tbuckley/cabot-search huggingface dataset:
Splenic artery embolization prior to splenectomy in end‐stage polycythemia vera
Authors: William G. Hocking, Herbert I. Machleder, David W. Golde
Journal: American Journal of Hematology (1980)

Abstract A patient with polycythemia rubra vera and myeloid metaplasia required splenectomy because of local symptoms attributable to a massively enlarged spleen. Preoperative embolization of the splenic circulation with inert materials was performed to reduce splenic size and vascularity in order to permit safe splenectomy. This case illustrates the utility of preoperative splenic embolization when routine splenectomy is contraindicated for technical reasons. The hazards of this technique and guidelines for its clinical use are outlined.
PEDF, PPAR-γ, p53: Deadly circuits arise when worlds collide
Authors: C GAETANO, C COLUSSI, M CAPOGROSSI
Journal: Cardiovascular Research (2007)

See article by Ho et al.  [6]  (pages 213–223) in this issue. 

The superfamily of serine proteinase inhibitors (serpins) is involved in a number of fundamental biological processes such as blood coagulation, complement activation, fibrinolysis, angiogenesis, inflammation and tumor suppression and are expressed in a cell-specific manner [1]. The pigment epithelium-derived factor (PEDF) is a 50-kD serpin that lacks inhibitory properties against either serine or cysteine proteinases [2]. PEDF was first identified in 1987 by Tombran-Tink and Johnson in conditioned medium from foetal human retinal pigment epithelium cell cultures (published in 1991 [3]). PEDF has been shown to be a neurotrophic/differentiation factor and an inhibitor of glial cell proliferation [4]. It is also a protein that is highly up-regulated in the G0 phase of early-passage cells compared with rapidly proliferating cells or senescent cells, and is thus also linked to both the cell cycle and cell senescence. Low-dose PEDF inhibits endothelial cell migration and proliferation, reducing VEGF, FGF-2 and other cytokines-dependent angiogenesis in the rat cornea, and, recently, PEDF has been found to be involved in endothelial cell apoptosis via FAS ligand (FASL) induction and caspase 8 and 9 activation. Although many findings suggest a receptor-like nature of PEDF action, the … 

*Corresponding author. Tel.: +39 0666462431; fax: +39 0666462430. gaetano{at}idi.it
Transpapillary iridium-192 wire in the treatment of malignant bile duct obstruction.
Authors: M D Levitt, B H Laurence, F Cameron, P F Klemp
Journal: Gut (1988)

Twenty four patients with malignant bile duct obstruction were treated with intraluminal radiotherapy using iridium-192 wire inserted through an endoscopically placed nasobiliary catheter. Biliary drainage after treatment was maintained by an endoprosthesis. The median dose of intraluminal radiotherapy was 6000 cGy; two patients with cholangiocarcinoma were given a second course because of disease extension; four patients with pancreatic carcinoma received additional external irradiation (3000 cGy). There was one early death from a cerebrovascular accident (30 day mortality, 4.2%). Cholangitis (30%) was the major early complication and stent blockage (40%) the major late complication; there were no complications directly attributable to radiotherapy. The median survival for patients with pancreatic carcinoma was 250 days and for cholangiocarcinoma, 300 days. This method is technically feasible and may prove safer than the transhepatic technique. The ability of intraluminal irradiation to improve palliation or lengthen survival in patients with malignant bile duct obstruction remains uncertain. Assessment by a prospective, controlled trial is essential.
Evolution of the AID/APOBEC Family of Polynucleotide (Deoxy)cytidine Deaminases
Authors: Silvestro G. Conticello, Cornelia J. F. Thomas, Svend K. Petersen-Mahrt, Michael S. Neuberger
Journal: Molecular Biology and Evolution (2004)

The AID/APOBEC family (comprising AID, APOBEC1, APOBEC2, and APOBEC3 subgroups) contains members that can deaminate cytidine in RNA and/or DNA and exhibit diverse physiological functions (AID and APOBEC3 deaminating DNA to trigger pathways in adaptive and innate immunity; APOBEC1 mediating apolipoprotein B RNA editing). The founder member APOBEC1, which has been used as a paradigm, is an RNA-editing enzyme with proposed antecedents in yeast. Here, we have undertaken phylogenetic analysis to glean insight into the primary physiological function of the AID/APOBEC family. We find that although the family forms part of a larger superfamily of deaminases distributed throughout the biological world, the AID/APOBEC family itself is restricted to vertebrates with homologs of AID (a DNA deaminase that triggers antibody gene diversification) and of APOBEC2 (unknown function) identifiable in sequence databases from bony fish, birds, amphibians, and mammals. The cloning of an AID homolog from dogfish reveals that AID extends at least as far back as cartilaginous fish. Like mammalian AID, the pufferfish AID homolog can trigger deoxycytidine deamination in DNA but, consistent with its cold-blooded origin, is thermolabile. The fine specificity of its mutator activity and the biased codon usage in pufferfish IgV genes appear broadly similar to that of their mammalian counterparts, consistent with a coevolution of the antibody mutator and its substrate for the optimal targeting of somatic mutation during antibody maturation. By contrast, APOBEC1 and APOBEC3 are later evolutionary arrivals with orthologs not found in pufferfish (although synteny with mammals is maintained in respect of the flanking loci). We conclude that AID and APOBEC2 are likely to be the ancestral members of the AID/APOBEC family (going back to the beginning of vertebrate speciation) with both APOBEC1 and APOBEC3 being mammal-specific derivatives of AID and a complex set of domain shuffling underpinning the expansion and evolution of the primate APOBEC3s.
Role of endothelial cell cytoskeleton in control of endothelial permeability.
Authors: D M Shasby, S S Shasby, J M Sullivan, M J Peach
Journal: Circulation Research (1982)

Increased permeability of the pulmonary microvasculature is felt to cause acute noncardiogenic lung edema, and histological studies of edematous lungs show gaps between apparently healthy endothelial cells. To determine whether alterations in endothelial cell cytoskeletons would alter endothelial permeability, we exposed monolayers of pulmonary artery endothelial cells grown on micropore filters to cytochalasin B or D. Cytochalasin exposed monolayers demonstrated a 2- to 3-fold increase in endothelial permeability that was readily reversible by washing the monolayers free of cytochalasins. Parallel phase contrast and fluorescence microscopy demonstrated retraction of cell cytoplasm and disruption of bundles of microfilaments in cytochalasin exposed cells. These changes also were readily reversed after washing the cells free from cytochalasins. To test the relevance of these findings to an in situ microvasculature, we added cytochalasin B to the perfusate of isolated rabbit lungs and observed that cytochalasin B caused a high permeability lung edema. These studies suggest that endothelial cell cytoskeletons may be important determinants of endothelial permeability.
Pure Red Cell Aplasia Secondary to Epoetin alpha Responding to Darbepoetin Alpha in a Patient on Peritoneal Dialysis
Authors: Ashwin Asari, Ram Gokal
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Recombinant Human Erythropoietin (EPO) is extensively used for anemia in renal failure patients. It is normally safe and effective, improving symptoms of anemia. We report here a case of renal anemia in a patient undergoing peritoneal dialysis (PD) for end stage renal failure from renovascular disease. He initially responded well to Epoetin alpha (Eprex) but subsequently developed EPO antibodies and pure red cell aplasia (PRCA), becoming blood transfusion dependent. Subsequently, he responded to Darbepoetin alpha (Aranesp), without any complications in the presence of persisting EPO antibodies. This positive response, which restored hemoglobin values to normal, occurred despite general belief that any form of EPO will cross-react to EPO antibodies. This is the first case report where PRCA with EPO antibodies responded well to another EPO preparation without intervention from immunosuppression therapy.
Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study
Authors: E. M. Boyle, G. Poulsen, D. J. Field, J. J. Kurinczuk, D. Wolke, Z. Alfirevic, M. A. Quigley
Journal: BMJ (2012)

<b>Objective</b> To investigate the burden of later disease associated with moderate/late preterm (32-36 weeks) and early term (37-38 weeks) birth. <b>Design</b> Secondary analysis of data from the Millennium Cohort Study (MCS). <b>Setting</b> Longitudinal study of infants born in the United Kingdom between 2000 and 2002. <b>Participants</b> 18 818 infants participated in the MCS. Effects of gestational age at birth on health outcomes at 3 (n=14 273) and 5 years (n=14 056) of age were analysed. <b>Main outcome measures</b> Growth, hospital admissions, longstanding illness/disability, wheezing/asthma, use of prescribed drugs, and parental rating of their children’s health. <b>Results</b> Measures of general health, hospital admissions, and longstanding illness showed a gradient of increasing risk of poorer outcome with decreasing gestation, suggesting a “dose-response” effect of prematurity. The greatest contribution to disease burden at 3 and 5 years was in children born late/moderate preterm or early term. Population attributable fractions for having at least three hospital admissions between 9 months and 5 years were 5.7% (95% confidence interval 2.0% to 10.0%) for birth at 32-36 weeks and 7.2% (1.4% to 13.6%) for birth at 37-38 weeks, compared with 3.8% (1.3% to 6.5%) for children born very preterm (&lt;32 weeks). Similarly, 2.7% (1.1% to 4.3%), 5.4% (2.4% to 8.6%), and 5.4% (0.7% to 10.5%) of limiting longstanding illness at 5 years were attributed to very preterm birth, moderate/late preterm birth, and early term birth. <b>Conclusions</b> These results suggest that health outcomes of moderate/late preterm and early term babies are worse than those of full term babies. Additional research should quantify how much of the effect is due to maternal/fetal complications rather than prematurity itself. Irrespective of the reason for preterm birth, large numbers of these babies present a greater burden on public health services than very preterm babies.
Cynomolgus monkey gallbladder bile contains high concentrations of fibroblast growth factor 19
Authors: Luna Luo, Faustine Luo, Tony Wang
Journal: Hepatology (2013)

Fibroblast growth factor 19 (FGF19) is a unique member of the FGF family. It is one of the three secreted FGFs (FGF19, FGF21, and FGF23) that are devoid of mitogenic activity and can be released into the circulation to fulfill an endocrine mode of action.1-3 It is intriguing that Zweers et al.4 reported that human bile contains FGF19. In fact, the levels of FGF19 in human gallbladder bile are 100-fold higher than the circulating FGF19 (21.9 ± 13.3 ng/mL versus 0.22 ± 0.14 ng/mL).4 In addition, they showed that the FGF19 gene is expressed in the adult human gallbladder, and high levels of FGF19 can be secreted from gallbladder mucosal explants.4 This indicates that a major source of FGF19 in the bile is from mucosal cells of the gallbladder. On the other hand, the messenger RNA (mRNA) of FGF15 (FGF19 ortholog) was virtually undetectable in murine gallbladder.4 Thus far, the human species is the only species being reported to have a high concentration of FGF19 in the gallbladder bile. To address the skeptical view of an endocrine factor appearing in an exocrine space, we examined gallbladder bile from cynomolgus monkeys (Macaca fascicularis) for the presence of FGF19. In addition, circulating concentrations of FGF19 in monkeys and its responses to the presence and absence of bile acid was determined. In normal male adult monkeys, the gallbladder bile FGF19 concentrations range from 3,827 to 23,961 pg/mL and average 10,533 pg/mL (Table 1). Interestingly, serum FGF19 concentrations in the monkeys range from 85 to 592 pg/mL and average 358 pg/mL (Table 1), which is similar to that in human (range 49 to 590 pg/mL)5 and 30-fold lower than that in gallbladder bile. Furthermore, serum concentrations of FGF19 increased significantly after enteral bile acid (chenodeoxycholic acid [CDCA]) stimulation, while it decreased substantially after enteral bile acid sequestration (cholestyramine) (Fig. 1). This is also consistent with the observations in human.5 This is the first report to document high levels of FGF19 detected in the gallbladder bile in monkeys. The finding enhances our confidence in the observation that the presence of FGF19 in bile is valid and most likely physiological. The similar serum FGF19 profile of the two species furthers our interest in using monkeys as a model to understand the potential dual endocrine/exocrine roles of FGF19. Luna Luo1* Faustine Luo1* Tony Wang, Ph.D.2 1Albany High School, Albany, CA 2Kunming Biomed International, Cheng-Gong District, Kunming, Yunan, China
A Mutant High-Density Lipoprotein Receptor Inhibits Proliferation of Human Breast Cancer Cells
Authors: Wen M. Cao, Koji Murao, Hitomi Imachi, Xiao Yu, Hiroshi Abe, Akira Yamauchi, Michio Niimi, Akira Miyauchi, Norman C. W. Wong, Toshihiko Ishida
Journal: Cancer Research (2004)

High-density lipoprotein (HDL) stimulates the growth of many types of cells, including those of breast cancer. High levels of HDL are associated with an increased risk of breast cancer development. A scavenger receptor of the B class (SR-BI)/human homolog of SR-BI, CD36, and LIMPII analogous-1 (CLA-1) facilitates the cellular uptake of cholesterol from HDL and thus augments cell growth. Furthermore, HDL is also believed to have antiapoptotic effects on various cell types, and this feature adds to its ability to promote cell growth. These collaborative roles of HDL and CLA-1 prompted us to assess the function of these components on human breast cancer cells. In this study, we created a mutant CLA-1 (mCLA) that lacked the COOH-terminal tail to determine its potential role in breast cancer cell growth. Expression of mCLA inhibited the proliferation of breast cancer cell line MCF-7. This inhibitory action of mCLA required the transcriptional factor activator protein-1 (AP-1), and the mutant receptor also affected the antiapoptotic features of HDL. The effect of HDL on AP-1 activation and [(3)H]thymidine incorporation was abrogated by wortmannin, a specific inhibitor of phosphoinositide 3-kinase. Furthermore, the dominant negative mutant of Akt abolished the ability of HDL to activate AP-1. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for breast cancer.
Tolerating the Nervous System
Authors: Eric S. Huseby, Joan Goverman
Journal: The Journal of Experimental Medicine (2000)

Experimental allergic encephalomyelitis (EAE) is an animal model of multiple sclerosis that is induced by immunization with myelin antigens ([1][1]). The ability to generate EAE by activating myelin-specific T cells in the periphery of healthy animals demonstrates that central and peripheral
Re: Leptin--A Growth Factor in Normal and Malignant Breast Cells and for Normal Mammary Gland Development
Authors: E. Oelmann, S. Haghgu, E. Kulimova, H. Serve, C. Schmitmann, W. E. Berdel
Journal: JNCI Journal of the National Cancer Institute (2003)

Leptin is an endogenous protein important for the control of body weight and body fat.Further, obesity is a risk factor for breast cancer in postmenopausal women.In a recent issue of the journal, Cleary and colleagues (1) reported the presence of OB-Rb, the signaling long form of the leptin receptor, on two breast cell lines including T-47D, the leptin stimulation of anchorage-dependent and -independent growth of T-47D cells, and some related intracellular signaling events.Additionally, these authors cited various other reports on the presence of OB-Rb on human tumor cell types derived from carcinomas and leukemias.Although the observations reported are specific and welldocumented, they may leave the impression that leptin might be a general inducer of tumor cell growth, which would greatly hamper its clinical utility.We studied the expression of transcripts for human leptin, OB-Rb, and OB-Ra (short, non-signaling form of the leptin receptor) in human malignant cell lines of different histologic origin (Table 1).We found wide expression of leptin, OB-Rb, and OB-Ra transcripts by reverse transcription-polymerase
Role of Calcium Cycling Versus Restitution in the Mechanism of Repolarization Alternans
Authors: Etienne J. Pruvot, Rodolphe P. Katra, David S. Rosenbaum, Kenneth R. Laurita
Journal: Circulation Research (2004)

T-wave alternans, a powerful marker of arrhythmic events, results from alternation in action potential duration (APD). The underlying cellular mechanism of APD alternans is unknown but has been attributed to either intracellular calcium (Ca 2+ ) cycling or membrane ionic currents, manifested by a steep slope of cellular APD restitution. To address these mechanisms, high-resolution optical mapping techniques were used to measure action potentials and Ca 2+ transients simultaneously from hundreds of epicardial sites in the guinea pig model of pacing-induced T-wave alternans (n=7). The pacing rates (ie, alternans threshold) at which T-wave (369±11 bpm), APD (369±21 bpm), and Ca 2+ (371±29 bpm) alternans first appeared were comparable. Importantly, the site of origin of APD alternans and Ca 2+ alternans consistently occurred together near the base of the left ventricle, not where APD restitution was steepest. In addition, APD and Ca 2+ alternans were remarkably similar both spatially and temporally during discordant alternans. In conclusion, the mechanism underlying T-wave alternans in the intact heart is more closely associated with intracellular Ca 2+ cycling rather than APD restitution.
Abstract 952: Stemofoline is a potent natural product modulator of the multidrug resistance-linked P-glycoprotein (ABCB1).
Authors: Shinobu Ohnuma, Wisinee Chanmahasathien, Koh Miura, Michiaki Unno, Suresh V. Abudkar, Pornngarm Limtrakul
Journal: Cancer Research (2013)

Abstract Background: Stemofoline is a plant alkaloid isolated form Stemona, which is native to southeastern Asia. P-glycoprotein (Pgp), a member of the ATP-binding cassette (ABC) transporter superfamily is implicated in multidrug resistance (MDR) in cancer cells. Aim: To investigate the effect of stemofoline on Pgp function. Methods and Results: Stemofoline stimulated Pgp-mediated ATP hydrolysis (conc. required for 50% stimulation= 10-12, μM), suggesting that this alkaloid seems to interact with drug-binding site of Pgp. Consistent with this view, stemofoline inhibited the photo-crosslinking of Pgp with [125I]-iodoarylazidoprazosin (IAAP), which is a transport substrate. Interestingly, stemofoline instead of inhibiting verapamil-stimulated ATP hydrolysis, it further enhanced the ATPase activity suggesting that stemofoline and verapamil bind simultaneously to Pgp in the drug-binding pocket. In addition, the efflux of the fluorescent substrate calcein-AM from P-gp expressing cervical cancer cells (KB-V1) was blocked by stemofoline in a concentration-dependent manner. Conclusion: These studies indicate that stemofoline could be developed as a potent modulator to overcome MDR in cancer cells. Citation Format: Shinobu Ohnuma, Wisinee Chanmahasathien, Koh Miura, Michiaki Unno, Suresh V. Abudkar, Pornngarm Limtrakul. Stemofoline is a potent natural product modulator of the multidrug resistance-linked P-glycoprotein (ABCB1). [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 952. doi:10.1158/1538-7445.AM2013-952
In vitro alteration of receptors for vasoactive intestinal peptide changes the in vivo localization of mouse T cells.
Authors: C A Ottaway
Journal: The Journal of Experimental Medicine (1984)

The capacity of T lymphocytes exposed in vitro to the neuropeptide vasoactive intestinal peptide (VIP) to bind VIP in vitro and to migrate to different tissues in vivo has been studied. VIP treatment of T cells resulted in a time- and dose-dependent loss of the ability of T cells to specifically bind radioiodinated VIP. Altered binding was due to a decrease in the expression of cellular receptors for VIP on the treated cells rather than an alteration in the affinity of the cells for the neuropeptide. Alteration of VIP receptor expression was not associated with a change in the expression of Thy-1, Lyt-1, or Lyt-2 surface markers by the treated cells. VIP treatment of T cells in vitro resulted, however, in a dose-dependent decrease in the ability of the treated cells to localize in mesenteric lymph nodes (MLN) and Peyer's patches of recipient animals at early times after cell transfer, and this was due to a selective decrease in the rate of accumulation of the treated cells in these tissues. There was no alteration in the distribution of VIP-treated cells in the blood, spleen, liver, or other major organs of the recipient animals. It is concluded that the presence of VIP receptors on T cells facilitates the entry of T cells into MLN and Peyer's patches in vivo, and it is proposed that this effect is mediated by T cell-VIP interactions in the vicinity of the specialized endothelium of those tissues.
Smudge Cells, Serum Albumin, and Prognosis in B-Cell Chronic Lymphocytic Leukemia
Authors: Ronald S. Go
Journal: Journal of Clinical Oncology (2009)

The interesting study by Nowakowski et al 1 showed that the percentage of smudge cells on blood smear at diagnosis was an independent predictor of overall survival in their cohort of patients with B-cell chronic lymphocytic leukemia.However, they did not show data on whether this finding was or was not impacted if serum albumin level was included in their multivariate analysis.It is known for a long time that the addition of bovine serum albumin in the preparation of blood smear reduces the number of smudge cells and allows better appreciation of lymphocyte morphology.Moreover, previous studies have shown prognostic importance of serum albumin. 2,3In theory, a higher level of serum albumin may result in a lower number of smudge cells.Therefore, the prognostic impact of the percentage of smudge cells may potentially be enhanced when it is adjusted for serum albumin level.
A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression
Authors: Gabrielle A. Josling, Michaela Petter, Sophie C. Oehring, Archna P. Gupta, Olivier Dietz, Danny W. Wilson, Thomas Schubert, Gernot Längst, Paul R. Gilson, Brendan S. Crabb, Suzette Moes, Paul Jenoe, Shu Wei Lim, Graham V. Brown, Zbynek Bozdech, Till S. Voss, Michael F. Duffy
Journal: Cell Host & Microbe (2015)