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  • 1
    Publication Date: 2020-09-02
    Description: Trafficking of toll-like receptor 3 (TLR3) from the endoplasmic reticulum (ER) to endolysosomes and its subsequent proteolytic cleavage are required for it to sense viral double-stranded RNA (dsRNA) and trigger antiviral response, yet the underlying mechanisms remain enigmatic. We show that the E3 ubiquitin ligase TRIM3 is mainly located in the Golgi apparatus and transported to the early endosomes upon stimulation with the dsRNA analog poly(I:C). TRIM3 mediates K63-linked polyubiquitination of TLR3 at K831, which is enhanced following poly(I:C) stimulation. The polyubiquitinated TLR3 is recognized and sorted by the ESCRT (endosomal sorting complex required for transport) complexes to endolysosomes. Deficiency of TRIM3 impairs TLR3 trafficking from the Golgi apparatus to endosomes and its subsequent activation.Trim3−/−cells and mice express lower levels of antiviral genes and show lower levels of inflammatory response following poly(I:C) but not lipopolysaccharide (LPS) stimulation. These findings suggest that TRIM3-mediated polyubiquitination of TLR3 represents a feedback-positive regulatory mechanism for TLR3-mediated innate immune and inflammatory responses.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 2
    Publication Date: 2020-04-07
    Print ISSN: 2190-4707
    Electronic ISSN: 2190-4715
    Topics: Chemistry and Pharmacology , Energy, Environment Protection, Nuclear Power Engineering
    Published by Springer
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  • 3
    ISSN: 1432-8798
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Adenovirus type 7 vaccine strain was engineered to express foreign antigens from both the E 3 early promoter in the E 3 region and the major late promoter inserted between the E 4 region and the right inverted terminal repeat. This multiple expression vector was used to express hepatitis B core antigen (HBcAg), hepatits B e antigen (HBeAg), and hepatitis B surface antigen (HBsAg). The gene inserted in the E 3 region was derived from the core gene of the hepatitis B virus genome. When the precore region was present, an immunoreactive group of proteins with molecular weights ranging from 15,000 to 19,000 was secreted into the media. Velocity sedimentation centrifugation of media and lysates from cells infected with recombinants containing the core gene with the precore region resulted in peaks of HBeAg at the top of the gradient where authentic HBeAg should be found. In addition to the core gene in the E 3 region, the surface antigen gene of hepatitis B virus was inserted behind the major late promoter in the E 4 region resulting in an adeno-hepatitis recombinant virus capable of expressing both the core gene and the HBsAg cells. Cells infected with the adeno-hepatitis recombinants could also be stained with peroxidase-conjugates after reacting to antibody against HBcAg. Inoculation of dogs with the recombinant viruses which contained the core gene, with and without the precore sequence, resulted in a significant antibody response to HBcAg/HBeAg. The dogs also produced a significant antibody response to HBsAg as well as neutralizing antibody to adenovirus.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0533
    Keywords: Multi-infarct dementia ; Cerebro-vascular disease ; Hereditary disease ; Immunohistochemistry Endothelin-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A report on a cerebro-vascular disease with autosomal dominant inheritance, characterised by stroke-like episodes beginning in early adulthood and progressive dementia, afflicting one family living in Sweden was presented in 1977. Another afflicted member showing gait and coordination disturbances and impaired cognitive functions is now introduced. Magnetic resonance imaging revealed multiple brain lesions indicating ischaemic injuries. Previous autopsy studies of other cases revealed white matter atrophy, multiple infarcts and lacunes. In one patient who had died from a cerebral haemorrhage, obliteration of intracerebral arteries, occasionally with organised thrombi was present. Autopsy material has now been reinvestigated with special attention to changes of intracerebral arterioles. Cases with long duration of the disease presented pronounced fibrous thickening of the wall of numerous intracerebral arterioles, degeneration of smooth muscle cells of the media and obliteration of the lumen. Immunohistochemistry showed marked expression of fibrillary collagen types I, III and V and of the basal lamina components collagen type IV and laminin. These depositions are probably induced by some primary dysfunction of smooth muscle cells or endothelial cells. Perivascular reactive astrocytes with endothelin-1-like immunoreactivity were present in some brain regions. Endothelin-1 is the most powerful vasoconstrictor peptide known to date. Structural remodelling of intracerebral arterial vessels, actions of different vasoactive factors and rheological disturbances may all interfere with local blood flow in this disease and cause the parenchymal changes of the brain.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0533
    Keywords: Key words: Multi-infarct dementia – Cerebro-vascular disease – Hereditary disease – Immunohistochemistry – Endothelin-1
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. A report on a cerebro-vascular disease with autosomal dominant inheritance, characterised by stroke-like episodes beginning in early adulthood and progressive dementia, afflicting one family living in Sweden was presented in 1977. Another afflicted member showing gait and coordination disturbances and impaired cognitive functions is now introduced. Magnetic resonance imaging revealed multiple brain lesions indicating ischaemic injuries. Previous autopsy studies of other cases revealed white matter atrophy, multiple infarcts and lacunes. In one patient who had died from a cerebral haemorrhage, obliteration of intracerebral arteries, occasionally with organised thrombi was present. Autopsy material has now been reinvestigated with special attention to changes of intracerebral arterioles. Cases with long duration of the disease presented pronounced fibrous thickening of the wall of numerous intracerebral arterioles, degeneration of smooth muscle cells of the media and obliteration of the lumen. Immunohistochemistry showed marked expression of fibrillary collagen types I, III and V and of the basal lamina components collagen type IV and laminin. These depositions are probably induced by some primary dysfunction of smooth muscle cells or endothelial cells. Perivascular reactive astrocytes with endothelin-1-like immunoreactivity were present in some brain regions. Endothelin-1 is the most powerful vasoconstrictor peptide known to date. Structural remodelling of intracerebral arterial vessels, actions of different vasoactive factors and rheological disturbances may all interfere with local blood flow in this disease and cause the parenchymal changes of the brain.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 3-dimensional tumor growth inhibition assay [18] has been adapted to test the cytotoxic activity of a panel of monoclonal antibodies directed to various antigenic determinants on the surface of mouse mammary tumor cells. Target cells can be prepared from either cultured cells or from pieces of fresh tumor. Antibody and complement are added when cells are growing actively and cell growth can be measured, non destructively, over a 7–10-day period. Effective diffusion of antibody through collagen gel and binding to target cells embedded in the gel is demonstrated by indirect immunofluorescent staining. The specificity of monoclonal antibody AMT 101 cytotoxicity for mouse mammary tumor cells is the same in trypan blue exclusion assays of single-cell suspensions as in collagen gel assays, with complete killing seen in the collagen gel assay only. The collagen gel assay allows the testing of repeated treatments in vitro, as well as combined treatment with multiple antibodies. It also allows cell-cell interaction and preserves all cell components in the tumor. The collagen gel assay has potential as a method of predicting the outcome of monoclonal antibody treatment of solid tumors.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0851
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary High-resolution two-dimensional polyacrylamide gel electrophoresis (PAGE) was employed to reveal tumor-associated polypeptide changes, using the BALB/c C4 line mouse mammary model system, for which phenotypic and immunogenic alterations accompanying tumor progression are well defined. In the first set of experiments, polypeptide patterns from 20 µg whole tissue lysates of normal mammary gland, C4 preneoplastic hyperplatic alveolar nodule outgrowth (HAN) and spontaneous tumor from C4 HAN were compared. In order to normalize for differential cellularity and extracellular protein content in the whole tissues, our analysis included polypeptide patterns from serum, increased concentration of protein from whole normal mammary gland, and primary cultures of epithelial cells from normal gland, HAN and tumor. Using a computer-based image-analysis system, 90 polypeptides were identified in C4 tumor that were absent in C4 HAN, normal mammary gland and serum. None of the 90 polypeptides could be shown to represent a definite qualitative change in the protein composition of tumor epithelium as they were found to be either present in a higher concentration of protein from whole normal gland, or present in the primary epithelial culture from HAN, or absent in the primary epithelial culture from tumor. Conversely in the second set of experiments, when epithelial cultures were used as the starting point for comparisons to locate tumor-associated polypeptides, none of the 15 polypeptides that were present in cultures from three different tumors, and absent in the culture from normal mammary gland was specific to C4 tumor, as they were present in whole tissues of normal gland. Thus our experimental approach detected significant quantitative but no qualitative polypeptide changes in whole tumor tissue, or in tumor-derived epithelial cell cultures. This finding may reflect the limitations of the two-dimensional PAGE method, and warrants caution in the use of such gel analysis alone to identify tumor-associated proteins.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    ISSN: 1600-0714
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The submandibular gland (SMG) is a major salivary gland, which plays an important role in maintenance the oral health. In this study, we intended to explore the role of the SMG's defense system of the animals in which experimental inflammation is induced.Methods:  The levels of mRNAs for inflammation cytokines and acute phase proteins were detected by reverse transcriptase-polymerase chain reaction (RT-PCR).Results:  The mRNAs for acute phase proteins were found to be increased in the SMG and extraorbital and intraorbital lacrimal gland (ELG and ILG) of rats at 24 h after subcutaneous injection of turpentine oil. The induction of mRNA for these inflammatory proteins by turpentine oil was preceded by a transient increase in the level of mRNAs for IL-1β, IL-6 and TNF-α at 6 h after subcutaneous injection of the oil. Such cytokine induction was similarly seen by lipopolysaccharide (LPS) injection, and involvement of Toll-like receptor 4 (TLR4) was strongly suggested from experiment using C3H/HeJ mice, a TLR4-deficient mutant strain.Conclusion:  The up-regulation of acute phase proteins and inflammation cytokines in the SMG, ELG and ILG by experimental inflammation suggests the existence of a strict defense system via the innate immune system in the SMG and other exocrine gland.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The minimal gene set essential for life has long been sought. We report the 860-kb genome of the obligate intracellular plant pathogen phytoplasma (Candidatus Phytoplasma asteris, OY strain). The phytoplasma genome encodes even fewer metabolic functions than do mycoplasma genomes. It lacks the ...
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1460-9592
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  A specifically designed ultrasound scanner may be helpful in percutaneous cannulation of the internal jugular vein in pediatric patients. We report a new two-dimensional (2D) ultrasound prelocation (UL) technique using a transesophageal echocardiography (TEE) intraoperative probe instead of the portable scanner, and have compared the new technique with conventional anatomical landmark method (AL) for central venous catheterization in infants and children.Methods:  Sixty-two infants (body weight 〈12 kg) undergoing elective surgery for congenital heart disease were randomized into two groups. In the AL group, the landmark for cannulation was the palpation of the common carotid pulsation or the sternocleidomastoid triangle. In the UL group, the central vein was located by 2D ultrasonic imaging using a TEE intraoperative probe for HP SONOS 4500. The number of cannulation attempts, success rate, and complication rate were recorded.Results:  For the UL and AL groups, the cannulation success rate was 100% and 80% (P 〈 0.05), the incidence of arterial puncture was 3.1% and 26.7% (P 〈 0.025), and the number of attempts was 1.57 ± 1.04 and 2.55 ± 1.76 (P 〈 0.001), respectively.Conclusions:  Two-dimensional ultrasound prelocated central venous catheterization in infants and children is convenient and can markedly increase cannulation success rate and reduce the incidence of complications.
    Type of Medium: Electronic Resource
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