associated sickle hemoglobin was removed by the Triton treatment. (d) No ISC-shaped ghosts or ISC-shaped Triton residues were formed when deoxygenated, sickled RSC's were lysed or Triton-extracted. ISC-shaped ghosts and Triton residues were never formed from normal cells. These observations suggest that a defect of the "spectrin-actin lattice" may be the primary abnormality of the ISC membrane. Since ISC's are rigid cells, the data support the postulate that spectrin is a major determinant of membrane deformability. Finally, they provide direct evidence that spectrin is important in determining erythrocyte shape.
Genes and the eye
Authors: M. Moosajee
Journal: Journal of the Royal Society of Medicine (2005)

For those who see genetics as the potential answer to many ills, these are exciting times. A vast flood of information from the Human Genome Project, completed just two years ago,1 is already elucidating the replication, recombination and segregation of chromosomes. For gene therapies, however, we require knowledge of products and their functions,2 and the next stage is to examine the transcriptome, the metabolome and the proteome. The Human Phenome Project,3 by determining the relations between genotypes and phenotypes, should move us towards an era of individualized prevention and treatment.4 An organ for which this approach holds particular promise, in 2005, is the eye.
Invasive Candida infections in surgical patients in intensive care units: a prospective, multicentre survey initiated by the European Confederation of Medical Mycology (ECMM) (2006–2008)
Authors: L. Klingspor, A.M. Tortorano, J. Peman, B. Willinger, P. Hamal, B. Sendid, A. Velegraki, C. Kibbler, J.F. Meis, R. Sabino, M. Ruhnke, S. Arikan-Akdagli, J. Salonen, I. Dóczi
Journal: Clinical Microbiology and Infection (2014)
Trichinosis: From Bismarck to Polar Bears
Authors: Robert H. Moser
Journal: JAMA (1974)

I can still remember an apocryphal tale told by Harold Jeghers. It might be called  Case of the Embarrassed Rabbi. Of course, it happened in Boston. This orthodox talmudic scholar developed a peculiar malady, ultimately identified as trichinosis! He was a devout man and ate only kosher food. It remained a considerable mystery until a persevering house officer ferreted out the small detail that while making trips to rural communities, this fastidious man always carried his own food. Many times this consisted of chicken prepared commercially under kosher conditions and placed in glass containers. The enterprising resident visited the plant where the food was prepared and ultimately discovered that indeed the chicken, on rare occasions, had been augmented surreptiously with pork! It was a marvelous story; it has remained with me for 28 years.  The recent appearance of a paper about trichinosis among Thai nationals in New York 1
Rickettsial-Pox
Authors: Paul D. Hoeprich, Gerald T. Kent, John H. Dingle
Journal: New England Journal of Medicine (1956)

THE most recently discovered of the human rickettsial diseases, rickettsial-pox, was first recognized in New York City in 1946.1 2 3 Since then, cases have been reported from a relatively circumscribed area, including Boston,4 , 5 Philadelphia6 and West Hartford, Connecticut.7 The present report extends the geographic locus of naturally occurring rickettsial-pox to Cleveland.Clinical, epidemiologic and laboratory data regarding rickettsial-pox have been reported in numerous communications.8 9 10 11 12 13 Although the course of the disease is benign, antibiotic therapy has been reported to hasten recovery.14 15 16 Case ReportM. M., a 43-year-old married female executive in a book-publishing firm, entered University Hospitals on January 17, 1955. About . . .
Chairman of Manpower Committee
Authors: D. Zuck
Journal: BMJ (1972)

753(300 unit dose) by this centre, supplying most of the needs of the Scottish community (5-2 million) for such products and now be- ginning to supply prophylactic treatment of haemophilia B.Even in the projected situ- ation of meeting all existing demand for this fraction it will not be possible to guarantee, beyond doubt, the fulfilment of every surge in such demand.It is difficult to visualize how output, even for the modestly estimated needs of six teaching hospitals, can be main- tained without functional distortion of a regional blood transfusion centre.It is even more disturbing to contemplate the proliferation of other small scale processing units, possibly ill-equipped to assess the potency and safety of potentially dangerous products.Human plasma is a scarce national re- source and must be carefully husbanded.Calculation of the plasma protein solution needs for Scotland indicate that the amount of plasma now available for processing is, almost certainly, inadequate to meet full use of this product.This calculation is in close accord with the rate of use in other European countries as described recently at a Washington conference in October 1971 on plasma derivatives for clinical use (unpub- lished).In this context, at a time when national fractionation centres in the United Kingdom are rapidly expanding and acquiring the capacity to satisfy need for all plasma products it seems retrograde to advocate fragmentation of our supplies of fresh plasma and of rare expertise.The national need for carefully stan- dardized preparations of all coagulation factors, albumin, plasma protein solution, and the widening range of immunoglobulin preparations can best be met by central, comprehensive fractionation of known quality plasma rather than by pooling the residues from unco-ordinated individual efforts, irrespective of the success of such efforts in a limited clinical context.-Weare, etc.,
Abstract C57: The expression of 2′-5′ oligoadenylate synthetase in prostate cancer and its effect on prostate cancer cell cycle
Authors: Sanjay Kumar Mandal, Jaideep Chaudhary
Journal: Cancer Research (2012)

Abstract 2-5 oligoadenylate synthetase (OAS) is an IFN inducible enzyme that is part of innate immune response. During viral infections 2′-5′ OAS is activated by viral dsRNA or cellular RNA with significant double strand structure to synthesize 2-5 oligoadenylates (2-5A) from ATP; which in turn activates RNaseL, the latent ribonuclease. RNAseL degrades infectious RNA which imparts antiviral protection to the cell. OAS-RNaseL system also degrades cellular RNA and inhibits protein synthesis. The role of RNAseL as a tumor suppressor has been studied in prostate cancer cell lines and has been linked to hereditary prostate cancer (HPC). However HPC accounts for less than 9% of the overall prostate cancer incidence but the role of RNAseL in sporadic prostate cancer has not been established. Since OAS1 is the rate limiting enzyme in RNaseL activation, we therefore hypothesized that OAS could potentially act as tumor suppressor in the context of sporadic prostate cancer. Methods: Immunohistochemistry was performed on human prostate cancer and normal prostate tissue to determine the expression of OAS1. RT-PCR and western blot was performed to detect the expression of OAS1 in LNCaP, DU145 and PC3 cell lines. Two alternative approaches were then used to investigate the effect of OAS1 on cell survival and its potential mechanism of action: OAS1 was over-expressed in LNCaP whereas it was silenced in DU145 cells. Cell cycle and apoptosis was quantitated by FACS analysis and the expression of key regulatory genes was determined by qRT-PCR and western blot analysis. Results: Immunohistochemistry demonstrated that OAS1 expression is high in the normal prostate but decreased progressively with stage in prostate cancer. OAS1 was not expressed in LNCaP cells but its expression was high in DU145 and PC3 prostate cancer lines. Overexpression of OAS1 in LNCaP cells induced apoptosis and G1 arrest that was associated with increased p53, BAX and p21 expression. Alternatively, silencing of OAS in DU145 cells led to an increase in S phase and G2 cell population with a concomitant decrease in apoptosis. Conclusion: Our prostate cancer cell line and prostate cancer tissue data strongly suggest that OAS1 is a candidate tumor suppressor that could be used as a potential biomarker for prostate cancer. Moreover, our previous study had shown a link between OAS1 polymorphism and prostate cancer incidence. Collectively data suggest the role of immune/inflammatory pathway in prostate cancer progression. Citation Format: Sanjay Kumar Mandal, Jaideep Chaudhary. The expression of 2′-5′ oligoadenylate synthetase in prostate cancer and its effect on prostate cancer cell cycle [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C57.
Woolly hair, premature loss of teeth, nail dystrophy, acral hyperkeratosis and facial abnormalities: possible new syndrome in a Dutch kindred
Authors: M.A.M. Van Steensel, M.I. Koedam, O.Q. Swinkels, F. Rietveld, P.M. Steijlen
Journal: British Journal of Dermatology (2001)

We describe a Dutch kindred with a possibly novel dominant syndrome of premature loss of curly, brittle hair, premature loss of teeth due to caries, nail dystrophy and acral keratoderma. We discuss the possibility that this ectodermal dysplasia of group 1‐2‐3‐4 is a variant of known disorders such as pachyonychia congenita. We conclude that none of these diagnoses fits the symptoms we observe in our patients and propose the name curly hair–acral keratoderma–caries syndrome in view of the most obvious abnormalities.
757-1 The Effect of Vasopressin V1 and V2 Receptor Antagonists on Heart Failure After Myocardial Infarction
Authors: Hisayoshi Fujita, Minoru Yoshiyama, Hiroyuki Yamagishi, Akihisa Hanatani, Iku Toda, Kaname Akioka, Masakazu Teragaki, Kazuhide Takeuchi, Hiroshi Iwao, Tadanao Takeda
Journal: Journal of the American College of Cardiology (1995)
Relation of Glucose Tolerance to Complications of Pregnancy in Nondiabetic Women
Authors: Lorenzo Tallarigo, Ottavio Giampietro, Giuseppe Penno, Roberto Miccoli, Giovanna Gregori, Renzo Navalesi
Journal: New England Journal of Medicine (1986)

An increase in fetal and maternal complications has been documented in cases of gestational diabetes, but the glucose levels that predict an increased risk have not been clearly defined. We evaluated the frequency of several neonatal complications (macrosomia, congenital anomalies, perinatal mortality, and prematurity) and maternal complications (toxemia, cesarean section, or both) in relation to glucose tolerance in 249 women in the third trimester of pregnancy. None of the women had previous evidence of diabetes, and all had normal results on an oral glucose-tolerance test, according to accepted criteria. On the basis of their two-hour plasma glucose levels, women were divided into three groups: A (glucose <100 mg per deciliter), B (glucose 100 to 119 mg per deciliter), and C (glucose 120 to 164 mg per deciliter). The higher two-hour plasma glucose levels were associated with a significant increase in the incidence of macrosomia (9.9, 15.5, and 27.5 percent in Groups A, B, and C, respectively), congenital abnormalities (0.7, 3.5, and 5.0 percent), and toxemia, cesarean section, or both (19.9, 25.9, and 40.0 percent). A significant correlation between the infant's weight and the mother's two-hour plasma glucose level was also observed. These data indicate that even limited degrees of maternal hyperglycemia, which are currently considered to be within the normal range, may affect the outcome of pregnancy. (N Engl J Med 1986; 315:989–92.)
Confronting Depression and Suicide in Physicians
Authors: Claudia Center, Miriam Davis, Thomas Detre, Daniel E Ford, Wendy Hansbrough, Herbert Hendin, John Laszlo, David A Litts, John Mann, Peter A Mansky, Robert Michels, Steven H Miles, Roy Proujansky, Charles F Reynolds, Morton M Silverman
Journal: JAMA (2003)

To encourage treatment of depression and prevention of suicide in physicians by calling for a shift in professional attitudes and institutional policies to support physicians seeking help.An American Foundation for Suicide Prevention planning group invited 15 experts on the subject to evaluate the state of knowledge about physician depression and suicide and barriers to treatment. The group assembled for a workshop held October 6-7, 2002, in Philadelphia, Pa.The planning group worked with each participant on a preworkshop literature review in an assigned area. Abstracts of presentations and key publications were distributed to participants before the workshop. After workshop presentations, participants were assigned to 1 of 2 breakout groups: (1) physicians in their role as patients and (2) medical institutions and professional organizations. The groups identified areas that required further research, barriers to treatment, and recommendations for reform.This consensus statement emerged from a plenary session during which each work group presented its recommendations. The consensus statement was circulated to and approved by all participants.The culture of medicine accords low priority to physician mental health despite evidence of untreated mood disorders and an increased burden of suicide. Barriers to physicians' seeking help are often punitive, including discrimination in medical licensing, hospital privileges, and professional advancement. This consensus statement recommends transforming professional attitudes and changing institutional policies to encourage physicians to seek help. As barriers are removed and physicians confront depression and suicidality in their peers, they are more likely to recognize and treat these conditions in patients, including colleagues and medical students.
Pimecrolimus cream 1% in erosive oral lichen planus- a prospective randomized double-blind vehicle-controlled study
Authors: T. Volz, U. Caroli, H. Lüdtke, M. Bräutigam, H. Kohler-Späth, M. Röcken, T. Biedermann
Journal: British Journal of Dermatology (2008)

Erosive oral lichen planus (EOLP) is a T-cell mediated inflammatory disease leading to severe pain and impairment. As current therapies are of limited efficacy, application of calcineurin inhibitors is considered to be a potential option.To investigate the efficacy of pimecrolimus cream 1% (Elidel) compared with vehicle cream in the treatment of EOLP.Twenty patients were enrolled in a prospective, double-blind, randomized, vehicle-controlled trial and assigned to either pimecrolimus or vehicle group. Study medication was applied for 30 days followed by 30 days of observation without therapy. In case of unresponsiveness, treatment was continued for 30 days with open-label pimecrolimus. EOLP was monitored on days 0, 30 and 60. Safety was assessed by patient documentation, measurement of pimecrolimus levels and blood counts.Within 30 days erosions cleared completely in seven of 10 patients treated with pimecrolimus and in two of 10 patients treated with vehicle. The clinical EOLP 'composite score' including mucosal erosions and pain sensation was significantly reduced in the pimecrolimus-treated group compared with vehicle (P = 0.025). In the three of 10 patients not responding to pimecrolimus, EOLP cleared after an additional 30 days of treatment with pimecrolimus. Following termination of the therapy, sustained remission of EOLP was detected in 83% of patients demonstrating long-lasting effects of pimecrolimus treatment. No severe adverse events were observed. In five patients pimecrolimus blood levels were detected, all of which stayed below 4 ng mL(-1).Pimecrolimus cream 1% effectively treats EOLP with long-lasting therapeutic effects and is therefore a promising therapeutic option for EOLP.
Antibody Response to Pretreatment Immunization and Post-treatment Boosting with Bacterial Polysaccharide Vaccines in Patients with Hodgkin's Disease
Authors: GEORGE R. SIBER
Journal: Annals of Internal Medicine (1986)

Overwhelming sepsis is a serious complication of staging splenectomy in Hodgkin's disease. To define an optimal immunization strategy, 51 patients received 14-valent pneumococcal, Haemophilus influenzae type b, and meningococcal group C vaccines before therapy and 2 to 12 months after completion of therapy. Natural antibody levels to bacterial polysaccharide antigens and the response to immunization were normal or only minimally impaired in patients with Hodgkin's disease compared with findings in healthy adults. The antibody response was not affected by the timing of immunization relative to splenectomy but was frequently impaired if chemotherapy was begun less than 10 days after immunization. Both post-immunization and "natural" antibody declines were significantly greater in patients with Hodgkin's disease than in healthy adults; the magnitude of the decline was related to the intensity of therapy. A spontaneous rebound in antibody concentrations was not seen during the 12 months after treatment. Booster immunizations of all three vaccines given during this period also failed to elicit an antibody increase.
Atrial Endocrine Function in Humans with Artificial Hearts
Authors: Thomas R. Schwab, Brooks S. Edwards, William C. DeVries, Robert S. Zimmerman, John C. Burnett
Journal: New England Journal of Medicine (1986)

THE artificial heart is currently under investigation as a means to restore cardiac function in patients with end-stage heart failure. During implantation, the Jarvik-7 artificial heart is anastomosed to the native pulmonary artery, aorta, and cardiac atria.1 Postoperatively, approximately 95 percent of the native atrial tissue remains in situ.The atria play a key part in the control of body-fluid homeostasis by monitoring blood volume and initiating appropriate changes in urine flow and sodium excretion. Until recently the polyuria that may accompany atrial tachycardia and atrial distension has been attributed to reflex stimulation of subendocardial neuronal stretch receptors.2 , 3 In 1981 . . .
Visualization of Reflux From Bladder to the Duodenal Portion of a Pancreatic-Duodenal Allograft
Authors: LENA PINKAS, RICHARD NAKACHE, ERNESTO LUBIN
Journal: Clinical Nuclear Medicine (1995)

A 40-year-old man with a history of end-stage renal disease secondary to insulin-dependent diabetes mellitus underwent a combined renal and pancreas transplant. Two weeks after transplantation the patient was referred for Tc-99m DTPA scintigraphy. The early scan revealed good perfusion to, and concentration in, the kidney and very well defined perfusion to the pancreas. The scan made 60 minutes later showed a remnant of activity in the kidney with a full bladder and reflux to the duodenal portion of the pancreatic transplant.
[324] ABOLISHED ACUTE PHASE RESPONSE AND ENHANCED LIVER INJURY AFTER BILE-DUCT LIGATION IN HEPATOCYTE SPECIFIC CONDITIONAL c-Met KNOCKOUT MICE
Authors: A. Giebeler, C. Klein, S. Erschfeld, M. Borowiak, C. Birchmeier, C. Trautwein, K. Streetz
Journal: Journal of Hepatology (2007)