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Biomedical subjects

M Aksoy

Publications and source records attributed to M Aksoy.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1987

An approximately 300 bp deletion involving part of the 5' beta-globin gene region is observed in members of a Turkish family with beta-thalassemia.

Detailed gene mapping analyses of genomic DNA from two Turkish subjects with a beta-thalassemia trait demonstrated an approximately 300 bp deletion, which is located between the Rsa I restriction site 128 bp 5' to the Cap site and the Acc I restriction site 284 bp 3' to the same Cap site; it includes the 5' beta promoter region, the first exon, and (part of) the IVS-I. Heterozygotes for this and two other beta-thalassemia types, which are also caused by deletions involving 5' beta promoter sequences, appear to have higher hemoglobin (Hb) A2 levels, perhaps because the loss of this promoter results in an increased transcription of the delta globin gene, as delta and beta promoters may be influenced by the same enhancing sequences 3' to the beta globin gene.

Adult↗
PubMed1986

Sickle cell anaemia among Eti-Turks: haematological, clinical and genetic observations.

Haematological and genetic observations have been made on 71 SS Eti-Turk patients and their relatives from Cukurova (southern Turkey) and of immigrant families in The Netherlands. Similar data were collected for 25 Black patients and their relatives from Surinam, Netherlands Antilles, and Kenya. Haematological and clinical results were the same for both groups; the haemolytic anaemia in the Turkish patients was as severe as in the others. Haplotyping, involving nine restriction sites, identified haplotype 19 (Antonarakis et al, 1984) as the major type among the Eti-Turks; this chromosome has previously primarily been observed among SS patients from West Africa. The suggestion that the beta S-chromosome among Eti-Turks originates from that area is supported by a relatively high incidence of alpha-thalassaemia-2 (the 3.7 kb deletion), also frequently present in the Black population of West Africa, and by the absence of other major haplotypes, such as types 20 and 3, characteristic for the beta S-chromosome in the population of Central Africa and Kenya, and in Senegal, respectively. The Saudi Arabian type of beta S chromosome in association with the haplotype 19 beta S chromosome was present in only one Eti-Turk patient; this 30-year-old female was mildly affected and exhibited a high level of fetal haemoglobin.

Adult↗
PubMed1985

Haplotypes and levels of fetal hemoglobin and G gamma to A gamma ratios in Mediterranean patients with thalassemia minor and major.

This study concerned the gamma chain composition of Hb F and the haplotypes of 44 patients with beta-thalassemia major or intermedia and many of their relatives. Seventeen patients came from Northern (Turkish) Cyprus, 12 from the Istanbul area, and 15 from Macedonia and Bulgaria. Analysis of the A gamma T-G gamma-A gamma I ratio was made by HPLC, while haplotyping involved seven restriction sites. Specific haplotypes were present in certain populations; haplotype I [1] is the dominant type among North Cypriot thalassemia patients. Numerous types were seen in the patients from the Balkan countries. A direct relationship between the A gamma to G gamma ratios and the haplotypes, which exists among black beta-thalassemia heterozygotes [3], was also observed among these Mediterranean patients, although such analyses were considerably complicated by extensive blood transfusion therapy. Haplotypes without the Hinc II restriction site within the psi beta gene were associated with lower G gamma values than those that had this polymorphic site. The A gamma T chain was observed in a small number of beta-thalassemia homozygotes and heterozygotes. Three thalassemia chromosomes with slightly different haplotypes and one normal chromosome with a related haplotype were associated with the gamma 75 Ile----Thr substitution. A few patients with a thalassemia intermedia were heterozygotes for beta-thalassemia with either haplotypes V or VII [1] while the "nonthalassemic" chromosome had a haplotype I, which is the most common "beta-thalassemic" haplotype among the Mediterranean population(s). Detailed analyses of this chromosome have not been completed.

Adolescent↗
PubMed1985

Malignancies due to occupational exposure to benzene.

There is no doubt about the leukemogenic effect of benzene in man. The evidence is as follows: (1) The incidence of leukemia in shoeworkers exposed to benzene in a period of 8 years in Istanbul was 13.6/100,000, which is significantly higher than that for leukemia in the general population. (2) Following the phase-out of benzene in Istanbul, the number of leukemic workers decreased and none were reported in the subsequent 3 years. (3) The development of leukemia in pancytopenic patients with benzene exposure was observed in 13 out of 51 patients. (4) The differences in the distribution of the types of leukemia in individuals exposed and in nonexposed groups were as follows: acute leukemia 96.1% in the former group, and 46% in the latter group. The high percentages of acute erythroleukemia and preleukemia were other interesting findings in the exposed group. (5) Two cases of leukemia were observed in a 6-year period at a tire cord manufacturing plant with 550 workers. At one location in the plant the concentration of benzene measured by gas chromatography was nearly 110 ppm. Additionally, we have studied 12 cases of malignant lymphoma, four cases of multiple myeloma, and six cases of lung cancer, all of whom were chronically exposed to benzene. The possible role of benzene in the etiology of these malignancies is discussed.

Adult↗
PubMed1985

Benzene as a leukemogenic and carcinogenic agent.

Today there seems to be sufficient data to incriminate benzene as a potent carcinogenic agent causing leukemia, malignant lymphoma, multiple myeloma and lung cancer, as well as numerous disorders of the bone marrow depression. Other factors (such as genetic and individual susceptibility) may have a role in the development of these different types of malignancies and hematologic disorders. In this paper, data concerning all these problems are presented and discussed.

Benzene↗
PubMed1985

Influence of experimental diets on hepatic glutathione levels in rats with methylnitrosourea-induced mammary carcinoma.

Mammary tumor development induced by methylnitrosourea in female Sprague-Dawley rats had no significant effect on hepatic glutathione levels. If the diets of methylnitrosourea-treated animals were supplemented with vitamin A and E an increased hepatic glutathione level was observed initially. A high fat diet (21% per weight) supplemented with the two vitamins led to a decreased hepatic glutathione level 2 months after tumor induction. Advanced tumor development under any of the diets tested had no effect on hepatic glutathione.

Animals↗
PubMed1985

Survey on haemoglobin variants, beta thalassaemia, glucose-6-phosphate dehydrogenase deficiency, and haptoglobin types in Turks from western Thrace.

A total of 102 apparently healthy and randomly selected Turks who either immigrated from Western Thrace or were still living there were studied for haemoglobin variants, high Hb A2 beta thalassaemia, G6PD deficiency, and haptoglobin types. The incidence of haemoglobins S and O Arab were 2.9 and 3.9% respectively. The incidence of high A2 beta thalassaemia was 10.8% and that of G6PD deficiency 5%. The gene frequencies of Hp1 and Hp2 were 0.326 and 0.674, respectively.

Adult↗