tbuckley/cabot-search huggingface dataset:
Nephropathy in human immunodeficiency virus-1 transgenic mice is due to renal transgene expression.
Authors: L A Bruggeman, S Dikman, C Meng, S E Quaggin, T M Coffman, P E Klotman
Journal: Journal of Clinical Investigation (1997)

HIV-associated nephropathy (HIVAN) is a progressive glomerular and tubular disease that is increasingly common in AIDS patients and one of the leading causes of end stage renal disease in African Americans. A major unresolved issue in the pathogenesis of HIVAN is whether the kidney disease is due to renal cell infection or a "bystander" phenomenon mediated by systemically dysregulated cytokines. To address this issue, we have used two different experimental approaches and an HIV-1 transgenic mouse line that develops a progressive renal disease histologically similar to HIVAN in humans. In the murine model, kidney tissue expresses the transgene and in heterozygous adults, renal disease develops shortly thereafter. We demonstrate by terminal deoxynucleotide transferase-mediated dUTP-biotin nick-end labeling assay that similar to the disease in humans, apoptosis of renal tubular epithelial cells is a component of the molecular pathogenesis. To determine whether apoptosis is due to transgene expression or environmental factors, we treated fetal kidney explants (normal and transgenic) with UV light to induce transgene expression. Apoptosis occurred in transgenic but not normal littermates after stimulation of transgene expression. To confirm a direct effect of HIV expression on the production of HIVAN, we transplanted kidneys between normal and transgenic mice. HIVAN developed in transgenic kidneys transplanted into nontransgenic littermates. Normal kidneys remained disease free when transplanted into transgenic littermates. Thus, the renal disease in the murine model is intrinsic to the kidney. Using two different experimental approaches, we demonstrate a direct effect of transgene expression on the development of HIVAN in the mouse. These studies suggest that in humans, a direct effect of HIV-1 expression is likely the essential cause of HIVAN, rather than an indirect effect of cytokine dysregulation.
Expression of <b> <i>POT1</i> </b> is Associated with Tumor Stage and Telomere Length in Gastric Carcinoma
Authors: Tomohiro Kondo, Naohide Oue, Kazuhiro Yoshida, Yoshitsugu Mitani, Kazuhito Naka, Hirofumi Nakayama, Wataru Yasui
Journal: Cancer Research (2004)

Abstract Pot1, a telomere end-binding protein in fission yeast and human, is proposed not only to cap telomeres but also to recruit telomerase to the ends of chromosomes. No study has been performed regarding Pot1 expression status in human cancers. Thus, we examined POT1 mRNA expression in 51 gastric cancer (GC) tissues and evaluated telomere length and 3′ telomeric overhang signals in 20 of the 51 GC tissues. Quantitative reverse transcription-PCR analysis showed that POT1 expression levels in the tumor relative to those in nonneoplastic mucosa (T/N ratio) were significantly higher in stage III/IV tumors than in stage I/II tumors (P = 0.005). Down-regulation of POT1 (T/n &amp;lt; 0.5) was observed more frequently in stage I/II GC (52.4%, 11 of 21) than in stage III/IV GC (23.3%, 7 of 30; P = 0.033), whereas up-regulation of POT1 (T/n &amp;gt; 2.0) was observed more frequently in stage III/IV GC (33.3%, 10 of 30) than in stage I/II GC (9.5%, 2 of 21; P = 0.048). POT1 expression levels showed decreased in accordance with telomere shortening (r = 0.713, P = 0.002). In-gel hybridization analysis showed that 3′ telomeric overhang signals decreased in accordance with decreases in POT1 expression levels (r = 0.696, P = 0.002) and telomere shortening (r = 0.570, P = 0.013). Reduced POT1 expression was observed in GC cell lines with telomeres shortened by treatment with azidothymidine. In addition, inhibition of Pot1 by antisense oligonucleotides led to telomere shortening as well as inhibition of telomerase activity in GC cells. Moreover, inhibition of Pot1 decreased 3′ overhang signals and increased the frequency of anaphase bridge (P = 0.0005). These data suggest that Pot1 may play an important role in regulation of telomere length and that inhibition of Pot1 may induce telomere dysfunction. Moreover, changes in POT1 expression levels may be associated with stomach carcinogenesis and GC progression.
Low-Dose Suramin Enhanced Paclitaxel Activity in Chemotherapy-Naïve and Paclitaxel-Pretreated Human Breast Xenograft Tumors
Authors: SaeHeum Song, Bei Yu, Yong Wei, M. Guillaume Wientjes, Jessie L.-S. Au
Journal: Clinical Cancer Research (2004)

Abstract We reported induction of broad-spectrum chemoresistance by acidic and basic fibroblast growth factors and chemosensitization by their nonspecific inhibitor suramin at nontoxic and subtherapeutic doses. This study evaluated whether low-dose suramin enhances paclitaxel activity in chemotherapy-naïve and paclitaxel-pretreated human MCF7 breast xenograft tumors in mice. Suramin, 10 mg/kg, and/or paclitaxel, 15 mg/kg, were administered intravenously, twice weekly for 2 to 3 weeks. In addition to conventional end points [tumor size change, median survival time (MST)], we also used clinically relevant end points [partial (PR) and complete response rates (CR); progressive disease (PD); stable disease (SD); time to tumor progression (TTP)]. In chemotherapy-naïve mice, the control and suramin groups showed identical TTP (3 days) and MST (21 days). Single-agent paclitaxel produced 47% PR and 24% CR, and prolonged both TTP and MST to 73 days. The addition of suramin further improved the total response rate to 100% with a dramatically greater 63% CR, shortened the time to attain PR and CR, and prolonged TTP and MST to ≥136 days. In the paclitaxel-pretreated group, single-agent paclitaxel resulted in 67% SD and 33% PD, whereas the combination produced 50% PR and 50% SD. Suramin also significantly enhanced the apoptotic effect of paclitaxel in tumors. In conclusion, suramin improved the activity of paclitaxel in both chemotherapy-naïve and paclitaxel-pretreated animals, without enhancing host toxicity (≤10% body weight loss in all groups). These data have led to the initiation of phase I/II trials of paclitaxel and low-dose suramin combination in advanced metastatic breast cancer patients.
Poor outcome in end‐stage heart failure patients with low circulating calcitriol levels
Authors: Armin Zittermann, Stefanie S. Schleithoff, Christian Götting, Oxana Dronow, Uwe Fuchs, Joachim Kuhn, Knut Kleesiek, Gero Tenderich, Reiner Koerfer
Journal: European Journal of Heart Failure (2008)
Hydrogen peroxide overproduction in megamitochondria of troglitazone-treated human hepatocytes
Authors: Shoichiro Shishido, Hironori Koga, Masaru Harada, Hiroto Kumemura, Shinichiro Hanada, Eitaro Taniguchi, Ryukichi Kumashiro, Hiromasa Ohira, Yukio Sato, Masayoshi Namba, Takato Ueno, Michio Sata
Journal: Hepatology (2003)

Troglitazone has been withdrawn from therapeutic options for diabetes mellitus because of its severe hepatocyte toxicity of unknown pathogenesis. The aim of the present study was to assess both morphologic and functional alterations in the mitochondria of troglitazone-treated hepatocytes. A polarized human hepatocyte cell line, OUMS-29, was used in this study. The mitochondrial volume and the mitochondrial transmembrane potential (ΔΨ m ) were examined using flow cytometry with nonylacridine orange (NAO) and rhodamine-123, respectively. An ultrastructural examination of the troglitazone-treated OUMS-29 cells was performed using transmission electron microscopy (TEM). Reactive oxygen species (ROS) production was assessed using flow cytometry with dihydroethidium and 2′,7′-dichlorodihydrofluorescein diacetate. A significant increase in the mitochondrial volume of the troglitazone-treated cells was found by the NAO analysis, in comparison with pioglitazone-treated and ciglitazone-treated cells. The increase in volume was due to a marked enlargement in the mitochondria. The markedly enlarged mitochondria with intramitochondrial electron-dense deposits were confirmed on TEM, which showed myelin-like structures, indicating degraded membrane constituents. The troglitazone-treated cells showed a significant decline in the ΔΨ m per unit mitochondrial volume but resulted in no clear cell death. ROS analysis revealed a significant production of hydrogen peroxide in the troglitazone-treated hepatocytes. This production was attenuated using an antioxidant, N -acetyl-l-cysteine. In conclusion, troglitazone caused overproduction of hydrogen peroxide, which deteriorated both mitochondrial membrane structures and mitochondrial function, leading to a possible priming for the severe hepatocyte toxicity.
Detection of anti-type VII collagen antibody in Sjögren's syndrome/lupus erythematosus overlap syndrome with transient bullous systemic lupus erythematosus
Authors: None Fujii, None Fujimoto, None Ueda, None Makino, None Arata
Journal: British Journal of Dermatology (1998)

Journal Article Detection of anti‐type VII collagen antibody in Sjögren's syndrome/lupus erythematosus overlap syndrome with transient bullous systemic lupus erythematosus Get access K. Fujii, K. Fujii Department of Dermatology, Okayama University Medical School, 2–5‐1, Shikata, Okayama 700, Japan Search for other works by this author on: Oxford Academic Google Scholar W. Fujimoto, W. Fujimoto Department of Dermatology, Okayama University Medical School, 2–5‐1, Shikata, Okayama 700, Japan Dr Fujimoto E‐mail: watarufu@ccews2.cc.okayama‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar M. Ueda, M. Ueda Department of Dermatology, Okayama University Medical School, 2–5‐1, Shikata, Okayama 700, Japan Search for other works by this author on: Oxford Academic Google Scholar E. Makino, E. Makino Department of Dermatology, Okayama University Medical School, 2–5‐1, Shikata, Okayama 700, Japan Search for other works by this author on: Oxford Academic Google Scholar J. Arata J. Arata Department of Dermatology, Okayama University Medical School, 2–5‐1, Shikata, Okayama 700, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 139, Issue 2, 1 August 1998, Pages 302–306, https://doi.org/10.1046/j.1365-2133.1998.02372.x Published: 01 August 1998
Clinical, angiographic, and intravascular ultrasound characteristics of early saphenous vein graft failure
Authors: Daniel A Caños, Gary S Mintz, Chalak O Berzingi, Sue Apple, Jun-ichi Kotani, Augusto D Pichard, Lowell F Satler, William O Suddath, Ron Waksman, Joseph Lindsay, Neil J Weissman
Journal: Journal of the American College of Cardiology (2004)
Narrative Review: The Promotion of Gabapentin: An Analysis of Internal Industry Documents
Authors: Michael A. Steinman, Lisa A. Bero, Mary-Margaret Chren, C. Seth Landefeld
Journal: Annals of Internal Medicine (2006)

Background: Internal documents from the pharmaceutical industry provide a unique window for understanding the structure and methods of pharmaceutical promotion. Such documents have become available through litigation concerning the promotion of gabapentin (Neurontin, Pfizer, Inc., New York, New York) for off-label uses. Purpose: To describe how gabapentin was promoted, focusing on the use of medical education, research, and publication. Data Sources: Court documents available to the public from United States ex. rel David Franklin vs. Pfizer, Inc., and Parke-Davis, Division of Warner-Lambert Company, mostly from 1994–1998. Data Extraction: All documents were reviewed by 1 author, with selected review by coauthors. Marketing strategies and tactics were identified by using an iterative process of review, discussion, and re-review of selected documents. Data Synthesis: The promotion of gabapentin was a comprehensive and multifaceted process. Advisory boards, consultants meetings, and accredited continuing medical education events organized by third-party vendors were used to deliver promotional messages. These tactics were augmented by the recruitment of local champions and engagement of thought leaders, who could be used to communicate favorable messages about gabapentin to their physician colleagues. Research and scholarship were also used for marketing by encouraging "key customers" to participate in research, using a large study to advance promotional themes and build market share, paying medical communication companies to develop and publish articles about gabapentin for the medical literature, and planning to suppress unfavorable study results. Limitations: Most available documents were submitted by the plaintiff and may not represent a complete picture of marketing practices. Conclusion: Activities traditionally considered independent of promotional intent, including continuing medical education and research, were extensively used to promote gabapentin. New strategies are needed to ensure a clear separation between scientific and commercial activity.
Empirical Bayes methods for smoothing data and for simultaneous estimation of many parameters.
Authors: T Yanagimoto, N Kashiwagi
Journal: Environmental Health Perspectives (1990)

A recent successful development is found in a series of innovative, new statistical methods for smoothing data that are based on the empirical Bayes method. This paper emphasizes their practical usefulness in medical sciences and their theoretically close relationship with the problem of simultaneous estimation of parameters, depending on strata. The paper also presents two examples of analyzing epidemiological data obtained in Japan using the smoothing methods to illustrate their favorable performance.
Is the Role of the Small Intestine in First-Pass Metabolism Overemphasized?
Authors: Jiunn H. Lin, Masato Chiba, Thomas A. Baillie
Journal: Pharmacological Reviews (1999)

The primary function of the small intestine is to absorb nutrients and water. This is achieved by mixing food with digestive enzymes to increase the contact of foodstuffs with the absorptive cells of the mucosa. In humans, the small intestine is about 5 to 6 m in length and comprises approximately 1
The impact of constructive feedback on training in gastrointestinal endoscopy using high-fidelity virtual-reality simulation: a randomised controlled trial
Authors: Irina Kruglikova, Teodor P Grantcharov, Asbjorn M Drewes, Peter Funch-Jensen
Journal: Gut (2009)

Background Recently, virtual reality computer simulators have been used to enhance traditional endoscopy teaching. Previous studies have demonstrated construct validity of these systems and transfer of virtual skills to the operating room. However, to date no simulator-training curricula have been designed and there is very little evidence on the impact of external feedback on acquisition of endoscopic skills. The aim of the present study was to assess the impact of external feedback on the learning curves on a VR colonoscopy simulator using inexperienced trainees. Materials and methods 22 trainees, without colonoscopy experience were randomised to a group which received structured feedback provided by an experienced supervisor and a controlled group. All participants performed 15 repetitions of task 3 from the Introduction colonoscopy module of the Accu Touch Endoscopy simulator. Retention/transfer tests on simulator were performed 4–6 weeks after the last repetition. The proficiency levels were based on the performance of eight experienced colonoscopists. Results All subjects were able to complete the procedure on the simulator. There were no perforations in the feedback group versus seven in the non-feedback group. Subjects in the feedback group reached expert proficiency levels in percentage of mucosa visualised and time to reach the caecum significantly faster compared with the control group. None of the groups demonstrated significant degradation of performance in simulator retention/transfer tests. Conclusion Concurrent feedback given by supervisor concur an advantage in acquisition of basic colonoscopy skills and achieving of proficiency level as compared to independent training.
Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development
Authors: Gary J. Kelloff, John M. Hoffman, Bruce Johnson, Howard I. Scher, Barry A. Siegel, Edward Y. Cheng, Bruce D. Cheson, Joyce O'Shaughnessy, Kathryn Z. Guyton, David A. Mankoff, Lalitha Shankar, Steven M. Larson, Caroline C. Sigman, Richard L. Schilsky, Daniel C. Sullivan
Journal: Clinical Cancer Research (2005)

Abstract 2-[18F]Fluoro-2-deoxyglucose positron emission tomography (FDG-PET) assesses a fundamental property of neoplasia, the Warburg effect. This molecular imaging technique offers a complementary approach to anatomic imaging that is more sensitive and specific in certain cancers. FDG-PET has been widely applied in oncology primarily as a staging and restaging tool that can guide patient care. However, because it accurately detects recurrent or residual disease, FDG-PET also has significant potential for assessing therapy response. In this regard, it can improve patient management by identifying responders early, before tumor size is reduced; nonresponders could discontinue futile therapy. Moreover, a reduction in the FDG-PET signal within days or weeks of initiating therapy (e.g., in lymphoma, non–small cell lung, and esophageal cancer) significantly correlates with prolonged survival and other clinical end points now used in drug approvals. These findings suggest that FDG-PET could facilitate drug development as an early surrogate of clinical benefit. This article reviews the scientific basis of FDG-PET and its development and application as a valuable oncology imaging tool. Its potential to facilitate drug development in seven oncologic settings (lung, lymphoma, breast, prostate, sarcoma, colorectal, and ovary) is addressed. Recommendations include initial validation against approved therapies, retrospective analyses to define the magnitude of change indicative of response, further prospective validation as a surrogate of clinical benefit, and application as a phase II/III trial end point to accelerate evaluation and approval of novel regimens and therapies.
Reduced Cardiac Myosin Adenosinetriphosphatase Activity in Dogs with Spontaneously Occurring Heart Failure
Authors: R. J. LUCHI, E. M. KRITCHER
Journal: Circulation Research (1969)

Cardiac myosin was isolated from the hearts of seven dogs with naturally occurring heart failure.Six of the seven dogs had heart failure secondary to acquired mitral valvular insufficiency; the seventh was believed to have a primary myocardiopathy.The characteristics of this myosin were compared to cardiac myosin from a group of normal dogs studied concurrently.Cardiac myosin was extracted from heart muscle with a phosphate salt solution and purified by repeated fractionation with ammonium sulfate in the presence of 2M lithium chloride.Myosin from dogs with heart failure had a significantly reduced adenosinetriphosphatase activity compared to myosin from the control group.Sulfhydryl group content, shown to influence myosin enzyme activity, was unchanged in myosin from dogs with heart failure.Molecular weight of myosin was similar in both groups.Sedimentation velocity of myosin from dogs with heart failure was suggestive of a configurational change in the molecule, but this was not confirmed by measurement of the intrinsic viscosity and helical content of the protein.These studies suggested that the reduced contractile performance of the myocardium in congestive heart failure complicating a disease process is, in part at least, the result of depressed myosin adenosinetriphosphatase activity. ADDITIONAL KEY WORDS adenosinetriphosphatase activity biochemistry of myosin contractile protein cardiac failure canine heart myosin• The reduced contractile performance of the heart in congestive heart failure is characterized by a depression of both the myocardial force-velocity and length-tension curves (1-3).Study of the pathophysiology and biochemistry of failing human and animal heart muscle has not revealed the cause of this
3-Nitrotyrosine inhibits fibroblast-mediated collagen gel contraction and chemotaxis
Authors: H. Sugiura, X. Liu, T. Ichikawa, M. Ichinose, S. I. Rennard
Journal: European Respiratory Journal (2009)

Reactive nitrogen species induce tissue inflammation and nitrate tyrosine residues of various kinds of proteins. Recent studies have established that the free amino acid form of 3-nitrotyrosine induces cytotoxity and growth inhibition and alters the cellular function in cultured cells. The aim of this study was to evaluate whether 3-nitrotyrosine could affect tissue remodelling in fibroblasts. To accomplish this, human fetal lung fibroblasts (HFL-1) were used to assess the fibroblast-mediated contraction of floating gels and chemotaxis towards fibronectin. In addition, the ability of fibroblasts to release fibronectin, transforming growth factor (TGF)-beta1, fibronectin and vascular endothelial growth factor (VEGF) was assessed. 3-Nitrotyrosine significantly inhibited gel contraction (p<0.01) compared with control and this inhibition was abolished by nitric oxide synthase (NOS) inhibitor. 3-Nitrotyrosine did not affect TGF-beta1 and VEGF but significantly decreased fibronectin release (p<0.01) into the media. 3-Nitrotyrosine significantly inhibited chemotaxis towards fibronectin through suppression of alpha(5)beta(1) integrin expression (p<0.01). NOS inhibitor also reversed 3-nitrotyrosine-inhibited chemotaxis (p<0.01). Finally, 3-nitrotyrosine enhanced the expression of the inducible type of NOS (p<0.01) and nitric oxide release (p<0.01) through nuclear factor-kappaB activation. These results suggest that the free amino acid form of 3-nitrotyrosine can affect the tissue repair process by modulating nitric oxide production.
Human Natural Cytotoxic Activity Mediated by Tumor Necrosis Factor: Regulation by Interleukin-2
Authors: E. C. Lattime, A. Stoppacciaro, A. Khan, O. Stutman
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Human Natural Cytotoxic Activity Mediated by Tumor Necrosis Factor: Regulation by Interleukin-2 Get access Edmund C. Lattime, Edmund C. Lattime * 3Immunology Program, Memorial Sloan-Kettering Cancer CenterNew York, NY. *Correspondence to: Dr. Edmund C. Lattime, Immunology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Search for other works by this author on: Oxford Academic PubMed Google Scholar Antonella Stoppacciaro, Antonella Stoppacciaro 3Immunology Program, Memorial Sloan-Kettering Cancer CenterNew York, NY. Search for other works by this author on: Oxford Academic PubMed Google Scholar Amanullah Khan, Amanullah Khan 4The Cancer Center at Wadley InstitutesDallas, TX. Search for other works by this author on: Oxford Academic PubMed Google Scholar Osias Stutman Osias Stutman 3Immunology Program, Memorial Sloan-Kettering Cancer CenterNew York, NY. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 13, 7 September 1988, Pages 1035–1038, https://doi.org/10.1093/jnci/80.13.1035 Published: 07 September 1988 Article history Received: 15 March 1988 Revision received: 10 June 1988 Accepted: 15 June 1988 Published: 07 September 1988