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Biomedical subjects

Abdullah Olgun

Publications and source records attributed to Abdullah Olgun.

9 recordsLinked to original sources

Functional analysis of MRG-1: the ortholog of human MRG15 in Caenorhabditis elegans.

Mortality Factor on Chromosome 4 (MORF4) induces senescence in several immortal human cell lines. MORF-related gene on chromosome 15 (MRG15), another expressed family member, is highly conserved and expressed in yeast to humans. To determine the biological functions of human MRG15 (hMRG15) we used RNA-mediated interference (RNAi) to silence mrg-1, the Caenorhabditis elegans ortholog, and its closest homolog Y37D8A.11. Expression of mrg-1 RNAi resulted in sterility, body wall defects, vulval protrusion, and posterior developmental defects in worms. We expressed mrg-1 under its own and the cytomegalovirus promoter in human cells. Both constructs were expressed, indicating that C. elegans promoter elements are functional in mammalian cells. Overexpression from the cytomegalovirus promoter eventually resulted in cell death, possibly due to competition with hMRG15 in endogenous nucleoprotein complexes. Recent data indicate a role for yeast and human MRG15 in transcriptional regulation via chromatin remodeling. Here we demonstrate the importance of mrg-1 in development and reproduction in C. elegans and discuss its potential to impact the aging process.

Aging↗

MEFV mutations in familial Mediterranean fever: association of M694V homozygosity with arthritis.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autosomal recessive recurrent polyserositis with a higher prevalence in some ethnic groups, including Turks. Mutations in the FMF gene (MEFV) were found associated with FMF. The aim of this study was to analyze MEFV gene mutations in FMF patients to gain insight into the mutation phenotype correlation. OBJECTIVES: We analyzed the most frequent mutations (M680I, M694V, V726A, and E148Q) in a group of young male Turkish FMF patients using an amplification refractory mutation system and a commercial kit. RESULTS: M694V mutation was detected in 80% of the patients. After making a strict diagnostic discrimination between arthralgia and arthritis, arthritis was present in 71% of homozygous and 29.4% of heterozygous patients for M694V mutation. Other mutations were not found to correlate with specific symptoms or findings. CONCLUSION: The homozygosity of M694V mutation in the MEFV gene is associated with arthritis in FMF patients.

Adult↗

The role of RBC destruction in vascular regions with high turbulence on atherosclerosis.

After intravascular red blood cell (RBC) destruction, released hemoglobin exceeding the binding capacities of haptoglobin and hemopexin would contribute, as free hemoglobin and/or hemin and/or methemalbumin, to the pathogenesis of atherosclerosis. Especially in some regions of vasculature with a high turbulence strong enough to destruct fragile or old RBCs, free hemoglobin concentrations can exceed locally the binding capacities of haptoglobin and hemopexin although their measured venous concentrations are normal. As a very simple model of this possible very local event we analysed free hemoglobin and methemalbumin levels after blood collection into evacuated tubes, and found that the increase of methemalbumin is more significant than free hemoglobin. The measurement of free hemoglobin and methemalbumin concentrations of arterial blood samples just from pre- and post-atherosclerotic lesions can likely shed new light on our understanding of the development of atherosclerosis.

Arteriosclerosis↗

[Plasma zinc and copper levels in boys with oppositional defiant disorder].

OBJECTIVE: Oppositional defiant disorder consists of negativistic, hostile, or defiant behavior, created in one of three domains of functioning (academic, occupational, or social), and lasting at least six months. Alterations in zinc and copper levels of plasma in animals and humans are associated with behavioral and cognitive abnormalities. The aim of this study is to compare plasma zinc and copper levels between children with oppositional defiant disorder (ODD) and controls. METHOD: Plasma zinc and copper levels were measured in 21 boys with ODD having a mean age of 8.6 +/- 2.0 years and in 24 healthy boys having a mean age of 8.3 +/- 2.1 years by atomic absorption spectrophotometry. An ODD diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). About 61% of the children with ODD had comorbid attention deficit hyperactivity disorder. RESULTS: Plasma zinc was significantly lower in ODD children compared to the controls (p < .05). No significant difference in plasma copper measurements was found between the two groups (p >.05). CONCLUSION: The results of the present study suggested that the plasma copper level in boys with ODD did not differ from that in normal subjects. Although ODD children had a lower plasma zinc level than normal subjects, the mean plasma zinc level was within the normal range for the population. Further studies investigating the Zn and Cu metabolism in ODD are needed.

Case-Control Studies↗

The effect of isoprenoid side chain length of ubiquinone on life span.

The isoprenoid side chain length of ubiquinone (Q) can have an effect on the life span of mammals. The short living mouse and rat have Q(9), while primates have Q(10) as the major form. Ubiquinones (Qs) having longer hydrophobic tail are likely more imbedded in the mitochondrial inner membrane than the ones having shorter tails. In case of short tail length, ubisemiquinone (Q(*-)) produced during electron transport can be more exposed to the aqueous phase on both sides of the membrane, generate more superoxide radical and damage the neighbouring macromolecules. Considering the inefficient subcellular distribution of exogenous Q, production of transgenic animals synthesizing Qs having longer than 10 isoprenoid units (Q(>10)) can increase their life span.

Animals↗

Peripheral blood telomerase activity in non-Hodgkin lymphoma.

Telomerase, a ribonucleoprotein, stabilizing chromosomes by adding telomeric repeats to their ends, is highly expressed in most neoplastic cells and has a critical role in cellular immortalization. In this study, telomerase activity was measured in the peripheral blood mononuclear cells of patients with non-Hodgkin lymphoma (NHL). A total of 18 patients with B-cell NHL and 12 healthy volunteers were included in the study. Of the patients 7 (38.9%) were found to have telomerase activity, but no activity was detected in control subjects. No correlation was found between the telomerase activity and the grade of the disease. When the patients were divided into two subgroups as follicular and non-follicular NHL, telomerase activity was detected in 5 of 10 follicular NHL (50%) and 2 of 8 non-follicular NHL (25%) samples, but these results were not found statistically significant. In conclusion, there is detectable telomerase activity in peripheral blood of some patients with NHL, possibly suggesting the existence of neoplastic cells in the circulation or activation of lymphocytes.

Adolescent↗

Genetics of cellular senescence.

Cellular senescence or replicative senescence is a state of irreversible growth arrest that somatic cells enter as a result of replicative exhaustion. This can be mimicked by culture manipulations such as Ras oncogene overexpression or treatment with various agents such as sodium butyrate and 5-azacytidine. It is believed that cellular senescence is one of the protective mechanisms against tumor formation. Genetic analyses of cellular senescence have revealed that it is dominant over immortality because whole cell fusion of normal with immortal cells yields hybrids with limited division potential. Only four complementation groups for indefinite division have been identified from extensive studies fusing different immortal human cell lines with each other. The senescence-related genes for three of the complementation groups B-D have been identified on human chromosomes 4, 1, and 7, respectively, by microcell-mediated chromosome transfer, though the existence of senescence-related genes on other chromosomes has been suggested. MORF4 was cloned as the senescence-related gene on human chromosome 4 and is a member of a new gene family, which has multiple transcription factor-like motifs. This gene family may affect cell division by modulating gene expression. Study of this novel gene family should lead to new insights regarding the mechanisms and function of cellular senescence in aging and immortalization.

Animals↗

Oxidative phosphorylation enzyme complexes in caloric restriction.

Free radicals, generated especially by electron leakage from mitochondrial electron transport chain (ETC), are accepted as one of the possible causes of aging. Long-term caloric restriction (CR) is known to increase the species specific average and maximum life spans. Thus it provides a means for investigating mechanisms of aging. There is evidence suggesting a decrease in the free radical production with CR. In this study, Blue-Native PAGE (BN-PAGE) technique was used to investigate the effect of CR on the oxidative phosphorylation enzyme complexes. Of the total 30 female Swiss Albino balb/c mice, 15 were used as control and the other 15 as CR group. Alternate day feeding regimen was used in the CR group for 66 weeks beginning at the end of 3rd month. In the control group, 5 (33.3%) mice died, 3 (20%) of them of breast cancer, 2 (13.3%) of unknown causes and no death cases were observed in the CR group during the study. BN-PAGE was performed on the extracts from brain mitochondrial fractions. Complexes II and V were excluded from the study due to some analytical limitations. No difference was found in the levels of complexes I and III between the groups. In the CR group, complex IV level was found increased and the ratio of complex III-IV decreased compared with the control group. Since there is a slight increase (108%) in the level of complex IV in the CR group, our results could suggest possible partial compensation of electron leakage in the upstream complexes in ETC, and the decrease of free radical production with CR.

Adenosine Triphosphatases↗

Diagnostic approach to prostate cancer using total prostate specific antigen-based parameters together.

This prospective study investigated the value of serum total prostate specific antigen (tPSA)-based parameters in the diagnosis of prostate cancer (PCa). Serum tPSA, free to tPSA ratio (f/tPSA), PSA density (PSAD), and PSA transition zone (PSAT) were evaluated in 110 patients with histologically confirmed benign prostate hyperplasia (BPH) and 98 patients with PCa. Once the serum tPSA was elevated (greater than 4 ng/ml) or digital rectal examination (DRE) was suspicious, transrectal ultrasound-guided biopsies were recommended. The tPSA, f/tPSA, PSAD, and PSAT levels were significantly different between the BPH and PCa groups. In patients with a tPSA level of 4.1-9.9 ng/ml or an abnormal DRE finding, only PSAT was found to have discriminating power. The cut-off values were 0.15 for f/tPSA, 0.30 for PSAT, and 0.15 for PSAD. The diagnostic sensitivity of a positive result for one of these parameters in the whole group was 84%, but 75% in patients with a tPSA of 4.1-9.9 ng/ml or an abnormal DRE finding. The diagnostic specificity of positive results for 3 parameters was 92% in the whole group and 93% in patients with a tPSA of 4.1-9.9 ng/ml or an abnormal DRE finding. All parameters were influenced by the histological grades. Histological grades showed a negative correlation (r = -0.56) with f/t PSA and a positive correlation (r = 0.44) with PSAT. No diagnostic marker investigated heretofore was able to rule out or detect early PCa in patients with a PSA level of 4.1-9.9 ng/ml. Using the PSA-based parameters together can be helpful in management of these patients. If all of the PSA-based parameters are negative, biopsy might be postponed; patients who have three positive PSA-based parameters should be biopsied. In case of one or two of the parameters, the patient's age and race should be considered in clinical decision-making.

Aged↗