Translation and validation of the Depression Anxiety Stress Scales for menopausal women in Indonesia.

OBJECTIVE: This study evaluated the construct validity of the Depression Anxiety Stress Scales-21 (DASS-21) for menopausal women in Indonesia. METHODS: This cross-sectional study included 236 women aged 45-60 years and assessed internal consistency using Cronbach's α. The study used convenience sampling. Test-retest reliability was measured twice on an extra 30 women at 1-week and 2-week intervals. Confirmatory factor analysis (CFA) was employed to investigate its structural model fit. RESULTS: The intraclass correlation coefficient for the test-retest reliability ranged between 0.95 and 0.96. The overall Cronbach's α coefficient of the DASS-21 was 0.95. The CFA results indicated that the goodness-of-fit index was 0.85, comparative fit index was 0.95, root-mean-square error of approximation was 0.07, related fit index was 0.91 and normed fit index was 0.92. CONCLUSIONS: This study's results indicated that the DASS-21 has satisfactory validity and reliability for detecting depression, anxiety and stress in menopausal women in Indonesia.

Construct validity of the Menopause Rating Scale in Indonesia.

Objective: This study assessed the construct validity of the Menopause Rating Scale (MRS) in Indonesia. Methods: The study included 240 women aged over 45 years in Indonesia. The MRS measures psychological, somatic-vegetative, and urogenital symptoms using 11 items obtained from participants' daily symptom records. The intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were measured to examine the test-retest reliability and internal consistency reliability. The test-retest reliability was evaluated by an extra 30 participants twice at 2-week intervals. For construct validity, exploratory factor analysis (EFA) was employed to assess factor structure and confirmatory factor analysis (CFA) was used to evaluate the structural model fit of the MRS. Results: The ICC for the test-retest reliability ranged between 0.90 and 0.95. The Cronbach alpha coefficients in the somatic-vegetative, psychological, and urogenital dimensions were 0.92, 0.93, and 0.95, respectively. The Kaiser-Meyer-Olkin value was 0.96, and the Bartlett's test of sphericity was statistically significant and adequate for EFA. CFA was tested using the second-order model with three first-order factors and yielded an excellent model fit. Conclusion: Results indicated that the brief questionnaire of the MRS possesses acceptable construct validity for evaluating menopause symptoms in Indonesian women.

Maternal plasma and breastmilk viral loads are associated with HIV-1-specific cellular immune responses among HIV-1-exposed, uninfected infants in Kenya.

Infants exposed to maternal HIV-1 provide an opportunity to assess correlates of HIV-1-specific interferon (IFN)-γ responses and may be informative in the development of HIV-1 vaccines. HIV-1-infected women with CD4 counts 200-500 cells/mm(3) were randomized to short-course zidovudine/nevirapine (ZDV/NVP) or highly active anti-retroviral therapy (HAART) between 2003 and 2005. Maternal plasma and breastmilk HIV-1 RNA and DNA were quantified during the first 6-12 months postpartum. HIV-1 gag peptide-stimulated enzyme-linked immunospot (ELISPOT) assays were conducted in HIV-1-exposed, uninfected infants (EU), and correlates were determined using regression and generalized estimating equations. Among 47 EU infants, 21 (45%) had ≥1 positive ELISPOT result during follow-up. Infants had a median response magnitude of 177 HIV-1-specific spot-forming units (SFU)/106 peripheral blood mononuclear cells (PBMC) [interquartile range (IQR)=117-287] directed against 2 (IQR = 1-3) gag peptide pools. The prevalence and magnitude of responses did not differ by maternal anti-retroviral (ARV) randomization arm. Maternal plasma HIV-1 RNA levels during pregnancy (P=0.009) and breastmilk HIV-1 DNA levels at 1 month (P=0.02) were associated with a higher magnitude of infant HIV-1-specific ELISPOT responses at 1 month postpartum. During follow-up, concurrent breastmilk HIV-1 RNA and DNA (cell-free virus and cell-associated virus, respectively) each were associated positively with magnitude of infant HIV-1-specific responses (P=0.01). Our data demonstrate the importance of antigenic exposure on the induction of infant HIV-1-specific cellular immune responses in the absence of infection.

Clinical characteristics of community-acquired acute pyelonephritis caused by ESBL-producing pathogens in South Korea.

OBJECTIVES: The aim of this study was to determine the risk factors and clinical characteristics of community-acquired acute pyelonephritis (CA-APN) caused by extended-spectrum ß-lactamase (ESBL)-producing organisms. METHODS: From March 2010 to February 2011, patients with CA-APN were recruited in 11 hospitals in South Korea. Clinical and microbiological data were collected prospectively, and the ESBLs and multilocus sequence types of the ESBL-producing Escherichia coli were characterized. Comparison between CA-APN caused by ESBL-producing Enterobacteriaceae and those by non-ESBL-producing organisms was performed. RESULTS: A total of 566 patients were recruited. Enterobacteriaceae were detected in 526 patients. Forty-six isolates (46/526, 8.7 %) were positive for ESBLs. Clinical and microbiological failure did not differ between the two groups, despite there being fewer patients with ESBL-positive isolates provided with appropriate antibiotics initially (19.6 vs. 93.8 %, p < 0.001). However, the duration of hospitalization was longer in the ESBL group (10.5 vs. 7.0 days, p = 0.012). In a logistic regression model, Charlson score ≥1 point [odds ratio (OR) 3.4, 95 % confidence interval (CI) 1.6-7.0, p = 0.001], antibiotics usage during the previous year (OR 3.1, 95 % CI 1.4-7.2, p = 0.008), and urinary catheterization during the previous month (OR 4.4, 95 % CI 1.1-17.6, p = 0.035) were associated with the risks of CA-APN by ESBL producers. CTX-M-15 (48 %) and CTX-M-14 (38 %) were the most common ESBLs. ST131 was the most common clone (7/24, 29.1 %), which was more frequently resistant to cefepime, fosfomycin, and temocillin. CONCLUSIONS: The risk factors for CA-APN by ESBL producers were Charlson score ≥1 point, antibiotics usage during the previous year, and urinary catheterization during the previous month.

Prevalence and determinants of human papillomavirus infection and cervical lesions in HIV-positive women in Kenya.

BACKGROUND: We assessed the association of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) with various characteristics, CD4 count and use of combination antiretroviral therapy (cART) among HIV-positive women. METHODS: Cross-sectional study of 498 HIV-positive women who underwent HPV PCR-based testing, cytology, and systematic cervical biopsy. RESULTS: In all, 68.7% of women were HPV-positive, 52.6% had high-risk (hr) HPV, and 40.2% multiple type infections. High-risk human papillomavirus-positivity did not vary significantly by age but it was negatively associated with education level. The most frequent types in 113 CIN2/3 were HPV16 (26.5%), HPV35 (19.5%), and HPV58 (12.4%). CD4 count was negatively associated with prevalence of hrHPV (P<0.001) and CIN2/3 among non-users of cART (P=0.013). Combination antiretroviral therapies users (≥2 year) had lower hrHPV prevalence (prevalence ratio (PR) vs non-users=0.77, 95% confidence interval (CI): 0.61-0.96) and multiple infections (PR=0.68, 95% CI: 0.53-0.88), but not fewer CIN2/3. The positive predictive value of hrHPV-positivity for CIN2/3 increased from 28.9% at age <35 years to 53.3% in ≥45 years. CONCLUSION: The burden of hrHPV and CIN2/3 was high and it was related to immunosuppression level. Combination antiretroviral therapies ( ≥2 year) use had a favourable effect on hrHPV prevalence but cART in our population may have been started too late to prevent CIN2/3.

HBV lamivudine resistance among hepatitis B and HIV coinfected patients starting lamivudine, stavudine and nevirapine in Kenya.

Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg positive and anti-HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤ 10,000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV coinfected patients with low baseline HBV DNA levels.

Seroprevalence of Toxocara canis infection among children in Swaziland, southern Africa.

As there appeared to be no data available on Toxocara canis infection in the children of Swaziland, a serological survey of T. canis infection was recently conducted among 92 children aged 3-12 years from rural slums in the low- and middle-veld. A child was considered seropositive if, in western blots based on the excretory-secretory antigens of larval T. canis, his or her serum gave a positive result when diluted 1 : 64. Forty-one (44.6%) of the children were found seropositive. There were no statistically significant differences in seroprevalence between the 49 boys and 43 girls investigated (46.9% v. 41.8%) or between the eight subjects aged 12 years and the 47 aged < or = 5 years (62.5% v. 38.3%); the corresponding odds ratios were 0.81 (95% confidence interval=0.36-1.86; P=0.62) and 2.69 (95% confidence interval=0.57-12.62; P=0.20), respectively. The 66 subjects from the middleveld were, however, significantly more likely to be seropositive than the 26 subjects from the lowveld (54.5% v. 19.2%; odds ratio=5.04, with a 95% confidence interval of 1.70-14.98; P<0.01). It seems likely that T. canis infection is common among the children who live in slums in Swaziland, particularly in the country's middleveld, probably as the result of poor hygiene and poor sanitation.

Thrombotic Ringed Polytetrafluoroethylene Graft With Infection After Living-Donor Liver Transplantation.

BACKGROUND: The safety of the living donor in living-donor liver transplantation (LDLT) is always the first priority, meanwhile, the graft-to-recipient weight ratio (GRWR) and the anatomy of the liver allograft must also not be compromised in order to warrant tranplatation success. When it comes to the allograft of the right lobe of the liver without the middle hepatic vein (R-M), the outflow and adequate drainage for the territory of middle hepatic vein (MHV) is one critical concern. Despite publications in some high-volume transplant centers on the positive results of using expanded polytetrafluoroethylene (ePTFE) grafts to substitute those of autologous veins, complications related to the ePTFE graft have not been well discussed. METHODS: From July 2012 to June 2016, 129 adult patients who underwent living donor liver transplantation in Taipei Veterans General Hospital were analyzed. There were 3 cases of adjacent organ erosion with gas bubbles in the lumen of an ePTFE graft, including gastrointestinal (GI) tract penetration in 2 out of the first 15 cases that used the venous graft of ringed expanded polytetrafluoroethylene (rPTFE). The patient survival rate during this period was compared and radiological findings of rPTFE function and clinical signs of erosion with infection were also examined to raise the concerns of safety as well as early detection of complications of rPTFE. RESULTS: The overall 1-year patient survival rate was 90%, of which the right lobe wih MHV (R+M) group was 93.5% and the R-M group was 91.9%. For the mean of GRWR, the R+M group was 1.05 ± 0.19 and R-M group was 1.19 ± 0.27, while those who needed reconstruction with vein grafts was 0.96 ± 0.11. Among the R-M group, 24 out of 88 cases (27.3%) needed reconstruction of MHV tributaries. Of the 24 cases, 15 cases were done with rPTFE and the 1-year patient survival rate of the rPTFE group was 73%, which is significantly worse (P = .008) than the non-rPTFE (89%) and non-reconstructed (97%) groups. The mean GRWR is significantly higher (P = .001) in the non-reconstructed group (1.19 ± 0.27) than in the rPTFE (0.99 ± 0.11) and non-rPTFE (0.94 ± 0.11) groups. The venous grafts patency rate between the different graft types is no different, and there is also significance in warm ischemic time (P = .009) between the non-reconstructed (49 ± 15), rPTFE (81 ± 51), and non-rPTFE (56 ± 18) groups in the mean minutes. CONCLUSION: In cases of fever of unknown cause in patients receiving LDLT with rPTFE graft, a regular computed tomography (CT) scan with contrast and gas bubbles within the graft lumen is the best way for early detection of graft related infection and suspicious GI tract penetration. To decrease the risks of tissue reaction induced by ePTFE graft in LDLT, omentum patches or other inert agents can be introduced as a buffer between the graft and adjacent organs, especially the GI tracts. However, research in material science shall be explored to solve the problem in the future.

Comparison of rocuronium-induced neuromuscular blockade in second trimester pregnant women and non-pregnant women.

BACKGROUND: This study set out to compare the onset and duration of rocuronium-induced neuromuscular blockade in second trimester pregnant women and non-pregnant women receiving general anesthesia. METHODS: Forty-seven pregnant (Group P) and forty-seven non-pregnant (Group C) women were enrolled. Anesthesia was induced with propofol 2.0 mg/kg and rocuronium 0.6 mg/kg, and neuromuscular blockade was assessed with an accelerometric sensor using train-of-four stimulation (TOF-Watch® SX). Tracheal intubation was performed at maximum depression of the first twitch (T1) and anesthesia was maintained with sevoflurane 1.5-2.5% and 50% oxygen in air. We recorded the times to maximum T1 depression and 5% and 25% T1 recovery, as well as the mean arterial pressure and heart rate at baseline, injection of rocuronium, intubation, and 5% and 25% T1 recovery. RESULTS: The onset of rocuronium-induced neuromuscular blockade (time to maximum T1 depression) did not differ significantly between the groups. The duration (time to 25% T1 recovery) was significantly longer in Group P than in Group C (45.7 ±â€¯12.9 min vs 40.6 ±â€¯10.4 min, P <0.037). During the recovery period from the blockade, the mean arterial pressure was significantly lower in Group P than in Group C. CONCLUSION: Our data showed that the rocuronium-induced neuromuscular blockade did not significantly differ in onset but lasted significantly longer in second trimester pregnant women compared with non-pregnant women.

Proximal esophageal adenocarcinoma presenting as a thyroid mass: case report and review of the literature.

Metastatic disease to the thyroid is not an unusual finding at autopsies, but it is rare to be found in clinical situations. We present the first case of adenocarcinoma of the proximal esophagus presenting as a thyroid mass in a young healthy patient without any previous history of malignancy. This case highlights the importance of thorough work-up when addressing a thyroid mass. A high index of suspicion should be maintained in order to be able to detect unusual etiologies of thyroid conditions, especially when histopathology is not characteristic for primary thyroidal malignancies.

The learning curve for hand-assisted laparoscopic colectomy: a single surgeon's experience.

BACKGROUND: Surgical experience and outcomes for hand-assisted laparoscopic colectomy were evaluated to define a learning curve. METHODS: This study included 60 patients who underwent hand-assisted laparoscopic colectomies performed by a single surgeon. They were analyzed as three consecutive equal groups: A, B, and C. Pearson's chi-square test and one-way analysis of variance (ANOVA) were used to compare differences in demographics and perioperative parameters. Operative times were analyzed to document the learning curve for the procedure. RESULTS: There were no significant differences between the three groups in terms of age, sex, operative procedure, or comorbidity. Groups B and C showed significantly shorter operative times, significantly earlier recoveries of gastrointestinal function, less blood loss, and shorter hospital stays than group A. The incidence of operative complications was not significantly different among the three groups (35% vs 5% vs 15%; p = 0.07). CONCLUSIONS: Approximately 21 to 25 cases were needed to achieve proficiency in this series.

Increased oxidative DNA damage in Helicobacter pylori-infected human gastric mucosa.

Helicobacter pylori causes type B gastritis. It shows strong association with the development of gastric carcinoma. A plausible hypothesis for the missing link between H. pylori infection and gastric carcinogenesis involves oxygen free radical-induced DNA damage. To test this hypothesis, we compared the amount of 9-hydroxydeoxyguanosine, a marker for oxygen free radical-induced DNA damage, in the DNA of human gastric mucosa with and without H. pylori infection. Gastric antral biopsies were taken from pediatric patients and volunteers to select H. pylori-positive and H. pylori-negative specimens. The 8-hydroxydeoxyguanosine content of the gastric mucosal DNA was measured after H. pylori-positive and H. pylori-negative volunteers were identified. The increased level of oxidative DNA damage suggests the mechanistic link between H. pylori infection and gastric carcinoma.

Leukemic cell line, KG-1 has a functional loss of hOGG1 enzyme due to a point mutation and 8-hydroxydeoxyguanosine can kill KG-1.

We tested the cytotoxic action of 8-hydroxyguanine (8ohG) by observing the viability of several leukemic cell lines (KG-1, U937, Jurkat and K 562) in the presence of 8-hydroxydeoxyguanosine (8ohdG), a nucleoside of 8ohG. It was found that 8ohdG showed cytotoxic action only to KG-1 and that only KG-1 showed a homozygous arginine 209 to glutamine mutation in the hOGG1 gene with an almost negligible hOGG1 enzyme activity. Possibly, the selective cytotoxicity in 8ohdG to KG-1 may be due to its low capacity to cope with an increase in the 8ohG level in DNA resulting from the incorporation of 8ohdG present in the culture media. The mutational impairment of hOGG1 in KG-1 is the first report in leukemic cell lines. Using KG-1 with impaired hOGG1, we demonstrated cytotoxicity of 8ohdG probably due to its incorporation into cellular DNA. This new property of KG-1 may allow it to serve as an useful tool for studies of OGG1, oxidative DNA damage and the cytotoxic action of 8ohG. Oncogene (2000) 19, 4476 - 4479.

Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats.

Cumulating evidence suggests that enhanced oxidative stress may contribute to diabetic angiopathy. The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-hydroxyguanine (8-OHG), indicators of oxidative DNA damage, in tissue or body fluid are increased in diabetic patients. However, it is unclear whether plasma 8-OHG correlates with tissue 8-OHdG and whether insulin or antioxidant treatment reduces plasma 8-OHG in diabetic state. In this study, we measured the 8-OHG levels in plasma as well as the 8-OHdG levels in liver and kidney in streptozotocin-induced diabetic rats (DR) treated with insulin (DR+I), insulin and probucol (DR+I/P), or insulin and vitamin E (DR+I/E). There was a correlation between plasma 8-OHG levels and tissue 8-OHdG levels (plasma 8-OHG vs. liver 8-OHdG: r = 0.64, P < 0.001; plasma 8-OHG vs. kidney 8-OHdG: r = 0.38, P = 0.06). DR had levels of plasma 8-OHG that were three times higher than control rats (CR), whereas they had levels of tissue 8-OHdG that were approximately 1.5-2 times higher. Plasma 8-OHG levels in DR were almost normalized by insulin treatment, although insulin partially corrected hyperglycemia (plasma 8-OHG: CR 3.3 +/- 2.7 pmol/ml; DR 10.4 +/- 2.3 pmol/ml, P < 0.05 vs. CR; DR with insulin 3.6 +/- 1.0 pmol/ml, P < 0.05 vs. DR). However, tissue 8-OHdG levels in DR were significantly decreased by combined treatment with insulin and antioxidant (probucol or vitamin E), but not by insulin treatment alone. This data suggests that plasma 8-OHG could be a useful biomarker of oxidative DNA damage in diabetic subjects. The mechanism of differential response of plasma 8-OHG and tissue 8-OHdG to insulin and antioxidant treatment remains to be elucidated.

Serum 8-hydroxy-guanine levels are increased in diabetic patients.

OBJECTIVE: The production of reactive oxygen species is increased in diabetic patients, especially in those will poor glycemic control. We have investigated oxidative damage in type 2 diabetic patients using serum 8-hydroxyguanine (8-OHG) as a biomarker. RESEARCH DESIGN AND METHODS: We studied 41 type 2 diabetic patients and compared them with 3 nondiabetic control subjects. Serum 8-OHG concentration was assayed using high-pressure liquid chromatography. RESULTS: The type 2 diabetic patients had significantly higher concentrations of 8-OHG in their serum than the control subjects (5.03 +/- 0.69 vs. 0.96 +/- 0.15 pmol/ml P < 0.01). There was no association between the levels of 8-OHG and HbA1c. We also could not and any correlation between serum 8-OHG levels and age, duration of diabetes, serum lipids, or creatinine or albumin exeretion rate. Creatinine clearance showed marginal correlation with serum 8-OHG levels (P = 0.06). Among the diabetic patients, those with proliferative retinopathy had significantly higher 8-OHG levels than those with nonproliferative retinopathy or without retinopathy. Likewise, the serum 8-OHG levels in patients who had advanced nephropathy (azotemia) were higher than in patients with normoalbuminuria, microalbuminuria, or overt proteinuria. CONCLUSIONS: Our findings show that measuring serum 8-OHG is a novel convenient method for evaluating oxidative DNA damage. Diabetic patients, especially those with advanced microvascular complications, had significantly higher serum 8-OHG levels; this suggests that such changes may contribute to the development of microvascular complications of diabetes.

Corpora amylacea: a marker for mesial temporal sclerosis.

Mesial temporal sclerosis (MTS) is the most frequently encountered abnormality in temporal lobectomies performed for medically intractable seizure disorders. The pathologic diagnosis of MTS relies on the identification of neuronal loss affecting various regions of the hippocampus. However, neuronal loss is often difficult to assess, particularly in lobectomies that are not performed en bloc. Because of this difficulty the presence of hippocampal pathology is often indeterminate. In this report we describe our experience with 73 temporal lobectomies performed for seizure disorders. In 58%, increased numbers of corpora amylacea (CoA) were found in association with MTS. The relationship between CoA and the pathogenetic mechanisms underlying MTS remains speculative. However, the association between MTS and corpora amylacea is important to recognize since the identification of abundant numbers of CoA provides a marker for MTS that can be useful in cases in which neuronal loss and gliosis are difficult to assess. For this purpose, it is strongly recommended that tissues resected from the hippocampus and amygdala for temporal lobe epilepsy be stained with LFB-PAS to highlight CoA.

Protection of DNA damage by dietary restriction.

Dietary restriction is known to retard the aging processes and delay the onset of age-related neoplastic diseases. The mechanisms underlying these remarkable actions of nutritional intervention are not known in spite of recently intensified research efforts. However, the last couple of years' research on dietary restriction produced strong evidence indicating that its effective antiaging actions might be related to its ability to modulate free radical damage. In the present study, DNA damage and attenuation of the damage by dietary restriction were assessed by measuring 8-hydroxydeoxyguanosine 8-OH dG) in both nuclear DNA (nuDNA) and mitochondrial DNA (mitDNA) fractions. The data show that substantially more damage (approximately 15 times) occurred in mitDNA compared to nuDNA. More interestingly, the DNA damage was significantly attenuated in dietarily restricted rats.

DNA damage in the kidneys of diabetic rats exhibiting microalbuminuria.

8-Hydroxydeoxyguanosine (8-OHdG), an oxygen radical induced modification of purine residue in DNA, was measured in the liver, pancreas, and kidney of streptozotocin-induced diabetic rats (STZR) exhibiting microalbuminuria. At 4 weeks after the injection of streptozotocin (50 mg/kg, i.v.), the rate of urinary albumin excretion was 0.5 +/- 0.1 and 2.0 +/- 0.2 mg/24 h in age-matched control rats (CR) and STZR, respectively. Compared to CR, STZR also showed a significantly increased level of 8-OHdG in the kidney but not the liver and pancreas. Amounts of 8-OHdG/10(5) dG for CR and STZR were 3.4 +/- 0.3 and 5.1 +/- 0.2 for renal cortices, and 4.1 +/- 0.2 and 20.0 +/- 3.7 for renal papillae. Daily injection of insulin (2 U, SC) starting on the third day after streptozotocin treatment significantly reduced both urinary albumin excretion and papillary 8-OHdG formation, which suggests that these are associated with the diabetic state induced by streptozotocin rather than a direct nephrotoxic effect of the drug. This study suggests that formation of 8-OHdG and, therefore, oxidative damage are closely related in the process of diabetic nephropathy.

Thermolabile 8-hydroxyguanine DNA glycosylase with low activity in senescence-accelerated mice due to a single-base mutation.

8-hydroxyguanine (8-oxoguanine; oh8Gua) DNA glycosylase (OGG1) repairs oh8Gua, a highly mutagenic oxidative DNA damage. In the present study, we compared two strains of senescence-accelerated mouse (SAM) expressing senescence-prone phenotypes, SAMP1 and SAMP8, with one strain of SAM expressing senescence-resistant phenotype, SAMR1. We found three distinct characteristics of OGG1 in SAMPs: (i) low activity (10-40% of the SAMRI enzyme in all organs and ages observed), (ii) thermolability, and (iii) mutation from Arg (CGG) in SAMR1 to Trp (TGG) at codon 304. There was no difference in the levels of mRNA and protein. As expected, oh8Gua level in tissues was higher in the SAMPs. In contrast, O6-methylguanine-DNA methyltransferase, which repairs alkylated DNA, showed no difference in its activity. The impairment of oh8Gua repair activity caused by the 304 mutation in OGG1 may be one of the factors contributing to the high somatic mutation rate and the accelerated senescence observed in these strains.

Mechanism of regulation of 8-hydroxyguanine endonuclease by oxidative stress: roles of FNR, ArcA, and Fur.

We found previously that 8-hydroxyguanine (oh8Gua) endonuclease in E. coli is induced in response to oxidative stress in a fashion similar to the oxidative response of the Mn-superoxide dismutase (MnSOD). In this study, attempts were made to identify the genes involved in the co-regulation of E. coli endonuclease and MnSOD (sodA). oh8Gua nuclease is induced by molecular oxygen and a superoxide radical generator (paraquat) but not by H2O2, suggesting that the regulation of this endonuclease is dependent on SoxRS but independent of OxyR. This enzyme was induced by paraquat in all of the soxRS mutant strains used (soxR-, soxS- and soxRc), whereas glucose-6-phosphate dehydrogenase (a member of the soxRS regulon) showed the expected responses; therefore, this possibility was excluded. The presence of metal chelators in the growth medium caused the induction of this enzyme, and this induction was suppressed by the addition of Fe++. Consistent with this finding, this enzyme was expressed under anaerobiosis in all of the mutant strains of fnr in particular, as well as fur, arcA, and combinations thereof. These findings suggest that the oxidative regulation of oh8Gua endonuclease is under control of fnr, fur, and arcA, where fnr plays a predominant role. The multiple involvement of regulatory genes as well as co-regulation with antioxidant enzyme will enhance the efficiency of cellular growth and survival in the aerobic environment.