Excessive Facial Wrinkling Is Associated with COPD Occurrence-Does COPD Damage Skin Beauty and Quality?

The aim of this study was to investigate facial wrinkling in COPD patients, its relationship with lung function parameters, and the differences in wrinkling between COPD patients and smokers without COPD. The study included 56 patients with COPD with smoking history and 84 controls. Wrinkle intensity was measured and classified using Daniell's grading system, and the total length of wrinkles was also estimated. The predominant grades of Daniell's scale were IV-V for COPD patients (89.3% of current and 75.0% of former smokers), III-V for controls who currently smoke (89.2%), and II-III for former (92.9%) and never smokers (100%) controls. These distributions were statistically significantly different, but current and former smokers with COPD and COPD former smokers and control current smokers did not differ. In terms of the total length of wrinkles, the COPD patients possessed significantly longer wrinkles than the control subgroups (all p-values were <0.004). Negative correlations between wrinkle length and lung parameters were found. This phenomenon seems to be independent of smoking, but the length of wrinkles is related to lung function parameters. It seems that not only smoking but also COPD damages skin beauty and quality.

Two Paralogous Gb3/CD77 Synthases in Birds Show Different Preferences for Their Glycoprotein and Glycosphingolipid Substrates.

Most glycosyltransferases show remarkable gross and fine substrate specificity, which is reflected in the old one enzyme-one linkage paradigm. While human Gb3/CD77 synthase is a glycosyltransferase that synthesizes the Galα1→4Gal moiety mainly on glycosphingolipids, its pigeon homolog prefers glycoproteins as acceptors. In this study, we characterized two Gb3/CD77 synthase paralogs found in pigeons (Columba livia). We evaluated their specificities in transfected human teratocarcinoma 2102Ep cells by flow cytofluorometry, Western blotting, high-performance thin-layer chromatography, mass spectrometry and metabolic labelling with 14C-galactose. We found that the previously described pigeon Gb3/CD77 synthase (called P) can use predominately glycoproteins as acceptors, while its paralog (called M), which we serendipitously discovered while conducting this study, efficiently synthesizes Galα1→4Gal caps on both glycoproteins and glycosphingolipids. These two paralogs may underlie the difference in expression profiles of Galα1→4Gal-terminated glycoconjugates between neoavians and mammals.

The role of MMP-12 gene polymorphism - 82 A-to-G (rs2276109) in immunopathology of COPD in polish patients: a case control study.

BACKGROUND: Major symptoms of chronic obstructive pulmonary disease (COPD) are chronic bronchitis and emphysema leading from lung tissue destruction, that is an effect of an imbalance between metalloproteinases (MMPs) and their tissue inhibitors activity. As potential factor involved in this COPD pathogenesis, MMP-12 is considered. We investigated the role of genetic polymorphism and protein level of MMP-12 in the COPD development among Poles. METHODS: We analyzed - 82 A > G SNP in the promoter region of MMP-12 gene (rs2276109) among 335 smoked COPD patients and 309 healthy individuals, including 110 smokers. Additionally, 60 COPD patients and 61 controls (23 smokers) were tested for serum levels of MMP-12 using ELISA. All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). RESULTS: We observed that -82G allele and -82GG homozygous genotype frequencies of the SNP rs2276109 were significantly lower in COPD patients than in controls (12.5% vs 16.9%, respectively; χ2 = 4.742, p = 0.02 for allele and 0.5% vs 3.9%, respectively; χ2 = 9.0331, p = 0.01 for genotype). Moreover, -82G allele was more frequent in controls smokers than in non-smokers (22.3% vs 14.1%, χ2 = 6.7588, p = 0.01). Serum level of MMP-12 was significantly higher in COPD patients than in controls groups (6.8 ng/ml vs 3.3 ng/ml, respectively; F = 7.433, p < 0.0001), although independently of analyzed gene polymorphisms. Additionally, no correlation between parameters of lung function (FEV1% and FEV1/FVC) and protein level was found. CONCLUSIONS: We found that -82G allele of SNP rs2276109 was associated with reduced risk of COPD, and COPD patients released more MMP-12 than healthy individuals, but independently on this SNP.

Gait and functional status analysis before and after total knee arthroplasty.

BACKGROUND: Among the procedures for severe gonarthrosis, total knee arthroplasty (TKA) is considered a successful method patient satisfaction and functional improvement; however, TKA is commonly associated with incompletely recovered gait function. The aim of this study was to evaluate the influence of TKA and physiotherapy programmes on gait features and patient-reported functional status and the relationship between them, leading to broader knowledge of the origins of long-term gait disturbances. METHODS: Walking speed, step length and single support time were analysed by GAITRite system in 60 healthy controls and 21 TKA patients analysed at four time points: one day before and five days after surgery and before and after a three-week rehabilitation (12 and 15 weeks after surgery). Functional status was assessed using the Western Ontario and McMaster Osteoarthritis Index (WOMAC). RESULTS: At all time points, the TKA subjects walked significantly slower than the controls, but walking speed continuously increased after surgery. Gait asymmetries were observed in single support time (before surgery) and step length (after surgery). Partial restoration of gait function was observed 12 weeks after surgery and completion of the rehabilitation programme. An indirect correlation between gait velocity and function WOMAC subscores was found. CONCLUSIONS: Patients after TKA were characterised by significant improvements in self-reported functionality and progressive reduction of gait abnormalities, probably related to pain reduction. However, at 15 weeks after surgery, patients exhibited step length asymmetry, which could be considered as an effect of habits of three-point crutch gait in the early postoperative period.

Role of thiamine in Huntington's disease pathogenesis: In vitro studies.

BACKGROUND: Oxidative stress accompanies neurodegeneration and also causes abnormalities in thiaminedependent processes. These processes have been reported to be diminished in the brains of patients with several neurodegenerative diseases. OBJECTIVES: The aim of this work was to conduct a comparative analysis of the impact of supplemented thiamine on the viability of human B lymphocytes with CAG abnormal expanded huntingtin gene (mHTT) (GM13509) and control, B lymphocytes without mHTT (GM14467) through the following studies: determination of the supplemented thiamine concentrations, which are effective for cell growth stimulation after incubation in thiamine deficit conditions; determination of cell capability to intake the exogenous thiamine; evaluation of exogenous thiamine influence on the profile of the genes related to thiamine and energy metabolism; determination of ATP synthesis and activities of thiamine-dependent enzymes, KGDHC and BCKDHC in the intact cells and upon the exogenous thiamine. MATERIAL AND METHODS: The following methods were used: EZ4U test for cell growth analysis; HPLC for determination of thiamine intake and ATP synthesis, qRT-PCR for evaluation of the gene profiles and spectrophotometric method for KGDHC and BCKDHC activities determination. RESULTS: Maximal cell growth stimulation was observed at 2.5 mM in GM14467 up to 135% of the control culture and at 5.0 mM in GM13509 cells up to 165% of the control culture. Native levels of total ATP and KGDHC and BCKDHC activities in both cell types were comparable and did not changed upon thiamine deficit or supplementation. GM13509 cells showed more of an increase in growth stimulation upon thiamine supplementation than GM14467 cells and this effect was reflected in the increase of intracellular thiamine concentration. CONCLUSIONS: The above results and reported changes in expression of GAPDH, IDH1 and SLC19A3 genes observed upon thiamine deficit conditions suggest that intracellular thiamine status and energy metabolism can have a role in HD pathogenesis.

The influence of KIR gene presence/absence polymorphisms on the development of periodontal disease in smokers and non-smokers.

INTRODUCTION: Periodontal diseases are highly prevalent inflammatory, multifactorial diseases. Smoking is one of the most important environmental risk factors for the development and severity of periodontal disease. Killer cell immunoglobulin-like receptors (KIRs) are members of the immunoglobulin (Ig) superfamily and play an essential role in the regulation of NK cell activity, allowing natural killer (NK) cells to sense and respond to human leukocyte antigen (HLA) class I. The aim of this study was to evaluate the influence of KIR gene presence/absence polymorphisms on the development of periodontal disease in smokers and non-smokers. MATERIAL AND METHODS: This study enrolled 400 Caucasian subjects (age range 25-69 years) from the West Pomeranian region of Poland. The subjects were categorized into four subgroups (smoking and non-smoking patients with periodontal disease; smoking and non-smoking subjects without periodontal disease - control subjects). RESULTS: The differences of KIR gene frequencies between non-smoking patients and non-smoking control subjects as well as smoking patients and control subjects were not statistically significant. In multivariate regression analysis advanced age of patients and smoking were independent factors associated with increased frequency of periodontal disease. CONCLUSIONS: The results of this study suggest that the main factor associated with increased risk of periodontal disease is smoking, whereas KIR presence/absence polymorphism is not a significant factor involved in the pathogenesis of periodontal disease.

Evaluation of an amino acid residue critical for the specificity and activity of human Gb3/CD77 synthase.

Human Gb3/CD77 synthase (α1,4-galactosyltransferase) is the only known glycosyltransferase that changes acceptor specificity because of a point mutation. The enzyme, encoded by A4GALT locus, is responsible for biosynthesis of Gal(α1-4)Gal moiety in Gb3 (CD77, Pk antigen) and P1 glycosphingolipids. We showed before that a single nucleotide substitution c.631C > G in the open reading frame of A4GALT, resulting in replacement of glutamine with glutamic acid at position 211 (substitution p. Q211E), broadens the enzyme acceptor specificity, so it can not only attach galactose to another galactose but also to N-acetylgalactosamine. The latter reaction leads to synthesis of NOR antigens, which are glycosphingolipids with terminal Gal(α1-4)GalNAc sequence, never before described in mammals. Because of the apparent importance of position 211 for enzyme activity, we stably transfected the 2102Ep cells with vectors encoding Gb3/CD77 synthase with glutamine substituted by aspartic acid or asparagine, and evaluated the cells by quantitative flow cytometry, high-performance thin-layer chromatography and real-time PCR. We found that cells transfected with vectors encoding Gb3/CD77 synthase with substitutions p. Q211D or p. Q211N did not express Pk, P1 and NOR antigens, suggesting complete loss of enzymatic activity. Thus, amino acid residue at position 211 of Gb3/CD77 synthase is critical for specificity and activity of the enzyme involved in formation of Pk, P1 and NOR antigens. Altogether, this approach affords a new insight into the mechanism of action of the human Gb3/CD77 synthase.

Joint Motion Quality in Chondromalacia Progression Assessed by Vibroacoustic Signal Analysis.

BACKGROUND: Because of the specific biomechanical environment of the patellofemoral joint, chondral disorders, including chondromalacia, often are observed in this articulation. Chondromalacia via pathologic changes in cartilage may lead to qualitative impairment of knee joint motion. OBJECTIVE: To determine the patellofemoral joint motion quality in particular chondromalacia stages and to compare with controls. DESIGN: Retrospective, comparative study. SETTING: Voivodship hospitals, university biomechanical laboratory. PATIENTS: A total of 89 knees with chondromalacia (25 with stage I; 30 with stage II and 34 with stage III) from 50 patients and 64 control healthy knees (from 32 individuals). METHODS: Vibroacoustic signal pattern analysis of joint motion quality. MAIN OUTCOME MEASUREMENTS: For all knees vibroacoustic signals were recorded. Each obtained signal was described by variation of mean square, mean range (R4), and power spectral density for frequency of 50-250 Hz (P1) and 250-450 Hz (P2) parameters. RESULTS: Differences between healthy controls and all chondromalacic knees as well as chondromalacia patellae groups were observed as an increase of analyzed parameters (P < .001) with only one exception. No statistically significant difference between control group and stage I of chondromalacia patellae was found. All chondromalacia groups were differentiated by the use of all analyzed parameters (P < .01), whose values correspond to the progress of chondromalacia. CONCLUSIONS: Chondromalacia generates abnormal vibroacoustic signals, and there seems to be a relationship between the level of signal amplitude as well as frequency and cartilage destruction from the superficial layer to the subchondral bone. LEVEL OF EVIDENCE: IV.

Joint motion quality in vibroacoustic signal analysis for patients with patellofemoral joint disorders.

BACKGROUND: Chondromalacia, lateral patellar compression syndrome and osteoarthritis are common patellofemoral joint disorders leading to functional and/or structural disturbances in articular surfaces. The objective of the study was to evaluate their impact on joint motion quality via the vibroacoustic signal generated during joint movement analysis. METHODS: Seventy-three patients (30 with chondromalacia, 21 with lateral patellar compression syndrome, and 22 with osteoarthritis) and 32 healthy controls were tested during flexion/extension knee motion for vibroacoustic signals using an acceleration sensor. Estimated parameters: variation of mean square (VMS), difference between mean of four maximum and mean of four minimum values (R4), power spectral density for frequency of 50-250 Hz (P1) and 250-450 Hz (P2) were analyzed. RESULTS: Vibroacoustic signals recorded for particular disorders were characterized by significantly higher values of parameters in comparison to the control group. Moreover, differences were found among the various types of patellofemoral joint disturbances. Chondromalacia and osteoarthritis groups showed differences in all parameters examined. In addition, osteoarthritis patients exhibited differences in VMS, P1 and P2 values in comparison to lateral patellar compression syndrome patients. However, only the value of R4 was found to differ between knees with lateral patellar compression syndrome and those with chondromalacia. CONCLUSION: Our results suggest that particular disorders are characterized by specific vibroacoustic patterns of waveforms as well as values of analyzed parameters.

A single point mutation in the gene encoding Gb3/CD77 synthase causes a rare inherited polyagglutination syndrome.

Rare polyagglutinable NOR erythrocytes contain three unique globoside (Gb4Cer) derivatives, NOR1, NOR(int), and NOR2, in which Gal(α1-4), GalNAc(ß1-3)Gal(α1-4), and Gal(α1-4)GalNAc(ß1-3)Gal(α1-4), respectively, are linked to the terminal GalNAc residue of Gb4Cer. NOR1 and NOR2, which both terminate with a Gal(α1-4)GalNAc- sequence, react with anti-NOR antibodies commonly present in human sera. While searching for an enzyme responsible for the biosynthesis of Gal(α1-4)GalNAc, we identified a mutation in the A4GALT gene encoding Gb3/CD77 synthase (α1,4-galactosyltransferase). Fourteen NOR-positive donors were heterozygous for the C>G mutation at position 631 of the open reading frame of the A4GALT gene, whereas 495 NOR-negative donors were homozygous for C at this position. The enzyme encoded by the mutated gene contains glutamic acid instead of glutamine at position 211 (substitution Q211E). To determine whether this mutation could change the enzyme specificity, we transfected a teratocarcinoma cell line (2102Ep) with vectors encoding the consensus Gb3/CD77 synthase and Gb3/CD77 synthase with Glu at position 211. The cellular glycolipids produced by these cells were analyzed by flow cytometry, high-performance thin-layer chromatography, enzymatic degradation, and MALDI-TOF mass spectrometry. Cells transfected with either vector expressed the P1 blood group antigen, which was absent from untransfected cells. Cells transfected with the vector encoding the Gb3/CD77 synthase with Glu at position 211 expressed both P1 and NOR antigens. Collectively, these results suggest that the C631G mutation alters the acceptor specificity of Gb3/CD77 synthase, rendering it able to catalyze synthesis of the Gal(α1-4)Gal and Gal(α1-4)GalNAc moieties.

KIR2DL2/S2 and HLA-C C1C1 genotype is associated with better response to treatment and prolonged survival of patients with non-small cell lung cancer in a Polish Caucasian population.

Non-small cell lung carcinoma (NSCLC) is a multifactorial disease influenced by both environmental and genetic factors. Here, we examined whether the repertoire of genes encoding killer immunoglobulin-like receptors (KIR) and genes for their ligands, C1/C2 and Bw4, may affect a susceptibility to NSCLC and response to treatment. We typed 269 NSCLC patients and 690 healthy control individuals for KIR genes and for their ligands. KIR genes were not associated with NSCLC. C1C2 genotype was less frequent whereas both C1C1 and C2C2 homozygotes were more frequent in patients than in controls (χ(2)=7.73; df=2; p=0.021). Patients positive for KIR2DL2 and KIR2DS2 gene and homozygous for the C1 ligand were 6 times more likely to respond to treatment than those with other genotypes (p=0.034). In accordance with this, patients with the KIR2DL2+/KIR2DS2+, C1C1 genotype survived longer than others (p=0.0094). Median survival was 23months for KIR2DL2/2DS2/C1C1-positive patients, but only 10 months for those with other genotypes.

HLA-C C1C2 heterozygosity may protect women bearing the killer immunoglobulin-like receptor AA genotype from spontaneous abortion.

Spontaneous abortion is the most common complication of human pregnancy. Natural killer (NK) cells expressing killer immunoglobulin-like receptors (KIRs), which may recognize HLA-C (i.e. its C1 or C2 groups) on trophoblast cells, constitute a large leukocyte population in the endometrium. This study investigated whether genetic polymorphisms in the KIR and HLA-C genes are risk factors for spontaneous abortion. One hundred and twenty-five couples with at least two spontaneous abortions, including eighty-five couples with idiopathic recurrent abortion (RSA; three or more abortions), and 117 control couples (with two or more healthy-born children) were tested. The frequencies of the individual KIR genes in the patients were similar to those in the controls. In the group of KIR AA women with HLA-C C2C2 partners, the HLA-C C1C2 heterozygotes were present in the controls but not in the patients (p=0.015 for all patients and p=0.0048 for RSA, but both comparisons lost significance after Bonferroni correction), whereas both homozygotes, C1C1 and C2C2, were absent in the control women but present among the aborting ones. Therefore, our results suggest that among KIR AA women who have HLA-C C2C2 partners, HLA-C heterozygous females show a trend towards an increased chance of successful pregnancy.

Does the KIR2DS5 gene protect from some human diseases?

BACKGROUND: KIR2DS5 gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation. METHODOLOGY/PRINCIPAL FINDINGS: In our studies on KIR2DS5 gene associations with human diseases, we compared the frequencies of this gene in patients and relevant controls. Typing for KIR2DS5 gene was performed by either individual or multiplex polymerase chain reactions which, when compared in the same samples, gave concordant results. We noted an apparently protective effect of KIR2DS5 gene presence in several clinical conditions, but not in others. Namely, this effect was observed in ankylosing spondylitis (p=0.003, odds ratio [OR]=0.47, confidence interval [CI]=0.28-0.79), endometriosis (p=0.03, OR=0.25, CI = 0.07-0.82) and acute rejection of kidney graft (p=0.0056, OR=0.44, CI=0.24-0.80), but not in non-small-cell lung carcinoma, rheumatoid arthritis, spontaneous abortion, or leukemia (all p>0.05). In addition, the simultaneous presence of KIR2DS5 gene and HLA-C C1 allotype exhibited an even stronger protective effect on ankylosing spondylitis (p=0.0003, OR=0.35, CI=0.19-0.65), whereas a lack of KIR2DS5 and the presence of the HLA-C C2 allotype was associated with ankylosing spondylitis (p=0.0017, OR=1.92, CI=1.28-2.89), whereas a lack of KIR2DS5 and presence of C1 allotype was associated with rheumatoid arthritis (p=0.005, OR=1.47, CI=1.13-1.92). The presence of both KIR2DS5 and C1 seemed to protect from acute kidney graft rejection (p=0.017, OR=0.47, CI=0.25-0.89), whereas lack of KIR2DS5 and presence of C2 seemed to favor rejection (p=0.0015, OR=2.13, CI=1.34-3.37). CONCLUSIONS/SIGNIFICANCE: Our results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.

Distribution of CTLA-4 polymorphisms in allergic asthma.

BACKGROUND: The CTLA-4 molecule is an important negative regulator of T cell activation. It is encoded on chromosome 2q33 and found to be associated with several allergic phenotypes including asthma. However, the association of CTLA-4 gene polymorphisms with allergic asthma is still controversial and therefore was the subject of this study. METHODS: By PCR-RFLP, the distribution of three single nucleotide polymorphisms (SNPs), -1147 C/T, -318 C/T, and +49 A/G, was examined in 219 Polish Caucasoid patients diagnosed with allergic asthma and in 102 ethnically matched healthy control individuals. (AT)(n) microsatellite polymorphism was also tested in the same individuals. RESULTS: No statistically significant differences in SNPs or microsatellite allele, genotype or haplotype frequencies between patients and controls were found. CONCLUSION: CTLA-4 polymorphisms do not seem to be a risk factor for allergic asthma in Poles.