tbuckley/cabot-search huggingface dataset:
Decreased hepatocyte membrane potential differences and GABAa-β3 expression in human hepatocellular carcinoma
Authors: Gerald Y. Minuk, Manna Zhang, Yuewen Gong, Leonard Minuk, Hans Dienes, Norman Pettigrew, Michael Kew, Jeremy Lipschitz, Dongfeng Sun
Journal: Hepatology (2007)

To determine whether hepatocyte membrane potential differences (PDs) are depolarized in human HCC and whether depolarization is associated with changes in GABAA receptor expression, hepatocyte PDs and gamma-aminobutyric acid (GABA)A receptor messenger RNA (mRNA) and protein expression were documented in HCC tissues via microelectrode impalement, real-time reverse-transcriptase polymerase chain reaction, and Western blot analysis, respectively. HCC tissues were significantly depolarized (-19.8+/-1.3 versus -25.9+/-3.2 mV, respectively [P<0.05]), and GABAA-beta3 expression was down-regulated (GABAA-beta3 mRNA and protein expression in HCC; 5,693+/-1,385 and 0.29+/-0.11 versus 11,046+/-4,979 copies/100 mg RNA and 0.62+/-0.16 optical density in adjacent tumor tissues, respectively [P=0.002 and P<0.0001, respectively]) when compared with adjacent nontumor tissues. To determine the physiological relevance of the down-regulation, human malignant hepatocytes deficient in GABAA-beta3 receptor expression (Huh-7 cells) were transfected with GABAA-beta3 complementary DNA (cDNA) or vector alone and injected into nu/nu nude mice (n=16-17 group). Tumors developed after a mean (+/-SD) of 51+/-6 days (range: 41-60 days) in 7/16 (44%) mice injected with vector-transfected cells and 70+/-12 days (range: 59-86 days) in 4/17 (24%) mice injected with GABAA-beta3 cDNA-transfected cells (P<0.005).The results of this study indicate that (1) human HCC tissues are depolarized compared with adjacent nontumor tissues, (2) hepatic GABAA-beta3 receptor expression is down-regulated in human HCC, and (3) restoration of GABAA-beta3 receptor expression results in attenuated in vivo tumor growth in nude mice.
Validation and patient acceptance of a computer touch screen version of the WOMAC 3.1 osteoarthritis index
Authors: H A Bischoff-Ferrari
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To validate the WOMAC 3.1 in a touch screen computer format, which applies each question as a cartoon in writing and in speech (QUALITOUCH method), and to assess patient acceptance of the computer touch screen version. <b>Methods:</b> The paper and computer formats of WOMAC 3.1 were applied in random order to 53 subjects with hip or knee osteoarthritis. The mean age of the subjects was 64 years (range 45 to 83), 60% were male, 53% were 65 years or older, and 53% used computers at home or at work. Agreement between formats was assessed by intraclass correlation coefficients (ICCs). Preferences were assessed with a supplementary questionnaire. <b>Results:</b> ICCs between formats were 0.92 (95% confidence interval, 0.87 to 0.96) for pain; 0.94 (0.90 to 0.97) for stiffness, and 0.96 (0.94 to 0.98) for function. ICCs were similar in men and women, in subjects with or without previous computer experience, and in subjects below or above age 65. The computer format was found easier to use by 26% of the subjects, the paper format by 8%, and 66% were undecided. Overall, 53% of subjects preferred the computer format, while 9% preferred the paper format, and 38% were undecided. <b>Conclusion:</b> The computer format of the WOMAC 3.1 is a reliable assessment tool. Agreement between computer and paper formats was independent of computer experience, age, or sex. Thus the computer format may help improve patient follow up by meeting patients' preferences and providing immediate results.
Radioimmunoassay of human plasma lecithin-cholesterol acyltransferase.
Authors: J J Albers, J L Adolphson, C H Chen
Journal: Journal of Clinical Investigation (1981)

A sensitive and precise competitive-displacement double-antibody radioimmunoassay was developed for the human plasma enzyme lecithin-cholesterol acyltransferase (LCAT; Ec 2.3 1.43). The ability of plasma from various animal species to displace labeled human LCAT from goat anti-human LCAT could be ranked in the following order: man and sheep > nonhuman primates > cat or dog > pig > rabbit or guinea pig > mouse > rat. Normolipidemic subjects had levels of LCAT of 6.14 +/- 0.98 micrograms/ml (mean +/- SD, n = 66). Subjects with dysbeta-lipoproteinemia had the highest plasma LCAT levels (7.88 +/- 0.39 micrograms/ml, n = 7, P < 0.05), followed by hypercholesterolemic subjects (7.00 +/- 1.30, n = 41) and hypertriglyceridemic subjects (6.96 +/- 1.3, n = 10). LCAT-deficient subjects had the lowest enzyme levels (0.89, 0.83, and 0.05 micrograms/ml, respectively, and two subjects with no detectable enzyme). Males had lower LCAT levels (6.42 +/- 1.05 micrograms/ml, n = 90, for all subjects; 5.99 +/- 1.03, n = 44, for normolipidemics) than females (7.01 +/- 1.14, n = 34, for all subjects P < 0.01; 6.44 +/- 0.79, n = 22, for normolipidemics, P < 0.01). LCAT levels correlated significantly with total cholesterol (males, r = 0.384, P < 0.001; females, r = 0.519, P < 0.002); and total triglyceride (only in females, r = 0.512, P < 0.002). LCAT levels in females correlated inversely with HDL cholesterol (r = 0.341, P < 0.05) and apoprotein D (r = 0.443, P < 0.02), but no such relationship existed in males.
Keratinocyte-derived cytokines after photodynamic therapy and their paracrine induction of matrix metalloproteinases in fibroblasts
Authors: S. Karrer, A.K. Bosserhoff, P. Weiderer, M. Landthaler, R.-M. Szeimies
Journal: British Journal of Dermatology (2004)

Background Recent studies have shown that collagen-degrading matrix metalloproteinase (MMP)-1 and MMP-3 are produced by fibroblasts in response to photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) and are considered to be involved in the antisclerotic effects of ALA-PDT observed in the treatment of localized scleroderma. Objectives As the primary target of topical PDT is epidermal keratinocytes, we studied the indirect participation of keratinocytes in the production of MMPs and collagen by dermal fibroblasts. Methods Keratinocytes were treated with sublethal doses of ALA (100 µmol L−1) and red light. The conditioned media were collected 24 h after PDT and primary human fibroblasts were exposed to these media for 6–48 h. Further, a coculture model, keratinocytes seeded on to collagen type IV-coated transwells in the upper chamber and fibroblasts in the lower chamber, was used to study paracrine effects of keratinocytes after PDT. Results Keratinocyte supernatants after PDT showed a significant, up to 10-fold increase of interleukin (IL)-1α and a 2·5-fold increase of tumour necrosis factor-α as determined by enzyme-linked immunosorbent assay, while IL-6, MMP-1 and MMP-3 were not altered significantly. Fibroblasts treated with keratinocyte-conditioned media after PDT showed an induction of MMP-1 and MMP-3 protein levels up to threefold in both models used, suggesting that ALA-PDT modulates MMP-1 and MMP-3 production via indirect mechanisms. Collagen type I mRNA expression by fibroblasts was not altered significantly in either model. The addition of an IL-1 receptor antagonist to the keratinocyte-conditioned media completely inhibited the induction of MMP-1 and MMP-3 in stimulated fibroblasts, suggesting that IL-1 is mainly responsible for the observed paracrine effects. Conclusions We present evidence that PDT can trigger MMP production in dermal fibroblasts not only directly as has been already shown, but also by an indirect paracrine loop mediated by soluble factors released by epidermal keratinocytes.
Living wills put on statutory footing
Authors: C. Dyer
Journal: BMJ (1998)

A new framework for taking decisions on behalf of mentally incompetent people is likely to be enacted in England and Wales, along lines originally recommended by the Law Commission in 1995.

The government, which has issued a new consultation paper, is taking up proposals left on the shelf by the previous (Conservative) government, amid controversy over whether they would lead to euthanasia. The proposals would put so-called living wills, or advance directives on medical treatment, already held to be enforceable by the courts, on a statutory footing.

The …
Clinical Features and Outcome of Hypertrophic Cardiomyopathy Associated With Triple Sarcomere Protein Gene Mutations
Authors: Francesca Girolami, Carolyn Y. Ho, Christopher Semsarian, Massimo Baldi, Melissa L. Will, Katia Baldini, Francesca Torricelli, Laura Yeates, Franco Cecchi, Michael J. Ackerman, Iacopo Olivotto
Journal: Journal of the American College of Cardiology (2010)
How Do Variable Substitution Rates Influence Ka and Ks Calculations?
Authors: Dapeng Wang, Song Zhang, Fuhong He, Jiang Zhu, Songnian Hu, Jun Yu
Journal: Genomics Proteomics & Bioinformatics (2009)

Abstract The ratio of nonsynonymous substitution rate (Ka) to synonymous substitution rate (Ks) is widely used as an indicator of selective pressure at sequence level among different species, and diverse mutation models have been incorporated into several computing methods. We have previously developed a new γ-MYN method by capturing a key dynamic evolution trait of DNA nucleotide sequences, in consideration of varying mutation rates across sites. We now report a further improvement of NG, LWL, MLWL, LPB, MLPB, and YN methods based on an introduction of gamma distribution to illustrate the variation of raw mutation rate over sites. The novelty comes in two ways: (1) we incorporate an optimal gamma distribution shape parameter a into γ-NG, γ-LWL, γ-MLWL, γ-LPB, γ-MLPB, and γ-YN methods; (2) we investigate how variable substitution rates affect the methods that adopt different models as well as the interplay among four evolutional features with respect to Ka/Ks computations. Our results suggest that variable substitution rates over sites under negative selection exhibit an opposite effect on ω estimates compared with those under positive selection. We believe that the sensitivity of our new methods has been improved than that of their original methods under diverse conditions and it is advantageous to introduce novel parameters for Ka/Ks computation.
Improved survival of patients with chronic myelogenous leukemia undergoing allogeneic bone marrow transplantation
Authors: Jan Moreb, Thomas Johnson, Paul Kubilis, Lesley Myers, David Oblon, Alan Miller, Gerald Elfenbein, Roy Weiner
Journal: American Journal of Hematology (1995)

A total of 28 patients with chronic myelogenous leukemia (CML) in chronic phase (CP) received bone marrow allografts from HLA-matched siblings at the University of Florida between August 1984-July 1992. The present study compares the disease-free survival (DFS) for those patients who were transplanted before or after August 1988 using the same conditioning regimen. The analysis shows significant difference in 3-year DFS for those patients transplanted post- vs. pre-August 1988 (69.6% vs. 20%, respectively; P = 0.006). A decrease in pneumonitis due to different etiologies from pre-August 1988 (6/13, 46%) to post-August 1988 (1/15, 7%) was statistically significant (P = 0.029). A decrease, although statistically insignificant, in the overall incidence and severity of acute and chronic graft vs. host disease (GVHD) after August 1988 was also noticed. This study indicates significantly improved outcome for patients with CML in CP who have been treated in the University of Florida after August 1988. Better supportive care and prophylaxis for GVHD most likely contributed to such improvement.
Captopril, an Angiotensin-Converting Enzyme Inhibitor, Promotes Growth of Immunogenic Tumors in Mice
Authors: Piotr J. Wysocki, Eliza P. Kwiatkowska, Urszula Kazimierczak, Wiktoria Suchorska, Dariusz W. Kowalczyk, Andrzej Mackiewicz
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Antitumor potential of angiotensin-converting enzyme inhibitors has been shown in different preclinical settings, which always involved immunocompromised organisms or nonimmunogenic tumor models. In our study, we wanted to evaluate the effect of captopril on growth of immunogenic tumors in immunocompetent animals. Experimental Design: We used different murine tumor models to evaluate the effect of captopril on tumor take and survival of tumor-bearing immunocompetent and immunocompromised mice. We used an orthotopic renal cell cancer model and highly immunogenic tumor model, which were based on kidney subcapsular injection of RenCa cells or s.c. injection of MethA cells, respectively. To show the influence of captopril on antigen-specific immune responses, we have used two model antigens (green fluorescent protein and β-galactosidase). Results: Captopril decreased survival of RenCa-bearing, immunocompetent mice in a dose-dependent manner and in adjuvant setting. In nephrectomized mice, captopril shortened their survival. Captopril promoted formation of immunogenic MethA sarcoma tumors but had no effect on nonimmunogenic melanoma cells (B78-H1). Treatment of immunocompromised mice bearing MethA tumors or RenCa kidney tumors with captopril did not affect tumor formation nor survival, respectively. Captopril-treated mice immunized with AdLacZ or AdGFP vectors did not generate or generated decreased numbers of antigen-specific CD8+ T cells, respectively. However, they showed B-cell responses represented by infiltration of MethA tumors with activated B cells and dramatically increased serum level of β-galactosidase-specific antibodies. Conclusions: Our results show a novel role of captopril in tumor biology and the tumor-promoting properties of captopril seem to be associated with its immunomodulatory potential.
Legal challenge to India's patent laws threatens access to generic drugs, says charity
Authors: P. Moszynski
Journal: BMJ (2011)

The Swiss multinational drug company Novartis is trying to undermine a key public health safeguard in Indian patent law specifically designed to prevent drug companies abusing patents of known drugs, says the medical aid charity Medecins Sans Frontieres (MSF).

It says that the success of a legal challenge in India’s Supreme Court would have “a devastating impact on access to affordable medicines across the developing world.”

Novartis is challenging a part of India’s patent law—Section 3(d)—which “read with other provisions of the patent law says that a new form of a known medicine can only be patented if it is not obvious and shows significantly improved therapeutic efficacy over existing medicines,” says the charity.

MSF says …
Synovial fluid pyrophosphate and nucleoside triphosphate pyrophosphatase: comparison between normal and diseased and between inflamed and non-inflamed joints.
Authors: M Pattrick, E Hamilton, J Hornby, M Doherty
Journal: Annals of the Rheumatic Diseases (1991)

Deposition of intra-articular calcium pyrophosphate is associated with both aging and arthropathy; increased concentrations of free pyrophosphate (PPi) may contribute to such deposition. Free pyrophosphate and nucleoside triphosphate pyrophosphatase (NTPase) were estimated in synovial fluids from 50 subjects with normal knees and from 44 patients with rheumatoid arthritis, 61 with pyrophosphate arthropathy, and 59 with osteoarthritis. For arthropathic knees clinically assessed inflammation was classified as active or inactive using a summated score of six clinical features. The order of PPi (mumol/l) and NTPase (mumol PPi/30 min/mg protein) was pyrophosphate arthropathy greater than osteoarthritis greater than rheumatoid arthritis (median PPi, NTPase respectively: for pyrophosphate arthropathy 15.9, 0.45; for osteoarthritis 9.3, 0.25; for rheumatoid arthritis 4.4, 0.18), with significant differences between all groups. In pyrophosphate arthropathy both PPi (mumol/l) and NTPase (mumol PPi/30 min/mg protein) were higher than normal (15.9, 0.45 v 8.6, 0.2 respectively), but findings in osteoarthritis did not differ from normal. The inflammatory state of the knee had a distinct but variable effect on synovial fluid findings in rheumatoid arthritis and pyrophosphate arthropathy, but not in osteoarthritis. There was no correlation of either PPi or NTPase with age, or between PPi and NTPase in any group. This study provides in vivo data for synovial fluid PPi and NTPase. It suggests that factors other than PPi need to be considered in a study of crystal associated arthropathy. Clinical inflammation, as well as diagnosis, is important in synovial fluid studies.
Abstract 512: Cell-based analysis of oxidative stress, lipid peroxidation and lipid peroxidation-derived protein modifications using fluorescence microscopy
Authors: Bhaskar S. Mandavilli, Robert Aggeler
Journal: Cancer Research (2014)

Abstract Oxidative stress plays an important role in the progression of several diseases including inflammation, atherosclerosis, aging and age-related degenerative disorders. Reactive oxygen species damage membrane bound lipids resulting in lipid peroxidation-derived protein modifications. Cell-based measurements of oxidative stress, lipid peroxidation and protein carbonylation by traditional fluorescence microscopy provide a powerful platform to quantitate oxidative stress and lipid peroxidation. Here, we used three different approaches to measure oxidative stress and lipid peroxidation in cells by fluorescence microscopy. 1) Two new fluorogenic probes, CellROX™ Orange and CellROX ™ Green Reagents to measure oxidative stress in cells, 2) Image-iT® Lipid Peroxidation Kit for a ratiometric determination of lipid peroxidation in live cells 3) Click-iT® Lipid Peroxidation Imaging Kit, a click chemistry-based approach which utilizes incorporation of an alkyne-modified unsaturated fatty acid analog, linoleamide, into the cellular membranes. The resulting oxidation products, like 9, 12-dioxo-10(E) dodecenoic acid (DODE) can readily modify proteins and these modifications were readily detected in fixed cells by the copper-catalyzed click reaction using fluorescent azides. Using these approaches, we measured oxidative stress and lipid peroxidation caused by several oxidants in cells. Increases in oxidative stress, lipid peroxidation, and protein modifications were assessed by high content imaging and analysis as well as traditional fluorescence microscopy. In the models tested, at least 2-3 fold increases were observed compared to controls was and responses were successfully inhibited by antioxidants. The three strategies described here provide powerful new tools for the assessment of oxidative stress in cells and convey distinct advantages over existing cell-based methods. Citation Format: Bhaskar S. Mandavilli, Robert Aggeler. Cell-based analysis of oxidative stress, lipid peroxidation and lipid peroxidation-derived protein modifications using fluorescence microscopy. [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 512. doi:10.1158/1538-7445.AM2014-512
The genomic landscape of Waldenström macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis
Authors: Zachary R. Hunter, Lian Xu, Guang Yang, Yangsheng Zhou, Xia Liu, Yang Cao, Robert J. Manning, Christina Tripsas, Christopher J. Patterson, Patricia Sheehy, Steven P. Treon
Journal: Blood (2013)
Microanatomy of glomic tissue of the pulmonary trunk
Authors: C. Edwards, D. Heath
Journal: Thorax (1969)

Glomic tissue occurs at the bifurcation of the pulmonary trunk. There is controversy as to its derivation, blood supply, and function. It has been regarded as one of the coronary glomera supplied by the intertruncal branch of the left coronary artery. On the other hand, it has been described as the true glomus pulmonale supplied by blood from the pulmonary trunk. The purpose of this article is to draw attention to its existence and to establish its microanatomical structure.
Report of Committee on the Mental and Physical Conditions of Children
Authors: F. Warner
Journal: BMJ (1897)

DICAL ~~~~~~~~~~~~~~~~~~~~~JOURN can be little doubt that a measure of the kind would be heartily welcomed, and would meet with great support.Your Committee trusts that the session will not terminate before the introduction of the promised Bill.Such a Bill should include: i.The compulsory therapeutic detention of habitual drunkards, after a judicial process, on sworn medical testi- mony, and with every possible safeguarding of the liberty of the subject.2. The establishment and management of special homes for inebriates for the poorest, for criminal and non-criminal inebriate offenders.3. The inclusion of intoxication by any narcotic in the term "'habitual drunkenness."4. The appearance of voluntary applicants for curative detention before one justice instead of two justices as at present, or before some other authorised official.5. Magisterial discretion to award a term of curative restraint in a reformatory or hospital, instead of a term of imprisonment in a gaol.It would also be desirable to have all habitual drunkards under curative treatment subject to State or municipal inspection.The Committee is glad to learn that in Austria, while the authorities are considering the project of special legislation for inebriates, one clinic has been set apart specially for the treatment of habitual drunkards.
The Action of Norepinephrine, Epinephrine and Isopropyl Norepinephrine on the Rhythmic Function of the Heart
Authors: MORRIS H. NATHANSON, HAROLD MILLER
Journal: Circulation (1952)

The actions of norepinephrine and isopropyl norepinephrine on the rhythmic property of the heart were studied and compared with that of epinephrine. Norepinephrine does not abolish cardiac standstill by carotid sinus stimulation, has no effect on the ventricular rate of heart block and induces a sinus bradycardia. Isopropyl norepinephrine acts similarly to epinephrine in that it abolishes the induced cardiac standstill, increases the ventricular rate of heart block and produces a sinus tachycardia. In the treatment of cardiac arrest, the isopropyl compound appears to possess optimum features as it is very potent in the prevention of cardiac standstill and does not predispose to ventricular fibrillation.
CORONARY PLAQUE NATURE IN DIABETIC PATIENTS OF ACUTE ST ELEVATION MYOCARDIAL INFARCTION
Authors: Sang-Wook Kim, Young Joon Hong, Sung Yun Lee, Wang Soo Lee, Jee-Eun Kwon, Joon Hwa Hong, Kwang Je Lee, Chee Jeong Kim, Tae Ho Kim
Journal: Journal of the American College of Cardiology (2012)