tbuckley/cabot-search huggingface dataset:
Workgroup 1: Access
Authors: Nola Ishmael, Isaac Dweben
Journal: Journal of the Royal Society of Medicine (2001)

In our workgroup, access to palliative care was discussed in the context of access to healthcare in general. At first it seemed, because of the great differences in healthcare financing and organization, that there would be marked differences between the USA and the UK regarding access to palliative care. But as discussion proceeded it became clear that ethnic populations, immigrants, those with substance abuse problems and those whose first language was not English faced somewhat similar barriers in the two settings.

The balance of discussion was directed to better defining access needs of the socially excluded and to exploring models and ideas for ways to overcome barriers to care.
Inflammatory Cytokines Impair Endothelium-Dependent Dilatation in Human Veins In Vivo
Authors: Kiran Bhagat, Patrick Vallance
Journal: Circulation (1997)

Background Endothelial dysfunction occurs in many diseases associated with increased cardiovascular risk. We examined the effects of pro-inflammatory cytokines on endothelial function. Methods and Results Subjects lay with one hand placed on an angled support. The diameter of a vein was recorded by measuring the linear displacement of a probe placed on the skin overlying the vein when the pressure in a congesting cuff placed around the upper arm was deflated from 40 to 0 mm Hg. A length of the vein was isolated by two wedges. TNF-α (1 ng), IL-1β (1 ng), or IL-6 (100 pg) were instilled for 1 hour, either individually or together. At the end of the hour, the wedges were removed and the vein reconnected with the circulation. Dose-response curves (bradykinin: 2, 4, and 8 pmol/min; arachidonic acid: 0.2, 2, and 20 nmol/min; and glyceryl trinitrate 1, 2, and 4 pmol/min) were constructed before and 1, 6, 24, and 48 hours after instillation. In another study, hydrocortisone (100 mg) was given 2 hours before the study. In a different study, subjects were given oral aspirin (75 mg or 1 g) 2 hours before the study. TNF-α and IL-1β alone but not IL-6 attenuated the dilatation to bradykinin and arachidonic acid; the response was greatest at 1 hour with recovery occurring by 6 hours. Combination of IL-1β and TNF-α prolonged the endothelial dysfunction, resulting in recovery at 24 hours. Hydrocortisone and high-dose aspirin prevented endothelial dysfunction. Conclusions The results demonstrate that pro-inflammatory cytokines induce transient and reversible endothelial dysfunction and indicate that cyclooxygenase activity may contribute to the genesis of the effect. If other vessels behave similarly, this may provide further insight into the mechanisms precipitating acute cardiovascular events after inflammatory disorders.
The two similarly expressed genes encoding U3 snRNA in Schizosaccharomyces pombe lack introns.
Authors: D A Selinger, G L Porter, P J Brennwald, J A Wise
Journal: Molecular Biology and Evolution (1992)

Both genes encoding U3 small nuclear RNA (snRNA) from the budding yeast Saccharomyces cerevisiae were recently shown to be interrupted by introns of the type removed by the pre-mRNA splicing machinery. We previously described one of the two U3 genes from the fission yeast Schizosaccharomyces pombe. In the present work, the second S. pombe U3 coding sequence was identified, and direct RNA sequence analysis was used to show that neither the U3A nor the U3B gene from this organism contains an intervening sequence. Our data also demonstrate that, as expected, the two RNAs exhibit great primary- and secondary-structure conservation. These similarities are not likely to be the result of a recent gene duplication or conversion event, because the DNA sequences flanking the U3A and U3B genes have diverged substantially. A notable exception is a 19-bp block, centered 36 nucleotides upstream from the transcriptional start site, in which the two loci match in 15 positions; this motif may represent an RNA polymerase II upstream regulatory element, because related sequences are found preceding fission yeast U1, U2, U4, and U5 snRNA genes. The significance of a short conserved sequence just downstream of the U3A and U3B genes is unknown, as it is not found 3' to other snRNA coding sequences in S. pombe. The 5' one-third of U3B RNA can be folded into a dual hairpin structure, as we previously proposed for Schizosaccharomyces pombe U3A and for other lower eukaryotic U3 homologues. Quantitation of fission yeast U3A and U3B indicates that, in contrast to snR17A and B in Saccharomyces cerevisiae, these RNAs accumulate to similar levels.
Microalbuminuria Reduction With Valsartan in Patients With Type 2 Diabetes Mellitus
Authors: Giancarlo Viberti, Nigel M. Wheeldon
Journal: Circulation (2002)

Background — Elevated urine albumin excretion (UAER) is a modifiable risk factor for renal and cardiovascular disease in type 2 diabetes. Blockade of the renin-angiotensin system lowers UAER, but whether this effect is independent of blood pressure (BP) reduction remains controversial. The MicroAlbuminuria Reduction With VALsartan (MARVAL) study was designed to evaluate the BP-independent effect of valsartan on UAER in type 2 diabetic patients with microalbuminuria. Methods and Results — Three hundred thirty-two patients with type 2 diabetes and microalbuminuria, with or without hypertension, were randomly assigned to 80 mg/d valsartan or 5 mg/d amlodipine for 24 weeks. A target BP of 135/85 mm Hg was aimed for by dose-doubling followed by addition of bendrofluazide and doxazosin whenever needed. The primary end point was the percent change in UAER from baseline to 24 weeks. The UAER at 24 weeks was 56% (95% CI, 49.6 to 63.0) of baseline with valsartan and 92% (95% CI, 81.7 to 103.7) of baseline with amlodipine, a highly significant between-group effect ( P &lt;0.001). Valsartan lowered UAER similarly in both the hypertensive and normotensive subgroups. More patients reversed to normoalbuminuria with valsartan (29.9% versus 14.5%; P =0.001). Over the study period, BP reductions were similar between the two treatments (systolic/diastolic 11.2/6.6 mm Hg for valsartan, 11.6/6.5 mm Hg for amlodipine) and at no time point was there a between-group significant difference in BP values in either the hypertensive or the normotensive subgroup. Conclusions — For the same level of attained BP and the same degree of BP reduction, valsartan lowered UAER more effectively than amlodipine in patients with type 2 diabetes and microalbuminuria, including the subgroup with baseline normotension. This indicates a BP-independent antiproteinuric effect of valsartan.
Analysis of IDH mutation, 1p/19q deletion, and PTEN loss delineates prognosis in clinical low-grade diffuse gliomas
Authors: N. Sabha, C. B. Knobbe, M. Maganti, S. Al Omar, M. Bernstein, R. Cairns, B. Cako, A. von Deimling, D. Capper, T. W. Mak, T.-R. Kiehl, P. Carvalho, E. Garrett, A. Perry, G. Zadeh, A. Guha, S. Croul
Journal: Neuro-Oncology (2014)

Grades II and III gliomas have unpredictable rates of progression, making management decisions difficult. Currently, several clinical and radiological characteristics are utilized to predict progression and survival but collectively are suboptimal. In this study, we analyzed a set of 108 nonenhancing hemispheric grade II–III gliomas. Demographic variables, including patient age, tumor diameter, extent of resection, and performance status, were combined with molecular data (IDH mutation status [mIDH], 1p/19q codeletion, PTEN deletion, and EGFR amplification). A complete dataset for all variables was compiled for 70 of the 108 patients. Both univariable and multivariable analyses were performed to determine whether the molecular data singly or in combination offer advantages over tumor type and grade for prediction of overall survival (OS) and/or progression-free rate (PFR). Patient age, clinical variables (tumor diameter, extent of resection, performance status), and pathology (tumor type and grade) were not predictive of OS or PFR. IDH mutation status alone was predictive of longer OS and PFR for the entire group of tumors; 1p/19q deletion alone was predictive of OS but not PFR. In the multivariable analysis, none of the clinical or demographic factors were predictive of OS or PFR. IDH mutation status, 1p/19q codeletion, and PTEN deletion were predictive of OS (P = .003, P = .005, P = .02, respectively). Both mIDH (P < .001) and the interaction term of 1p/19q and PTEN (P < .001) were found to be predictive of PFR. We conclude that the combination of mIDH, 1p/19q codeletion, and PTEN deletion may be particularly effective in discriminating good prognosis from poor prognosis hemispheric gliomas. We propose that such a scheme merits testing on larger prospective cohorts. Should our findings be confirmed, routine clinical analysis of hemispheric gliomas for mIDH, 1p/19q codeletion, and PTEN deletion would be justified.
Mutations in PLK4, encoding a master regulator of centriole biogenesis, cause microcephaly, growth failure and retinopathy
Authors: Carol-Anne Martin, Ilyas Ahmad, Anna Klingseisen, Muhammad Sajid Hussain, Louise S Bicknell, Andrea Leitch, Gudrun Nürnberg, Mohammad Reza Toliat, Jennie E Murray, David Hunt, Fawad Khan, Zafar Ali, Sigrid Tinschert, James Ding, Charlotte Keith, Margaret E Harley, Patricia Heyn, Rolf Müller, Ingrid Hoffmann, Valérie Cormier Daire, Hélène Dollfus, Lucie Dupuis, Anu Bashamboo, Kenneth McElreavey, Ariana Kariminejad, Roberto Mendoza-Londono, Anthony T Moore, Anand Saggar, Catie Schlechter, Richard Weleber, Holger Thiele, Janine Altmüller, Wolfgang Höhne, Matthew E Hurles, Angelika Anna Noegel, Shahid Mahmood Baig, Peter Nürnberg, Andrew P Jackson
Journal: Nature Genetics (2014)
Amino acid sequence similarity of Hev b 3 to two previously reported 27‐ and 23‐kDa latex proteins allergenic to spina bifida patients
Authors: H.Y. Yeang, M.A. Ward, A.S.M. Zamri, M.S. Dennis, D.R. Light
Journal: Allergy (1998)

Separate studies have reported spina bifida patients to be especially allergic t o proteins of 27 and 23 kDa found in the serum of centrifuged natural rubber latex. An insoluble latex protein located on the surface of small rubber particles, Hev b 3, has similarly been found to be allergenic to spina bifida patients. In this study, internal amino acid sequences of Hev b 3 showed similarity to the published sequences for the 27‐ and 23‐kDa latex proteins. The latter allergens are hence identified as Hev b 3. Determination of the molecular weight of Hev b 3 revealed various species of 22–23 kDa. The consistent gaps of about 266 Da observed between various forms of the intact protein suggest that the protein undergoes post‐translational modification. To determine whether Hev b 3 also occurs i n a soluble form in the latex serum, its presence in molecular‐filtered serum was checked by ELISA and Western blot, TTie results showed Hev b 3 to be largely absent in the C‐serum from fresh latex. The protein is therefore insoluble in its native state. However, a small amount of the solubilized protein was detected in ammonia‐stabilized latex (commonly used in the manufacture of latex products).
Differential Effects of Hypoxia on the Disposition of Propranolol and Sodium Taurocholate by the Isolated Perfused Rat Liver
Authors: Brian D. Jones, George W. Mihaly, Richard A. Smallwood, Lorraine K. Webster, Denis J. Morgan, Norman P. Madsen
Journal: Hepatology (1984)

Although the adverse effect of hypoxia on drug metabolism is well documented in subcellular systems, its effect on drug clearance by the intact liver has not been defined. This study was undertaken in the isolated perfused rat liver to examine the effects of acute hypoxia on the hepatic elimination of two highly cleared substances-propranolol and sodium taurocholate. Hypoxia was established by equilibrating the perfusate with 100% nitrogen rather than 100% oxygen. This led to a fall in portal vein PO 2 from 300 to 30 mm Hg, and a 10-fold rise in hepatic venous lactate:pyruvate ratio, indicating a profound alteration in hepatic cellular redox state. In bolus dose studies, propranolol uptake was unimpaired by hypoxia, with a monoexponential decline in perfusate concentrations from 2,000 to 30 ng per ml, (t½ uptake = 2.5 min). After 20 min of hypoxia, perfusate propranolol concentrations rose from 30 to 80 ng per ml, indicating release of propranolol from the liver back into the perfusate. Reoxygenation of perfusate restored hepatic extraction of propranolol to normal (t½ uptake = 2.37 ± 0.19 min vs. 2.55 ± 0.60 min p ± 0.1) such that perfusate concentrations were undetectable by 30 min. In steady-state studies, perfusate propranolol concentrations rose from 1.55 ± 0.50 to 4.08 ± 1.47 μ g per ml (p &lt; 0.005), after 1 hr of hypoxia indicating a change in propranolol clearance from 15 ml per min to less than 6 ml per min. Reoxygenation resulted in a fall in perfusate propranolol concentrations towards control values (2.78 ± 1.13 vs. 1.80 ± 0.41 /xg per ml, p ± 0.1). By contrast, steady-state sodium taurocholate concentrations were unaffected by hypoxia [control (76.6 ± 41.0) vs. hypoxia (50.4 ± 13.6 nmoles per ml), p ± 0.1]. These studies demonstrate that although propranolol uptake is unchanged by hypoxia, overall elimination is greatly reduced, consistent with reduced activity of hepatic mixed function oxidases. By contrast, sodium taurocholate uptake remains unimpaired, affirming the low oxygen dependence of this transport process.
Antiproteinuric Therapy and Fabry Nephropathy
Authors: Hindia Tahir, Leslie L. Jackson, David G. Warnock
Journal: Journal of the American Society of Nephrology (2007)

This report describes an open-label, nonrandomized, prospective evaluation of the effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy on patients who have Fabry disease and also received enzyme replacement therapy with agalsidase-beta, given at 1 mg/kg body wt every 2 wk. Previous placebo-controlled phase III and phase IV trials with agalsidase-beta demonstrated clearing of globotriaosylceramide from vascular endothelia but little effect on proteinuria or progressive loss of kidney function in patients with Fabry disease and severe chronic kidney disease marked by overt proteinuria and/or estimated GFR <60 ml/min per 1.73 m2. Angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker therapy is the standard of care for patients with proteinuric kidney diseases, but their use is challenging in patients with Fabry disease and low or low-normal baseline systemic BP. A group of patients with Fabry disease were treated with antiproteinuric therapy, in conjunction with agalsidase-beta; sustained reductions in proteinuria with stabilization of kidney function were achieved in a group of six patients who had severe Fabry nephropathy; the progression rate was -0.23 +/- 1.12 ml/min per 1.73 m2 per yr with 30 mo of follow-up.
Rolling of Human Bone-Metastatic Prostate Tumor Cells on Human Bone Marrow Endothelium under Shear Flow Is Mediated by E-Selectin
Authors: Charles J. Dimitroff, Mirna Lechpammer, Denise Long-Woodward, Jeffery L. Kutok
Journal: Cancer Research (2004)

Abstract Prostate tumor cells preferentially adhere to bone marrow endothelial cells (BMECs) compared with endothelial linings from other tissue microvessels, implicating the importance of BMEC adhesion in the predilection of prostate tumor metastasis to bone. E (endothelial)-selectin, which functions as an initiator of leukocyte adhesion to target tissue endothelium, is constitutively expressed on BMECs, suggesting that prostate tumor cells could use this adhesive mechanism to initiate their migration into bone. In this report, we demonstrate for the first time that human bone-metastatic prostate tumor cells roll on human BMECs under physiological flow conditions. We show that these dynamic adhesive interactions are dependent on the expression of BMEC E-selectin and sialylated glycoconjugates on bone-metastatic prostate tumor cells. We also establish the importance of both glycoprotein(s) and glycosphingolipid structures displaying sialyl Lewis X epitopes as potential E-selectin ligands on bone-metastatic prostate tumor cells. Coexpression of sialylated glycoproteins and glycolipids on bone-metastatic prostate tumor cells triggers robust E-selectin binding activity, which is identical to that observed on human hematopoietic progenitor cells. By Western blot analysis, we identify candidate E-selectin glycoprotein ligand(s); distinct sialyl Lewis X (or HECA-452 antigen)-bearing membrane proteins were resolved at Mr 130,000 and Mr 220,000 as well as others ranging from Mr 100,000 to Mr 220,000. Immunohistochemical analysis of HECA-452 antigen expression on normal prostate tissue and on low- and high-grade prostate adenocarcinoma shows that HECA-452 antigen expression is directly associated with prostate tumor progression and may indicate acquisition of E-selectin ligand expression. These findings provide novel insight into potential adhesive mechanisms promoting hematogenous dissemination of prostate tumor cells into bone.
INTERFERENCE BETWEEN THE INFLUENZA VIRUSES
Authors: James E. Ziegler, Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1944)

Reciprocal interference between influenza A, influenza B, and swine influenza viruses has been demonstrated in the chick embryo. Certain temporal and quantitative factors which influence the production of interference in this host-virus system have been studied. The implications of these observations in relation to the mechanism by which interference is produced are discussed.
Early Differential Effects of 3-Methylcholanthrene and Its “K-Region” Epoxideon Mouse Skin. Possible Implication in the Two-Stage Mechanism of Tumorigenesis2
Authors: Kurt Bürki, J. E. Wheeler, Yasuyuki Akamatsu, J. E. Scribner, Graciela Candelas, Bresnick Edward
Journal: JNCI Journal of the National Cancer Institute (1974)

Repeated percutaneous coadministration of 1.5 μmoles 1,1,I-trichloro-2-propene oxide (TCPO) with 1.5-3 μmoles 3-methylcholanthrene (MCA) increased the carcinogenic effect of the polycyclic hydrocarbon on mouse skin, presumably by inhibition of the hydration of MCA-ll,12-oxide, which would increase the effective intracellular concentration of the carcinogenic epoxide. A single administration of TCPO also increased the tumor incidence and shortened the latency period in experiments where MCA was the initiator and phorbol ester, the promotor. Topically applied MCA-11,12-oxide after either single or repeated administration with or without TCPO was only weakly tumorigenic on mouse skin, as compared to the parent MCA. Measured morphometrically and cytokinetically, the epidermal hypertrophy and hyperplasia seen after MCA treatment were absent after application of the 11,12-oxide. The oxide, on the other hand, caused a thinning of intrafollicular epidermis due to a decrease in total number of epithelial cells.
A case of orbital myositis associated with rheumatoid arthritis
Authors: S Nabili
Journal: Annals of the Rheumatic Diseases (2002)

A 51 year old woman with a 34 year history of seropositive, erosive, nodular rheumatoid arthritis (RA) complained of non-specific headache and diplopia of insidious onset at a routine appointment with her ophthalmologist. Her RA was generally well controlled with sulfasalazine 2 g daily, which she had taken for four years. Other drugs were bendrofluazide 2.5 mg and atenolol 50 mg daily for hypertension along with hypromellose eye drops for dry eyes. She had no other medical history of note. She had previously been treated with intramuscular gold from 1977 until 1985 and with auranofin from 1987 until 1996.

Physical examination showed weakness of the right medial, lateral, and superior recti. The most likely cause was thought to be ocular nerve palsy, but a magnetic resonance (MR) scan of …
Beyond VEGF: Inhibition of the Fibroblast Growth Factor Pathway and Antiangiogenesis
Authors: Christopher Lieu, John Heymach, Michael Overman, Hai Tran, Scott Kopetz
Journal: Clinical Cancer Research (2011)

Fibroblast growth factor (FGF) signaling regulates cell proliferation, differentiation, survival, angiogenesis, and wound healing. Compelling evidence for deregulated FGF signaling in tumorigenesis continues to emerge, and a growing body of research suggests that FGF may also play an integral role in the resistance to anti-VEGF therapy. Although agents targeting FGF signaling are early in development, the potential to target both the VEGF and FGF pathways may translate into improvements in the clinical care of cancer patients.
Glucose and Amino Acid Turnover in Untreated Gestational Diabetes
Authors: Dawn M Zimmer, Alan M Golichowski, Cheryl A Karn, Ginger Brechtel, Alain D Baron, Scott C Denne
Journal: Diabetes Care (1996)

OBJECTIVE Although gestational diabetes affects as many as 3% of all pregnant women, specific aspects of glucose and protein metabolism in this population have not been clearly delineated. We tested the hypothesis that gestational diabetes mellitus (GDM) results in increased glucose production and proteolysis during fasting. RESEARCH DESIGN AND METHODS Using tracer isotope infusions, the rate of appearance (Ra) of glucose, leucine, phenylalanine and tyrosine, phenylalanine hydroxylation, leucine oxidation, and urea nitrogen excretion were determined after an overnight fast in 10 GDM subjects, within 2 weeks of diagnosis and before initiation of treatment, and in a matched control group of nine healthy nondiabetic pregnant women. RESULTS Fasting glucose Ra was similar in GDM patients and control subjects (GDM, 12.8 ± 1.1 vs. control subjects, 12.8 ± 0.9 μumol · kg−1 . min−1). Leucine and phenylalanine Ra (reflecting proteolysis) also were not different between GDM patients and control subjects (GDM leucine Ra, 128 ± 14 vs. control subjects, 124 ± 5; phenylalanine Ra GDM, 35 ± 4 vs. control subjects, 40 ± 2 μumol · kg−1 · h−1). Furthermore, leucine oxidation and phenylalanine hydroxylation were not increased in GDM subjects, urea nitrogen excretion was actually lower in GDM patients. However, fasting insulin concentrations were significantly elevated in GDM subjects (GDM, 165 ± 35 vs. control subjects, 30 ± 5 pmol/l; P &amp;lt; 0.01). CONCLUSIONS Hepatic glucose release and whole-body proteolysis in GDM patients were remarkably similar to matched pregnant control subjects. This was achieved with insulin concentrations three- to fivefold higher than normal, suggesting significant insulin resistance for both glucose and protein metabolism in GDM.
Differential involvement of CD4+ cells in mediating skin graft rejection against different amounts of transgenic H-2K(b) antigen.
Authors: M Kawai, Y Obata, N Hamasima, T Takahashi, A Uenaka, M Monden, T Mori, H Shiku, E Nakayama
Journal: The Journal of Experimental Medicine (1991)

Differential involvement of CD4+ cells in mediating class I-disparate skin graft rejection was investigated using quantitatively different Kb transgenic mice as donors under conditions in which CD8+ cells were blocked in vivo by administration of anti-CD8 monoclonal antibody (mAb). Tg.H-2Kb-1 and -2 are C3H transgenic mice with 14 and 4 copies, respectively, of the H-2Kb gene. Cell surface expression of Kb antigen and the Kb antigenicity of skin for eliciting graft rejection with homozygous and heterozygous transgenic mice were correlated with the copy number. In vivo administration of anti-Lyt-2.1 (CD8) mAb markedly prolonged survival of heterozygous and homozygous C3H Tg.H-2Kb-2 skin grafted onto C3H mice, but prolonged survival of heterozygous Tg.H-2Kb-1 skin grafts much less and did not prolong survival of homozygous Tg.H-2Kb-1 grafts. Administration of anti-L3T4 (CD4) mAb alone did not have any effect on skin graft rejection. Administration of anti-L3T4 (CD4) mAb with anti-Lyt-2.1 (CD8) mAb blocked rejection in all combinations. These findings indicate that a quantitative difference of class I antigen caused differential activation of CD4+ cells under conditions in which CD8+ cells were blocked.