tbuckley/cabot-search huggingface dataset:
858. In Vivo Engineering of Hepatic Tissues Expressing Factors VIII and IX as a Potential New Therapy toward Hemophilia
Authors: Kazuo Ohashi, Takashi Yokoyama, Hiroyuki Kuge, Masayuki Yamato, Akira Yoshioka, Yoshiyuki Nakajima
Journal: Molecular Therapy (2006)

Background: Recent success in clinical liver transplantation toward hemophilia patients has encouraged further investigation into bioengineering hepatic tissues as a cell_based therapy. Since factors VIII and IX are synthesized primarily by hepatocytes, it would be reasonable to hypothesize that engineering a functional hepatic tissue in vivo using isolated hepatocytes would provide potential impact as a new therapy toward hemophilia. This study describes several approaches to engineer hepatic tissues that express factors VIII and IX gene expressions. Methods and Results: [1] Engineering hepatic tissue under the kidney capsule. Hepatocytes were isolated and purified from adult mice using two_step collagenase perfusion method and were transplanted under the kidney capsule space of isogenic mice. In order to increase initial cell engraftment rate, EHS extracellular matrix components were provided to the hepatocytes at the time of transplantation. With this procedure, the transplanted hepatocytes demonstrated persistent survival resulting in engineering stable hepatic tissues composing of differentiated hepatocytes. When chronic liver regeneration stimulus were introduced to the recipient mice, the engineered hepatic tissues under the kidney capsule demonstrated repeated proliferation leading to a formation of large hepatic tissue mass. mRNA analyses of the engineered hepatic tissues demonstrated factors VIII and IX expressions at similar levels to the naïve livers. When we engineered hepatic tissues in hemophilia A mice, therapeutic levels of clotting activities were obtained, demonstrating a therapeutic efficacy of this tissue engineering approach. [2] Engineering hepatic tissue into subcutaneous space. Transplantation of the isolated hepatocytes into the subcutaneous space with EHS extracellular matrix components failed to provide persistent hepatocyte survival. However, preparing the local transplantation sites in advance with FGF_releasing device in order to create functional vascular network followed by hepatocyte transplantation allowed persistent hepatocyte survival and functional hepatic tissue engineering. mRNA analyses of the engineered hepatic tissues that were precisely obtained by laser capture microdissection method confirmed similar expression levels of factors VIII and IX to the host naïve livers. Conclusions: This study demonstrates several novel approaches for engineering hepatic tissues and their ability for clotting factor gene expressions as a potential cell_based therapy toward hemophilia.
Abstract LB-266: Generation of antagonistic anti-TIM-3 and anti-LAG-3 monoclonal antibodies for potential novel immunotherapy combinations
Authors: H. Toni Jun, Patricia A. McNeeley, Andrew Lassen, Brandon Hynes, Larry Altobell, Mark Chhoa, Jesus Olvera, Josh MacLaren, Minjee Do, Michael Brown, Jean da Silva Correia, David King
Journal: Cancer Research (2014)

Abstract Among the most promising approaches in the treatment of cancer is the activation of antitumor immunity by blockade of immune checkpoints. These inhibitory immune checkpoints are crucial for maintaining self-tolerance in the normal immune system but can be co-opted in cancer to allow tumor escape from immune surveillance. Therapeutic validation has been provided using antibodies that inhibit the CTLA-4 and PD-1 signaling pathways, which have shown significant clinical activity. Interestingly, blockade of other T-cell inhibitory signaling molecules TIM-3 and LAG-3 has also been shown to be effective in mouse models of cancer. Potential therapeutic molecules that inhibit the negative signaling of TIM-3 or LAG-3 were identified by screening the AnaptysBio Evolvable Library (ABEL) of fully human germline antibodies. The initial ABEL screens used the soluble extra cellular domains (ECD) of either TIM-3 or LAG-3, followed by screening on cell-surface expressed antigens. The resulting panels of human antibodies were matured to high affinity and potency using SHM-XEL™ which uses mammalian cell display of human IgG followed by in vitro somatic hypermutation (SHM). We have explored the activity of these antibodies both as single agents as well as simultaneous blockade of multiple pathways in in vitro cell-based assays. Inhibition of each pathway in isolation demonstrated immune stimulatory activity as evidenced by increased secretion of IL-2 in a mixed lymphocyte reaction or an activated T-cell assay. Combination of an anti LAG-3 or an anti TIM-3 antibody with an anti-PD-1 inhibitory antibody could increase IL-2 secretion over that seen with blockade of a single checkpoint alone. The magnitude of this effect was donor cell dependent. These data are suggestive that combination immunotherapy towards these targets is worthy of clinical evaluation and may lead to increased efficacy. Citation Format: H. Toni Jun, Patricia A. McNeeley, Andrew Lassen, Brandon Hynes, Larry Altobell, Mark Chhoa, Jesus Olvera, Josh MacLaren, Minjee Do, Michael Brown, Jean da Silva Correia, David King. Generation of antagonistic anti-TIM-3 and anti-LAG-3 monoclonal antibodies for potential novel immunotherapy combinations. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-266. doi:10.1158/1538-7445.AM2014-LB-266
Is Elevated Serum Cholesterol Level a Risk Factor for Coronary Heart Disease in the Elderly?
Authors: Richard Benfante
Journal: JAMA (1990)

Since serum cholesterol is a major component in the causal pathway of atherosclerosis, a pathological process that usually progresses with age, we have evaluated reported findings of a diminished association between serum cholesterol level and coronary heart disease in the elderly. In the Honolulu (Hawaii) Heart Program, 1480 men aged 65 years and older and free of coronary heart disease were followed up for an average of 12 years. Incidence rates of coronary heart disease increased progressively from the lowest to the highest quartile of serum cholesterol level. The independent role of serum cholesterol level as a predictor of coronary heart disease risk was evaluated with other major risk factors using a Cox multivariate regression model. The upper-lower quartile relative risk for serum cholesterol level was 1.64 (95% confidence interval, 1.14 to 2.36). The relative risk for middle-aged men was also 1.64. The results suggest that serum cholesterol level is an independent predictor of coronary heart disease, even among men older than 65 years. Thus, an elevated serum cholesterol level in the elderly should be regarded, as in middle-aged men, to be an indicator for further evaluation of lipoprotein levels and possible intervention.
Health in Gaza.
Authors: M Shani, T H Tulchinsky
Journal: BMJ (1993)

shown would be equivalent to (and hence would obscure) about two weeks and six months of normal weight gain in babyhood and mid- childhood respectively; when being weighed, infants should be naked and children should wear minimum clothing compatible with modesty.Despite the expensive apparatus featured in the photographs measurements of height as shown would be only an approximation of the true value, making any later inferences about rate of growth meaningless.At a time when paediatricians and the govem- ment are trying to promote high quality child health surveillance such illustrations serve only to underline how much basic education still needs to be given to those who should know better.
THE TREATMENT OF ULCERS OF THE LEG.Read in the Section on Dermatology and Syphilography at the Forty-fourth Annual Meeting of the American Medical Association.
Authors: LOUIS FRANK
Journal: JAMA (1894)

The treatment of ulcers of the leg has at all times been the<i>crux medicorum</i>and has heretofore, as a rule, been assigned to the field of the surgeon, although in most cases a true affection of the skin. The vast number of remedies advocated for the relief of this pathologic condition only speak for the difficulties offered in its treatment. The entire old arsenal and an array of new remedies, as iodoform, salol, dermatol, europhen, aristol, ichthyol, etc., have been successively brought forth as remedies, par excellence, in the therapeutics of ulcers of the leg. The cause of the failure in the accomplishment of the required result lies not so much in the non-efficaciousness of the above named drugs as in the faulty adaptation to the pathologic condition of the parts. A close study of the relations and the etiologic condition ought to convince us that a particular drug
Urologist recommends daily Viagra to prevent impotence
Authors: R. Moynihan
Journal: BMJ (2003)

Sildenafil (Viagra), which is approved to treat erectile dysfunction, could now be taken daily to prevent it, a high profile professor of urology has advised.

Professor Irwin Goldstein of Boston University, Massachusetts, said at a recent continuing medical education event (sponsored chiefly by the drug's manufacturer, Pfizer) that he was a “strong believer” in taking sildenafil on a daily basis to “prevent impotence.”

Before a large audience of primary care doctors and others attending a sexual function update at New York University in December, Professor Goldstein said he had “hundreds of men” using Viagra for prevention: “If you would like to be sexually active in five years' time, take a quarter …
Low bone mineral density in adult patients with moderate to severe atopic dermatitis
Authors: I.M. Haeck, N.A.T. Hamdy, L. Timmer-de Mik, E.G.W.M. Lentjes, H.J.J. Verhaar, M.J. Knol, M.S. de Bruin-Weller, C.A.F.M. Bruijnzeel-Koomen
Journal: British Journal of Dermatology (2009)

Atopic dermatitis (AD) is a chronic inflammatory skin disease commonly treated with topical corticosteroids. The inflammatory nature of this disorder and the use of topical corticosteroids represent potential risk factors for bone loss.The aim was to assess the prevalence of osteoporosis and osteopenia in adult patients with moderate to severe AD. In addition, the associations between topical/oral corticosteroid use and bone mineral density (BMD) and between disease activity and BMD were studied.We studied 125 adult patients with moderate to severe AD. Using dual-energy X-ray absorptiometry, BMD was measured at lumbar spine and hips. The cumulative dose of topical and oral corticosteroids was calculated from pharmacy prescription records. Lifestyle parameters were collected by a questionnaire. Biochemical parameters of bone metabolism and disease activity [serum concentration of thymus and activation-regulated chemokine (TARC) levels] were also measured.Osteoporosis was documented in six patients (4.8%) and osteopenia in 41 patients (32.8%); 30.4% of the patients had a Z-score <or= -1 (low BMD), with more men (43.8%) than women (16.4%) affected. There was no significant association between low BMD and biochemical parameters of bone metabolism, serum TARC levels and cumulative dose of topical and oral corticosteroids during the 5 years prior to inclusion.We document a Z-score <or= -1 in about one-third of predominantly male patients with moderate to severe AD, being independent of the cumulative dose of topical and corticosteroids used within 5 years prior to study. Whether the relatively high prevalence of low BMD is due to the cumulative dose of topical corticosteroids beyond 5 years prior to the study or the chronicity of the underlying inflammatory process or a combination of these, remains to be established.
Friend erythroleukemia antigen. A viral antigen specified by spleen focus-forming virus and differentiation antigen controlled by the Fv-2 locus.
Authors: R Risser
Journal: The Journal of Experimental Medicine (1979)

Serum from C57BL/6 (B6) mice hyperimmunized with NB-tropic Friend virus complex (FV) was cytotoxic for FV-induced erythroleukemic spleen cells and B6 Friend-murine leukemia virus (F-MuLV) lymphoma cells. Cytotoxic activity for erythroleukemia cells remained after repeated absorption of B6 anti-FV antiserum with Friend-Moloney-Rauscher MuLV lymphoma cells but was removed by absorption with erythroleukemia cells induced by FV or Rauscher Vrus. This serologic test system identified a previously unrecognized cell-surface antigen of mouse leukemia, designated Friend Erythroleukemia (FE) antigen to signify its appearance as a determinant of virally induced erythroleukemic differentiation. FE antigen was not detected on 15 transplanted or primary hematopoietic neoplasms, nor was it detected on cells infected with ecotropic, xenotropic, or dualtropic MuLV isolates in tissue culture. Two spleen focus-forming virus (SFFV) nonproducer cells of rats and one of mice express FE antigen in amounts comparable to primary erythroleukemia cells. Absorption tests with FE typing serum indicated that FE antigen was expressed on bone marrow and spleen but not thymus, lymph node, or peripheral blood of uninfected AKR, BALB/c, DBA, and SWR mice; all five tissues from B6 and C57L were negative. Quantitiative absorption tests indicated that the expression of FE antigen, though much lower than on erythroleukemic cells, was greatest on fetal liver, less on bone marrow, and lowest on spleen from BALB and SWR mice. Treatment of BALB/c or SWR fetal liver, bone marrow, spleen, thymus, or lymph node cells with FE typing serum did not result in significant lysis. These observations are consistent with the interpretation that FE antigen is expressed by a minor cell population present in fetal liver, bone marrow, and spleen. Expression of FE antigen, determined by absorption with bone marrow cells, cosegregated with inheritance of the Fv-2s allele in the 17 inbred, 7 recombinant inbred, and 4 congenic mouse strains tested. In summary, the FE antigenic system identifies a cell-surface determinant that has the properties of a SFFV-specified antigen and hematopoietic differentiation alloantigen controlled by the Fv-2 locus. The similarity of FE antigen to Abelson antigen may provide insight into the pathogenic properties of defective transforming MuLV.
Polymorphisms involved in the folate metabolizing pathway and risk of multiple myeloma
Authors: Hee Nam Kim, Yeo‐Kyeoung Kim, Il‐Kwon Lee, Je‐Jung Lee, Deok‐Hwan Yang, Kyeong‐Soo Park, Jin‐Su Choi, Moo Rim Park, Deog Yeon Jo, Hyeoung‐Joon Kim
Journal: American Journal of Hematology (2007)

Abstract Folate and methionine metabolism plays an essential role in both DNA synthesis and methylation. Polymorphisms in the genes of the folate‐dependent enzymes have been shown to affect disease susceptibility. We conducted a Korean population‐based case‐control study to evaluate whether genetic variation in folate metabolism may have a role in the risk of multiple myeloma (MM). The study subjects were 173 patients with MM and 1,700 population‐based controls. The polymorphisms studied include methylenetetrahydrofolate reductase (MTHFR) 677 C &gt; T and 1298 A &gt; C, methionine synthase (MS) 2756 A &gt; G, methionine synthase reductase (MTRR) 66A &gt; G, thymidylate synthase (TS) 28‐bp repeat (2R→3R) and 6‐bp deletion/insertion. MS 2756 AG genotypes were associated with a 1.5‐fold lower risk of MM (OR = 0.66, 95%CI; 0.43–0.99, P = 0.047). There was no association between MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R and 6‐bp deletion/insertion polymorphisms and MM. These results suggest that MTHFR C677T, A1298C, MTRR A66G, TS 2R→3R, and 6‐bp deletion/insertion do not significantly factor into the pathogenesis of MM in the Korean population, but that MS A2756G polymorphism may play an important role. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.
IgE antibodies to <i>ω</i>‐5 gliadin in children with wheat‐induced anaphylaxis
Authors: T. Daengsuwan, K. Palosuo, S. Phankingthongkum, N. Visitsunthorn, O. Jirapongsananuruk, H. Alenius, P. Vichyanond, T. Reunala
Journal: Allergy (2004)

Background: Wheat can cause severe immunoglobulin E (IgE)‐mediated systemic reactions including anaphylaxis but knowledge on relevant wheat allergens at the molecular level is scanty. Methods: Seven children (aged from 6 months to 13 years) experiencing from 2 to 10 anaphylactic reactions in a year after eating food‐containing wheat were examined. Purified ω ‐5 gliadin was used as an allergen in IgE enzyme‐linked immunosorbent assay (ELISA) and in skin prick testing (SPT). Wheat CAP radioallergosorbent test (RAST) and SPT were also examined. Results: All seven anaphylactic children, but none of 15 control subjects had IgE antibodies to ω ‐5 gliadin in ELISA. Five of the six tested anaphylactic children showed positive SPT to ω ‐5 and crude gliadin, and all seven had positive wheat CAP RAST and SPT. One child was challenged with wheat, which caused anaphylaxis. After adherence to a wheat‐free diet four children remained symptomless and three experienced one to two anaphylactic reactions. Conclusion: The present results show that wheat ω ‐5 gliadin is a major sensitizing allergen in children with wheat‐induced anaphylaxis. They also suggest that ω ‐5 gliadin IgE ELISA could be used as a diagnostic test for this severe allergy.
Osteoblasts support B-lymphocyte commitment and differentiation from hematopoietic stem cells
Authors: Jiang Zhu, Russell Garrett, Younghun Jung, Yi Zhang, Nacksung Kim, Jingcheng Wang, Gerard J. Joe, Elizabeth Hexner, Yongwon Choi, Russell S. Taichman, Stephen G. Emerson
Journal: Blood (2007)
TCT-202 Effect of Contralateral Occlusion on Index Internal Carotid Artery (ICA) Duplex Doppler Velocities: Quantitative Analysis Using Intravascular Ultrasound (IVUS) to Match Index ICA Stenosis Severity
Authors: Piotr Musialek, Lukasz Tekieli, Piotr Pieniazek, Anna Kablak-Ziembicka, Tadeusz Przewlocki, Karolina Dzierwa, Mariusz Trystula, Krzysztof Zmudka, Wieslawa Tracz, Piotr Podolec
Journal: Journal of the American College of Cardiology (2012)
Glomerular Endothelial Cells in Uranyl Nitrate-induced Acute Renal Failure in Rats
Authors: P. S. Avasthi, A. P. Evan, D. Hay
Journal: Journal of Clinical Investigation (1980)

In uranyl nitrate (UN)-induced acute renal failure (ARF) glomerular ultrafiltration coefficient (Kf) decreases because of unknown reasons. Since transport of water across the glomerular capillary wall occurs predominantly extracellularly through the endothelial fenestrae (EF), a reduction in the diameter and/or the density of EF can reduce the extracellular filtration area and the glomerular Kf. To examine this possibility, ARF was induced in rats by intravenous administration of UN in low (15 mg/kg) and high doses (25 mg/kg). Fenestral density (¯x±SEM) per 5 cm2 from the scanning electron micrographs (×30,000) was 107±10, 103±9, and 101±11 at 2, 7, and 17 h after the intravenous administration of bicarbonate saline to the control rats. In the low-dose UN group the EF density was 91±2, 52±8, and 45±11 at 2, 7, and 17 h after the injection, whereas for the high-dose group at corresponding time intervals the EF density was 95±3, 54±9, and 44±10. Fenestral diameters, in Angstrom units (¯x±SEM), were 751±53, 765±43, and 764±37 at 2, 7, and 17 h after the injection of bicarbonate saline to control rats. At corresponding intervals after the administration of UN, the fenestral diameters were 501±61, 472±28, and 438±98 for the low-dose group and 525±43, 470±39, and 440±56 for the high-dose group. 2, 7, and 17 h after the injection of UN, fenestral area of the low-dose group decreased to 52.1, 30.1, and 24.6% of the controls, whereas in the high-dose group, the fenestral area declined to 54.3, 30.2, and 23.6% of the controls. Administration of UN (15 mg/kg) to sodium-loaded rats did not alter renal function or endothelial cell morphology. It is suggested that in UN-induced ARF the morphological alterations in endothelial cells reduce the Kf of glomerular capillaries by reducing the filtration area.
The inducible deletion of Drosha and microRNAs in mature podocytes results in a collapsing glomerulopathy
Authors: Olga Zhdanova, Shekhar Srivastava, Lie Di, Zhai Li, Leila Tchelebi, Sara Dworkin, Duncan B. Johnstone, Jiri Zavadil, Mark M. Chong, Dan R. Littman, Lawrence B. Holzman, Laura Barisoni, Edward Y. Skolnik
Journal: Kidney International (2011)
Identification of 92-kD Gelatinase in Human Coronary Atherosclerotic Lesions
Authors: David L. Brown, Margaret S. Hibbs, Marianne Kearney, Carrie Loushin, Jeffrey M. Isner
Journal: Circulation (1995)

Acute coronary ischemia is usually initiated by rupture of atherosclerotic plaque, leading to intracoronary thrombosis and clinical sequelae. The proximate cause of plaque rupture is unknown. Accordingly, we investigated the potential role of the 92-kD gelatinase member of the matrix metalloproteinase family in acute coronary ischemia.Coronary atherectomy specimens from patients with atherosclerosis and an acute ischemic syndrome consistent with recent plaque rupture (unstable angina) (n = 12) were immunostained for the presence of 92-kD gelatinase; the results were compared with those obtained by identical study of atherectomy specimens from patients with atherosclerosis and angina but without acute ischemia (stable angina) (n = 12). Positive immunostaining for 92-kD gelatinase was present in 83% of specimens from both unstable and stable angina patients. However, intracellular localization of enzyme (indicating active synthesis) was documented in 10 of 10 positively stained specimens from patients with unstable angina compared with 3 of 10 positively stained specimens from patients with stable angina. Macrophages and smooth muscle cells were the major sources of 92-kD gelatinase in all specimens examined by immunostaining of adjacent sections.92-kD gelatinase is commonly expressed in coronary arterial atherosclerotic lesions. Active synthesis of 92-kD gelatinase by macrophages and smooth muscle cells in atherosclerotic lesions may play a pathogenic role in the development of acute coronary ischemia.
107 Cholangiocytes contain primary cilia that function as sensory organelles: potential role in ductal bile formation
Authors: A MASYUK, T MASYUK, P SPLINTER, B HUANG, N LARUSSO
Journal: Hepatology (2003)

Cholangiocytes, epithelial cells that line the biliary epithelium, are the primary target cells for cholangiopathies including primary sclerosing cholangitis and primary biliary cholangitis. Quiescent cholangiocytes respond to biliary damage and acquire an activated neuroendocrine phenotype to maintain the homeostasis of the liver. The typical response of cholangiocytes is proliferation leading to bile duct hyperplasia, which is a characteristic of cholestatic liver diseases. Current studies have identified various signaling pathways that are associated with cholangiocyte proliferation/loss and liver fibrosis in cholangiopathies using human samples and rodent models. Although recent studies have demonstrated that extracellular vesicles and microRNAs could be mediators that regulate these messenger/receptor axes, further studies are required to confirm their roles. This review summarizes current studies of biliary response and cholangiocyte proliferation during cholestatic liver injury with particular emphasis on the secretin/secretin receptor axis. This article is part of a Special Issue entitled: Cholangiocytes in Health and Diseaseedited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.
Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity
Authors: Biao Wang, Yang Xiao, Bei-Bei Ding, Na Zhang, Xiao-bin Yuan, Lü Gui, Kai-Xian Qian, Shumin Duan, Zhengjun Chen, Yi Rao, Jian-Guo Geng
Journal: Cancer Cell (2003)