PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-10 (10)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
1.  Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project 
Experimental gerontology  2011;46(11):934-945.
In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90 years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition.
From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50–75 years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies).
Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7 years the number of families with all participating siblings aged 95 years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.
doi:10.1016/j.exger.2011.08.005
PMCID: PMC3622890  PMID: 21871552
Longevity; Healthy ageing; Nonagenarian sib pairs; Genetics; Europe
2.  C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk 
British Journal of Cancer  2009;100(12):1846-1851.
Growing evidence points to a role for inflammation in prostate carcinogenesis. The significance of C-reactive protein (CRP), an inflammatory and innate immunity molecule, has not been evaluated thoroughly in prostate cancer (PC). In this study of 739 Finnish patients with PC and 760 healthy men, we evaluated the associations of CRP genotypes and haplotypes with total PC risk and PC progression, using prostate-specific antigen (PSA) as a marker of metastatic disease. Although the haplotype frequencies were similar in patients and controls, an association between haplotype ACCCA and patients' PSA levels was found. The carriers more often had a high PSA than non-carriers (P=0.0002) and the SNP rs2794521 A-allele and rs1800947 C-allele carriers had a higher PSA than non-carriers (P=0.009 and P=0.0004, respectively). A trend for a younger age at diagnosis was found among the carriers of ACCCA (P=0.07) and the rs1800947 C-allele (P=0.06), as well as a trend for the latter to have more likely metastases (P=0.06), but not after Bonferroni correction (α=0.00208). This is the first study to suggest association between PSA and CRP variants in PC and, therefore, further studies are warranted. CRP alleles previously found to protect against increased CRP levels are now suggested to be associated with metastatic PC, indicated by elevated PSA.
doi:10.1038/sj.bjc.6605081
PMCID: PMC2714238  PMID: 19436291
prostate cancer; inflammation; immunology; CRP gene; association study
3.  Polymorphism at position +896 of the toll‐like receptor 4 gene interferes with rapid response to treatment in rheumatoid arthritis 
Annals of the Rheumatic Diseases  2006;65(9):1241-1243.
The aim of this study was to determine whether the +896 A→G substitution of the Toll‐like receptor 4 (TLR4) gene, causing the Asp299→Gly change in the extracellular domain of TLR4, influences treatment response in recent‐onset rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were treated either with only one disease‐modifying antirheumatic drug (DMARD) with or without prednisolone (single group), or with three DMARDs and prednisolone (combination group). Patients homozygotic for the wild‐type +896A allele were compared with those having the polymorphic G allele in terms of early clinical response (at 6 months) by the 28‐joint Disease Activity Score (DAS28). 1 of 20 (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with TLR4 +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in remission (p = 0.001). DAS28 of the single group with TLR4 +896AG or GG was higher than with AA (p = 0.019). In the combination group, remission rates and DAS28 values were comparable between the genotypes. The polymorphic TLR4 +896G allele may impair treatment response to single DMARD treatment in recent‐onset rheumatoid arthritis.
doi:10.1136/ard.2006.055137
PMCID: PMC1798301  PMID: 16606645
4.  Th2 cytokine genotypes are associated with a milder form of primary Sjögren's syndrome 
Annals of the Rheumatic Diseases  2005;65(5):666-670.
Background
Immunohistological studies on salivary and lacrimal glands have yielded conflicting results on the Th1/Th2 balance in primary Sjögren's syndrome (pSS).
Objective
To establish whether pSS is a Th1 or Th2 directed autoimmune disease by analysing the polymorphism of the genes encoding for cytokines involved in the regulation of Th1/Th2 differentiation.
Methods
The polymorphisms of the genes encoding for interleukin 4 (IL4) −590 C/T, interleukin 13 (IL13) +2044 G/A, and interferon γ (IFNG) +874 T/A were analysed in 63 white Finnish patients with pSS (61 female, two male) and in 63 healthy controls. The clinical and immunological data on the pSS patients were analysed in relation to these cytokine gene polymorphisms.
Results
There were no significant differences in the genotype or allele frequencies of IL4 −590, IL13 +2044, or IFNG +874 between pSS patients and controls. The erythrocyte sedimentation rate and concentrations of serum IgA and serum β2 microglobulin were lower in pSS patients carrying the IL4 −590 T allele or the IL13 +2044 A allele than in those not carrying the respective alleles. The IL4 −509 T allele and IL13 +2044 A allele carriers less often had purpura than the corresponding non‐carriers.
Conclusions
The frequencies of the cytokine genotypes regulating Th1/Th2 differentiation did not differ between pSS patients and controls. However, the presence of cytokine genotypes with increased susceptibility to atopic and other Th2 diseases was associated with signs of a milder form of pSS. This finding would favour a hypothesis envisaging pSS as primarily a Th1 mediated autoimmune disease.
doi:10.1136/ard.2005.040956
PMCID: PMC1798135  PMID: 16166103
gene polymorphism; interleukin 4; interleukin 13; primary Sjögren's syndrome; Th2 genotypes
6.  IL-1 haplotypes and lung function decline 
Thorax  2002;57(6):561-562.
doi:10.1136/thorax.57.6.561-a
PMCID: PMC1746346  PMID: 12037235
8.  Surgical treatment of patellar tendon pain in athletes. 
A series of surgically treated patellar tendon lesions among athletes is presented. The material was collected during 5 years from three sports injury clinics and from two hospitals. During this period the authors treated about 150 cases of jumper's knee, of which 34 cases were treated by operation. The athletes were mostly volley ball players, jumpers or runners. The operation revealed a necrotic focus of the patellar tendon in 21 cases, the retinaculum was thick and adherent in 16 patients and an exostosis of the patellar insertion was seen in two cases. The necrotic areas were excised, the thick and adherent retinaculum was divided and the exostoses were excised and drilled. Surgical treatment of chronic patellar tendon pains may give good results in selected cases.
PMCID: PMC1478326  PMID: 3814988
9.  Uukuniemi virus maturation: immunofluorescence microscopy with monoclonal glycoprotein-specific antibodies. 
Journal of Virology  1984;51(1):137-146.
Monoclonal antibodies directed against Uukuniemi virus glycoproteins G1 and G2 in combination with polyclonal antibodies against the nucleoprotein (N) were used to study the maturation of the virus in Golgi complexes of infected chicken embryo fibroblasts and BHK cells. Of 25 monoclonal antibodies obtained, 10 were shown to be G1 specific and 15 were shown to be G2 specific by immunoblotting and immunoprecipitation. In double-staining experiments, some of the monoclonal antibodies gave similar distributions of fluorescence as compared with the staining obtained from polyclonal rabbit anti-G1-G2 antibodies. Others, however, preferentially stained either the glycoproteins in the Golgi complex or those at the cell surface. This may indicate that the glycoproteins underwent conformational changes during their transport. Uukuniemi virus infection resulted in the vacuolization of the membranes of Golgi complexes where the maturation of the virus was taking place. Double-staining experiments with monoclonal antibodies which preferentially stained the Golgi-associated viral glycoproteins and with anti-N polyclonal rabbit antiserum showed a correlation between the progressive vacuolization of the Golgi complex and the accumulation of viral nucleoprotein in the Golgi region, suggesting that a morphological alteration of the Golgi complex may be a prerequisite for intracellular maturation of the virus. Treatment of Uukuniemi virus-infected cells with tunicamycin, a drug which inhibits N-linked glycosylation, resulted in the accumulation of both glycoproteins at an intracellular location, apparently representing the endoplasmic reticulum. Double-staining experiments showed a parallel accumulation of nucleoprotein at these sites, indicating that local accumulation of glycoproteins is required for nucleoprotein binding to intracellular membranes.
Images
PMCID: PMC254411  PMID: 6374166
10.  Analysis of Campylobacter jejuni antigens with monoclonal antibodies. 
Journal of Clinical Microbiology  1984;19(2):129-133.
To develop monoclonal reagents for antigenic analysis and serotyping of Campylobacter spp., hybridoma cell lines were produced by fusion of mouse myeloma cells and spleen cells from mice immunized with Formalin-treated Campylobacter jejuni organisms. An enzyme immunoassay was used for preliminary screening of the cell culture supernatants and ascites. Twenty-nine clones which reacted with the immunogen were obtained. Seven of these clones were positive in passive hemagglutination tests with sheep erythrocytes coated with boiled saline extract of whole bacteria; four of these reacted with the purified polysaccharide preparation and with the autoclaved saline extract, but not with lipopolysaccharide prepared from the immunogen strain. Two of the antipolysaccharide clones agglutinated live bacteria in slide tests. Four additional clones gave positive slide agglutination tests with live bacteria, but in tube testing no clones agglutinated Formalin-treated bacteria. No cross-reactions with unrelated bacteria were seen, but several clones reacted in the enzyme immunoassay with many of the 24 Campylobacter strains studied. The clone which gave the highest mean enzyme immunoassay values with Campylobacter coli and C. jejuni strains also reacted with Campylobacter fetus subsp. veneralis and C. fetus subsp. fetus strains. This clone also gave the highest enzyme immunoassay value with an acid glycine extract of the immunogen, which indicates the presence of common antigens in the extract. The results suggest that monoclonal antibodies may be used to devise serotyping schemes for Campylobacter spp.
PMCID: PMC271001  PMID: 6365954

Results 1-10 (10)