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1.
Barbara A. Booth Jouni Uitto 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,675(1):117-122
Human skin fibroblasts were cultured under conditions optimized for collagen synthesis, and the effects of ascorbic acid on procollagen production, proline hydroxylation and the activity of prolyl hydroxylase were examined in cultures. The results indicated that addition of ascorbic acid to confluent monolayer cultures of adult human skin fibroblasts markedly increased tha amount of [3H]hydroxyproline syntehsized. Ascorbic acid, however, did not increase the synthesis of 3H-labeled collagenous polypeptides assayed independently of hydroxylation of proline residues, nor did it affect the amount of prolyl hydroxylase detectable by an in vitro enzyme assay. Also long-term cultures of the cells or initiation of fibroblast cultures in the presence of ascorbic acid did not lead to an apparent selection of a cell population which might be abnormally responsive to ascorbic acid. Thus, ascorbic acid appears to have one primary action on the synthesis of procollagen by cultured human skin fibroblasts: it is necessary for synthesis of hydroxyproline, and consequently for proper triple helix formation and selection of procollagen. 相似文献
2.
Toshiro Nagayoshi Marie-Genevive Mattei Edith Passage Robert Knowlton Mon-Li Chu Jouni Uitto 《Genomics》1989,5(4):932-935
Laminin, an integral component of basement membranes, consists of three subunit polypeptides, A, B1, and B2 chains. We have recently isolated cDNAs corresponding to human laminin A chain. These cDNAs were utilized for chromosomal in situ hybridizations to establish the genomic location of the laminin A chain gene. Metaphase chromosomes of PHA-stimulated human peripheral blood leukocytes were examined by in situ hybridization with 3H-labeled cDNAs, and the chromosomes were identified by R-banding (fluorochrome-photolysis-Giemsa method). The results indicated that the human laminin A chain is at locus 18p11.3. Since human laminin B1 and B2 chain genes have been previously mapped to chromosomes 7 and 1, respectively, the results indicate that genes encoding human laminin chains reside in separate chromosomes. 相似文献
3.
Interactions between cells and basement membrane components are crucial for the regulation of epithelial cell differentiation and polarization. We have studied by immunohistochemical methods the distribution of integrin adhesion proteins and some of their basement membrane ligands in foetal (16--19 weeks) and adult thyroid follicular epithelia. A diffuse immunoreactivity for only 3, v and 1 integrins was found in foetal follicular epithelium, whereas in adult follicular epithelium these integrins were expressed basally in a polarized manner. Additionally, 3 integrin was seen in a more basolaterally confined manner in adult follicular epithelium. Among basement membrane components, laminin 1, 1, 1 and 2 chains were found in epithelial basement membranes of the foetal thyroid gland, suggestive of the presence of laminins-1 and -3. In contrast, the basement membranes of adult follicular epithelium presented a much weaker immunoreactivity for the laminin 2 chain. Furthermore, immunoreactivity for the laminin 2 chain was occasionally seen in adult thyroid glands, apparently confined to myofibroblasts. Immunoreactivity for type IV collagen 1 and 2 (IV) chains was found in follicular basement membranes of foetal as well as adult thyroid gland. The results suggest that during maturation of foetal thyroid follicular epithelium a distinct polarization of integrins takes place. In mature thyroid follicular epithelium, the presumable adhesion-mediating integrin complexes are 31, v1 and/or v3 mediating adhesion to laminin-1 (1-1- 1) and type IV collagen trimer 12 (IV) 相似文献
4.
Lasse Ryhänen Elaine M.L. Tan Sirpa Rantala-Ryhänen Jouni Uitto 《Archives of biochemistry and biophysics》1982,215(1):230-236
Chick embryo sterna, which actively synthesize type II procollagen, were pulse-labeled with radioactive proline; protein synthesis was then inhibited by unlabeled proline and cycloheximide. After the inhibition of protein synthesis, several amino acids, polyamines, or structurally related compounds were added to the incubation medium. The conversion of procollagen, first to two intermediates, pC-collagen and pN-collagen, and then to collagen, was monitored by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. The addition of 50 mm β-alanine, arginine, asparagine, glutamine, hydroxylysine, lysine, or ornithine, as well as agmatine, ?-aminocaproic acid, S-2-aminoethylcysteine, cadaverine, canavanine, putrescine, or spermine clearly inhibited the removal of the carboxy-terminal extension and pC-collagen accumulated; the removal of the amino-terminal extension was not affected. The inhibition of the conversion was reversible and unaffected by fetal calf serum. The results suggest that the conversion of type II procollagen to collagen requires at least two separate proteinases for the removal of amino-terminal and carboxy-terminal extensions. The results further suggest that naturally occurring molecules may be used to modulate the rate of conversion of procollagen to collagen, and development of analogs of these compounds may provide the means to interfere with excessive deposition of collagen in diseases with tissue fibrosis. 相似文献
5.
Turunen P Jalkanen J Heikura T Puhakka H Karppi J Nyyssönen K Ylä-Herttuala S 《Journal of lipid research》2004,45(9):1633-1639
Oxidation of LDL generates biologically active platelet-activating factor (PAF)-like phospholipid derivatives, which have potent proinflammatory activity. These products are inactivated by lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme capable of hydrolyzing PAF-like phospholipids. In this study, we generated an adenovirus (Ad) encoding human Lp-PLA2 and injected 10(8), 10(9), and 10(10) plaque-forming unit doses of Adlp-PLA2 and control AdlacZ intra-arterially into rabbits to achieve overexpression of Lp-PLA2 in liver and in vivo production of Lp-PLA2-enriched LDL. As a result, LDL particles with 3-fold increased Lp-PLA2 activity were produced with the highest virus dose. Increased Lp-PLA2 activity in LDL particles decreased the degradation rate in RAW 264 macrophages after standard in vitro oxidation to 60-80% compared with LDL isolated from LacZ-transduced control rabbits. The decrease was proportional to the virus dose and Lp-PLA2 activity. Lipid accumulation and foam cell formation in RAW 264 macrophages were also decreased when incubated with oxidized LDL containing the highest Lp-PLA2 activity. Inhibition of the Lp-PLA2 activity in the LDL particles led to an increase in lipid accumulation and foam cell formation. It is concluded that increased Lp-PLA2 activity in LDL attenuates foam cell formation and decreases LDL oxidation and subsequent degradation in macrophages. 相似文献
6.
Background
Atopic diseases, including allergic rhinitis, allergic dermatitis and asthma, are common diseases with a prevalence of 30–40% worldwide and are thus of great global public health importance. Allergic inflammation may influence the immunity against infections, so atopic individuals could be susceptible to respiratory infections. No previous population-based study has addressed the relation between atopy and respiratory infections in adulthood. We assessed the relation between atopic disease, specific IgE antibodies and the occurrence of upper and lower respiratory infections in the past 12 months among working-aged adults.Methods and Findings
A population-based cross-sectional study of 1008 atopic and non-atopic adults 21–63 years old was conducted. Information on atopic diseases, allergy tests and respiratory infections was collected by a questionnaire. Specific IgE antibodies to common aeroallergens were measured in serum. Adults with atopic disease had a significantly increased risk of lower respiratory tract infections (LRTI; including acute bronchitis and pneumonia) with an adjusted risk ratio (RR) 2.24 (95% confidence interval [CI] 1.43, 3.52) and upper respiratory tract infections (URTI; including common cold, sinusitis, tonsillitis, and otitis media) with an adjusted RR 1.55 (1.14, 2.10). The risk of LRTIs increased with increasing level of specific IgE (linear trend P = 0.059).Conclusions
This study provides new evidence that working-aged adults with atopic disease experience significantly more LRTIs and URTIs than non-atopics. The occurrence of respiratory infections increased with increasing levels of specific IgE antibodies to common aeroallergens, showing a dose-response pattern with LRTIs. From the clinical point of view it is important to recognize that those with atopies are a risk group for respiratory infections, including more severe LRTIs. 相似文献7.
Veli-Matti Kangas Laura Kvist Sauli Laaksonen Tuire Nygrén Jouni Aspi 《European Journal of Wildlife Research》2013,59(5):613-627
Genetic structures of Holarctic species are largely formed by Pleistocene colonisation history, dispersal capacity and interactions between biotic and abiotic factors, even though the human impact can also be significant. The Holarctic moose (Alces alces) arrived in Fennoscandia around 9,000–8,000 years ago, and it has been exploited by humans ever since. During the last 400 years, the Finnish moose population has suffered from several population declines, and even local and regional extirpations have occurred. The purpose of the present study is to describe the genetic variation and population structure of the Finnish moose in order to clarify how historical events and human exploitation have influenced the present-day genetic patterns. Altogether 130 moose individuals from seven sampling sites in Finland were analysed at ten microsatellite loci. A variety of population genetic and coalescent-based methods was applied. The Finnish moose population was found to be divided into southern and northern subpopulations with additional lower hierarchical genetic structure. The estimated time of divergence between these two subpopulations was about 96–238 years ago. In addition, an isolation-by-distance pattern was discovered. 相似文献
8.
Environmentally transmitted pathogens face ecological interactions (e.g., competition, predation, parasitism) in the outside-host environment and host immune system during infection. Despite the ubiquitousness of environmental opportunist pathogens, traditional epidemiology focuses on obligatory pathogens incapable of environmental growth. Here we ask how competitive interactions in the outside-host environment affect the dynamics of an opportunist pathogen. We present a model coupling the classical SI and Lotka–Volterra competition models. In this model we compare a linear infectivity response and a sigmoidal infectivity response. An important assumption is that pathogen virulence is traded off with competitive ability in the environment. Removing this trade-off easily results in host extinction. The sigmoidal response is associated with catastrophic appearances of disease outbreaks when outside-host species richness, or overall competition pressure, decreases. This indicates that alleviating outside-host competition with antibacterial substances that also target the competitors can have unexpected outcomes by providing benefits for opportunist pathogens. These findings may help in developing alternative ways of controlling environmental opportunist pathogens. 相似文献
9.
Ori Eytan Fanny Morice-Picard Ofer Sarig Khaled Ezzedine Ofer Isakov Qiaoli Li Akemi Ishida-Yamamoto Noam Shomron Tomer Goldsmith Dana Fuchs-Telem Noam Adir Jouni Uitto Seth?J. Orlow Alain Taieb Eli Sprecher 《American journal of human genetics》2013,93(4):752-757
The coexistence of abnormal keratinization and aberrant pigmentation in a number of cornification disorders has long suggested a mechanistic link between these two processes. Here, we deciphered the genetic basis of Cole disease, a rare autosomal-dominant genodermatosis featuring punctate keratoderma, patchy hypopigmentation, and uncommonly, cutaneous calcifications. Using a combination of exome and direct sequencing, we showed complete cosegregation of the disease phenotype with three heterozygous ENPP1 mutations in three unrelated families. All mutations were found to affect cysteine residues in the somatomedin-B-like 2 (SMB2) domain in the encoded protein, which has been implicated in insulin signaling. ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which is responsible for the generation of inorganic pyrophosphate, a natural inhibitor of mineralization. Previously, biallelic mutations in ENPP1 were shown to underlie a number of recessive conditions characterized by ectopic calcification, thus providing evidence of profound phenotypic heterogeneity in ENPP1-associated genetic diseases. 相似文献
10.
Diseases of epidermal keratins and their linker proteins 总被引:3,自引:0,他引:3
Epidermal keratins, a diverse group of structural proteins, form intermediate filament networks responsible for the structural integrity of keratinocytes. The networks extend from the nucleus of the epidermal cells to the plasma membrane where the keratins attach to linker proteins which are part of desmosomal and hemidesmosomal attachment complexes. The expression of specific keratin genes is regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Progress in molecular characterization of the epidermal keratins and their linker proteins has formed the basis to identify mutations which are associated with distinct cutaneous manifestations in patients with genodermatoses. The precise phenotype of each disease apparently reflects the spatial level of expression of the mutated genes, as well as the types and positions of the mutations and their consequences at mRNA and protein levels. Identification of specific mutations in keratinization disorders has provided the basis for improved diagnosis and subclassification with prognostic implications and has formed the platform for prenatal testing and preimplantation genetic diagnosis. Finally, precise knowledge of the mutations is a prerequisite for development of gene therapy approaches to counteract, and potentially cure, these often devastating and currently intractable diseases. 相似文献