tbuckley/cabot-search huggingface dataset:
Ischemia-Reperfusion Injury at the Microvascular Level
Authors: Leonarda Galiuto, Anthony N. DeMaria, Ughetta del Balzo, Karen May-Newman, Stephen F. Flaim, Paul L. Wolf, Michael Kirchengast, Sabino Iliceto
Journal: Circulation (2000)

Background —The purpose of this study was to verify whether endothelin A–antagonist administration at the time of coronary reperfusion preserves postischemic microvasculature and whether myocardial contrast echo (MCE) is able to detect pharmacologically induced changes in microvascular reflow. Methods and Results —Twenty dogs underwent 90 minutes of LAD occlusion (OCC) followed by 180 minutes of reperfusion (RP). Five minutes before LAD reopening, an intravenous bolus (5 mg/kg) of LU 135252 was given in 10 dogs and vehicle in the remaining 10. At baseline (BSL), OCC, and 90 and 180 minutes of RP, microvascular flow (BF) was assessed by microspheres, and MCE was performed with intravenous echo contrast. MCE videointensity and BF were expressed as risk area/control ratio. Myocardial thickness of the risk area was calculated by 2D echo. No differences in BF between the 2 groups were observed at BSL, OCC, and 90 minutes of RP. At 180 minutes of RP, BF was decreased in controls (70±7.4% of BSL; P &lt;0.005 versus BSL) and preserved in LU 135252–treated animals (89±4% of BSL; P =NS versus BSL; P &lt;0.05 versus controls). Videointensity at MCE closely followed the changes in BF observed in both groups throughout the protocol. Myocardial thickness at 180 minutes of RP increased to 138.6±9.9% of BSL in controls and remained at 108.9±7.4% of BSL in treated dogs ( P &lt;0.05). Conclusions —Endothelin A–antagonist treatment at the time of reperfusion significantly limited the progressive decrease in postischemic microvascular reflow and the increase in myocardial thickness. MCE allowed a reliable evaluation of pharmacologically induced changes in microvascular flow.
Effect of an ATP sensitive potassium channel opener, levcromakalim, on coronary arterial microvessels in the beating canine heart
Authors: K. Sato, H. Kanatsuka, N. Sekiguchi, K. Akai, Y. Wang, A. Sugimura, T. Kumagai, T. Komaru, K. Shirato
Journal: Cardiovascular Research (1994)

The aim was to clarify the site in the coronary microcirculation that is dilated by an ATP sensitive potassium channel opener, levcromakalim, and to examine whether the magnitude of dilatation is size dependent.Coronary arterial microvessels were observed through an intravital microscope equipped with a floating objective in beating canine left ventricles in situ. Flow velocity of the left anterior descending coronary artery was measured with a suction-type Doppler probe. Heart rate and aortic pressure were maintained at control levels throughout the experiments. Three doses of levcromakalim (0.01-1.0 microgram.kg-1.min-1) or a single dose (1.0 microgram.kg-1.min-1) were infused into the coronary artery in groups, with or without intracoronary glibenclamide pretreatment (200 or 400 micrograms.kg-1). The effect of levcromakalim on different sized vessels was assessed by dividing them into three groups according to control diameter (small, internal diameter < 100 microns; medium, > or = 100, < 200 microns; large, > or = 200 microns).The lowest dose of levcromakalim dilated only the small vessels. The two higher doses dilated vessels of all sizes, but the magnitude of dilatation was greater in the small vessel group than in the other two groups. Coronary resistance significantly decreased dose dependently during the infusion of 0.1 and 1.0 microgram.kg-1.min-1 of levcromakalim. Pretreatment with glibenclamide markedly attenuated the levcromakalim induced dilatation of all vessel groups and the reduction in coronary vascular resistance.Levcromakalim heterogeneously dilates coronary arterial microvessels via the opening of ATP sensitive potassium channels, and small vessels are more sensitive to levcromakalim.
Abstract PR13: microRNAs: Master regulators of human tumor dormancy
Authors: Nava Almog, Lili Ma, Briggs Christine, Edward Rietman, Afshin Beheshti, Amir Abdollahi
Journal: Cancer Research (2013)

Abstract Tumor dormancy refers to a critical stage in cancer progression in which tumors remain small and occult for a prolonged period until they eventually progress and become clinically apparent. Although escape from tumor dormancy has long been recognized as an important problem in the treatment of cancer, the molecular and cellular regulators underlying this transition remain poorly understood. We have previously generated and characterized in vivo models of human tumor dormancy. In these models dormancy of micro-tumors is angiogenesis dependent and the spontaneous escape of the tumors from dormancy requires a stable transcriptional reprogramming. We show here that dormant tumors undergo a stable microRNA switch during their transition to the fast-growing angiogenic phenotype and report the identification of a consensus set of dormancy-associated microRNAs (DmiRs). Loss of DmiR expression is associated with the spontaneous transition of dormant tumors to rapid growth. The expression pattern of two DmiRs was confirmed to correlate with disease stage in human glioma specimens. Reconstitution of a single DmiR (miR580, 588 or 190) led to phenotypic reversal of fast-growing tumors towards prolonged tumor dormancy. Transcriptional reprogramming of tumors via DmiR over-expression resulted in downregulation of pro-angiogenic factors such as TIMP-3, bFGF, TGF alpha or Bv8 and decreased tumor recruitment of pro-angiogenic bone marrow-derived CD11b+ Gr-1+ myeloid cells. In contrast, antiangiogenic and dormancy promoting pathways such as EphA5 and Angiomotin were upregulated in DmiR expressing tumors. We further investigated the transcriptional targets of mir-190 which exerts the strongest tumor inhibiting effect and show that mir-190 affects mRNA levels of a very large set of genes in both direct and indirect ways. Many of the genes affected by mir-190 are related to the transcription process, are associated with tumor suppressors and with the interferon pathway. The identification of tumor dormancy associated microRNAs, along with improved understanding of their mechanistic actions could lead to the development of novel means to revert the malignant tumor phenotype to a dormant state. This work may also provide promising targets for early detection or prevention of cancer. This abstract is also presented as Poster C97. Citation Format: Nava Almog, Lili Ma, Briggs Christine, Edward Rietman, Afshin Beheshti, Amir Abdollahi. microRNAs: Master regulators of human tumor dormancy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr PR13.
Mucocutaneous Lymph Node Syndrome (Kawasaki Disease) in Adults
Authors: James K. Todd
Journal: JAMA (1980)

<h3>To the Editor.—</h3> The case reports presented by E. Dale Everett, MD (242:542, 1979), purports to describe adult cases of mucocutaneous lymph node syndrome (Kawasaki disease). Before this association becomes ingrained in the general medical literature, I would like to urge a note of caution. Mucocutaneous lymph node syndrome was originally described in Japanese children, and its epidemiology in Japan strongly emphasizes its rarity in persons older than 5 years. Its diagnostic criteria are sufficiently broad to include many other distinct clinical entities (eg, Stevens-Johnson's syndrome, scarlet fever, and leptospirosis) if clinical criteria are interpreted too liberally or a full etiologic evaluation is not completed. Even from the case descriptions given, Everett's patients differ from those with Kawasaki disease in a number of the following important ways: they are adult and female, and they have a more acute and severe multisystem illness. In most respects, these cases are far more
Focal Fat Spared Area in the Liver Masquerading as Hepatic Metastasis on F-18 FDG PET Imaging
Authors: N C. Purandare, Venkatesh Rangarajan, Anshu Rajnish, Sneha Shah, Abhishek Arora, Sujata Pathak
Journal: Clinical Nuclear Medicine (2008)

Fatty infiltration of the liver is not an uncommon imaging finding with modalities like ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). However, when it manifests as a focal fatty change or areas of focal fat sparing, an appearance of a mass lesion is produced. Focal tracer uptake seen in the liver on F-18 fluorodeoxyglucose-positron emission tomography (FDG-PET) when it is performed as a part of a metastatic work up for colorectal cancer is highly suggestive of hepatic metastasis. We present an unusual finding of focal FDG uptake in a fat-spared area in the liver masquerading as a hepatic metastasis.
Comparative Hemodynamics During Open vs Closed Cardiac Resuscitation
Authors: Stanley Pappelbaum
Journal: JAMA (1965)

Because of the controversy concerning techniques of cardiac resuscitation, it was decided to return to the laboratory to evaluate the hemodynamic benefits of these techniques under more controlled conditions. The experimental design revealed closed-chest massage to be an effective technique when compared to open-chest resuscitation. Closed-chest massage is proposed as a scientifically valid interim resuscitative measure which, if applied within the crucial four-minute limit, will maintain life until definitive diagnostic and therapeutic procedures can be instituted.
Serine/threonine kinase PKR: A sentinel kinase that discriminates a signaling pathway mediated by TLR4 from those mediated by TLR3 and TLR9
Authors: Yusuke Asakura, Yoshihiro Fujiwara, Naoko Kato, Yuko Sato, Toru Komatsu
Journal: American Journal of Hematology (2006)

Abstract Cells of the innate immune system discriminate between “noninfectious self” and “infectious nonself” via pattern recognition receptors known as Toll‐like receptors (TLRs). Though TLRs and the related interleukin 1 receptors share considerable homology in their cytoplasmic domains and adaptor molecules, signaling cascades may substantially differ from one another depending on the adaptor proteins recruited. Here we show that ectopic overexpression of catalytically inactive dominant‐negative PKR expression system suppressed NF‐ κ B activation mediated by TLR3, TLR9, TNF receptor 1 and 2 (TNF‐R 1/2), but not by TLR4. Physiological relevance of the observations described here are discussed. Am. J. Hematol 2007. © 2006 Wiley‐Liss, Inc.
Plasma Amino-acids in the Nigerian Nutritional Ataxic Neuropathy
Authors: B. O. Osuntokun, J. E. Durowoju, H. McFarlane, J. Wilson
Journal: BMJ (1968)

Investigation of nine patients with tropical ataxic neuropathy showed an absence or diminution of sulphur-containing amino-acids-cysteine and methionine-and a variable concentration of most other essential amino-acids. The pattern was unlike that found in kwashiorkor. The levels of serum cholesterol and total protein were normal, and the serum vitamin B(12) levels were normal or high. Plasma thiocyanate concentration was high.All the patients gave a history of a monotonous diet of cassava derivatives. Cassava contains a cyanogenetic glycoside (linamarin) from which cyanide is released on hydrolysis. The excessive cyanide detoxication may be responsible for the low concentration of the sulphur-containing amino-acids.
Aortic Aneurysm
Authors: BROOKE ROBERTS, GORDON DANIELSON, WILLIAM S. BLAKEMORE
Journal: Circulation (1957)

An evaluation of the management of patients with aneurysm of the aorta seems timely because of new and promising methods of treatment. The risks of nonoperative and operative treatment are presented from the experiences with 101 patients admitted to the Hospital of the University of Pennsylvania during the years 1950 through 1955. Follow-up data indicate that the mortality of nonoperative treatment is considerably greater than that of excision of the lesion, in spite of the poor operative risk of many patients in this group. The nonoperative mortality within 1 year of diagnosis was approximately 50 per cent. Many of these patients died of rupture of the aneurysm.
Clinical Implications of Diffuse Hepatic Uptake Observed in Postablative and Post-Therapeutic I-131 Scans
Authors: Özgür Ömür, Ayşegül Akgün, Zehra Özcan, Çiğdem Şen, Hayal Özklç
Journal: Clinical Nuclear Medicine (2008)

Diffuse hepatic uptake of I-131 either on diagnostic or post-therapeutic scans is a usual finding in patients with differentiated thyroid carcinoma. The aim of this study was to evaluate the frequency and clinical significance of diffuse hepatic uptake of radioiodine on post-therapeutic (PT) and postablative (PA) whole-body scans.A total of 720 PA and 172 PT I-131 scans in a total of 732 patients with differentiated thyroid carcinoma were retrospectively reviewed. Residual thyroid tissue and diffuse liver uptake of I-131 were classified from 0 to 4. The correlation between the liver and thyroid remnant uptake score, dose of radioiodine, serum thyroglobuline (Tg), liver function test levels (ALT, AST), liver ultrasonography, presence of metastatic foci, and recurrent disease were examined.Diffuse hepatic uptake was observed in 701 of 722 (94.2%) PA and 162 of 172 (97%) PT whole body I-131 scans. Hepatic radioiodine uptake was positively correlated with the dose of administered I-131 and increased levels of serum AST and ALT. Liver uptake scores of patients with hepatosteatosis were significantly higher than all study groups. However, no evidence of a relationship between diffuse visualization of liver and serum thyroglobulin levels, uptake score of thyroid remnants, presence of local or distant metastatic foci on I-131 scan, and recurrence rate could be demonstrated.The lack of correlation between hepatic radioactive iodine (RAI) uptake and Tg levels, functioning metastatic tissue or thyroid remnants suggests that this finding may be related to factors other than thyroid tissue. The positive correlation between administered RAI dose, hepatic enzymes and hepatosteatosis support the conclusion that diffuse hepatic RAI uptake may be related to different mechanisms as well.
Autosomal Dominant Polycystic Kidney Disease
Authors: Burcin Ekser, Paolo Rigotti
Journal: New England Journal of Medicine (2010)

A 48-year-old man presented for evaluation of the transplantation of a kidney from a living donor. He had a 14-year history of autosomal dominant polycystic kidney disease with progression to end-stage renal disease that required hemodialysis. Initially, transplantation was not possible because his voluminous, bilateral polycystic kidneys did not leave any space in his abdomen (Panel A). He underwent bilateral nephrectomy; the removed kidneys weighed a total of 22 kg (48.4 lb; 21.6% of his total body weight), and the larger right kidney measured 51 cm (Panel B). Three months after the nephrectomy, he underwent successful kidney transplantation from a . . .
Is gastric cancer part of the tumour spectrum of hereditary non-polyposis colorectal cancer? A molecular genetic study
Authors: A Gylling, W M Abdel-Rahman, M Juhola, K Nuorva, E Hautala, H J Jarvinen, J-P Mecklin, M Aarnio, P Peltomaki
Journal: Gut (2007)

<b>Background:</b> Gastric cancer is the second most common extracolonic malignancy in individuals with hereditary non-polyposis colorectal cancer (HNPCC)/Lynch syndrome. As gastric cancer is relatively common in the general population as well, it is not clear whether or not gastric cancer is a true HNPCC spectrum malignancy. <b>Aim:</b> To determine whether or not gastric cancer is a true HNPCC spectrum malignancy. <b>Subjects and methods:</b> The molecular and clinicopathological profiles of gastric cancers (n = 13) from HNPCC mutation carriers were evaluated and compared with the profiles of sporadic gastric cancers (n = 46) stratified by histology and microsatellite instability (MSI) status. <b>Results:</b> This study on sporadic and HNPCC gastric cancers revealed several important universal associations. Loss of heterozygosity in the adenomatous polyposis coli (APC) region was associated with intestinal histology regardless of the MSI (p = 0.007). KRAS-mutations (p = 0.019) and frameshift mutations in repeat tracts of growth-regulatory genes (p&lt;0.001) were associated with MSI tumours being absent in microsatellite stable (MSS) tumours. The average number of methylated tumour suppressor gene loci among the 24 genes studied (methylation index) was higher in MSI than in MSS tumours regardless of histology (p&lt;0.001). Gastric cancers from HNPCC mutation carriers resembled sporadic intestinal MSI gastric cancers, except that MLH1 promoter methylation was absent (p&lt;0.001) and the general methylation index was lower (p = 0.038), suggesting similar, but not identical, developmental pathways. All these lacked the mismatch repair protein corresponding to the germline mutation and displayed high MSI. <b>Conclusion:</b> The present molecular evidence, combined with the previous demonstration of an increased incidence relative to the general population, justify considering gastric cancers as true HNPCC spectrum malignancies.
Effect of sulphapyridine, 5-aminosalicylic acid, and placebo in patients with idiopathic proctitis: a study to determine the active therapeutic moiety of sulphasalazine.
Authors: P A van Hees, J H Bakker, J H van Tongeren
Journal: Gut (1980)

Suppositories of sulphapyridine, 5-aminosalicylic acid, and placebo were used in 45 patients with idiopathic proctitis to determine the active part of sulphasalazine. Each patient used one of the suppositories twice daily for four weeks in a double-blind controlled trial. Complete clinical remission with normal rectal mucosa on sigmoidoscopy occurred in 60% of patients given 5-aminosalicylic acid, but in only 13% and 27% of those given sulphapyridine and placebo respectively. Twelve patients were included twice. In eight of these patients 5-aminosalicylic acid was given one time and sulphapyridine (two patients) or placebo (six patients) another time. Clinical remission occurred in each patient with 5-aminosalicylic acid, but in only one patient during other therapy. The results suggest that 5-aminosalicylic acid is the active therapeutic moiety of sulphasalazine.
Phytoestrogens: epidemiology and a possible role in cancer protection.
Authors: H Adlercreutz
Journal: Environmental Health Perspectives (1995)

Because many diseases of the Western Hemisphere are hormone-dependent cancers, we have postulated that the Western diet, compared to a vegetarian or semivegetarian diet, may alter hormone production, metabolism, or action at the cellular level by some biochemical mechanisms. Recently, our interest has been mainly focused on the cancer-protective role of some hormonelike diphenolic phytoestrogens of dietary origin, the lignans and the isoflavonoids. The precursors of the biologically active compounds originate in soybean products (mainly isoflavonoids), whole grain cereal food, seeds, and probably berries and nuts (mainly lignans). The plant lignan and isoflavonoid glycosides are converted by intestinal bacteria to hormonelike compounds with weak estrogenic but also antioxidative activity; they have now been shown to influence not only sex hormone metabolism and biological activity but also intracellular enzymes, protein synthesis, growth factor action, malignant cell proliferation, differentiation, and angiogenesis in a way that makes them strong candidates for a role as natural cancer-protective compounds. Epidemiologic investigations strongly support this hypothesis because the highest levels of these compounds in the diet are found in countries or regions with low cancer incidence. This report is a review on recent results suggesting that the diphenolic isoflavonoids and lignans are natural cancer-protective compounds.
Macrophage induction of T-suppressor cells in pesticide-exposed and protozoan-infected mice.
Authors: L D Loose
Journal: Environmental Health Perspectives (1982)

The use of infectious pathogens has allowed the detection of the development of synergism between pathogens and ubiquitous environmental chemical contaminants. This synergism has been demonstrated to result in a state of immunosuppression which either did not occur in the independent and singular presence of the chemical or pathogen and/or was greater than additive when both were combined. The immunosuppression was distinct with regard to the organochloride used and, therefore, is not a ubiquitous characteristic of all organohalides. The production of a macrophage soluble factor which appeared to induce T-suppressor cells was demonstrated in hepatic Kupffer cells from mice administered 5 ppm of dieldrin for 10 weeks and then infected with Leishmania tropical promastigotes. The factor was not generated in mice administered dieldrin and infected with malaria nor in mice administered only dieldrin nor in mice only infected with Leishmania. Additional studies revealed a profound impairment in macrophage antigen processing with macrophages obtained from mice administered dieldrin. The use of pathogen models may allow the immunosuppressive potential of environmental chemical contaminants to be expressed in a more sensitive manner.
Abstract 67: Selective cytotoxic targeting of von Hippel-Lindau-deficient renal cell carcinoma cells
Authors: Edwin W. Lai, Denise A. Chan, Michael P. Hay, Amato J. Giaccia
Journal: Cancer Research (2010)

Abstract Loss of the von Hippel-Lindau (VHL) tumor suppressor gene, an essential alteration in the development of renal cancer, can be targeted through a synthetic lethal manner. In our screen we identified a compound, STF-31536, which is selectively cytotoxic toward VHL-deficient renal cancer cells in a HIF-dependent manner. This compound did not induce apoptosis and inhibits glucose transport. These findings are significant since we have previously shown another compound STF-62247 was cytotoxic toward VHL-deficient cells and induced autophagy in a HIF-independent manner. We have also shown that STF-31536 induces cell death in vitro and in vivo, however the mechanism and target of this compound is currently unknown. In order to identify the target of STF-31536, we have coupled analogs of STF-31536 to an affinity resin. Activity of these analogs was confirmed by cytotoxicity assays. Selected affinity chromatography reagents coupled to resin were used for binding assays to determine direct drug-target interactions. The potential targets were purified and identified by gel electrophoresis after collecting fractions from the column. Renal cell carcinoma cells deficient in VHL are characterized by elevated expression of VEGF and glucose transporter 1 (Glut-1). Immunoblots for Glut-1 transporter in protein fractions eluted from the column show binding of STF-31536 to Glut-1. Therefore, we show loss of the von Hippel-Lindau (VHL) tumor suppressor gene can be targeted by this small molecule through a synthetic lethal manner by disrupting glucose transport. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 67.