tbuckley/cabot-search huggingface dataset:
Abstract B42: Dichotomus role of profilin in early vs. late steps of breast cancer metastasis
Authors: Partha Roy
Journal: Cancer Research (2013)

Abstract Profilin1 (Pfn1), an essential control element for actin polymerization, plays indispensable role in migration and proliferation of normal cells. Seemingly contrary to these essential cellular functions of Pfn1, its expression is downregulated in breast cancer, the significance of which is unclear. In this study, expression profiling of Pfn1 in human breast cancer specimens of various histopathological stages correlate lower Pfn1 expression levels with propensity to metastasize. Xenograft studies uncover a unique dichotomous role of Pfn1 in early vs late steps of breast cancer metastasis. Specifically, loss of Pfn1 expression promotes dissemination of breast cancer cells from the primary mammary tumor but metastatic colonization of breast cancer cells is critically dependent on Pfn1's function. In the context of dissemination, breast cancer cells exhibit increased sustenance of PI3K signaling and acquire a hyper-invasive phenotype (marked by MMP9 upregulation, faster invasion through collagen matrix) involving a PI3K-PI(3,4)P2 signaling axis when Pfn1 expression is suppressed. In addition, Pfn1-deficient breast cancer cells display increased proficiency to cross through an endothelial cell barrier (an obligatory step for vascular dissemination) in a VEGF-dependent manner, respectively. Gene expression profiling combined with biochemical analyses of secreted proteins show that loss of Pfn1 impacts expression of several other pro-invasive and pro-metastatic genes. Finally, correlated with hyper-invasive phenotype of breast cancer cells caused by Pfn1 depletion, we found that mammary-specific deletion of Pfn1 gene expedites ductal outgrowth. In summary, contrasting the well-established pro-migratory role of Pfn1 in the physiological contexts, our findings set the first in vivo example of a context-specific effect of loss of Pfn1 in cell motility-dependent processes such as mammary gland morphogenesis and metastatic dissemination. Citation Format: Partha Roy. Dichotomus role of profilin in early vs. late steps of breast cancer metastasis. [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 B42.
Noncontraceptive Estrogens and Abnormalities of Endometrial Proliferation
Authors: NOEL S. WEISS
Journal: Annals of Internal Medicine (1978)

Use of estrogen preparations among menopausal women has been causally associated with the development of hyperplasia and adenocarcinoma of the endometrium. The magnitude of the association seems to be greater for the hyperplastic and least aggressive malignant lesions, and smaller for tumors of higher stage and grade. This observed inverse relation of estrogen use to degree of malignancy is probably due to relatively early or overly liberal diagnoses of endometrial cancer among estrogen users, but could mean simply that estrogens promote less aggressive tumors. It appears the current increased incidence of endometrial cancer in the United States will not be followed by a corresponding increase in mortality from the disease.
HLA class II genes in primary sclerosing cholangitis and chronic inflammatory bowel disease: no HLA-DRw52a association in Swedish patients with sclerosing cholangitis.
Authors: H Zetterquist, U Broome, K Einarsson, O Olerup
Journal: Gut (1992)

The familial predisposition to chronic inflammatory bowel disease and the increased concordance rate in monozygotic twins with Crohn9s disease, suggest that genetic factors influence disease susceptibility. A 100% association with the supertypic HLA class II specificity DRw52a was recently described in white North American patients with primary sclerosing cholangitis, with or without concurrent ulcerative colitis. HLA class II alleles of the DR, DQ, and DP subregions were determined by genomic typing techniques in a large group of Swedish patients with ulcerative colitis or Crohn9s disease as well as in a series of patients with primary sclerosing cholangitis. No statistically significant HLA class II association was observed in any of the investigated diseases or when the patients were subgrouped according to disease site or occurrence of extraintestinal manifestations, except an insignificant increase of the DRw17, DQw2 haplotype in patients with primary sclerosing cholangitis. The failure to confirm the well established DRw17 association in Swedish patients with sclerosing cholangitis probably represents a statistical type II error. Furthermore, this study did not verify the recently described strong DRw52a association in sclerosing cholangitis--52% of the patients were DRw52a positive compared with 28% of the controls (p less than 0.05, pc NS). This discrepancy was probably caused by different typing techniques. The DRw52a specificity was determined directly by hybridising HLA-DRB3 genes, group specifically amplified by the polymerase chain reaction, with an allele specific oligonucleotide probe, whereas in the previously mentioned study DRw52a was assigned by indirect serological criteria, which overestimate the frequency of this allele.
The vascular endothelial growth factor receptor KDR/Flk-1 is a major regulator of malignant ascites formation in the mouse hepatocellular carcinoma model
Authors: Hitoshi Yoshiji, Shigeki Kuriyama, Daniel J. Hicklin, James Huber, Junichi Yoshii, Yasuhide Ikenaka, Ryuichi Noguchi, Toshiya Nakatani, Hirohisa Tsujinoue, Hiroshi Fukui
Journal: Hepatology (2001)

The vascular endothelial growth factor-A (VEGF-A), also known as the vascular permeability factor (VPF), has been shown to play an important role in malignant ascites formation. The effects of VEGF-A are mediated through flt-1 and kinase insert domain-containing receptor/fetal liver kinase (KDR/Flk-1) receptors. It has been shown that KDR/Flk-1 is a predominant receptor in solid hepatocellular carcinoma (HCC) development, but the role of this receptor in hepatic ascites formation has not yet been elucidated. In this study, we examined the role of KDR/Flk-1 in the murine MH134 hepatic malignant ascites formation by means of VEGF-A- and KDR/Flk-1-specific neutralizing antibodies (VEGF-A nAb and KDR/Flk-1 nAb, respectively). The mean volume of ascites, number of tumor cells in ascites, and the peritoneal capillary permeability were significantly suppressed by VEGF-A nAb and KDR/Flk-1 nAb treatment. These inhibitory effects of KDR/Flk-1 nAb were more potent than those of VEGF-A nAb. The autophosphorylation of KDR/ Flk-1 in the peritoneal wall was almost completely abolished by KDR/ Flk-1 nAb, whereas a certain level of activation was still shown by VEGF-A nAb treatment. Another VEGF-family, VEGF-C, which also binds KDR/Flk-1, was detected in the ascites. Furthermore, in the therapeutic experiment, although both VEGF-A nAb and KDR/Flk-1 nAb prolonged the survival rate of ascites-bearing mice, the latter showed a more significant impact on the survival of animals. These results suggest that KDR/Flk-1 is a major regulator of malignant hepatic ascites formation, and that in addition to VEGF-A, VEGF-C may also be involved in the malignant ascites formation via KDR/ Flk-1 activation.
David Gordon Sim
Authors: Fiona M Sim
Journal: BMJ (2004)

Former general practitioner Southend-on-Sea (b Edinburgh 1913; q Edinburgh 1938), d 18 June 2004.

In 1939 David joined the Royal Army Medical Corps. He served throughout the second world war as an officer, including as a “desert rat” in the 8th Army under Montgomery. Probably the event that touched him most during his army career was the liberation of Bergen-Belsen. In 1947 he set up in practice in Southend-on-Sea, initially singlehanded and later in partnership, until his retirement in 1978. He leaves a wife and two daughters.
Ruptured Baker's Cyst and Thrombophlebitis
Authors: Alfred Miller
Journal: JAMA (1979)

To the Editor.—  The article entitled Ruptured Baker's Cyst Simulating Acute Thrombophlebitis (240:1517, 1978) serves to heighten my suspicion of a possible ruptured Baker's cyst when considering the condition of a patient with an apparent clinical picture of thrombophlebitis. However, in the past two years I have had three patients with a similar clinical picture, and in all three the diagnosis of ruptured Baker's cyst and concomitant thrombophlebitis existed. These diagnoses were established and confirmed using phlebograms and arthrograms.  Therefore, I would encourage the use of both arthrograms and phlebograms in such patients instead of having the diagnosis of ruptured Baker's cyst established without the secure elimination of the diagnosis of thrombophlebitis and its potentially disastrous sequelae. In all three of these patients the thrombophlebitis was treated in the conventional manner, and the ruptured Baker's cyst did not require surgery.  I suspect that the Baker's cysts compress the venous return
A CASE OF PYOSALPINX IN A YOUNG GIRL, WITH SPECIMENS AND REMARKS ON SPECIAL SURGICAL TECHNIQUE.
Authors: HENRY L. E. JOHNSON
Journal: JAMA (1897)

I have the honor of presenting for your consideration an interesting case of pyosalpinx in a young girl, for the relief of which laparotomy was performed one year ago. Miss—consulted me in the early part of November of last year, giving the following history of her disease, the cause of which is quite direct: She was white, single, 19 years of age, and had always enjoyed good health, the present being her first serious illness. Family, social and moral history excellent. In August, 1895, she visited the sea-shore, where she bathed daily. When she was over-heated from walking on one occasion she entered the surf, which was rather cold, during the first day of a menstrual period, remaining two hours, and while there she was taken with violent uterine tenesmus and pain in the lower portion of the abdomen, particularly in the right inguinal regions. The flow ceased suddenly and
Second Opinions for Patients Recommended for Coronary Angiography
Authors: Ronald Feldman
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The article by Graboys et al<sup>1</sup>brought forth a spate of dissenting Letters to the Editor in<i>JAMA</i>. The letter from Dr Schneider<sup>2</sup>inadvertently focuses on what I believe to be the major problem that leads to the overuse of coronary angiography and other high-tech procedures (which are also high-cost), such as magnetic resonance imaging, computed tomography, vascular laboratories, and special blood tests. He says, "Coronary angiography has become the cornerstone of both the accurate diagnosis and clinical management of patients suspected of having coronary artery disease." Few would deny that angiography is the criterion standard, but the cornerstone of diagnosis was, is, and shall always be a detailed history and careful physical. Appropriate noninvasive tests may be added, and only in the most unusual instance is angiography necessary for diagnosis. If it were reserved for those patients who were bona fide candidates for intervention
GRENZ RAYS IN DERMATOLOGY
Authors: Frederick Kalz
Journal: British Journal of Dermatology (1942)

Journal Article GRENZ RAYS IN DERMATOLOGY Get access Frederick Kalz, M.D. Frederick Kalz, M.D. Royal Victoria Hospital, Montreal Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 54, Issue 7, 1 July 1942, Pages 215–216, https://doi.org/10.1111/j.1365-2133.1942.tb10685.x Published: 01 July 1942
Proapoptotic effects of the chemokine, CXCL 10 are mediated by the noncognate receptor TLR4 in hepatocytes
Authors: Hacer Sahin, Erawan Borkham-Kamphorst, Nicole T. do O, Marie-Luise Berres, Michaela Kaldenbach, Petra Schmitz, Ralf Weiskirchen, Christian Liedtke, Konrad L. Streetz, Kathrin Maedler, Christian Trautwein, Hermann E. Wasmuth
Journal: Hepatology (2012)

Aberrant expression of the chemokine CXC chemokine ligand (CXCL)10 has been linked to the severity of hepatitis C virus (HCV)-induced liver injury, but the underlying molecular mechanisms remain unclear. In this study, we describe a yet-unknown proapoptotic effect of CXCL10 in hepatocytes, which is not mediated through its cognate chemokine receptor, but the lipopolysaccharide receptor Toll-like receptor 4 (TLR4). To this end, we investigated the link of CXCL10 expression with apoptosis in HCV-infected patients and in murine liver injury models. Mice were treated with CXCL10 or neutralizing antibody to systematically analyze effects on hepatocellular apoptosis in vivo. Direct proapoptotic functions of CXCL10 on different liver cell types were evaluated in detail in vitro. The results showed that CXCL10 expression was positively correlated with liver cell apoptosis in humans and mice. Neutralization of CXCL10 ameliorated concanavalin A-induced tissue injury in vivo, which was strongly associated with reduced liver cell apoptosis. In vitro, CXCL10 mediated the apoptosis of hepatocytes involving TLR4, but not CXC chemokine receptor 3 signaling. Specifically, CXCL10 induced long-term protein kinase B and Jun N-terminal kinase activation, leading to hepatocyte apoptosis by caspase-8, caspase-3, and p21-activated kinase 2 cleavage. Accordingly, systemic application of CXCL10 led to TLR4-induced liver cell apoptosis in vivo.The results identify CXCL10 and its noncognate receptor, TLR4, as a proapoptotic signaling cascade during liver injury. Antagonism of the CXCL10/TLR4 pathway might be a therapeutic option in liver diseases associated with increased apoptosis.
Researchers commit to greater openness on research involving animals in the UK
Authors: I. Torjesen
Journal: BMJ (2014)

Genetic fine mapping of the first locus identified for genetically complex forms of stroke, STRK1 (which has been mapped to chromosome 5q12 in Icelandic families), has identified the phosphodiesterase 4D gene (<i>PDE4D</i>) gene as a good candidate gene. Association analysis of single nucleotide polymorphisms (SNPs) in the <i>PDE4D</i> gene in an Icelandic stroke cohort demonstrated genetic association between six SNPs in the 5′ region of <i>PDE4D</i> and ischaemic stroke. The present study aimed to test whether the same six SNPs in <i>PDE4D</i> were also associated with stroke in a large stroke cohort from northern Germany (stroke patients with acute completed ischaemic stroke: n = 1181; population based controls: n = 1569). None of the six SNPs showed significant association with ischaemic stroke in the whole stroke sample before and after adjustment for conventional stroke risk factors (age, sex, hypertension, diabetes, and hypercholesterolaemia). Haplotype analysis did also not reveal any significant association. Marginally positive statistical measures of association in the subgroup with cardioembolic stroke did not remain significant after correction for multiple testing. In conclusion, this study was unable to demonstrate an association between the six SNPs which had showed significant single marker association with stroke in the Icelandic stroke cohort and ischaemic stroke in a large German cohort.
Atherosclerotic Plaque Burden and CK-MB Enzyme Elevation After Coronary Interventions
Authors: Roxana Mehran, George Dangas, Gary S. Mintz, Alexandra J. Lansky, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent, Gregg W. Stone, Martin B. Leon
Journal: Circulation (2000)

Background —Elevation of serum creatine kinase MB fraction (CK-MB) after percutaneous coronary interventions has been associated with early and late mortality; however, the pathogenesis of CK-MB elevation is still unknown. We hypothesized that CK-MB elevation was related to atherosclerotic plaque burden as assessed by preintervention intravascular ultrasound (IVUS). Methods and Results —We studied 2256 consecutive patients who underwent intervention of 2780 native coronary lesions and had complete high-quality preintervention IVUS imaging in the era before routine use of platelet glycoprotein IIb/IIIa inhibitors. Patients were divided into 3 groups: CK-MB within normal range (1675 patients; 2061 lesions); CK-MB elevation 1 to 5 times upper limit of normal (292 patients; 355 lesions); and CK-MB elevation ≥5 times upper limit of normal (289 patients; 364 lesions). Qualitative angiographic lesion morphology and quantitative analysis were similar among the 3 groups. On preintervention IVUS, progressively more reference segment and lesion site plaque burden and lesion site calcium occurred in the groups with CK-MB elevation. Positive remodeling was more common in lesions with CK-MB elevation. As levels of CK-MB increased, cross-sectional narrowing (percentage plaque burden) increased, both at the reference site (mean cross-sectional narrowing values were 45.1%, &lt;49.3%, and &lt;52.2% for normal CK-MB, 1 to 5 times upper limit of normal, and ≥5 times upper limit of normal groups, respectively; P =0.03) and at the lesion site (81.9%, &lt;85.4%, and &lt;87.1%, respectively; P =0.04). Multivariate analysis indicated that de novo lesions, atheroablative technique, plaque burden at the lesion and reference segments, and final minimal lumen diameter were independent predictors of CK-MB elevation. Conclusions —CK-MB elevation correlates with a greater atherosclerotic plaque burden. CK-MB elevation after intervention may be a marker of diffuse atherosclerotic disease or a consequence of catheter-based intervention in more diseased arteries or both.
A Polymer-Based, Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease
Authors: Gregg W. Stone, Stephen G. Ellis, David A. Cox, James Hermiller, Charles O'Shaughnessy, James Tift Mann, Mark Turco, Ronald Caputo, Patrick Bergin, Joel Greenberg, Jeffrey J. Popma, Mary E. Russell
Journal: New England Journal of Medicine (2004)

Restenosis after coronary stenting necessitates repeated percutaneous or surgical revascularization procedures. The delivery of paclitaxel to the site of vascular injury may reduce the incidence of neointimal hyperplasia and restenosis.At 73 U.S. centers, we enrolled 1314 patients who were receiving a stent in a single, previously untreated coronary-artery stenosis (vessel diameter, 2.5 to 3.75 mm; lesion length, 10 to 28 mm) in a prospective, randomized, double-blind study. A total of 652 patients were randomly assigned to receive a bare-metal stent, and 662 to receive an identical-appearing, slow-release, polymer-based, paclitaxel-eluting stent. Angiographic follow-up was prespecified at nine months in 732 patients.In terms of base-line characteristics, the two groups were well matched. Diabetes mellitus was present in 24.2 percent of patients; the mean reference-vessel diameter was 2.75 mm, and the mean lesion length was 13.4 mm. A mean of 1.08 stents (length, 21.8 mm) were implanted per patient. The rate of ischemia-driven target-vessel revascularization at nine months was reduced from 12.0 percent with the implantation of a bare-metal stent to 4.7 percent with the implantation of a paclitaxel-eluting stent (relative risk, 0.39; 95 percent confidence interval, 0.26 to 0.59; P<0.001). Target-lesion revascularization was required in 3.0 percent of the group that received a paclitaxel-eluting stent, as compared with 11.3 percent of the group that received a bare-metal stent (relative risk, 0.27; 95 percent confidence interval, 0.16 to 0.43; P<0.001). The rate of angiographic restenosis was reduced from 26.6 percent to 7.9 percent with the paclitaxel-eluting stent (relative risk, 0.30; 95 percent confidence interval, 0.19 to 0.46; P<0.001). The nine-month composite rates of death from cardiac causes or myocardial infarction (4.7 percent and 4.3 percent, respectively) and stent thrombosis (0.6 percent and 0.8 percent, respectively) were similar in the group that received a paclitaxel-eluting stent and the group that received a bare-metal stent.As compared with bare-metal stents, the slow-release, polymer-based, paclitaxel-eluting stent is safe and markedly reduces the rates of clinical and angiographic restenosis at nine months.
And Then There Were None
Authors: George D. Lundberg
Journal: JAMA (1995)

In the summer of 1993, three national medical television networks existed: Lifetime Medical Television, Medical News Network, and American Medical Television. In August 1993, Lifetime Medical Television ceased operations after nearly 10 years of significant educational service. And then there were two. In August 1994, Medical News Network was cancelled, after having never really gotten off the ground except in elaborate program development and national market testing. And then there was one. In December 1994, after 5 years of successful programming for physicians, other health professionals, and patients, first on the Discovery Channel, and then on CNBC, the owners of American Medical Television (NBC Cable, the American Medical Association, the Orbis Broadcast Group, and Dr Art Ulene) voted to dissolve the partnership, ceasing operations before February 1995.<sup>1</sup>And then there were none. As with any complex venture, the reasons for these failures were complex. But the common reason was
The general practitioner's role
Authors: A. Douglas
Journal: BMJ (1995)

In commenting on this article, I am conscious of the dangers of drawing conclusions from only one side of the story, and so I shall concentrate on some general issues raised.

Firstly, who is the patient? M's needs are the subject of the letter and are the responsibility of the doctors caring for her. Her parents, however, will have needs of their own, and attempts should be made to ensure that the two are not confused. Both will need to be addressed but not necessarily by the same professional.

Decisions about treatment are ideally taken by the patient based on advice from doctors …
Reducing Plantar Pressure in the Neuropathic Foot: A comparison of footwear
Authors: Lawrence A Lavery, Steven A Vela, John G Fleischli, David G Armstrong, David C Lavery
Journal: Diabetes Care (1997)

OBJECTIVE To compare the effectiveness of therapeutic, comfort, and athletic shoes with and without viscoelastic insoles. RESEARCH DESIGN AND METHODS We compared pressure reduction at ulcer sites under the hallux (n = 10), first metatarsal (n = 10), and lesser metatarsals (n = 12), using extra-depth, athletic, and comfort shoes with and without viscoelastic insoles. A rubber-soled canvas oxford was used to establish baseline pressure values. RESULTS When used in conjunction with a viscoelastic insole, all shoe types reduced mean peak plantar pressure better than their non-insoled counterparts (P &amp;lt; 0.05). Consistently, comfort shoes reduced pressure significantly better than both the cross trainers and extra-depth shoes for ulcers under the first and lesser metatarsals (P &amp;lt; 0.05). For each shoe type, the addition of the viscoelastic insole provided a significant reduction in mean peak pressure (P &amp;lt; 0.05). Compared with stock insoles, viscoelastic insoles reduced pressures an additional 5.4-20.1% at ulcer sites. The same trend was also observed at regions of the foot not associated with an ulceration. CONCLUSIONS When used in conjunction with a viscoelastic insole, both the comfort and athletic cross-trainer shoes studied were as, if not more, effective than commonly prescribed therapeutic shoes in reducing mean peak first and lesser metatarsal pressures. Furthermore, comfort shoes were as effective as therapeutic shoes in reducing pressure under the great toe. Both of these shoe types may be viable options to prevent the development or recurrence of foot ulcers.