Glutathione S-transferase mu (GST mu) enzyme detoxifies carcinogens in tobacco smoke. We assessed... more Glutathione S-transferase mu (GST mu) enzyme detoxifies carcinogens in tobacco smoke. We assessed the clinical usefulness of serum assay of GSTm in determining the risk for lung cancer. Fifty-nine patients with primary lung cancer and 32 control cases were enrolled. GSTm detection was performed by the method ELISA. GSTm enzyme positivity rate of the patient group (39%) was significantly lower than the control group (59.4%) (p < 0.05). The GSTm positivity rates were 28.6% for the non-smoker patients with a cancer history of relatives, 31.6% for the smoker patients with the cancer history of relatives, 14.6% for the non-smoker patients with the lung cancer history of relatives and 16.7% for the smoker patients with the lung cancer history of relatives. We concluded that if the people lacking GSTm are smokers and have a cancer and/or lung cancer history among their relatives, they would challenge a greater risk of lung cancer than the individuals having GST mu isoenzyme.
It is known that tissue and serum sialic acid levels may be altered by malignant transformation. ... more It is known that tissue and serum sialic acid levels may be altered by malignant transformation. In this study, sialic acid levels were determined in bronchoalveolar lavage fluid (BAL) and serum in two groups of patients with lung cancer and non-malignant diseases of the lung. Colorimetric methods were used for determination sialic acid in serum and in BAL samples. Flexible bronchoscopy was used to obtain the latter. Sialic acid levels in bronchoalveolar lavage fluid and serum did not show any statistically significant difference between subjects with malignant and the non-malignant lung diseases (p > 0.05). Sialic acid levels were also unrelated to the stage and localization of the tumor (p > 0.05). Sialic acid levels do not appear to be a good marker for discriminating malignant from non-malignant diseases of the lung.
Widespread external and internal changes in body morphology have long been known to be hallmarks ... more Widespread external and internal changes in body morphology have long been known to be hallmarks of the process of metamorphosis. However, more subtle changes, particularly at the molecular level, are only now beginning to be understood. A number of transcription factors have recently been shown to alter expression either in levels of message or in isoforms expressed. In this article, we describe a dramatic increase in the expression of the homeobox gene HoxA5 in the heart and aorta of the Mexican axolotl Ambystoma mexicanum during the process of thyroxin-induced metamorphosis. Immunohistochemical analysis with anti-HoxA5 antibody in thyroxin-induced metamorphosing animals showed a pattern of expression of HoxA5 comparable to that in spontaneously metamorphosing animals. Further, by in situ hybridization, we were able to show significant qualitative differences in the expression of this gene within the heart. Maximum HoxA5 expression occurred at the midpoint of metamorphosis in the myocardium, whereas the hearts of completely metamorphosed animals had the highest levels of expression in the epicardium and endocardium. In the aorta, smooth-muscle cells of the tunica media as well as cells of the tunica adventitia had an increase in expression of HoxA5 with thyroxin-induced metamorphosis. HoxA5 expression significantly changed in cells of the aorta and ventricle with treatment by thyroid hormone. HoxA5, a positive regulator of p53, may be involved with the apoptotic pathway in heart remodeling during amphibian metamorphosis.
Objective. The aim of this study was to investigate the quality of life of renal donors during lo... more Objective. The aim of this study was to investigate the quality of life of renal donors during long-term follow-up. Patients and Methods. The short form health survey (SF-36) questionnaire was compared between renal donors and the general population. We evaluated the relationship to postoperative complications and preoperative information with the quality of life. Results. Fifty renal donors of mean age 55.8 Ϯ 12 years (range, 29 -70 years) had a mean follow-up of 55.1 Ϯ 47.2 months (range, 12-168 months). Complications after donor nephrectomy were related with physical function loss (r ϭ Ϫ.397; P Ͻ .05) and vitality (r ϭ Ϫ.463; P ϭ .01). Renal donor candidates who did not have satisfactory information before the operation experienced difficulty with decision making (r ϭ Ϫ.555; P ϭ .0001). Physical function, limitation of physical role and limitation of emotional role were comparable to the general population. Pain scale was worse among donors compared with the general population (P ϭ .001). Educational status of renal donors was related to the pain scale and vitality (r ϭ .369; P Ͻ .05 and r ϭ .523; P Ͻ .05, respectively). General health perception, vitality, mental health, and social functioning were worse compared with the general population (P ϭ .0001, P ϭ .002, P ϭ .0001, and P ϭ .001, respectively). Health problems occurring after donation were related to negation of interfamily relations (r ϭ .695; P ϭ .0001).
Aim. Anti-donor antibodies, denoted as "panel-reactive antibodies" (PRAs), are one of the most im... more Aim. Anti-donor antibodies, denoted as "panel-reactive antibodies" (PRAs), are one of the most important factors influencing graft survival after renal transplantation. PRA is generally analyzed with enzyme-linked immunosorbent assay or flow cytometry (FC), which identify the HLA antigen specific for the preformed antibody. Patients and methods. We tested 66 patients for FC crossmatch (FCXM) when they were called for cadaveric renal transplantation. Thirty of 66 patients were FCXM-positive; 36 were FCXM-negative. Among the FCXM positive crossmatches, 21 were T-and B-cell positive; seven B positive; and two T positive. The HLA antibodies in the sera of FCXM-positive patients were reanalyzed using flow-PRA. Results. We detected HLA antibodies in 28/66 sera with flow PRA. The sera of 16/21 T-/B-, FCXM-positive patients contained both class I and II anti-HLA antibodies, five had only class I anti-HLA antibodies. One out of seven B-cell FCXM-positive patients had class I and class II anti-HLA antibodies, three, class I and 1 class II anti-HLA antibodies; the other two were negative. Class I and class II HLA antibodies were observed in two T-cell FCXM-positive patients. Four of 36 patients who were FCXM-negative were flow PRA positive: one had both class I and class II HLA antibodies and three, only class I HLA antibody. The comparison of FCXM and flow PRA results was significant (P ϭ .001). Conclusion. FCXM results may be confirmed by flow PRA tests, an important method to differentiate HLA versus non-HLA antibodies.
Living donor kidneys from spouses and children (from offspring to parents) are currently consider... more Living donor kidneys from spouses and children (from offspring to parents) are currently considered to be important organ sources. However, pregnancy-induced alloimmunization may provoke acute rejection episodes after kidney transplantation. being flow cytometry cross-match (FCXM) we studied donor-specific antibodies (DSAs) in the sera of recipients planned for living kidney transplantation from their spouse or children. When the FCXM was positive, we confirmed the existence of anti-human leukocyte antigen (HLA) antibodies using flow cytometry panel-reactive antibody (flow-PRA). Between March 2005 and November 2010, we tested 85 pretransplantation sera from renal transplant recipients for DSAs. The recipients included 37 wives (group I) and 48 husbands (group II). FCXM-positive sera were tested using a flow-PRA screening method using HLA class I and class II antigen-coated beads. The mean recipient age was 48.1 ± 9.8 (range, 28-69) years and the mean donor age was 45.1 ± 11.1 (range, 23-69 years). Among group I were 18 (48.6%) FCXM-positive cross-matches; for group II, 5 (10.4%) cases (P = .001). Sensitized patients were 37.9% FCXM-positive, whereas nonsensitized patients were 3.7% positive (P = .001). FCXM-positive patients were re-evaluated for anti-HLA antibodies using flow-PRA. Seventeen of 18 group I tests (94.4%) were FCXM-positive, whereas 3 of 5 (60%) were positive among group II. We concluded that flow cytometry-based cross-match and PRA techniques can be used to detect anti-HLA antibodies using spousal or children donors for kidney transplantation.
Radiocontrast administration is an important cause of acute renal failure. In this study, compare... more Radiocontrast administration is an important cause of acute renal failure. In this study, compared the plasma creatinine levels with spot urine IL-18 levels following radiocontrast administration. Twenty patients (11 males, 9 females) underwent radiocontrast diagnostic and therapeutic-enhanced examinations. The RIN Mehran risk score was low (≤5). The radiocontrast agents used were 623 mg/mL Iopromid (1.5 mL/kg), and 100 mL of 650 mg/mL meglumine diatrizoate as three-way oral and rectal contrast material for abdominal computed tomography (CT) scans. Serum blood urea nitrogen, creatinine, Na, K, Cl, Ca, P, creatinine clearance, and spot urine IL-18 levels were analyzed before and repeated at 24, 48, and 72 h after radiocontrast administration. Six and 24-h urinary IL-18 levels were measured with a human IL-18 ELISA kit following radiocontrast administration. An increase in plasma creatinine 24 and 48 h following radiocontrast administration was observed compared with precontrast values, but it was not statistically significant (P=0.052 and P=0.285, respectively). A statistically significant increase in IL-18 levels was observed at 6 and 24 h, compared with precontrast values (P=0.048 and P=0.028, respectively). A tendency for postcontrast 24-h urinary IL-18 levels to increase was observed compared with 6 h, but the increase was not statistically significant (P=0.808). Our results show that plasma creatinine starts to increase at 24(th) hour; however, spot urine IL-18 levels go up at 6(th) hour following radiocontrast administration implying urine IL-18 to be an earlier parameter for kidney injury.
It is well known that thoracotomy leads to several complications. In this study, effects of thora... more It is well known that thoracotomy leads to several complications. In this study, effects of thoracotomy on cellular and humoral immunities have been investigated. Leukocyte counts and lymphocyte counts of 100 patients operated by thoracotomy have been determined preoperatively and on the postoperative 3rd hour, and 1st, 2nd, 3rd, 5th days. Also lymphocyte surface markers (CD3, CD4, CD8, CD4/CD8, CD19, CD16/56) and immunoglobulin levels (IgG, IgA, IgM, IgE) in 40 out of 100 patients in the preoperative period and postoperatively twice on 7th day and then in the 3rd week have been detected. For the methodology hemocounter, flow cytometer, immunoprecipitation, and enzyme-linked immunosorbent assay were used. A marked increase in leukocyte count while a marked decrease in lymphocyte count has been observed after thoracotomy (P&amp;amp;amp;amp;lt;0.001). There was not any significant alteration in levels of lymphocyte surface markers and immunoglobulins in the postoperative period (P&amp;amp;amp;amp;gt;0.2). According to these results, leucocytosis occurred but lymphocyte count decreased in the early postoperative period. Immunoglobulin levels and subpopulation of lymphocytes were not affected from the operative stress.
A precise organization of contractile proteins is essential for contraction of heart muscle. With... more A precise organization of contractile proteins is essential for contraction of heart muscle. Without a necessary stoichiometry of proteins, beating is not possible. Disruption of this organization can be seen in diseases such as familial hypertrophic cardiomyopathy and also in acquired diseases. In addition, isoform diversity may affect contractile properties in such functional adaptations as cardiac hypertrophy. The Mexican axolotl provides an uncommon model in which to examine specific proteins involved with myofibril formation in the heart. Cardiac mutant embryos lack organized myofibrils and have altered expression of contractile proteins. In order to replicate the disruption of myofibril formation seen in mutant hearts, we have developed procedures for the introduction of contractile protein antibodies into normal hearts. Oligonucleotides specific to axolotl tropomyosin isoforms (ATmC-1 and ATmC-3), were also successfully introduced into the normal hearts. The antisense ATmC-3 oligonucleotide disrupted myofibril formation and beating, while the sense strands did not. A fluoresceintagged sense oligonucleotide clearly showed that the oligonucleotide is introduced within the cells of the intact hearts. In contrast, ATmC-1 anti-sense oligonucleotide did not cause a disruption of the myofibrillar organization. Specifically, tropomyosin expression can be disrupted in normal hearts with a lack of organized myofi-brils. In a broader approach, these procedures for whole hearts are important for studying myofibril formation in normal hearts at the DNA, RNA, and/or protein levels and can complement the studies of the cardiac mutant phenotype. All of these tools taken together present a powerful approach to the elucidation of myofibrillogenesis and show that embryonic heart cells can incorporate a wide variety of molecules with cationic liposomes.
Glutathione S-transferase mu (GST mu) enzyme detoxifies carcinogens in tobacco smoke. We assessed... more Glutathione S-transferase mu (GST mu) enzyme detoxifies carcinogens in tobacco smoke. We assessed the clinical usefulness of serum assay of GSTm in determining the risk for lung cancer. Fifty-nine patients with primary lung cancer and 32 control cases were enrolled. GSTm detection was performed by the method ELISA. GSTm enzyme positivity rate of the patient group (39%) was significantly lower than the control group (59.4%) (p < 0.05). The GSTm positivity rates were 28.6% for the non-smoker patients with a cancer history of relatives, 31.6% for the smoker patients with the cancer history of relatives, 14.6% for the non-smoker patients with the lung cancer history of relatives and 16.7% for the smoker patients with the lung cancer history of relatives. We concluded that if the people lacking GSTm are smokers and have a cancer and/or lung cancer history among their relatives, they would challenge a greater risk of lung cancer than the individuals having GST mu isoenzyme.
It is known that tissue and serum sialic acid levels may be altered by malignant transformation. ... more It is known that tissue and serum sialic acid levels may be altered by malignant transformation. In this study, sialic acid levels were determined in bronchoalveolar lavage fluid (BAL) and serum in two groups of patients with lung cancer and non-malignant diseases of the lung. Colorimetric methods were used for determination sialic acid in serum and in BAL samples. Flexible bronchoscopy was used to obtain the latter. Sialic acid levels in bronchoalveolar lavage fluid and serum did not show any statistically significant difference between subjects with malignant and the non-malignant lung diseases (p > 0.05). Sialic acid levels were also unrelated to the stage and localization of the tumor (p > 0.05). Sialic acid levels do not appear to be a good marker for discriminating malignant from non-malignant diseases of the lung.
Widespread external and internal changes in body morphology have long been known to be hallmarks ... more Widespread external and internal changes in body morphology have long been known to be hallmarks of the process of metamorphosis. However, more subtle changes, particularly at the molecular level, are only now beginning to be understood. A number of transcription factors have recently been shown to alter expression either in levels of message or in isoforms expressed. In this article, we describe a dramatic increase in the expression of the homeobox gene HoxA5 in the heart and aorta of the Mexican axolotl Ambystoma mexicanum during the process of thyroxin-induced metamorphosis. Immunohistochemical analysis with anti-HoxA5 antibody in thyroxin-induced metamorphosing animals showed a pattern of expression of HoxA5 comparable to that in spontaneously metamorphosing animals. Further, by in situ hybridization, we were able to show significant qualitative differences in the expression of this gene within the heart. Maximum HoxA5 expression occurred at the midpoint of metamorphosis in the myocardium, whereas the hearts of completely metamorphosed animals had the highest levels of expression in the epicardium and endocardium. In the aorta, smooth-muscle cells of the tunica media as well as cells of the tunica adventitia had an increase in expression of HoxA5 with thyroxin-induced metamorphosis. HoxA5 expression significantly changed in cells of the aorta and ventricle with treatment by thyroid hormone. HoxA5, a positive regulator of p53, may be involved with the apoptotic pathway in heart remodeling during amphibian metamorphosis.
Objective. The aim of this study was to investigate the quality of life of renal donors during lo... more Objective. The aim of this study was to investigate the quality of life of renal donors during long-term follow-up. Patients and Methods. The short form health survey (SF-36) questionnaire was compared between renal donors and the general population. We evaluated the relationship to postoperative complications and preoperative information with the quality of life. Results. Fifty renal donors of mean age 55.8 Ϯ 12 years (range, 29 -70 years) had a mean follow-up of 55.1 Ϯ 47.2 months (range, 12-168 months). Complications after donor nephrectomy were related with physical function loss (r ϭ Ϫ.397; P Ͻ .05) and vitality (r ϭ Ϫ.463; P ϭ .01). Renal donor candidates who did not have satisfactory information before the operation experienced difficulty with decision making (r ϭ Ϫ.555; P ϭ .0001). Physical function, limitation of physical role and limitation of emotional role were comparable to the general population. Pain scale was worse among donors compared with the general population (P ϭ .001). Educational status of renal donors was related to the pain scale and vitality (r ϭ .369; P Ͻ .05 and r ϭ .523; P Ͻ .05, respectively). General health perception, vitality, mental health, and social functioning were worse compared with the general population (P ϭ .0001, P ϭ .002, P ϭ .0001, and P ϭ .001, respectively). Health problems occurring after donation were related to negation of interfamily relations (r ϭ .695; P ϭ .0001).
Aim. Anti-donor antibodies, denoted as "panel-reactive antibodies" (PRAs), are one of the most im... more Aim. Anti-donor antibodies, denoted as "panel-reactive antibodies" (PRAs), are one of the most important factors influencing graft survival after renal transplantation. PRA is generally analyzed with enzyme-linked immunosorbent assay or flow cytometry (FC), which identify the HLA antigen specific for the preformed antibody. Patients and methods. We tested 66 patients for FC crossmatch (FCXM) when they were called for cadaveric renal transplantation. Thirty of 66 patients were FCXM-positive; 36 were FCXM-negative. Among the FCXM positive crossmatches, 21 were T-and B-cell positive; seven B positive; and two T positive. The HLA antibodies in the sera of FCXM-positive patients were reanalyzed using flow-PRA. Results. We detected HLA antibodies in 28/66 sera with flow PRA. The sera of 16/21 T-/B-, FCXM-positive patients contained both class I and II anti-HLA antibodies, five had only class I anti-HLA antibodies. One out of seven B-cell FCXM-positive patients had class I and class II anti-HLA antibodies, three, class I and 1 class II anti-HLA antibodies; the other two were negative. Class I and class II HLA antibodies were observed in two T-cell FCXM-positive patients. Four of 36 patients who were FCXM-negative were flow PRA positive: one had both class I and class II HLA antibodies and three, only class I HLA antibody. The comparison of FCXM and flow PRA results was significant (P ϭ .001). Conclusion. FCXM results may be confirmed by flow PRA tests, an important method to differentiate HLA versus non-HLA antibodies.
Living donor kidneys from spouses and children (from offspring to parents) are currently consider... more Living donor kidneys from spouses and children (from offspring to parents) are currently considered to be important organ sources. However, pregnancy-induced alloimmunization may provoke acute rejection episodes after kidney transplantation. being flow cytometry cross-match (FCXM) we studied donor-specific antibodies (DSAs) in the sera of recipients planned for living kidney transplantation from their spouse or children. When the FCXM was positive, we confirmed the existence of anti-human leukocyte antigen (HLA) antibodies using flow cytometry panel-reactive antibody (flow-PRA). Between March 2005 and November 2010, we tested 85 pretransplantation sera from renal transplant recipients for DSAs. The recipients included 37 wives (group I) and 48 husbands (group II). FCXM-positive sera were tested using a flow-PRA screening method using HLA class I and class II antigen-coated beads. The mean recipient age was 48.1 ± 9.8 (range, 28-69) years and the mean donor age was 45.1 ± 11.1 (range, 23-69 years). Among group I were 18 (48.6%) FCXM-positive cross-matches; for group II, 5 (10.4%) cases (P = .001). Sensitized patients were 37.9% FCXM-positive, whereas nonsensitized patients were 3.7% positive (P = .001). FCXM-positive patients were re-evaluated for anti-HLA antibodies using flow-PRA. Seventeen of 18 group I tests (94.4%) were FCXM-positive, whereas 3 of 5 (60%) were positive among group II. We concluded that flow cytometry-based cross-match and PRA techniques can be used to detect anti-HLA antibodies using spousal or children donors for kidney transplantation.
Radiocontrast administration is an important cause of acute renal failure. In this study, compare... more Radiocontrast administration is an important cause of acute renal failure. In this study, compared the plasma creatinine levels with spot urine IL-18 levels following radiocontrast administration. Twenty patients (11 males, 9 females) underwent radiocontrast diagnostic and therapeutic-enhanced examinations. The RIN Mehran risk score was low (≤5). The radiocontrast agents used were 623 mg/mL Iopromid (1.5 mL/kg), and 100 mL of 650 mg/mL meglumine diatrizoate as three-way oral and rectal contrast material for abdominal computed tomography (CT) scans. Serum blood urea nitrogen, creatinine, Na, K, Cl, Ca, P, creatinine clearance, and spot urine IL-18 levels were analyzed before and repeated at 24, 48, and 72 h after radiocontrast administration. Six and 24-h urinary IL-18 levels were measured with a human IL-18 ELISA kit following radiocontrast administration. An increase in plasma creatinine 24 and 48 h following radiocontrast administration was observed compared with precontrast values, but it was not statistically significant (P=0.052 and P=0.285, respectively). A statistically significant increase in IL-18 levels was observed at 6 and 24 h, compared with precontrast values (P=0.048 and P=0.028, respectively). A tendency for postcontrast 24-h urinary IL-18 levels to increase was observed compared with 6 h, but the increase was not statistically significant (P=0.808). Our results show that plasma creatinine starts to increase at 24(th) hour; however, spot urine IL-18 levels go up at 6(th) hour following radiocontrast administration implying urine IL-18 to be an earlier parameter for kidney injury.
It is well known that thoracotomy leads to several complications. In this study, effects of thora... more It is well known that thoracotomy leads to several complications. In this study, effects of thoracotomy on cellular and humoral immunities have been investigated. Leukocyte counts and lymphocyte counts of 100 patients operated by thoracotomy have been determined preoperatively and on the postoperative 3rd hour, and 1st, 2nd, 3rd, 5th days. Also lymphocyte surface markers (CD3, CD4, CD8, CD4/CD8, CD19, CD16/56) and immunoglobulin levels (IgG, IgA, IgM, IgE) in 40 out of 100 patients in the preoperative period and postoperatively twice on 7th day and then in the 3rd week have been detected. For the methodology hemocounter, flow cytometer, immunoprecipitation, and enzyme-linked immunosorbent assay were used. A marked increase in leukocyte count while a marked decrease in lymphocyte count has been observed after thoracotomy (P&amp;amp;amp;amp;lt;0.001). There was not any significant alteration in levels of lymphocyte surface markers and immunoglobulins in the postoperative period (P&amp;amp;amp;amp;gt;0.2). According to these results, leucocytosis occurred but lymphocyte count decreased in the early postoperative period. Immunoglobulin levels and subpopulation of lymphocytes were not affected from the operative stress.
A precise organization of contractile proteins is essential for contraction of heart muscle. With... more A precise organization of contractile proteins is essential for contraction of heart muscle. Without a necessary stoichiometry of proteins, beating is not possible. Disruption of this organization can be seen in diseases such as familial hypertrophic cardiomyopathy and also in acquired diseases. In addition, isoform diversity may affect contractile properties in such functional adaptations as cardiac hypertrophy. The Mexican axolotl provides an uncommon model in which to examine specific proteins involved with myofibril formation in the heart. Cardiac mutant embryos lack organized myofibrils and have altered expression of contractile proteins. In order to replicate the disruption of myofibril formation seen in mutant hearts, we have developed procedures for the introduction of contractile protein antibodies into normal hearts. Oligonucleotides specific to axolotl tropomyosin isoforms (ATmC-1 and ATmC-3), were also successfully introduced into the normal hearts. The antisense ATmC-3 oligonucleotide disrupted myofibril formation and beating, while the sense strands did not. A fluoresceintagged sense oligonucleotide clearly showed that the oligonucleotide is introduced within the cells of the intact hearts. In contrast, ATmC-1 anti-sense oligonucleotide did not cause a disruption of the myofibrillar organization. Specifically, tropomyosin expression can be disrupted in normal hearts with a lack of organized myofi-brils. In a broader approach, these procedures for whole hearts are important for studying myofibril formation in normal hearts at the DNA, RNA, and/or protein levels and can complement the studies of the cardiac mutant phenotype. All of these tools taken together present a powerful approach to the elucidation of myofibrillogenesis and show that embryonic heart cells can incorporate a wide variety of molecules with cationic liposomes.
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Papers by G. Isitmangil