tbuckley/cabot-search huggingface dataset:
EUREKA! AND OTHER PLEASURES
Authors: H. Metzger
Journal: Annual Review of Immunology (1998)

At first one is very pleased at being invited to write a Prefatory Chapter, but as the delivery deadline draws closer one begins to think, “Oh my God! What on earth can I say that all but family members and few close friends will not find a great bore?” One solution is to write a scientific essay, but I concluded that that was a cop-out. I decided that perhaps the best tack to follow was to try to convey to the reader the personal characteristics I bring to my science and to other aspects of my professional career. The writing of this chapter has certainly convinced me that my particular background influenced what problems I chose to work on and how I approached their solution, but I hope that my results have a more ecumenical significance. There's been much written recently about how one's cultural background affects one's science, but I think that thesis can also be exaggerated. Science is a method of inquiry that by using certain guidelines permits rational individuals to observe Nature in a way that their findings will agree and have permanence. We shouldn't be diffident about defending that claim of objectivity.
Association of blood pressure in late adolescence with subsequent mortality: cohort study of Swedish male conscripts
Authors: J. Sundstrom, M. Neovius, P. Tynelius, F. Rasmussen
Journal: BMJ (2011)

<b>Objective</b> To investigate the nature and magnitude of relations of systolic and diastolic blood pressures in late adolescence to mortality. <b>Design</b> Nationwide cohort study. <b>Setting</b> General community in Sweden. <b>Participants</b> Swedish men (n=1 207 141) who had military conscription examinations between 1969 and 1995 at a mean age of 18.4 years, followed up for a median of 24 (range 0-37) years. <b>Main outcome measures</b> Total mortality, cardiovascular mortality, and non-cardiovascular mortality. <b>Results</b> During follow-up, 28 934 (2.4%) men died. The relation of systolic blood pressure to total mortality was U shaped, with the lowest risk at a systolic blood pressure of about 130 mm Hg. This pattern was driven by the relation to non-cardiovascular mortality, whereas the relation to cardiovascular mortality was monotonically increasing (higher risk with higher blood pressure). The relation of diastolic blood pressure to mortality risk was monotonically increasing and stronger than that of systolic blood pressure, in terms of both relative risk and population attributable fraction (deaths that could be avoided if blood pressure was in the optimal range). Relations to cardiovascular and non-cardiovascular mortality were similar, with an apparent risk threshold at a diastolic blood pressure of about 90 mm Hg, below which diastolic blood pressure and mortality were unrelated, and above which risk increased steeply with higher diastolic blood pressures. <b>Conclusions</b> In adolescent men, the relation of diastolic blood pressure to mortality was more consistent than that of systolic blood pressure. Considering current efforts for earlier detection and prevention of risk, these observations emphasise the risk associated with high diastolic blood pressure in young adulthood.
Detection of heterozygotes of X-linked ichthyosis by measuring steroid sulphatase activity of lymphocytes. Mode of inheritance in three families
Authors: M. OKANO, Y. KITANO, T. NAKAMURA, Y. MATSUZAWA
Journal: British Journal of Dermatology (1985)

Steroid sulphatase activity in peripheral blood lymphocytes was assayed in all available members of three families in which cases of X-linked ichthyosis were frequently seen. Lymphocytes from all the patients with this disease lacked steroid sulphatase activity and some female members who were probably heterozygotes, showed significantly lower enzyme activity compared with other healthy family members and normal controls. This suggest that females heterozygous for X-linked ichthyosis in these families could be traced enzymatically. Three childless females in these families were found to be possible heterozygotes in view of their lower enzyme levels. It was found that polyacrylamide gel electrophoretic mobility of serum low-density lipoproteins was increased in X-linked ichthyosis patients but was not changed in the probable heterozygotes. The detection of individuals heterozygous for X-linked ichthyosis, for the purpose of precise genetic counselling, may be possible by measuring steroid sulphatase activity of peripheral blood lymphocytes.
Immature Public Policy for Vascular Access
Authors: Steve J. Schwab, Kennard D. Brown
Journal: Journal of the American Society of Nephrology (2010)

The article by Hurst et al. 1 in this issue of JASN demonstrates a much greater proportion of patients with chronic kidney disease (CKD) initiate hemodialysis (HD) with a native arteriovenous fistula (AVF) when they are patients of the Veterans Administration or Department of Defense, federally capitated systems, versus patients in the US Renal Data System, who receive care in the commercial market. The problems of evaluating retrospective databases are widely known. Nonetheless, the magnitude of the difference described here argues for the validity of the observation. We accept both the premise that this measured event, preemptive AVF formation, and the Fistula First Initiative2 are critically important for patient outcome and that the differences described in the databases are real. Thus, the key question becomes what accounts for these differences; some of them are socioeconomic or racially demographic3,4 but not all.

Long-term reliable access to the circulation remains the largest technical barrier to successful long-term HD. The cumulative data as derived by the Dialysis Outcome Quality Initiative (DOQI) reveal that elective AVFs before initiation of dialysis are the most complication-limited, reliable, and long-lived form …
Hydroxyurea: Possible Relationship of Cytotoxicity to Inhibition of Skin Carcinogenesis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Henry Hennings
Journal: JNCI Journal of the National Cancer Institute (1971)

Intraperitoneal injection of mice with hydroxyurea (0.5 mg/g body wt) resulted in the loss of about 60% of the DNA-synthesizing cells from normal mouse epidermis. The same dose of hydroxyurea was not cytotoxic in rapidly proliferating epidermis 1 day after croton oil application. When a second hydroxyurea injection was given 2 days after croton oil, about 30% of the DNA-synthesizing cells were destroyed. Inhibition of skin carcinogenesis by hydroxyurea may be due to its toxicity to potential tumor cells.
Lymphadenopathy in a patient with systemic onset juvenile chronic arthritis
Authors: R Munro, D R Porter, R D Sturrock
Journal: Annals of the Rheumatic Diseases (1998)

Case historyA boy aged 12 years presented to the local general hospital with a four week history of fever, rash, and arthralgia in September 1982.The rash was migratory and appeared urticarial, the most commonly aVected sites were his trunk and thighs.The arthropathy was asymmetrical and mainly aVected medium and large joints.At presentation he complained of discomfort in his ankles, left knee, and right wrist.Clinical examination confirmed the presence of the rash and active synovitis of his right wrist.There was no evidence of lymphadenopathy, organomegaly or cardiac murmurs.Initial investigations included a raised erythrocyte sedimentation rate (ESR) at 34 mm 1st h and a moderate leucocytosis.Radiology of the aVected joints was unremarkable and his electrocardiogram was normal.His rheumatoid factor and anti-nuclear antibodies were negative.An infection screen included negative blood cultures, negative serology for toxoplasmosis and brucella but an increased antistreptolysin (ASO) titre of 500 Todd units.The initial diagnosis was considered to be rheumatic fever.However, despite treatment for two to three weeks with salicylates and benzyl penicillin his symptoms including fever continued unabated.A diagnosis of systemic onset juvenile chronic arthritis (SOJCA) was made and he was given prednisolone 60 mg/day (approximately 1 mg/kg).This led to a rapid improvement in his joint symptoms and resolution of his rash.His systemic features remained problematic over the next few months reappearing with attempted reductions in his corticosteroid dose.However, they eventually settled by July 1983 and he was maintained with nonsteroidal agents alone.His care at this stage was transferred to the local paediatric rheumatologist.His joint disease however deteriorated over the next six months and corticosteroids had to be given again with prednisolone 40 mg (0.7 mg/kg) on alternate days.In August 1985 when he was 15 years old azathioprine 100 mg daily (1.5 mg/kg) was added to his regimen on the basis of a recent report of its usefulness in the treatment of juvenile chronic arthritis. 1His corticosteroid requirements generally ranged from 5-20 mg/day.Radiological examinations showed progression of his joint disease with erosions appearing
Statins for prevention of hepatocellular cancer: One step closer?
Authors: Siddharth Singh, Preet Paul Singh
Journal: Hepatology (2013)

Abstract Purpose: Statins may have protective effects against cancer, but no studies have focused on their effects in patients with chronic hepatitis C virus (HCV) infection. The purpose of this study was to investigate the association between use of statins and risk of hepatocellular carcinoma (HCC) in HCV-infected patients. Patients and Methods: Ours was a population-based cohort study of 260,864 HCV-infected patients enrolled in the Taiwan National Health Insurance Research Database since January 1, 1999, and observed through December 31, 2010. Cox proportional hazards regression with time-dependent covariates for drug exposures was employed to evaluate the association between statin use and HCC risk. Results: There were 27,883 cases of HCC in the HCV cohort during a follow-up period of 2,792,016.6 person-years. Among the 35,023 patients using statins (defined as ≥28 cumulative defined daily doses [cDDDs]), 1,378 had HCC. Among the 225,841 patients not using statins (&lt;28 cDDDs), 26,505 were diagnosed with HCC. A dose-response relationship between statin use and HCC risk was observed. The adjusted hazard ratios were 0.66 (95% CI, 0.59 to 0.74), 0.47 (95% CI, 0.40 to 0.56), and 0.33 (95% CI, 0.25 to 0.42) for patients with 28 to 89, 90 to 180, and &gt;180 cDDDs per year, respectively, relative to nonusers. The reduction in risk also demonstrated a progressive duration-response relationship in patients with ≥28 cDDDs per year when compared with nonusers. Conclusion: Among patients with HCV infection, statin use was associated with reduced risk of HCC. Further research is needed to elucidate the mechanism responsible for this effect.
Blood level of mitochondrial aspartate aminotransferase as an indicator of the extent of ischemic necrosis of the rat liver
Authors: Tadashi Nishimura, Yukuo Yoshida, Fusao Watanabe, Masato Koseki, Toshiro Nishida, Kunio Tagawa, Yasunaru Kawashima
Journal: Hepatology (1986)

To assess the severity of ischemic liver injury, we examined release of mitochondrial aspartate aminotransferase (EC 2.6.1.1) and its cytoplasmic isozyme from the ischemic rat liver into the circulation. Their patterns of leakage were quite different: the level of cytoplasmic aspartate aminotransferase reached a peak soon after the circulation to the ischemic liver was restored, while that of mitochondrial aspartate aminotransferase increased slowly, reaching a maximum after more than 10 hr. On anoxic incubation of mitochondria isolated from the normal liver, oxidative phosphorylation capacity was lost within 2 hr, at which time no leakage of matrix enzymes was observed: more than 10 hr after-loss-of-oxidative phosphorylation were needed for the matrix enzymes to leak out of the mitochondrial membrane. Since the viability of cells is considered to depend on the capacity of oxidative phosphorylation, it is highly likely that the delayed appearance of mitochondrial aspartate aminotransferase in blood indicates the postmortem changes of injured cells. In fact, the cumulative activity of mitochondrial aspartate aminotransferase but not cytoplasmic aspartate aminotransferase in circulation after ischemic liver injury correlated fairly well with the decrease of total adenine nucleotides which were monitored to measure viable cells. The difference between mitochondrial aspartate aminotransferase and cytoplasmic aspartate aminotransferase as quantitative indices of hepatic necrosis may be due to the relative stability of the former and significant inactivation of the latter during hepatic ischemia. Therefore, the determination of mitochondrial aspartate aminotransferase in blood may be useful in the assessment of liver necrosis after ischemic injury.
Mechanism of Pulsus Paradoxus in Clinical Shock*
Authors: Jay N. Cohn, Alan L. Pinkerson, Felix E. Tristani
Journal: Journal of Clinical Investigation (1967)

An inspiratory fall in systolic arterial pressure of more than 10 mm Hg (pulsus paradoxus) was noted in 30 of 61 patients with shock. Inspiratory right atrial pressures and total blood volumes were significantly lower in patients with pulsus paradoxus. Rapid infusion of dextran in 22 patients usually was effective in reversing the exaggerated inspiratory fall in systolic pressure. Total peripheral vascular resistance tended to be higher in the patients with pulsus paradoxus and administration of vasoconsrictor drugs often accentuated the respirator pressure variation. Respiratory effects on blood flow in the aorta, pulmonary artery, and venae cavae were studied in anesthetized, closed-chest dogs. In the control state, pulmonary arterial flow increased during inspiration but aortic flow remained nearly constant. After hemorrhage a sharp inspiratory fall in aortic flow was associated with decreased central blood volume and attenuation of the usual inspiratory increase in venae caval and pulmonary arterial flows. The respiratory changes in aortic flow after hemorrhage could be attributed both to depletion of the pulmonary reservoir and to alterations in pulmonary inflow related to changes in systemic venous return. These data indicate that blood volume depletion may precipitate pulsus paradoxus both in the anesthetized dog and in the critically ill patient. The occurrence of pulsus paradoxus may aid in the clinical recognition of the common syndrome of occult hypovolemia in patients with shock in the absence of signs of blood loss.
Evolution of Sarcomeric Myosin Heavy Chain Genes: Evidence from Fish
Authors: K. McGuigan
Journal: Molecular Biology and Evolution (2004)

Myosin heavy chain (MYH) is a major structural protein, integral to the function of sarcomeric muscles. We investigated both exon-intron organization and amino acid sequence of sarcomeric MYH genes to infer their evolutionary history in vertebrates. Our results were consistent with the hypothesis that a multigene family encoded MYH proteins in the ancestral chordate, one gene ancestral to human MYH16 and its homologues and another ancestral to all other vertebrate sarcomeric MYH genes. We identified teleost homologues of mammalian skeletal and cardiac MYH genes, indicating that the ancestors of those genes were present before the divergence of actinopterygians and sarcopterygians. Indeed, the ancestral skeletal genes probably duplicated at least once before the divergence of teleosts and tetrapods. Fish homologues of mammalian skeletal MYH are expressed in skeletal tissue and homologues of mammalian cardiac genes are expressed in the heart but, unlike mammals, there is overlap between these expression domains. Our analyses inferred two other ancestral vertebrate MYH genes, giving rise to human MYH14 and MYH15 and their homologues. Relative to the skeletal and cardiac genes, MYH14 and MYH15 homologues are characterized by evolution of intron position, differences in evolutionary rate between the functionally differentiated head and rod of the myosin protein, and possible evolution of function among vertebrate classes. Tandem duplication and gene conversion appear to have played major roles in the evolution of at least cardiac and skeletal MYH genes in fish. One outcome of this high level of concerted evolution is that different fish taxa have different suites of MYH genes, i.e., true orthologs do not exist.
Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells
Authors: Karl R. N. Baumforth, Joanne R. Flavell, Gary M. Reynolds, Gillian Davies, Trevor R. Pettit, Wenbin Wei, Susan Morgan, Tanya Stankovic, Yasuhiro Kishi, Hiroyuki Arai, Marketa Nowakova, Guy Pratt, Junken Aoki, Michael J. O. Wakelam, Lawrence S. Young, Paul G. Murray
Journal: Blood (2005)
American College of Cardiology training statement on recommendations for the structure of an optimal adult interventional cardiology training program11Endorsed by the Society for Cardiac Angiography and Interventions and the Diagnostic and Interventional Catheterization Committee on the Council on Clinical Cardiology, American Heart Association22This document was approved by the American College of Cardiology Board of Trustees in September 1999. Address for Reprints: This document is available …
Authors: John W Hirshfeld, John S Banas, Michael Cowley, Stephen G Ellis, David P Faxon, Alice K Jacobs, Raymond D Magorien, Stephen Oesterle, Mark Taubman, Ronald E Vlietstra, Bruce H Brundage, Gregory J Dehmer, Gordon A Ewy, David R Holmes, William C Little, Michael A Nocero, Carl J Pepine, Carl Tommaso, Robert Vogel, James S Forrester, Pamela S Douglas, David P Faxon, John D Fisher, Gabriel Gregoratos, Judith S Hochman, Adolph M Hutter, Sanjiv Kaul, Robert A O’Rourke, William L Winters, William S Weintraub, Michael J Wolk
Journal: Journal of the American College of Cardiology (1999)
Comparison of Limbus-Based and Fornix-Based Trabeculectomy: Success, Bleb-Related Complications, and Bleb Morphology
Authors: Jason F. Solus, Henry D. Jampel, Patricia A. Tracey, Donna L. Gilbert, Tara L. Loyd, Joan L. Jefferys, Harry A. Quigley
Journal: Ophthalmology (2012)
Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial
Authors: Philip D Home, Stuart J Pocock, Henning Beck-Nielsen, Paula S Curtis, Ramon Gomis, Markolf Hanefeld, Nigel P Jones, Michel Komajda, John JV McMurray
Journal: The Lancet (2009)
cT3N0 Rectal Cancer: Potential Overtreatment With Preoperative Chemoradiotherapy Is Warranted
Authors: José G. Guillem, Juan A. Díaz-González, Bruce D. Minsky, Vincenzo Valentini, Seung-Yong Jeong, Miguel A. Rodriguez-Bigas, Claudio Coco, Rebecca Leon, José L. Hernandez-Lizoain, José J. Aristu, Elyn R. Riedel, Donato Nitti, W. Douglas Wong, Salvatore Pucciarelli
Journal: Journal of Clinical Oncology (2008)

Purpose Although combined-modality therapy (CMT) is the preferred treatment for T3 and/or lymph node (LN)-positive rectal cancer, the German rectal cancer study published in 2004 demonstrated that 18% of patients deemed suitable for preoperative CMT by endorectal ultrasound (ERUS) may be overstaged. Because data also suggest that LN-negative rectal cancer after total mesorectal excision may not require radiotherapy, it is reasonable to consider omitting radiotherapy for the cT3N0 subset. We therefore determined the accuracy of pre-CMT ERUS or magnetic resonance imaging (MRI) staging, to explore the validity of a nonpreoperative CMT approach for cT3N0 disease. Patients and Methods One hundred eighty-eight ERUS-/MRI-staged T3N0 rectal cancer patients received preoperative CMT (fluorouracil based and 45-50.4 Gy) followed by radical resection. Rates of pathologic complete response (pCR) and mesorectal LN involvement were determined. Results Tumors were located a median of 5 cm from the anal verge. Sphincter-preserving surgery was performed in 143 patients (76%). Overall pCR was 20%, and 41 patients (22%) had pathologically positive mesorectal LNs. The incidence of positive LNs significantly increased with T stage: ypT0, 3%; ypT1, 7%; ypT2, 20%; ypT3-4, 36% (P = .001). Conclusion The accuracy of preoperative ERUS/MRI for staging mid to distal cT3N0 rectal cancer is limited because 22% of patients have undetected mesorectal LN involvement despite CMT. Therefore, ERUS-/MRI-staged T3N0 rectal cancer patients should continue to receive preoperative CMT. Although 18% may be overstaged and therefore overtreated, our data suggest that an even larger number would be understaged and require postoperative CMT, which is associated with significantly inferior local control, higher toxicity, and worse functional outcome.
Resistin: a newly identified chemokine for human CD4-positive lymphocytes
Authors: D. Walcher, K. Hess, R. Berger, M. Aleksic, P. Heinz, H. Bach, R. Durst, A. Hausauer, V. Hombach, N. Marx
Journal: Cardiovascular Research (2009)

Increased levels of resistin, a peptide secreted by adipocytes and inflammatory cells, circulate in patients with insulin resistance and early type 2 diabetes, a high-risk population for the development of a diffuse and extensive pattern of arteriosclerosis. Recent data suggest that resistin may activate vascular cells such as smooth muscle cells and endothelial cells, but hitherto nothing is known about the role of resistin in CD4-positive lymphocytes. Therefore, the present study examined the effect of resistin on CD4-positive lymphocyte migration, an important process in early atherogenesis. Resistin stimulated CD4-positive cell chemotaxis in a concentration-dependent manner with a maximal induction of 2.25 ± 0.54 at 100 ng/mL (P < 0.05, n = 7). This process involves pertussis toxin-sensitive G-proteins as well as activation of Src- and phosphoinositide 3-kinase (PI 3-K). Biochemical analysis showed that resistin induces phosphorylation of Src and PI 3-K activation in human CD4-positive cells. In addition, resistin activates RhoA, Rac-1, and Cdc42 in these cells as shown by affinity precipitation experiments. Finally, resistin-induced phosphorylation of myosin light chain was inhibited by Src short interference RNA transfection, underscoring the importance of the upstream signalling molecule Src in resistin-induced migration. These data support an active role of resistin in CD4-positive lymphocyte chemotaxis and elucidate molecular mechanisms in resistin-induced cell migration.
Early ribavirin pharmacokinetics, HCV RNA and alanine aminotransferase kinetics in HIV/HCV co-infected patients during treatment with pegylated interferon and ribavirin
Authors: Harel Dahari, Marianthi Markatou, Marija Zeremski, Ivan Haller, Ruy M. Ribeiro, Teresa Licholai, Alan S. Perelson, Andrew H. Talal
Journal: Journal of Hepatology (2007)