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M Aksoy

Publications and source records attributed to M Aksoy.

At least 19 recordsLinked to original sources
PubMed1992

The molecular basis of beta-thalassemia in Turkey.

By using oligonucleotide hybridization, restriction endonuclease analysis and direct sequencing of amplified genomic DNA, we have been able to characterize 18 different mutations in the beta-globin genes of 161 beta-thalassemia homozygotes and 107 beta-thalassemia heterozygotes from Turkey (429 beta-thalassemia chromosomes). Previous studies dealing with beta-thalassemia in Mediterranean countries have shown that, in most Mediterranean populations, only a few mutations are prevalent. In contrast, beta-thalassemia in Turkey does not seem to be associated with a few predominant mutations. The six most frequent alleles, IVS-I-110 (G----A), IVS-I-6(T----C), FSC-8 (-AA), IVS-I-1(G----A), -30(T----A) and FSC-5 (-CT), account for only 69.3% of the disease genes; indeed, all 26 mutations assayed represent 85.8% of the disease genes, confirming the considerable molecular heterogeneity of beta-thalassemia among Turks, and indicating the possible presence of rare, previously undefined, mutations in the population. Two mutations observed in this study, IVS-I-116 (T----G) and Cd44(-C), have not been reported in the Turkish population to date. Since preventive medical services, such as genetic counseling and prenatal diagnosis, are greatly improved by detailed knowledge of the molecular pathology of beta-thalassemia, we strongly believe that the presented data will facilitate the intended establishment of a prenatal diagnosis center, based on DNA analysis, in Turkey.

Alleles↗
PubMed1990

Differential relationship of vitamin A and E levels in methylnitrosourea-induced Sprague-Dawley rats following prolonged feeding of fatty diets enriched with the vitamins.

Prolonged supplementation of vitamins A and E (2500 IU and 11.3 IU/rat daily) in 10.3% and 21.6% fatty diets administered to methylnitrosourea-induced Sprague-Dawley rats caused alterations in plasma and liver levels of both vitamins as well as of the total lipids. Liver vitamin A levels increased steadily (more than fourfold) until termination of the experiment, whereas plasma vitamin A levels only showed a minor increase at the end of the study in comparison to rats fed a standard diet. Liver vitamin E levels initially showed no difference from those of rats treated with a standard diet, and were decreased at the end of the experiment, whereas the respective plasma levels were increased throughout the study, only showing a decrease relative to initial values at termination of the experiment. Plasma total lipids increased with age and following supplementation of the vitamins in the high-fat diet, whereas liver total lipids were influenced less by aging than by the fat and vitamin contents of the respective diets. The observed alterations were, however, not related to significant chemopreventive activity of the vitamins A and E contained in high-fat diets.

Animals↗
PubMed1990

Beta-thalassemia in Turkey.

A review is presented of the various beta-thalassemia alleles observed in nearly 191 patients with beta-thalassemia major and their 182 heterozygous relatives. Determination was by gene amplification and dot-blot hybridization with synthetic probes, specific for 27 different mutations. Eighteen mutations have been observed; six of these account for nearly 83% of all thalassemia abnormalities. A new mutation, i.e. a G----C mutation at the acceptor splice site of IVS-I, was found in one teenager who was homozygous for this disease. The high consanguinity among the families was considered the main reason for the high number of patients with a homozygosity for the IVS-I-110 (G----A) mutation. Combinations of different mutations were present in many patients; some were mildly affected because of the specific mutation present on one chromosome. Combinations of classical beta-thalassemia and an abnormal hemoglobin mainly concerned Hb S. Hbs Knossos and Lepore were rare occurrences. A comparison of hematological data for adults with heterozygosities for some of the common alleles confirmed the low Hb A2 values in IVS-I-6 (T----C) heterozygotes and the high Hb F values for codon 8 (-AA), IVS-II-1 (G----A), and IVS-I-1 (G----A) heterozygotes.

Adolescent↗
PubMed1990

Effects of different levels of dietary fat on methyl-nitrosourea-induced mammary carcinogenesis in correlation with parameters of fat metabolism in female Sprague-Dawley rats.

The aim of this study was to elucidate the effects of different levels of dietary fat on methyl-nitrosourea-induced rat mammary carcinogenesis in correlation with parameters of the fat metabolism. 90 female Sprague-Dawley rats were initiated i.v. with 25 mg MNU/kg on day 50 of life. For a period of 6 months, beginning after the day of initiation, the animals received either a control diet (12% of total energy as fat, Group I) or one of the fat-enriched semisynthetic diets (25 en% of fat, Group II, or 45 en%, Group III, respectively) at an isocaloric level of 50 kcal/rat/day. The principal observations of this experiment were: (1) The fat content of diet did not significantly influence mammary carcinogenesis. (2) The values of plasma total lipids, cholesterol and triglycerides and their density separated VLDL and LDL-fractions showed a significant time-dependent increase. (3) HDL-values of cholesterol and triglycerides showed no changes in dependence to time and fat content of the diet. (4) The liver lipid concentrations of groups increased significantly with dietary fat content.

Animals↗
PubMed1989

A C----T substitution at nt--101 in a conserved DNA sequence of the promotor region of the beta-globin gene is associated with "silent" beta-thalassemia.

Sequence analyses and dot-blot analyses with synthetic oligonucleotide probes have identified eight individuals in three Turkish families and one Bulgarian family with one chromosome having a C----T mutation at nucleotide position--101 relative to the Cap site of the beta-globin gene. This nucleotide is part of one of the conserved blocks of nucleotides within the promoter region; in vitro expression analyses with the chloramphenicol acetyltransferase system showed that this substitution will decrease the effectiveness of transcription. Five subjects had a thalassemia intermedia due to the additional presence of a known classical high hemoglobin (Hb) A2 beta-thalassemia mutation on the second chromosome; their hematologic condition was relatively mild. The three persons with a heterozygosity for the--101 C----T mutation had normal hematologic data without microcytosis but with high-normal levels of Hb A2 and a mild imbalance in chain synthesis. The newly discovered mutation is considered one of the silent types of beta-thalassemia. It is relatively rare because it was absent among several hundred normal and beta-thalassemia chromosomes.

Base Sequence↗
PubMed1989

Hematotoxicity and carcinogenicity of benzene.

The hematotoxicity of benzene exposure has been well known for a century. Benzene causes leukocytopenia, thrombocytopenia, pancytopenia, etc. The clinical and hematologic picture of aplastic anemia resulting from benzene exposure is not different from classical aplastic anemia; in some cases, mild bilirubinemia, changes in osmotic fragility, increase in lactic dehydrogenase and fecal urobilinogen, and occasionally some neurological abnormalities are found. Electromicroscopic findings in some cases of aplastic anemia with benzene exposure were similar to those observed by light microscopy. Benzene hepatitis-aplastic anemia syndrome was observed in a technician with benzene exposure. Ten months after occurrence of hepatitis B, a severe aplastic anemia developed. The first epidemiologic study proving the leukemogenicity of benzene was performed between 1967 and 1973 to 1974 among shoe workers in Istanbul. The incidence of leukemia was 13.59 per 100,000, which is a significant increase over that of leukemia in the general population. Following the prohibition and discontinuation of the use of benzene in Istanbul, there was a striking decrease in the number of leukemic shoe workers in Istanbul. In 23.7% of our series, consisting of 59 leukemic patients with benzene exposure, there was a preceding pancytopenic period. Furthermore, a familial connection was found in 10.2% of them. The 89.8% of our series showed the findings of acute leukemia. The possible factors that may determine the types of leukemia in benzene toxicity are discussed. The possible role of benzene exposure is presented in the development of malignant lymphoma, multiple myeloma, and lung cancer.

Anemia, Aplastic↗
PubMed1989

Beta-thalassemia intermedia in two Turkish families is caused by the interaction of Hb Knossos [beta 27(B9)Ala----Ser] and of Hb City of Hope [beta 69(E13)Gly----ser] with beta (0)-thalassemia.

We have studied a few members of two Turkish families, who had a beta-thalassemia of the intermediate type. An abnormal hemoglobin was found in both families, which when present in association with beta(0)-thalassemia was considered to be the primary cause for the increased severity of the disease. In the first family this variant was Hb Knossos [beta 27(B9)Ala----Ser] which occurred together with the frameshift in codon #8 type of beta(0)-thalassemia. This compound heterozygosity, observed for the first time in the Turkish population was characterized by a considerable increase in Hb F production, mainly of the G gamma type, as expected for a chromosome with haplotype IV. In the second family, the variant was Hb City of Hope [beta 69(E13)Gly----Ser] which was present in combination with an unknown type of beta-thalassemia. The increase in Hb F production in the compound heterozygote was minimal. Reversed phase high performance liquid chromatography and the DNA amplification-synthetic oligonucleotide probe procedure were major tools in identifying the different abnormalities.

Adult↗
PubMed1988

Mild and severe beta-thalassemia among homozygotes from Turkey: identification of the types by hybridization of amplified DNA with synthetic probes.

Through the procedure of gene amplification combined with hybridization to synthetic 19 base pair (bp) oligonucleotide probes, it has been possible to identify nine different mutations in the DNA of 47 subjects from Turkey and Northern Cyprus with a beta-thalassemia homozygosity. The IVS-I nucleotide (nt) 110 G----A and the IVS-I nt 6 T----C substitutions and the frameshift at codon 8 were most frequently observed. Direct correlations were made between these data and clinical observations; mild disease was associated with homozygosity for IVS-I nt 6 T----C, for frameshift at codon 8, for the C----G substitution at nt -87, and for IVS-I nt 5 G----T, and for a double heterozygosity for some of these conditions. Moderate disease, observed in some of the patients, could be explained by combinations of specific mutations. All mutations were associated with specific haplotypes, while in some the observed beta zero-thalassemia was of the mild type due to a considerable production of Hb F.

DNA↗
PubMed1987

Comparison between the effects of dietary fat level and of calorie intake on methylnitrosourea-induced mammary carcinogenesis in female SD rats.

The aim of this study was to separate the effects of calorie intake on tumorigenesis from those of fat content and fat composition in an animal model. Our principal observations were the following. Decreasing the calorie level by 30% significantly inhibited tumor development in any observed parameter of tumorigenesis, independently of the level of fat. The fat content of semi-synthetic diets, although varying by 44.4%, did not significantly influence mammary tumorigenesis; in fact, carcinogenic expression was discontinuously related to the fat level. A plateau of tumor incidence was observed at the level of 35 energy percentage of fat. Fat composition did not influence tumorigenesis or body weight gain. The role of caloric restriction is thus stressed in relation to possible dietary prevention of cancer.

Animals↗
PubMed1987

Effects of vitamin A and E supplementation to diets containing two different fat levels on methylnitrosourea-induced mammary carcinogenesis in female SD-rats.

The aim of this study was to elucidate the effects of dietary vitamin A and E supplementation on tumorigenesis in correlation to the fat content of the respective diet in an animal model. One hundred and twenty female SD rats were initiated intravenously with 25 mg MNU kg-1 on day 50 of life. For a period of 6 months, beginning after the day of initiation, all animals received a semisynthetic diet containing 25% or 45% of the energy as fat, supplemented either with a 10-fold higher amount of naturally occurring vitamins A and E than in rat standard diets or, with a normal level of these vitamins. The experiment showed: (1) Vitamin A and E supplementation showed no significant chemopreventive effect against mammary tumour development. (2) This result was independent from the supplied fat level of the respective diet. (3) The fat content per se did not significantly influence mammary tumorigenesis.

Animals↗
PubMed1987

The influence of different levels of dietary fat on the incidence and growth of MNU-induced mammary carcinoma in rats.

This study describes the influence of isocalorically fed diets (containing different amounts of fat) on tumor incidence and parameters of fat metabolism in female Sprague-Dawley rats. Comparisons are made between rats induced with methylnitrosourea (25 mg/kg body wt) and untreated controls (Group I). The animals received either control diets (3.9% fat by weight, Groups I and II) or fat-enriched diets (10.7%, Group III; 15.6%, Group IV; 21.4%, Group V) over a period of 180 days. At the termination of the experiment, intake of the diet containing 10.7% fat by weight (24% fat per total calories) was associated with the highest tumor incidence. Comparing the different diets, liver lipid concentrations in the individual groups increased with increasing dietary fat, whereas the total lipid in plasma decreased. During the feeding period, total lipid of the liver and plasma, and plasma cholesterol, increased in all groups, but triglycerides of plasma decreased. However, when plasma cholesterol and triglycerides were calculated as a relative amount of total lipid in plasma, cholesterol was found to be significantly decreased in Groups III and IV, and triglycerides were increased in Group III but decreased significantly in Groups I, II, and V at the end of the experiment.

Animals↗
PubMed1987

Exposure to benzene in Turkey between 1983 and 1985: a haematological study on 231 workers.

A study was performed to determine the content of benzene in the air and solvents and thinners used by 231 workers in 40 small or large workplaces in Istanbul and Izmit. The benzene value in the air of a tyre cord manufacturing factory where two cases of acute leukaemia were recorded in a six year period was 110 ppm. In nine of 47 thinners (19.1%) the benzene content ranged between 0% and 6.4% whereas it was between 0.7% and 7.64% in 26 of 34 solvents used. A haematological study on 231 workers showed that there were mild abnormalities in 14 workers including leucopaenia in nine (3.9%), thrombocytopaenia in four (2.16%), and pancytopaenia in one (0.54%). This study shows that despite the considerable decrease in the content of benzene in the solvents and thinners available in Istanbul and Izmit the percentages of benzene in most of the materials are still above permissible limits.

Adolescent↗