tbuckley/cabot-search huggingface dataset:
Matrix metalloproteinase (MMP)-9: A proximal biomarker for cardiac remodeling and a distal biomarker for inflammation
Authors: Ganesh V. Halade, Yu-Fang Jin, Merry L. Lindsey
Journal: Pharmacology & Therapeutics (2013)

Adverse cardiac remodeling following myocardial infarction (MI) remains a significant cause of congestive heart failure. Additional and novel strategies that improve our ability to predict, diagnose, or treat remodeling are needed. Numerous groups have explored single and multiple biomarker strategies to identify diagnostic prognosticators of remodeling progression, which will improve our ability to promptly and accurately identify high-risk individuals. The identification of better clinical indicators should further lead to more effective prediction and timely treatment. Matrix metalloproteinase (MMP-9) is one potential biomarker for cardiac remodeling, as demonstrated by both animal models and clinical studies. In animal MI models, MMP-9 expression significantly increases and is linked with inflammation, diabetic microvascular complications, extracellular matrix degradation and synthesis, and cardiac dysfunction. Clinical studies have also established a relationship between MMP-9 and post-MI remodeling and mortality, making MMP-9 a viable candidate to add to the multiple biomarker list. By definition, a proximal biomarker shows a close relationship with its target disease, whereas a distal biomarker exhibits non-targeted disease modifying outcomes. In this review, we explore the ability of MMP-9 to serve as a proximal biomarker for cardiac remodeling and a distal biomarker for inflammation. We summarize the current molecular basis and clinical platform that allow us to include MMP-9 as a biomarker in both categories.
Newer Concepts Concerning Inflammation: Humoral Mechanisms.
Authors: Oscar D. Ratnoff
Journal: Annals of Internal Medicine (1965)

s1 May 1965Newer Concepts Concerning Inflammation: Humoral Mechanisms.Oscar D. Ratnoff, M.D.Oscar D. Ratnoff, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-62-5-1089_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA number of different humoral agents have been implicated in the pathogenesis of inflammation. Histamine, proposed by T. Lewis, increases vascular permeability and dilates blood vessels. Although it can be found in early inflammatory exudates, it cannot be detected at later stages of the inflammatory reaction. The biologically active polypeptide "kinins" increase vascular permeability, dilate blood vessels, induce pain, and attract leukocytes to the site of their injection, suggesting that these agents may also participate in the inflammatory reaction. The kinins may be elaborated in plasma through the action of a proteolytic enzyme, kallikrein. Kallikrein is normally present in plasma... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Oscar D. Ratnoff, M.D.Affiliations: Cleveland, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1965Volume 62, Issue 5Page: 1089-1090KeywordsBlood plasmaBlood vesselsEnzymesHistamineInflammationPathogenesisPolypeptidesVascular permeability ePublished: 1 December 2008 Issue Published: 1 May 1965 PDF downloadLoading ...
HIV infection: increase in public awareness and anxiety.
Authors: C Sonnex, A Petherick, M W Adler, D Miller
Journal: BMJ (1987)

Between the end of September and mid-November 1986 the number of patients who requested antibody testing for human immunodeficiency virus (HIV) at this department increased by over 300%. This increase followed a media campaign that emphasised the potential heterosexual spread of HIV. After pretest counselling roughly one quarter of the women and of the heterosexual men decided not to be tested. The reason given most often by women for testing was previous sexual intercourse with bisexual or possibly bisexual men. Heterosexual men were most often concerned about previous casual encounters or contact with prostitutes. Of the 641 tests for HIV antibody performed during the last three months of 1986, 37 (5-8%) were positive. Because an increasing number of patients are attending sexually transmitted diseases clinics for HIV antibody testing staffing levels in these clinics need to be reappraised now.
Angiosarcoma of the liver in Great Britain, 1963-73.
Authors: P J Baxter, P P Anthony, R N MacSween, P J Scheuer
Journal: BMJ (1977)

Deaths attributed to primary angiosarcoma of the liver (ASL) in Great Britain between 1963-73 were reviewed by submitting available histological material to a panel of histopathologists and by obtaining full occupational and residential histories for the cases agreed as ASL by the panel. On average four recorded cases of ASL occurred a year, but in only one-third of the cases submitted did the panel agree with the original diagnosis. Only one of the agreed cases could be confidently associated with exposure to vinyl chloride.
EXPERIMENTAL STUDIES ON THE ETIOLOGY OF TYPHUS FEVER
Authors: Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1922)

The results of the foregoing experiments show that the typhus virus, found in the blood of guinea pigs during the height of typical experimental typhus fever, does not survive at 37 degrees C. in anaerobic media for as long a period as in the same media under aerobic conditions. In media from which oxygen is excluded, the viability period is 24 to 48 hours; in the same media having no barrier to atmospheric oxygen, the period is usually 5 days, in one instance, 3 days. The dead virus fails to induce not only the typical experimental disease but also an immunity to further injections of typhus virus. That the death of the virus is due to exclusion of oxygen from the medium, rather than to a change in the hydrogen ion concentration therein is inferred from the fact that media with varying hydrogen ion concentrations, such as broth (pH 7.4), horse serum (pH 7.8), and human ascitic fluid (pH 8.0) have the same comparative effect on the virus, when under aerobic and anaerobic conditions. That is, in all, the anaerobic state causes a shortening of the viability period of the typhus virus. In the Smith-Noguchi tissue, ascitic fluid, sealed medium in which bacteria resembling Plotz' bacilli grow luxuriantly and remain viable for several weeks, the typhus virus does not increase in virulence, and even dies after 24 hours. This evidence supports the conclusion previously presented that the Bacillus typhi exanthematici of Plotz is not identical with the active agent of typhus virus.
International variations in the clinical, diagnostic, and treatment characteristics of emergency department patients with acute heart failure syndromes
Authors: Sean P. Collins, Peter S. Pang, Christopher J. Lindsell, Demetrios N. Kyriacou, Alan B. Storrow, Judd E. Hollander, J. Douglas Kirk, Chadwick D. Miller, Richard Nowak, W. Frank Peacock, Miguel Tavares, Alexandre Mebazaa, Mihai Gheorghiade
Journal: European Journal of Heart Failure (2010)
Associations Between Dietary Fiber and Inflammation, Hepatic Function, and Risk of Type 2 Diabetes in Older Men: Potential Mechanisms for the Benefits of Fiber on Diabetes Risk
Authors: S. Goya Wannamethee, Naveed Sattar
Journal: Diabetes Care (2010)

We thank Ghanim, Chaudhuri, and Dandona (1) for their interest in our article (2) and for providing some potential mechanisms linking a high-fiber diet with lower diabetes risk and anti-inflammatory …
Detection and Treatment of Ductal Carcinoma In Situ of the Breast-Reply
Authors: Virginia L. Ernster
Journal: JAMA (1996)

In Reply.  —We described the recent epidemic of DCIS, a breast lesion for which detection has increased with increased mammography utilization. Most reporters grasped the essential message that the increased detection of DCIS poses a clinical enigma and has probably resulted in considerable overtreatment. (Headlines ranged from Ability to Find a Tiny Tumor Poses a Dilemma in the New York Times to Some Breast Cancer May Be Overtreated in USA Today .)  There are no good data on the extent to which DCIS in young women leads to invasive cancer in older women. We did not suggest that these lesions are best left undetected but did say that,  a large proportion of cases of DCIS never become clinically apparent or life-threatening, it may be that many if not most women with mammographically detected DCIS will not benefit from treatment. Assuming that some women with DCIS eventually have their tumors progress to invasive
Abstract 4703: Genome &amp; exome analysis of early colon cancers reveals new targets
Authors: Avijit Majumdar, Jian Chen, Sue Hwa Lin, Lior Katz, Gottumukkala Subba Raju, Kirti Shetty, Jon White, Xifeng Wu, Asif Rashid, John S. McMurray, Kenna R. Shaw, Xiaoping Su, Brian Weston, Selvi Thirumurthi, Aiwu Ruth He, Lopa Mishra
Journal: Cancer Research (2014)

Abstract Introduction: Advanced colorectal cancer (CRC) remains lethal and difficult to treat with over 140,000 new cases a year in the United States. One contributing factor that has emerged is the rapid development of cancers in small, sessile adenomas(polyps) (less than 1cm), which might be overlooked. Results: Using whole genome and whole exome sequence (WGS) analyses of four pairs of colorectal adenoma (early CRC) tissue samples along with their normal counterparts, we observe dramatic genomic instability in two of the samples, suggesting that these two adenomas could be on the brink of overt CRC. We proceeded to analyze a further 20 samples through RNA sequence and/or immunohistochemical analysis. The two polyps are associated with hyper mutated profile of multiple genes including Carcinoembryonic antigen (CEA) and CEACAM6 in one of the samples. Analyses of the expression levels of CEA and TGF-β signaling pathway members in 20 early adenomas and normal colon tissues demonstrate a marked increase in CEA expression in 25% of adenoma samples linked to a concomitant loss of TGF-β signaling. We proceeded to mechanistic studies examining CEA and it role in inactivating the tumor suppressive arm of transforming growth factor-β (TGF-β) signaling, providing crucial new information for CEA in promoting aggressive CRC. We found that CEA interacts directly with the transforming growth factor-β (TGF-β) receptor 1 (TBR1) with inhibition of downstream TGF-β tumor suppressor signaling through its B3 domain. Moreover, we previously found that deletion of Smad3/4 adaptor β2SP results in loss of TGF-β signaling, with dramatic and spontaneous formation of adenomas as well as CRC. Ectopic expression of CEA also induces CRC metastases, potentially indirectly through activation of STAT3 and stimulating production of IL-6, IL-10 and others, in addition to inactivating TGF-β tumor suppressor signaling. Conclusions: Our data suggest that enhanced CEA levels and oncogenic mutations in the colon adenomas can be used as prognostic markers for early detection of aggressive CRC and the B3 domain of CEA can be targeted by monoclonal antibody/peptide inhibitors/small molecule inhibitors targeting CEA and CRC cell proliferation. Citation Format: Avijit Majumdar, Jian Chen, Sue Hwa Lin, Lior Katz, Gottumukkala Subba Raju, Kirti Shetty, Jon White, Xifeng Wu, Asif Rashid, John S. McMurray, Kenna R. Shaw, Xiaoping Su, Brian Weston, Selvi Thirumurthi, Aiwu Ruth He, Lopa Mishra. Genome &amp; exome analysis of early colon cancers reveals new targets. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4703. doi:10.1158/1538-7445.AM2014-4703
Explaining the Familial Colorectal Cancer Risk Associated with Mismatch Repair (MMR)-Deficient and MMR-Stable Tumors
Authors: Lauri Aaltonen, Louise Johns, Heikki Järvinen, Jukka-Pekka Mecklin, Richard Houlston
Journal: Clinical Cancer Research (2007)

Abstract Purpose: There is a paucity of data quantifying the familial risk of colorectal cancer associated with mismatch repair (MMR)-deficient and MMR-stable tumors. To address this, we analyzed a population-based series of 1,042 colorectal cancer probands with verified family histories. Experimental Design: Constitutional DNA from probands was systematically screened for MYH variants and those with cancers displaying microsatellite instability (MSI) for germ-line MMR mutations; diagnoses of familial adenomatous polyposis and juvenile polyposis were established based on clinical phenotype and mutational analysis. Familial colorectal cancer risks were enumerated from age-, sex-, and calendar-specific population incidence rates. Segregation analysis was conducted to derive a model of the residual familial aggregation of colorectal cancer. Results: Germ-line predisposition to colorectal cancer was identified in 37 probands [3.4%; 95% confidence interval (95% CI), 2.4-4.6]: 29 with MLH1/MSH2 mutations, 2 with familial adenomatous polyposis, 1 with juvenile polyposis, and 5 with biallelic MYH variants. The risk of colorectal cancer in first-degree relatives of probands with MSI and MMR-stable cancers was increased 5.01-fold (95% CI, 3.73-6.59) and 1.31-fold (95% CI, 1.07-1.59), respectively. MSH2/MLH1 mutations were responsible for 50% of the overall excess familial risk and 80% of the risk associated with MSI cancers but 32% of the familial risk was unaccounted for by known loci. Genetic models based on major gene loci did not provide a better explanation of the residual familial aggregation than a simple polygenic model. Conclusions: The information from our analyses should be useful in quantifying familial risks in clinical practice and in the design of studies to identify novel disease alleles.
The Therapeutic Challenge of Systolic Hypertension
Authors: Jan Koch-Weser
Journal: New England Journal of Medicine (1973)

WE usually consider the treatment of hypertension in terms of diastolic pressure and accord only benign neglect to elevated systolic pressure. This posture arises from three widely held misconceptions. Diastolic more than systolic hypertension is thought to reflect excessive peripheral vascular resistance, the major hemodynamic abnormality in chronic primary hypertension. Diastolic pressure supposedly correlates better than systolic with the complications of hypertension. Pharmacotherapeutics is judged ineffective for the reduction of systolic hypertension. None of these notions hold water.Increases in total peripheral resistance cannot elevate diastolic pressure preferentially, and the rise in systolic pressure is not a "secondary phenomenon." Cardiac . . .
The pattern of London's health services is still shadowy
Authors: J Smith
Journal: BMJ (1994)

Ninety per cent of all health care takes place outside hospital, but 90% of people's image of health care is of hospitals: large, imposing institutions, often reflecting a past era of civic pride.

So last week's announcement of the end of Guy's as one of London's acute hospitals (see p 496) was much more dramatic than the simultaneous announcement of extra funds for London's primary care. Guy's is visible - not only physically but also in the mythology of the new NHS. Clinical directorates were born there, and it was one of the first and most prominent of hospital trusts. Compared with high profile, specialist services, its new function as a site for academic work and locally based services and “for exploring the boundaries of medicine” doesn't sound so important. To a public weary of the tendency to rename any public service that doesn't work well “exploring …
Computational Identification of Sweet Wormwood (<i>Artemisia Annua</i>) microRNA and Their mRNA Targets
Authors: Alok Pani, Rajani Kanta Mahapatra, Niranjan Behera, Pradeep Kumar Naik
Journal: Genomics Proteomics & Bioinformatics (2011)

Despite its efficacy against malaria, the relatively low yield (0.01%-0.8%) of artemisinin in Artemisia annua is a serious limitation to the commercialization of the drug. A better understanding of the biosynthetic pathway of artemisinin and its regulation by both exogenous and endogenous factors is essential to improve artemisinin yield. Increasing evidence has shown that microRNAs (miRNAs) play multiple roles in various biological processes. In this study, we used previously known miRNAs from Arabidopsis and rice against expressed sequence tag (EST) database of A. annua to search for potential miRNAs and their targets in A. annua. A total of six potential miRNAs were predicted, which belong to the miR414 and miR1310 families. Furthermore, eight potential target genes were identified in this species. Among them, seven genes encode proteins that play important roles in artemisinin biosynthesis, including HMG-CoA reductase (HMGR), amorpha-4,11-diene synthase (ADS), farnesyl pyrophosphate synthase (FPS) and cytochrome P450. In addition, a gene coding for putative AINTEGUMENTA, which is involved in signal transduction and development, was also predicted as one of the targets. This is the first in silico study to indicate that miRNAs target genes encoding enzymes involved in artemisinin biosynthesis, which may help to understand the miRNA-mediated regulation of artemisinin biosynthesis in A. annua.
Systematic Review and Meta-Analysis of Robotic-Assisted versus Conventional Laparoscopic Pyeloplasty for Patients with Ureteropelvic Junction Obstruction: Effect on Operative Time, Length of Hospital Stay, Postoperative Complications, and Success Rate
Authors: Luis H.P. Braga, Kenneth Pace, Jorge DeMaria, Armando J. Lorenzo
Journal: European Urology (2009)
Autopsy Findings with Permanent Pervenous Pacemakers
Authors: STANLEY J. ROBBOY, J. WARREN HARTHORNE, ROBERT C. LEINBACH, CHARLES A. SANDERS, W. GERALD AUSTEN
Journal: Circulation (1969)

Of 130 patients who received permanent pervenous pacemakers in the last 2 years at the Massachusetts General Hospital, 21 have died; complete postmortem data are available on seven who died 5 days to 18 months after insertion of the pacemaker. No deaths were related to pacemaker malfunction. No patient received routine anticoagulant therapy. The intracardiac portions of all pacemaker electrodes were 30 to 80% endothelialized. In three cases tiny, organized mural thrombi formed on these sheaths, but none appeared to give rise to pulmonary emboli. All pacemaker electrode tips were wedged firmly beneath the trabecular system of the right ventricular apex and elicited varying degrees of local fibrous tissue reaction. Further focal fibrotic attachments occurred in the right atrium and superior vena cava. Although in four cases the electrodes adhered to the chordae tendineae, the long-term presence of an electrode did not appear to compromise tricuspid valve function. Late removal of an electrode may be hazardous because of its firm attachments to the endocardium and tricuspid valve.
Selection of T lymphocytes bearing limited TCR-Vbeta regions in the lung of hypersensitivity pneumonitis and sarcoidosis.
Authors: L Trentin, R Zambello, M Facco, C Tassinari, R Sancetta, M Siviero, A Cerutti, A Cipriani, G Marcer, M Majori, A Pesci, C Agostini, G Semenzato
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Hypersensitivity pneumonitis (HP) and sarcoidosis are interstitial lung disorders (ILD) characterized by a lymphocytic alveolitis that, in the active phase of the disease, is sustained by different T-cell subsets, i.e., CD8+ cells in HP and CD4+ lymphocytes in sarcoid patients. To address the question of whether a bias in T-cell selection occurs in the lung of patients with HP and sarcoidosis, we analyzed the T-cell receptor beta chain variable region (TCR-Vbeta) repertoire by flow cytometry and polymerase chain reaction (PCR) analyses in blood and lung lymphocytes of 14 HP and 25 sarcoid patients. To verify whether these cells can be activated in vitro through the TCR, blood and lung lymphocytes were also assessed for their responsiveness to different superantigenic stimuli represented by staphylococcal enterotoxins, including SEA, SEB, SEC1, SEC2, SED, and SEE. Flow cytometry and PCR analyses demonstrated an overexpression of cells bearing Vbeta2, Vbeta3, Vbeta5, Vbeta6, and Vbeta8 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments in the lung of HP patients as compared with the peripheral blood. In sarcoid patients cells bearing Vbeta2, Vbeta5, and Vbeta6 gene segments were overrepresented in the lung rather than in the blood. Both in HP and sarcoid patients almost all T cells bearing the dominant Vbeta segment belonged to the T-cell subset that sustains the alveolitis, i.e., CD8 in HP patients and CD4 in sarcoid subjects. Follow-up studies demonstrated that the recovery of the alveolitis was characterized by the disappearance of cells bearing a limited T-cell repertoire. Interestingly, T-lymphocyte response to different superantigens demonstrated that the proliferation elicited by different staphylococcal toxins was more pronounced in the lung than in the blood. Taken together, our findings indicate a compartmentalization of cells bearing discrete Vbeta gene products in the pulmonary microenvironment and suggest that the expansion of specific Vbeta region subsets occurring in the lung might result from triggering by a specific antigen. In fact, the removal from exposure in HP patients or specific treatment in sarcoidosis resulted in the decrease of the overrepresented cell population accounting for the lymphocytic alveolitis.
Measurement of Gastrointestinal Protein Loss Using Ceruloplasmin Labeled with 67Copper*
Authors: Thomas A. Waldmann, Anatol G. Morell, R. Dean Wochner, Warren Strober, Irmin Sternlier
Journal: Journal of Clinical Investigation (1967)

Ceruloplasmin labeled with (67)copper and administered intravenously to dogs, control human subjects, and patients with excessive gastrointestinal loss was shown to fulfill the requirements for a label for quantification of gastrointestinal protein loss. The radiocopper moiety was poorly absorbed from the gastrointestinal tract, not actively secreted into the intestinal tract, and did not alter significantly the metabolism of ceruloplasmin. Approximately 70% of the body pool of ceruloplasmin in both dog and man was within the intravascular space. In control human subjects the mean ceruloplasmin concentration was 30 mg per 100 ml with total circulating and total body ceruloplasmin pools of 15.5 and 22 mg per kg, respectively. In patients with excessive gastrointestinal protein loss secondary to intestinal lymphangiectasia, the serum ceruloplasmin concentration was reduced to 16 mg per 100 ml with a comparable reduction in the total circulating and total body ceruloplasmin pools to 8.8 and 12 mg per kg. The survival half-time of ceruloplasmin was 6.1 days in normal human subjects and 4.5 days in normal dogs. From 1.0 to 1.9% of the intravascular pool of ceruloplasmin was lost into the gastrointestinal tract of the dog per day, representing less than 11% of the over-all metabolism of this protein. In control human subjects from 1.9 to 3.9% of the intravascular pool was lost into the gastrointestinal tract each day, representing a maximum of from 11 to 22% of the over-all metabolism of this molecule. In contrast, patients with intestinal lymphangiectasia had a markedly shortened ceruloplasmin survival of 3.1 days, with from 15 to 40% of the intravascular pool of ceruloplasmin cleared into the gastrointestinal tract daily. This represented 76% of the over-all metabolism of this protein. Thus, although bulk loss of serum proteins into the gastrointestinal tract does not normally appear to be a significant factor in protein metabolism in normal dogs and men, such loss is a major factor in the pathogenesis of the hypoceruloplasminemia noted in patients with intestinal lymphangiectasia.