tbuckley/cabot-search huggingface dataset:
THE ROLE OF AFFERENT LYMPHATICS IN THE REJECTION OF SKIN HOMOGRAFTS
Authors: Clyde F. Barker, R. E. Billingham
Journal: The Journal of Experimental Medicine (1968)

Experiments have been carried out on guinea pigs of two isogenic strains to elucidate the role of afferent lymphatic vessels in the rejection of orthotopic skin homografts. Graft beds were prepared in partially isolated skin flaps with an intact sustaining vascular "umbilical cord" in which a lymphatic connection with the host could be retained or abolished at will. In the absence of demonstrable lymphatic connections between flap and host, intra-flap homografts long outlived similar grafts transplanted to conventional sites in intact skin and, rather than being specifically rejected, died as a consequence of ischemic necrosis of the flap. When lymphatic drainage was retained, intra-flap homografts were rejected in the usual manner. Hosts of long-term intra-flap homografts did not develop sensitivity, as evidenced by the "first set" type rejection of subsequent test grafts, or by the long-term survival of a second skin graft transplanted to a new flap raised on the opposite side of the host's body. Intra-flap skin homografts were rejected if (a) the hosts had been presensitized, (b) they were grafted concomitantly with a skin homograft placed in a conventional site, or inoculated with a suspension of donor lymphoid cells, or (c) if the lymphatic drainage was restored by reimplantation of the hitherto partially isolated flap to an appropriate vascular bed. These findings and others indicate that an intact lymphatic drainage in its bed is essential for an orthotopic skin homograft to sensitize its host. Various experiments were carried out in which intra-flap homografts were used as "indicators" for the acquisition of specific active or adoptive immunity by their hosts. By transplanting skin homografts to conventional beds concomitantly with intra-flap grafts and then excising the former at various intervals, it has been found that a graft must be in residence for a minimum period of 4 days to evoke the development of a detectable level of sensitivity in the host. Furthermore, by replacing either freshly prepared or long-term skin flaps bearing skin homografts in vascular beds on the trunk and determining the subsequent survival times of the homografts, evidence has been obtained suggesting that reestablishment of a functional lymphatic system in a free skin graft may take as long as 9 days. Using intra-flap homografts as indicators of adoptive immunization of the host, we found that as few as 50 x 10(6) isologous peripheral blood leukocytes from a specifically sensitized animal will transfer an effective level of sensitivity. We also found that hyperimmune serum, in relatively large amount, exerts a weak but definite adverse effect upon either freshly or recently transplanted intra-flap grafts.
The Coronary-Care Unit
Authors: Thomas P. Hackett, N. H. Cassem, Howard A. Wishnie
Journal: New England Journal of Medicine (1968)

THE frequency of psychiatric difficulties in intensive-care units ranges from 30 to 70 per cent. Confinement in these units is described as an "ordeal,"1 and the patient's expected psychologic response is presented as one of "catastrophic reaction."2 Although the study from which this last term developed was conducted on postcardiotomy patients in the setting of the recovery room, there has been a growing tendency to apply it to all situations of intensive care. This is an unfortunate application because intensive-care settings differ remarkably as do the emotional responses of the patients they house. The question of whether patients in coronary-care . . .
Effects of Losartan on Renal and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Nephropathy
Authors: Barry M. Brenner, Mark E. Cooper, Dick de Zeeuw, William F. Keane, William E. Mitch, Hans-Henrik Parving, Giuseppe Remuzzi, Steven M. Snapinn, Zhonxin Zhang, Shahnaz Shahinfar
Journal: New England Journal of Medicine (2001)

Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not available for patients with type 2, the most common form of diabetes. We assessed the role of the angiotensin-II-receptor antagonist losartan in patients with type 2 diabetes and nephropathy.A total of 1513 patients were enrolled in this randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-channel antagonists, diuretics, alpha-blockers, beta-blockers, and centrally acting agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage renal disease, or death. Secondary end points included a composite of morbidity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease.A total of 327 patients in the losartan group reached the primary end point, as compared with 359 in the placebo group (risk reduction, 16 percent; P=0.02). Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25 percent; P=0.006) and end-stage renal disease (risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blood pressure. The composite of morbidity and mortality from cardiovascular causes was similar in the two groups, although the rate of first hospitalization for heart failure was significantly lower with losartan (risk reduction, 32 percent; P=0.005). The level of proteinuria declined by 35 percent with losartan (P<0.001 for the comparison with placebo).Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated.
Reversible blockade of cardiac efferents with procaine instilled into the pericardium of cats
Authors: L F SAMODELOV, M. POHL, J. O ARNDT
Journal: Cardiovascular Research (1982)

Journal Article Reversible blockade of cardiac efferents with procaine instilled into the pericardium of cats Get access L F SAMODELOV, L F SAMODELOV * From the Department of Experimental Anaesthesia, University of Dusseldorf, Germany *Author's address: Leonid F. Samodelov, Research Assistant, Abt Experimentelle Anästhesiologie, d Institutes für Anästhesiologie, d Universität Düsseldorf, Gebaude 23.02.01, Universi-tatsstrasse 1, 4000 Diisseldorf, Germany. Search for other works by this author on: Oxford Academic PubMed Google Scholar MICHAEL POHL, MICHAEL POHL From the Department of Experimental Anaesthesia, University of Dusseldorf, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar JOACHIM O ARNDT JOACHIM O ARNDT From the Department of Experimental Anaesthesia, University of Dusseldorf, Germany Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 16, Issue 4, April 1982, Pages 187–193, https://doi.org/10.1093/cvr/16.4.187 Published: 01 April 1982
Perspectives in radiation and health: reflections on the International Conference in Beer Sheva.
Authors: K F Baverstock
Journal: Environmental Health Perspectives (1997)

Insofar as international conferences reflect the state of development of the subject under discussion, they provide an opportunity to question, at a rather fundamental level, the direction of and progress in the subject. With regard to the effects of radiation on health, many of the problems faced today, including uncertainties in the relationship between risk and dose and the origins of the psychosocial phenomena associated with many aspects of environmental radiation exposure, arise from a lack of adequate frameworks within which to understand the radiopathological impact of radiation exposure and the psychological and social implications of such exposures. It is concluded that in seeking an understanding of the relationship of health effects to exposure, through the underlying radiobiological processes, the perturbation of the dynamic interactions within the components of the organism should receive more emphasis. The public perception of risk from environmental radiation exposures appears to encompass factors in addition to the accrued health detriment. It is argued that the radiological protection of the public might be seen more beneficially in the context of other environmental risks.
NF-κB Regulates Radioresistance Mediated By β1-Integrin in Three-Dimensional Culture of Breast Cancer Cells
Authors: Kazi Mokim Ahmed, Hui Zhang, Catherine C. Park
Journal: Cancer Research (2013)

Abstract β1-integrin induction enhances breast cancer cell survival after exposure to ionizing radiation (IR), but the mechanisms of this effect remain unclear. Although NF-κB initiates prosurvival signaling pathways post-IR, the molecular function of NF-κB with other key elements in radioresistance, particularly with respect to extracellular matrix-induced signaling, is not known. We discovered a typical NF-κB–binding site in the β1-integrin promoter region, indicating a possible regulatory role for NF-κB. Using three-dimensional laminin-rich extracellular matrix (3D lrECM) culture, we show that NF-κB is required for β1-integrin transactivation in T4-2 breast cancer cells post-IR. Inhibition of NF-κB reduced clonogenic survival and induced apoptosis and cytostasis in formed tumor colonies. In addition, T4-2 tumors with inhibition of NF-κB activity exhibit decreased growth in athymic mice, which was further reduced by IR with downregulated β1-integrin expression. Direct interactions between β1-integrin and NF-κB p65 were induced in nonmalignant breast epithelial cells, but not in malignant cells, indicating context-specific regulation. As β1-integrin also activates NF-κB, our findings reveal a novel forward feedback pathway that could be targeted to enhance therapy. Cancer Res; 73(12); 3737–48. ©2013 AACR.
Distinct association of factor V-Leiden and prothrombin G20210A mutations with deep venous thrombosis in Tunisia and Lebanon
Authors: Lobna Bouaziz-Borgi, Wassim Y. Almawi, Nabil Mtiraoui, Brahim Nsiri, Sose H. Keleshian, Raghid Kreidy, Bessem Louzir, Nathalie Hezard, Touhami Mahjoub
Journal: American Journal of Hematology (2006)

Factor V G1691A (FV-Leiden) and prothrombin (PRT) G20210A single nucleotide polymorphisms (SNPs) were associated with venous thrombosis among Caucasians. We assessed the contribution of both SNPs to the genetic susceptibility of deep venous thrombosis (DVT) among Lebanese and Tunisian patients. Subjects comprised 198 DVT patients and 540 healthy controls from Lebanon and 126 Tunisian DVT patients and 197 control subjects; FV-Leiden (MnlI) and PRT G20210A (HindIII) genotyping was done by PCR-RFLP. While the prevalence of FV-Leiden mutant A allele and the G/A and A/A genotypes were significantly higher among DVT patients from Lebanon and Tunisia, the association of PRT G20210A with DVT was pronounced among Lebanese but not Tunisian patients. The prevalence of PRT G20210A mutant A allele (P < 0.001 vs. P = 181) and G/A genotype (P < 0.001 vs. P = 0.994) was significantly higher among Lebanese but not Tunisians, respectively. While FV-Leiden was a common genetic risk factor for DVT in both communities, the contribution of PRT G20210A to the genetic susceptibility of DVT differed among Lebanese and Tunisians, which underscores the need to determine prothrombotic gene polymorphisms associated with DVT among Arab and Mediterranean basin communities. Am. J. Hematol. 81:641–643, 2006. © 2006 Wiley-Liss, Inc.
Abstract A17: Antagonizing HOX function triggers apoptosis in prostate cancer cells
Authors: Richard Morgan, Guy Simpson, Angela Boxall, Agnieszka Michael, Hardev Pandha
Journal: Cancer Research (2012)

Abstract The HOX genes are a family of transcription factors that determine the identity of cells and tissues during embryonic development and in adult stem cell maturation, and are known to have an oncogenic function in a number of hematological and solid malignancies. HOX genes are also highly expressed in prostate tumors relative to normal prostate tissue, but the redundant nature of HOX function has made the significance of these observations hard to assess by conventional gene knock out studies. Here we use the previously characterized antagonist HXR9 to target the post translational association of HOX proteins with the PBX co-factor and show that this is sufficient to trigger apoptosis in the prostate derived cell lines LNCaP, PC3 and DU145, in vitro. Furthermore HXR9 causes tumor shrinkage in murine and CAM models of prostate cancer. These results suggest that the interaction between HOX proteins and their PBX cofactor might be a therapeutic target in prostate cancer. Note: This abstract was not presented at the conference because the presenter was unable to attend. Citation Format: Richard Morgan, Guy Simpson, Angela Boxall, Agnieszka Michael, Hardev Pandha. Antagonizing HOX function triggers apoptosis in prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A17.
PTU-006 The sequential organ failure assessment (SOFA) score is an effective triage marker following staggered paracetamol (acetaminophen) overdose
Authors: D G Craig, S Zafar, T Reid, J Davidson, K Martin, P C Hayes, K J Simpson
Journal: Gut (2012)

<h3>Introduction</h3> The Sequential Organ Failure Assessment (SOFA) score is an effective triage marker following single time point paracetamol (acetaminophen) overdose,<sup>1</sup> but has not been evaluated following staggered paracetamol overdose. The aims of this study were to evaluate the prognostic accuracy of the SOFA score in a cohort of severe acute liver injury patients following staggered paracetamol overdose. <h3>Methods</h3> Time-course analysis of 50 staggered paracetamol overdoses admitted to a tertiary liver centre. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time from admission, and the daily SOFA score calculated. <h3>Results</h3> A total of 39/50 (78%) patients developed hepatic encephalopathy, and therefore acute liver failure. The area under the SOFA receiver operator characteristic for death/liver transplantation was 87.4 (95% CI 73.2 to 95.7), 94.3 (95% CI 82.5 to 99.1), and 98.4 (95% CI 84.3 to 100.0) at 0, 24, and 48 h respectively post-admission. A SOFA score of &lt;6 at tertiary care admission predicted survival with a sensitivity of 100.0% (95% CI 76.8% to 100.0%) and specificity of 58.3% (95% CI 40.8% to 74.5%), compared with 85.7% (95% CI 60.6% to 97.4%) and 75.0% (95% CI 65.2% to 79.5%) respectively for the modified Kings College criteria. Only 2/21 patients with an admission SOFA score &lt;6 required renal replacement therapy or intracerebral pressure monitoring. SOFA significantly outperformed the Model for End-stage Liver Disease at 0 (p=0.0013), 24 (p=0.0001) and 48 h (p=0.0193) following admission. <h3>Conclusion</h3> A SOFA score &lt;6 at tertiary care admission following a staggered paracetamol overdose carries a high negative predictive value. The SOFA score could improve triage of high risk staggered paracetamol overdose patients. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Craig DG</b>, Reid TW, Martin KG, <i>et al</i>. The systemic inflammatory response syndrome and sequential organ failure assessment scores are effective triage markers following paracetamol (acetaminophen) overdose. <i>Aliment Pharmacol Ther</i> 2011;<b>34</b>:219–28.
Is there a role for extraretinal factors in the maintenance of stability in a structured environment?
Authors: Eugene Chekaluk
Journal: Behavioral and Brain Sciences (1994)

The calibration solution to the stability of the world despite eye movements depends, according to Bridgeman et al., upon a combination of three factors which presumably all need to operate to achieve the goal of stability. Although the authors admit (sect. 4.3, para. 5) that the relative contributions of retinal and extraretinal factors will depend on the particular viewing situation, Figure 5 (sect. 4.3) makes it clear in its representation that the role of perceptual factors is relatively minor compared to extraretinal ones. It is with this representation that this commentary wishes to take issue, believing that it occurs as a result of some assumptions about terminology that may be ambiguous, as well as some misconceptions about the circumstances in which there is a need for stability.
Body Iron Stores and Dietary Iron Intake in Relation to Diabetes in Adults in North China
Authors: Zumin Shi, Xiaoqun Pan
Journal: Diabetes Care (2008)

A study on the association between iron status and diabetes in adults in North China has recently been reported by Luan et al. (1). The results partly confirmed our previous finding from South China (2). In Luan et al.’s study, only heme iron was found to be associated with risk of diabetes. However, the intake of heme iron in their dataset is very low: mean intake ± SD in first quartile only 0.3 ± 0.3 mg/day. Thus, the reference group …
CCR5 Receptor Antagonists Block Metastasis to Bone of v-Src Oncogene–Transformed Metastatic Prostate Cancer Cell Lines
Authors: Daniela Sicoli, Xuanmao Jiao, Xiaoming Ju, Marco Velasco-Velazquez, Adam Ertel, Sankar Addya, Zhiping Li, Sebastiano Andò, Alessandro Fatatis, Bishnuhari Paudyal, Massimo Cristofanilli, Mathew L. Thakur, Michael P. Lisanti, Richard G. Pestell
Journal: Cancer Research (2014)

Abstract Src family kinases (SFK) integrate signal transduction for multiple receptors, regulating cellular proliferation, invasion, and metastasis in human cancer. Although Src is rarely mutated in human prostate cancer, SFK activity is increased in the majority of human prostate cancers. To determine the molecular mechanisms governing prostate cancer bone metastasis, FVB murine prostate epithelium was transduced with oncogenic v-Src. The prostate cancer cell lines metastasized in FVB mice to brain and bone. Gene expression profiling of the tumors identified activation of a CCR5 signaling module when the prostate epithelial cell lines were grown in vivo versus tissue cultures. The whole body, bone, and brain metastatic prostate cancer burden was reduced by oral CCR5 antagonist. Clinical trials of CCR5 inhibitors may warrant consideration in patients with CCR5 activation in their tumors. Cancer Res; 74(23); 7103–14. ©2014 AACR.
Abstract LB-142: Regulation of MYCN stability by reactive oxygen species in neuroblastoma
Authors: Naohiko Ikegaki, Paul L. Regan, Sakeenah L. Hicks, Nolan Maloney, Xao X. Tang
Journal: Cancer Research (2011)

Abstract Neuroblastoma (NB) is the most common extracranial solid tumor in children. Amplification of the MYCN proto-oncogene is associated with older age, rapid tumor progression, and the worst outcome of this disease. As MYCN amplification leads to its over-expression, high-level expression of MYCN is thought to cause an aggressive behavior of MYCN amplified tumors. In fact, the forced reduction of MYCN protein expression by siRNA results in growth suppression and apoptosis of NB cells with MYCN amplification. We have identified several compounds that can rapidly destabilize the MYCN protein (within a few hours), in NB cells and cause growth suppression. The compounds include FCCP, OSU-03012, and Salinomycin. Our recent data suggest that a common effect of the above compounds appears to be the inhibition of mitochondrial functions. Moreover, ascorbic acid, an anti-oxidant, abolishes the effect of these compounds on MYCN protein stability. It is known that inhibition of mitochondrial oxidative phosphorylation increases the production of reactive oxygen species (ROS), which include superoxide (O2-), hydroxyl radical (•OH), and hydrogen peroxide (H2O2). Anti-oxidants are also known to quench ROS. Preliminary data showed that ROS was detected when the IMR5 NB cells were treated with OSU-03012 for three hours. In addition, we have found that forced over-expression of pVHL, an E3 ubiquitin ligase, in NB cell lines results in reduction of MYCN protein levels. We are currently testing whether ROS regulates MYCN stability by hydroxylation of proline residues on MYCN, and whether pVHL recognizes the ROS-modified MYCN, which is then subjected to rapid proteasome-dependent degradation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-142. doi:10.1158/1538-7445.AM2011-LB-142
Ischemic duodenitis without involvement of the large abdominal arteries
Authors: L. Korswagen, H. Voerman, J. Peterse
Journal: Endoscopy (2007)

An 80-year-old woman presented with weight loss and diffuse abdominal pain that was worse after meals. She had a history of diabetes, hypertension, chronic renal insufficiency and chronic lymphatic leukemia. Palpation of the right lower abdominal quadrant was painful. Laboratory investigations, abdominal ultrasound, and a barium enema of the colon revealed no relevant abnormalities.
Ischaemically induced alterations in electrical activity and mechanical performance of isolated blood perfused canine myocardial preparations
Authors: N. Himori, A. P Walls, A. M Burkman
Journal: Cardiovascular Research (1990)

Study objective – The aim was to investigate the direct effect of ischaemic insult on the electrical activity or mechanical performance of the sinoatrial node, atrioventricular node or Purkinje fibres (ventricular papillary muscle) of the dog heart. Design – The three isolated tissues independently mounted in a water jacketed glass container were cross circulated through their respective arteries at a constant pressure (120 mm Hg) with arterial blood from a heparinised supporting dog under sodium pentobarbitone anaesthesia. Rate of automatic rhythmical contractions (automaticity) or tension development was measured before, during, and after ischaemia (30 min). Experimental preparations – Seven sinoatrial nodes, five atrioventricular nodes, and 11 papillary muscles were prepared from the heart of mongrel dogs, weighing 11.5–15 kg. Measurements and main results – The automaticity of the sinoatrial node and atrioventricular node exhibited a high degree of resistance to ischaemia, whereas both the automaticity (Purkinje fibres) and the tension development of papillary muscle were more susceptible to ischaemia and ultimately disappeared during ischaemia. Upon resumption of the blood supply, contractility rapidly returned to preischaemic levels. However, force-frequency analyses revealed that even after reperfusion, papillary muscle had lost the ability to respond normally to stimulus frequencies greater than 2 Hz. Conclusions – The findings suggest (1) that in the special excitatory and conductive system, the more distal the segment is to the sinoatrial node, the more vulnerable it is to ischaemia; (2) that the myocardium impaired by ischaemic insult lacks functional reserve, as evidenced by enlargement of the differences between the alternate tensions of pulsus alternans; and (3) that cessation of the blood supply does not predominantly damage those tissues whose functions are mainly regulated by a slow inward calcium current.