Serum immunoglobulin levels and the risk of bladder cancer in the AMORIS Cohort

BackgroundThe anti-tumour T-cell response in bladder cancer has been shown to correlate with response to treatment and prognosis. However, little is known about the role of humoral immunity in this highly immunogenic human cancer, which is characterised by a high mutation-associated neoantigen load and a strong response to immunotherapy. In the present study, we interrogated the Swedish Apolipoprotein Mortality Risk Study (AMORIS) to explore the relationship between pre-diagnostic serum immunoglobulin levels and the risk of developing bladder cancer.MethodsOur analysis included all AMORIS participants aged 20 years or older, who had all three major serum immunoglobulins (IgA, IgM, IgG) recorded at the same baseline measurement (n = 29,876). All participants were free from bladder cancer at the time of measurement. Samples were obtained between 1985–1996, with follow-up information until 2011. Multivariate Cox proportional hazards regression was used to investigate the association between bladder cancer risk and different levels of pre-diagnostic serum immunoglobulins.ResultsDuring a mean follow-up period of 15.31 years, 163 (0.5%) individuals were diagnosed with bladder cancer. Multivariate Cox regression showed an inverse association between pre-diagnostic serum IgM levels ≥ 1.4 g/L and bladder cancer risk compared to serum IgM levels < 1.4 g/L [HR: 0.68 (95% CI 0.45–1.03)]. Corresponding associations could not be established for serum IgA or IgG.ConclusionOur findings implicate serum IgM in the pathogenesis of bladder cancer and suggest that the concept of humoral immune surveillance against cancer warrants further mechanistic investigation.     

Blood group and protein polymorphism gene frequencies for seven breeds of horses in the United States

Gene frequencies at 20 blood group and protein polymorphism loci ( A, C, D, K, P, Q, U, Al, Tf, Pi, Xk, Es, Gc, PGD, CA, Cat, PGM, AP, Hb and PHI ) are given for seven horse breeds in the United States (Thoroughbred, Arabian, Standard bred, Morgan, Quarter Horse, Paso Fino and Peruvian Paso). These data are used to calculate that the battery of tests is at least 96% effective for recognizing incorrect paternity in these breeds. In addition to paternity testing, these tests can be applied to studies of breed relationships.     

Classical genetic markers and DNA markers: A commensal marriage

In this paper, we present an overview of classical genetic markers in nonhuman primates and then contrast the discriminatory powers of these markers with DNA markers. We have restricted the scope of our discussion to genetic markers found in blood, since they have been studied most extensively over the past 30 years. For example, immunoglobulin allotypes, complement markers, transferrins, and other protein markers can be identified using serum or plasma. Lymphocytes carry the major histocompatibility complex (MHC) markers, which are very polymorphic in most nonhuman primates. Lymphocytes are also used as a source of DNA. Finally, red blood cells carry an enormous array of blood group as well as isozyme markers. Our discussion will be limited to three species: rhesus monkeys (Macaca mulatta), baboons (Papio hamadryas), and chimpanzees (Pan troglodytes), although the principles are applicable to all nonhuman primates.     

The relationship between airway immunoglobulin activity and eosinophils in COPD

In chronic obstructive pulmonary disease (COPD), the effects of inhaled corticosteroids are predicted by blood eosinophil counts. We previously briefly reported increased immunoglobulin (Ig)A and IgM levels in bronchoalveolar lavage (BAL) of COPD patients with higher (eosinophil^high) compared to lower (eosinophil^low) blood eosinophils (>250/μL versus < 150/μL), suggesting differences in adaptive immune function. An inverse relationship exists between eosinophil counts and airway pathogenic bacteria levels. The mechanistic reasons for these associations between eosinophils, corticosteroids and pathogenic bacteria are unclear. IgA, IgM and IgG levels were assessed in BAL, bronchial biopsies and epithelium collected from eosinophil^high (n = 20) and eosinophil^low (n = 21) patients. Bronchial B-cell numbers were measured by immunohistochemistry. B-cell activity was assessed in bronchial samples and following exposure to BAL from eosinophil^high and eosinophil^low patients. BAL levels of non-typeable Haemophilus influenza (NTHi)-specific immunoglobulins were quantified. Results showed airway expression of IgA, IgG1 and IgM were lower in eosinophil^low compared to eosinophil^high patients, with lower levels of NTHi-specific IgA and IgM. Bronchial B-cell numbers were similar in both groups, but B-cell activity was lower in eosinophil^low patients. In conclusion, COPD eosinophil^low patients show differences in adaptive immune function compared to COPD eosinophil^high patients. These differences may cause different microbiomes in these COPD phenotypes.     

Sheep blood polymorphism and genetic divergence between French Rambouillet and Spanish Merino: role of genetic drift

Rambouillet sheep originating from Spanish Merino have been maintained in France as a small and closed flock since their importation. After 190 years of independent evolution, the flock has markedly differentiated from its Spanish parental population. The observed differences between them were characterized by the fixation in Rambouillet of the Mb and F30 alleles, which occurred in Spanish Merino with frequencies of 0.90 and 0.80 respectively (at two distinct blood group loci M and F30) and by the absence in Rambouillet of other alleles or phenogroups (at the Tf and the A, B, C blood group loci) which were observed in Spanish Merino with frequencies ranging from 0.10 to 0.28. On the basis of their phenotypic distributions at 11 blood polymorphic loci, the two populations differed significantly from each other (total chi 2 values = 352.62, 23 df, P less than 0.001). By comparing the observed magnitude of gene frequency differences between Rambouillet and Spanish Merino with the estimate of inbreeding coefficient for Rambouillet obtained from pedigrees, it appeared that the observed genetic differences could be attributed to the evolutionary change due to random drift in the small and closed flock of Rambouillet.     

Serum and urinary selenium levels in obese children: A cross-sectional study

ObjectiveTo determine serum and urinary selenium (Se) levels in children with and without obesity, and to assess if Se influences the risk of obesity.Subjects and methodsHigh-resolution-continuum source-atomic absorption spectrometry (HR-CS-AAS) was used to determine the content of Se in 80 children (age 6–17; 40 boys, 40 girls). Correlations between variables were tested with the use of Spearman's correlation coefficient. U Mann–Whitney test was applied to assess the difference of Se contents in samples. Measured metabolic risk factors (blood pressure, glucose level, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol), age, gender, and BMI were correlated. Logistic regression models were fitted to identify predictors of obesity interacting with selenium content in serum and urine, separately.ResultsObese children, regardless of gender, had lower Se content. Se level in serum (p = 0.001, OR 0.74, 95%CI 0.62–0.88) and total cholesterol (p = 0.001, OR 1.19, 95%CI 1.08–1.31) were the independent factors significantly influencing the risk of obesity in children. Two separate models were observed for Se in urine: (i) Se level (p < 0. 0001, OR 0.70, 95%CI 0.58–0.84) and glucose level (p < 0.0001, OR 1.22, 95%CI 1.10–1.35), and (ii) Se level (p = 0.002, OR 0.60 95%CI 0.43–0.83) and total cholesterol level (p = 0.003, OR 1.16, 95%CI 1.05–1.28).ConclusionThe current study suggests a possible role of Se in obesity. Further research needs to be performed to check if obese children are an at-risk group for Se deficiency.     

Genetic polymorphism in varietal identification and genetic improvement

Summary New sources of genetic polymorphisms promise significant additions to the number of useful genetic markers in agricultural plants and animals, and prompt this review of potential applications of polymorphic genetic markers in plant and animal breeding. Two major areas of application can be distinguished. The first is based on the utilization of genetic markers to determine genetic relationships. These applications include varietal identification, protection of breeder's rights, and parentage determination. The second area of application is based on the use of genetic markers to identify and map loci affecting quantitative traits, and to monitor these loci during introgression or selection programs. A variety of breeding applications based on these possibilities can be envisaged for Selfers, particularly for those species having a relatively small genome size. These applications include: (i) screening genetic resources for useful quantitative trait alleles, and introgression of chromosome segments containing these alleles from resource strain to commercial variety; (ii) development of improved pure lines out of a cross between two existing commercial varieties; and (iii) development of crosses showing increased hybrid vigor. Breeding applications in segregating populations are more limited, particularly in species with a relatively large genome size. Potential applications, however, include: (i) preliminary selection of young males in dairy cattle on the basis of evaluated chromosomes of their proven sire; (ii) genetic analysis of resource strains characterized by high values for a particular quantitative trait, and introgression of chromosome segments carrying alleles contributing to the high values from resource strain to recipient strain.Contribution from The Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel, No. 767-E, 1983 Series     

Genetic variation in the blood of llamas, Llama glama, and alpacas, Llama pacos

Blood samples of llamas and alpacas were typed using haemolytic, electrophoretic and isoelectric focusing procedures to assay polymorphism at 13 loci. Blood group variation was assessed using six antibody specificities produced by allo- and heteroimmunizations. Two red cell factors (A and B) behave as autosomal, codominant alleles at a closed A locus. The other four factors (C, D, E and F) behave as autosomal, dominant traits. Biochemical variation was found for red cell enzymes catalase, phosphogluconate dehydrogenase, glucose phosphate isomerase and for plasma proteins transferrin and post-albumin. No variants were found for haemoglobin, phosphoglucomutase and albumin. Estimates of probability of exclusion were 0.883 for llamas and 0.681 for alpacas, which are adequate initial levels of efficacy for purposes of parentage verification. Preliminary estimate of Nei's genetic distance measure (D) suggests that llamas and alpacas are more likely related as subspecies than as separate species.     

Genetic blood markers in Arabian, Barb and Arab-Barb horses in Morocco

Gene frequencies at 16 blood group and protein polymorphism loci (A, C, D, K, P, Q, U, Al, Gc, Es, A1B, Tf, PGD, PGM, GPI and Pi) are given for three horse breeds in Morocco (Arabian, Arab-Barb and Barb). These data are used to calculate average heterozygosity (h), Nei's standard genetic distance (D_N) and probability of exclusion (PE). Variability expressed as the average heterozygosity was lower in the Arabian (0.330 ± 0.066), while it was higher and almost the same in the Arab-Barb (0.413 ± 0.071) and the Barb (0.414 A ± 0–070). The shortest genetic distance was found between Barb and Arab-Barb. The 16 loci used are at least 95% effective for recognizing incorrect paternity in these breeds. The Barb and Arab-Barb genetic profiles obtained showed the rare variants interesting perhaps in the context of European and American breeds: notably D^cfgkm, D^dekl, Es-N, Tf-A and Pi-W.     

Screening of mitochondrial mutations in Saudi women diagnosed with gestational diabetes mellitus: A non-replicative case-control study

IntroductionAmong metabolic disorders, gestational diabetes mellitus (GDM) is specified as hyperglycemia caused by glucose or carbohydrate intolerance defects. GDM is distinguished by oxidative stress, and has been connected to mitochondrial dysfunction. Previous studies have documented the relation between A12026G, A8344G and A3243G mutations in ND4, tRNA^Leu(UUR), and tRNA^Lys genes in different modes of diabetes.AimThe purpose of this study was to investigate into the relationship between GDM women and common mitochondrial mutations including A12026, A8344G, and A3243G in Saudi women.MethodsIn this case-control study, we have opted 96 GDM and 102 non-GDM pregnant women and DNA was extracted using EDTA blood and based on specific primers, Polymerase Chain Reaction was followed and then Restriction Fragment Length Polymorphism (RFLP) analysis was performed. Restriction enzymes was cross-checked with Lambda DNA and 10% of the purified PCR products were performed the Sanger sequencing analysis to reconfirm the RFLP analysis of the studied results.ResultsNone of the heterozygous and homozygous mutations were not observed in our study. All the subjects were turned to be homozygous normal genotypes.ConclusionThis study confirms that A12026, A8344G, and A3243G mutations have no role in the Saudi women with GDM.     

A natural genetic polymorphism affects retroactive interference in Drosophila melanogaster

As environments change, animals update their internal representations of the external world. New information about the environment is learned and retained whereas outdated information is disregarded or forgotten. Retroactive interference (RI) occurs when the retrieval of previously learned information is less available owing to the acquisition of recently acquired information. Even though RI is thought to be a major cause of forgetting, its functional significance is still under debate. We find that natural allelic variants of the Drosophila melanogaster foraging gene known to affect rover and sitter behaviour differ in RI. More specifically, rovers who were previously shown to experience greater environmental heterogeneity while foraging display RI whereas sitters do not. Rover responses are biased towards more recent learning events. These results provide an ecological context to investigate the function of forgetting via RI and a suitable genetic model organism to address the evolutionary relevance of cognitive tasks.     

Synthesis of Two New Acetanilide Derivatives and Their Effect on the Serum Antioxidant Vitamins (A,E, and C) and the MDA Level in Rats

Acetanilide derivatives, 2,2′-thiobis[N-(4-nitrophenyl)acetamide] and 2,2′-thiobis[N-(4-chlorophenyl)acetamide], were synthesized and characterized. They were shown to cause a considerable oxidative stress in rats.     

Blood groups as genetic markers in chimpanzees: Their importance for the national chimpanzee breeding program

Severe restrictions on the importation of chimpanzees emphasize the importance and urgency of domestic breeding as a sole means to assure an uninterrupted supply of animals for medical research. An insight into the genetic structure of the self-sustained captive population of animals is indispensable to prevent the effects of inbreeding and to preserve the animals' reproductive capacity. This can be achieved by study of sets of genetic markers in the form of heritable molecular or antigenic variations detectable by relatively simple methods. Among chimpanzee blood components so far identified as possible genetic markers, red cell antigens appear to be the most useful and most readily available. The amount of information concerning blood groups of chimpanzees, their serology and genetics, number of polymorphic types, etc, surpasses data on other heritable traits in this species. A concise review of the present status of knowledge of chimpanzee blood groups and, particularly, of serology and genetics of two complex blood group systems, V-A-B-D and R-C-E-F, is given together with a few examples of their application in cases of disputed parentage. Finally, a list of practical steps is suggested dealing with introduction and use of genetic markers as elements of the national chimpanzee breeding program.     

Blood groups and biochemical polymorphism in the Namaqua sheep breed

Summary. The Namaqua is an indigenous fat-tailed African breed of sheep which has remained relatively isolated and which at one time dwindled to near extinction. Frequency data are given for blood group antigens, red cell glutathione and potassium types, for electrophoretic variants of red cell haemoglobin, 'X' protein, nucleoside phosphorylase, NADH-diaphorase, lysine and carbonic anhydrase and of plasma esterase, transferrin and albumin. Of particular interest was the occurrence of the i blood group, a bimodal distribution in red cell glutathione concentrations and red cell potassium concentrations of around 57 mmo1/1 cells, i.e. neither typically LK nor HK type.     

Exploring variation in binding of Protein A and Protein G to immunoglobulin type G by isothermal titration calorimetry

Bacterial Protein A (PrtA) and Protein G (PrtG) are widely used for affinity purification of antibodies. An understanding of how PrtA and PrtG bind to different isotypes of immunoglobulin type G (IgG) and to their corresponding Fc fragments is essential for the development of PrtA and PrtG mimetic ligands and for the establishment of generic processes for the purification of various antibodies. In this paper, the interactions between the two IgG-binding proteins and IgG of two different subclasses, IgG1 and IgG4, as well as their analogous Fc fragments have been studied by isothermal titration calorimetry. The results indicate that both protein ligands bind IgG and Fc fragments strongly with Ka values in the range of 10(7) -10(8) M(-1) and for both ligands, the interaction with both IgG isotypes is enthalpically driven though entropically unfavorable. Moreover, variation in the standard entropic and standard enthalpic contribution to binding between the two isotypes as well as between IgG and Fc fragment implies that the specific interaction with PrtA varies according to IgG isotype. In contrast to PrtA, PrtG bound to F(ab')(2) fragment with a Ka value of 5.1 × 10(5) M(-1) ; thus underscoring the usefulness of PrtA as a preferred ligand for generic antibody purification processes.     

The Cytochrome P4501A1 gene polymorphisms and idiopathic male infertility risk: A meta-analysis

Studies of the relationship between male infertility and CYP1A1 polymorphisms are inconclusive. To drive a more precise estimation, we performed a meta-analysis based on 1060cases and 1225 controls from 7 published case–control studies. PubMed and CNKI literature search were conducted to identify all eligible studies investigating such a relationship. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of CYP1A1*2A genotype was significantly associated with susceptibility to idiopathic male infertility. Further stratified analysis by ethnicity showed notable association between the polymorphism and the risk of idiopathic male infertility in Asians. In conclusion, these results support that the CYP1A1*2A genotype polymorphism mainly contributes to idiopathic male infertility susceptibility in Asians but not in Caucasians.     

The effect of ABCB1 C3435T polymorphism on pharmacokinetics of tacrolimus in liver transplantation: A meta-analysis

Objectives

The effect of ABCB1 C3435T SNP on the pharmacokinetics of immunosuppressive drug tacrolimus in different studies was conflicting. So a meta-analysis was employed to study the correlation of ABCB1 C3435T SNP and the pharmacokinetics of tacrolimus at different post-transplantation times.

Method

Several studies about ABCB1 C3435T polymorphism and the pharmacokinetics of tacrolimus were collected through the search on PubMed and the Cochrane Library. After the extraction of pharmacokinetic parameters from these studies, a meta-analysis was performed on the software STATA version11.0.

Results

A total of 9 studies were adopted including 558 liver transplant recipients. For the dose of tacrolimus, the subjects with wild-type CC had a significantly higher tacrolimus dose than homozygous mutated genotype TT within 1 week (WMD = 0.01 (0.00, 0.02), P = 0.014) and the similar result in recipients with heterozygous CT compared with TT after transplantation for 1 month (WMD = 0.01 (0.00, 0.02), P = 0.002). For the tacrolimus concentration/dose ratio, subjects with CT had higher C/D ratio than those with CC and TT at different post-transplantation times. A subgroup analysis based on different ethnic populations was also carried out. Donors' genotypes were also considered in this meta-analysis.

Conclusion

Through this meta-analysis for the including studies about the pharmacokinetics of tacrolimus and ABCB1 C3435T SNP, several significant associations were obtained. Particularly, the Caucasians showed more significant associations between the C/D ratio and ABCB1 C3435T polymorphism; however, the correlations were not steady at different post-transplantation times.