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Biomedical subjects

G Akyol

Publications and source records attributed to G Akyol.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of the effect of transplant-related factors and tissue injury on donor-derived hepatocyte and gastrointestinal epithelial cell repopulation following hematopoietic cell transplantation.

The aim of this study was to detect donor-derived hepatocytes and gastrointestinal epithelial cells in recipients of sex-mismatched allogeneic hematopoietic cell transplants, and to assess the effect of tissue injury on the extent of the repopulation. A total of 29 paraffin-embedded biopsy samples were reviewed. Double labeling by immunohistochemistry and fluorescence in situ hybridization was performed. Eighty-nine percent of sex-mismatched samples with histologic evidence of injury demonstrated the presence of donor-derived hepatocytes and gastrointestinal epithelial cells (mean 2.4%). None of the hepatocytes and gastrointestinal epithelial cells in samples obtained from female recipients with female donors showed a Y chromosome signal. The proportion of donor-derived hepatocyte and gastrointestinal epithelial cells in samples with severe graft-versus-host disease was greater than that of samples with mild/moderate graft-versus-host disease (P = 0.09). No relationship between the source of stem cells and the population rate was detected (P > 0.05). We conclude that some recipient hepatocytes and gastrointestinal tract epithelial cells are replaced by donor-derived cells during tissue injury. The severity of tissue injury seems to influence on the extent of this repopulation.

Adolescent↗
PubMed2005

Fibrinogen storage disease without hypofibrinogenemia associated with estrogen therapy.

BACKGROUND: Cytoplasmic inclusion bodies within hepatocytes may have different etiologies, including the Endoplasmic Reticulum Storage Diseases (ERSDs). ERSD is a pathological condition characterized by abnormal accumulation of proteins destined for secretion in the endoplasmic reticulum of hepatocytes; it may be congenital (primary) or acquired (secondary). Fibrinogen storage disease is a form of ERSD. CASE PRESENTATION: We present a case of fibrinogen storage disease secondary to estrogen replacement therapy. Its causal relationship to the drug is shown by histological, immunohistochemical and ultrastructural studies of paired liver biopsies obtained during and after the drug therapy. CONCLUSION: The liver biopsies of patients with idiopathic liver enzyme abnormalities should be carefully evaluated for cytoplasmic inclusion bodies and, although rare, fibrinogen deposits.

Adult↗
PubMed2002

The protective effect of taurine pretreatment on carbon tetrachloride-induced hepatic damage--a light and electron microscopic study.

The results regarding taurine pretreatment on CCl(4)-induced hepatic injury are controversial. To assess the therapeutic efficacy of taurine on rat liver injury, hepatic malondialdehyde, glutathione, and hydroxyproline levels together with morphologic alterations in the liver following CCl(4) administration were investigated. The rats were divided into three groups. Taurine-treated animals received 15 ml/kg/day of a 5% taurine solution by a gastric tube for 5 days before administering CCl(4) (2 ml/kg, intraperitoneally, in a single dose). CCl(4)-treated rats received the same amount of saline solution. Control animals received no treatment. The increase of hepatic malondialdehyde formation in the CCl(4)-treated group was partially prevented by taurine pretreatment, but taurine had no significant effect on the glutathione and hydroxyproline content in the CCl(4)-treated rats. Taurine pretreatment induced a marked beneficial effect regarding the prevention of hepatocellular necrosis and atrophy as demonstrated morphologically. In conclusion, these results suggest that taurine pretreatment might not significantly change the biochemical parameters, but prevents the morphologic damage caused by CCl(4) in the early stages.

Animals↗
PubMed2002

Keratocyte apoptosis and corneal antioxidant enzyme activities after refractive corneal surgery.

PURPOSE: Refractive corneal surgery induces keratocyte apoptosis and generates reactive oxygen radicals (ROS) in the cornea. The purpose of the present study is to evaluate the correlation between keratocyte apoptosis and corneal antioxidant enzyme activities after different refractive surgical procedures in rabbits. METHODS: Rabbits were divided into six groups. All groups were compared with the control group (Group 1), after epithelial scraping (Group 2), epithelial scrape and photorefractive keratectomy (PRK) (traditional PRK: Group 3), transepithelial PRK (Group 4), creation of a corneal flap with microkeratome (Group 5) and laser-assisted in situ keratomileusis (LASIK, Group 6). Terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labelling assay (to detect DNA fragmentation in situ) and light microscopy were used to detect apoptosis in rabbit eyes. Glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities of the corneal tissues were measured with spectrophotometric methods. RESULTS: Corneal Gpx and SOD activities decreased significantly in all groups when compared with the control group (P<0.05) and groups 2, 3 and 6 showed a significantly higher amount of keratocyte apoptosis (P<0.05). Not only a negative correlation was observed between corneal SOD activity and keratocyte apoptosis (cc: -0.3648) but Gpx activity also showed negative correlation with keratocyte apoptosis (cc: -0.3587). CONCLUSION: The present study illustrates the negative correlation between keratocyte apoptosis and corneal antioxidant enzyme activities. This finding suggests that ROS may be partly responsible for keratocyte apoptosis after refractive surgery.

Analysis of Variance↗
PubMed2002

Effect of mechanical vs dilute ethanol epithelial removal on keratocyte apoptosis and polymorphonuclear leukocyte migration.

PURPOSE: To investigate keratocyte apoptosis and polymorphonuclear (PMN) cell infiltration to the corneal stroma after mechanical epithelial scraping and chemical de-epithelialization with 18% ethanol solution. METHODS: Twelve New Zealand Albino rabbits (24 eyes) were randomly divided into three groups. Group A was the control group with no epithelial removal. Group B underwent a 7.5-mm mechanical epithelial removal with a blunt spatula. Group C underwent 7.5-mm chemical de-epithelialization with 18% ethanol-balanced salt solution. Corneas were stained with terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) assay after 24 h. Only nuclear staining in keratocytes was counted. Polymorphonuclear (PMN) leukocyte densities were also assessed by light microscopy. RESULTS: Mechanical de-epithelialization (group B) and chemical de-epithelialization with 18% ethanol (group C) showed no difference in keratocyte apoptosis compared with the control group. There was also no difference between groups B and C. Group B showed no difference in PMN leukocyte counts compared with the control group. But the number of PMN leukocytes observed in group C was significantly higher than those encountered in the corneas of the control group (P < 0.05) and group B (P < 0.05). CONCLUSIONS: Dilute alcohol induces more PMN cell infiltration when compared with mechanical de-epithelialization although there is no difference in the apoptosis rates.

Animals↗
PubMed2001

Expression of Bcl-2 and c-ErbB-2 in colorectal neoplasia.

Several studies have been demonstrated the value of c-ErbB-2 and Bcl-2 in predicting the biological behaviour of tumors. The aim of this study was to investigate Bcl-2 and c-ErbB-2 expression in colorectal carcinomas and the correlation between their presence and other clinicopathologic parameters. Eighty-six colorectal carcinomas and 17 adenomas were stained with Bcl-2 and c-ErbB-2 immunohistochemically. Staining patterns were assessed semi-quantitatively and correlated with tumor size, Duke s classification, tumor differentiation, mucinous characteristic and anatomic locations. We detected Bcl-2 expression in 10 of 17 adenomas (58.8 %) and 31 of 86 carcinomas (36.04 %). Positive staining in normal mucosa was observed only in the compartment of cryptic cells. However neither the difference in the rates of Bcl-2 positivity in adenoma and carcinoma groups, nor the correlation with other mentioned clinicopathological parameters, were found statistically significant. Bcl-2 expression was found to be significantly high in mucinous carcinomas. Expression of c-ErbB-2 was observed in 12 of 86 (13.95 %) carcinomas. It was not detected in adenomas and normal mucosa. Although the incidence of c-ErbB-2 in nonmucinous carcinoma was higher than that of mucinous carcinoma, this was not significant. In addition we were unable to show any significant relation between c-ErbB-2 expression and other clinicopathologic features. Our result suggest that c-ErbB-2 protein expression in colorectal carcinomas, is not very frequent event. There is no correlation between c-ErbB-2 expression and malignant potential of colorectal carcinomas. Higher expressions of Bcl-2 in adenomas than carcinomas suggest us a possible role of Bcl-2 in early carcinogenesis of colon. However since we were unable to find any significant correlation between Bcl-2 expression and other parameters the impact of this gene on biological behavior is still unclear for us.

Adenoma↗
PubMed2001

Association between the severity of heart failure and the susceptibility of myocytes to apoptosis in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Bcl-2 proto-oncogene, an inhibitor of apoptosis and Bax proto-oncogene, an inducer of apoptosis play critical roles in the molecular circuit controlling apoptosis in cardiac muscle. The ratio of Bax to Bcl-2 proto-oncogene determines survival or death after an apoptotic stimulus. We speculated that susceptibility of myocytes to apoptosis determined as the Bax/Bcl-2 ratio might vary with the severity of heart failure. METHODS AND RESULTS: We studied immunohistochemically 108 endomyocardial biopsy specimens from 30 patients with idiopathic dilated cardiomyopathy (mild heart failure, n=14; moderate or severe heart failure, n=16) with the use of Bcl-2 and Bax monoclonal antibodies. The expression of each protein was determined semiquantitatively as the fraction of myocytes labeled with specific monoclonal antibodies using a digital morphometric analysis system. Patients with mild heart failure showed significantly increased Bax/Bcl-2 ratio than the patients with advanced heart failure (1.59+/-1.26 vs. 0.34+/-0.43, P=0.002). The expression of Bcl-2 was found to be independent of the severity of heart failure whereas the expression of Bax was significantly higher in patients with mild heart failure compared to the patients with moderate or severe heart failure (52.1+/-29.3 vs. 21.6+/-22.4%, P=0.005). Additionally, Bax/Bac-2 ratio was inversely correlated with the mitral E-interventricular septum distance, left ventricular end-systolic and end-diastolic diameter. CONCLUSION: The susceptibility of myocytes to apoptosis is significantly increased in the early phase of heart failure but it decreases with worsening of the disease due to depressed expression of Bax onco-protein. Increased myocyte susceptibility to apoptosis may have a role in the transition from mild heart failure to severe in patients with idiopathic dilated cardiomyopathy.

Adult↗
PubMed2001

Investigation of the ototoxic effects of interferon alpha2A on the mouse cochlea.

This prospective randomized study investigates the possible toxic effects of interferon (IFN) alpha2A on the mouse cochlea. Thirty-six albino Swiss mice that were randomly assigned to 3 groups underwent baseline auditory brain stem response testing bilaterally to objectively assess baseline hearing levels. The first group received a single dose of 50,000 units, and the second group received 100,000 units of IFN-alpha2A intraperitoneally, whereas the third group was given no medication. Repeat auditory brain stem response testing revealed a significant rise in mean baseline peak equivalent sound pressure level thresholds in the groups that received IFN (P < 0.001). Histologically, the cochleae of mice that received IFN had a decreased number of fibroblasts in the spiral limbus, as well as prominent cytoplasmic vacuolation of these cells, compared with control animals. Loss of hair cells was not observed. It is possible that reversible biochemical and metabolic changes in the cochlea, rather than morphologic abnormalities, manifest IFN ototoxicity.

Animals↗
PubMed1999

Hematopoietic stem cell transplantation from non-replicative hepatitis B virus carriers is safe.

BACKGROUND/AIMS: Hepatitis B virus can cause serious problems in individuals undergoing organ transplantation. The aim of this study was to evaluate the hepatic events among HBs-Ag positive recipients and HBs-Ag negative recipients who received products from hepatitis B virus carriers. METHODS: A total of 151 patients received an allogeneic hematopoietic stem cell transplantation at the Department of Hematology-Oncology, University of Ankara, between June 1989 and June 1998. Among these, eight HBs-Ag positive and four HBs-Ag negative recipients received a product from a hepatitis B virus positive donor. The median follow-up period for these 12 patients was 13.2 months. RESULTS: Three of the eight HBs-Ag positive recipients died (one from hepatic failure); of the remainder, two are HBs-Ag negative, two HBs-Ag positive with normal liver injury tests and one HBs-Ag positive with elevated ALT levels. Of the four HBs-Ag negative recipients who received stem cells from a hepatitis B positive donor, two died; none of the patients in this group became HBs-Ag positive after transplantation. CONCLUSION: Hepatitis B virus infection is a common problem in patients being considered for allogeneic hematopoetic stem cell transplantation, especially in areas where hepatitis B virus infection is endemic. We believe that the presence of HBs-Ag positivity is not an absolute contraindication for allogeneic hematopoetic stem cell transplantation unless the hepatitis B virus is in a replication phase.

Adolescent↗
PubMed1999

P53 and proliferating cell nuclear antigen (PCNA) expression in non-tumoral liver diseases.

The tumor suppressor gene p53 is known to be involved in the negative regulation of cell growth. Proliferating cell nuclear antigen (PCNA), which is a nuclear protein and a component of the DNA replication process, is also involved in growth regulation. Both have been studied as progression markers in various tumors including hepatocellular carcinoma. In the present study, the aberrant p53 protein and PCNA expressions in non-tumoral liver diseases were investigated. Using monoclonal antibodies anti-p53 (D07-DAKO) and anti-PCNA (PC10-DAKO), 149 samples were stained, including 10 normal and 10 tumoral control liver tissues. p53 Overexpression was detected in 52 specimens (35%) whereas PCNA positivity was found in 96 (64%). There were 21 different pathological entities but most of the positive samples could be grouped into four types of diseases; namely, non-specific reactive hepatitis, steatohepatitis, chronic hepatitis and cirrhosis. Statistical analyses performed on these groups revealed that p53 positivity was found to be significantly higher in steatohepatitis (P < 0.05), while PCNA positivity did not show any statistical significance. The number of samples showing both p53 and PCNA positivity was 42 but their coexistence was not found to be significant. Certain cytological alterations like nuclear pleomorphism, steatosis and cholestasis, in addition to necroinflammatory activity, were evaluated for their possible impact on p53 and/or PCNA positivity. Necroinflammatory activity in steatohepatitis and steatosis in chronic hepatitis was found to be significant for p53 positivity (P < 0.05). In contrast, nuclear pleomorphism in non-specific reactive hepatitis was found to be significant for PCNA positivity (P < 0.05).

Cell Nucleus↗
PubMed1999

Expression of c-erbB-2 oncoprotein in gastric carcinoma: correlation with histopathologic characteristics and analysis of Ki-67.

Amplification and overexpression of the c-erbB-2 gene has been demonstrated in several tumors and thought to be important determinants of biologic behaviors of carcinomas. In this study, correlation between c-erbB-2 expression und histopathologic parameters, including proliferative activity of gastric carcinomas was evaluated. Paraffin-embedded tissue sections from 62 patients who underwent curative resection of gastric carcinoma were analyzed immunohistochemically for the expression of c-erbB-2 and Ki-67. Strong membrane staining for c-erbB-2 was detected in 11 of 62 gastric carcinomas (17,7%) and no positive reaction was evident in noncancerous tissue. The incidence of c-erbB-2 positivity in intestinal type carcinomas (24,3%) was higher than that of diffuse type carcinomas (4,76%). Positive staining for c-erbB-2 was present in one of the 9 (11,1%) early gastric carcinomas and 10 of 53 (18, 8%) advanced gastric carcinomas. However, no statistically significant relationships were found between c-erbB-2 expression and histopathologic type, depth on invasion, the tumor size or lymph node metastases. Among the metastatic lymph nodes, 3 were positively stained with c-erbB-2 whereas the primary tumors of two cases had been found to be negative. Additionally, no correlation was found between c-erbB-2 reactivity and proliferative activity of carcinoma cells. The results suggest that expression of c-erbB-2 protein may occur selectively in intestinal type of gastric carcinomas. However, c-erbB-2 expression is not a reliable marker of malignant potential in gastric carcinomas.

Humans↗
PubMed1999

Differences in liver pathology and clinical outcome between two patients with hepatitis B virus and graft versus host disease.

Our two patients undergoing allogeneic bone marrow transplantation (AlloBMT) had both Hepatitis B virus (HBV) and graft-versus-host disease (GVHD). In the first patient, liver enzymes elevated three months after AlloBMT, and GVHD was diagnosed. Two weeks after the diagnosis of GVHD, HBsAg appeared in his serum. At that time, liver biopsy was not able to discriminate two disorders, but his sequential liver biopsies disclosed GVHD. Despite the patient was treated with cyclosporin A (CsA), he died for chronic GVHD. In contrast to the first patient, the second patient had HBsAg prior to GVHD. His liver enzymes deterioration was detected in the first month after AlloBMT, and reached the highest level in the third month while withdrawing CsA. In the fifth month he developed scleradermatous skin changes, and skin biopsy revealed chronic GVHD, whereas concurrent liver biopsy revealed chronic active hepatitis. This observation showed that immunosuppressive conditions such as GVHD or its prophylaxis may affect the appearance of liver pathology caused by HBV, which depends on the time of GVHD development, and the duration and depth of GVHD prophylaxis.

Adult↗
PubMed1997

Correlation of nuclear p53 over-expression with clinical and histopathological features of transitional cell bladder cancer.

Forty-four pathologic specimens of 39 bladder cancer patients were analyzed immunohistochemically with D07 monoclonal antibody to detect over-expression of mutant p53 gene. The findings were interpreted by correlating with patient age, sex, cigarette smoking, number and macroscopic appearance of tumour, histological tumour grade, muscular invasion, vascular invasion, necrosis and urothelial atypia or dysplasia. Mutant p53 gene was over-expressed in 8 (18.2%) specimens. Statistically significant correlation with grade, vascular invasion, necrosis and patient sex was found with p53 over-expression. Available follow-up data were insufficient to draw a conclusion about the prognostic role of p53 over-expression. Prospective studies with larger number of patients are needed to define the exact place of nuclear p53 over-expression in transitional cell bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1997

Hepatitis B virus infection in allogeneic bone marrow transplantation.

Fourty-four patients who underwent allogeneic bone marrow transplantation (alloBMT) were studied for hepatitis B virus (HBV)-related complications. The mean follow-up period was 15.3 months. Positivity for HBV surface antigen (HBsAg) was observed in 10 patients (22.7%) throughout the study. Four of the 10 patients were HBsAg carriers before alloBMT, while the remaining six became HBsAg(+) after alloBMT. During the follow-up period (from 6 months to 45 months), an elevation in serum ALT activity was observed in the four carriers when immunosuppression was reduced or withdrawn. All of the four HBsAg carriers developed hepatitis, but none of them died of liver failure due to HBV. Only one death due to GVHD and diabetic ketoacidosis was observed in this group. Two of the four carriers received marrow from anti-HBs positive donors and one of them cleared HBsAg from his serum via adoptive immunity 8 months after transplantation. The remaining six patients acquired HBV after alloBMT, but we were unable to demonstrate the source of HBV. Five of them had a moderate increase in serum ALT activity while the other patient had a normal ALT. Two patients seroconverted to anti-HBs spontaneously. Two patients died during the follow-up, one due to intracranial hemorrhage and the other due to GVHD and accompanying pulmonary infection. The rest of the study group (34 patients) remained HBsAg(-) throughout the study. Two of them had an HBsAg(+) donor, but neither developed HBV infection in their follow-up period. The acquisition rate of HBV infection was relatively low in recipients who were positive for anti-HBs compared to those who were negative for anti-HBs (8 vs 19%). Anti-HBs positivity remained for a longer period in recipients who received marrow from anti-HBs positive donors compared to those recipients who had anti-HBs negative donors (median 12 vs 3 months). We think that HBV is a frequent cause of liver dysfunction in alloBMT patients where HBV infection is endemic. Whether the disease is in the form of reactivation of HBsAg-positive recipients, or is acquired from unknown sources in recipients who never had contact with the virus, the course of the disease is not fatal. Silent serologic changes can be demonstrated if viral serologic markers are sought serially. Among them, the disappearance of serum anti-HBs may be important as it increases the risk of HBV contamination in recipients.

Adolescent↗
PubMed1996

Intestinal endotoxins as co-factors of liver injury in obstructive jaundice.

The concept of endotoxin-mediated rather than direct liver injury in biliary obstruction was investigated using the experimental rat model of bile duct ligation (BDL) and small bowel bacterial overgrowth (SBBO). Small identical doses of intravenous endotoxin (bacterial LPS) caused a significantly more severe liver injury in rats with BDL, compared with sham-operated rats, suggesting the possible contribution of LPS in this type of liver damage. BDL was then combined with surgically created jejunal self-filling blind loops, which resulted in SBBO. Plasma LPS level increased significantly, and once again a more severe liver injury, determined by liver histology and serum gamma-glutamyl transpeptidase levels, was observed compared with the control group of rats with BDL+self-emptying blind loops. The data presented suggest that small amounts of exogenous LPS and/or the ordinarily innocous amounts of LPS constantly absorbed from the intestinal tract may be critical in the hepatic damage caused by obstruction of the biliary tract.

Animals↗
PubMed1996

Propylthiouracil-induced hepatic damage.

OBJECTIVE: To report a case of propylthiouracil-induced hepatic damage. CASE SUMMARY: A 64-year-old white woman with hyperthyroidism received propylthiouracil 250 mg/d for 1 year. She developed hepatitis after 1 year of therapy. Alcohol and drug abuse were ruled out and all serologic tests for hepatitis A, B, and C were negative. Cytomegalovirus and Epstein-Barr virus infection were also ruled out. Antinuclear antibody, antimitochondrial antibody, and antismooth muscle antibody were negative. The clinical picture was similar to that of viral hepatitis characterized by nausea, vomiting, and jaundice. Histologic examination of a liver biopsy specimen showed chronic active hepatitis. The patient developed cirrhosis during follow-up. DISCUSSION: Propylthiouracil is widely used in the treatment of hyperthyroidism. Despite its widespread use, there have been only a few reported cases of propylthiouracil-induced hepatotoxicity. The precise mechanism of the injury is unknown, although immunologic factors are suggested. CONCLUSIONS: Hepatic damage induced by propylthiouracil is a rare complication. However, the danger of permanent hepatic damage should be kept in mind. The best way of preventing propylthiouracil hepatotoxicity is careful screening of patients considered for treatment.

Antithyroid Agents↗
PubMed1995

Adult extrarenal Wilms' tumor. A case report.

Wilms' tumor or nephroblastoma is a malignant tumor of childhood and there are less than 200 cases in adults reported in the literature. An extrarenal location is also a rare situation for these tumors. A 48-year-old patient, referred to our gynecology department because of an abdominal mass, was operated on with a preoperative diagnosis of a possible ovarian tumor. The diagnosis of an extrarenal Wilms' tumor (ERWT) was made pathologically. Since it is a very rare entity, ERWT of adult origin is presented and the related literature is reviewed.

Abdominal Neoplasms↗