tbuckley/cabot-search huggingface dataset:
Genome-Wide Analysis of the Zebrafish ETS Family Identifies Three Genes Required for Hemangioblast Differentiation or Angiogenesis
Authors: Feng Liu, Roger Patient
Journal: Circulation Research (2008)

ETS domain transcription factors have been linked to hematopoiesis, vasculogenesis, and angiogenesis. However, their biological functions and the mechanisms of action, remain incompletely understood. Here, we have performed a systematic analysis of zebrafish ETS domain genes and identified 31 in the genome. Detailed gene expression profiling revealed that 12 of them are expressed in blood and endothelial precursors during embryonic development. Combined with a phylogenetic tree assay, this suggests that some of the coexpressed genes may have redundant or additive functions in these cells. Loss-of-function analysis of 3 of them, erg , fli1 , and etsrp , demonstrated that erg and fli1 act cooperatively and are required for angiogenesis possibly via direct regulation of an endothelial cell junction molecule, VE-cadherin, whereas etsrp is essential for primitive myeloid/endothelial progenitors (hemangioblasts) in zebrafish. Taken together, these results provide a global view of the ETS genes in the zebrafish genome during embryogenesis and provide new insights on the functions and biology of erg , fli1 , and etsrp , which could be applicable to higher vertebrates, including mice and humans.
Can multiple bootstrapping provide means of very early conceptual development?
Authors: Maciej Haman, Mikołaj Hernik
Journal: Behavioral and Brain Sciences (2011)

Abstract Carey focuses her theory on initial knowledge and Quinian bootstrapping. We reflect on developmental mechanisms, which can operate in between. Whereas most of the research aims at delimitating early cognitive mechanisms, we point at the need for studying their integration and mutual bootstrapping. We illustrate this call by referring to a current debate on infants' use of featural representations.
BENZIMIDAZOLE DERIVATIVES: NEW ENHANCERS OF INFLUENZA VIRUS MULTIPLICATION
Authors: Igor Tamm
Journal: The Journal of Experimental Medicine (1973)

The enhancing activity of 5-methyl-2-D-ribobenzimidazole on influenza B (Lee) virus yield in chorioallantoic membranes from 10-day old embryonated eggs was compared with that of eight other polyhydroxyalkyl-benzimidazoles. No marked differences in activity were noted with the following six derivatives: 5,6-dimethyl-2-D-ribo; 2-D-gluco; 5-methyl-2-D-gluco; 5,6-dimethyl-2-D-gluco; 5-methyl-2-D-galacto; and 5-methyl-2-L-rhamno. None caused morphological damage to the membranes at a concentration of 3.5 mM. The solubility of the 5-methyl-2-D-arabo and 5-methyl-2-D-manno derivatives was too low to permit quantitative comparisons, but both were active and nontoxic at a concentration of 1.75 mM. 5-Hydroxy-1-methylbenzimidazole and 5-methoxy-1-methylbenzimidazole are more active than 5-methyl-2-D-ribobenzimidazole both with respect to specific activity and maximal enhancement at the highest tolerated dose. The hydroxyl substituent is superior to the methoxyl grouping. Substitution at position 5 is superior to substitution at position 6 with respect to the tolerated dose level and therefore the maximal effect obtainable, but the 6-hydroxy-1-methyl derivative showed the highest specific activity. 5-Methoxy-1-methylbenzimidazole increases the yield to a comparable extent as measured by infectivity and hemagglutination titrations. The responses of membranes from individual chicken embryos to the enhancing action of 5-methoxy-1-methylbenzimidazole and 5-methyl-2-D-ribobenzimidazole are similar. 5-Methoxy-1-methylbenzimidazole restores the capacity of membranes from older chicken embryos to produce a large amount of virus after a small inoculum. This derivative increases the yield of virus in membranes treated before infection only. Maximal enhancement is obtained with prolonged treatment, starting before, and continuing after infection. 5-Methoxy-1-methyl-benzimidazole increases the yield of virus from COFAL-negative embryos in which the control yield is very low. Combined treatment with moderate doses of 5-methoxy-1-methylbenzimidazole and 5-methyl-2-D-ribobenzimidazole gives an additive effect.
Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2.
Authors: M A Caligiuri, C Murray, M J Robertson, E Wang, K Cochran, C Cameron, P Schow, M E Ross, T R Klumpp, R J Soiffer
Journal: Journal of Clinical Investigation (1993)

The immunologic consequences of prolonged infusions of rIL-2 in doses that produce physiologic serum concentrations of this cytokine were investigated. rIL-2 in doses of 0.5-6.0 x 10(6) U/m2 per d (3.3-40 micrograms/m2 per d) was administered by continuous intravenous infusion for 90 consecutive days to patients with advanced cancer. IL-2 concentrations (25 +/- 25 and 77 +/- 64 pM, respectively) that selectively saturate high-affinity IL-2 receptors (IL-2R) were achieved in the serum of patients receiving rIL-2 infusions of 10 micrograms/m2 per d and 30 micrograms/m2 per d. A gradual, progressive expansion of natural killer (NK) cells was seen in the peripheral blood of these patients with no evidence of a plateau effect during the 3 mo of therapy. A preferential expansion of CD56bright NK cells was consistently evident. NK cytotoxicity against tumor targets was only slightly enhanced at these dose levels. However, brief incubation of these expanded NK cells with IL-2 in vitro induced potent lysis of NK-sensitive, NK-resistant, and antibody-coated targets. Infusions of rIL-2 at 40 micrograms/m2 per d produced serum IL-2 levels (345 +/- 381 pM) sufficient to engage intermediate affinity IL-2R p75, which is constitutively expressed by human NK cells. This did not result in greater NK cell expansion compared to the lower dose levels, but did produce in vivo activation of NK cytotoxicity, as evidenced by lysis of NK-resistant targets. There was no consistent change in the numbers of CD56- CD3+ T cells, CD56+ CD3+ MHC-unrestricted T cells, or B cells during infusions of rIL-2 at any of the dosages used. This study demonstrates that prolonged infusions of rIL-2 in doses that saturate only high affinity IL-2R can selectively expand human NK cells for an extended period of time with only minimal toxicity. Further activation of NK cytolytic activity can also be achieved in vivo, but it requires concentrations of IL-2 that bind intermediate affinity IL-2R p75. Clinical trials are underway attempting to exploit the differing effects of various concentrations of IL-2 on human NK cells in vivo.
Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250.
Authors: M G Steffens, O C Boerman, J C Oosterwijk-Wakka, G O Oosterhof, J A Witjes, E B Koenders, W J Oyen, W C Buijs, F M Debruyne, F H Corstens, E Oosterwijk
Journal: Journal of Clinical Oncology (1997)

PURPOSE Pharmacokinetics, biodistribution, immunogenicity, and imaging characteristics of iodine 131 (131I)-labeled chimeric monoclonal antibody (mAb) G250 (cG250) were studied in patients with renal cell carcinoma (RCC) to determine the therapeutic potential of this antibody. PATIENTS AND METHODS Sixteen patients with RCC received a single intravenous (IV) infusion of 6 mCi 131I-labeled cG250. Five protein dose levels were investigated (2 to 50 mg). Planar scintigraphic images were acquired, and normal tissue biopsies and tumor samples were obtained of surgery (7 days postinjection). The immunogenicity of cG250 was investigated using a sandwich enzyme-linked immunosorbent assay (ELISA) and dosimetric analysis was performed. RESULTS In all patients with antigen-positive tumors (n = 13), the primary tumors and all known metastases were clearly visualized. Overall uptake, expressed as the percentage of the injected dose (%ID), in the primary tumors ranged from 2.4 to 9.0. Focally, 131I-cG250 uptake as high as 0.52% ID/g was observed. However, intratumoral uptake was highly heterogeneous. 131I-cG250 uptake in nontumorous tissues remained low. Dosimetric analysis showed that up to .48 Gy/mCi was guided to the primary tumors. Selected "hot areas" within these tumors received up to .72 Gy/mCi. A bone metastasis received .23 Gy/mCi and regional lymph node metastases received .20 Gy/mCi. Minimal human antichimeric antibody (HACA) levels were detected in two of 16 patients. CONCLUSION 131I-cG250 tumor uptake is among the highest reported in clinical studies with antitumor antibodies in solid tumors. Since tumor-sterilizing levels may be guided to the tumor when high doses 131I-cG250 are administered (&gt; 100 mCi) and cG250 appears to be immunosilent, cG250 is a promising vehicle for radioimmunotherapy in RCC.
Critical Role for Kit-mediated Src Kinase But Not PI 3-Kinase Signaling in Pro T and Pro B Cell Development
Authors: Valter Agosti, Selim Corbacioglu, Imke Ehlers, Claudia Waskow, Gunhild Sommer, Georgina Berrozpe, Holger Kissel, Christine M. Tucker, Katia Manova, Malcolm A.S. Moore, Hans-Reimer Rodewald, Peter Besmer
Journal: The Journal of Experimental Medicine (2004)

The Kit receptor functions in hematopoiesis, lymphocyte development, gastrointestinal tract motility, melanogenesis, and gametogenesis. To investigate the roles of different Kit signaling pathways in vivo, we have generated knock-in mice in which docking sites for PI 3-kinase (KitY719) or Src kinase (KitY567) have been mutated. Whereas steady-state hematopoiesis is normal in KitY719F/Y719F and KitY567F/Y567F mice, lymphopoiesis is affected differentially. The KitY567F mutation, but not the KitY719F mutation, blocks pro T cell and pro B cell development in an age-dependent manner. Thus, the Src family kinase, but not the PI 3-kinase docking site in Kit, mediates a critical signal for lymphocyte development. In agreement with these results, treatment of normal mice with the Kit tyrosine kinase inhibitor imatinib (Gleevec®) leads to deficits in pro T and pro B cell development, similar to those seen in KitY567F/Y567F and KitW/W mice. The two mutations do not affect embryonic gametogenesis but the KitY719F mutation blocks spermatogenesis at the spermatogonial stages and in contrast the KitY567F mutation does not affect this process. Therefore, Kit-mediated PI 3-kinase signaling and Src kinase family signaling is highly specific for different cellular contexts in vivo.
Injury trends in sanctioned mixed martial arts competition: a 5-year review from 2002 to 2007
Authors: K M Ngai, F Levy, E B Hsu
Journal: British Journal of Sports Medicine (2008)

Background: Professional mixed martial arts (MMA) competition is a full-contact sport that has risen rapidly in popularity in recent years. However, there is limited information regarding the incidence of competition injuries after sanctioning by an athletic commission. Methods: We conducted a retrospective cohort study to examine MMA injury patterns during a 5 year period after sanctioning in the state of Nevada. Data from all regulated MMA competitions during the study period from March 2002 to September 2007 (1270 fight exposures) was obtained. Injury odds ratios were calculated by conditional logistic regression on match outcome, age, weight, and fight experience, using a pair-matched case-control design (n = 464) and by multiple logistic regression on match outcome, age, fight experience, weight, combat minutes, and scheduled rounds. Results: During the 635 professional MMA matches, 300 of the 1270 athletes sustained documented injuries with an injury rate of 23.6 per 100 fight participations. Most common reported injuries were lacerations and upper limb injuries. Severe concussion rate was 15.4 per 1000 athlete exposures, or 3% of all matches. No deaths or critical sports-related injuries resulted from any of the regulated matches during the study period. Age, weight and fight experience did not statistically increase the likelihood of injuries after controlling for other covariates. Conclusions: Injury rates in regulated professional MMA competition are similar to other combat sports; the overall risk of critical sports-related injury seems to be low. Additional study is warranted to achieve a better understanding of injury trends and ways to further lower injury risk in MMA.
Pravastatin Inhibits the Rho/CCN2/Extracellular Matrix Cascade in Human Fibrosis Explants and Improves Radiation-Induced Intestinal Fibrosis in Rats
Authors: Valérie Haydont, Céline Bourgier, Marc Pocard, Antoine Lusinchi, Jocelyne Aigueperse, Denis Mathé, Jean Bourhis, Marie-Catherine Vozenin-Brotons
Journal: Clinical Cancer Research (2007)

Abstract Purposes: Intestinal complications after radiotherapy are caused by transmural fibrosis and impair the quality of life of cancer survivors. Radiation fibrosis was considered permanent and irreversible, but recently, its dynamic nature was shown, providing new opportunities for the development of antifibrotic therapies. Among these new targets, we identified the Rho/ROCK pathway and thought to investigate whether pravastatin treatment inhibits Rho pathway activation and elicits an antifibrotic action. Experimental Design: Rho and ROCK activities were monitored in human explants presenting radiation fibrosis remodeling after incubation with pravastatin. Subsequent modulation of CCN2, type I collagen, and fibronectin expression were assessed ex vivo and in intestinal smooth muscle cells derived from radiation enteropathy. Then, the therapeutic relevance of the antifibrotic action of pravastatin was explored in vivo in a rat model of chronic radiation fibrosis (19 Gy X-rays) treated with 30 mg/kg/d pravastatin in the drinking water. Results: The results obtained with human explants show that pravastatin specifically inhibits Rho activity in submucosal mesenchymal cells. Pravastatin also elicits ROCK inhibition, and subsequent CCN2 production in human explants and smooth muscle cells isolated from radiation enteropathy. Inhibition of type I collagen and fibronectin does occur, showing that pravastatin modulates the secretory phenotype of mesenchymal cells. Lastly, curative pravastatin administration improves radiation enteropathy in rats. This structural improvement is associated with decreased deposition of CCN2 and subsequent decreased extracellular matrix deposition. Conclusion: Targeting established fibrosis with pravastatin is an efficient and safe antifibrotic strategy in radiation-induced enteropathy, and is easily transferable into the clinic.
Endogenous Sex Hormones and Progression of Carotid Atherosclerosis in Elderly Men
Authors: Majon Muller, Annewieke W. van den Beld, Michiel L. Bots, Diederick E. Grobbee, Steven W.J. Lamberts, Yvonne T. van der Schouw
Journal: Circulation (2004)

The burden of atherosclerosis especially afflicts the increasing older segment of the population. Recent evidence has emphasized a protective role of endogenous sex hormones in the development of atherosclerosis in aging men.We studied the association between endogenous sex hormones and progression of atherosclerosis in 195 independently living elderly men. Participants underwent measurements of carotid intima-media thickness (IMT) at baseline in 1996 and again in 2000. At baseline, serum concentrations of testosterone (total and free) and estradiol (total and free E2) were measured. Serum free testosterone concentrations were inversely related to the mean progression of IMT of the common carotid artery after adjustment for age (beta=-3.57; 95% CI, -6.34 to -0.80). Higher serum total and free E2 levels were related to progression of IMT of the common carotid artery after adjustment for age (beta=0.38; 95% CI, -0.11 to 0.86; and beta=0.018; 95% CI, -0.002 to 0.038, respectively). These associations were independent of body mass index, waist-to-hip ratio, presence of hypertension and diabetes, smoking, and serum cholesterol levelsLow free testosterone levels were related to IMT of the common carotid artery in elderly men independently of cardiovascular risk factors.
Metabolism of 9-β-d-Arabinofuranosyladenine by Mouse Fibroblasts
Authors: William Plunkett, Seymour S. Cohen
Journal: Cancer Research (1975)

The metabolism of 9-β-d-arabinofuranosyladenine (araA) by exponentially growing mouse fibroblasts in suspension culture has been investigated. After a 4-hr incubation with 0.1 mm [3H]araA, only 0.14% of the total 3H was in the cell fraction, whereas 48% of the araA in the medium had been deaminated to 9-β-d-arabinofuranosylhypoxanthine. Of the cellular 3H, 80% was acid soluble, and of these 75% was associated with adenine nucleotides and 25% was associated with nucleosides. 9-β-d-arabinofuranosylhypoxanthine comprised 80% of the labeled nucleosides, the rest being araA or adenosine. Following dephosphorylation of the acid-soluble fraction, 80% of the 3H was in araA and 9-β-d-arabinofuranosylhypoxanthine, and 18% was in adenosine. Ninety % of the 3H in the adenine-containing triphosphates was shown to be in arabinosyl compounds, and the remainder was in adenosine and deoxyadenosine. The concentration of cellular 9-β-d-arabinofuranosyladenine 5′-triphosphate was calculated to be 20 µm.

The RNA fraction contained 16% of the total cellular 3H. Over 90% of the 3H was associated with the adenosine 2′(3′)-phosphate fraction; the remainder was nucleoside, mainly araA. When the adenosine 2′(3′)-phosphate fraction was dephosphorylated, nearly 70% of the 3H was contained in adenosine, indicating extensive metabolism of araA. The remaining 3H was associated with arabinosyl compounds.

The DNA fraction contained 2% of the cellular 3H. After degradation to 5′-monophosphates, the 3H was found mainly in 9-β-d-arabinofuranosyladenine 5′-phosphate; after dephosphorylation 95% of the 3H was in araA. Following degradation to 3′-monophosphates and terminal nucleosides, the majority of the 3H was associated with 9-β-d-arabinofuranosyladenine 3′-phosphate, whereas a minor portion was in the nucleoside.

These results suggest that, after incubation with mouse fibroblasts, most of the exogenous araA is deaminated and remains in the medium or is otherwise metabolized. A small amount is phosphorylated to arabinosyl nucleotides that attain inhibitory cellular concentrations, and some 9-β-d-arabinofuranosyladenine 5′-triphosphate is subsequently incorporated in internucleotide linkage into DNA.
Depot medroxyprogesterone and vaginal bleeding in the puerperium.
Authors: M Thiery, R Staelens, C Sanctorum, R L Cliquet
Journal: BMJ (1980)

A single intramuscular injection of 150 mg MPA (medroxyprogesterone acetate) administered during the early puerperium is an effective contraceptive which does not interfere with lactation or predispose women to thromboembolic complications.  MPA does however involve the risk of prolonged vaginal bleeding.  Use of this method of contraception until tubal sterilization could be performed during the 1st postpartum menstrual period has proven psychologically unacceptable for many women.  Deferring the 1st injection until a postpartum menstrual period has occurred is more acceptable.
The prevalence of obstructive sleep apnoea and its association with aortic dilatation in Marfan's syndrome
Authors: M Kohler, E Blair, P Risby, A H Nickol, P Wordsworth, C Forfar, J R Stradling
Journal: Thorax (2008)

<h3>Background:</h3> Craniofacial abnormalities and increased pharyngeal collapsibility due to abnormal connective tissue suggest the possibility of an increased prevalence of obstructive sleep apnoea (OSA) in patients with Marfan's syndrome but the actual prevalence is uncertain. Aortic dilatation and dissection are life threatening manifestations of Marfan's syndrome and case reports have suggested a possible association with OSA but data from cohort studies are not available. <h3>Methods:</h3> A sleep study was performed in 61 patients with Ghent criteria positive Marfan's syndrome (mean age 38.3 (SD 12.9) years; 37 females) and in 26 control subjects matched for age, gender, height and weight. OSA was defined using two conventional levels of apnoea–hypopnoea index (AHI), &gt;5 and &gt;15/h. In patients with Marfan's syndrome, aortic root diameter was measured by echocardiography. <h3>Results:</h3> More patients with Marfan's syndrome than controls had OSA (AHI &gt;5, 32.8% compared with 11.5%, mean difference +21.3%, 95% CI 4.2% to 38.3%, p = 0.04; AHI &gt;15, 18.0% compared with 0%, mean difference +18.0%, 95% CI 8.4% to 27.7%, p = 0.02). AHI was correlated with aortic root diameter (r = 0.50, 95% CI 0.26 to 0.69, p = 0.0003), and mean aortic root diameter was significantly greater in patients with OSA (4.5 (SD 0.6) cm) compared with those without OSA (3.7 (0.6) cm) (mean difference 0.8 cm, 95% CI 0.4 to 1.2 cm, p&lt;0.0001). <h3>Conclusions:</h3> In patients with Marfan's syndrome, the prevalence of OSA is considerably higher than in matched control subjects. OSA may be a risk factor for aortic root dilatation in Marfan's syndrome.
Antigen presentation in the murine T-lymphocyte proliferative response. I. Requirement for genetic identity at the major histocompatibility complex
Authors: A Yano, RH Schwartz, WE Paul
Journal: The Journal of Experimental Medicine (1977)

A method is described for stimulating proliferation in primed populations of murine T lymphocytes using antigen bound to mitomycin-C-treated spleen cells. This form of antigen presentation appears to be an active process because heat-killed spleen cells are ineffective, and because genetic similarity at the major histocompatibility complex (MHC) between the responder T cells and the presenting spleen cells is required for effective interactions. At all times examined, from day 3 to day 6 of the proliferative response, syngeneic spleen cells presented antigen better to peritoneal exudate T-lymphocyte-enriched cells (PETLES) than semisyngeneic F(1) spleen cells, which in turn could present antigen better than totally allogeneic spleen cells. Spleen cell mixing experiments demonstrated that these genetic restrictions were not the result of suppression by the ongoing mixed lymphocyte reactions (MLR) in the allogeneic and F(1) cases. Furthermore, incompatibility at the Mls locus generated a strong MLR but failed to prevent antigen presentation if the spleen cells and PETLES were compatible. Genetic mapping studies demonstrated that compatibility at only the I-A subregion of the MHC was sufficient for effective presentation of the antigen, dinitrophenylated ovalbumin. Compatibility at only the K region, or the K and D regions was not sufficient. These results support the concept that functional activation of primed, proliferating T lymphocytes requires the participation of gene products coded for by the I region of the MHC. This conclusion is consistent with a growing body of evidence which suggests that most T cells recognize antigen in association with MHC gene products.
Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 ‘clinically aggressive’ cases
Authors: L. Righi, M. Volante, V. Tavaglione, A. Billè, L. Daniele, T. Angusti, F. Inzani, G. Pelosi, G. Rindi, M. Papotti
Journal: Annals of Oncology (2009)