tbuckley/cabot-search huggingface dataset:
Expression of Functional B7-H2 and B7.2 Costimulatory Molecules and Their Prognostic Implications in<i>De novo</i>Acute Myeloid Leukemia
Authors: Hideto Tamura, Kazuo Dan, Koji Tamada, Kyoko Nakamura, Yumiko Shioi, Hideya Hyodo, Sheng-Dian Wang, Haidong Dong, Lieping Chen, Kiyoyuki Ogata
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The B7 family molecules have been shown to regulate immune responses in both positive and negative fashions. Their roles in the progression of human cancers, however, are not well established. The aim of this study was to examine whether leukemic cells of acute myeloid leukemia express functional B7 family molecules and, if so, whether such expression has any clinical significance. Experimental Design: The expression of four B7 family molecules, B7.1, B7.2, B7-H1, and B7-H2, on leukemic cells from acute myeloid leukemia patients was analyzed by flow cytometry. The function of the expressed molecules was examined by the allogeneic mixed lymphocyte-leukemic cell reaction, and their relationship to the clinical data and survival was analyzed. Results: Although B7.1 and B7-H1 expressions were rare, the cells from a substantial number of acute myeloid leukemia cases expressed B7.2 and B7-H2 molecules [mean percentages of B7.2- and B7-H2-positive cells were 28.9% (n = 58) and 15.3% (n = 59), respectively]. Patients in whom &amp;gt;25% of leukemic cells expressed B7-H2 had significantly shorter survival, and this B7-H2 positivity had the strongest prognostic value when B7-H2 and other prognostic factors were analyzed together by multivariate analysis (P = 0.0108). Furthermore, B7.2 expression was associated with hyperleukocytosis (P = 0.026). Consistent with this finding, acute myeloid leukemia cells expressing B7.2 and B7-H2 induced allogeneic CD4+ T cells to proliferate and secrete interleukin-4 and interleukin-10 in vitro, effects that were partially blocked by antibodies against B7.2 and B7-H2. Conclusions: Our results indicate the expression of functional B7.2 and B7-H2 molecules, and these molecules may facilitate progression of acute myeloid leukemia.
Erythropoietin life span in rats with hypoplastic and hyperplastic bone marrows
Authors: Ettore Piroso, Allan J. Erslev, Kristen K. Flaharty, Jaime Caro
Journal: American Journal of Hematology (1991)

Abstract The metabolic fate of erythropoietin (EPO) remains unknown. Urinary excretion does not appear to play a major role and liver catabolism has been shown to occur only after terminal sugars on the hormone have been removed. However, it has been proposed that EPO is eliminated by consumption in the bone marrow. In order to examine the extent of such consumption we measured the half‐life of radioidinated recombinant EPO injected intravenously (IV) to rats with bone marrows suppressed by cyclophosphamide or hypertransfusion and marrows stimulated by phenylhydrazine or bleeding. The mean half‐life or erythropoietin in normal rats was 179 ± 16 min, with similar half‐lives found in the other rats regardléss of decreased or increased bone marrow activity. The results indicate that it is unlikely that erythroid activity determines EPO life span and catabolism.
CD44-Positive Cancer Stem Cells Expressing Cellular Prion Protein Contribute to Metastatic Capacity in Colorectal Cancer
Authors: Lei Du, Guanhua Rao, Hongyi Wang, Baowei Li, Weili Tian, Jiantao Cui, Leya He, Brian Laffin, Xiuyun Tian, Chunyi Hao, Hongmin Liu, Xin Sun, Yushan Zhu, Dean G. Tang, Maryam Mehrpour, Youyong Lu, Quan Chen
Journal: Cancer Research (2013)

Abstract Cancer stem cells are implicated in tumor progression, metastasis, and recurrence, although the exact mechanisms remain poorly understood. Here, we show that the expression of cellular prion protein (PrPc, PRNP) is positively correlated with an increased risk of metastasis in colorectal cancer. PrPc defines a subpopulation of CD44-positive cancer stem cells that contributes to metastatic capacity. PrPc+CD44+ colorectal cancer stem cells displayed high liver metastatic capability, unlike PrPc−CD44+ stem cells, that was inhibited by RNAi-mediated attenuation of PrPc. Notably, administration of PrPc monoclonal antibodies significantly inhibited tumorigenicity and metastasis of colorectal cancer stem cells in mouse models of orthotopic metastasis. PrPc promoted epithelial to mesenchymal transition (EMT) via the ERK2 (MAPK1) pathway, thereby conferring high metastatic capacity. Our findings reveal the function of PrPc in regulating EMT in cancer stem cells, and they identify PrPc as candidate therapeutic target in metastatic colorectal cancer. Cancer Res; 73(8); 2682–94. ©2013 AACR.
Langerhans cell (LC) proliferation mediates neonatal development, homeostasis, and inflammation-associated expansion of the epidermal LC network
Authors: Laurent Chorro, Aurélien Sarde, Mei Li, Kevin J. Woollard, Pierre Chambon, Bernard Malissen, Adrien Kissenpfennig, Jean Baptiste Barbaroux, Richard Groves, Frédéric Geissmann
Journal: The Journal of Experimental Medicine (2009)

Most tissues develop from stem cells and precursors that undergo differentiation as their proliferative potential decreases. Mature differentiated cells rarely proliferate and are replaced at the end of their life by new cells derived from precursors. Langerhans cells (LCs) of the epidermis, although of myeloid origin, were shown to renew in tissues independently from the bone marrow, suggesting the existence of a dermal or epidermal progenitor. We investigated the mechanisms involved in LC development and homeostasis. We observed that a single wave of LC precursors was recruited in the epidermis of mice around embryonic day 18 and acquired a dendritic morphology, major histocompatibility complex II, CD11c, and langerin expression immediately after birth. Langerin(+) cells then undergo a massive burst of proliferation between postnatal day 2 (P2) and P7, expanding their numbers by 10-20-fold. After the first week of life, we observed low-level proliferation of langerin(+) cells within the epidermis. However, in a mouse model of atopic dermatitis (AD), a keratinocyte signal triggered increased epidermal LC proliferation. Similar findings were observed in epidermis from human patients with AD. Therefore, proliferation of differentiated resident cells represents an alternative pathway for development in the newborn, homeostasis, and expansion in adults of selected myeloid cell populations such as LCs. This mechanism may be relevant in locations where leukocyte trafficking is limited.
Public Health in the Twentieth Century: Advances and Challenges
Authors: Jonathan E. Fielding
Journal: Annual Review of Public Health (1999)

▪ Abstract Substantial advances in public health methods, practice, and the health of the public have occurred in the twentieth century. Some of the contributions most notable for their impact on mortality and longevity are vaccine development and widespread use, smallpox eradication, large reductions in communicable disease epidemics, and the rise and decline of several serious chronic diseases. Many methodological advances have facilitated better understanding of disease processes and opportunities for control. Epidemiological methods have advanced, but studies often ignore the determinants of health at the community level and above, leading to simplistic formulations of multiple risk factors contributing to chronic and other diseases and injuries. Occupational and environmental health developed as disciplines in this century, making significant contributions to current and future population health. The health care system became more organized, technologically sophisticated, and costly. New tools to assess health and the burden of ill health, to improve the effectiveness of interventions, and to measure economic effects of alternative investments promise greater efficiency and effectiveness for public health. An increasingly fragmented public health infrastructure must confront unprecedented challenges including dramatic global population growth, increased aging of the population associated with enhanced longevity, and possible irreversible changes in key environmental health determinants.
Smoking as a risk factor for end-stage renal failure in men with primary renal disease
Authors: S R Orth, A Stöckmann, C Conradt, E Ritz, M Ferro, W Kreusser, G Piccoli, M Rambausek, D Roccatello, K Schäfer, H G Sieberth, C Wanner, B Watschinger, P Zucchelli
Journal: Kidney International (1998)
A Small Molecule CXCR4 Inhibitor that Blocks T Cell Line–tropic HIV-1 Infection
Authors: Tsutomu Murakami, Toshihiro Nakajima, Yoshio Koyanagi, Kazunobu Tachibana, Nobutaka Fujii, Hirokazu Tamamura, Nobuaki Yoshida, Michinori Waki, Akiyoshi Matsumoto, Osamu Yoshie, Tadamitsu Kishimoto, Naoki Yamamoto, Takashi Nagasawa
Journal: The Journal of Experimental Medicine (1997)

Several members of the chemokine receptor family have been shown to function in association with CD4 to permit human immunodeficiency virus type 1 (HIV-1) entry and infection. The CXC chemokine receptor CXCR4/fusin is a receptor for pre–B cell growth stimulating factor (PBSF)/stromal cell–derived factor 1 (SDF-1) and serves as a coreceptor for the entry of T cell line–tropic HIV-1 strains. Thus, the development of CXCR4 antagonists or agonists may be useful in the treatment of HIV-1 infection. T22 ([Tyr5,12,Lys7]-polyphemusin II) is a synthesized peptide that consists of 18 amino acid residues and an analogue of polyphemusin II isolated from the hemocyte debris of American horseshoe crabs (Limulus polyphemus). T22 was found to specifically inhibit the ability of T cell line–tropic HIV-1 to induce cell fusion and infect the cell lines transfected with CXCR4 and CD4 or peripheral blood mononuclear cells. In addition, T22 inhibited Ca2+ mobilization induced by pre–B cell growth stimulating factor (PBSF)/SDF-1 stimulation through CXCR4. Thus, T22 is a small molecule CXCR4 inhibitor that blocks T cell line–tropic HIV-1 entry into target cells.
Fertility watchdog says that donor identity should be revealed
Authors: C. Dyer
Journal: BMJ (2002)

Sperm and egg donors in the United Kingdom should lose their right to anonymity, the Human Fertilisation and Embryology Authority has recommended in its response to a Department of Health consultation paper canvassing views on a possible change in the law.

The fertility watchdog's call for a reversal of government policy will dismay many infertility specialists who fear it would cause the supply …
Scorpion venoms: taking the sting out of lung disease.
Authors: D. F. Rogers
Journal: Thorax (1996)

Scorpion venoms contain specific toxins which block large conductance calcium-activated potassium (BKCa) channels. Use of these toxins has shown that a significant proportion of the action of bronchodilators such as beta-agonists, theophylline, and nitric oxide occurs as a result of the opening of BKCa channels. Similarly, these toxins have shown that inhibitors of airway neurotransmission also operate via BKCa channels. Drugs that open BKCa channels may be alternative bronchodilators (possibly "airway selective" and with fewer side effects) as well as inhibitors of pathophysiological neurogenic influences in asthma, chronic coughing and sneezing, and chronic bronchitis.
We don't need another 400 plastic surgeons
Authors: M Justin S Zaman
Journal: BMJ (2007)

I recently overheard a junior doctor complaining about the new career pathway structure in the United Kingdom for trainees (Modernising Medical Careers). Apparently there are 400 plastic surgical trainees competing for only 20 training programmes. The complaint from this aggrieved young trainee was of how many of them were being “cast aside” and how few trainees were being allowed to train in their chosen field. My immediate thought on this was whether the UK actually needed that many plastic surgeons. Is there really that amount of burns and reconstructive work here? Perhaps plastic surgical trainees all want to be cosmetic surgeons? Surely not… 

When, during my second year at medical school, I decided on cardiology as my career choice, one of my reasons was that …
Hyperbilirubinemia, Augmentation of Endothelial Function, and Decrease in Oxidative Stress in Gilbert Syndrome
Authors: Tatsuya Maruhashi, Junko Soga, Noritaka Fujimura, Naomi Idei, Shinsuke Mikami, Yumiko Iwamoto, Masato Kajikawa, Takeshi Matsumoto, Yasuki Kihara, Kazuaki Chayama, Kensuke Noma, Ayumu Nakashima, Hirofumi Tomiyama, Bonpei Takase, Akira Yamashina, Yukihito Higashi
Journal: Circulation (2012)

Background— Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. We evaluated the role of oxidative stress in endothelial function in patients with Gilbert syndrome under normal conditions without cardiovascular risk factors. Methods and Results— A total of 108 young men with Gilbert syndrome without cardiovascular risk factors and 108 age-matched healthy men (normal controls) were enrolled in this study. Serum concentrations of bilirubin were higher in patients with Gilbert syndrome than in control subjects (29.2±11.6 versus 9.4±2.7 μmol/L; P &lt;0.001). Serum concentrations of malondialdehyde-modified low-density lipoprotein and urinary excretion of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as indices of oxidative stress, were lower in patients with Gilbert syndrome than in control subjects (61.8±24.5 versus 72.5±21.8 U/L, P =0.034; 7.8±2.4 versus 10.4±3.2 ng/mg creatinine, P =0.001, respectively). Flow-mediated vasodilation was greater in patients with Gilbert syndrome than in normal control subjects (7.2±2.2% versus 5.9±1.7%; P &lt;0.001). Vascular responses to nitroglycerine were not significantly different between the 2 groups. Flow-mediated vasodilation correlated with serum concentration of bilirubin ( r =0.44, P &lt;0.001), malondialdehyde-modified low-density lipoprotein ( r =−0.25, P =0.01), and urinary excretion of 8-OHdG ( r =−0.27, P =0.004) in patients with Gilbert syndrome but not in control subjects. In addition, serum concentration of bilirubin correlated with malondialdehyde-modified low-density lipoprotein ( r =−0.20, P =0.04) and 8-OHdG ( r =−0.21, P =0.02) in patients with Gilbert syndrome but not in control subjects. Conclusions— Patients with Gilbert syndrome had low levels of oxidative stress associated with hyperbilirubinemia and enhancement of endothelium-dependent vasodilation. Clinical Trial Registration— URL: http://www.umin.ac.jp . Unique identifier: UMIN000003409.
The need for atrial flutter ablation following pulmonary vein antrum isolation in patients with and without previous cardiac surgery
Authors: Fethi Kilicaslan, Atul Verma, Hirosuke Yamaji, Nassir F. Marrouche, Oussama Wazni, Jennifer E. Cummings, Steven Hao, Michelle Williams Andrews, Salwa Beheiry, Ahmad Abdul-Karim, William A. Belden, Stephen Minor, J. David Burkhardt, Walid Saliba, Robert A. Schweikert, Andrea Natale
Journal: Journal of the American College of Cardiology (2005)
Health care utilization and mortality among elderly patients with myelodysplastic syndromes
Authors: K.J. Lindquist, M.D. Danese, J. Mikhael, K.B. Knopf, R.I. Griffiths
Journal: Annals of Oncology (2010)

Mortality in patients with myelodysplastic syndromes (MDS) is high, and patients are likely to require hospitalizations, emergency department (ED) visits, and transfusions. The relationships between these events and the MDS complications of anemia, neutropenia, and thrombocytopenia are not well understood.A total of 1864 patients registered in the United States' Surveillance Epidemiology and End Results (SEER) program and aged ≥ 66 years old when diagnosed with MDS in 2001 or 2002 were included. Medicare claims were used to identify MDS complications and utilization (hospitalizations, ED visits, and transfusions) until death or the end of 2005. Mortality was based on SEER data. Kaplan-Meier incidence rates were estimated and multivariable Cox models were used to study the association between complications and outcomes.The 3-year incidence of anemia, neutropenia, and thrombocytopenia was 81%, 25%, and 41%, and the incidence of hospitalization, ED visit, and transfusion was 62%, 42%, and 45%, respectively. Median survival time was 22 months. Cytopenia complications were significantly associated with each of these outcomes.All types of cytopenia are common among patients with MDS and are risk factors for high rates of health care utilization and mortality. Management of the complications of MDS may improve patient outcomes.
Comparison of ciprofloxacin or trimethoprim therapy for venous leg ulcers: Results of a pilot study
Authors: Saara Huovinen, Pirkko Kotilainen, Helinä Järvinen, Ken Malanin, Seppo Sarna, Inkeri Helander, Pentti Huovinen
Journal: Journal of the American Academy of Dermatology (1994)
Early-Stage Melanoma: Staging Criteria and Prognostic Modeling
Authors: Merrick I. Ross
Journal: Clinical Cancer Research (2006)

Abstract Accurate risk assessment is central to the process of making rational surgical and systemic treatment recommendations for melanoma patients and in establishing appropriate clinical trial stratification criteria. The current American Joint Commission on Cancer melanoma staging system incorporated relevant prognostic variables to provide a framework for the estimation of risk for recurrence; however, significant prognostic heterogeneity exists within the stage groupings. In the stage I/II group, survival rates range from 40% to 95% as defined by the combination of tumor thickness and ulceration. The use of novel prognostic factors, such as mitotic rate, sentinel node biopsy, and prognostic modeling using a variety of factors, can minimize this prognostic heterogeneity and provide a more accurate and individualized prognostic profile. Recent modifications in the stage III criteria include the number of positive nodes, whether the nodal disease is microscopic or clinically apparent, and the presence of an ulcerated primary. Through these factors, survival estimates can be provided, but like the stage I/II group, wide ranges in prognosis exist. The complexion of the stage III population is in evolution as a result of increasing numbers of patients being diagnosed as having microscopic sentinel node disease. Contemporary efforts are focused on defining the prognosis and natural history of this group. Through prognostic modeling using the number of nodes involved, ulceration status, and a measure of disease burden—disease in the sentinel node—relatively homogeneous subgroups can be identified. Long-term follow-up of patients staged with PCR molecular techniques on sentinel nodes shows conflicting value in assessing prognosis and therefore cannot be routinely used outside a clinical trial. The combination of genomic profiling using microarray analyses and the development of targeted therapy holds the future promise of individualizing prognosis and therapy.
Persistence of Solitary Mammary Carcinoma Cells in a Secondary Site: A Possible Contributor to Dormancy
Authors: George N Naumov, Ian C MacDonald, Pascal M Weinmeister, Nancy Kerkvliet, Kishore V Nadkarni, Sylvia M Wilson, Vincent L Morris, Alan C Groom, Ann F Chambers
Journal: Cancer Research (2002)

Tumors can recur years after treatment, and breast cancer is especially noted for long periods of dormancy. The status of the cancer during this period is poorly understood. As a model to study mechanisms of dormancy, we used murine D2.0R mammary carcinoma cells, which are poorly metastatic but form occasional metastases in liver and other organs after long latency. Highly metastatic D2A1 cells provided a positive, metastatic control. Our goals were to learn how the cell lines differ in survival kinetics in a secondary site and to seek evidence for the source of D2.0R dormancy. In spontaneous metastasis assays from mammary fat pad injections, we found evidence for dormancy because of a persistence of large numbers of solitary cells in the liver. To quantify the fate of cells after arrival in liver, experimental metastasis assays were used. To permit identification of cells that had not divided, cells were labeled before injection with fluorescent nanospheres, which were diluted to undetectable levels by cell division. Cancer cells were injected i.v. to target them to the liver and coinjected with reference microspheres to monitor cell survival. Dormancy was defined as retention of nanosphere fluorescence in vivo, as well as negative staining for the proliferation marker Ki67. A large proportion of D2.0R cells persisted as solitary dormant cells. No metastases formed, but viable cells could be recovered from the liver 11 weeks after injection. Large numbers of solitary, dormant, Ki67-negative D2A1 cells were also detected against a background of progressively growing metastases. Thus, this study identified a possible contributor to tumor dormancy: solitary, dormant cells that persist in tissue. If such cells are present in patients, they could contribute to tumor recurrence and would not be susceptible to current therapeutic strategies targeting proliferating cells.
Identification of tryptic peptides unique to a 110,000-molecular weight polyprotein encoded by the T-8 isolate of murine leukemia virus.
Authors: W J van de Ven, F H Reynolds, J Blomberg, J R Stephenson
Journal: The Journal of Experimental Medicine (1980)

Mink cells nonproductively-infected with the weakly-transforming T-8 isolate of murine leukemia virus (MuLV) express a 110,000 mol wt polyprotein designated T-8 P110. By immunoprecipitation analysis, T-8 P110 is shown to contain AKR-MuLV amino terminal gag gene-specific components (p15, p12) but to lack p30, p10, gp70, and p15(E) antigenic determinants. These observations are further substantiated by tryptic peptide analysis indicating T-8 P110 to share approximately six lysine-containing tryptic peptides with AKR-MuLV Pr65gag, and none with AKr-MuLV Pr82env. Furthermore, of seven methionine-containing T-8 P110 tryptic peptides, at least four can be conclusively shown not to be present in either AKr-MuLV Pr180gag/pol or Pr82env. A clonal mink cell line nonproductively infected by T-8, and expressing high levels of P110, although not morphologically transformed, is shown to lack elevated levels of tyrosine-specific protein kinase activity and reduction of epidermal growth factor binding sites characteristic of cells transformed by many other RNA-transforming viruses. These findings argue either that the T-8 viral genome contains acquired cellular sequences encoding a portion of P110, or that T-8 P110 represents an inphase deletion of AKR-MuLV Pr180gag/pol with extensive posttranlational modification and that an as yet unidentified protein is responsible for T-8 associated transformation.
Role of Growth arrest-specific gene 6-Mer axis in multiple myeloma
Authors: J S Waizenegger, I Ben-Batalla, N Weinhold, T Meissner, M Wroblewski, M Janning, K Riecken, M Binder, D Atanackovic, H Taipaleenmaeki, D Schewe, S Sawall, V Gensch, M Cubas-Cordova, A Seckinger, W Fiedler, E Hesse, N Kröger, B Fehse, D Hose, B Klein, M S Raab, K Pantel, C Bokemeyer, S Loges
Journal: Leukemia (2014)