C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

Elevated levels of homocysteine is a risk factor for coronary artery disease. The C677T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population. We analysed the association between the MTHFR C677T polymorphism and serum homocysteine concentrations in patients with coronary artery disease (CAD). Allele frequencies for the 'C' (wild-type) and 'T' alleles were 0.71 and 0.29 in CAD patients and 0.70 and 0.30 in controls, respectively. There was no difference in the distribution of MTHFR genotypes between patients with CAD and control subjects (p > 0.05). In the patient group, homocysteine levels were higher than controls but not significantly (13.99 +/- 7.44 vs. 11.77 +/- 5.18 micromol l(-1); p > 0.05). Serum homocysteine concentration was significantly higher in the TT genotype with respect to CC and CT genotypes in both the control group (p < 0.01) and patient group (p < 0.01). Systolic and diastolic blood pressures in subjects with different MTHFR genotypes did not differ significantly. In conclusion, MTHFR C677T mutation was significantly related to hyperhomocysteinemia. In spite of the clear effect of the MTHFR polymorphism on elevated homocysteine levels, we did not observe any associations among the MTHFR genotypes with a the risk of CAD in the Turkish population.     

Homozygosity for the met30 transthyretin gene in a Turkish kindred with familial amyloidotic polyneuropathy

Summary A Turkish family is described with two members suffering from familial amyloidotic polyneuropathy. Their transthyretin genes were examined using the polymerase chain reaction, and both patients possessed the met30 mutation in both of their transthyretin genes. In this family, only individuals who are homozygous for the met30 mutation have developed symptoms.     

Autoreactive sites of human λ light chain mapped by comprehensive peptide synthesis

Autoantibodies reactive against immunoglobulins are associated with autoimmune disorders as well as with immunization and infection. Moreover, recent interest is focused on auto-antidiotypes because of their possible role in immunoregulation. In this study, we used a set of overlapping synthetic peptides duplicating the structure of the monoclonal human λ light chain Mcg to map autoreactive dterminants recognized by natura lantibodies present in normal polycolonal human IgG. We found that autoantibodies in human IgG react strongly with two distinct Vλ determinants corresponding to the first complementarity determining region (CDR1) and the third framework (Fr3). Antibodies showing weak reactivities against three regions of the constant domain also occur in the preparations. The antibodies directed against light chain peptides comprise less than 0.1% of the IgG pool. Analysis by direct binding and by competitive ELISA inhibition established that affinity purified antibodies specific for CDR1 and Fr3 peptide determinants react with the intact light chain Mcg as well as with the corresponding peptide. Competitive inhibition studies comparing total IgG and affinity-purified antibodies indicate that natural antibodies showing a wide range of affinities are present. The polyclonal nature of the natural antibodies is further shown by the presence of both κ and λ light chains in the purified antibodies. Although the role of such natural antibodies remains to be determined, the cross-reactivity between Vλ peptides and the intact chain suggest that they can function in regulation of antibody formation.     

Mutations in capillary morphogenesis gene-2 result in the allelic disorders juvenile hyaline fibromatosis and infantile systemic hyalinosis

Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are autosomal recessive syndromes of unknown etiology characterized by multiple, recurring subcutaneous tumors, gingival hypertrophy, joint contractures, osteolysis, and osteoporosis. Both are believed to be allelic disorders; ISH is distinguished from JHF by its more severe phenotype, which includes hyaline deposits in multiple organs, recurrent infections, and death within the first 2 years of life. Using the previously reported chromosome 4q21 JHF disease locus as a guide for candidate-gene identification, we identified and characterized JHF and ISH disease-causing mutations in the capillary morphogenesis factor-2 gene (CMG2). Although CMG2 encodes a protein upregulated in endothelial cells during capillary formation and was recently shown to function as an anthrax-toxin receptor, its physiologic role is unclear. Two ISH family-specific truncating mutations, E220X and the 1-bp insertion P357insC that results in translation of an out-of-frame stop codon, were generated by site-directed mutagenesis and were shown to delete the CMG-2 transmembrane and/or cytosolic domains, respectively. An ISH compound mutation, I189T, is predicted to create a novel and destabilizing internal cavity within the protein. The JHF family-specific homoallelic missense mutation G105D destabilizes a von Willebrand factor A extracellular domain alpha-helix, whereas the other mutation, L329R, occurs within the transmembrane domain of the protein. Finally, and possibly providing insight into the pathophysiology of these diseases, analysis of fibroblasts derived from patients with JHF or ISH suggests that CMG2 mutations abrogate normal cell interactions with the extracellular matrix.     

Plasma xanthine oxidase, superoxide dismutase and glutathione peroxidase activities and uric acid levels in severe and mild pre-eclampsia

The aim of the present study was to measure plasma uric acid (UA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and xanthine oxidase (XO) activities and to evaluate the relationship between these parameters and the severity of pre-eclampsia. Twenty-five pre-eclamptic, 15 healthy pregnant and 15 non-pregnant women were enrolled in this study. Increased mean plasma XO activity was found to be higher in both pre-eclampsia groups than in the healthy pregnant group. Plasma UA levels were the highest in the severe pre-eclampsia group among the study groups. SOD and GSH-Px activities were significantly lower in both pre-eclampsia groups than in the healthy pregnant group (p < 0.005 and p < 0.001, respectively). Increased XO and decreased SOD and GSH-Px activities may contribute to the pathophysiological mechanisms of pre-eclampsia and increased UA may serve a protective role responding to superoxide radicals arising from increased XO activity or other sources in pre-eclampsia.     

Methylene tetrahydrofolate reductase C677T mutation and left ventricular hypertrophy in Turkish patients with type II diabetes mellitus

This study was designed to investigate, in the Turkish population, the association of methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism and left ventricular hypertrophy (LVH) in patients with type II diabetes mellitus. Our study included 249 patients with type II diabetes mellitus (102 men, 147 women) and 214 healthy volunteers as controls (91 men, 123 women). MTHFR C677T genotypes were determined by polymerase chain reaction, restriction fragment length polymorphism techniques. No differences were observed in the distribution of MTHFR genotypes or allele frequencies in the cases versus the controls. The frequency of the MTHFR-mutated allele (T) was 31.7% in the type II diabetes mellitus versus 31.1% of the controls. The homozygous mutation (T/T) in the MTHFR gene was identified in 12% of the type II diabetes mellitus versus 9.3% of the controls. Patients with the TT genotype showed a higher prevalence of LVH when compared to patients with the CC and CT genotypes (p = 0.01). The MTHFR gene C677T mutation may be a possible risk factor for the development of LVH in the type II diabetic patients.     

Synthesis of Murrayaquinone-A Derivatives and Investigation of Potential Anticancer Properties

A series of novel murrayaquinone a derivatives were synthesized and their anti-cancer activity were evaluated on healthy colon cell lines (CCD-18Co), primary (Caco-2) and metastatic (DLD-1) colon cancer cell lines. The results showed that the cytotoxicity of murrayaquinone molecules is significantly high even in micromolar levels. The DNA binding, cell cycle arrest and metabolic activity studies of these molecules were also carried out and the results showed that these molecules induce apoptosis. In conclusion, the data support further studies on murrayaquinone derivatives toward selection of a candidate for cancer treatment.