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  • 1
    Keywords: Medicine ; Gene Therapy ; Molecular Biology ; Pharmacology ; Biomedicine ; Pharmacology/Toxicology ; Gene Therapy ; Molecular Medicine ; Springer eBooks
    Description / Table of Contents: Overview: gene transfer strategies, principles, applications -- Manufacturing viral gene therapy vectors: general approaches and challenges -- Retrovirus- and lentivirus-based vectors -- Preclinical and clinical applications of retroviral vectors -- Preclinical and clinical applications of lentiviral vectors -- Retrovirus and lentivirus integration -- Adenovirus-based vectors for gene therapy -- Adenoviral vector-host interactions -- Helper-dependent adenoviral vectors -- Gene therapy for cancer treatment -- Oncolytic adenoviruses for cancer treatment -- Vaccination by gene transfer vectors -- AAV vectors: general features and applications -- Adaptive immune response to viral vector delivery -- Herpes viruses: general features and applications -- RNA interference-based strategy for treatment of human diseases -- Antisense oligonucleotide based therapeutics -- Gene editing strategies -- Nonviral vectors
    Abstract: In this book, leading international experts analyze state-of-the-art advances in gene transfer vectors for applications in inherited disorders and also examine the toxicity profiles of these methods. The authors discuss the strengths and weaknesses of available vectors in the clinical setting, and specifically focus on the challenges and possible solutions that researchers are testing in order to improve the safety of gene therapy for genetic diseases. This comprehensive and authoritative overview of vector development is a necessary text for researchers, toxicologists, pharmacologists, molecular biologists, physicians, and students in these fields
    Pages: IX, 220 p. 32 illus., 19 illus. in color. : online resource.
    ISBN: 9783319534572
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  • 2
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Type 2 diabetes mellitus is a widespread disease, affecting millions of people globally. Although genetics and environmental factors seem to have a role, the cause of this metabolic disorder is largely unknown. Here we report a genetic flaw that markedly reduced the intracellular expression of the ...
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2018-01-28
    Description: Background/Aim: The High-Mobility Group A1 (HMGA1) protein has been implicated in human malignancies, playing an important role in cancer proliferation, angiogenesis and metastasis. Increased HMGA1 expression has been found in skin mouse tumors, whereas Hmga1-null mice were protected against skin carcinogenesis. Here, we examined the expression of HMGA1 in human skin tumors, squamous cell carcinoma and basal cell carcinoma. Materials and Methods: Tumor and normal skin tissues from 15 affected patients were surgically excised, and mRNA and protein extraction was performed. mRNA and protein content for both HMGA1 and MMP-11, a proteinase enzyme that plays a role in tumor development and progression, was measured by real-time PCR and western blotting, respectively. Data were analyzed by the SPSS software. Results: HMGA1 mRNA and protein expression patterns were higher in neoplastic skin lesions, compared to normal skin (p〈0.001). Similar results were observed for MMP-11. Conclusion: Our data confirm previous observations in mice studies, and suggest that HMGA1 and MMP-11 may play a key role in the proliferation and progression of skin tumors in humans.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
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  • 4
    Keywords: CELLS ; IN-VIVO ; DISEASE ; GENES ; SEQUENCES ; MUCIN ; HUMAN GUT MICROBIOME ; OCCULT-BLOOD-TESTS ; COLON TUMORIGENESIS ; FUSOBACTERIUM
    Abstract: Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved 〉 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host-microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.
    Type of Publication: Journal article published
    PubMed ID: 25432777
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  • 5
    Keywords: ACTIVATED PROTEIN-KINASE ; PROGRAMMED CELL-DEATH ; ISOLATED RAT HEPATOCYTES ; ENDOPLASMIC-RETICULUM STRESS ; CHAPERONE-MEDIATED AUTOPHAGY ; BREAST-CANCER CELLS ; STARVATION-INDUCED AUTOPHAGY ; VACUOLE TARGETING PATHWAY ; GLUCAGON-INDUCED AUTOPHAGY ; BETAINE HOMOCYSTEINE METHYLTRANSFERASE
    Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
    Type of Publication: Journal article published
    PubMed ID: 22966490
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  • 6
    Keywords: Germany ; IN-VIVO ; MICROSCOPY ; VIVO ; CLASSIFICATION ; imaging ; DISEASE ; liver ; PROTEIN ; SAMPLE ; SAMPLES ; NUCLEAR-MEDICINE ; PATIENT ; MR ; MAGNETIC-RESONANCE-SPECTROSCOPY ; METABOLITES ; SPECTROSCOPY ; NO ; STAGE ; US ; PARAMETERS ; MULTIVARIATE ; PREDICTION ; nuclear medicine ; radiology ; RE ; LIGHT ; EX-VIVO ; analysis ; methods ; NUCLEAR ; PROFILES ; technique ; correlation ; metabolomics ; VARIABLES ; LIGHT-MICROSCOPY ; ENGLAND ; SET ; MEDICINE ; quantitative ; PROFILE ; alanine ; CLINICAL-PRACTICE ; metabonomics ; BRAIN ABSCESSES ; cystic echinococcosis ; Echinococcus granulosus ; GRANULOSUS ; H-1-MRS ; high field ; hydatid disease ; INTRACRANIAL HYDATID CYST ; MULTILOCULARIS ; PERCUTANEOUS TREATMENT ; SUCCINATE
    Abstract: Cystic echinococcosis is a worldwide disease caused by larval stages of the parasite Echinococcus granulosus (canine tapeworm). In clinical practice, staging of cyst development by ultrasonography (US) has allowed treatment options to be tailored to individual patient needs. However. the empirical correlation between cyst morphology and parasite viability is not always dependable and has, until now,. required confirmation by invasive assessment of cyst content by light microscopy (LM), for example. Alternatively. high-field H-1 MRS may be used to examine cyst fluid ex vivo and prepare detailed quantitative metabolite profiles. enabling a multivariate metabolomics approach to cyst staging. One-dimensional and two-dimensional H-1 and H-1/C-13 MRS at 600 MHz (14.1 T) was used to analyze 50 cyst aspirates of various US and LM classes. MR parameters and concentrations relative to internal valine were determined for 44 metabolites and four substance classes. The high concentrations of succinate, fumarate, malate, acetate, alanine, and lactate found in earlier studies of viable cysts were confirmed, and additional metabolites such as myo-inositol, sorbitol, 1.5-anhydro-D-glucitol, betaine, and 2-hydroxyisovalerate were identified. Data analysis and cyst classification were performed using univariate (succinate), bivariate (succinate VS fumarate), and multivariate partial least squares discriminant analysis (PSL-DA) methods (With LIP to 48 metabolite variables). Metabolic classification of 23 viable and 18 nonviable cysts oil the basis of succinate alone a,reed with LM results. However. for seven samples, I-M and MRS gave opposing results. Reclassification of these samples and two unclassified samples by PLS-DA prediction techniques led to a set of 50 samples that could be completely separated into viable and nonviable MRS classes with no overlap, using as few as nine variables: succinate. formate, malate, 2-hydroxyisovalerate, acetate, total protein content. 1.5-anhydro-D-glucitol alanine, and betaine. Thus. future noninvasive in vivo applications of MRS would appear promising. Copyright (C) 2008 John Wiley & Sons, Ltd
    Type of Publication: Journal article published
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  • 7
    ISSN: 1573-6903
    Keywords: Aging ; axonal transport ; choline-phosphoglycerides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The anterograde axonal transport of choline-phosphoglycerides was studied in sciatic nerve motoneurons of adult (3-month-old) and aged (24-month-old) rats. After the spinal cord injection of [2-3H]glycerol, choline-phosphoglycerides; the major phospholipid class was transported along the nerve. The axonal transport rate was determined by plotting the distance covered by the front of transported radioactivity as a function of the time employed. In aged animals the rate of the choline-phosphoglyceride anterograde axonal transport was about 68% lower than that of adults; furthermore, the rate slowed down along the nerve in the proximal-distal direction. This alterated axonal transport mechanism might contribute to the degenerative processes observed in distal regions of peripheral nerve fibers of aged animals.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The incorporation of cytidine-containing precursors (CDP-Cho and CDP-Etn) into the main phospholipid classes of cellular fractions enriched in neurons and glial cells from whole rat brains of different ages was examined. The rate of synthesis of choline phosphoglycerides in neuronal homogenates significantly decreased with age up to 18 months; after this time no additional decrease was found. The decrease of CDP-Etn incorporation in neurons was found to be less significantly affected by age up to 18 months, but the enzymic activity decreased after 18 months of age. No changes were found in the corresponding glial activity at any age. Biochemical phenomena that occur in 18-month-old rat brain (aged animals) were compared with phenomena occurring in 2-month-old rat brain (adult animals). No significant variations of lipid composition were found in neurons from either 18-month-old or 2-month-old rat brain. These results, together with some kinetic parameters, suggest that ethanolamine and choline phosphotransferases are affected differently by aging.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-6903
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The turnover of ethanolamine glycerophospholipids (EGP) has been determined in six different cerebral areas of 4-month and 22-month-old rats, by injecting [3H]glycerol together with [14C]ethanolamine into the lateral ventricle of the brain. The areas examined behave quite differently in respect to their utilization of the most simple precursors of phosphoglyceride biosynthesis. The incorporation of both glycerol and ethanolamine is already complete as early as 2–4 hours and then reutilization begins, at least for the so called fast pools of phosphoglycerides. The different slopes of the specific activity of the two precursors in EGP suggest a high degree of variance among catabolic rates in the different brain regions. In aged rats the utilization of the water-soluble precursors of EGP synthesis decreases in all brain areas and these data suggest that aging may have a different effect on the catabolic activities as well as phospholipid biosynthesis.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Neurological sciences 19 (1998), S. 116-119 
    ISSN: 1590-3478
    Keywords: Epilepsy ; Costs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Epilepsy is the most prevalent chronic neurologic condition. In developed countries, its incidence is 30–50 per 100 000 population per year and the prevalence is approximately 5–8 cases per 1 000 population. The rapid growth of health care expenditures has led to increased interest in economic evaluation of health care programs. We reviewed studies on the costs of epilepsy to assess the significance of their quantitative results, through a specific scheme of analysis. The main findings of our study are that a general consensus on cost of illness evaluation is still remote and many studies lack technical details, making difficult any useful comparison of results. New efforts should be realized to achieve a major degree of standardization in methodological processes.
    Type of Medium: Electronic Resource
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