tbuckley/cabot-search huggingface dataset:
Coronary endothelial and cardiac protective effects of a monoclonal antibody to intercellular adhesion molecule-1 in myocardial ischemia and reperfusion.
Authors: X L Ma, D J Lefer, A M Lefer, R Rothlein
Journal: Circulation (1992)

BACKGROUND Intercellular adhesion molecule-1 (ICAM-1) is a major ligand on endothelial cells for adherence of activated polymorphonuclear leukocytes (PMNs). The major purpose of this study was to study the effects of RR1/1, a monoclonal antibody against ICAM-1 (i.e., MAb RR1/1), on myocardial injury and endothelial dysfunction associated with myocardial ischemia and reperfusion. METHODS AND RESULTS Either MAb RR1/1 (2 mg/kg, n = 7), an antibody that was found to bind selectively to endothelial cells in the cat, or MAb R3.1 (2 mg/kg, n = 7), a nonbinding control antibody, was given as an intravenous bolus 10 minutes before reperfusion. Two hundred eighty minutes later, hearts were excised. The left ventricle area-at-risk (AAR) was similar in MAb RR1/1 (29 +/- 2%) and MAb R3.1 (30 +/- 3%) groups. In MAb R3.1-treated cats, 90 minutes of myocardial ischemia plus 4.5 hours of reperfusion induced a significant myocardial injury (necrotic tissue/AAR, 28 +/- 2%), high myeloperoxidase activity (0.65 +/- 0.16 units/100 mg ischemic tissue), and a marked decrease in endothelium-dependent vasorelaxation in isolated left anterior descending coronary arteries (vasorelaxation to acetylcholine, 29 +/- 3%) with no change in endothelium-independent vasorelaxation (relaxation to NaNO2, 91 +/- 3%). However, cats treated with MAb RR1/1 developed significantly less myocardial necrosis (10 +/- 2% of the AAR, p less than 0.01), lower myeloperoxidase activity in ischemic myocardial tissue (0.2 +/- 0.03 units/100 mg ischemic tissue, p less than 0.01), and enhanced vasorelaxant responses to endothelial-dependent relaxation to acetylcholine (53 +/- 5%) compared with ischemic/reperfused cats treated with Mab R3.1. Furthermore, addition of MAb RR1/1 in vitro significantly inhibited unstimulated PMN adherence to ischemic-reperfused coronary artery endothelium. CONCLUSIONS These results suggest that ICAM-1-dependent PMN adherence plays an important role in reperfusion injury, and that PMN adherence and infiltration contribute significantly to coronary endothelial dysfunction.
Notch Signaling Drives Stemness and Tumorigenicity of Esophageal Adenocarcinoma
Authors: Zhiqiang Wang, Thiago G. Da Silva, Ke Jin, Xiaoqing Han, Prathibha Ranganathan, Xiaoxia Zhu, Avencia Sanchez-Mejias, Feng Bai, Bin Li, Dennis Liang Fei, Kelly Weaver, Rodrigo Vasquez-Del Carpio, Anna E. Moscowitz, Vadim P. Koshenkov, Lilly Sanchez, Lynne Sparling, Xin-Hai Pei, Dido Franceschi, Afonso Ribeiro, David J. Robbins, Alan S. Livingstone, Anthony J. Capobianco
Journal: Cancer Research (2014)

Esophageal adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for esophageal adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating esophageal adenocarcinoma, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in esophageal adenocarcinoma treatment.
Microchip Spots Rare Tumor Cells in Blood
Authors: Tracy Hampton
Journal: JAMA (2008)

TUMORS SHED CELLS INTO THE BLOOD of patients with cancer, but researchers have long sought a reliable way to detect these rare cells. Now, however, investigators atMassachusetts GeneralHospitalinBostonreportsuccessful tests with a unique microchip-based device thatcanefficientlyandselectively separatecirculating tumorcells fromperipheral blood samples (Nagrath S et al. Nature. 2007;450[7173]:1235-1239). The technology has been used to identify these cells in the blood of patients with various types of metastatic cancer and to effectively monitor individuals’ responses to therapy. Ultimately, the inventors hope, the device will someday enable physicians to characterize and monitor cancer status in patients in a noninvasive way. While the presence of circulating cancer cells seems to correlate with prognosis in some studies, however, it remains to be seen whether the detection of these cells has any clinical benefit. Patients with metastatic cancer have as few as one circulating tumor cell per 10 hematologic cells in their blood. In previous work, researchers have used flow cytometry, immunomagnetic beads, high-throughput optical imaging systems, and fiber optic array scanning to detect these cells. However, in the work reported by the Boston-based investigators, the new chip technology is more streamlined and isolates greater numbers of viable cells, according to senior author Mehmet Toner, PhD, who is director of Massachusetts General Hospital’s BioMicroElectroMechanical Systems Resource Center. “The beauty of the technology is its simplicity—it uses whole blood with no preprocessing and it’s gentle on the cells,” Toner said. In addition, the device can handle large volumes of blood, unlike other techniques that are limited to microliter amounts of liquid. Other researchers note additional qualities of the device. “The data show that it’s far more sensitive than earlier technologies, and it purifies these rare circulating tumor cells, which is ex-
Redefinitions of Medical Education
Authors: Ray E. Brown
Journal: JAMA (1971)

Following a period of several decades during which about the only change in medical school catalogs was the date on the cover, medical education has entered into an era of explosive change. These changes are so profound that about the only thingunchangedin some medical school catalogs is the name on the cover. No feature of medical education has escaped the sweep of these changes. Admission requirements, content, sequence, and duration have all been redefined in a variety of ways. In a real sense, medical education is approaching a state where the only common denominator may be the MD degree.  Change in medical education is laudable and was too slow in coming. For too many years medical education had failed to respond to the world that was evolving around it. It was due for an overhaul, but evidence is increasing that it may be getting an overkill. The nature
Bile acid transport: Lessons from the intestine
Authors: Richard H. Moseley
Journal: Hepatology (1987)

The transport of bile acid was studied in basolateral membrane vesicles isolated from rat small intestine. Taurocholate transport into an osmotically reactive intravesicular space was Na + independent. The uptake of taurocholate in jejunal and ileal vesicles preloaded with sulfate was stimulated with respect to uptake in unpreloaded vesicles. Glycocholate inhibited the transstimulation of taurocholate uptake by sulfate. Sulfate and taurocholate uptake in ileal vesicles preloaded with bicarbonate was stimulated with respect to uptake in unpreloaded vesicles. Taurocholate inhibited the transstimulation of sulfate uptake by bicarbonate. When ileal vesicles were loaded with p -aminohippurate, an early transstimulation of taurocholate was found that exceeded equilibrium uptake, was insensitive to a K + diffusion potential, and was cis -inhibited by taurocholate, glycocholate, pyruvate, p -aminohippurate, probenecid, chloride, sulfate, and bicarbonate. These data indicate the presence of an anion exchanger in intestinal basolateral membrane vesicles that may be involved in the exit of bile acids from the enterocyte.
La mano de DIOS…was the PIAMA intervention study intervened upon?
Authors: B. Brunekreef, R. Van Strien, A. Pronk, M. Oldenwening, J. C. De Jongste, A. Wijga, M. Kerkhof, R. C. Aalberse
Journal: Allergy (2005)

The PIAMA study evaluates whether application of mite impermeable mattress covers reduces exposure to mite allergen sufficiently to reduce the incidence of asthma and mite allergy. The study started in 1996. Baseline measurements of mite allergen levels were conducted on mattresses of newborn children and their parents, mostly in 1997. Mite allergen levels were surprisingly low in this study compared with previous studies among school children and infants. Mite allergen levels were measured again on mattresses in the PIAMA study in the years 2000/2001 when the children were 4 years old, and in a new study among 6–12 year old school children conducted in the fall of 2001. Data on winter climate were collected as well. In the winters of 1995/1996 and 1996/1997, which preceded and coincided with the PIAMA baseline measurements, temperatures had been extremely low, and precipitation had been extremely low as well. It is likely that these unusual winter weather conditions affected the baseline allergen levels in the PIAMA study so that the effect of the planned intervention (mite impermeable mattress covers) was considerably smaller than it could have been.
Phylogenetic perspective reveals abundant Ty1/Ty2 hybrid elements in the Saccharomyces cerevisiae genome
Authors: I. K. Jordan, J. F. McDonald
Journal: Molecular Biology and Evolution (1999)

Retrotransposons are a class of repetitive mobile elements which transpose via the reverse transcription of an RNA intermediate (Boeke et al. 1985).These eukaryotic elements are abundant and widespread and are hypothesized to be of major evolutionary significance (Miller, Kruckenhauser, and Pinsker 1996;Kidwell and Lisch 1997;McDonald 1998).The yeast Ty retrotransposons (Ty1-Ty5) are arguably the best-characterized retrotransposons (Boeke 1989).A vast number of studies have elucidated in detail the mechanisms of Ty retrotransposition and the molecular interactions between Ty elements and their host genomes (Garfinkel 1992).The sequencing of the Saccharomyces cerevisiae genome (Goffeau et al. 1996) provides an unprecedented opportunity to examine the patterns of molecular variation existing among an entire complement of retrotransposons residing within a genome.Detailed analysis of these Ty element sequences promises to yield deep insight into the nature of Ty element evolution and retroelement evolution in general.Recent studies demonstrate the potential power of such analyses and have shed new light on retroelement-host coevolution (Hani and Feldman 1998;Jordan and McDonald 1998;Kim et al. 1998).We recently performed phylogenetic analyses on sequence alignments of Ty1 and Ty2 elements characterized during the yeast genome project.Also included in our analyses were previously reported Ty1 (Ty1-H3 and Ty1-912) and Ty2 (Ty2-117) sequences (Clare and Farabaugh 1985;Warmington et al. 1985;Boeke et al. 1988).The Ty1 and Ty2 element families consist of closely related elements that are similar in size and sequence.These elements consist of two long terminal repeats (LTRs), known as ␦ sequences, which flank two open reading frames (ORFs) TYA and TYB.The ␦ sequences are made up of the U3-R-U5 regions as defined by the initiation and termination of transcription (Boeke et al. 1985).Ty1 and Ty2 elements were previously thought to share similar ␦ sequences but differ in their open reading frames (Curcio and Garfinkel 1994).The TYA ORF is homologous to the gag locus of retroviruses and encodes structural proteins of the viral-like particle (Clare and Farabaugh 1985).TYB is homologous to the pol locus and encodes the catalytic proteins protease
Scintigraphic and Magnetic Resonance Studies in a Patient with Gaucher??s Disease
Authors: ITALO ZANZI, SHARON TAYLOR, ELAINE GOULD, STEVEN L. ALLEN, STEVEN KROOP, STANLEY ASNIS, DONALD MARGOULEFF
Journal: Clinical Nuclear Medicine (1988)

ln-111 chloride imaging was used in the evaluation of a patient with Type I Gaucher's disease before splenectomy for pancytopenia. This case is the first report of its use in this clinical setting. The image demonstrated the presence of adequate marrow reserve, thereby suggesting that the pancytopenia was due to hypersplenism rather than marrow replacement. Normalization of blood counts after splenectomy confirmed this interpretation. Eight months later, the patient had acute pain in the left knee. Bone imaging suggested a left lateral tibial plateau fracture that was not seen on plain radiographs or magnetic resonance imaging, but was confirmed by x-ray tomography. The significance and implications of these findings are discussed.
MiR-29b replacement inhibits proteasomes and disrupts aggresome+autophagosome formation to enhance the antimyeloma benefit of bortezomib
Authors: S Jagannathan, N Vad, S Vallabhapurapu, S Vallabhapurapu, K C Anderson, J J Driscoll
Journal: Leukemia (2014)

Evading apoptosis is a cancer hallmark that remains a serious obstacle in current treatment approaches. Although proteasome inhibitors (PIs) have transformed management of multiple myeloma (MM), drug resistance emerges through induction of the aggresome+autophagy pathway as a compensatory protein clearance mechanism. Genome-wide profiling identified microRNAs (miRs) differentially expressed in bortezomib-resistant myeloma cells compared with drug-naive cells. The effect of individual miRs on proteasomal degradation of short-lived fluorescent reporter proteins was then determined in live cells. MiR-29b was significantly reduced in bortezomib-resistant cells as well as in cells resistant to second-generation PIs carfilzomib and ixazomib. Luciferase reporter assays demonstrated that miR-29b targeted PSME4 that encodes the proteasome activator PA200. Synthetically engineered miR-29b replacements impaired the growth of myeloma cells, patient tumor cells and xenotransplants. MiR-29b replacements also decreased PA200 association with proteasomes, reduced the proteasome's peptidase activity and inhibited ornithine decarboxylase turnover, a proteasome substrate degraded through ubiquitin-independent mechanisms. Immunofluorescence studies revealed that miR-29b replacements enhanced the bortezomib-induced accumulation of ubiquitinated proteins but did not reveal aggresome or autophagosome formation. Taken together, our study identifies miR-29b replacements as the first-in-class miR-based PIs that also disrupt the autophagy pathway and highlight their potential to synergistically enhance the antimyeloma effect of bortezomib.
Let's talk about error
Authors: J. L Reinertsen
Journal: BMJ (2000)

In the time it will take you to read this editorial eight patients will be injured, and one will die, from preventable medical errors. Medication error—wrong drug, wrong dose, wrong route of administration, wrong patient, wrong time—is the most common single preventable cause of patient injury. When all sources of error are added up the likelihood that a mishap will injure a patient in hospital is at least 3% and probably much higher.1–4 This is a serious public health problem. When one considers that a typical airline handles customers' baggage at a far lower error rate than we handle the administration of drugs to patients, it is also an embarrassment.

Given the prevalence of errors in our work, and given also that one of our first principles is “first do no harm,” it is strange that we talk so little in our hospitals and consulting rooms about this problem. Perhaps it is because we tend to view most errors as …
Sodium channels gone wild: resurgent current from neuronal and muscle channelopathies
Authors: Stephen C. Cannon, Bruce P. Bean
Journal: Journal of Clinical Investigation (2010)

Voltage-dependent sodium channels are the central players in the excitability of neurons, cardiac muscle, and skeletal muscle. Hundreds of mutations in sodium channels have been associated with human disease, particularly genetic forms of epilepsy, arrhythmias, myotonia, and periodic paralysis. In this issue of the JCI, Jarecki and colleagues present evidence suggesting that many such mutations alter the gating of sodium channels to produce resurgent sodium current, an unusual form of gating in which sodium channels reopen following an action potential, thus promoting the firing of another action potential (see the related article beginning on page 369). The results of this study suggest a widespread pathophysiological role for this mechanism, previously described to occur normally in only a few types of neurons.
Intramural coronary delivery of advanced antisense oligonucleotides reduces neointimal formation in the porcine stent restenosis model
Authors: Nicholas N Kipshidze, Han-Soo Kim, Patrick Iversen, Hamid A Yazdi, Balram Bhargava, Gishel New, Roxana Mehran, Fermin Tio, Christian Haudenschild, George Dangas, Gregg W Stone, Sriram Iyer, Gary S Roubin, Martin B Leon, Jeffrey W Moses
Journal: Journal of the American College of Cardiology (2002)
Plasma Ip(a) concentration is inversely correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene.
Authors: D Gavish, N Azrolan, J L Breslow
Journal: Journal of Clinical Investigation (1989)

Plasma Lp(a) levels correlate with atherosclerosis susceptibility. This lipoprotein consists of an LDL-like particle attached to a large glycoprotein called apo(a). Apo(a) is a complex glycoprotein containing multiple Kringle domains, found to be highly homologous to plasminogen Kringle IV, and a single Kringle domain homologous to plasminogen Kringle V. Lp(a) levels appear to be inversely correlated with apo(a) size in a given individual. In this study, we have used probes specific to the Kringles IV and V domains of apo(a) cDNA in quantitative Southern blotting analysis. By this method, we have determined the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene of 53 unrelated individuals with different plasma concentrations of Lp(a). This ratio was found to be inversely correlated with log Lp(a) levels (r = -0.90, P less than 0.0001) and directly correlated with apo(a) apparent molecular weight (Mr) (r = 0.79, P less than 0.0001). In summary, by showing that Lp(a) concentrations and apo(a) apparent size are highly correlated with the ratio of Kringle IV/Kringle V encoding domains in the apo(a) gene, we provide a DNA marker for this atherosclerosis risk factor as well as an important insight into the genetic mechanism regulating Lp(a) levels.
EndNote Plus: Enhanced Reference Database and Bibliography Maker
Authors: S. Satya-Murti
Journal: JAMA (1993)

<i>EndLink: EndNote's Link to Online Databases</i>, by Niles &amp; Associates Inc, IBM PC and compatibles version, one 3.5-in or 5.25-in diskette, Macintosh version also available; documentation: 52-pp spiral manual, requirements: as above, modem, and account with an on-line database service, $99, Berkeley, Calif, Niles &amp; Associates Inc, 1991. Manuscript submission requirements vary from journal to journal. Bibliographic citation styles differ widely among the physical and biological sciences and even within medical specialties. The tedium of reformatting the reference list of a rejected manuscript before resubmission is well known to any aspiring author. What are the prospects for embracing a universal citation style? They are quite dim, indeed; Esperanto and monotheism stand a better chance at gaining universal acceptance. Thus, there is a need for a reference database manager and bibliography generator. I know of three products in the market that address this need; this is a review of one of
Clues and cure sought for HCV in Hispanics
Authors: P. Cotton
Journal: JAMA (1991)

HISPANICS have a four times higher incidence of non-A, non-B hepatitis than whites or blacks in the United States (JAMA. 1990;264:2231-2235).  There are no clues as to why, says Miriam Alter, PhD, chief of hepatitis epidemiology at the Centers for Disease Control (CDC), Atlanta, Ga, and first author of the study.  In fact, since the start this past year of blood bank screening for the hepatitis C virus (HCV), the cause of most non-A, non-B hepatitis, the transmission route of 40% of infections cannot be deduced.  More pressing is the question of who should be treated, since a Food and Drug Administration advisory panel has recommended approval for interferon alfa therapy.  With a 6-month course of 3 million units of interferon alfa three times a week, 38% to 50% of patients respond with normalized transaminase levels and histologic improvement within 12 weeks vs 3% to 5% improvement for untreated controls.
Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen.
Authors: Y Kurokawa, A Maekawa, M Takahashi, Y Hayashi
Journal: Environmental Health Perspectives (1990)

Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.
CD11b<sup>+</sup>Gr1<sup>+</sup>bone marrow cells ameliorate liver fibrosis by producing interleukin-10 in mice
Authors: Yang-Gun Suh, Ja Kyung Kim, Jin-Seok Byun, Hyon-Seung Yi, Young-Sun Lee, Hyuk Soo Eun, So Yeon Kim, Kwang-Hyub Han, Kwan Sik Lee, Gregg Duester, Scott L. Friedman, Won-Il Jeong
Journal: Hepatology (2012)

Clinical trials and animal models suggest that infusion of bone marrow cells (BMCs) is effective therapy for liver fibrosis, but the underlying mechanisms are obscure, especially those associated with early effects of BMCs. Here, we analyzed the early impact of BMC infusion and identified the subsets of BMCs showing antifibrotic effects in mice with carbon tetrachloride–induced liver fibrosis. An interaction between BMCs and activated hepatic stellate cells (HSCs) was investigated using an in vitro coculturing system. Within 24 hours, infused BMCs were in close contact with activated HSCs, which was associated with reduced liver fibrosis, enhanced hepatic expression of interleukin (IL)-10, and expanded regulatory T cells but decreased macrophage infiltration in the liver at 24 hours after BMC infusion. In contrast, IL-10–deficient (IL-10−/−) BMCs failed to reproduce these effects in fibrotic livers. Intriguingly, in isolated cells, CD11b+Gr1highF4/80− and CD11b+Gr1+F4/80+ BMCs expressed more IL-10 after coculturing with activated HSCs, leading to suppressed expression of collagen and α-smooth muscle actin in HSCs. Moreover, these effects were either enhanced or abrogated, respectively, when BMCs were cocultured with IL-6−/− and retinaldehyde dehydrogenase 1−/− HSCs. Similar to murine data, human BMCs expressed more IL-10 after coculturing with human HSC lines (LX-2 or hTERT), and serum IL-10 levels were significantly elevated in patients with liver cirrhosis after autologous BMC infusion. Conclusion : Activated HSCs increase IL-10 expression in BMCs (CD11b+Gr1highF4/80− and CD11b+Gr1+F4/80+ cells), which in turn ameliorates liver fibrosis. Our findings could enhance the design of BMC therapy for liver fibrosis.