Biomedical subjects

T Toyota

Publications and source records attributed to T Toyota.

At least 55 records · Page 3Linked to original sources

PubMed2000

Activation of adenosine A1-receptor pathway induces edema formation in the pancreas of rats.

BACKGROUND & AIMS: Adenosine has been shown to modulate various pathophysiologic conditions through receptor-mediated mechanisms. However, the role of adenosine in the pathogenesis of acute pancreatitis has not been described. We examined the effect of adenosine-receptor stimulation or inhibition on the pathologic changes of the pancreas. METHODS: Rats received intraperitoneal injections of selective agonists of A1, A2a, and A3 adenosine receptors: 2-chloro-N(6)-cyclopentyladenosine (CCPA), CGS-21680 (CGS), or 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-be ta-D-ribofuranuronamide (IB-MECA), respectively. Serum amylase activity and pathologic changes of the pancreas were evaluated. The effects of a specific A1-receptor antagonist (FK-838) on the pathologic findings of cerulein- and taurocholate-induced pancreatitis were also examined. RESULTS: Administration of a selective A1 agonist induced hyperamylasemia and morphologic changes in the pancreas characterized by interstitial edema and leukocyte infiltration; neither A2a nor A3 agonist produced such changes. Treatment with an A1-receptor antagonist significantly attenuated the outcome induced by A1 agonist stimulation. In addition, the A1-receptor antagonist significantly ameliorated pancreatic edema in both pancreatitis models, although it did not improve the acinar cell damage of the pancreas or the increase of serum amylase. CONCLUSIONS: Activation of the adenosine A1-receptor pathway may have an important role in the pathogenesis of acute pancreatitis.

Acute Disease↗

PubMed2000

Fas-mediated cholangiopathy in the murine model of graft versus host disease.

Bile-duct injury observed in hepatic graft versus host disease (GVHD) is regarded as an immune-mediated injury, although its precise mechanism is unclear. However, recent studies have suggested the involvement of Fas-mediated cell death in this immune-mediated cholangiopathy. In this study, we first showed the constitutive expression of Fas receptor by cholangiocytes in situ from normal BALB/c mice, which was upregulated in GVHD mice. Also, we confirmed the Fas protein expression in the isolated cholangiocytes from normal BALB/c mice by immunocytochemistry and immunoblotting. Furthermore, the addition of agonistic Fas antibody-(Jo2)-induced cholangiocyte apoptosis confirmed by DNA-ladder formation and annexin V staining. Cholangiocytes from Fas-deficient mice (MRL lpr/lpr) did not show Jo2-induced apoptosis. Interferon-gamma augmented Fas expression and Fas-mediated cell death, respectively. Following these observations, experimental GVHD was induced by transfer of splenocytes from B10.D2 mice to irradiated (800 rad) BALB/c mice. Liver-infiltrating lymphocytes from the recipient showed dose-dependent cytotoxicity against (51)Cr-labeled cholangiocytes isolated from BALB/c mice. Moreover, the addition of blocking Fas-Fc fusion protein reduced this cytotoxicity to 44.7%. Finally, administration of this Fas-Fc protein to the BALB/c mice, which had been adoptively transferred with splenocytes of B10.D2 mice, prevented the development of hepatic GVHD in vivo. These results showed the involvement of Fas-mediated cell death in cholangiopathy observed in GVHD, and a soluble Fas-Fc protein may have a therapeutic potential for hepatic GVHD.

Animals↗

PubMed2000

Tyrosine hydroxylase gene microsatellite polymorphism associated with insulin resistance in depressive disorder.

A high association between type 2 diabetes mellitus and depressive illness has been reported. Insulin resistance during depressive illness might contribute to the linkage between depression and type 2 diabetes. To determine whether the genetic polymorphisms of the tyrosine hydroxylase ([TH] HUMTH01) and insulin (INS-VNTR) genes contribute to insulin resistance in depressive illness, we analyzed the association between the polymorphisms and insulin resistance in 41 Japanese patients with depressive disorder, 204 normal control subjects, 161 cohort subjects with normal glucose tolerance (NGT) and without depressive symptomatology, and 59 NGT subjects with depressive symptomatology. The depressive patients had a significantly lower insulin sensitivity index (SI) than the control subjects (P= .016). Depressive NGT subjects had a significantly higher homeostasis model assessment (HOMA) insulin resistance index [HOMA(R)] than the nondepressive NGT subjects (P < .0001). The depressive patients and NGT subjects had more HUMTH01 allele 7 (TH7) than the controls and nondepressive NGT subjects. SI was significantly lower in patients with the TH7/7 homozygote versus patients with the other genotypes and the controls. TH7 was associated with higher HOMA(R) as compared with the other alleles in the NGT subjects. Insulin resistance was associated with depressive disorders. The HUMTH01 and INS-VNTR were associated with insulin resistance and depressive symptoms.

Adult↗

PubMed2000

Nitric oxide decreases endothelial activation by rat experimental severe pancreatitis-associated ascitic fluids.

To clarify the roles of nitric oxide (NO) in acute pancreatitis (AP), we examined the effects of NO on the endothelial activation induced by ascitic fluids from rats with experimental severe AP. Necrotizing hemorrhagic pancreatitis was induced in male Wistar rats with sodium taurocholate. Six hours later, peritoneal exudates were collected, centrifuged, and human umbilical vein endothelial cells were treated with the supernatants. Then (a) the mRNA level of endothelial-type NO synthase (ecNOS) was examined by reverse transcription-polymerase chain reaction; (b) effects of an NO donor, sodium nitroprusside (SNP) and an inhibitor of NOS, N(omega)-nitro-L-arginine (L-NNA) on the ascitic fluids-induced expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-8 were assessed by enzyme-linked immunoassay; (c) nuclear translocation of nuclear factor-kappa B (NF-kappaB) was examined by electrophoretic mobility shift assay; and (d) effects of SNP and L-NNA on the adhesion of U937 cells to endothelial monolayer were assessed. The ecNOS mRNA level was decreased by the ascitic fluids; ascitic fluids-induced expression of adhesion molecules and interleukin-8 as well as the nuclear translocation of NF-kappaB were attenuated by SNP, whereas L-NNA augmented them; and the effects on the endothelial activation were paralleled by the altered adhesion of U937 cells to endothelium. The ability of NO to limit endothelial activation and inhibit leukocyte adhesion might contribute to its antiinflammatory properties in AP.

Acute Disease↗

PubMed2000

The pattern of CPP32/caspase-3 expression reflects the biological behavior of the human pancreatic duct cell tumors.

Caspase-3/CPP32, a member of the Ced-3-family of cysteine proteases, is an important mediator of programmed cell death (apoptosis). Intraductal papillary-mucinous tumor of the pancreas (IPMT) is a unique tumor that grows intraductally with rare stromal invasion. However, it is not possible to distinguish noninvasive from invasive IPMT preoperatively. To examine whether caspase-3 expression reflects the biological behavior of pancreatic tumors, we investigated this enzyme expression by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in 22 pancreatic duct cell carcinomas (PDC) and 13 IPMT cases. Caspase-3 mRNA was overexpressed in PDC and IPMT with carcinoma when compared with normal pancreatic tissue or IPMT with adenoma. The immunoreactivity of this enzyme was predominantly found in the cytoplasm of invasive tumors (PDC and invasive IPMT). There was a significant correlation between the cytoplasmic staining and malignant grade of the tumors. In contrast, the nuclear expression of this enzyme was significantly higher in noninvasive than in invasive tumors (p = 0.0015). Cytoplasmic expression of caspase-3 may be related to the invasiveness of pancreatic tumors. In contrast, nuclear expression of this enzyme may reflect the benign biological behavior of IPMT.

Apoptosis↗

PubMed2000

Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. South Tohoku District Study Group.

OBJECTIVE: We evaluated the measurements of serum alpha-fetoprotein (AFP) and the protein induced by vitamin K absence (PIVKA-II) in 734 patients with chronic hepatitis (CH) and liver cirrhosis (LC) who had been followed-up for the development of hepatocellular carcinoma (HCC). METHODS: Serum AFP and PIVKA-II were measured every month and abdominal ultrasonography was performed every 3 months. Youden's index (sensitivity + specificity -1) was calculated. RESULTS: On an average follow-up period of 374.5 days, HCC was detected in three HBsAg-positive LC patients (10.0%/yr), four anti-HCV-positive CH patients (1.35%/yr), 21 anti-HCV-positive LC patients (7.8%/yr), and one patient with both HBsAg- and anti-HCV-positive LC (22.7%/yr). At the time of HCC detection, the size of HCC was 4.7+/-0.6 (mean +/- SD) cm in HBsAg-positive patients and 2.4+/-1.3 cm in anti-HCV-positive patents. Cut-off values of 20 ng/ml for AFP (Youden's index = 0.422) and 60 mAU/ml for PIVKA-II (Youden's index = 0.316) gave the highest index for each marker. When these two markers were combined, cut-off values of 40 ng/ml for AFP and 80 mAU/ml for PIVKA-II gave the highest index (Youden's index = 0.500, sensitivity = 65.5%, specificity = 85.5%, positive predictable value = 14.8%, negative predictable value = 98.3%). The levels of AFP or PIVKA-II increased within three months before the detection of HCC. CONCLUSIONS: Simultaneous measurements of serum AFP and PIVKA-II levels that are performed every 3 months are useful for detecting a developing HCC. The optimal cut-off values for AFP and PIVKA-II may be 40 ng/ml and 80 mAU/ml, respectively.

Adult↗

PubMed2000

Successful treatment of cap polyposis by avoidance of intraluminal trauma: clues to pathogenesis.

"Cap polyposis" is a rarely-encountered condition in which distinctive inflammatory polyps are located from the rectum to the distal descending colon. Microscopically, the polyps consist of elongated, tortuous, and distended crypts covered by a "cap" of inflammatory granulation tissue. Although the pathogenesis is unknown, mucosal prolapse has been postulated to be an important etiological factor, given certain clinical and histological similarities. We describe two cases of cap polyposis with protein-losing enteropathy. One was treated successfully by avoidance of straining at defecation. Another resolved after double-barreled transverse colostomy. Both successful treatments support a causal link of polyposis to prolapse.

Adult↗

PubMed2000

Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication.

BACKGROUND: It remains controversial whether or not Helicobacter pylori infection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed. AIM: To investigate by EGT the effects of H pylori eradication on the state of gastric acid secretion in patients with peptic ulcer. METHODS: Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whom H pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication. RESULTS: In patients with duodenal ulcer, the mean EGT value before H pylori eradication was higher than that in H pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer before H pylori eradication was lower than that in H pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value. CONCLUSIONS: The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.

Adult↗

PubMed2000

11Beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human placenta.

In mineralocorticoid target organs, 11beta-hydroxysteroid dehydrogenase type II (11beta-HSD2) confers specificity on the mineralocorticoid receptor (MR) by converting biologically active glucocorticoids to inactive metabolites. Placental 11beta-HSD2 is also thought to protect the fetus from high levels of circulating maternal glucocorticoid. In this study, we examined the immunoreactivity of 11beta-HSD2 and MR in human placenta from 5 weeks gestation to full term using immunohistochemistry, 11beta-HSD2 messenger RNA (mRNA) expression using Northern blot analysis, and MR mRNA expression using RT-PCR analysis. Marked 11beta-HSD2 immunoreactivity was detected in placental syncytiotrophoblasts at all gestational stages. MR immunoreactivity was moderately detected in syncytiotrophoblasts, some cytotrophoblasts, and interstitial cells of the villous core. Marked mRNA expression of 11beta-HSD2 was detected in placenta by Northern analysis. RT-PCR analysis of MR in placental tissues showed an amplified product consistent in length with the primers selected. These results suggest that placental 11beta-HSD2 is involved in not only regulating the passage of maternal active glucocorticoids into the fetal circulation but also in regulation of maternal-fetal electrolyte and water transport in the placenta, as in other mineralocorticoid target organs.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2000

Variations in vitamin D-binding protein (group-specific component protein) are associated with fasting plasma insulin levels in Japanese with normal glucose tolerance.

The locus of the vitamin D-binding protein (DBP; also known as group-specific component protein or Gc) gene, chromosome 4q12, has been reported to be associated with glucose metabolism in several ethnic groups, including Pima Indians. We have recently reported the association of the DBP genotype with type 2 diabetes mellitus in Japan. The aim of this study was to investigate whether genetic variations of DBP have any influence on glucose metabolism without secondary effects of hyperglycemia or diabetes mellitus using 82 Japanese with normal glucose tolerance. The variations of the DBP gene (Gc 1F, 1S, and 2) were determined by PCR-restriction fragment length polymorphism. Fasting plasma insulin concentration and homeostasis model assessment, an index of insulin resistance, were significantly different based on the DBP genotype (P < 0.01 and P < 0.05, respectively). The people with Gc 1S-2 (5.73 +/- 2.57 microU/mL) and 1S-1S (5.30 +/- 3.46 microU/mL) had significantly higher fasting plasma concentrations than those with 1F-1F (2.84 +/- 1.67 microU/mL) (P < 0.01 and P < 0.03, respectively). There was no significant difference in plasma glucose concentration, body mass index, total cholesterol, triglyceride, and blood pressure. In conclusion, genetic variations of DBP are associated with insulin resistance in Japanese with normal glucose tolerance, which might contribute to the development of type 2 diabetes.

Asian People↗

PubMed2000

Paradoxical progression of biliary strictures against recovery of biochemical parameters under ursodeoxycholic acid treatment in a case of primary sclerosing cholangitis with ulcerative colitis.

Ursodeoxycholic acid (UDCA) treatment for primary sclerosing cholangitis (PSC) has been considered a rational therapy, though its effectiveness in the clinical course is still open to discussion. In this report, we describe a 22-year-old man with PSC at an early stage, which was associated with ulcerative colitis (UC). He showed progressive strictures of bile ducts over a 1.5-year period in spite of an improvement in the biochemical parameters by UDCA treatment. Therefore, care should be taken in interpreting the effectiveness of UDCA, because the biochemical parameters may not change in parallel with the clinical course of PSC.

Adult↗

PubMed2000

[Clinical effect and side effect of troglitazone].

Troglitazone, a PPAR-gamma agonist, is a new drug for type 2 diabetes. The drug decreases blood glucose via enhancing insulin action. Recently Sankyo pharmaceutical company is warning severe hepatotoxicity by troglitazone. It recommends to examine liver function every month in diabetic patients treated with the drug in order early to find drug-induced hepatitis. In Japan 153 diabetic patients treated with the drug developed severe hepatitis and 8 of them died of drug-side effects. Quinone metabolite of troglitazone predominantly in the liver to a sulfate conjugate and activation of PPAR gamma and PXR(pregnane X receptor) by troglitazone are supposed to be factors of hepatotoxic mechanism.

Chemical and Drug Induced Liver Injury↗

PubMed2000

Age-related increases in plasma phosphatidylcholine hydroperoxide concentrations in control subjects and patients with hyperlipidemia.

BACKGROUND: The basal lipid peroxide concentration in the plasma of patients with hyperlipidemia may be related to atherosclerosis. Quantitative determination of lipid peroxides in the plasma is an important step in the overall evaluation of the biochemical processes leading to oxidative injury. Unfortunately, the currently available methods for lipid peroxidation lack specificity and sensitivity. METHODS: Hyperlipidemic patients (44 males and 50 females), ages 12-82 years (mean +/- SE, 53 +/- 2.3 years for males, 58 +/- 2.0 years for females, and 56 +/- 14 years for total cases), and normolipidemic volunteers (controls, 32 males and 15 females), ages 13-90 years (49 +/- 4 years for males, 65 +/- 4 years for females, and 55 +/- 24 years for total cases), were recruited in the present study. Plasma phosphatidylcholine hydroperoxide (PCOOH) was determined by chemiluminescence-HPLC (CL-HPLC). RESULTS: Plasma PCOOH concentrations increased with age in both controls and hyperlipidemic patients. However, the mean plasma PCOOH concentration in patients with hyperlipidemia (331 +/- 19 nmol/L; n = 94) was significantly (P <0.001) higher than in the controls (160 +/- 65 nmol/L; n = 47). Plasma PCOOH concentrations were similar in three hyperlipidemic phenotypes: hypercholesterolemia (IIa), hypertriglyceridemia (IV), and combined hyperlipidemia (IIb). The mean plasma PCOOH in patients with treatment-induced normalized plasma lipids was 202 +/- 17 nmol/L. There was no significant correlation between plasma PCOOH concentration and total cholesterol, triglycerides, or phospholipids in hyperlipidemic patients. For all subjects, there was a significantly positive correlation between plasma PCOOH and each lipid (total cholesterol, P = 0.0002; triglycerides, P = 0.0137; and phospholipids, P <0.0001). Analysis of fatty acids composition of plasma phosphatidylcholine showed significantly low concentrations of n-6 fatty acids moieties (linoleic acid and arachidonic acid) in patients compared with controls. CONCLUSIONS: Our results suggest that an increase in plasma PCOOH in patients with hyperlipidemia may be related to the development and progression of atherosclerosis, particularly in the elderly. Measurement of plasma PCOOH is useful for in vivo evaluation of oxidative stress.

Adolescent↗

PubMed2000

Association study on the DUSP6 gene, an affective disorder candidate gene on 12q23, performed by using fluorescence resonance energy transfer-based melting curve analysis on the LightCycler.

We introduced a new genotyping method, fluorescence resonance energy transfer-based melting curve analysis on the LightCycler, for the analysis of the gene, DUSP6 (dual specificity MAP kinase phosphatase 6), in affective disorder patients. The DUSP6 gene is located on chromosome 12q22-23, which overlaps one of the reported bipolar disorder susceptibility loci. Because of its role in intracellular signalling pathways, the gene may be involved in the pathogenesis of affective disorders not only on the basis of its position but also of its function. We performed association analysis using a T>G polymorphism that gives rise to a missense mutation (Leu114Val). No evidence for a significant disease-causing effect was found in Japanese unipolars (n = 132) and bipolars (n = 122), when compared with controls (n = 299). More importantly, this study demonstrates that melting curve analysis on the LightCycler is an accurate, rapid and robust method for discriminating genotypes from biallelic markers. This strategy has the potential for use in high throughput scanning for and genotyping of single nucleotide polymorphisms (SNPs).

Adult↗

PubMed2000

Can three-dimensional helical CT cholangiography before laparoscopic cholecystectomy be a substitute study for endoscopic retrograde cholangiography?

The study investigated the usefulness of three-dimensional helical computed tomography (3D-CT) before laparoscopic cholecystectomy (LSC) when compared with that of endoscopic retrograde cholangiography (ERC). Forty-five patients referred for LSC, who had undergone 3D-CT cholangiography and ERC simultaneously, participated in the study. Endoscopic retrograde cholangiography and 3D-CT cholangiography were compared in each patient with regard to opacification of the biliary tree, stones, and anatomic variations. Three-dimensional helical CT cholangiography and ERC imaging for predicting operative difficulties in LSC also were compared. The common bile duct and cystic duct were shown in the patients by the images, but the gallbladder was shown in 43 patients (96%) with use of 3D-CT cholangiography and in 36 patients (80%) with use of ERC. A third or more peripheral branches were shown completely with use of 3D-CT cholangiography in 33 patients (73%) and in 32 patients (71%) with use of ERC. Cystic duct stones were found in two of three patients with use of 3D-CT cholangiography and ERC. Common bile duct stones in five of seven patients were detected with use of 3D-CT cholangiography, but all of the common bile duct stones were detected with use of ERC. Anatomic variations of the bile duct were shown in three of four patients by 3D-CT cholangiography and in all patients with use of ERC. No significant differences in findings of the angle of bifurcation and presence of Heister valves between operative easy and complex cases were shown by 3D-CT cholangiography and ERC, despite the more accurate assessment of the cystic duct anatomy with use of 3D-CT cholangiography than with use of ERC. Three-dimensional helical CT cholangiography is useful clinically in preoperative assessment of biliary anatomy, but it is not reliable in the detection of common bile duct stones, and it is not helpful in predicting technical difficulty during LSC.

Adult↗

PubMed1999

The T3(b) gene promoter directs intestinal epithelial cell-specific expression in transgenic mice.

Although a few promoters that direct intestinal epithelial cell-specific expression in transgenic animals have been reported, they are not necessarily appropriate for transgenic studies in terms of activity and tissue specificity. Here, we examined the tissue specificity of transgene expression directed by the 2.8-kb promoter region of the T3(b) gene, which encodes one of the non-classical major histocompatibility complex class I molecules. The transgene was expressed exclusively in the epithelial cells of the small and large intestines at high levels. The results indicate that the T3(b) promoter is useful for directing transgene expression specifically in intestinal epithelial cells.

Animals↗

PubMed1999

Telomere shortening and the clinicopathologic characteristics of human colorectal carcinomas.

BACKGROUND: It has been reported that shortening of telomeres and strong activation of telomerase occur frequently in colorectal carcinomas. In the current study, the authors examined the correlations between the telomere length of colorectal carcinomas and their clinicopathologic characteristics as well as the activity of telomerase to clarify whether telomere length might represent the biologic behavior of tumors and the mode of tumor development. METHODS: Telomere length was examined by Southern blot analysis in 61 invasive colorectal carcinomas and corresponding normal mucosas. Telomerase activity was assayed by the telomeric repeat amplification protocol with minor modifications. RESULTS: Shortening of the telomere was detected in 38 (62.3%) and elongation in 3 (4. 9%) of the 61 carcinomas. The telomere shortening occurred more frequently in nonulcerating polypoid carcinomas than in ulcerating carcinomas (P = 0.0373) and also occurred more frequently in ascending colon carcinomas than in sigmoid colon or rectal carcinomas (P = 0.0259 and P = 0.0407, respectively). However, no significant correlation was found between the activity of telomerase and the length of telomere. CONCLUSIONS: The results of this study indicate that telomere length may represent the biologic behavior of individual tumors and possibly the mode of development of colorectal carcinomas.

Aged↗

PubMed1999

Oxidative DNA damage in diabetes mellitus: its association with diabetic complications.

AIMS/HYPOTHESIS: Augmented oxidative stress induced by hyperglycaemia possibly contributes to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine to 8-oxo, 2'-deoxyguanosine in DNA. To investigate the possible contribution of oxidative DNA damage to the pathogenesis of diabetic complications, we measured the content of 8-oxo, 2'-deoxyguanosine in the urine and the blood mononuclear cells of Type II (non-insulin-dependent) diabetic patients. METHODS: We studied 53 Type II diabetic patients and 39 age-matched healthy control subjects. We assayed 8-oxo, 2'-deoxyguanosine by HPLC-electrochemical detection method. RESULTS: The content of 8-oxo, 2'-deoxyguanosine in the urine and the mononuclear cells of the Type II diabetic patients was much higher than that of the control subjects. Urinary 8-oxo, 2'-deoxyguanosine excretion and the 8-oxo, 2'-deoxyguanosine content in the mononuclear cells from the diabetic patients with complications were higher than those from the diabetic patients without complications. Urinary excretion of 8-oxo, 2'-deoxyguanosine was significantly correlated with the 8-oxo, 2'-deoxyguanosine content in the mononuclear cells. The 8-oxo, 2'-deoxyguanosine content in the urine and mononuclear cells was correlated with the haemoglobin A1c value. CONCLUSIONS/INTERPRETATION: This is the first report of a direct association between oxidative DNA damage and the complications of diabetes. The augmented oxidative DNA damage in diabetes is speculated to contribute to the pathogenesis of diabetic complications.

8-Hydroxy-2'-Deoxyguanosine↗