Antigenic mapping of a human λ light chain: Correlation with three dimensional structure

Although the amino acid sequence and three-dimensional structure of human immunoglobulin light chains have been known for more than 15 years, the location of antigenic markers characteristic of chains has not been determined. Here, we use a set of synthetic overlapping peptides to completely model the sequence of the chain Mcg and test these for the binding or rabbit and goat antisera specific for chain determinants. We assess peptide contributions to -antigenic reactivity and also to identify a portion of C-region where conformational factors contribute to the antigenicity. Specific determinants occur both in the constant and variable (first and third framework) domains of the molecule. The fourth framework of the variable region, a segment specified by the joining gene, is also recognized and cross-reacts antigenically with the homologous region of T cell receptor chains. Major specific determinants are localized in the N- and C-terminal segments, which are linear and devoid of major conformational folding. Other segments that are strongly antigenic, such as the third framework of the V region (residue 78–93) and a segment of the constant region (residues 177–192), show strong conformational dependence in antigenicity.     

Hydrophobic cluster analysis reveals duplication in the external structure of human alpha-interferon receptor and homology with gamma-interferon receptor external domain

Evidence is presented, based on sequence comparison according to Hydrophobic Cluster Analysis, of a structural and evolutionary relationship between the human alpha/beta-interferon receptor and the human and mouse gamma-interferon receptor. These results predict that the human alpha/beta-interferon receptor extracellular part is organised in two homologous subdomains connected by a proline linker. They also predict that both subdomains present some homologies to the external domain of mouse and human gamma interferon receptor.     

The effect of caffeic acid phenethyl ester (CAPE) on metabolic enzymes including acetylcholinesterase,butyrylcholinesterase, glutathione S-transferase,lactoperoxidase, and carbonic anhydrase isoenzymes I,II, IX,and XII

Caffeic acid phenethyl ester (CAPE) is an active component of honeybee propolis extracts. Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread and intensively studied metalloenzymes present in higher vertebrates including humans as many diverse isoforms. Acetylcholinesterase (AChE) is responsible for acetyl choline (ACh) hydrolysis and plays a fundamental role in nerve impulse transmission by terminating the action of the ACh neurotransmitter at cholinergic synapses and neuromuscular junctions. Butyrylcholinesterase (BChE) is another enzyme abundantly present in the liver and released into blood in a soluble form. Lactoperoxidase (LPO) is an enzyme involved in fighting pathogenic microorganisms whereas glutathione S-transferases (GSTs) are dimeric proteins present both in prokaryotic and eukaryotic organisms and involved in cellular detoxification mechanisms. In the present study, the inhibition effect of CAPE on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII, AChE, BChE, LPO, and GST was evaluated. CAPE inhibited these enzymes with K_is in the range between micromolar to picomolar. The best inhibitory effect was observed against AChE and BChE.     

Investigation of class 1 integrons and virulence genes in the emergent Salmonella serovar Infantis in Turkey

International Microbiology - The emerging situation of Salmonella enterica subsp. enterica serovar Infantis (S. Infantis) in Turkey was investigated in terms of virulence genes and mobile genetic...     

Paraoxonase 55 and 192 polymorphism and its relationship to serum paraoxonase activity and serum lipids in Turkish patients with non-insulin dependent diabetes mellitus

We investigated the effect of PON 55 and PON 192 polymorphisms on serum PON1 activity and lipid profiles in 213 non-insulin dependent diabetes mellitus (NIDDM) individuals and 116 non-diabetic controls among Turkish subjects. The distribution of PON 55/192 gene polymorphism was determined by polymerase chain reaction-based restriction fragment length polymorphism. Serum lipid levels were measured enzymically. PON activity was measured by spectrophotometric assay of p-nitrophenol production following addition of paraoxon. We found that PON 55 and 192 genotype distribution was similar in patients and controls and paraoxonase activity was generally lower in diabetics than in control subjects. We showed that PON 55 and 192 genotypes have a major effect on serum PON activity. PON 192 BB homozygotes had significantly higher PON activity than AA and AB genotypes among the control and NIDDM populations (p<0.001). PON 55 MM homozygotes had significantly lower PON activity than did LL and LM genotypes in control and NIDDM populations (p<0.05). The PON1 55 and 192 polymorphisms did not consistently influence the serum lipid profiles in either population. In conclusion, our results suggest that the paraoxonase activities are affected by PON1 genetic variability in Turkish NIDDM patients and controls.     

X-linked cone-rod dystrophy (locus COD1): identification of mutations in RPGR exon ORF15

X-linked cone-rod dystrophy (COD1) is a retinal disease that primarily affects the cone photoreceptors; the disease was originally mapped to a limited region of Xp11.4. We evaluated the three families from our original study with new markers and clinically reassessed all key recombinants; we determined that the critical intervals in families 2 and 3 overlapped the RP3 locus and that a status change (from affected to probably unaffected) of a key recombinant individual in family 1 also reassigned the disease locus to include RP3 as well. Mutation analysis of the entire RPGR coding region identified two different 2-nucleotide (nt) deletions in ORF15, in family 2 (delAG) and in families 1 and 3 (delGG), both of which result in a frameshift leading to altered amino acid structure and early termination. In addition, an independent individual with X-linked cone-rod dystrophy demonstrated a 1-nt insertion (insA) in ORF15. The presence of three distinct mutations associated with the same disease phenotype provides strong evidence that mutations in RPGR exon ORF15 are responsible for COD1. Genetic heterogeneity was observed in three other families, including the identification of an in-frame 12-nt deletion polymorphism in ORF15 that did not segregate with the disease in one of these families.     

PRMT1 promotes the tumor suppressor function of p14ARF and is indicative for pancreatic cancer prognosis

The p14^ARF protein is a well‐known regulator of p53‐dependent and p53‐independent tumor‐suppressive activities. In unstressed cells, p14^ARF is predominantly sequestered in the nucleoli, bound to its nucleolar interaction partner NPM. Upon genotoxic stress, p14^ARF undergoes an immediate redistribution to the nucleo‐ and cytoplasm, where it promotes activation of cell cycle arrest and apoptosis. Here, we identify p14^ARF as a novel interaction partner and substrate of PRMT1 (protein arginine methyltransferase 1). PRMT1 methylates several arginine residues in the C‐terminal nuclear/nucleolar localization sequence (NLS/NoLS) of p14^ARF. In the absence of cellular stress, these arginines are crucial for nucleolar localization of p14^ARF. Genotoxic stress causes augmented interaction between PRMT1 and p14^ARF, accompanied by arginine methylation of p14^ARF. PRMT1‐dependent NLS/NoLS methylation promotes the release of p14^ARF from NPM and nucleolar sequestration, subsequently leading to p53‐independent apoptosis. This PRMT1‐p14^ARF cooperation is cancer‐relevant and indicative for PDAC (pancreatic ductal adenocarcinoma) prognosis and chemotherapy response of pancreatic tumor cells. Our data reveal that PRMT1‐mediated arginine methylation is an important trigger for p14^ARF’s stress‐induced tumor‐suppressive function.     

Erdosteine modulates radiocontrast‐induced hepatotoxicity in rat

It has been suggested that reactive oxygen species (ROS) plays an important role in radio contrast media (RCM)‐induced ischemia reperfusion tissue injury although antioxidants may have protective effects on the injury. We investigated the effects of erdosteine as an antioxidant agent on RCM‐induced liver toxicity in rats by evaluation of lipid peroxidation (as TBARS), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH) and glutathione peroxidase (GSH‐Px) values and histological evaluation. Twenty‐one rats were equally divided into three groups as follows: control, RCM, and RCM plus erdosteine. RCM was intraperitoneally administered for 1 day. Erdosteine was administered orally for 2 days after RCM administration. Liver samples were taken from the rats and they homogenized in a motor‐driven tissue homogenizer. TBARS levels were significantly (p < 0.005) higher in RCM group than in control although SOD activities significantly (p < 0.05) decreased in RCM group. TBARS levels were lower in RCM plus erdosteine group than in control although SOD activity and GSH level increased (p < 0.05) in liver as compared to RCM alone. Erdosteine showed also histopathological protection (p < 0.0001) against RCM induced hepatotoxicity. GSH‐Px and CAT activities were not statistically changed by the erdosteine. According to our results, it can be concluded that radiocontrast media can induce oxidative stress in liver as suggested by previous studies. Erdosteine seems to be protective agent on the radiocontrast media‐induced liver toxicity by inhibiting the production of ROS via the enzymatic antioxidant system. Copyright © 2009 John Wiley & Sons, Ltd.