tbuckley/cabot-search huggingface dataset:
620. Liposome-Based Therapeutic Vaccine for Cervical Cancer
Authors: Weihsu Claire Chen, Leaf Huang
Journal: Molecular Therapy (2006)

Top of pageAbstract
Cervical cancer is the second most common cancer among women worldwide. More than 99% of cervical cancers contain human papillomavirus (HPV) DNA while HPV type 16 is the most common subtype and is associated with 50% of cervical cancer cases. Preventive vaccine against HPV infection is already available on market, however, there is not yet a therapeutic vaccine thus far for replacing of the traumatic surgery on patients with cervical carcinoma. The E7 viral protein of HPV16, which is continuously expressed in cervical cancer cells and pre-cancerous lesions, is also a unique antigen for targeting cervical tumor and can be used a potential therapeutic strategy. Previous work in our lab has led to the development of a liposome-based non-viral vaccine delivery system, LPD. The nanoparticle LPD is self-assembled from cationic lipid, protamine and plasmid DNA. We have demonstrated that LPD formulated with a peptide epitope from the HPV16 E7 protein can be taken up by the dendritic cells and the vaccine induces both preventive as well as therapeutic activity against TC-1, a murine cancer cell line which is HPV16-DNA positive and a model for human cervical cancer. In order to study the mechanism how LPD plays a novel adjuvant for stimulating both humoral and cellular immune responses, we have found that DOTAP liposome can stimulate murine dendritic cells (professional antigen presenting cells) toward the expression of costimulatory molecules, i.e. CD80 and CD86. The results were also confirmed in human DC-like cell line, KG-1. Surface markers on KG-1 for identifying DC lineage, i.e. CD11c CD80, CD83 and CD86 were increased via DOTAP liposome stimulation and the amount of the increase was DOTAP dose-dependent. Since high dose of liposome has been reported to cause possible unwanted toxicity, we have tested serum TNF-alpha cytokine secretion from the mice received our LPD/E7 formulation and we found that very low or not detectable amount of TNF-alpha were measured after mice received s.c. injection. In order to optimize our vaccine formulation, we have found that the reduced amount of liposome can also elicit efficient activity and provide therapeutic effect on tumor-bearing mice. All the results obtained from mouse system are being confirmed on human primary DC isolated from human peripheral mononuclear cells (PBMC). Success of these experiments will constitute a strong rationale for a future phase I clinical trial. Supported by Mary Kay Ash Charitable Foundation.
THE TREATMENT OF INOPERABLE SEPTIC PERITONITIS.
Authors: HORACE G. WETHERILL
Journal: JAMA (1902)

The acceptance of this title presupposes that you will permit me to assume that certain cases of septic peritonitis of appendiceal, intestinal and tubal origin may become inoperable, i. e., that the interests of the patient may be better served at times through the adoption of non-surgical measures. This position must be conceded by the radical appendicitis operators in the "operate as soon as the diagnosis is made" class, when they are pinned down to particularly grave cases, for they all meet some cases in which they are unwilling to operate. Septic peritonitis usually has its origin in some local point of infection and the gravity of the symptoms depends upon the virulence of the infection and the area of peritoneum involved through the diffusion of the process; those measures that tend to limit the spread of the infection and favor its localization to a circumscribed area must favor the
Analysis of intramedullary cell density by MRI using the multiple spin-echo technique
Authors: Akira Masumoto, Shuji Yonekura, Munetaka Haida, Noriharu Yanagimachi, Tomomitsu Hotta
Journal: American Journal of Hematology (1997)

Analysis of the intramedullary cell distribution by magnetic resonance imaging (MRI) using conventional techniques involves subjectively interpreting images and estimating the cell distribution on the basis of signal intensity characteristics. In recent years, attempts have been made to achieve more precise analysis by new techniques, including chemical shift imaging. The multiple spin-echo (MSE) technique offers some advantages over conventional MRI. Since it allows measurement of the transverse magnetization decay curve at 32 or more points, it is capable of separating several tissue components with different relaxation times. In addition, this technique can be used with MRI instruments having a static magnetic field as low as 1.0 Tesla. In the present study, the intramedullary cell density was assessed by MRI using the MSE technique in 4 patients with aplastic anemia (AA), 4 patients with myelodysplastic syndrome (MDS), and 5 normal subjects. The water component of the marrow (with a short relaxation time) and the fat component (with a long relaxation time) were separated from each other by analyzing MR images obtained using the MSE technique, and the signal intensity ratio of the 2 components was calculated. The ratio was significantly higher in the AA group than in the other groups (AA vs. MDS, P = 0.0209, AA vs. normal controls, P = 0.0143). The present technique appears promising for quantitative assessment of the intramedullary cell density.
Effect of diphenylhydantoin on synaptosome sodium-potassium-ATPase
Authors: Barry W. Festoff, Stanley H. Appel
Journal: Journal of Clinical Investigation (1968)

Previous studies have demonstrated that electrically induced seizures in rat result in an increased brain intracellular sodium which can be decreased by treatment with sodium diphenylhydantoin (DPH). The correlation of cation transport with membrane-oriented sodium-potassium-adenosine triphosphatase (Na-K-ATPase) prompted an investigation of the effect of DPH upon ATPase enzyme activity.Rat cerebral cortical synaptosomes isolated in Ficoll gradients were employed as the source for Na-K-ATPase. With 50 mM Na, 10 mM K, 7.5 mM Mg, and 1.8 mM ATP, the specific activity of the preparation was 70 mumoles P(i) released/mg synaptosomal protein per 30 min. The ionic and substrate concentrations yielding one-half maximal velocity were 0.5 mM K, 5 mM Na, and 8.5 x 10(-5) M ATP, respectively. At 50 mM Na and 0.2 mM K, DPH produced an average of 92% stimulation of P(i) release above control. The ratio of Na:K rather than the absolute levels of the ions was critical in determining the effect of DPH. DPH produced significant stimulation of enzyme activity under conditions of a high Na:K ratio (25-50:1). At ratios of 5-10:1, DPH produced little or no effect, and at low Na:K ratios (less than 5:1), DPH was inhibitory. Under all ionic conditions examined, DPH produced no apparent change in enzyme affinity for ATP. Assuming the proposed association of Na-K-ATPase with cation transport in brain, the data suggest the possibility that DPH may control seizures by its stimulation of Na-K-ATPase activity.
miR-382 Inhibits Osteosarcoma Metastasis and Relapse by Targeting Y Box-Binding Protein 1
Authors: Meng Xu, Hua Jin, Cheng-Xiong Xu, Bo Sun, Zhi-Gang Song, Wen-Zhi Bi, Yan Wang
Journal: Molecular Therapy (2014)

Lung metastasis and relapse in osteosarcoma (OS) patients indicate poor prognosis. Here, we identified significantly decreased expression of miR-382 in highly metastatic OS cell lines and relapsed OS samples compared to their parental cell lines and primary OS samples, respectively. In addition, our clinical data showed that the miR-382 expression level was inversely associated with relapse and positively associated with metastasis-free survival in OS patients. The overexpression of miR-382 suppressed epithelial-mesenchymal transition (EMT) and metastasis. This overexpression also decreased the cancer stem cell (CSC) population and function in OS cells. In contrast, inhibition of miR-382 stimulated EMT and metastasis and increased CSC population in OS cells. In addition, our in vivo experiments showed that the overexpression of miR-382 inhibited CSC-induced tumor formation, and the combination of miR-382 with doxorubicin prevented disease relapse in OS patients. Furthermore, we demonstrated that miR-382 exerted its tumor-suppressing potential by directly targeting Y box-binding protein 1 (YB-1) in OS. Taken together, our findings suggest that miR-382 functions as a tumor suppressor function and that the overexpression of miR-382 is a novel strategy to inhibit tumor metastasis and prevent CSC-induced relapse in OS.
Mineralocorticoid Receptor Phosphorylation Regulates Ligand Binding and Renal Response to Volume Depletion and Hyperkalemia
Authors: Shigeru Shibata, Jesse Rinehart, Junhui Zhang, Gilbert Moeckel, María Castañeda-Bueno, Amy L. Stiegler, Titus J. Boggon, Gerardo Gamba, Richard P. Lifton
Journal: Cell Metabolism (2013)
Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested case-control study
Authors: Agnetha M Josefsson, Patrik KE Magnusson, Nathalie Ylitalo, Per Sørensen, Pernilla Qwarforth-Tubbin, Per Kragh Andersen, Mads Melbye, Hans-Olov Adami, Ulf B Gyllensten
Journal: The Lancet (2000)
The polymerase chain reaction patents: going, going,... still going
Authors: D. McDowell
Journal: Journal of the Royal Society of Medicine (2006)

The story of the polymerase chain reaction (PCR) rumbles on. The foundational patents for this key technology expired in March last year in the USA and will do the same in Europe in March 2006. Will this result in a genetic free-for-all as many have predicted with the demise of licence and royalty fees? The answer is far from clear.

So what is polymerase chain reaction and why all the hype. Genetics affects all living things. It is what makes us different, not just at a superficial physical level, but in ways that dramatically affect our lives. The polymerase chain reaction is the almost ubiquitously preferred method for facilitating such genetic analysis; it can be used not only for diagnosing a disease but in telling us what diseases we are more likely to suffer from in later life and how to adjust our lifestyles accordingly. It can even tell us how we will respond to therapeutic drugs such that we can avoid adverse reactions by tailoring dosage or selecting alternative therapies as appropriate. It is in areas such as these that the analytical power and potential of polymerase chain reaction for the provision of genetic analysis has been proven time and time again over the last two decades. However, whilst the success of polymerase chain reaction has been backed by significant financial and technological investment, some would argue that it has also been constrained by a strong patent position such that exploitation has been restricted to a few large players with sufficient financial muscle to enter this market.
Abstract S3-1: Lapatinib vs Trastuzumab in Combination with Neoadjuvant Anthracycline-Taxane-Based Chemotherapy: Primary Efficacy Endpoint Analysis of the GEPARQUINTO STUDY (GBG 44)
Authors: M Untch, S Loibl, J Bischoff, H Eidtmann, M Kaufmann, J-U Blohmer, J Hilfrich, D Strumberg, PA Fasching, R Kreienberg, H Tesch, C Hanusch, B Gerber, M Rezai, C Jackisch, J Huober, T Kuehn, V Nekljudova, G. von Minckwitz
Journal: Cancer Research (2010)

Abstract Background: The tyrosine-kinase inhibitor lapatinib (L) has shown to improve efficacy of cytotoxic and endocrine treatment in HER2-positive metastatic breast cancer (BC). Improved pathological complete response (pCR) rates were demonstrated by adding trastuzumab (T) to neoadjuvant chemotherapy. However, so far no head-to-head comparison of the two anti-HER2-agents is available. One primary aim of the GeparQuinto study was to improve the pCR rate by adding L instead of T to anthracycline-taxane-based neoadjuvant chemotherapy. We previously reported interim safety data of this study showing more diarrhea, skin changes, and hot flushes, but no cardiac events with L compared to T (von Minckwitz G et al, Ann Oncol 2010 in press). Patients and Methods: Patients (P) with untreated HER2-positive BC were eligible if they had cT3/4a-d; or estrogen (ER) and progesterone (PgR) receptor-negative; or ER/PgR-positive tumors with clinically N+ (for cT2) or pNSLN+ (for cT1) disease, and no increased cardiac risks. P were randomized to receive 4 cycles epirubicin/cyclophosphamide (EC) (90/600 mg/m2) q3w followed by 4 cycles docetaxel (D) (100mg/m2) given in combination with either T 6 (loading dose 8) mg/kg every 3 weeks or L 1000-1250 mg/d throughout all cycles. pCR was defined as no invasive or non-invasive tumor residuals in breast and nodes. We assumed a pCR rate of 26% with ECT-DT (based on GeparQuattro) and expected a pCR of 37% for ECL-DL (odds ratio 1.67). A two-sided Pearson's Chi2 with α=0.05 and β=0.20 calculated a sample size of 613 P. Results: Between May ‘07 and June ‘10 597 P were randomized to ECT-DT (N=299) and ECL-DL (N=298). Median tumor size was 40/40 [T/L] mm (clinically) and 28/29 mm (sonographically); 4.7%/4.3% had T4a-c, 14.8%/14.2% T4d, 2.9%/1.8% bilateral, 17.0%/17.7% multifocal, and 9.0%/12.1% multicentric disease, 96.7%/97.9% had non-lobular, 45.6%/48.9% grade 3, 70.0%/67.7% node-positive, and 56.5%/56.0% ER and PgR-negative disease. Baseline characteristics were well balanced between the treatment arms. The last randomized P will have surgery early Dec'10. Final results on histological response and surgical outcome will be reported. Conclusion: The GeparQuinto trial will provide for the first time randomized phase III efficacy data on the comparison of L and H in combination to chemotherapy for patients with early breast cancer. As pCR has been confirmed as being a surrogate marker for long-term outcome after T treatment, this result will give insight on the overall efficacy of L in patients with early breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S3-1.
Prevention of the initial host immuno-inflammatory response determines the long-term survival of encapsulated myoblasts genetically engineered for erythropoietin delivery
Authors: Bernard Laurent Schneider, Frank Schwenter, William François Pralong, Patrick Aebischer
Journal: Molecular Therapy (2003)

The present study investigates the respective roles of both the host immune response and the metabolic requirements in determining the long-term survival of erythropoietin-secreting myoblasts within encapsulating polymer membranes. Hollow-fiber capsules loaded with a high density of erythropoietin-secreting C2C12 myoblasts survived poorly in the subcutaneous tissue of syngeneic mice, inducing variable hematocrit responses. To determine the role and the nature of the host response, recipients were treated with anti-inflammatory (diclofenac) and immunosuppressive (dexamethasone, FK506) agents. Only immunosuppressive drugs led to improved graft survival after 5 weeks of implantation, indicating an immune process as the cause of cell death. Furthermore, transient blocking of this process allowed long-term preservation of the implanted cells (> 100 days). The formation of necrotic cell cores inside densely packed devices elicited a local chronic inflammatory reaction. Hence, implants were designed to limit early cell death by inserting a supporting matrix and decreasing the number of loaded cells. The most efficient erythropoietin delivery was obtained with matrix-containing capsules that had received the lowest myoblast density. These results highlight the critical role of initial engraftment in the long-term acceptance of encapsulated myoblasts and the need to limit early cell death in the device to prevent subsequent host immuno-inflammatory responses.
Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis
Authors: Lucio Amitrano, Vincenzo Brancaccio, Maria Anna Guardascione, Maurizio Margaglione, Luigi Iannaccone, Giovanna D’Andrea, Riccardo Marmo, Paul R. Ames, Antonio Balzano
Journal: Hepatology (2000)

The prevalence and pathogenesis of portal vein thrombosis (PVT) in patients with cirrhosis without hepatocellular carcinoma are not clearly defined. The role of thrombophilic genetic factors is well established in other venous thrombotic diseases, as well as in noncirrhotic portal thrombosis. Recently, new, inherited thrombophilic disorders (factor V Leiden [FVL], mutation G20210A of prothrombin [PTHR A 20210 ], and mutation TT677 of methylenetetrahydrofolate reductase [MTHFR C677→T]) have been identified and associated with increased risk of venous thrombosis. The aim of our study was to investigate the role of these thrombophilic disorders in the pathogenesis of PVT in cirrhotic patients. Twenty-three cirrhotic patients with PVT and 40 cirrhotics without PVT were included. A group of 184 patients with deep vein thrombosis (DVT) and 431 healthy persons served as controls. The FVL, PTHR A 20210 , and MTHFR C 677 →T genotypes were identified by a polymerase chain reaction and restriction analysis. The frequencies of FVL, PTHR A 20210 mutation, and homozygous MTHFR C 677 →T were 13%, 34.8%, and 43.5% in cirrhotic patients with PVT and 7.5%, 2.5%, and 5% in cirrhotic patients without PVT, respectively. Five patients in the former group had associated defects. A thrombophilic genotype was detected in 69.5% of the patients with PVT. Identification of this high-risk group may have implications in patients who are candidates for major surgery or liver transplantation, and may influence the duration of oral anticoagulation.
THE SURGICAL IMPORTANCE OF THE CERVICAL RIB.
Authors: CARL BECK
Journal: JAMA (1905)

While the supernumerary ribs of the lumbar vertebræ possess an academic interest only, the accessory rib of the cervical portion of the spinal column commands practical importance. Literature does not contain a single case in which the lumbar rib has caused any discomfort whatsoever. In contrast hereto the observations concerning more or less great disturbances, due to cervical rib, are multiplying with each year. The Roentgen ray has enabled us to obtain more accurate anatomic knowledge of this region and has also given us a means to determine the accuracy of surgical procedures. We have learned to use the Roentgen picture as a reliable guide in outlining the plan of operation. Naturally it was the anatomists who gave us the etiology at a period when we did not as yet value the clinical importance of the cervical rib. As the pioneer in this direction we may consider Hunauld.<sup>1</sup>
Determination of reliability criteria for liver stiffness evaluation by transient elastography
Authors: Jérôme Boursier, Jean-Pierre Zarski, Victor de Ledinghen, Marie-Christine Rousselet, Nathalie Sturm, Brigitte Lebail, Isabelle Fouchard-Hubert, Yves Gallois, Frédéric Oberti, Sandrine Bertrais, Paul Calès
Journal: Hepatology (2012)

Liver stiffness evaluation (LSE) is usually considered as reliable when it fulfills all the following criteria: ≥10 valid measurements, ≥60% success rate, and interquartile range / median ratio (IQR/M) ≤0.30. However, such reliable LSE have never been shown to be more accurate than unreliable LSE. Thus, we aimed to evaluate the relevance of the usual definition for LSE reliability, and to improve reliability by using diagnostic accuracy as a primary outcome in a large population. 1,165 patients with chronic liver disease from 19 French centers were included. All patients had liver biopsy and LSE. 75.7% of LSE were reliable according to the usual definition. However, these reliable LSE were not significantly more accurate than unreliable LSE with, respectively: 85.8% versus 81.5% well-classified patients for the diagnosis of cirrhosis ( P = 0.082). In multivariate analyses with different diagnostic targets, LSE median and IQR/M were independent predictors of fibrosis staging, with no significant influence of ≥10 valid measurements or LSE success rate. These two reliability criteria determined three LSE groups: “very reliable” (IQR/M ≤0.10), “reliable” (0.10&lt; IQR/M ≤0.30, or IQR/M &gt;0.30 with LSE median &lt;7.1 kPa), and “poorly reliable” (IQR/M &gt;0.30 with LSE median ≥7.1 kPa). The rates of well-classified patients for the diagnosis of cirrhosis were, respectively: 90.4%, 85.8%, and 69.5% ( P &lt; 10−3). According to these new reliability criteria, 9.1% of LSE were poorly reliable (versus 24.3% unreliable LSE with the usual definition, P &lt; 10−3), 74.3% were reliable, and 16.6% were very reliable. Conclusion : The usual definition for LSE reliability is not relevant. LSE reliability depends on IQR/M according to liver stiffness median level, defining thus three reliability categories: very reliable, reliable, and poorly reliable LSE. (Hepatology 2013)
Functional Respiratory Chain Analyses in Murid Xenomitochondrial Cybrids Expose Coevolutionary Constraints of Cytochrome b and Nuclear Subunits of Complex III
Authors: M. McKenzie
Journal: Molecular Biology and Evolution (2003)

The large number of extant Muridae species provides the opportunity of investigating functional limits of nuclear/mitochondrial respiratory chain (RC) subunit interactions by introducing mitochondrial genomes from progressively more divergent species into Mus musculus domesticus mtDNA-less (ρ0) cells. We created a panel of such xenomitochondrial cybrids, using as mitochondrial donors cells from six murid species with divergence from M. m. domesticus estimated at 2 to 12 Myr before present. Species used were Mus spretus, Mus caroli, Mus dunni, Mus pahari, Otomys irroratus, and Rattus norvegicus. Parsimony analysis of partial mtDNA sequences showed agreement with previous molecular phylogenies, with the exception that Otomys did not nest within the murinae as suggested by some recent nuclear gene analyses. Cellular production of lactate, a sensitive indicator of decreased respiratory chain ATP production, correlated with divergence. Functional characterization of the chimeric RC complexes in isolated mitochondria using enzymological analyses demonstrated varying decreases in activities of complexes I, III, and IV, which have subunits encoded in both mitochondrial and nuclear genomes. Complex III showed a striking decline in electron transfer function in the most divergent xenocybrids, being greatly reduced in the Rattus xenocybrid and virtually absent in the Otomys xenocybrid. This suggests that nuclear subunits interacting with cytochrome b face the greatest constraints in the coevolution of murid RC subunits. We sequenced the cytochrome b gene from the species used to identify potential amino acid substitutions involved in such interactions. The greater sensitivity of complex III to xenocybrid dysfunction may result from the encoding of redox center apoproteins in both nuclear and mitochondrial genomes, a unique feature of this RC complex.
Focal Infarction of Muscle in Diabetics
Authors: C S Chester, B Q Banker
Journal: Diabetes Care (1986)

Diabetic patients may develop a painful mass in the leg as a manifestation of spontaneous infarction of muscle. Experience with six patients with focal infarction of muscle without peripheral gangrene has demonstrated a stereotyped clinical presentation. The use of an open muscle biopsy to confirm the diagnosis has been associated with increased signs and symptoms. Clinical exacerbations occur during vigorous physical therapy. We delineate the characteristic clinical and pathologic findings and the course of the illness with emphasis on the importance of recognition of the syndrome so that biopsy and overzealous therapy are avoided.