380 research outputs found

    Ultrastructure of a hyaluronic acid matrix

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    Freeze-etch replicas of a hylauronic acid matrix were visualized by electron microscopy. In water a coarse branching fibrillar network of hyaluronic acid aggregates was seen. The high solvent permeability of this matrix suggests that the spaces observed are relatively devoid of unaggregated polymer. Addition of calcium disordered the matrix, resulting in a more dispersed felt of polymer

    Electrochemical titrations and reaction time courses monitored in situ by magnetic circular dichroism spectroscopy

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    Magnetic circular dichroism (MCD) spectra, at ultraviolet–visible or near-infrared wavelengths (185–2000 nm), contain the same transitions observed in conventional absorbance spectroscopy, but their bisignate nature and more stringent selection rules provide greatly enhanced resolution. Thus, they have proved to be invaluable in the study of many transition metal-containing proteins. For mainly technical reasons, MCD has been limited almost exclusively to the measurement of static samples. But the ability to employ the resolving power of MCD to follow changes at transition metal sites would be a potentially significant advance. We describe here the development of a cuvette holder that allows reagent injection and sample mixing within the 50-mm-diameter ambient temperature bore of an energized superconducting solenoid. This has allowed us, for the first time, to monitor time-resolved MCD resulting from in situ chemical manipulation of a metalloprotein sample. Furthermore, we report the parallel development of an electrochemical cell using a three-electrode configuration with physically separated working and counter electrodes, allowing true potentiometric titration to be performed within the bore of the MCD solenoid

    The intra-nucleus integration of mitochondrial DNA (mtDNA)in cervical mucosa cells and its relation with c-myc expression

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    <p>Abstract</p> <p>Objective</p> <p>To explore the relationship between the integration of mitochondrial DNA(mtDNA) in the nuclei of cervical epithelium cells and the expression of c-myc.</p> <p>Methods</p> <p>The expression of c-myc protein was measured by immunohistochemical test in 40 cases of the uterine cervix cancer, 30 cases of cervical intraepithelial neoplasia (CIN) and 30 cases of normal cervical epithelium; the sequence of mtDNA in the nuclei was detected by in situ hybridization technique.</p> <p>Results</p> <p>The detection rates of mtDNA in the nuclei of cervical epithelium cells were 27.5%, 13.3% and 0% in cervical carcinoma, CIN, and normal cervical epithelium respectively. The expression rate of c-myc in cervical mucoma cells was 67% in the mtDNA sequence positive group and was significantly higher than that in the negative group (36%).</p> <p>Conclusion</p> <p>The integration of mtDNA into the nuclei of cervical epithelium cells may be involved in the carcinogenesis of cervical epithelium cells and the expression of c-myc might be related to the integration of mtDNA sequence into nuclei of cervical epithelium cells.</p

    Surveillance for Unexplained Deaths and Critical Illnesses

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    Population-based surveillance for unexplained death and critical illness possibly due to infectious causes (UNEX) was conducted in four U.S. Emerging Infections Program sites (population 7.7 million) from May 1, 1995, to December 31, 1998, to define the incidence, epidemiologic features, and etiology of this syndrome. A case was defined as death or critical illness in a hospitalized, previously healthy person, 1 to 49 years of age, with infection hallmarks but no cause identified after routine testing. A total of 137 cases were identified (incidence rate 0.5 per 100,000 per year). Patients’ median age was 20 years, 72 (53%) were female, 112 (82%) were white, and 41 (30%) died. The most common clinical presentations were neurologic (29%), respiratory (27%), and cardiac (21%). Infectious causes were identified for 34 cases (28% of the 122 cases with clinical specimens); 23 (68%) were diagnosed by reference serologic tests, and 11 (32%) by polymerase chain reaction-based methods. The UNEX network model would improve U.S. diagnostic capacities and preparedness for emerging infections

    The dimensional structure of the functional abilities in cases of long-term sickness absence

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    <p>Abstract</p> <p>Background</p> <p>The health problems that working people suffer can affect their functional abilities and, consequently, can cause a mismatch between those abilities and the demands of the work, leading to sickness absence. A lasting decrease in functional abilities can lead to long-term sickness absence and work disability, with negative consequences for both the worker and the larger society. The objective of this study was to identify common disability characteristics among large groups of long-term sick-listed and disabled employees.</p> <p>Methods</p> <p>As part of the disability benefit entitlement procedure in the Netherlands, an insurance physician assesses the functional abilities of the claimant in a standardised form, known as the List of Functional Abilities (LFA), which consists of six sections containing a total of 106 items. For the purposes of this study, we compiled data from 50,931 assessments. These data were used in an exploratory factor analyses, and the results were then used to construct scales. The stability of dimensional structure of the LFA and of the internal consistency of the scales was studied using data from 80,968 assessments carried out earlier, under a slightly different legislation.</p> <p>Results</p> <p>Three separate factor analyses carried out on the functional abilities of five sections of the LFA resulted in 14 scale variables, and one extra scale variable was based on the items from the sixth section. The resulting scale variables showed Cronbach's Alphas ranging from 0.59 to 0.97, with the exception of one of 0.54. The dimensional structure of the LFA in the verification population differed in some aspects. The Cronbach's Alphas of the verification population ranged from 0.58 to 0.97, again with the exception of the same scale: Alpha = 0.49.</p> <p>Conclusion</p> <p>The differences between the dimensional structures of the primary data and the earlier data we found in this study restrict the possibilities to generalise the results. The scales we constructed can be utilised to produce a compact description of the functional abilities of groups of claimants in the Netherlands. Moreover, the matching work demands can be used to identify jobs low on those demands as being the most accessible for the specific type of disabled employees, particularly severely disabled individuals.</p

    Cleavage of the urokinase receptor (uPAR) on oral cancer cells : regulation by transforming growth factor - beta 1 (TGF-beta 1) and potential effects on migration and invasion

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    Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Methods: Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - beta 1 (TGF-beta 1). The role of uPAR cleavage in cell proliferation and migration was analysed using real- time cell analysis and invasion was assessed using the myoma invasion model. Results: We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-beta 1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. Conclusions: These results show that soluble factors in the tumour microenvironment, such as TGF-beta 1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.Peer reviewe

    How Hepatitis D Virus Can Hinder the Control of Hepatitis B Virus

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    BACKGROUND: Hepatitis D (or hepatitis delta) virus is a defective virus that relies on hepatitis B virus (HBV) for transmission; infection with hepatitis D can occur only as coinfection with HBV or superinfection of an existing HBV infection. Because of the bond between the two viruses, control measures for HBV may have also affected the spread of hepatitis D, as evidenced by the decline of hepatitis D in recent years. Since the presence of hepatitis D is associated with suppressed HBV replication and possibly infectivity, it is reasonable to speculate that hepatitis D may facilitate the control of HBV. METHODOLOGY AND PRINCIPAL FINDINGS: We introduced a mathematical model for the transmission of HBV and hepatitis D, where individuals with dual HBV and hepatitis D infection transmit both viruses. We calculated the reproduction numbers of single HBV infections and dual HBV and hepatitis D infections and examined the endemic prevalences of the two viruses. The results show that hepatitis D virus modulates not only the severity of the HBV epidemic, but also the impact of interventions for HBV. Surprisingly we find that the presence of hepatitis D virus may hamper the eradication of HBV. Interventions that aim to reduce the basic reproduction number of HBV below one may not be sufficient to eradicate the virus, as control of HBV depends also on the reproduction numbers of dual infections. CONCLUSIONS AND SIGNIFICANCE: For populations where hepatitis D is endemic, plans for control programs ignoring the presence of hepatitis D may underestimate the HBV epidemic and produce overoptimistic results. The current HBV surveillance should be augmented with monitoring of hepatitis D, in order to improve accuracy of the monitoring and the efficacy of control measures
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