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T Coskun

Publications and source records attributed to T Coskun.

At least 19 recordsLinked to original sources
PubMed1999

Identification of mutations in the galactose-1-phosphate uridyltransferase (GALT) gene in 16 Turkish patients with galactosemia, including a novel mutation of F294Y. Mutation in brief no. 235. Online.

Classical galactosemia caused by deficiency of galactose-1-phosphate uridyltransferase (GALT) is a severe autosomal recessive disorder. We report here molecular analysis of 16 unrelated Turkish galactosemia index cases without GALT activity. Almost 84% of all mutant alleles were identified in this study. The most common molecular defect observed in the Turkish population was Q188R (replacement of glutamine-188 by arginine) (57%). In order to facilitate the determination of unknown mutations in the entire coding region of GALT, we established an approach based on GALT cDNA synthesis and direct sequencing. We have identified one novel candidate galactosemia mutation, a T-to-A transversion at the codon 294 (F294Y) in exon 9 in addition to previously reported three missense (M142K K285N, A320T), one stop codon (E340X), and one silent (L218L) mutations in galactosemia patients which reflect considerable genetic heterogeneity in the Turkish population.

Alleles↗
PubMed1999

Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene.

Classical galactosemia is caused by a deficiency in activity of the enzyme galactose-1-phosphate uridyl transferase (GALT), which, in turn, is caused by mutations at the GALT gene. The disorder exhibits considerable allelic heterogeneity and, at the end of 1998, more than 150 different base changes were recorded in 24 different populations and ethnic groups in 15 countries worldwide. The mutations most frequently cited are Q188R, K285N, S135L, and N314D. Q188R is the most common mutation in European populations or in those predominantly of European descent. Overall, it accounts for 60-70% of mutant chromosomes, but there are significant differences in its relative frequency in individual populations. Individuals homoallelic for Q188R tend to have a severe phenotype and this is in keeping with the virtually complete loss of enzyme activity observed in in vitro expression systems. Globally, K285N is rarer, but in many European populations it can be found on 25-40% of mutant chromosomes. It is invariably associated with a severe phenotype. S135L is found almost exclusively in African Americans. In vitro expression results are discrepant, but some individuals carrying S135L appear to exhibit GALT activity in some tissues. Duarte 1 (or Los Angeles) and Duarte 2 (or Duarte) variants carry the same amino acid substitution, N314D, even though D1 is associated with increased erythrocyte GALT activity and D2 with reduced activity. N314D is in linkage disequilibrium with other base changes that differ on the D1 and D2 alleles. N314D does not impair GALT activity in in vitro expression systems. However, there are differences in the abundance of GALT protein in lymphoblastoid cells lines from D2 and D1 individuals. It is unclear whether the specific molecular changes that distinguish the D1 and D2 alleles account for the different activities. The considerable genetic heterogeneity documented to date undoubtedly contributes to the phenotypic heterogeneity that is observed in galactosemia. The additional effects of nonallelic variation and other constitutional factors on phenotypic variability remain to be elucidated.

Alleles↗
PubMed1999

Motor neuron degeneration due to aluminium deposition in the spinal cord: a light microscopical study.

For a long time, aluminium has been considered as an indifferent element from a toxicological point of view. In recent years, it became clear that aluminium is a potential toxic agent in humans and has been implicated in the pathogenesis of several clinical disorders, such as dementia, respiratory tract disorders and allergic reactions. Chronic exposure to aluminium fumes, inhalation of aluminium and aluminium-oxide powder increase the risk to develop serious central nervous system pathology, in particular Alzheimer's disease and amyotrophic lateral sclerosis (ALS). In the present study, 3 experimental and 1 control group of rats were used to study the effects of aluminium on the central nervous system. Aluminium was injected intracisternally as a single dose (50 micrograms for group I, 100 micrograms for group II and 300 micrograms for group III) to the experimental groups (n = 5 in each group). The same dose was given at 3 months after the first injection to all groups. The control group (n = 5) was intracisternally given a physiological salt solution. Electromyography (EMG) was applied to the rats of the experimental groups. Rats were decapitated at 3 months after the second injections. Spinal cord samples from lumbar and cervical regions were removed and histological examination was performed. Light microscopical investigations revealed severe degeneration in motor neurons of the rats treated with 300 micrograms. Neurofibrillary tangle formation, chromatolysis and abnormal localization of the nuclei were found in swollen perikarya. Extreme loss of motor neurons with "ghost cell" appearance was found in that group. Sections of spinal cords of rats treated with lower doses of aluminium showed a moderate degree of motor neuron damage. EMGs of rats treated with the high dose of aluminium revealed severe acute denervation whereas treatment with lower doses resulted in moderate denervation. We conclude that aluminium may cause severe motor neuron damage in rat spinal cord resembling ALS.

Aluminum↗
PubMed1999

Autologous skin graft, human dura mater and polypropylene mesh for the repair of ventral abdominal hernias: an experimental study.

OBJECTIVE: To compare primary repair and grafting with one of two materials (one biological human dura mater, and one synthetic polypropylene mesh) or autologous skin, with primary repair alone in abdominal wall hernias in rats. DESIGN: Randomised experiment. SETTING: Teaching hospital, Turkey. ANIMALS: 72 male Wistar albino rats randomised into 4 groups of 18 rats each. These were further randomly divided into subgroups of 6 each that were killed on days 15, 30,and 45 postoperatively. INTERVENTIONS: Each test material was sutured to the abdominal wall by an onlay technique. MAIN OUTCOME MEASURES: Macroscopic and microscopic appearance, and strength of the abdominal wall. RESULTS: Macroscopically, dura mater grafts lost their original shape, but polypropylene and skin did not. When completely incorporated the skin grafts had developed a new fascia. Dura mater and polypropylene induced a pronounced inflammatory reaction at all three times postoperatively, and there were significantly more fibroblasts in the dura mater group on days 15 and 30, and in the skin graft group on day 45, than in the other groups (p < 0.05). Mechanical resistance and mean breaking strength were significantly greater in the skin graft group than in the other groups at all times tested (p < 0.05). CONCLUSION: Full thickness autologous skin grafts were stronger than both human dura mater and polypropylene mesh when used to reinforce primary repairs of abdominal wall hernias in rats.

Animals↗
PubMed1998

Effect of hydrogen peroxide on permeability of the main pancreatic duct and morphology of the pancreas.

BACKGROUND: The direct effect of free oxygen radicals, if any, on the morphology of the pancreas has never been studied in vivo. This study was designed to evaluate the effects of hydrogen peroxide (H2O2) on permeability of the main pancreatic duct (MPD) and morphology of pancreas in cats when administered intraductally or intraarterially. METHODS: Thirty-six mongrel cats were randomly allocated into three groups, and all groups were divided into two subgroups. In group I and III, MPD was perfused with either standard perfusate (group IA and IIIA) or H2O2 at a concentration of 150 microM (group IB and IIIB) for 3 hours. In group II, the splenic artery was infused either with 0.9% sodium chloride (group IIA) or H2O2 (group IIB) for 3 hours. After 3 hours, in group I and II, MPD was perfused with 99mTc labelled dextran, and the percentage of the dextran permeated from the MPD into the portal vein was calculated for the evaluation of the pancreatic duct permeability. Then, tissue samples were obtained for the examination of early histopathological changes in pancreas. In group III, following ductal perfusion studies, the cats were allowed to recover. After 24 hours animals were killed, and samples were taken for the examination of late histological changes in pancreas. In all groups, an inflammatory score was created for each animal based on the pathological changes in pancreas: edema, leukocyte infiltration, parenchymal necrosis, and hemorrhage. RESULTS: Group I: All cats developed acute edematous pancreatitis with significantly higher inflammatory scores than controls (P < 0.01). Desquamation of the single layer of columnar epithelium that normally lined the duct and leukocyte infiltration around the MPD duct were found. Pancreatic duct permeability was found to be increased significantly (P < 0.01). Group II: There were no statistical differences in inflammatory scores and pancreatic duct permeability between experimental and control groups (P > 0.05). Group III: All animals developed gross acute edematous pancreatitis after 3 hours of intraductal H2O2 perfusion. Histopathological changes at 24 hours were much more pronounced in group IIIB than in group IIIA including focal necrosis and hydropic degeneration of acinar cells. CONCLUSION: This study has shown that intraductal H2O2 perfusion induced acute edematous pancreatitis with marked histopathological changes and increased pancreatic duct permeability in cats. Intraarterial H2O2 infusion, however, has no effect on the permeability of the MPD and morphology of pancreas in our model.

Acute Disease↗
PubMed1998

Delayed-onset profound biotinidase deficiency.

Children with biotinidase deficiency usually exhibit symptoms at several months to years of age. We describe four children who had symptoms later in childhood or during adolescence; they had motor limb weakness, spastic paresis, and eye problems, such as loss of visual acuity and scotomata, rather than the more characteristic symptoms observed in young untreated children with the disorder. These older children each have different mutations, but they are the same as those of children who have exhibited symptoms at an early age. Biotinidase deficiency should be considered in older children who suddenly experience limb weakness and/or spastic paresis and eye symptoms.

Acyltransferases↗
PubMed1997

Heights and weights of primary school children of different social background in Ankara, Turkey.

A cross-sectional anthropometric survey was carried out in a low socio-economic and high socio-economic region of Ankara, Turkey, to measure the weights and heights of school children. The study group consisted of 5289 children between the ages of 5 and 11 years. Both boys and girls from the high socio-economic group had superior body measurements compared to those of the low socio-economic group. The difference between the mean weight for age values of two groups was statistically significant (P < 0.05), whereas no statistically significant difference was found on the basis of height for age values among all age groups. To make a comparison both with National Centre for Health Statistics and World Health Organisation (NCHS-WHO) standards and Turkish standards we used the data from high socio-economic group only. Our results showed that the mean height and weight values of boys and girls were higher than the 50th centile height and weight values of NCHS-WHO standards. Almost 25 years have passed since the measurements of Turkish standards were taken. The height differences were in the range of 0.24-1.51 cm/decade, with a mean value of 0.96 cm/ decade. These results led us to conclude that, local/regional standards for height and weight are needed, and repeated assessments are useful for follow-up of populations.

Anthropometry↗
PubMed1996

Cold restraint stress-induced gastric mucosal dysfunction. Role of nitric oxide.

The objectives of this study were to determine the cold restraint stress-induced changes in gastric mucosal permeability and to assess whether nitric oxide synthesis inhibition affects gastric mucosal integrity after cold-restraint administration. Cold-restraint stress caused multiple gastric lesions in 90% of animals. The lesion index was found to be 3.87 +/- 0.97 mm. Gastric mucosal permeability to the [51CR]EDTA molecule was significantly elevated in the cold-restraint group compared to control. In order to evaluate the role of nitric oxide in cold restraint stress-induced gastropathy, L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME) was given as a bolus (10 mg/kg, intravenously) and infused at a rate of 2 mg/ml/hr for 2 hr after cold-restraint administration. L-NAME greatly exacerbated gastric mucosal dysfunction associated with cold-restraint stress. D-NAME, the biologically inactive enantiomer, did not enhance mucosal dysfunction, whereas L-arginine, the substrate for nitric oxide, reversed the effect of L-NAME. In an additional group of experiments, effects of cold-restraint stress and L-NAME on net transmucosal fluid flux as well as tissue myeloperoxidase activity (MPO) were assessed. Cold-restraint stress administration significantly reduced the absorptive capacity of stomach, whereas L-NAME treatment did not affect the stress-induced alterations on net fluid absorption. Furthermore, L-NAME treatment did not affect the cold restraint stress-induced changes in tissue MPO activity. Our results suggest that gastric barrier function is altered after cold-restraint stress and nitric oxide production is important in minimizing mucosal barrier dysfunction associated with cold-restraint stress administration. Our results also indicate that L-NAME-induced alterations on mucosal permeability are not related to net transmucosal fluid flux and tissue neutrophils.

Animals↗
PubMed1994

Infantile spasms as the initial symptom of biotinidase deficiency.

Two patients with biotinidase deficiency had diagnoses of infantile spasms made at 1 month of age. Biotinidase deficiency may be seen early in the neonatal period without the characteristic findings such as alopecia and seborrheic dermatitis. This diagnosis should be considered in patients with infantile spasms.

Amidohydrolases↗
PubMed1990

Defects in the E2 lipoyl transacetylase and the X-lipoyl containing component of the pyruvate dehydrogenase complex in patients with lactic acidemia.

Three patients with chronic lacticacidemia and deficiency of the pyruvate dehydrogenase complex demonstrated in cultured skin fibroblasts showed abnormalities on Western blotting with anti-pyruvate dehydrogenase complex antiserum which were not located in the E1 (alpha and beta) component of the complex. One of these patients had an enzymatically demonstrable deficiency in the E2 dihydrolipoyl transacetylase segment of the complex and very low observable E2 protein component on Western blotting of fibroblast proteins. The other two patients had abnormalities observable in the X component but no observable reduction in either E1, E2, or E3 enzymatic activities. One patient appeared to have a missing X component while the other had two distinct bands where X should be on Western blotting of fibroblast proteins. All three patients appeared to have severe clinical sequelae resulting from these defects. This is the first time that defects in either the E2 or the X component of the pyruvate dehydrogenase complex have been observed in the human population.

Acetyltransferases↗