tbuckley/cabot-search huggingface dataset:
Abstract 5132: Hypo-glycosylation of vascular endothelial growth factor receptor-1 may contribute to intracrine signaling in human colorectal cancer cells
Authors: Xiangcang Ye, Shaija Samuel, Yunfei Zhou, Fan Fan, Ling Xia, Jia Lu, Eric Sceusi, Federico Tozzi, Lee M. Ellis
Journal: Cancer Research (2011)

Abstract Introduction: Vascular endothelial growth factor receptor-1 (VEGFR-1) is highly expressed in endothelial cells, macrophages and cancer cells in the tumor microenvironment. VEGFR-1 plays an important role in tumor angiogenesis, inflammation and metastasis. In colorectal cancer (CRC) cells with hyperactive Wnt signaling, its function has been linked to cell motility, anchorage-independent growth, and cell survival. To better understand the role of VEGFR-1 in CRC, we performed studies to define the subcellular location and post-translational modifications of VEGFR-1 in human CRC cells. Methods/Results: Utilizing IHC analysis, GFP-tagged imaging and cell surface receptor assays, we observed that VEGFR-1 locates mostly in intracellular compartments in CRC cells, which is distinct from its membrane receptor status in endothelial cells. Moreover, spontaneous apoptosis was increased with endogenous VEGF knockout whereas treatment with the VEGF neutralizing antibody bevacizumab had no effect on apoptosis (Samuel et al. Oncogene, in press); these studies suggest that CRC cells require VEGF/VEGFR-1 intracrine signaling for suppression of apoptosis. In order to understand the means by which VEGFR-1 cellular localization is determined, we analyzed the glycosylation of VEGFR-1 in CRC cells, endothelial cells and clinical specimens of metastatic CRC from the liver. We found that VEGFR-1 is partially N-glycosylated by high mannose oligosaccharides in the CRC cells and human tumors, in contrast to complex, mature N-glycosylation of VEGFR-1 in the endothelial cells and normal liver tissue. Conclusion: VEGFR-1 is differentially post-translationally modified and intracellularly localized in CRC cells and metastatic tumors. Because N-glycosylation is critical for the membrane receptor's intracellular trafficking and ligand interaction on the cell surface, hypo-glycosylation of VEGFR-1 in CRC cells likely contributes to its cytoplasmic localization and intracrine activation through a non-RTK pathway. The implications of intracrine function of VEGFR-1 in CRC warrant further investigation. 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 5132. doi:10.1158/1538-7445.AM2011-5132
Topographic Analysis of Proliferative Activity in Carotid Endarterectomy Specimens by Immunocytochemical Detection of the Cell Cycle–Related Antigen Ki-67
Authors: Richard Brandl, Thomas Richter, Klaus Haug, Manfred G. Wilhelm, Peter C. Maurer, Walter Nathrath
Journal: Circulation (1997)

Background On the basis of contradictory results found in animal experiments and coronary atherectomy tissue, there is an ongoing debate about the significance of cellular proliferation in human atherosclerosis. In the present prospective study, the cell cycle–related antigen Ki-67 was detected for topographic determination of cell turnover in distinct regions of human carotid endarterectomy specimens harvested en bloc by surgical biopsy. Methods and Results After en bloc resection, serial sections of 26 consecutive carotid lesions were analyzed by histomorphological examination and immunohistochemistry. Thereby, 319 high-power fields were attributed to separate plaque regions defined as follows: distal boundary of the lesion with normal intima, plaque shoulder, core region, and diffuse intimal thickening. Endothelial cells, smooth muscle cells, T cells, and macrophages were identified by immunostaining of factor VIII–related protein, α-actin, CD68, and CD45R0. An overall proliferation index of 0.49±1.05% was yielded by positive anti–Ki-67 immunolabeling, predominantly in macrophage-rich areas characterized by high cell density (&gt;1000 cells/mm 2 ) as well as in reparative sites in the perimeter of atheroma, intramural thrombosis, plaque hemorrhage, and neovascularization (P&lt;.01). Few or no signs of proliferation activity were found in normal intima, in areas of dense α-actin positivity, or adjacent media. As shown by double immunostaining, macrophages and unspecified mesenchymal cells represented the prevailing proliferating cell type. Conclusions Our results suggest that proliferation in advanced human carotid lesions is confined to the intima and focally concentrated in central plaque regions negative for α-actin. Furthermore, it apparently occurs primarily as part of inflammatory processes and structural repair predominantly involving macrophages, as well as unspecific mesenchymal cells.
The Acute Respiratory Distress Syndrome
Authors: L B Ware, M A Matthay
Journal: New England Journal of Medicine (1996)

Acute respiratory distress syndrome (ARDS) continues to be a major cause of morbidity and mortality in critically ill patients. In this issue of the Journal, Anzueto et al.1 report the results of a large, multicenter, randomized trial that was carried out to evaluate the potential benefit of aerosolized surfactant therapy in patients with ARDS. Disappointingly, there was no benefit. It is important to analyze the results of this trial carefully, so that the possibility of success in future trials can be maximized.Although the cellular and molecular mechanisms that cause injury to the lung may not be the same in . . .
The Coronary Artery
Authors: Mark D. Altschule
Journal: JAMA (1983)

This book consists of 28 chapters, 25 of them reviews of recent findings in one area or another of arterial biochemistry and physiology. The authors of the individual scientific reviews have themselves worked in the separate fields and show themselves to be informed of the work of others. The reviews range in quality from good to excellent. Clinical medicine is a concern of the three terminal chapters on regression of atherosclerosis, limitations of infarct size, and coronary artery surgery as described in the clinical literature of a few years ago. Physicians will not find in these chapters definitive conclusion on these controversial matters. There are reservations as regard each scientific review and the book as a whole. With respect to the reviews, several matters deserve mention. It takes time to prepare a book for publication, and in a work created by many authors the convoy system must prevail: the slowest
Inquiry into Welsh E coli outbreak opens in Cardiff
Authors: Roger Dobson
Journal: BMJ (2006)

A public inquiry into the South Wales outbreak of Escherichia coli opened in Cardiff last week. The outbreak led to the death of a 5 year old and to 150 other people being taken ill.

Hugh Pennington, professor emeritus of medical microbiology at Aberdeen University, who has been appointed to lead the inquiry, said that it would be independent, and inquisitorial rather than adversarial.

“It is a means of seeking out the facts in a way that would …
HCV core expression in hepatocytes protects against autoimmune liver injury and promotes liver regeneration in mice
Authors: Hiroki Kawamura, Sugantha Govindarajan, Fred Aswad, Keigo Machida, Michael M.C. Lai, Vicky M.‐H. Sung, Gunther Dennert
Journal: Hepatology (2006)

Hepatitis C virus (HCV) infection causes acute and chronic liver disease often leading to liver cirrhosis and hepatocellular carcinoma. Numerous studies have shown that despite induction of virus specific immunity, a curative response is often not attained; this has led to the hypothesis that HCV genes modulate immunity, thereby enabling chronic infections. This study examined the effects on immune-mediated liver injury in transgenic mice expressing core protein throughout the body and bone marrow chimeras expressing core protein in either the lymphoid compartment or liver parenchyma. Presence of core protein in the liver parenchyma but not in lymphoid cells protects from autoimmune hepatitis induced by mitogen concanavalin A (ConA). Consistent with this observation, core transgenic hepatocytes are relatively resistant to death induced by anti-Fas antibody and tumor necrosis factor alpha (TNFalpha). This protective effect is associated with preferential activation of signal transducer and activation of transcription factor 3 (STAT3) versus STAT1 in livers of ConA-injected animals. In agreement with this effect of core protein on the Janus kinase (JAK)-STAT signaling pathway, transgenic mice accelerate liver regeneration after partial hepatectomy but are not protected from hepatocyte death. In conclusion, HCV core inhibits STAT1 and stimulates STAT3 activation, which protects infected hepatocytes from attack by the cell-mediated immune system and promotes their proliferation.
An in Vitro Test of Cellular Immunity in Allergic Encephalomyelitis.
Authors: George E. Seiden
Journal: Annals of Internal Medicine (1966)

s1 May 1966An in Vitro Test of Cellular Immunity in Allergic Encephalomyelitis.George E. Seiden, M.D., F.A.C.P.George E. Seiden, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1168_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA sensitive method was developed for measuring cytotoxic effects produced by lymphoid cells harvested from rats with allergic encephalomyelitis. Allergic encephalomyelitis was produced by immunizing Lewis rats with 2.5 µg of Kies protein emulsified with Freund's complete adjuvant. Peritoneal cells were harvested 10 to 14 days after immunization. Harvested cells from specifically immunized rats were compared for cytopathic effect with equal numbers of control nonspecifically sensitized peritoneal cells. Cytopathic effect was measured by interacting lymphoid cells with HeLa or L cells, which had been grown in the presence of14C thymidine and subsequently "coated" with a solution of Kies protein... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: George E. Seiden, M.D., F.A.C.P.Affiliations: Bronx, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1168-1168KeywordsCellsEncephalomyelitisImmunityLymphocytesProteinsThymidines ePublished: 1 December 2008 Issue Published: 1 May 1966 PDF downloadLoading ...
Findings for looked after children are not generalisable
Authors: B. Farrell
Journal: BMJ (2003)

EDITOR—Hill et al's paper on meningococcal C immunisation in looked after children showed that looked after children were more than twice as likely not to receive meningococccal vaccine as were children at home.1 They say that their findings are likely to be generalisable. This is not the case.

As part of …
Functionally restricted, allospecific, human helper T cell lines that amplify either B cell or cytolytic T cell responses.
Authors: S M Friedman, G S Thompson
Journal: The Journal of Experimental Medicine (1983)

Using a panel of partially cloned, OKT4+, DRw-1-specific, alloproliferative human T cell lines, we have identified two functionally restricted and reciprocating types of helper T cells. One provides major histocompatibility complex-restricted help for plaque-forming cell responses by DRw 1+ allogeneic B cells; the other preferentially amplifies the generation of allospecific cytotoxic T lymphocytes (CTL) from CTL precursors that have been suboptimally triggered by alloantigen.
Smoking and Atherosclerotic Cardiovascular Disease in Men With Low Levels of Serum Cholesterol
Authors: Sun Ha Jee, Il Suh, Il Soon Kim, Lawrence J. Appel
Journal: JAMA (1999)

Few studies have examined the interactive effects of smoking and serum cholesterol level on morbidity and mortality from cardiovascular dieseases. In East Asia, where the prevalence of smoking is among the highest in the world, morbidity and mortality from ischemic heart disease (IHD) is rapidly escalating.To determine whether cigarette smoking is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD) in the Republic of Korea (South Korea), a population that has relatively low levels of serum cholesterol, and to determine whether serum cholesterol levels modify the risk relationship between smoking and ASCVD.Prospective cohort study with a follow-up period of 6 years (1993-1998).A total of 106745 Korean men aged 35 to 59 years who received health insurance from the Korea Medical Insurance Corporation and who had biennial medical evaluations in 1990 and 1992.Hospital admissions and deaths from IHD, cerebrovascular disease (CVD), and total ASCVD.At baseline, 61389 (58%) were current cigarette smokers and 64482 (60%) had a total cholesterol level of less than 5.17 mmol/L (200 mg/dL). Between 1993 and 1998, 1006 IHD events (176 per 100000 person-years), 1364 CVD events (238 per 100000 person-years), and 716 other ASCVD events (125 per 100000 person-years) occurred. In multivariate Cox proportional hazard models controlling for age, hypertension, hypercholesterolemia, and diabetes, current smoking increased the risk of IHD (risk ratio [RR], 2.2; 95% confidence interval [CI], 1.8-2.8), CVD (RR, 1.6; 95% CI, 1.4-1.8), and total ASCVD (RR, 1.6; 95% CI, 1.5-1.8). For each outcome, there were significant dose-response relationships with amount and duration of smoking. Throughout the range of serum cholesterol levels, current smoking significantly increased the risk of IHD and CVD. In the lowest quartile of serum cholesterol levels (<4.42 mmol/L [171 mg/dL]), the RR from current smoking was 3.3 (95% CI, 1.7-6.2) for IHD and 1.6 (95% CI, 1.2-2.3) for CVD. There was no evidence of an interaction between smoking and serum cholesterol (P for interaction = .75, .87, and .92 for IHD, CVD, and total ASCVD, respectively).This study demonstrates that in Korea smoking is a major independent risk factor for IHD, CVD, and ASCVD and that a low cholesterol level confers no protective benefit against smoking-related ASCVD.
Consultants' attitude of mind criticised Standards advisory group should have a higher profile BMA says that learning should be student centred Labour party wants investigation into negligence claims BMA calls for end to pension discrimination
Authors: L. Beecham
Journal: BMJ (1995)

# Consultants' attitude of mind criticised {#article-title-2}

Consultants need to make “a culture change in their minds,” according to a parliamentary select committee in a report last week. It says that it is time that all consultants were aware of the need to work with others in the provision of complete and effective care.

The committee, which shadows the work of the health service ombudsman, was commenting on a case where a consultant surgeon in Walsall failed to tell anyone that he suspected cancer in a patient who died, although nurses reassured relatives about his recovery (BMJ 1994;309:1461). In their report the MPs say that they were appalled to come across such haphazard arrangements. It was the consultant's responsibility to ensure that effective communication of the suspected diagnosis took place. Dealing with patients suffering from terminal illness, and with their relatives, demands the utmost care and sensitivity, they state—recommending that all health authorities and trusts be reminded of the need for clear instructions on communicating with relatives through all stages of serious illness.

At the heart of the failings in the Walsall case was the unwillingness of the consultant and chief executive to accept the full extent of their responsibilities. The MPs conclude: “We see the need for a culture change in the minds of many of the consultants who appear before us.”

In another case they recommend a national initiative to train accident and emergency staff in the needs of mental health patients. This follows the death of …
Post-ischemic myocardial fibrosis occurs independent of hemodynamic changes
Authors: T Tsuda
Journal: Cardiovascular Research (2003)

Myocardial fibrosis is a major component of ventricular remodeling after large myocardial infarction (MI). The present study tests the hypothesis that post-ischemic myocardial fibrosis can occur independent of hemodynamic changes.A mouse model of distal left coronary artery ligation was established to induce a small infarct (less than 15% of the left ventricle) in order to avoid significant mechanical overload after permanent myocardial ischemia. Left heart catheterization was performed to evaluate the post-infarct hemodynamics. Tissues from both ischemic and non-ischemic myocardium were examined for mRNA and protein expression at 24, 72 h and 7 days after ligation.Heart/body weight ratio after ligation was increased by approximately 10% over sham control although there is no statistically significant difference in hemodynamic parameters between the two groups. Non-ischemic myocardium distant from the infarct site showed molecular evidence of myocardial fibrosis 72 h and 7 days after ligation. There was marked up-regulation of mRNAs for extracellular matrix (ECM) proteins and their cross-linking enzyme, such as collagens type I, III and VI, and lysyl oxidase. Immunohistochemical study confirmed that the expression of these ECM proteins was significantly increased in the non-ischemic myocardium after 7 days. TGF-beta1 was up-regulated after 72 h in both ischemic and non-ischemic myocardium.Molecular and histopathological findings demonstrate that abnormal myocardial fibrosis can be induced by a small infarct independent of secondary hemodynamic changes.
Dipstick urinalysis screening of asymptomatic adults for urinary tract disorders. II. Bacteriuria
Authors: Richard J. Pels, David H. Bor, Steffie Woolhandler, David U. Himmelstein, Robert S. Lawrence
Journal: JAMA (1989)

Using criteria adopted by the US Preventive Services Task Force, we evaluated use of the dipstick urinalysis to screen for bacteriuria. When the leukocyte esterase and nitrite dipstick tests are combined, the positive predictive value for detecting bacteriuria exceeded 12% in groups with a 5% or higher prevalence of bacteriuria: women who are pregnant, diabetic, or over 60 years of age and all institutionalized elderly. Conventional antimicrobial regimens for asymptomatic bacteriuria have proved efficacious only for pregnant women. We conclude that pregnant women should be screened for bacteriuria, but with the more sensitive urine culture, because treatment prevents serious fetal and maternal sequelae. Dipstick screening may be justified in women who are over 60 years of age or diabetic. The prevalence of bacteriuria in other groups is too low to justify screening.
The Human Psyche
Authors: Sidney Schulman
Journal: JAMA (1981)

<i>The Human Psyche</i>is the second series of ten Gifford Lectures delivered at the University of Edinburgh by Sir John Eccles in 1979. The first set of ten, given in 1978, has been published separately under the title<i>The Human Mystery</i>. The combined lectures present a wide-ranging survey of the present state of understanding of the origin of the universe, of life, and the evolution of man and human culture in the first volume, and the physiology of the brain in the second. There is no question that<i>The Human Psyche</i>will be useful to anyone wishing a quick overview of some of the themes of contemporary research on the physiology of the nervous system from someone who has contributed immensely to the field. But the overview is very quick. One is plunged into one complex set of observations and data after another, each covered by a few paragraphs and
Enhanced coronary vasoconstriction in the Syrian myopathic hamster supports the microvascular spasm hypothesis
Authors: R. S Conway, B. H Natelson, W. H. Chen, W. Ting
Journal: Cardiovascular Research (1994)

Journal Article Enhanced coronary vasoconstriction in the Syrian myopathic hamster supports the microvascular spasm hypothesis Get access Robert S Conway, Robert S Conway Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place – CN19, New Brunswick, NJ 08903, USA: R S Conway, W H Chen, W Ting; Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA: B H Natelson. Correspondence to Dr Conway. Search for other works by this author on: Oxford Academic PubMed Google Scholar Benjamin H Natelson, Benjamin H Natelson Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place – CN19, New Brunswick, NJ 08903, USA: R S Conway, W H Chen, W Ting; Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA: B H Natelson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Wen Hwei Chen, Wen Hwei Chen Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place – CN19, New Brunswick, NJ 08903, USA: R S Conway, W H Chen, W Ting; Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA: B H Natelson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Windsor Ting Windsor Ting Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, 1 Robert Wood Johnson Place – CN19, New Brunswick, NJ 08903, USA: R S Conway, W H Chen, W Ting; Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA: B H Natelson. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 28, Issue 3, March 1994, Pages 320–324, https://doi.org/10.1093/cvr/28.3.320 Published: 01 March 1994 Article history Received: 27 May 1993 Accepted: 28 September 1993 Published: 01 March 1994